Book Der Fru

A HISTORY OF HUMAN
HELMINTHOLOGY
DAVID I. GROVE
MD. FRACP, FRCPA, DTM&H
Department of Clinical Microbiology and Infectious Diseases

The Queen Elizabeth Hospital
Woodville
South Australia
C.A.B INTERNATIONAL
C.A.B. International
Wallingford
Oxon OX10 8DE
UK
Tel: Wallingford (0491) 32111

Telex: 87964 (COMAGG G)
Telecom Gold/Dialcom: 84: CAU001
Fax: (0491) 33508
©C.A.B International 1900. All rights reserved. No part of this

publication may be reproduced in any form or by any means,
electronically, mechanically, by photocopying, recording or otherwise,
without the prior permission of the copyright owners
British Library Cataloguing in Publication Data

Grove, David I
A history of human helminthology
1. Man. helminthic diseases
I. Title
616.962
ISBN 0-86198-689-7
Printed and bound in the UK by Bookcraft (Bath) Ltd

CONTENTS
Preface vii
Acknowledgements viii
1. The nomenclature and classification of worms 1
2. Understanding the origin and transmission of worms 33
3. The discovery and development of anthelmintics 75
4. Fasciola hepatica and fascioliasis 103
5. Fasciolopsis buski and fasciolopsiasis 127
6. Clonorchis sinensis and clonorchiasis 141
7. Paragonimus westermani and paragonimiasis 159
8. Schistosoma haematobium and schistosomiasis haematobia 187
9. Schistosoma mansoni and schistosomiasis mansoni 233
10. Schistosoma japonicum and schistosomiasis japonica 263
11. Trematode infections of lesser importance 297
12. Echinococcus granulosus and echinococcosis or hydatid

disease 319
13. Taenia solium and taeniasis solium and cysticercosis 355
14. Taenia saginata and taeniasis saginata 385
15. Diphyllobothrium latum and diphyllobothriasis 397
16. Cestode infections of lesser importance 421
17. Enterobius vermicularis and enterobiasis 439

Contents
18. Trichuris trichiura and trichuriasis 455
19. Ascaris lumbricoides and ascariasis 469
20. Anyclostoma duodenale, Necator americanus and

hookworm disease 499
21. Strongyloides stercoralis and strongyloidiasis 543
22. Trichinella spiralis and trichinosis 571
23. Wuchereria bancrofti, Brugia species and filariasis 597
24. Loa loa and loiasis 641
25. Onchocerca volvulus and onchocerciasis 661
26. Dracunculus medinensis and Guinea worm disease 693
27. Nematode infections of lesser importance 721
28. Miscellanea 765
29. Biographies 783
Person index 823
Subject index 836

PREFACE
In his History of Tropical Medicine published in 1939, HH Scott wrote :

"Ankylostomiasis is almost the only helminthic infestation of man in the tropics which
can be said to have a history, at all events a history of sufficient interest to call for any
detail". Scott was wrong. Many worms a re visible to the naked eye and some have been
recognized for millenia. The study of worms has been an integral component of Man's
struggle to come to grips with the origin s of infectious diseases and the means by which
they are transmitted from one to another. This book is an attempt to describe th e
unfolding of those events which have led to our current understanding of helminth s
infecting humans. They have occupied many centuries and have been undertaken b y
diverse men and women in many locations and climes.
The first three chapters of the book are gen eral in nature, the next eight are concerned
with trematodes (flukes), the next five deal with cestodes (tapeworms and cysti c
worms), the following eleven consider nematodes (roundworms) and the final chapter
covers various miscellaneous items. Chapters concerned with specific worm infections
follow a consistent plan, beginning with the discovery of the parasite and then its life
cycle, followed by an historical treatment of how the clinical features have bee n
recognized, diagnostic techniques developed, treatment evolved, the epidemiolog y
understood and preventive and control measures applie d. Short biographies of the major
research workers are appended at the end of the book.
This work has been a labour of love from its conception some dozen years ago till the
presentation of the typeset manuscript to the publisher. History is a dynamic subject,
and it is my hope that others will build upon and refine all that is recounted herein.
ACKNOWLEDGEMENTS
I am very grateful to the University of Western Australia for twelve months' sabbatical
leave during which time much of the basic research for this book was undertaken in the
United Kingdom. Special tribute must be paid to two key sources. The first is th e
magnificent Tropical Medicine and Parasitology: Classic Investigations edited by BH
Kean, KE Mott and AJ Russell (Cornell University Press, Ithaca, 1978) in whic h
translations of many of the most important original articles are brought together. The
second is the Tropical Diseases Bulletin in which the helminthological literature has
been abstracted since the early part o f this century. Thanks are due to Dr CR Morris for
providing a photograph of his grandfather, WH Ransom, to Dr John Walker fo r
obtaining a photograph of H Dew from the University of Sydney, and to Prof J
Bailenger for assistance in collecting biographical details of L Normand and C Bavay.
The photographic plates were expertly put together by Mr J Hadaway and Mr C
Hentschke. Publication of these plates has been made possible by a generous grant from
the Pathology Advisory Fund Committee of the Queen Elizabeth Hospital, Woodville,
South Australia. This book has been produced on a personal computer using Wor d
Perfect 5.1 (Word Perfect Corporation, Utah) and Glyphix (SWFTE International ,
Delaware). Finally, and most importantly, I must express my gratitude to my wife ,
Marilyn, and my children, Duncan, Graham, Br onwen and Lachlan, for the patience and
forbearance they have shown during the many hours that this book has taken to prepare.
Chapter 1
THE NOMENCLATURE AND CLASSIFICATIO N

OF WORMS
THE NATURE OF WORMS
Worms are multicellular invertebrate animals, each of which belongs to one of

several phyla or classes in the animal kingdom. The name "worm" is an in -
definite though emotive and evocative term which conjures up in the popula r
mind visions of any elongated, creeping thing that is not obviously something
else. This is not at all surprising, for the word, which is derived from the Latin
"vermis", has been used down the centuries as an all-embracing description to
apply to all worm-like creatures, whether they be earthworms, insect larvae in
fruit, in vegetables or in trees, or parasitic worms in animals 34. Indeed,
Linnaeus in the eighteenth century was even more liberal and used the titl e
"Vermes" in his Systema Naturae to include a wide range of multicellula r
organisms which we might now classify as invertebrates 32. Since worm-like
creatures have been found in many branches of the animal kingdom, variou s
authorities have drawn different lines of demarcation between worm an d
non-worm. Worms are now, however, commonly considered to encompass the
following phyla and classes: Nematoda (roundworms), Platyhelminthes (flat -
worms), Acanthocephala (thorny-headed worms), Nematomorpha (hairworms
or gordiid worms) and Annelida (segmented worms including earthworms and
leeches). These various groups differ from each other in both externa l
appearance and fundamental organization, the sal ient features being summarized
briefly as follows:
(1) Nematoda The worms are elongated and cylindroidal in shape with a basically
bilateral symmetrical arrangement. The integument consists of a non-nucleated cuticle
secreted by the underlying hypodermis. They have a pseudocoele (a body cavity which
is not lined with mesothelium), a complete gastrointestinal tract, and those that are
parasitic in humans are unisexual.
(2) Platyhelminthes These helminths are bilaterally symmetrical and are compressed
dorsoventrally to give a leaf-like or tape-like shape. The integument generally consists of
a syncitial cytoplasmic covering continuous with nucleated portions of the cytoplasm
situated in the parenchyma beneath the muscle layer. They lack a body cavity, with the
region between the internal organs being filled with spongy, mesenchymatous cells.
Flatworms of human importance fall into two classes:
a.Trematoda The worms are unsegmented and the adult forms are usually endowed with
suckers and an incomplete gut (one aperture only). They may be either unisexual or
1
2 A History of Human Helminthology
hermaphroditic.
b. Cestoda The adult worms are usually segmented with the body being divided
transversely into separate, sexually complete units called proglottids. The scolex (head)
is provided with suckers + hooks. They have no gut and are hermaphroditic.
(3) Acanthocephala The adult worms have a proboscis armed with hooks which is
retractile into a sheath. The elongated, more or less cylindroidal worms have an
integument that is perforated by canals, a large pseudocoele, no gastrointestinal tract and
are unisexual. Transmission occurs through an arthropod intermediate host.
(4) Nematomorpha These elongated, cylindroidal worms have a true body cavity, the
mouth and anus is frequently absent, and the pharynx is degenerate. They have no
excretory system and the sexes are separate. The adult forms are free-living in the soil
while the juvenile stages are parasitic in arthropods.
(5) Annelida These are bilaterally symmetrical, segmented creatures with a well-defined
gut, body cavity and excretory, vascular and nervous systems. Earthworms
(oligochaetes) and leeches (hirudines) are hermaphroditic, with the latter possessing
suckers.
The early physicians and naturalists, however, regarded parasitic worms a s

an homogenous but separate an d discrete group of creatures without backbones
that were characterized by the possession of a soft, elongated body without any
locomotor appendage or well-developed hea d, and that were found in the bodies
of other animals. In the early nineteenth century, Carl Rudolphi coined a ne w
word, "Entozoa", to describe such organisms; this indicated that they wer e
animals living inside the bodies of other animals 39. This word, which mean s
literally "animal within" was derived from the Greek words (ENTOS)
meaning "within" or "inside" and (ZOON) meaning "animal". This was
a particularly useful term for parasitic worms and held sway while the concept
that parasitic worms were a distinct systematic group persisted until the latter
half of the nineteenth century. Eventually, however, with the discovery of th e
complex life cycles and migrations of many worms, it became clear that th e
word was inappropriate for describing the eggs and larvae of parasitic worms
that might be found in the external environment. The word is rarely met wit h
nowadays and worms are generally qualified as being either free-living o r
parasitic worms or helminths.
The latter word, "helminth", has much the same meaning in modern par-
lance as does "worm". It is derived from the Greek word, µ
(HELMINS) [Combining form µ - (HELMINTHO-)] which was used by
the ancient Greek physicians and naturalists to denote worms found in th e
intestines of animals. "Helminthology", or the study of worms, is derived from
a combination of µ (HELMINTHO-) and (LOGOS) meaning
"account", "reason" or "discourse". Although the word may have no exac t
meaning in zoological classification, it is common in medical terminology and
is still used in the same sense as it was by Sir William Ramsay, physician t o
King Charles II of England, in 1668. He published a volume entitle d
Elminthologia, or some Physical Considerations of the Matter, Origination,
Nomenclature and Classification 3
and Several Species of Worms Macerating and Direfully Cruciating every part
of the Bodies of Mankind etc. which appears to be the first English textbook on
this subject. In his book, Ramsay dealt with worms and their origin, thei r
distribution within the human body, the effects of age and other factors o n
susceptibility to infection, the clinical features, the prognosis, treatment an d
methods of prevention of worm infections 35. Although used by some parasit -
ologists such Dujardin (Histoire naturelle des helminthes ou vers intestinaux ,
184517) and Diesing (Systema Helminthum, 1849-1851 16), the term was not us-
ually adopted in general pathological and medical texts until Requin (1852) in
his "Élémens de pathologie médicale " argued that the term "la maladi e
vermineuse" (wormy illness) was complex, clumsy and embarrassing, an d
championed the use of the word "helminthiasis", derived from a combination of
µ (HELMINTHIAN) meaning "to suffer from worms", and
(ASIS), to denote "the condition of" suffering from a worm infection 38. There
were, however, some opponents. Davaine (1877), for example, wrote that h e
did not believe that medical language gained in clarity or conciseness by th e
introduction of the expression 15. Nevertheless, the terms "helminth" an d
"helminthiasis" found favour with many subsequent authors and are no w
well-entrenched in the medical literature.
AWARENESS OF PARASITIC WORMS DOWN THE AGES
The Greek and Roman physicians of the M editerranean basin before and around
the time of Christ recognized two, sometimes three, worms as parasitizing the
human frame. All these worms were large and inhabited the gastrointestina l
tract, hence they were appreciated relatively easily. Thus, Celsus (c.30 BC-38
AD)12 and Pliny (23-79 AD) 11 spoke of tapeworms and roundworms, whereas
Hippocrates (c.460-374 BC) 22, Aristotle (384-c.322 BC) 4 and Galen (129-c.200
AD)19 were familiar with tapeworms ( Taenia species), round worms ( Ascaris
lumbricoides) and threadworms (Enterobius vermicularis ). Ascaris
lumbricoides was called in Greek µ (HELMINS
STRONGYLE), meaning "round worm", Enterobius vermicularis was termed
(ASKARIS, ASCARIS - there have been two transliterations, th e
former said to be closer to the original etymologically and the latte r
phonetically), and the tapeworm was known as µ (HELMINS
PLATEIA) meaning "flatworm" or, more rarely, a s (TAINIA, TAENIA)
meaning "band" or "ribbon worm".
The Romans and those who wrote in Latin translated the word µ
(HELMINS) by "lumbricus". They used this expression to encompass all th e
intestinal worms, and also earthworms which they believed were closel y
related. Thus, the word "lumbricus" was a group term analogous to a generi c
description and was modified by an adjective to indicate the type in the fol -
lowing manner: "lumbricus teres" ("teres" = "round, cylindrical") for Ascaris
Table 1.1. Classification of worms infecting humans according to Linnaeus, 1758 33.
(Worms found rarely or not then recognized as being pathogenic for humans have been
omitted in Tables 1-14)
___________________________________________________________________
Classis Vermes CURRENT NAME

Ordo Intestina
Gordius medinensis Dracunculus medinensis
Ascaris vermicularis Enterobius vermicularis
Ascaris lumbricoides Ascaris lumbricoides
Fasciola hepatica Fasciola hepatica
Ordo Mollusca
Ordo Testacea
Ordo Lithophyta
Ordo Zoophyta
Taenia solium Taenia solium
Taenia lata Diphyllobothrium latum
____________________________________________________________________
lumbricoides, "lumbricus latus" ("latus" = "broad, wide") for Taenia species,

and "lumbricus terrenus" ("terrenus" = "earth") for the common earthworm.
Following the fall of Rome in the fifth century AD, medical learning wa s
largely maintained and developed throughout the Dark Ages by Persian an d
Arabic physicians. These authors recognized three, four, or sometimes five ,
species of worms. They were all familiar with Ascaris lumbricoides and
Enterobius vermicularis, but their understanding of tapeworms varied .
Serapion (c. ninth century), for example, regarded the Taenia proglottids as
distinct and independent worms which he called "cucurbitini" in view of their
fancied resemblance to pumpkin seeds. He did not recognize Taenia itself as
a worm but as a membrane formed by the intestine to hold and develop th e
cucurbitini41. Avicenna (981-1037), in contrast, spoke of roundworms, thread-
worms, tapeworms and cucurbitini, with the last-named being considered as
a distinct parasite 5. In addition, the Arabo-Persian physicians were familia r
with dracunculiasis (Guinea worm infection) as a clinical entity, but th e
verminous nature of the condition was a matter of debate amongst them (se e
chapter 26).
This was the situation which presented itself to the European physicians and
naturalists of the Renaissance. The person who had the greatest and mos t
profound influence on the nomenclature of helminths was the Swede, Carl von
Linné (Carolus Linnaeus). This effect resulted, not from a prime consideration
of helminths themselves, but as a consequence of his general treatment of al l
living things. Following the classical line of thought, Linnaeus initially (1735)
recognized three forms of worms as infecting humans: lumbrici (now known
as Ascaris lumbricoides), ascarides (Enterobius vermicularis ) and taeniae
(Taenia species and Diphyllobothrium latum )32. Linnaeus had divided th e
animal world into six classes - Mammalia (mammals), Aves (birds), Amphibia
Table 1.2. Classification of worms infecting humans according to Goeze, 1782 21

____________________________________________________________________
Genus CURRENT NAME

Ascaris vermicularis cauda subulata Enterobius vermicularis
Trichocephalos Trichuris trichiura
Gordius Dracunculus medinensis
Planaris latiuscula Fasciola hepatica
Taenia cucurbitina grandis saginata Taenia saginata
Taenia cucurbitina plana pellucida Taenia solium
Taenia visceralis socialis granulosa Echinococcus granulosus
____________________________________________________________________
(frogs etc.), Pisces (fish), Insecta (arthropods and crustaceans) and Verme s
(other invertebrates). He then subdivided these classes into various orders, the
Class Vermes being partitioned into five orders (Table 1.1). There wer e
justifiable criticisms of his class ification. For example, George Louis Leclerc de
Buffon, a wealthy French count and keeper of the Jardin du Roi, wrote wit h
some acerbity that no-one could imagine that a mollusc was a worm or tha t
crayfish were insects. With the publication of the tenth edition of his work i n
1758 33 , Linnaeus introduced a major change in the manner of describin g
animals. He had derived his concepts of genus and species from Greek logic ,
and in the earlier editions of his Systema Naturae had used several lines o f
descriptive text to define and differentiate various species. In this edition ,
however, he limited the species designation to a single word in order to reduce
the expenses of publication. Thus, by a combination of force of circumstances
and Greek logic, binary nomenc lature was born. By 1758, he acknowledged six
species of worms, which were placed in two different orders, as being capable
of infecting humans (Table 1.1). The differentiation between Taenia solium and
Taenia lata (now known as Diphyllobothrium) was clearly established .
Fasciola hepatica, which he had at one time regarded as a leech, now found its
rightful place among the helminths, and Gordius medinensis (= Dracunculus
medinensis) was becoming accepted increasingly by various authorities as being
of a verminous nature.
In 1782, the German pastor, Johann Goeze (Göze) published a major work
on the natural history of worms inhabiting the bodies of animals entitle d
Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper 21.
This book was written primarily for submission to the Royal Academy o f
Science in Copenhagen which had set in 1780 a prize essay on the subject o f
the origin of parasitic worms. Goeze argued for the spontaneous origin o f
helminths and received second prize. His work, however, is a major contribu-
tion to the helminthological literature, particularly from a systematic point o f
Table 1.3. Classification of worms infecting humans according to Gmelin, 1788-1793 20

____________________________________________________________________
Classis Vermes CURRENT NAME

Ordo Intestina
Trichocephalus hominis Trichuris trichiura
Filaria medinensis Dracunculus medinensis
Fasciola hominis Fasciola hepatica
Taenia vulgaris Diphyllobothrium latum
Taenia visceralis Echinococcus granulosus
Taenia cellulosae Taenia solium
____________________________________________________________________
view. Goeze did not follow the binary system of nomenclature and often used a
number of adjectives to describe each parasite. He divided worms into te n
genera: Ascaris, Trichocephalos, Gordius, Cucullanus, Strongylus, Pseudo-
echinorhynchus, Planaria, Fasciola, Taenia and Chaos. He recognized nine
species of worms as infecting the human body reasonably commonly (Tabl e
1.2). The additions to the worms described by Linnaeus were due to th e
differentiation of Taenia saginata from T. solium by Goeze, his appreciatio n
that hydatid cysts (Echinococcus granulosus ) were wormy in nature when he
found the characteristic taeniid heads within each cyst, and the discovery in
the interim by others of Trichuris, which Goeze renamed Trichocephalos
when he found that what had been identified previously as the tail was in fact
the head.
Between 1788 and 1793, JF Gmelin issued a revised version of Linnaeus' s
work which was published as the thirteenth edition of Systema Naturae 20.
Gmelin retained the basic format used by Linnaeus. The total number o f
parasitic species listed by Gmelin remained the same (Table 1.3), but th e
number of species which are recognized today fell by one. Gmelin failed t o
maintain Goeze's distinction between Taenia solium and Taenia saginata and
this separation fell into oblivion for another 60 years. On the other hand, h e
recognized correctly the helminthic nature of Cysticercus cellulosae , which he
called Taenia cellulosae. He was completely unaware, however, that this org-
anism was merely a stage in the life cycle of Taenia solium, and accorded it
separate specific status.
In 1798, G Cuvier in his Tableau élémentaire de l'histoire naturelle de s
animaux, produced a classification which divided worms into two groups - the
"cavitaires" and the "parenchymateux". Worms in the first group had a distinct-
ive digestive cavity with an anus. The second group lacked complete digestive
tubes: if there was a gut at all, it was incomplete with the anus being absent 14.
In 1800, the German naturalist, Johann Zeder, published what was purport-
Table 1.4. Classification of worms infecting humans according to Zeder, 1800 43 and
180044
____________________________________________________________________
Zeder, 1800 Zeder, 1803 CURRENT NAME
Rundwürmer Rundwürmer
Fusaria lumbricoides Fusaria lumbricoides Ascaris lumbricoides
Fusaria dispar Mastigodes hominis Trichuris trichiura
Fusaria vermicularis Enterobius vermicularis
Hakenwürmer Hakenwürmer
Saugwürmer Saugwürmer
Distoma hepaticum Distoma hepaticum Distoma hepaticum
Bandwürmer Bandwürmer
Halysis solium Taenia solium
Halysis lata Diphyllobothrium latum
Blasenwürmer Blasenwürmer
Polycephalus hominis Polycephalus echinococcus Echinococcus granulosus
Cysticercus finna Taenia solium
(also C. pyriformis,
C. albopunctatus)
___________________________________________________________________
ed to be a revision of Goeze's work (Erster Nachtrag zur Naturgeschichte der

Eingeweidewürmer mit Zusätzen und Anmerkungen herausgegeben von JGH
Zeder), but was in fact so different as to be hardly recognizable as such 43. Not
only did he revert to binary nomenclature and co mpletely change the generic and
many of the specific names, but Zeder introduced a novel system of classifying
worms which was the forerunner of the modern system of classification. H e
divided the entozoa into five groups: Rundwürmer (roundworms) ,
Hakenwürmer (hookworms, equivalent to the modern Acanthocephala o r
thorny-headed worms and not ancylostomes), Saugwürmer (sucking worms) ,
Bandwürmer (tapeworms) and Blasenwürmer (cystic worms) (Table 1.4). The
Rundwürmer would become the modern nematodes and the Saugwürmer th e
modern trematodes. The Bandwürmer and the Blasenwürmer would eventually
be combined to form the cestodes, but this division by Zeder inhibite d
realization that the two groups were related, and more than 50 years were t o
pass before the relationship was proven with the recognition that cystic worms
were intermediate stages in the life cycles of tape worms. Being a revision o f
Goeze's work, this edition was n ot all-encompassing and a number of important
human pathogens were omitted.
In 1803, Zeder produced a new book entitled Anleitung zur Naturgeschichte
der Eingeweidewürmer 44. He again used the same classification as he ha d
employed three years earlier. Although he generally gave the worms different
names, he recognized the same species as infecting humans as di d
Table 1.5. Classification of worms infecting humans according to Rudolphi. 1808-1810 39

____________________________________________________________________
Ordo Nematoideorum CURRENT NAME

Trichocephalus dispar Trichuris trichiura
Ordo Trematodorum
Distoma hepaticum Fasciola hepatica
Ordo Cestoideorum
Ordo Cysticorum
Cysticercus cellulosae Taenia solium
Echinococcus hominis Echinococcus granulosus
(also E. simiae
E. veterinorum)
___________________________________________________________________
Gmelin (Table 1.4). He divided (incorrectly) Gmelin's Taenia cellulosae into

three species and placed them in a new genus named Cysticercus. The worm
infecting humans he called C. finna, that infecting subhuman primates he des-
ignated C. pyriformis, and that infecting other animals he labelled C. albo-
punctatus.
Between 1808 and 1810, the German physician, Carl Rudolphi published a
massive opus totalling 1,370 pages entitled Entozoorum, sive vermium intest-
inalium historia naturalis meaning the natural history of entozoa or intestinal
worms 39 . He took the same basic five groups as proposed by Zeder and con -
verted the German names into classical ones. It was from these names that the
modern words nematode, trematode and cestode are derived.
(1) The roundworms became t he Entozoa Nematoidea. This name was derived
from a combination of the Greek words µ (NEMA) [combining for m
µ - (NEMATO)] = "thread" and (ODES) = "like, of the nature of",
to indicate their filiform or thread-like sh ape. He defined them as being "corpore
elongato, cylindrico, tenuissime, an ulato, elastico" 39meaning that the body of the
worm was elongated, cylindrical, thin, ringed and elastic.
(2) the "hookworms" became the Entozoa Acanthocephala. This name was de-
rived from a combination of the Greek words (AKANTHA,
ACANTHA) = "spine" or "thorn" and (KEPHALE, CEPHALE)
= "head", to indicate the characteristic hooks on the head of the worms. H e
defined them as being "corpore teretiusculo, utriculari, subelastico, proboscide
seriatim uncinata, retractili" 39 meaning that the body was slightly rounded ,
bag-shaped and partly elastic, while the probosc is or head had a row of retractile
hooks.
(3) The sucking worms became the Entozoa Trematoda. This name was de-
Table 1.6. Classification of worms infecting humans according to Bremser, 1819 10

____________________________________________________________________
Nematodeorum CURRENT NAME

Oxyuris vermicularis Enterobius vermicularis
Filaria dracunculus Dracunculus medinensis
Trematodorum
Cestoideorum
Bothriocephalus latus Diphyllobothrium latum
Cysticorum
Echinococcus hominis Echinococcus granulosus
(also E. veterinorum)
____________________________________________________________________
rived from the Greek word µ (TREMATODES) meanin g

"foraminous" or "pierced with holes", to reflect the fact that they were usually
provided with conspicuous suckers ( µ is a combination of µ
= "hole" or "orifice" and (ODES) = "of the nature of"). Rudolphi defined
them as being "corpore depresso vel teretiusculo, molli, poris suctoriis" 39
meaning that the body was flattened or slightly rounded, soft and provided with
sucking holes.
(4) The tapeworms became the Entozoa Cestoidea. This name was derive d
from a combination of the Gre ek words (KESTOS, CESTOS) = "tape",
"belt" or "ribbon" and (ODES) = "of the nature of", to indicate that they
are elongated, ribbon-like organisms. He defined them as being "corpor e
elongata, depresso, molli"39 meaning that the body was elongated, flattened and
soft.
(5) The cystic worms became the Ento zoa Cystica. This name was derived from
the Greek word (KUSTIS, CYSTIS) meaning "bladder". He define d
them as being "membranacei, plerumque rugosi, intus cavi, capitis coron a
uncinata, cystide inclusi" 39 meaning that they had a generally wrinkle d
membrane and an internal cavity containing heads crowned with hooks.
The species of worms that Rudolphi recognized as being of huma n
importance are indicated in Table 1.5. It can be seen that there were n o
significant changes from those published by Zeder. Rudolphi gave the generic
name of Echinococcus to hydatids and divided them (incorrectly) into thre e
species, hominis, simiae, and veterinorum to reflect their location in human ,
subhuman primate, and domestic or other animal hosts.
In 1819, Rudolphi produced a revision of his opus entitled Entozoorum
Synopsis 40. He listed a total of 993 species of parasitic worms, 552 of whic h
he considered as definite and 441 as being dubious. There were no majo r
Table 1.7. Classification of worms infecting humans according to Dujardin, 1845 17

____________________________________________________________________
Nématoides CURRENT NAME

Filaria oculi humani Loa loa
(also F. lacrymalis)
Oxyuris vermicularis Ascaris lumbricoides
Trichina spiralis Trichinella spiralis
Trématodes
Cestoïdes (Cestoidea et Cystica of Rudolphi)
Echinococcus veterinorum Echinococcus granulosus
____________________________________________________________________
changes to the parasites infecting humans in this volume, other than hi s

acceptance of the separation by Bremser of Diphyllobothrium latum from the
genus Taenia and his placement of it in the genus Bothriocephalus.
In the same year (1819), JG Bremser, custodian of the Imperial museum in
Vienna published his book entitled Ueber lebende Würmer im lebende n
Menschen 10. No new worms of human importance were listed (Table 1.6), but
he transferred Ascaris vermicularis to the genus Oxyuris and, as mentioned,
reclassified Taenia lata as Bothriocephalus latus. He recognized two species
of Echinococcus, E. hominis and E. veterinorum in other animals.
In 1845, the Frenchman Felix Dujardin produced his Histoire naturelle des
helminthes ou vers intestinaux 17. His classification had features of bot h
Rudolphi's and Cuvier's systems. He divided the parasitic worms into two basic
groups which were in turn partitioned into subclasses. The animals of the first
group had a gut. This category was then subdiv ided depending upon whether the
gut was complete or incomplete, and whether the worms were unisexual o r
hermaphroditic. Unisexual worms with a complete gut but no spines on th e
proboscis were placed in the subclass Nématoï des, while those with spines were
located in the subclass Acanthothèques. Hermaphroditic worms with a n
incomplete gut were in the subclass Trématodes. The second group had n o
intestines or true mouth and were in turn partitioned. Those with separate sexes
were placed in the subclass Acanthocéphales, while those which wer e
hermaphroditic were set in the subclass C estoïdes. This last group encompassed
both the Cestoidea and Cystica of Rudolphi. Two major additions to huma n
helminths were listed (Table 1.7). Trichina spiralis was described in detail, and
the worm now known as Loa loa was mentioned and stated as being definitely
different from Dracunculus medinensis , although no details were provided.
Table 1.8. Classification of worms infecting humans according to Diesing, 1849-1851 16

____________________________________________________________________
Nematoidea CURRENT NAME

(also T. affinis)
Ankylostomum duodenale Ancylostoma duodenale
Trematoda
Cephalocotylea
Echinococcus polymorphus Echinococcus granulosus
Dibothrium latum Diphyllobothrium latum
____________________________________________________________________
Soon afterwards, in 1849 and 1851, the German CM Diesing issued his two
volume Systema Helminthum totalling 1,267 pages16. Human helminths fell into
three orders, the Nematoidea, Myzelmintha and Cephalocotylea. The orde r
Myzelmintha included two suborders, the Cercariaea and Trematoda. Th e
Cercariaea contained many species of the genera Cercaria of Müller and Redia
of de Filippi which were later shown to be larval stages of adult worms placed
in the suborder Trematoda. In this book, another species of human importance,
Anchylostomum duodenale , was now listed (Table 1.8).
The labours of Goeze, Zeder, Rudolphi, Dujardin, Diesing and others ha d
expanded helminthology greatly, developing it into a specialized study of th e
metazoan parasites of the internal organs and structures of Man and animals. In
the process, however, the relationship between these worms and non-parasitic
animals was largely lost, for the parasitic helminths were generally considered
to be a separate and peculiar class of animals. There were opponents of thi s
view, such as CE von Baer and FS Leuckart, but this error was not correcte d
finally until the middle of the nineteenth century when Carl Vogt united th e
various groups of parasitic helminths with those of the free-living animals with
which they were closely relate d42. Thus, Vogt classified the parasitic nematodes
together with the free-living nematodes in the Nemathelminthes, and cas t
parasitic cestodes and trematodes with free-living flatworms such a s
turbellarians in the Platyhelminthes.
While this was satisfying for the zoologist, it was not particularly relevant to
the medical practitioner who was less interested in systematics and preferred to
consider the helminths as a biological group. With the appearance in 1855 of
Friedrich Küchenmeister's book Die in und an dem Körper des lebende n
Menschen vorkommenden Parasiten 28, medical helminthology leaves th e
Table 1.9. Classification of worms infecting humans according to Küchenmeister,

185528
____________________________________________________________________
Nematelmia CURRENT NAME

Ancylostoma duodenale Ancylostoma duodenale
Trematodea
Distoma haematobium Schistosoma haematobium
Cestoidea
Taenia mediocanellata Taenia saginata
Taenia nana Hymenolepis nana
Echinococcus altricipariens Echinocococcus granulosus
Echinococcus scolicipariens Echincococcus granulosus
____________________________________________________________________
Table 1.10. Classification of worms infecting humans according to Cobbold, 1864 13

____________________________________________________________________
Nematoda CURRENT NAME

Sclerostoma duodenale Ancylostoma duodenale
Dracunculus medinensis Dracunculus medinensis
Dracunculus loa Loa loa
Trematoda
Bilharzia haematobia Schistosoma haematobium
Cestoda
Taenia flavopunctata Hymenolepis diminuta
Taenia elliptica Dipylidium caninum
Taenia echinococcus Echinococcus granulosus
____________________________________________________________________
Table 1.11. Classification of worms infecting humans according to Davaine, 1877 15

____________________________________________________________________
Nématodes CURRENT NAME

Anchylostoma duodenale Ancylostoma duodenale
Anguillula stercoralis Strongyloides stercoralis
Anguillula intestinalis Strongyloides stercoralis
Filaria sanguinis hominis Wuchereria bancrofti
Trématodes
Distomum hepaticum Fasciola hepatica
Distomum crassum Fasciolopsis buski
Distomum haematobium Schistosoma haematobium
Cestoïdes
Taenia flavopunctata Hymenolepis flavopunctata
Tania echinococcus Echinococcus granulosus
____________________________________________________________________
major works of systematic helminthology. From Küchenmeister's time, a series

of texts appeared which were devoted primarily or exclusively to human helm-
inthology. The worms discussed by Küchenmeister are listed in Table 1.9 .
Several major advances had occurred by then. Schistosoma haematobium and
the common but relatively innocuous Hymenolepis nana had been discovered
by Bilharz, and Küchenmeister himself had rediscovered the difference between
Taenia solium and T. saginata. He blotted his copybook a little, however, by
making a false subdivision of Echinococcus granulosus into E. scolicipariens
and E. altricipariens. Perhaps most importantly of all, new understandings of
the transmission of worms had led to alterations in the manner of classification.
The publication by Steenstrup in 1842 of the Alternation of Generations in
which he showed that cercariae and rediae were merely stages in th e
reproduction of trematodes (see chapters 2,4), culminated in the disappearance
of these genera from the list of flatworms as promulgated by Dujardin an d
Diesing. Similarly, the demonstration of the relationship between cystic worms
and tapeworms by Küchenmeister, von Siebold and others (see chapters 2, 12,
13), eliminated bladderworms such as Cysticercus cellulosae as separate
species.
The major addition by the time of Cobbold's book in 1864 13 was acceptance
of Loa loa as a distinct nematode that was not uncommon in certain parts o f
Table 1.12. Classification of worms infecting humans according to Blanchard,

1885-18908
____________________________________________________________________
Nematodes CURRENT NAME

Ankylostoma duodenale Ancylostoma duodenale
Rhabdonema intestinale Strongyloides stercoralis
Filaria loa Loa loa
Filaria sanguinis hominis Wuchereria bancrofti
Trematodes
Distoma sinense Clonorchis sinensis
Distoma japonicum Clonorchis sinensis
Distoma buski Fasciolopsis buski
Distoma ringeri Paragonimus westermani
Distoma heterophyes Heterophyes heterophyes
Bilharzia haematobia Schistosoma haematobium
Cestodes
Taenia saginata Taenia saginata
Taenia canina Dipylidium caninum
____________________________________________________________________
the world (Table 1.10). In addition, the parasites now known as Hymenolepis
diminuta and Dipylidium caninum were listed as infecting humans. Two new
nematodes and another trematode made their appearance in Davaine's text i n
187715 (Table 1.11). Strongyloides stercoralis was discovered in the pre-ceding
year, but it was not at first realized that the parasitic female worm and th e
first-stage larva were different stages in the life cycle of the same parasite, and
they were each given separate specific s tatus. Microfilariae had been discovered
a number of years earlier by Demarquay then had been identified in the blood
by Lewis in 1872, hence their designation as Filaria hominis sanguinis .
Although the adult worm had be en discovered in 1876 by Bancroft, news of the
find came too late to be incorporated into Davaine's book and his descriptio n
was based upon the microfilaria l stage. Fasciolopsis buski had been discovered
more than forty years before by Busk, but the finding of further cases in th e
1870's renewed interest in a previously obscure parasite.
By the appearance of Blanchard's two volume work in 1885-1890 8, the ident-
ity of Anguillula intestinalis and A. stercoralis had been determined an d
Table 1.13. Classification of worms infecting humans according to Braun, updated by

Sambon and Theobald, 1906
___________________________________________________________________
Nematoda CURRENT NAME

Strongyloides intestinalis Strongyloides stercoralis
Filaria bancrofti Wuchereria bancrofti
Filaria diurna Loa loa
Filaria perstans Mansonella perstans
Filaria ozzardi Mansonella ozzardi
Filaria loa Loa loa
Filaria volvulus Onchocerca volvulus
Trichocephalus trichiurus Trichuris trichiura
Trichinella spiralis Trichinella spiralis
Ankylostoma duodenale Ancylostoma duodenale
Uncinaria americana Necator americanus
Trematoda
Fasciolopsis buski Fasciolopsis buski
Paragonimus westermani Paragonimus westermani
Opisthorchis felineus Opisthorchis felineus
Opisthorchis sinensis Clonorchis sinensis
Schistosomum haematobium Schistosoma haematobium
Schistosomum japonicum Schistosoma japonicum
Cestoda
Dibothriocephalus latus Diphyllobothrium latum
Dipylidium caninum Diphylidium caninum
Hymenolepis nana Hymenolepis nana
Hymenolepis diminuta Hymenolepis diminuta
Taenia saginata Taenia saginata
Echinococcus multilocularis Echinococcus multilocularis
_________________________________________________________________________
Blanchard called the parasite Rhabdonema intestinale (Table 1.12). Two new
flukes of some importance had been discovered - Clonorchis sinensis by
McConnell and Paragonimus westermani in humans by Ringer and Manson .
Baelz had incorrectly divided the former parasite into two species and Blan -
chard perpetuated the error. Mention was also made of the parasite now called
Heterophyes heterophyes .
By 1906, when the English version of Braun's textbook was published 9,
several new nematodes had been described (Table 1.13). Manson had reported
in 1893 a portion of Leuckart's description of Onchocerca volvulus from
specimens sent to him from West Africa by a missionary, and Stiles had diff -
erentiated Necator americanus from Ancylostoma duodenale . In addition, two
new filarial parasites, Filaria ozzardi and Filaria perstans had been
discovered. Similarly, major fin ds had been made with the trematodes. Katsur-
Table 1.14. Classification of worms according to Faust, 1939 18

____________________________________________________________________
Nematodes Trematodes Cestodes

Trichinella spiralis Schistosoma haematobium Diphyllobothrium latum
Trichocephalus trichiurus Schistosoma mansoni Hymenolepis nana
Strongyloides stercoralis Schistosoma japonicum Hymenolepis diminuta
Ancylostoma duodenale Fasciola hepatica Dipylidum caninum
Necator americanus Fasciolopsis buski Taenia solium
Enterobius vermicularis Opisthorchis species Taenia saginata
Ascaris lumbricoides Clonorchis sinensis Echinococcusgranulosus
Wuchereria bancrofti Paragonimus westermani
Onchocerca volvulus
Acanthocheilonema perstans
Mansonella ozzardi
Loa loa
Dracunculus medinensis
microfilaria malayi
_________________________________________________________________________
ada had discovered Schistosoma japonicum in 1904 and Opisthorchis felineus

was now appreciated as infecting humans. Finally, a number of authors wer e
beginning to accept the specificity of Echinococcus multilocularis .
The second edition of Faust's text on human helminthology 18 in 1939
incorporated two major changes (Table 1.14). The specific systematic position
of Schistosoma mansoni proposed in 1908 by Sambon had been proven b y
transmission experiments, and Lichtenstein and Brug had appreciated tha t
certain microfilariae in Southeast Asia were different from those of Wuchereria
bancrofti and these had been labelled microfilaria malayi. Furthermore,
infections with Opisthorchis viverrini had been recognized. These represented
the last major discoveries of worms important for human medicine althoug h
worms of limited geographical distribution such as Capillaria philippinensis ,
Brugia timori and Schistosoma mekongi would be discovered or differentiated
in the next few decades. Table 1.15 lists those worms which have been des -
cribed in Beaver, Jung and Cupp's 1984 revision of Craig and Faust's Clinical
Parasitology as infecting humans 6. These parasites range from exceedingl y
common worms, such as Ascaris lumbricoides which infects nearly one billion
people, to extremely rare ones which have been encountered in humans onl y
once or twice.
THE RULES OF ZOOLOGICAL NOMENCLATURE
It is clear from the foregoing discussion that many different names were often
used to describe the same worm. This led to chaos and confusion and inhib-
ited the flow of ideas and the generation of new discoveries, for unles s
everyone possessed a common language, there was considerable uncertainty
Table 1.15. Classification of worms according to Beaver, Jung and Cupp, 1984 6.
____________________________________________________________________
Class Nematoda Class Trematoda Class Cestoidea

Ancylostoma ceylanicum Achillurbania species Bertiella species
Ancylostoma duodenale* Alaria species Diphyllobothriumcordatum
Angiostrongylus species Clonorchis sinensis* Diphyllobothrium latum*
Anisakis species Dicrocoelium dendriticum Diplogonoporus grandis
Ascaris lumbricoides* Echinostoma species Dipylidium caninum
Brugia malayi* Fasciola gigantica Echinococcusgranulosus*
Brugia timori Fasciola hepatica Echinococcus
multilocularis
Capillaria species Fasciolopsis buski Echinococcus vogeli
Dioctophyma renale Gastrodiscoides hominis Hymenolepis diminuta
Dirofilaria species Heterophyes heterophyes Hymenolepis nana*
Dracunculus medinensis* Metagonimus yokogawai Inermicapsifer
madagascariensis
Enterobius vermicularis* Opisthorchis felineus Mesocestoides variabilis
Gnathostoma spinigerum Opisthorchis viverrini Raillietina demerariensis
Gongylonema pulchrum Paragonimus westermani* Sparganum species
Haemonchus contortus Plagiorchis species Spirometra houghtoni
Lagochilascaris minor Poikilorchis species Taenia brauni
Loa loa* Schistosoma haematobium* Taenia multiceps
Mammomonogamus laryngeus Schistosoma intercalatum Taenia saginata*
Mansonella ozzardi Schistosoma japonicum* Taenia serialis
Mansonella perstans Schistosoma mansoni* Taenia solium*
Mansonella streptocerca Schistosoma margrebowiei Taenia taeniaeformis
Metastrongylus elongatus Schistosoma mattheei
Necator americanus* Schistosoma rodhaini
Phocanema species Spelotrema species
Oesophagostomum species Troglotrema salmincola
Onchocerca volvulus* Watsonius watsoni
Phocanema species
Physaloptera caucasica
Strongyloides fülleborni
Strongyloides stercoralis*
Ternidens deminutus
Thelazia species
Toxocara species
Trichinella spiralis*
Trichuris trichiura*
Wuchereria bancrofti*
* common or relatively common
____________________________________________________________________
as to what other writers were saying. This problem applied not just to medical
helminthology, but was even more germane to zoologists who had to deal with
more than a million animal species.
In an attempt to produce uniformity and order, the Frenchman, Raphae l
Blanchard, presented a Code to the First International Zoological Congress in
Paris in 1889. This code was adopted by that and the subsequent Congress in
1892 but failed to receive universal support. The Third Congress in 189 5
appointed an international commission to develop a code which would be ac-
ceptable to all zoologists. Progress reports were delivered at the Fourth (1898)
and Fifth (1901) Congresses. At the Sixth Congress in 1904, the International
Code of Zoological Nomenclature was p resented and the commission was made
permanent.
The code consisted of 36 articles supplemented with various recommend -
ations including a code of ethics and conditions for the suspension of the rules
in certain cases. The naming of animals was based upon the binary system o f
nomenclature. Article 26 provided the foundation stone upon which the whole
edifice was erected for this statement confirmed that the starting point for such
an arrangement began with the publication in 1758 of the tenth edition o f
Linnaeus's Systema Naturae. The 36 basic articles which were adopted ar e
reproduced in Table 1.16.
In addition to these articles, a code of ethics was laid down in which it wa s
suggested that when an author published a name of a new genus or specie s
which was preoccupied, the person discovering the error should inform th e
author and give him ample opportunity to propose a new name. Furthermore,
a procedure was devised whereby the rules could be suspended in certai n
cases. The circumstance in which this could arise would be when the com -
mission judged that a strict application of the rules would result in greate r
confusion than uniformity. In such cases, notice of at least one year had to b e
given in two or more of the following publications: Bulletin de la Société
Zoologique de France, Monitore Zoologica, Nature, Science, or Zoologischer
Anzeiger in order to allow debate. If the vote of the commission was no t
unanimous, then the matter would be referred to the next Internationa l
Congress which would appoint a special boar d of three members to make a final
decision.
The accumulation of knowledge over the years has in many instances necess-
itated the splitting of a species or the subdivision of a genus. An example of the
former is the differentiation of the Taenia solium and Taenia saginata. In like
manner, the genus Distoma of Retzius 1790 has been subdivided into man y
genera including Clonorchis, Fasciolopsis, Paragonimus and Schistosoma. On
some occasions, a name has been applied which had already been used fo r
another member of the animal kingdom. Thus, Trichina spiralis of Owen 1835
was changed to Trichinella spiralis by Railliet in 1895 when it was realized that
the generic name had already b een used for an insect. This is an example where
a name is a homonym, i.e. where the same name has been applied to two o r
more different animals. This contra sts with synonyms which are different names
used for the same animal.
All these eventualities were covered in the rules, but the article which gave
rise to the greatest dissent and concern, particularly in the medical sphere, was
Article 25 which described the law of priority. This law required that the valid
name of a genus or species was the name under which it was first described ,
provided the principles of binary nomenclature were followed and the nam e
was accompanied by an indication, definition or description of the organism .
Table 1.16. The rules of zoological nomenclature (cited in 18)

____________________________________________________________________
"Article 1. - Zoological nomenclature is independent of botanical nomenclature in the sense that

the name of an animal is not to be rejected simply because it is identical with the name of a plant.
If, however, an organism is transferred from the vegetable to the animal kingdom its botanical
names are to be accepted in zoological nomenclature with their original botanical status; and if an
organism is transferred from the animal to the vegetable kingdom its names retain their zoological
status.
"Article 2. - The scientific designation of animals is uninominal for subgenera and all higher
groups, binominal for species, and trinominal for subspecies.
"Article 3. - The scientific names of animals must be words which are either Latin or Latinized,
or considered and treated as such in case they are not of classic origin.
"Article 4 - The name of a family is formed by adding the endingidae, the name of a subfamily
by adding inae, to the root of the name of its type genus.
"Article 5 - The name of a family or subfamily is to be changed when the name of its type genus
is changed.
"Article 6 - Generic and subgeneric names are subject to the same rules and recommendations,
and from a nomenclatural standpoint they are coordinate, that is, they are of the same value.
"Article 7 - A generic name becomes a subgeneric name, when the genus so named becomes a
subgenus and vice versa
"Article 8 - A generic name must consist of a single word, simple or compound, written with a
capital initial letter, and employed as a substantive in the nominative singular. Examples:Canis,
Perca, Ceratodus, Hymenolepis.
"Article 9 - If a genus is divided into subgenera, the name of the typical subgenus must be the
same as the name of the genus (see Article 25).
"Article 10 - When it is desired to cite the name of a subgenus, this name is to be placed ni
parenthesis between the generic and the specific names. Examples:Vanessa (Pyrameis) cardui.
Article 11 - Specific and subspecific names are subject to the same rules and recommendations,
and from a nomenclatural standpoint they are coordinate, that is, they are of the same value.
"Article 12 - A specific name becomes a subspecific name when the species so named becomes
a subspecies, and vice versa.
"Article 13 - While specific substantive names derived from names of persons may be written
with a capital initial letter, all other specific names are to be written with a small initial letter.
Examples: Rhizostoma Cuvieri or R. cuvieri, Francolinus Lucani or F. lucani, Hypoderma Diana
or H. diana, Laophonte Mohammed or L. mohammed, Oestrus ovis, Corvus corax.
Article 14 - Specific names are:
"(a) Adjectives, which must agree grammatically with the generic name. Example: Felis
marmorata.
"(b) Substantives in the nominative in apposition with the generic name. Example:Felis leo.
"(c) Substantives in the genitive. Examples: rosae, sturionis, antilarum, galliae, sancti-pauli,
sanctae-helenae. "If the name is given as a dedication to one or several persons, the genitive si
formed in accordance with the rules of Latin declination in case the name was employed and
declined in Latin. Examples: plini, aristotelis, victoris, antonii, elisabethae, petri (given name).
"If the name is a modern patronymic, the genitive is always formed by adding, to the exact and
complete name, an i if the person is a man, or an ae if the person is a woman, even if the name has
a Latin form; it is placed in the plural if the dedication involves several persons of the same name.
Examples: cuvieri, möbiusi, nuñezi, merianae, sarasinorum, bosi (not bovis), salmoni (not
salmonis).
"Article 15 - The use of compound proper names indicating dedication, or of compound words
indicating a comparison with a simple object, does not form an exception to Article 2. In these cases
the two words composing the specific name are written as one word with or without the hypen.
Example: sanctae-catharinae or sanctaecatharinae, jan-mayeni or janmayeni, cornu-pastoris
or cornu-pastoris, cor-angium or coranguinum, cedo-nulli or cedonulli.
Expressions like rudis palnusque are not admissible as specific names.

"Article 16 - Geographical names are to be given as substantives in the genitive, or are to be
placed in the adjectival form. Examples: sancti-pauli, sanctae-helenae, edwardiensis, diemensis,
magellanicus, burdigalenesis, vindobonensis.
Article 17 - If it is desired to cite the subspecific name, such is written immediately following the
specific name, without the interposition of any mark of punctuation. Example:Rana esculenta
marmorata Hallowell, but not Rana esculenta (marmorata) or Rana marmorata, Hallowell.
Article 18 - The notation of hybrids may be given in several ways; in all cases the name of the
male parent precedes that of the female parent, with or without the sexual signs:
"(a) The names of the two parents are united by the sign of multiplication (X) Example:Capra
hircus male X Ovis aries female and Capra hircus X Ovis aries are equally good formulae.
"(b) Hybrids may also be cited in form of a fraction, the male parent forming the numerator and
the female parent the denominator.
Example: Capra hircus/Ovis aries. This second method is in so far preferable that it permits the
citation of the person who first published the hybrid form as such. Example: Bernicla
canadensis/Anser cygnoides Rabé.
"(c) The fractional form is also preferable in case one of the parents is itself a hybrid. Example:
Tetrao tetrix X Tetrao urogallus/Gallus gallus. In the latter case, however, parenthesis may be
used. Example: (Tetrao tetrix X Tetrao urogallus) X Gallus gallus.
"(d) When the parents of the hybrid are not known as such (parents), the hybrid takes
provisionally a specific name, the same asif it were a true species, namely, as if it were not a hybrid;
but the generic name is preceded by the sign of multiplication. Example: X Coregonus dolosus
Fatio.
"Article 19 - The original orthography of a name is to be preserved unless an error of
transcription, a lapsus calami, or a typographical error is evident.
"Article 20 - In forming names derived from languages in which the Latin alphabet is used, the
exact original spelling, including diacritic marks, is to be retained. Examples: Selysius, Lamarckia,
Köllikeria, Mülleria, Stilia, Krøyeria, Ibañesia, möbiusi, medi i, c j eki, spitzbergensis,
islandicus, paraguayensis, patagonicus, barbadensis, faröensis.
"Article 21 - The author of a scientific name is that person who first publishes the name ni
connection with an indication, a definition or a description unless it is clear from the contents of the
publication that some other person is responsible for said name and its indication, definition, or
description.
"Article 22 - If it is desired to cite the author's name, this should follow the scientific name
without interposition of any mark of punctuation; if other citations are desirable (date, sp n.,
emend., sensu stricto, etc.,), these follow after the author's name, but are separated from it bya
comma or by parentheses. Examples: Primates Linné, 1758, or Primates Linné (1758).
"Article 23 - When a species is transferred to another than the original genus or the specific name
is combined with any other generic name than that which it was originally published, the name of
the author of the specific name is retained in the notation but placed in parentheses. Example:
Taenia lata Linné, 1758, and Dibothriocephalus latus (Linné, 1758); Fasciola hepatica Linné,
and Distoma hepaticum (Linné, 1758).
If it is desired to cite the author of the new combination, his name follows the parentheses.
Example: Limnatis nilotica (Savigny, 1820) Moquin-Tandon, 1826.
"Article 24 - When a species is divided, the restricted species to which the original specific name
of the primitive species is attributed may receive a notation indicating both the name of the original
author and the name of the reviser. Example: Taenia solium Linné partim, Goeze.
"Article 25 - The valid name of a genus or species can be only that name under which it was first
designated on the condition:
"(a) That this name was published and accompanied by an indication, or a definition, ora
description; and
"(b) That the author has applied the principles of binary nomenclature.
"Article 26 - The tenth edition of Linné's Systema Naturae, 1758, is the work which inaugurated
the consistent general application of the binary nomenclature in zoology. The date 1758, therefore,
is accepted as the starting point of zoological nomenclature and of the law of priority.
"Article 27 - The law of priority obtains and consequently the oldest available name is retained:
"(a) When any part of an animal is named before the animal itself;
"(b) When the larva is named before the adult;
"(c) When the two sexes of an animal have been considered as distinct species or even as
belonging to distinct genera;
"(d) When an animal represents a regular succession of dissimilar generations which have been
considered as belonging to different species or even to different genera.
"Article 28 - A genus formed by the union of two or more genera or subgenera takes the oldest
valid generic or subgeneric name of its components. If the names are of the same date, that selected
by the first reviser shall stand.
"The same rule obtained when two or more species or subspecies are united to form a single
species or subspecies.
"Article 29 - If a genus is divided into two or more restricted genera, its valid name must be
retained for one of the restricted genera.
"If a type was originally established for said genus, the generic name is retained for the restricted
genus containing said type.
"Article 30 - The designation of type species of genera shall be governed by the following rules
(a to g), applied in the following order of precedence:
"I. Cases in which the generic type is accepted solely upon the basis of the original publication:
"(a) When in the original publication of a genus, one of the species is definitely designated as a
type, this species shall be accepted as type, regardless of any other considerations. (Type by original
designation.)
"(b) If in the original publication of a genus, typicus or typus is used as a new specific name for
one of the species, such use shall be construed as 'type by original designation.'
"(c) A genus proposed with a single original species takes that species as its type. (Monotypical
genera.)
"(d) If a genus, without originally designated (see a) or indicated (see b) type, contains among
its original species one possessing the generic name as its specific or subspecific name, either as
valid name or synonym, that species or subspecies becomes ipso facto type of the genus. (Type by
absolute tautonymy.)
"II. Cases in which the generic type is accepted not solely upon basis of original publication:
"(e) The following species are excluded in determining the types of genera.
"Species which were not included under the generic name at the time of its original publication.
"Species which were species inquirendae from the standpoint of the author of the generic name
at the time of its publication.
"Species which the author of the genus doubtfully referred to it.
"(f) In case a generic name without originally designated type is proposed as substitute for another
generic name, with or without type, the type of either, when established, becomes ipso facto the type
of the other.
"(g) If an author, in publishing a genus with more than one valid species, fails to designate (see
a) or to indicate (see b, d) its type, any subsequent author may select the type, and such designation
is not subject to change.
(Type by subsequent designation.)
"The meaning of the expression 'select the type' is to be rigidly construed. Mention of a species
as an illustration or example of a genus does not constitute a selection of a type.
"Article 31 - The division of a species into two or more restricted species is subject to the same
rules as the division of a genus. But a specific name which undoubtedly rests upon an error of
identification cannot be retained for the misdetermined species even if the species in question are
afterward placed in different genera. Example: Taenia pectinata Goeze, 1782 = Cittotaenia
pectinata (Goeze), but the species erroneously determined by Zeder, 1800, as Taenia ' pectinata
Goeze' = Andrya rhopalocephala (Riehm); the latter species does not take the name Andrya
pectinata (Zeder).
"Article 32 - A generic or a specific name, once published, cannot be rejected even by its author,
because of inappropriateness. Example: Names like Polyodon, Apus, albus, etc., when once
published, are not to be rejected because of a claim that they indicatecharacters contradictory to
those possessed by the animals in question.
"Article 33 - A name is not to be rejected because of tautonymy, that is, because the specific or
the specific and subspecific names are identical with he generic name. Examples:Trutta trutta,
Apus apus.
"Article 34 - A generic name is to be rejected as a homonym when it has previously been used
for some other genus of animals. Example: Trichina Owen, 1835, nematode, is rejected as
homonym of Trichina Meigen, 1830, insect.
"Article 35 - A specific name is to rejected as a homonym when it has previously been used for
some other species of the same genus. Example: Taenia ovilla Rivolta, 1878 (n. sp.) is rejected as
homonym of T. ovilla Gmelin, 1790.
"When in consequence of the union of two genera, two different animals having the same specific
or subspecific name are brought into one genus, the more recent specific or subspecific name is to
be rejected as a homonym.
"Specific names of the same origin and meaning shall be considered homonyms if they are
distinguished from each other only by the following differences:
"(a) The use of ae, oe and e, as coeruleus, cereleus; ei, i and y as chiropus, cheiropus; c and
k as microdon, mikrodon.
"(b) The aspiration or non-aspiration of a consonant, asoxyryncus, oxyrhynchus.
"(c) The presence or absence of a c before t, as autumnalis, auctumnalis.
"(d) By a single or double consonant, litoralis, littoralis.
"(e) By the ending ensis and iensis to a geographical name, as timorensis, timoriensis.
"Article 36 - Rejected homonymscan never be again used. Rejected synonyms can again be used
in case of the restoration of erroneously suppressed groups. Example: Taenia Giardi Moniez, 1879,
was suppressed as a synonym of Taenia ovilla Rivolta, 1878; later it was discovered that Taenia
ovilla was preoccupied (Taenia ovilla Gmelin, 1790). Taenia ovilla, 1878, is suppressed as a
homonym and can never again be used, it was still-born and cannot be brough to life, even when the
species is placed in another genus (Thysanosoma). Taenia Giardi, 1879, which was suppressed as
a synonym, becomes valid upon the suppression of the homonymTaenia ovilla Rivolta.
____________________________________________________________________
This applied whether or not a particular name was in common or popular use.
Thus, Bilharzia haematobia, a name which had been used for decades to des-
ignate the worm discovered by Bilharz, had to be altered to Schistosoma
haematobium because the latter name was given to the parasite several months
before Cobbold published his designation. Such occurrences led the British
Medical Journal in an editorial in 1926 to complain tha t
"archaeoparasitologists" or:
assiduous individuals have spent their days and nights ransacking musty archives and
long-forgotten tombs. From these they have extracted a galaxy of paradoxically new
yet old names which they have tacked on to the familiar names of our youth. 1
Nevertheless, such changes were essential if the rules were to produce th e
uniformity and stability for which they were designed. A major difficulty ,
however, lay in knowing who real ly said what about which worm. Not only was
much of the literature inaccessible or unavailable, but there was ofte n
considerable doubt as to the acceptability or completeness of an accompanying

description which would allow the organism to be identified with certainty, or
in other words, to answer the question as to what really was the name first given
to any animal29. Having begun by saying that zoological nomenclature was a
sore point with everybody, especially the medical profession, th e
above-mentioned editorial concluded by observing that:
What the mass of zoologists want is a system which will secure stability, which will
obviate the necessity for antiquarian research, which, at the same time, will reject
enigmatical descriptions, and will insist on the reference of all species to a central
authority.1
As a result of sentiments such as as these, the International Commission o n
Zoological Nomenclature appo inted a small advisory committee to consider the
names of certain worms. In a series of opinions, they fixed the generic names of
a number of helminths which were the subject of some contention:
Opinion 66 (February 1915): Ancylostoma, type duodenale; Ascaris, type lumbri-
coides; Dracunculus, type medinensis; Gnathostoma, type spinigerum; Necator, type
americanus; Strongyloides, type stercoralis; Trichostrongylus, type retortaeformis 24.
Opinion 77 (31 January 1922): Schistosoma, type haematobium; Hymenolepis,type
diminuta 25.
Opinion 84 (16 December 1925): Dicrocoelium, type lanceolatum (vel dendriticum
sub judice); Fasciola, type hepatica; Heterophyes, type heterophyes; Davainea, type
proglottina; Dipylidium, type caninum; Echinococcus, type granulosus; Taenia, type
solium 26.
Nevertheless, not everyone was satisfied. Leiper (1926), for example ,
declaimed against "the tyranny of nomenclatural rules in medicine." 31 He
declared that alterations flowing from the rule of priority had been a source
of considerable annoyance to medical men and of bitter complaint from med-
ical students. Leiper noted that one of the requisites of this law stated that the
rules of binary nomenclature had to be applied but this was often not bein g
observed. For example, Taenia mediocanellata of Küchenmeister had bee n
replaced by Taenia saginata of Goeze even though the latter had actually des-
cribed the worm as Taenia cucurbitina, grandis, saginata . Similarly, vern-
acular names were sometimes being used as generic or specific names. Thus,
the term "dracunculus" had been used in the vernacular sense until Cobbol d
gave it generic status in 1864, by which time it had been pre-occupied as th e
name for a group of reptiles. Again, specific names were sometimes aband-
oned without, in Leiper's opinion, sufficient justification. He regarded thi s
state of affairs as intolerable and demanded that the International Com -
mission should use its plenary powers to suspend those rules which cause d
greater confusion than conformity. Further, he believed that steps should b e
taken to press for an extension of this power by allowing well-establishe d
names to be placed upon the list of accepted names 29. An editorial in the
British Medical Journal applauded this suggestion, remarking that "there is no
reason why such a list of names should be beyond the forensic powers of ou r
biological and medical legislators" 2 but added with cynical realism that "W e
fear, however, that Professor Leiper's pl ea will bring him neither tranquillity nor
peace"2. It ought to be added in parenthesis, moreover, that Leiper himself was
no saint in these matters, for he sought to use the rules to his own advantag e
when he attempted (unsuccessfully) to rename Dracunculus medinensis as
Fuellebornius medinensis 30.
Nevertheless, comments such as these did have one solid effect. In order to
leave no room for uncertainty as to the features of an organism being newl y
named, the International Zoological Congress which met in Budapest in 1927
added a new section (c) to the law of priority, article 25:
(c) But no generic name nor specific name, published after December 31, 1930, shall
have any status of availability (hence also of validity) under the Rules, unless and until
it is published either
1. with a summary of characters (seu diagnosis; seu definition; seu condensed
description) which differentiate or distinguish the genus from other genera or
species.
2. or with a definite bibliographic reference to such summary of characters (seu
diagnosis; seu definition; seu condensed description). And further
3. In the case of a generic name, with the definite unambiguous designation of the type
species (seu genotype; seu autogenotype; seu orthotype). (Cited in 18).
One major change in medical te rminology occurred subsequently, not under the
auspices of the International Commission on Zoological Nomenclature, but as
an opinion of the committee on terminology of the American Society o f
Parasitologists when it reported in December 1940 that:
It was of the opinion of the Committee that under the International Rules of
Zoological Nomenclature Trichuris rather than Trichocephalus is the valid generic
name.37
The committee also indicated that it felt that Dioctophyma renale was the
correct name for the giant kidney worm which infects humans very rarely.
In July 1958, the XV International Congress of Zoology adopted a new ,
complete official transcript of the International Code of Zoological Nomen -
clature. This was published in London in 1961 with alternate pages set i n
French and English and has set the seal on the nomenclature of animals 27.
PARASITISM
Another word in need of definition is the term "parasite". This word was derived
from the Greek word (PARASITOS) which means literally "on e
who eats at the table of another" and was formed by a combination of
(PARA) = "besides" and (SITOS) = "food". Küchenmeister in 185 5
defined parasites in the following manner:
Parasites are independent organised beings, descended from peculiar animal or
vegetable parents, which require, in order that they may be enabled to complete their
development, growth, or reproduction, to take up their abode either constantly or
temporarily in or upon a second animal or vegetable organism of a different kind, from
which they also derive their nourishment. Human parasites are those which select the
human body as this second organism.28

In a similar vein, Cobbold (1864) wrote that:
The happiest way of studying the entozoa is to regard them as a peculiar fauna destined
to occupy an equally peculiar territory i.e. the interior of the bodies of man and
animals.13
while Braun (1906) penned:
By the term parasites is understood living organisms which for the purposes of
procuring food take up their abode, temporarily or permanently, on or within a living
organism.4
The idea of a parasite was well-expressed in the lay literature in the lines o f
Swift who, in response to the discovery by Leeuwenhoek when using hi s
microscope that the fleas which infest man were in turn parasitized by mites ,
wrote:
So, naturalists observe, a flea
Has smaller fleas that on him prey:
And these have smaller still to bite 'em.
And so proceed ad infinitum
PJ van Beneden (1889) recognized that there were varying relationships be -
tween two animals which lived in close relationship with each other. He called
them parasites, mess-mates and mutualists, and described them thus:
The parasite is he whose profession it is to live at the expense of his neighbour, and
whose only employment consists in taking advantage of him....He is a pauper who
needs help lest he should die on the public highway....The parasite instals himself
either temporarily or definitively in the house of his neighbour; either with his consent
or by force, he demands from him his living, and very often his lodging. The
mess-mate is he who is received at the table of his neighbour to partake with him of
the produce of the day. He does not live at the expense of his host; all that he desires
is a home or his friend's superfluities. Mutualists are animals which live on each other
without being either parasites or mess mates.7
These concepts find modern expression in the terms parasite, where th e
organism does harm, commensal, where the organism neither helps nor hinders,
and symbiote or mutualist, where the two organisms assist each other in some
way.
Van Beneden also noted that whereas the beast of prey kills its victim in order
to eat the flesh, it is generally profitable f or the parasite if it does not kill its host.
With respect to the damage caused by these creatures, Küchenmeister (1855)
believed that the most dangerous worms were larvae engaged in migratio n
through the tissues; these were followed in turn by mature worms migrating in
gut, then large encysted worms, then finally, small encysted worms 28. Braun
(1906) expressed modern concepts when he remarked that the pathogenicity of
helminths was largely determined by the location, numbers and movement o f
worms9.
INFECTION VERSUS INFESTATION
The word "infest" has sometimes been used instead of "infect" to denote th e
presence of worms in a host. "Infect" and "infection" are derived from the Latin
word "infectus", the past participle of "inficere" meaning "to dip in", "put into",
"taint" or "stain". Its use long antedated the knowledge of pathogeni c
microorganisms and implied tainting with morbid matter, or contamination with
noxious effluvia, vapours and miasmata. Thus, there was a connotation o f
trouble caused by invisible, internal agents. "Infest" and "infestation" on th e
other hand, are derived from the Latin word "infestus", the past participle o f
"infestare", meaning "to make hostile, unsafe, disturbed or troublesome", an d
referred to obvious external agents such as pirates, thieves, rats and fleas which
molested or harassed the victim. These ideas were embodied in Dr. Samue l
Johnson's Dictionary of 1785 whic h defined infect as to "act upon by contagion;
to taint; to poison; to pollute" while to infest was "to harass; to disturb; t o
plague". The same concepts are enjoined in the modern Oxford Englis h
Dictionary which gives the meaning of infect as "to affect (a person, animal or
part of a body) with disease" while to infest is "to trouble (a country or place)
with hostile attacks....said of persons (e.g . robbers, pirate), animals (e.g. wolves,
vermin, insects), diseases or other evils".
Nevertheless, as pathological processes due to organisms capable o f
independent multiplication within the host such as bacteria, protozoa, fungi
and viruses became increasingly recognized, there was an attempt to limit the
term infection to such organisms, while infestation was proposed for thos e
organisms which do not (or usually do not) multiply within the host such a s
helminths and insects. Further, the argument was expressed that intestina l
worms are not truly within the body, though this idea has never been used t o
assert that non-invasive gastrointestinal bacterial infections should be calle d
infestations.
In view of this confusion, the American Society of Parasitology in 193 3
appointed a committee to investigate the matter. They concluded:
We believe that 'infest' and 'infestation' ought to revert to their original use in
connection with external, and in most cases, visible agents. There would be retained
the long established use of these terms in connection with most insects in speaking of
such conditions as dogs "infested" with fleas, "infestations" of mosquitoes and the like.
On the other hand, we believe the terms 'infect' and 'infection' are properly applicable
wherever the parasite invades and establishes itself within the body of the host,
including in this sense, the gastro-intestinal tract. This would apply then, not only to
bacteria and protozoa, but also to helminths....We fail to see any reason for continuing
the use of the term 'infestation' as applied to internal parasites and believe that the
present confusion will disappear only as its use be discontinued. 36
This view was supported in 1960 by an editorial in the British Medical Journal
which remarked that "Consistency and common sense would therefore seem to
favour the use of the word infection for intestinal helminths." 3 This concept has
largely held sway and most technical works now refer to helminth infection s
rather than infestations.
REFERENCES
1. ANONYMOUS. Zoological nomenclature. British Medical Journal ii: 1989-1990, 1910

2. ANONYMOUS. The nomenclature of parasitology. British Medical Journal ii: 1129, 1926
3. ANONYMOUS. Infect and infest. British Medical Journal ii: 1724, 1960
4. ARISTOTLE. Opera omnia, graece et latine, cum indice nominum et rerum absolutissimo, F
Dübner, E Heitz and UC Bussemaker (Editors), Didot, Parisiis, five volumes, 1848-1874
5. AVICENNA. Libri in re medica omnes, qui hactenus ad nos pervenere. Id est, libri canonis
quinque, De viribus cordis, De removendis nocumentis in regimine sanitas, De sirupo acetosa
et cautica, translated by JP Mongio Hydruntino et J Costaeo Laudens, V Valgrisius, Venetiis,
pp 966, 1564. Original arabic "Al Canon fi al Tib" c. 1000 AD
6. BEAVER PC, JUNG RC, CUPP EW. Clinical parasitology, ninth edition, Lea and Febiger,
Philadelphia, pp 825, 1984
7. van BENEDEN PJ. Animal parasites and mess-mates, fourth edition, Kegan Paul, Tranch and
Co., London, pp 274, 1889
8. BLANCHARD R. Traité de zoologie médicale, J-B Baillière et fils, Paris, two volumes, pp
1691, 1885-1890
9. BRAUN M. The animal parasites of man. A handbook for students and medical men, translated
by P Falck, revised by LW Sambon and FV Theobald, John Bale, Sons and Danielsson,
London, pp 453, 1906
10. BREMSER JG. Ueber lebende Würmer im lebenden Menschen. Ein Buch für ausübende
Aertze. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. Nebst einem Anhange
über Pseudo-Helminthen, Carl Schaumburg und Comp., Wien, pp 284, 1819
11. CAIUS PLINIUS SECUNDUS. Historia naturalis, translated by J Bostock and HT Riley,
Bohn's Classical Library, London, six volumes, 1855-1857.
12. CELSUS AC. De medicina, translated by WG Spencer, Loeb Classical Library, Heinemann,
London, three volumes, 1948-1953
13. COBBOLD TS. Entozoa: an introduction to the study of helminthology with reference, more
particularly, to the internal parasites of man, Groombridge and Sons, London, pp 480, 1864
14. CUVIER JG. Tableau élémentaire de l'histoire naturelle des animaux, Paris, 1798
15. DAVAINE C. Traité des entozaires et des maladies vermineuses de l'homme et des animaux
domestiques, second edition, J-B Baillière et fils, Paris, pp 1003, 1877
16. DIESING CM. Systema helminthum, Wilhelmum Braumüller, Vindobonae, two volumes, pp
1267, 1849-1851
17. DUJARDIN F. Histoire naturelle des helminthes ou vers intestinaux, Librairie encyclopédique
de Roret, Paris, pp 652, 1845
18. FAUST EC. Human helminthology. A manual for physicians, sanitarians and medical
zoologists, second edition, Henry Kimpton, London, pp 780, 1939
19. GALENUS CC. Works of, In: Medicorum Graecorum opera quae exstant, edited by KG Kühn
(Greek text with Latin translation), Leipzig, 20 volumes, 1821-1833
20. GMELIN JF. Systema naturae per regna tria naturae, secundum classes, ordines, genera,
species, cum characteribus differentiis, synonymis, locis, thirteenth edition, GE Beer, Lipsiae,
8 volumes, pp 3021-3909, 1788-1793
21. GOEZE JAE. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper, PA
Pape, Blankenburg, pp 471, 1782
22. HIPPOCRATES. Works of, translated by WH Jones and ET Whithington, Loeb Classical
Library, Heinemann, London, four volumes, 1948-1953
23. HOEPPLI R. Parasites and parasitic infections in early medicine and science, University of
Malaya Press, pp 526, 1959
24. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. Nematode
and Gordiacea names placed in the official list of generic names (Opinion 66), Smithsonian
Institution Publication 2359, Washington, DC, pp 171-176, 1915
25. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. Thirty five

generic names in Protozoa, Coelenterata, Trematoda, Cestoda, Cirrepoda, Tunicata and Pisces
placed in the official list of generic names (Opinion 77), Smithsonian Miscellaneous
Collections, Smithsonian Institution, Washington, DC, Publication 2657, 73: 71-73, 1922
26. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. Trematode,
Cestode and Acanthocephala names placed in the official list of generic names (Opinion 84),
Smithsonian Miscellaneous Collections, Smithsonian Institution, Washington, DC, Publication
2830, 73: 11-12, 1925. Also, Nature 117: 414, 1926
27. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. International
code of zoological nomenclature adopted by the XV International Congress of Zoology,
International Trust for Zoological Nomenclature, London, pp 176, 1961
28. KÜCHENMEISTER F. Die in und an dem Körper des lebenden Menschen vorkommenden
Parasiten. Ein Lehr- und Handbuch der Diagnose und Behandlung der thierischen und
pflanzischen Parasiten des Menschen, BG Teubner, Leipzig, two volumes, pp 486, 1855. On
animal and vegetable parasites of the human body. A manual of their natural history, diagnosis
and treatment. Volume 1. Animal parasites belonging to the group Entozoa, translated byE
Lankester, The Sydenham Society, London, pp 452, 1857
29. LANE C The correct names of the helminths of man. Indian Medical Gazette 51: 165-173,
1916
30. LEIPER RT. Discussion on the validity of certain generic names at present in use in medical
helminthology. Archiv für Schiffs- und Tropen-Hygiene 30: 484-491, 1926
31. LEIPER RT. Cited in, Zoological nomenclature in medical literature. British Medical Journal
ii: 1122-1123, 1926
32. LINNAEUS C. Systema naturae, sive regna tria naturae systematice proposita per classes,
ordines, genera et species, first edition, Theodorum Haak, Lugduni Batavorum, 1735
33. LINNAEUS C. Systema naturae per regna tria naturae, secundum classes, ordines, genera,
species cum characteribus, differentiis, synonymis, locis, tenth edition, L Salvii, Holmiae, two
volumes, pp 823, 1758
34. MOULÉ L. La parasitologie dans la littérature antique. II Les parasites du tube digestif.
Archives de Parasitologie 14: 353-383, 1911
35. RAMSAY W. Elminthologia, or some physical Considerations of the Matter, Origination, and
Several Species of Wormes macerating and Direfully Cruciating every part ofthe Bodies of
Mankind etc., 1668
36. REPORT OF THE COMMITTEE ON TERMINOLOGY. Infection vs. infestation. Journal
of Parasitology 23: 325-326, 1937
37. REPORT OF THE COMMITTEE ON NOMENCLATURE. Trichuris Roederer 1761 vs.
Trichocephalus Schrank 1788. Journal of Parasitology 27: 277, 279-282, 1941
38. REQUIN AP. Élémens de pathologie médicale, Paris, volume 3, p 193, 1852
39. RUDOLPHI CA. Entozoorum, sive vermium intestinalium historia naturalis, Treuttel & Würtz,
Paris, three volumes, pp 1370, 1808-1810
40. RUDOLPHI CA. Entozoorum synopsis cui accedunt mantissima duplex et indices
locupletissima, Sumtibus Augusti Rücker, Berolini, pp 811, 1819
41. SERAPION (YUHANNA IBN SARA-BIYUN). Practica etc., translated, Venetiis, 1497. Cited
in 23
42. VOGT C. Zoologische Briefe, Naturgeschichte der lebenden und untergegangen Thiere,
Frankfurt, two volumes, 1851
43. ZEDER JG. JAE Goeze's Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer mit
Zusätzen und Anmerkungen herausgegeben von Johan Georg Heinrich Zeder, Siegfried
Lebrecht Crusius, Leipzig, pp 320, 1800
44. ZEDER JG. Anleitung zur Naturgeschichte der Eingeweidewürmer, Bamberg, pp 432, 1803
Chapter 2
UNDERSTANDING THE ORIGIN AND TRANS-

MISSION OF WORMS
The finding of worms within the bodies of humans and animals inevitably led
to questions concerning how those so afflicted became infected. For much o f
recorded history, the most comfortable and gen erally accepted explanation given
was that the parasites had arisen by a process of spontaneous generation. This
was a theory not easily denied, and a critical battle raged for over a century and
a half from the late seventeenth century until near the middle of the nineteenth
century before the protagonists of this theory were finally silenced. There were
two key factors which determined the outcome of this conflict of opinion. The
first was the invention of the microscope which allowed discovery of th e
presence of ova and spermatozoa and demonstration of the cellular basis o f
animals, including helminths. As will be shown, this was not enough t o
persuade many students of the subject, and the argument was only settled when
the second factor, experiment, was introdu ced into helminthology. Nevertheless,
even after it was agreed that wor ms multiplied by sexual and asexual processes,
many years often elapsed before the precise details of the mode of transmission
of a particular parasite were defined.
How and when these various discoveries were m ade are recounted for specific
worms in the various chapters that follow. In particular, the events leading to the
demonstration of the phenomenon of alternation of generations in trematodes are
reviewed in chapter 4 while the controversy that led to the recognition of th e
relationship between cystic w orms and tapeworms is covered in chapter 12. the
present chapter attempts to provide the historical sequence in which thes e
disparate threads unfolded and the interpretations which they engendered in the
minds of helminthologists.
FROM EARLY TIMES TO THE MIDDLE OF THE SEVENTEENT H

CENTURY
Belief in the spontaneous generation of certain plants and animals goes back to
ancient times and probably began when man started to speculate on the origins
of life. This process of "spontaneous generation", sometimes known a s
"equivocal generation" or, more latterly, "abiogenesis" provided the simples t
and most obvious explanation for many puzzling observations. How else could
the sudden appearance of mus hrooms after a heavy rain or the plague of locusts
or rodents in certain seasons be explained? As has been described in th e
29
previous chapter, several intestinal roundworms and tapeworms have bee n

recognized for millenia and these were regarded as an excellent proof of thi s
doctrine, for it seemed impossible to account in any other way for the existence
of such large organisms in the human intestine, as they clearly had not bee n
ingested as such.
Examples of such beliefs have been recorded from many regions of th e
ancient world. Thus, the ancient Egyptians believed that the sacred copro -
phagous scarab beetles took their origin from balls of dung. Maggots an d
intestinal worms were thought by them to be produced from decomposing food
and putrefying wounds in the intestines, espe cially under the influence of fever 77.
In the same vein, ancient Babylonian texts have been found which alleged that
worms were generated from the mud of canals 118. Likewise, the Persians of old
believed that bees were generated in the dead bodies of bulls 58. Concepts like
these were behind the Old Testament accounts of the plagues of Egypt such as
the derivation of frogs from water and insects from dust (Exodus 8). Similarly,
in Judges 14: 5-9, the story is told how Samso n killed a lion with his bare hands,
then on returning to the scene after a tryst with his beloved, found the carcass
swarming with bees and honey.
The Greeks and Romans in the centuries around the time of Christ wer e
equally at home with such ideas. Hippocrates (c.460-375 BC) regarded intest-
inal worms as originating in excrements in the fetus before birth 76. Aristotle
(384-322 BC) considered that there were four kinds of generation, includin g
spontaneous generation. He claimed that many worms, insects, sponges an d
coelenterates arose in this way, even if they produced offspring of a sort; these
he regarded as a dead end:
Among the bloodless animals....there are.... groups which, although they generate, do
not generate offspring identical with their parents. Such are the creatures which come
into being not as the result of the copulation of living animals, but out of putrescent
soil and out of residues....(some) insects moreover are not produced out of animals at
all but out of putrefying fluids (in some cases, solids). 6
Many Romans, including Virgil, Ovid, Pliny and Celsus, accepted this doctrine
of spontaneous generation, particul arly as it applied to arthropods. In particular,
Galen (129-c.200 AD) believed in the spontaneous generation of intestina l
helminths, considering that they took their origin from the gut contents 64.
Likewise, Oribasius (325-403 AD), physician to the emperor Julian th e
Apostate, considered that worms arose in the humours 155. According to
Aldrovandi2, Oribasius regarded Enterobius as arising in the black humour ,
Ascaris in the bilious humour, and tapeworms in the mucous humour.
Similar ideas were found in the Orient. In India, bed bugs were thought to be
derived from blood while intestinal worms were assumed to have arisen from
faeces, phlegm, and blood as a result of a poor diet, insufficient exercise, bad
sleeping habits, or excessive warmth 83. In China, intestinal worms wer e
considered to be the result of transformation of stagnating food in the bowe l
under the influence of heat, moisture, "aura", and wind 77.
Origin and Migration of Worms 31
These beliefs persisted into the Middle Ages and the Renaissance. Th e
Arabians of the Dark and Middle Ages provided the prime link between th e
literature of the past and the Renaissance in Europe. Avicenna (Ibn Sina )
(980-1037) was convinced that intestinal worms arose from the intestina l
contents in combination with moisture and various other factors:
There are four kinds of worms....They are different because of different origin and
surrounding. Some are formed from moisture not divided or broken up by attraction
of the liver, or excess of fermentation. Others are formed from moisture divided or
broken up by the attraction of the liver and fermentation....Thirdly, some are formed
by an intermediate condition.8
Moreover, Avicenna even believed that with a proper mixing of the element s
and under the influence of the stars, all animal s and even man could be produced
by spontaneous generation. Another Arab, Al-Qaz wini (died 1283), propounded
a novel explanation for the existence of these worms. He suggested that divine
wisdom determined that parasites should take their origin from putrefyin g
substances so that they could absorb them as food and hence purify the air and
prevent epidemic diseases 3.
These concepts were accepted by a number of European writers of the Middle
Ages such as Albertus Magnus (Albert von Baellstaedt, c.1193-1280) 9,
Villanovanus (Arnauld de Villeneuve, c.1300) 198, Edward Wotton
(1492-1555) 207 and Cardanus of Pavia (1501-1576)33 . Thus, Villanovanus
considered that there were four kinds of worms: long, round worms bred from
"salt Fleghm"; short, round worms in "sharp Fleghm"; long, broad worms i n
"sweet Fleghm"; and short, broad worms in "natural Fleghm or Mucus" 198.
Cardanus believed that slow putrefaction produced lower animals such a s
worms while rapid putrefaction resulted in higher animals such as birds 33. This
belief in the influence of temperature was taken up by other writers such a s
Gabucinus (1547) who wrote that the lower temperature of the intestine led to
the formation of tapeworms 63, while Mercurialis (1623) claimed that different
temperatures influenced the formation of small and large intestinal worms 130.
Paracelsus (1493-1541) had similar fantastic ideas:
many things will be changed in putrefaction so that they give birth to a noble fruit,
because putrefaction is a reversal and death of all things and a destruction of the
original character of all natural things. From this comes rebirth and a new birth with
thousandfold improvement.160
Thus, Paracelsus considered that worms were produced from "sperma" an d
putrefaction, a bird could be recreated from its own ashes in horse manure ,
while a pigmy could be similarly produced fro m putrefied human sperm if it was
kept under the correct conditions. Likewise, Ambroise Paré, one of the fathers
of modern surgery, believed that intestinal worms were created by spontaneous
generation in decomposing humours:
The worms are formed by a thick, sticky and crude material which decomposes in the
stomach and then descends into the intestines....On account of its stickiness which
makes it adherent to the intestines, it cannot be discharged from the abdomen. Being
retained, it undergoes still further putrefaction wherefrom worms are produced and
take their origin by the action of the warmth.161

Spigelius (Adrian van der Spiegel) wrote in 1618 that pinworms were produced
by a mixture of phlegm and ex crements at the proper temperature, roundworms
were dependent upon phlegm and bile, and tapeworms arose in thick, viscous
phlegm185.
William Harvey (1578-1657), despite the doctrine of "omne vivum ex ovo"
(all life comes out of eggs) attributed mistakenly to him by many subsequen t
commentators, believed that "imperfect animals" such as worms and insect s
arose by spontaneous generation. He considered that this occurred as a
consequence of a special principle existing in putrescent material:
Many animals, especially insects....are supposed to have arisen spontaneously, or from
decomposition because their ova are nowhere to be found....For even in fortuitous
semina there is an inherent motive principle of generation, which procreates from itself
and of itself; and this is the same as that which is found in the semina of congenerative
animals, a power to wit, of forming a living creature. 74
In fact, the words which appeared on the allegorical title-page of his De
generatione animalium were "Ex ovo omnia" (all creatures come from an egg).
This statement adorned an opened egg h eld by Jove from which many creatures,
embryos of man, mammals, reptiles and fish were escaping. Harvey had no t
seen the minute ova of viviparous creatures and he may well have been using
the image figuratively 183. Moreover, he was an Aristotelian and at times use d
language which is entirely consistent with a belief in spontaneous generation.
In any case, Harvey was more concerned with embryological development than
with the origin of generation. His postulate that in higher animals the organs are
successively formed out of the indifferent matter in the egg came to be known
as "epigenesis".
Common threads can be discerned in these writings over the centuries. Most
authors considered that intestinal worms arose in the gut contents wherea s
ectoparasites were produced by perspiration and dirt, all being influenced in an
undefined way by some special principle. These basic concepts wer e
systematized in various theories. Certain Western and Eastern schools o f
thought regarded Man as a microcosm which took its origin in the macrocosm.
When the balance and harmony between microcosm and macrocosm were dis-
turbed, disease occurred and parasites were created. Others, such as the Greeks,
Democritus (c.460-360 BC) and Epicurus (341-270 BC), considered that al l
matter was composed of minute un its or atoms, and that when these atoms were
agglomerated and amalgamated by a special force, spontaneous generation took
place. A variation upon this theme was expounded by Aristotle who proclaimed
that spontaneous generation occurred when there was a disharmony of the four
elements (fire, air, water, earth), the four qu alities (heat, cold, dryness, moisture)
and the four humours (blood, phlegm, yellow bile, black bile), in decomposing
substances, all under the influence of a vital force. This "vital force" has been
given many names including "nous" (Anaxagorus), "physis" (Hippocrates) ,
"psyche" (Plato and Aristotle), "pneuma" (Plato and others), "virtus vivificata"
(Albertus Magnus), "archaeus" (Paracelsus), "principe vital" (Theophile d e
Bordeu) and "Lebenskraft" (F riedrich Casimir Medicus). The way in which this
invisible and imperceptible vital principle was supposed to act was described
differently by the various schools of philosophy. In general, however, it wa s
believed that the vital force either created living creatures directly out of its own
metaphysical properties or it generated them by its action upon primordia l
matter.
THE SECOND HALF OF THE SEVENTEENTH CENTURY
Not everyone was happy with such ideas, however. Thus, Sir Thoma s
Browne (1645) questioned "whether mice may be bred by putrefaction?" 27
Browne, however, only refuted error with error, or at least with opinions that
seemed more reasonable than did the original ones. It was around this period
that the doctrine of "preformation" was evolved. The central thesis of pre-
formation was that the act of procreation merely permitted the appearance
in an organized and formed state of a being that was already pre-existent .
The theory first appeared in the scientific literature in Swammerdam's book
on insects in 1669189, then the theme was taken up by others. Marcell o
Malpighi, for example, believed that he could discern the form of an embryo
in an unincubated egg126,127. This led to the supposition that a complete being
lay in an egg and only a suitable stimulus was required to cause it to unfold.
This view extended to the concept of "emboitement" or "syngenesis" i n
which it was held that the being in the egg held, in its own ovaries, egg s
which in turn held secondary ova and so on. Thus, Eve was considered to
contain within her gonads the forms of all the men and women that wer e
ever to be. Thus, de Malebranche in 1673, in propounding his "principle of
plenitude" wrote:
all the bodies of men and beasts, which shall be born or produced till the end of the
world, were possibly created from the beginning of it. 125
This concept of preformation was then applied to the origin of worms, but this
led to all sorts of philosophical and theological difficulties, particularly in th e
first half of the eighteenth century, as will be described later.
It was at this stage that two events of epochal importance occurred: (1) Redi
began to experiment on the origin of invertebrate animals and (2) th e
microscope was invented then its use in microbiology popularized b y
Leeuwenhoek. Both of these fac tors were ultimately to have immense effects on
the acceptance of the theory of spontaneous generation.
Francisco Redi, court physician to the Duke of Tuscany, published in 1668 his
monumental work, Esperienze intorno alla generazione degl'insett i
(Experiments on the generation of insects )169. Redi could not accept the view
that "worms" were produced in dead animals or plants but postulated that they
were generated by insemination in putrefying matter, the latter merely serving
as a suitable nest in which animals could deposit their eggs and in which th e
resultant offspring could find nourishment. In contrast to his predecessors ,
however, Redi undertook a large number of experiments in order to test thi s
view. First, he killed three snakes and placed them in an open box to decay .
Soon afterwards, he found that they were covered with maggots (which he called
worms). Once all the meat had been consumed, however, the maggot s
disappeared. In order to determine what had become of them, he repeated the
experiment but, on this occasion, he covered ev ery exit from the box. He noticed
that some of the worms became quiet, appeared to shrink and assumed a shape
similar to an egg. Furthermore, he recognized that there was a variety of shapes
amongst these pupae, so he separated them into different glass container s
covered with paper. After a week or so, the shells of the eggs (pupae) broke and
flies came forth, the same kind of fly appearing from the same type of pupa .
Thereupon, he repeated the experiments on many occasions with various kind
of dead animals, and in every case the result was the same with one or othe r
kind of fly developing, sometimes all k inds. Moreover, he also observed that the
meats became covered with true eggs fr om which the maggots hatched. This led
him to the conclusion:
Having considered these things, I began to believe that all worms found in meat were
derived directly from the droppings of flies, and not from the putrefactions of meat. 169
This seemed especially likely as flies of the same kind as those that were bred
had hovered over the meat before it grew maggotty. Nevertheless, compare d
with other observers, Redi made a crucial step, remarking "Belief would be vain
without the confirmation of experiment" 169. Thereupon, he put a snake, som e
fish, some eels and a slice of veal from a m ilk-fed cow, each into separate, large,
wide-mouthed flasks. Each flask was carefully sealed, then a duplicate serie s
was set up except that the mouth of each vessel was left open to the atmosphere.
He watched and found that no maggots developed in the closed flasks whereas
flies entered and left the open containers at will and maggots eventuall y
appeared. Redi repeated these experiments on many occasions. He not onl y
showed that maggots were not bred spontaneously from meat, but traced th e
development of eggs through larval and pupal sta ges to adulthood. Nevertheless,
it must be conceded that Redi was led astray in his studies of the appearance of
larvae in galls on plants. He began with the same hypothesis as he had proven
with flies on meat, but was unable to demonstrate any way in which eggs could
enter a plant. This led him back to an acceptance of spontaneous generation for
these creatures:
Hence I have changed my opinion and I think it probable that the generation of worms
in trees does not....proceed from the eggs deposited by flies. 169
Redi believed that the principle which created the flowers and fruit in the first
place was the same as that which produced the grubs:
the efficient cause resided in the peculiar potency of that kind of soil or principle which
creates the flowers and fruits of living plants, and is the same that produces the worms
of these plants.169
Moreover, Redi thought that worms found in the intestines and other parts o f
humans probably arose in an analogous fashion by spontaneous generatio n
through the agency of the same vital force:
In this same manner it could perhaps be true, and I feel disposed to believe it, that in
the intestines and other parts of man, are born the lumbricoids and flesh worms. 169
Thus, Redi showed clearly that some parasites arose from ova, but concede d
that other parasites may arise by a process akin to spontaneous generation.
Redi's experiments were soon followed by publication of the observations of
the Dutchman, Jan Swammerdam. In 1669, he published his Algemeene
verhandeling von bloedloose diertjens (General account of bloodless ani -
malculae) which dealt with the modes of transformation of insects and high -
lighted the different manner of development of the various types of insects. He
also showed that the pupa was not an egg but a stage in development of the life
cycle of a single individual. He demonstrated clearly, for example, that lic e
developed from eggs, that insects found in various plant galls resulted from eggs
laid by certain flies, and he noted that certain parasitic "worms" sometime s
found in caterpillars or butterflies were the offspring of other insect s
(Ichneumon flies) that were in the habit of laying their eggs beneath the skin of
the caterpillars 189. The experiments and observations of these two pioneers were
to prove turning points in the understanding of the origin of "lesser animals", as
they were commonly known at that time.
The Englishman, Edward Tyson, writing in 1683, was well aware of th e
studies of Redi and others, which he described as indicating "univoca l
generation", i.e. natural generation from the same type of organism:
The consideration of Insects, and their manner of generation, as it is a subject of
curious speculation; so of late hath been much illustrated by the laborious researches
of many inquisitive persons: whose travels therein, tho' they have much advanced the
doctrine of univocal generation; and bid very fair the exploding of that, too easily
received, and common error, of their production from, putrefaction. 194
Tyson demonstrated the sexual apparatus o f roundworms (Ascaris lumbricoides
which he called Lumbricus teres) by dissection and believed that once present
in the gut, these worms reproduced sexually:
yet once there, there is nothing more plain, than that the Lumbricus Teres propogated
by univocal Generation; there being in this Sort so perfect a Distinction of Sexes,
Male and Female.195
Tyson had greater trouble with tapeworms. He studied in detail their anatomy,
discovering their head, but he could find no evidence of two sexes. Moreover,
he could not conceive how these organs could have had their origins fro m
outside of the body for they resembled nothing in the external world:
yet one great difficulty still remains with me, how to account for several of those, that
are bred in Animal bodies not such as we may suppose to be hatched from the eggs of
the like kind, that are received with food or in other ways; but with whom we cannot
meet with a parallel, or of the same Species, out of the body, in the whole world as is
known besides.194
This problem was so insuperable for Tyson that he ended the title of his paper
with the words "and the whole urged, as a difficulty against the doctrine o f
univocal generation" 194.
Meanwhile, the invention of the microscope had opened up a new world of
microorganisms. Furthermore, this technology was essential for the demon -
stration of ova and spermatozoa, the manner in which new life was produced,
and the ways in which animal tissues were organized. These new vistas wer e
ultimately to sound the death knell for the theory of spontaneous generation. It
is difficult to assign proper credit for the invention of this instrument. The art of
making convex and concave lenses had long been learnt, but the use of suc h
lenses in microscopes first took place around the end of the sixteenth or th e
beginning of the seventeenth century. It is not known with certainty wh o
invented the compound microscope, but Harting 72 concluded that the accolade
probably belongs to the Dutchman, Cornelius Drebbel of Almaar, or hi s
countrymen, Hans and Zacharias Janssens of Middleburg.
Little heed was paid at first to this innovation but it began to be used by a
number of scientists including the Englishmen, Robert Hooke (1653-1703) and
Nehemiah Grew (1641-1712), the Dutchman, Swammerdam, and the Italian,
Marcello Malpighi (1628-1694). Most of these workers concentrated o n
microscopical aspects of macroscopic plants and animals, however, and the real
discoverer of the invisible world of microscopical living creatures was th e
Dutch microscopist, Antony van Leeuwenhoek (1632-1723). Leeuwenhoe k
made his own microscopes and improved upon their optics. In 1673, he pub-
lished his first paper, in the Philosophical Transactions of the Royal Society ,
which dealt with mould, the morphology of the eye of the bee, and the micro-
scopical appearances of lice. Over th e next fifty years, Leeuwenhoek sent letters
to the Royal Society covering an eno rmous field of observations on microscopic
biological matters101. Not only did he describe in abundance the group o f
unicellular organisms now known as protozoa, but he was the first to visualize
bacteria, a feat which was not repeated until improvements in microscope s
made it possible for others to see them. Thomas Huxley suggested many years
later that this demonstration of the abundance of microorganisms with thei r
manifest provision for multiplication made it seem to many observers that the
doctrine of spontaneous generation was not only untrue but also absurd 80.
Leeuwenhoek himself was a preformationist and a firm opponent of the theory
of spontaneous generation. Being aware of the general belief that Fasciola
infection was acquired by animals feeding on contaminated pastures, h e
examined green sods from a meadow on which some infected sheep had fed and
looked for microscopical creatures resembling flukes, but failed to find any 100.
Nevertheless, observations that many o f the innumerable small organisms found
in water and moist soil resembled helminths led naturally to the conjecture by
many helminthologists that, after their almost unavoidable introduction in th e
human system, these creatures would grow into parasitic worms. The evolution
of such ideas, both correctly and in error, will be traced in the followin g
sections.
As the century drew to a close, there were still many staunch believers in the
theory of spontaneous generation. But the o pponents were becoming more vocal
and were exemplified by Bidloo, who, no doubt girded by his discovery of eggs
in Fasciola, in 1698 laid it:
down as a certain truth, that these, as well as other small living creatures, are produced
from their like, by the means of eggs, seed or spawn, according to the nature implanted
in them at their first creation.16
and considered that these "seeds" were ingested in contaminated water.
THE FIRST HALF OF THE EIGHTEENTH CENTURY
The new century saw the publication in 1700 of a book on helminthology b y

Nicholas Andry in which he attempted stoutly to refute the theory of spont -
aneous generation. Andry had been stimulated to write his book following a n
incident with one of his patients. On 4 June 1698, Andry went to see a thirt y
year old man with fever, haemoptysis, left-sided chest pain and dyspnoea who
five days later became delirious and passed a tapeworm 4 ells 3 inches long (an
English ell is 45" [113 cm] and a Flemish ell is 27" [68 cm]). Andry firs t
defined worms then went on to a consideration of their origins:
Worms breed in the bodies of men and other animals, by means of a seed that enters
there, in which those worms are enclosed. For all animals....are bred of a seed which
contains them....this Seed of Animals, contains in no little Bulk, the Animal that is to
be formed in it, and that Microscopes discover them to us sometimes quite formed. 5
Andry went on to consider whence this "seed" first arose:
the seeds of all Animals were created by the first Being, and put in the first individuals
of the species.5
Next, he discussed the manner in which these "seeds" could enter human an d
other animal bodies:
there is nothing in Nature, into which the seeds of insects may not insinuate itself, and
that a great Quantity of them may enter into the body of Man, as well as into those of
other Animals, by means of the Air and Aliments....they likewise enter the Flesh very
often by the outside....the skin is full of cavities. 5
Andry seems to have become a little confused, however, as to the course o f
events once the seed entered a body, for he appears to have believed that th e
internal milieu determined the type of worm that developed:
a Man, whose body abounds with a certain sort of Humour, will produce Worms of
a certain sort, whilst he who abounds with another Humour, will produce Worms of
another; and he who has no Humour proper for the Eggs of Worms, will produce
none, and so be free of them.5
By the latter remark, Andry foreshadowed the concept of immunity, whethe r
natural or acquired, that was to become so important 200 years later. It must be
admitted that Andry based his arguments upon logic and philosophy rather than
upon experimentation, as is exemplified by his challenge to the proponents of
spontaneous generation:
Some Philosophers, pretend that the worms and several other Insects are bred of
Corruption, only by a Fortuitous Combination of Matter without any seed. But if these
Philosophers could explain to me two things, the one how casual disorder could range
with so much order the Organical parts of Animals, and the other, from whence it
comes that we see no new Species of Insect bred, since that must happen according
to their System.5
In order to support his arguments, Andry included quotations from two of his
correspondents. On 26 February 1699, Mr Niklaas Hartsoeker of Amsterdam
had written to him:
There's nothing has life, be it Animal or Plant, but which comes from Seed, and
nothing is ever engendered by corruption....I am of the opinion that those Worms
ingender by Male and Female in the Bowels, and that some of their coming to issue
with the Excrements, and to fal l upon some Herb or other thing, are swallowed
by another, in whose Intreals the Worms contain'd in those Eggs come forth and are
fed.73
In like manner, Giorgio Baglivi in Rome wrote on 14 July of the same year:
You ask me 1. If it proceeds from an Egg?....The beginning and original of all Animals
and Vegetables is from an Egg....Since no Man says that Plants rise from Putrefaction,
they ought not in reason to deduce the Original of Insects and other baser Animals
from thence.... Worms Eggs lying hid in the Intestines are enliven'd and
brought forth.... Therefore the Flat Worm derives its Original from an Egg of its own
kind.11
Clericus (1721) accepted the views of Redi , Andry and those of like mind, but
considered that "The most difficu lt Question remains yet to be discussed, to wit,
From whence the first Seed of Worms is derived" 37.
Not everyone was convinced by these arguments, however. Vallisnerius, for
example, vigorously opposed the views of Andry and endeavoured to explain
the presence of entozoa by supposing them to be transmitted from parent t o
child via the placenta or through the breast milk 197. Vallisnerius was in fact a
proponent of "emboitement" which was mentioned earlier. A logical extension
of this theory was that Adam, the first man, harboured not only all mankind to
be, but all of his worms as well. This created appalling theological problem s
and Vallisnerius put the issues:
It is not reasonable to suppose that God would have placed the first worm in his body,
forasmuch as Man in this state of innocence was to be free of all kinds of
diseases....But if on the other hand, after the lapsed state of Adam, we allow that
worms were formed by God.... a greater difficulty will arise....for....it will follow that
God made a new creation of worms, which is contrary to Holy Writ; since God hath
taught us, that before Man was made, all other animals were created. 197
Vallisnerius attempted to solve this dilemma by assuming that before the Fall,
parasitic worms ate contentedly from Adam's superfluities and even performed
good works by gently licking any holes in the gut and healing them. But when
Adam fell:
all things were suddenly changed; so that these worms were made Ministers of Divine
justice and raised an insurrection upon him.197
Other ideas were also canvassed. The discovery of microscopic animal s

everywhere, including in food a nd drinking water, led to the development of the
theory of heterogony, i.e. that these creatures were introduced into the human
body and under the influence of heat and nutriment matured into entozoa. Thus,
men like Boerhaave 20 and Hoffmann78 erroneously traced many cestodes an d
nematodes back to microscopic animals which in their free state were totall y
different in appearance to the parasitic adult worms.
THE SECOND HALF OF THE EIGHTEENTH CENTURY
The advocates of the theory of sponta neous generation received staunch support
as the eighteenth century entered its second half from the writings of Georges
Leclerc, Comte de Buffon (17017-1788) and John Turbeville Needha m
(1713-1781). In 1749, Buffon's monumental Histoire Naturelle began to appear
in France30. In this work, Buffon developed the idea that vitality was a n
indestructible property of all living things. He regarded living matter as being
composed of indestructible organic molecules which, in the process o f
spontaneous generation, were rearranged to constitute vitality:
excess molecules, unable to penetrate the interior mould of the animal, reunite with
several particles of brute matter in the food and form organized bodies....This is the
origin of tapeworms, ascarides, flukes and all other worms which are born in the liver,
stomach and intestines.30
Similar views were expressed by Needham in Britain. Needham undertoo k
some experiments which he interpreted as supporting these concepts. Fo r
example, he took a portion of an almond germ and placed it in water in a phial
closed with cork; subsequently, he claimed to see a swarm of minute, moving
objects of "animalcules" which he believed came from the almond. Needha m
repeated the experiment with hot mutton gravy which, despite being sealed ,
swarmed with life a few days later. Similar results were obtained in othe r
experiments and Needham concluded that the organisms derived from a
"vegetative force in every microscopic po int of matter and every visible filament
of which the whole animal or vegetable texture consists" 146.
The views of Buffon and Needham were attacked by the Italian abbott ,
Lazzarro Spallanzani (1729-1799) who undertook numerous, well-conceived
experiments which included heating infusions as well as hermetically-sealin g
them. He concluded that animalcules may be carried into the infusions by the air
and that this was the explanation of their supposed spontaneous generation 184.
Moreover, Spallanzani found that there were two distinct classes of thes e
microscopical creatures, or "infusoria". One, which he called ordini superior i
(superior order), was easily destroyed by boiling for half a minute, whereas the
other, which was exceedingly minute microscopically and which he calle d
ultime ordini, sometimes survived boiling for half an hour; these wer e
presumably bacteria. Nevertheless, Spallanzani was criticized by the proponents
of spontaneous generation on the gr ound that he had "spoiled" the air by heating
it.
Some of the various erroneous ideas were expanded and magnified by many
students of helminthology in the latter years of the century. Thus, the grea t
classifier, Linnaeus, took the theory of heterogony and applied it to large r
free-living creatures. He found a free-living tapeworm, Schistocephalus solidus ,
and regarded it as an immature tapeworm which would develop into the adult
broad tapeworm, Diphyllobothrium latum , when swallowed. Similarly, h e
believed that he had discovered the free-living stages of Fasciola hepatica and
Enterobius vermicularis; he mistook a planarian for the former and a free-living
Rhabditis-like worm for the latter 117.
The discovery of the existence of eggs in many helminths was explained i n
different ways. Some believed that eggs hatched out in the external world gave
birth to free-living creatures and that these in turn were transformed into adult
worms after their introduction into the intestines. Such concepts fitted nicel y
with the theory of heterogony as developed by Linnaeus. Others would hav e
none of this and considered them mere by-products. Others again seized hold
of Vallisnieri's idea that entozoa were transmitted by the transplacental o r
transmammary routes or by kissin g. The major evidence for this hypothesis was
the assertion by a number of observers that they had found entozoa, not only in
the young of animals, but even in the fetus within the body of the mother. Other
investigators, however, adduced the se same observations in favour of the theory
of spontaneous generation.
Such was the interest in the origins of parasitic worms that the Royal Society
of Copenhagen in 1780 set a prize essay on this subject. The first prize was won
by Marcus Bloch, a medical practitioner from Berlin, while the second wa s
taken by the Reverend Johann Goeze in Dudlinburg, Germany. Both of thes e
men argued for the spontaneous origin of parasitic worms. Among the twelve
"facts" which Bloch used to support this position were:
- worms are sometimes located in very young animals, recently born animals, and even
in abortions
- many worms which are never found in the gut occur in the interior parts of the
animal without any passage to the exterior
- worms live in locations where other organisms are digested
- worms die rapidly on removal from the host body
- most animals have their own peculiar parasitic worms 19
Bloch believed that worms destined to live in a particular location within a
particular animal could not have arrived there by chance and that therefore they
must have been generated spontaneously. He acknowledged that many worms
produced a vast number of eggs, as did Goeze who considered that egg s
excreted in the faeces were lost for ever as far as the parasitic intestinal worm
was concerned though they may serve as food for other animals 65.
There were opponents of such views, however. Pallas wrote that:
It cannot be doubted that the eggs of Entozoa are scattered abroad and undergo various
changes without loss of vitality, and that immediately they reach the body of a suitable
animal, through the medium of its food and drink, they grow into worms. 158
Pallas even attempted to prove hi s views by experiment. In 1781, he introduced
the small red eggs of the dog tapeworm, now known as Dipylidium caninum,
through a small wound into the abdominal cavity of a pup. One month later, he
claimed to be able to find there small tapeworms and adduced this observation
as in favour of his views 159. Whereas, in general, his hypothesis that worm s
arose from eggs was correct, his experiment was totally in error and the worms
he found, in retrospect, had nothing whatever to do with the ova h e
administered.
The concept of heterogony, however, led to an extremely important observ-
ation in 1790 by the Dane, Peter Christian Abildgaard. Abildgaard noticed that
a cestode worm which lived in the intestine of the little fish known as a
stickleback had no reproductive organs but bore certain resemblances to tape-
worms that he had seen in mergan sers and other fish-eating birds. He wondered
whether the worms in the fish cou ld be an immature form of the bird parasite so
he decided to test this hypothesis:
I collected a great number of stickleback fishes and for three days I fed those to two
ducks. After another three days I killed the ducks and opened their intestines. In one
of the duck's intestines I found 63 pieces of the tapeworm from the fish; they were all
living and more active and faster in their movements than those taken from the belly
of the fishes. They had the same length and shape as in the before-mentioned seabirds.
In the other duck, I found only one tapeworm which was living. 1
This epochal observation was the first successful experiment designed t o
elucidate the life cycle and transmission of an internal parasite.
Voices like his, however, were largely crying in the wilderness. As thousands
of animals were examined for the presence of parasites and as the number o f
known entozoa became larger and larger, helminthology became separated from
zoology and was treated as a distinct discipline. It became mere descriptiv e
enumeration hardly concerned at all with the life-histories and development of
the animals that were so carefully registered. Helminthologists were content to
point out the inadequacy of earlier attempts to explain the presence an d
acquisition of entozoa and returned to the convenient theory of spontaneou s
generation. This trend seemed to be supported by the discovery that many cysts
were verminous in nature (described in chapter 12) but were manifestly devoid
of reproductive organs as were the microscopic organisms now known a s
cercariae that had been discovered by OF Müller in 1773 and which h e
classified as belonging to the "Infusoria" 136.
THE FIRST QUARTER OF THE NINETEENTH CENTURY
Some of the foremost helminthologists of the early nineteenth century including

Rudolphi and Bremser continued to proclaim the doctrine of spontaneou s
generation. Rudophi, for example, discovered the tapeworm now recognized
as Echinococcus granulosus and concluded that it arose from the intestina l

epithelium172. Bremser considered it very improbable that eggs could b e
transmitted through the medium of food, water or air in the case of intestina l
worms and believed that this was even more so in the case of hydatid cyst s
which appeared to have no access to the external environment 25. In support of
this thesis, he cited the experiment of Schreiber 173 who fed a polecat for six
weeks with milk containing eggs of various species of intestinal worms, ye t
when it was killed, not a single worm was found. Furthermore, the acceptance
by these authors of the claims by Kerckringiu s85, Brendel26 and Doloeus 47, Reim
and others that intestinal worms had been found in the bowels of newbor n
children and even in the fetus seemed to settle the point. Thus, Bremser wrote
in 1819:
The original formation of these worms, in my opinion, takes place in the following
way. A part of the intestinal mucus, the living unformed substance, coagulates
forming a more solid mass which covers itself by an epidermis and then lives its own
life. Subsequently the head is formed and ultimately the generative organs also
appear.25
Nevertheless, critical observations continued to be made which would lead
to a turning of the tide. CL Nitzsch in Germany took up the study of th e
organisms discovered by Müller and which Müller had placed in the genu s
Cercaria. Nitzsch noticed that many of these cercariae transformed into a
"pupa" or else "encysted" on foreign bodies and he also recognized a resem -
blance between the anterior part of the body of these organisms with flukes. He
was not able to put these pie ces of information together correctly, however. He
assumed that the pupal stage merely signified the termination of life 148 and
concluded that a cercaria was a combination of a fluke with a vibrio, which he
believed provided the characteristic tail of the cercaria 149.
At the beginning of the winter of 1817-1818, a momentous discovery wa s
made by the German, Ludwig Bojanus. While dissecting some snails obtained
from a fresh-water pond, he noticed that s ome cercariae crept out of motile sacs
in the viscera of the snails and concluded that they were probably generate d
within them. He called these sacs "royal yellow worms":
When the Lymnaea [snails] were taken from the dish, a very large number of royal,
yellow, living, but in movement very indolent, cylindrical worms (Distomata?) were
found in many of them....In the yellow worm one saw, under the microscope, active
movements which came from the enclosed winding animals....Some of the animals
succeeded, finally, at various places, in breaking through. All that slipped out by
themselves had the appearance of....cercariae.21
It caused much astonishment that cercariae were not derived from parent s
resembling themselves, but came from these peculiar, royal yellow worm s
(subsequently called Redia by de Filippi 57). Oken, in whose journal Bojanu s
published news of his discovery, re marked that "observations of this kind make
one dizzy"151. With great perspicacity, he went on to add "one might lay a wager
that these cercariae are the embryos o f distomes"152. There, however, the matter
was to lay for some years.
In the year after Bojanus published his observations, another importan t

phenomenon was described, although its relevance to the life cycles of certain
parasitic worms was not immediately recognized. The German, A von Cham-
isso, showed that in the Salpae, a form of marine animal, free individuals and
individuals bound together in chains alternated with one another in eac h
successive generation. To this phenomenon, Chamisso gave the name "Altern-
ation of Generations" 34. This theme was to be taken up again and applied t o
parasitic helminths nearly 25 years later by Steenstrup, as will be described in
the next section.
THE SECOND QUARTER OF THE NINETEENTH CENTURY
Criticism of the theory of spontaneous generation began to gather apace. In his

review of worms in 1829, the English surgeon, William Rhind, wrot e
disparagingly:
If we admit that a complex worm could be formed by spontaneous action of
combination of animal particles, there would be no end to the extension of the theory.
A field of meadow gas, by the spontaneous arrangement of its particles might produce
an ox, or the fermenting dunghill, charged with animal particles in abundance, might
be the matrix from whence springs the hog that feeds on it. 170
Likewise, one wit, in commentating cynically on the improbable spontaneous
generation of dioecious worms, wrote:
two clots must consult together in order to determine into what they shall become
transformed. Without this millions of males might be formed without a corresponding
female, and millions of females be condemned to live and die in single blessedness. 48
Pari passu with comments like this, important observations of trematode s
continued to be made which would eventually allow all the pieces in the puzzle
to fall into place. In 1827, CE von Baer confirmed Bojanus's observations and
showed that cercariae developed from "germ granules" within the royal yellow
worms or "germinating tubes" (rediae) 10. Several years later (1831), Mehli s
discovered that the eggs of certain flukes contained a larva which in shape and
ciliation resembled some of the known "Infusoria" for he saw an infusorian-like
embryo slip out of the eggs of worms then known as Monostomum flavum and
Distomum hians 129. This observation was confirmed in the following year by
von Nordmann in Helsinki, Finland, who speculated that these embryos:
always sojourn during their first life period in water, and subsequently enter the body
of some animal where they lose their eye-specks and become sexually mature. 150
Similar observations were report ed in 1837 by Creplin 42 who, incidentally, had
confirmed in 1829 Abildgaard's reports on larval tapeworms in fish and their
maturation after ingestion by birds 41.
The next important link in the chain of evidence concerning these trematodes
was furnished in 1835 by the German, Carl von Siebold, in present-day Poland.
Von Siebold examined large numbers of the fluke, Monostomum mutabile ,

which lived in the orbital cavities of geese. Like Mehlis, he noted the hatching
of ciliated larvae (now called miracidia) from the eggs and watched the m
swimming around in water. After a wh ile, they died and disintegrated, each one
releasing from its interior a motile, cylindrical body with two short latera l
processes and furnished with a pharynx and simple gut. Von Siebold realized
that these organisms were closely related to the rediae (or cercaria-sacs) that
he had seen before in snails. Although he was not able to actually witness the
process, he theorized that adult trematodes may produce eggs from whic h
larvae hatch, swim around to find an appropriate snail host, penetrate th e
tissues of the mollusc, then die releasing rediae containing cercaria 174. Shortly
afterwards, von Siebold made another important observation when he showed
that some cercariae such as Cercaria echinata encysted in snails 175. It
remained, however, for Steenstrup in 1842 to put all these disparat e
observations together, as will be detailed below.
Progress in the understanding of the life cycles of cestodes, and especiall y
nematodes, lagged somewhat behind these discoveries concerning trematodes.
In the same year (1835) that von Siebold correlated miracidia with rediae, he
made an important discovery about tapeworm eggs when he found that the y
contained an embryo furnished with six hooklets within them 174, but he did not
follow up the implications of this finding. Speculation about the life cycles of
tapeworms and other helminths was undertaken by Eschricht. After recalling
Abildgaard's experiments with fish worms and bird tapeworms and remarking
on the great fertility of intestinal worms, he wrote in 1841:
Their limitation to distinct species is too well ascertained, their anatomy too
complicated, and their fertility too striking, not to force the conviction upon us, that
intestinal worms are the offspring of other similar worms. 54
He then went on to add:
If this view be correct, the entozoon will spread by a kind of emigration....The life
history of Entozoa must be considered as analogous on the whole to that of the
parasitic larvae of ichneumon or bot flies but that each instance demands a special
explanation on account of the complexities possibly introduced - the various asexual
parasites so frequently met with e.g. Trichina spiralis must be regarded as immature
forms retaining their primitive larval situations.54
Many of these ideas were formalized in the following year (1842) when the
Dane, Johannes Japetus Steenstrup, publ ished his seminal work entitled On the
alternation of generations; or, the propogation and development of animals
through alternate generations: a peculiar form of fostering the young i n
lower classes of animals 186. Steenstrup brought together numerous, divers e
observations and proposed a unifying hypothesis to explain the various phen-
omenona. Steenstrup considered first coelenterates (medusae and clavifor m
polyps), then pelagic tunicates (Salpae), and finally trematodes. In all of them
he found a common phenomenon whic h he summarized in the following terms:
An animal bears young which are, and remain, dissimilar to their parent, but bring
forth a new generation, whose members either themselves, or in their descendants,
return to the original form of the parent animal. 186

Thus, Steenstrup believed that just as the polyp originating from the ovum of
a medusa represented an alternate generation, so did the redia and cercariae
derived from the miracidium of a fluke. He observed that in some of th e
Trematoda, the latter generations remained within the earlier forms until they
attained full development, whereas others forsook them sooner to becom e
free-swimming then underwent a complete metamorphosis. Steenstru p
conjectured that cercariae might penetrate into other animals, lose their tails
and become adult flukes. He knew that Cercaria echinata encysted in snails
so he extracted them at various inter vals after encystation and observed typical
fluke-like forms. He was mistaken, however, in supposing that the worm s
matured in the body of the snail host. This idea was contradicted by vo n
Siebold who maintained that further developm ent could not take place until the
encysted trematodes were transmitted to some other host, for example, when
they were devoured together with the snails by an animal 176,177. Von Siebold
came to realize, however, that many encysted cercariae were located i n
organisms which would never be consumed by another animal in which a n
adult fluke would develop. This led him to the concept of "stray" worms ,
doomed to perish, which was to bedevil his views on the relationship between
cystic worms and tapeworms. Likewise, Dujardin, who accepted spontaneous
generation at first, considered that cercariae would never become adult worms
once they had been shut in an "excreted prison" 49.
Steenstrup failed to make the c orrect deductions with regard to cestodes. He
conjectured that cystic worms were early stages in the development o f
helminths that were unknown to him. He argued that they should no longer be
classified as a separate group but he did not connect cystic worms wit h
tapeworms. This is rather surprising as not only had Pallas and Goeze in the
previous century recognized the relationship, but a number of more contemp-
orary authors including Nitzsch, FS Leuckart and F Müller had urged aband-
onment of this unnatural cleavage of cystic worms from tapeworms.
Nevertheless, Steenstrup's promulgation of the doctrine of "Alternation of
Generations" put others on the right tr ack. Dujardin in France in 1845 asserted
that cystic worms were formed by the germs of tapeworms which, instead of
going into the intestines of their natural hosts, somehow arrived in the tissues,
and under the influence of an unusual dwelling-place, developed abnormally
to become "monstrous" cystic worms 49. At about the same time, von Siebold
began to express similar convictions. Initially, von Siebold held the correc t
view that cystic worms were simply undeveloped, larval tapeworms 177.
Moreover, he thought that the adult and larval forms of the worms must b e
found in different animal hosts since the two forms rarely occurred together.
He then modified this theory and began to move down the wrong path, con-
tending that cystic worms were strayed larval tapeworms which becam e
dropsically degenerated when they reached aberrant sites 181.
Little advance in understanding of nematodes was achieved during this period

although some attention was paid to the mode o f transmission of Guinea worm.
With the realization at this time that the adult worms released large numbers
of embryos, there was conside rable speculation that transmission occurred via
water. In 1838, Forbes tried to transmit infection by administering orally t o
two pups larvae that had been obtained from a human patient; he found dead
worms in the gut thus giving credence to some earlier suggestions based upon
epidemiological evidence that infection was acq uired by worms penetrating the
skin59.
THE THIRD QUARTER OF THE NINETEENTH CENTURY
The second half of the nineteenth century opened with a flurry of speculation
and activity concerning tapeworms and cystic wo rms. Following the statements
of Dujardin and von Siebold, the Belgian, PJ van Beneden, theorized that the
head of a tapeworm is produced from the eggs of a tapeworm and conjectured
that if the egg reached the gut of a suitable animal host, then the jointed adult
tapeworm would mature. On the other hand, he postulated that if the egg found
its way into the gut of an unsuitable host, then the larva would develop but the
hind part would become inflated and the head would sink into it, thus forming
a cysticercus13. Van Beneden was correct in deducing that bladderworms were
larval tapeworms but was wrong in his belief that adult worms would develop
directly from eggs when ingested by an appropriate host. In any case, h e
provided no hard evidence to substantiate his views.
It was at this point that a major wind of change blew upon the scene .
Friedrich Küchenmeister in Germany became interested in the problem o f
cystic worms and tapeworms and began to experiment in order to solve th e
problem. Although there had been previous essays into experimentation i n
helminthology, some of which had been successful, by investigators such as
Pallas, Abildgaard Creplin and Herbst, none had been as dramatic as Küchen-
meister's were to prove, nor did they achieve such widespread recognition .
Küchenmeister began with two of the most easily accessible bladderworms,
Cysticercus pisiformis, of the rabbit and C. fasciolaris of the mouse. In 1851,
Küchenmeister fed a large number of C. pisiformis to foxes which are natural
predators of rabbits, then recovered many young tapeworms which he initially
called Taenia crasscipes (= crassiceps = Taenia pisiformis)92,93. He wrote in
Gunsburg's Zeitschrift für klinische Medicin :
Preliminary communication: I hereby give notice, in order to achieve priority for my
scientific observations and the further development of this subject, that between 18
March and 19 April 1851, I recovered 35 individual Taenia crasscipes from foxes
that had been given approximately 40 Cysticercus pisiformis of rabbits 22, 15 and
8 days and 30 hours previously.92
Küchenmeister then gave C. fasciolaris to a cat and again succeeded in rearing
tapeworms that were rapidly approaching maturity 94. Furthermore, he showed

that when cysticerci were fed to an inappropriate host, the cysticerci died and
no development took place. He concluded that cystic worms were not strayed,
dropsical tapeworms as portrayed by von Siebold, but were tapeworm larvae
that were an essential stage in the development and maturation of taenia:
the larva (Cysticercus) is not a wandering strayed dropsical tapeworm nurse, in the
sense of Steenstrup's Alternation of Generations, but a tapeworm larva provided with
a temporary organ, probably functioning as a reservoir of nourishment. 95
Küchenmeister's first reports were received with some scepticism, partl y
because he changed his identification of the tapeworms that he reared in foxes
several times. Shortly afterwards (1853), however, he successfully reare d
tapeworms in dogs from Cysticercus tenuicollis and from Coenurus cerebralis
of sheep96.
Von Siebold lost little time in repeating Küchenmeister's experiments. I n
1852 he confirmed the metamorphoses of C. pisiformis and C. fasciolaris then
reported the same phenomenon with Coenurus 178,179. For a number of years
von Siebold clung to his theory that cystic worms were degenerate, straye d
worms which would develop properly when transplanted to the correct site .
Moreover, he also believed that, with the exception of echinococci, all th e
cystic worms were derived from on e species of tapeworm, Taenia serrata, the
nature of the cysticercus depending upon the host in which it developed 181.
These observations also stimulated von Siebold to begin feeding exper -
iments with hydatid cysts in 1852. He obtained cysts from sheep, saturate d
milk with echinococcal scolices, then fed it to a number of dogs. Dogs were
killed after varying periods and von Siebold found innumerable small adul t
tapeworms, which were producing ova, in the intestines 180. Von Siebold's
experiments were repeated and his results confirmed by Küchenmeiste r
(1853), Wagner (1854) and others who used hydatid cysts obtained fro m
sheep, pigs and cattle. It was not until 1863, however, that Naunyn succeeded
in rearing adult echinococci in the intestines of a dog fed with hydatid cys t
material obtained from a human 145.
To prove beyond all doubt that cystic worms were necessary steps in th e
development of tapeworms, however, it was also necessary to show thei r
development from taeniid eggs. Such an experiment was first undertaken by
Küchenmeister with the parasite he knew as Coenurus cerebralis (= Taenia
multiceps). First he obtained coenuri from sheep then he administered them to
a dog in order to obtain mature proglottids of the tapeworm. These in tur n
were fed to a healthy sheep on 25 July 1853. Sixteen days later, the shee p
became vertiginous and when it was kill ed three days later, small coenuri were
found on the surface of the brain 96. In collaboration with Haubner, Küchen -
meister obtained similar results with Cysticercus pisiformis , C. tenuicollis and
C. cellulosae 99. The first person to have demonstrated the generation of C.
cellulosae, in fact, was van Beneden. In 1853, he fed large numbers of Taenia
solium eggs to a pig then slaughtered it four and a half months later at which
time he found a large number of cysticerci 14. At around the same period ,
Leuckart was able to produce C. fasciolaris in the livers of mice after feeding
these animals with eggs from T. crassicollis from cats. It was not until 1867,
however, that Leuckart produced hydatid cysts in suckling pigs after feeding
them with ova of Taenia echinococcus (= Echinococcus granulosus )112.
Another observation which helped finally to spell the lie to von Siebold' s
concepts of "strayed tapeworms" flowed from t he studies in 1852 of the Prague
zoologist, von Stein. Von Stein examined the development of a small blad -
der-worm in the larva of the meal-worm, Tenebrio molitor, and demonstrated
that, as Goeze had already proven in the case of C. fasciolaris of mice (but
which had been ignored), the caudal vesicle was formed first and then th e
scolex developed within it, whereas von Siebold believed that the scolex was
formed first and that the tail then underwent hydropic degeneration 187. This,
together with an increasing m ass of experimental observations made it abund-
antly clear that development of these cestodes is divided between two kinds of
animals. In one, the definitive host, the adult tapeworm is found, while in the
other, the intermediate host, some form or other of an intermediary stag e
occurs.
Although, as indicated above, Küchenmeister was able to produce C. cell-
ulosae by feeding Taenia solium eggs to pigs, success did not attend his efforts
to generate the adult tapeworm w hen he fed cysticerci to dogs. Others, such as
von Siebold and May, claimed to be able to do so, but Küchenmeister (quite
correctly) did not believe them. He ther efore determined to examine the effects
of administering C. cellulosae to humans under the sentence of death. In 1854,
in collaboration with two medical colleag ues, he induced a convicted murderer
(unknowingly) to ingest over 70 cysticerci during the several days prior t o
execution. Forty eight hours after de ath, he found a number of small, immature
tapeworms in the intestine of the condemned man 97. In the same year that
Küchenmeister reported these observations (1855), Aloys Humbert produced
a patent infection in himself; three months after consuming 13 C. cellulosae,
he began to pass T. solium segments79. A similar experiment with like result
was undertaken by Leuckart in the following year 108. In late 1859 and early
1860, Küchenmeister had an opportunity to repeat his original experimen t
except that on this occasion he was able to infect the prisoner twice severa l
months before execution. On this occasion, he recovered eleven tapeworms,
the largest of them being five feet in length 98.
It took a little time to define the life cycle of the related human parasit e
Taenia saginata. In late 1861 and early 1862, Leuckart undertook a number
of experiments in which he fed T. saginata segments to calves and eventually
recovered the cysticercus known as C. bovis 111. Leuckart's findings were soon
confirmed by Mosler and many others. No-one has ever gone to Küchen -
meister's lengths and fed C. bovis to criminals in order to recover adult T.
saginata from the intestines at autopsy. In 1870, John Oliver in India in some
poorly-controlled experiments claimed to produce patent infections after feed-

ing C. bovis to three human subjects 153, then Perroncito in Italy in 187 7
administered cysticerci to a subject who began to pass segments eight weeks
later and from whom an adult worm over four metres long was recovered after
treatment with anthelmintics 163.
Despite the mass of accumulated evidence, there were still some recal -
citrants. Pouchet and Verrier in 1862 attacked the whole concept of the cystic
migration of tapeworms, claiming that all these experiments were "to o
successful". Despite all argument to the contrary, they remained obdurate ,
writing:
we cannot believe that a microscopic embryo of a taenia enclosed in the intestines of
a sheep can make for itself a passage up into the brain of the ruminant, and then
undergo transformation into a vesicle, which engenders numerous scolices. 166
Nevertheless, this was the last gasp of the sceptics and the views o f
Küchenmeister and others became generally accepted.
In reviewing all of these events, and in particular Küchenmeister's con -
tribution, Leuckart wrote a few years later:
It was only with introduction of Helminthological experiment that a new path was
opened to the field of knowledge....It was not merely the proof that bladderworms
which had for so long formed an impregnable fortress for the theory of spontaneous
generation, were really the immature stages that excited so wide an interest, but it
was also the circumstance that Küchenmeister....did not discover it merely by chance,
but by direct experiment, by the method of feeding, which is so easy to control and
repeat.116
It must be remarked, however, that the feeding experiments of Küchenmeister
and others were not designed primarily to refute the doctrine of spontaneous
generation55. This was not an issue in the minds of these investigators. Rather,
they were interested in defining the relationship between cystic worms an d
tapeworms. Nevertheless, these studies inevitably had a critical effect on the
tenability of the hypothesis of spontaneous generation.
The successes with these tapeworms did not similarly attend at this tim e
attempts to elucidate the life cycle of the other tapeworm of major huma n
importance, Diphyllobothrium latum . Indeed, such experiments as wer e
undertaken were positively misleading. A number of workers includin g
Schubart, Kölliker, Knoch, Leuckart and Bertolus independently observed the
hatching of larvae from D. latum eggs but their subsequent fate remained a
mystery. Knoch claimed in 1862 that there was direct transmission from one
vertebrate host to another when he asserted that he had found diphyllobothria
in the intestines of dogs after administration of ova whereas he had bee n
unable to infect potential intermediate hosts 87.
Trematodes did not evoke interest and activity comparable to that seen with
the cestodes in the third quarter of the nineteenth century although severa l
important contributions were made. La Valette de St. George provide d
important information in 1855. He showed that when tailed, non-encyste d
cercariae were administered orally to experimental animals they failed t o
develop, yet when certain encysted cerc ariae were ingested, the larvae escaped
rapidly from the cyst walls and matured in the gut. Thus, Cercaria echinifera
was converted very rapidly in the intestine of warm-blooded animals int o
Distoma echinfera while C. flavum became transformed into Monostomum
flavum in finches and sparrows 196. Likewise, G Wagener in 1857 proved that
the original hypothesis of von Sieb old was correct when he witnessed in snails
the metamorphosis of the miracidium of Distoma cygnoides of the frog into a
redia204.
Investigations of the life cycles of nematodes during this period wer e
sporadic and did not follow a common theme. The most significant advances
were made with Trichinella spiralis. The larvae of this parasite had bee n
discovered in 1835 and although von Siebold had suggested that they wer e
intermediate stages awaiting tran sfer to another host, it was uncertain how this
was achieved. In 1851, however, Herbst reported a major discovery. A fe w
years earlier, he had tried without success to transmit infection to a cat b y
inserting cysts subcutaneously. In November 1850, he fed some trichinou s
flesh obtained from a dead badger to three dogs then identified trichinellae in
their muscles at variable intervals thereafter 75. This report was treated wit h
much reservation, however, and the problem was not solved for anothe r
decade. After a false start in which Leuckart concluded that Trichuris trichiura
adults developed in pigs after they were fed trichinous flesh 109, Virchow in
1859 discovered the adult T. spiralis in the intestines of a dog three and a half
days after it was fed with trichinous meat 200-202. This finding was confirmed by
Leuckart110, then shortly thereafter, Zenker identified the adult worms in th e
small bowel of a human 212. All three of these investigators demonstrated the
migration of newborn larvae, thus making the complete life cycle clear (se e
chapter 22).
Some desultory experiments were undertaken with Ascaris lumbricoides
during this period. Davaine faile d to infect a cow with A. lumbricoides but did
observe that larvae hatched from the eggs and were passed in the faeces when
ova were fed to rats45. Davaine thought it unlikely that an intermediate hos t
was required for transmission, but this view was challenged by others, partic-
ularly in view of a number of negative experiments: Mosler in 1860 failed to
infect himself by swallowing eggs 134, while Leuckart in 1867 was unable t o
infect a variety of animals with embryonated A. lumbricoides eggs or a horse
with Ascaris megacephala (= Parascaris equorum), a dog with Ascaris
marginata (= Toxocara canis), or a cat with Ascaris mystax (= Toxocara
cati) ova112. Nevertheless, Unterberger in 1868 showed that Ascaris maculosa
(= Ascaridia columbae) of the pigeon developed directly while Henry in 1873
demonstrated direct transmission of T. cati to cats.
Success was achieved, however, with such challenge infections with on e
important nematode parasitic in humans, Enterobius vermicularis. In 1865,
Leuckart and three of his students swallowed a few dozen eggs of this worm
that had been kept in a humidified incubator. Over the next several weeks, they
all recovered adult parasites from their faeces 112.

An important landmark also occurred in 1865 when Leuckart reported that
the embryos that had hatched from ova of the nematode, Cucullanus elegans,
a parasite of perch, developed in minute water crustaceans. In 1869 ,
Fedchenko made use of Leuckart's observations and himself made a majo r
discovery concerning the transmission of Dracunculus medinensis . In July of
that year, a doctor brought him a Guinea worm in a small bottle. In th e
surrounding water, Fedchenko noticed some small crustaceans, Cyclops, in
which he saw larvae similar to those of the Guinea worm. He therefore under-
took an experiment in which he added fresh embryos to parasite-free Cyclops
and noted that they were ingested by the crustaceans. Further, he observed the
moulting and development of these larvae within the crustaceans over the next
several weeks. He was unable to complete the life cycle but speculated tha t
infected Cyclops may be ingested by humans with release of the larvae in the
gut and their subsequent development in the tissues 56.
The effects of all these experiments on the doctrine of spontaneous gen -
eration of worms must also be viewed in the light of two other factors which
had become apparent by this time. The first was the development of histo -
pathology which climaxed in the cellular pathology of Virchow. Vircho w
expounded the dictum "omnis cellula e cellula" (all cells out of cells). Th e
corollary was that an organized being could not be formed out of formles s
fluid. Thus, he wrote in 1859:
Just as little as we can now admit that a Taenia can arise out of saburral [= foul]
mucus, or that of the residue of the decomposition of animal and vegetable matter an
infusorial animal....can be formed, equally little are we disposed to concede....that a
new cell builds itself up out of any noncellular substance. Where the cell arises, there
a cell must have previously existed....in pathology we can now go so far as to
establish, as a general principle, that no development of any kind begins de novo and
consequently as to reject the theory of spontaneous generation. 199
The other factor was the grad ual acceptance of the value of statistical methods
in medicine and biology. Statistics had been popularized by Laplace in hi s
Philosophical Essay on Probability then was put to use by Pierre-Charle s
Louis in his 1828 Researches on the Typhoid Affection or Fever . Not only
was this eventually to aid in the interpretati on of the results of experimentation,
but the chance element in transmission, which had previously seemed to be a
point in favour of spontaneous generation, now appeared to be an example of
a general biological law. Thus, the great fecundity of worms was now seen as
a response to the low probability of continuity and survival of the species.
The coup-de-grâce was finally delivered to the theory of spontaneou s
generation during this period. The theory had gradually become intermingled
with the problems of fermentation and putrefaction which were generally re-
garded as the result of some spontaneous chemical change in fermentible or
putrescible matter. For many years, the influence of air on fermentation an d
putrefaction had been the subject of much discussion. A number of important
experiments were made by Schulze, S chwann, Helmholtz, Schroeder and Ber-
nard, but the critical experiments were those of Louis Pasteur which wer e
published in 1860 and 1861.
In 1858, however, FA Pouchet had begun to present a series of papers to the
Academy of Sciences in Paris in which he claimed to have proved th e
existence of spontaneous gene ration, which he called heterogenesis, by exper-
iments using flasks, air, hay, water and heat. In 1859, he published his book,
Hétérogonie, in the preface of which he explained how he had come to study
the phenomenon:
when by meditation it was evident to me that spontaneous generation was one of the
means employed by nature for the reproduction of living things I applied myself to
discover the methods by which this takes place.165
Pouchet believed that spontaneous generation required the presence of a vital
force coming from pre-existin g living matter; he did not believe that life could
be generated from non-living matter.
Meanwhile, Pasteur had become interested in the problems of fermentation.
In 1857 he isolated a ferment (since shown to be bacterial) that soured milk,
then he showed that yeasts or moulds on grapes were necessary for th e
fermentation of sugar into alcohol in the making of wine. These observations
convinced him that fermentation and putrefaction were vital processes; thi s
view compared starkly with that of Baron von Liebig, the premier authority on
the matter, who regarded fermentation as being "of the nature of death". Like
Spallanzani, Pasteur believed that organisms associated with fermentatio n
came from the air. The major criticism of Spallanzani's work had been that in
boiling his sealed flasks, he had also altered in some way the contained air .
Pasteur therefore set about proving the crux of his hypothesis, that is that air
carried germs. First, he showed that germs or bodies resembling them existed
in the air by filtering air through gun-cotton then examining the sedimen t
microscopically; these were similar to the organisms that had already bee n
observed in fermenting substances. The next problem was to demonstrate that
these germs were alive. This he did by showing that sterile infusion s
containing air which had been heated became infected if dust from the air was
introduced into it. He then took a series of flasks containing an infusion o f
fermentable substances but in which the neck of each flask was very narrow
and long, more or less horizontal in orientation, and drawn out into an "s "
shape. The flasks and their contents were then heated to boiling point for a
long period. Even though they were then left for months, the contents did not
ferment. When the neck was seve red, however, fermentation became apparent
within a few hours and organisms were demonstrated in it under the micro -
scope.
These experiments were brought together in Pasteur's Mémoire sur les
corpuscles organisés qui existent dans l'atmosphère. Examen de la doctrine
des générations spontanées which was published in 1861 162. The success of
these experiments was the final turning point and marked the downfall of the
doctrine of spontaneous generation, although a vociferous rear-guard actio n
was fought for a number of years by a few workers including Pouchet, Häckel,
and the English physician, Charlton Bastian, who a few years earlier had des-
cribed in detail the anatomy of the Guinea worm. The word "biogenesis" was
coined by TH Huxley80 in 1870 to express the hypothesis that living matte r
always arises by the agency of pre-existing living matter, while the ter m
"abiogenesis" was used for the opposite view. Perhaps the most extreme sup-
porter of abiogenesis during this period was Bastian who, in a book of greater
that one thousand pages published in 1872, promulgated the doctrine o f
"archebiosis", i.e. that animals can be gen erated spontaneously from non-living
matter12. Bastian continued the fight until his death in 1915. He is a classi c
example of the principle enunciated by Max Planck:
A new scientific truth does not become accepted by way of convincing and
enlightening the opposition. Rather, the opposition dies out and the rising generation
becomes well-acquainted with the new truth from the start. 164
THE FINAL QUARTER OF THE NINETEENTH CENTURY
It took some time for the dust to clear and for the controversy over spont -
aneous generation to be seen in perspective. In reviewing the whole question
in 1881, the learned The New Sydenham's Society's Lexicon of Medicine and
the Allied Sciences summarized the problem thus:
This subject has attracted much attention of late years. Pouchet in France, Häckel in
Germany and Bastian in this country have been its most prominent supporters....The
most ingenious apparatus and modifications of experiments have been suggested by
both sides....Unfortunately, the evidence that one side regards as irrefutable is either
entirely ignored or met with a direct denial by the other. The results of one's
experiments are the negative ones of his opponent....On the whole, it may be said
that no conclusive proof has been obtained of the occurrence of abiogenesis. 167
In the event, the proponents of spontaneous generation gradually disappeared
from view and the doctrine of spontaneous generation became abandoned by
biologists. Certainly, no experimental helminthologists still supported th e
concept. All their time and energy was devoted to elucidate the complex and
mysterious life cycles of many parasitic worms.
The first major success came with Fasciola hepatica when Thomas in
England190,191 and Leuckart in Germany113-115 independently worked out the life
cycle of this parasite between 1879 and 1882. In a series of epidemiological
studies and laboratory experiments, both authors discovered that miracidi a
hatched from Fasciola eggs invaded Lymnaea snails and there
metamorphosed into brood sacs or sporocysts in which rediae subsequentl y
developed. The latter in turn developed cercariae within them. Bot h
investigators were uncertain as to the subsequent course of events, postulating
that either the snails containing cercariae were ingested or that cercaria e
escaped from the molluscs, encysted on grass, then were ingested. The matter
was not settled until 1892 when Lutz showed that Fasciola cercariae were
liberated from damaged or dead snails then en cysted on plant or other material.
He then demonstrated that when these cysts were fed to guinea pigs, the life
cycle was completed 123. These findings with Fasciola led to an intensive
search for a snail intermediate host for Schistosoma haematobium , but as is
related in chapter 8, nothing was found and controversy continued until well
into the next century as to whether an intermediate host was necessary.
The remaining cestode of major human importance of which the life cycle
was obscure was Diphyllobothrium latum . A partial solution to this problem
was provided during this period by Max Braun in the eastern Baltic region. He
found immature worms, the head of which resembled that of the broa d
tapeworm, in a variety of fresh-water fish (pike, perch, ruff and burbot). H e
then fed in 1881 these parasites to dogs and eventually recovered adult D.
latum 22, then repeated the experimental process in humans 22,23 . The second
intermediate host was now clear, but how the fish became infected remained
unsolved for another 35 years.
During this period, observations were made upon the life cycles of certain
cestodes of lesser significance for humans. Grassi found in 1887 tha t
Hymenolepis nana could be transmitted directly from one definitive host to the
next68. In 1889, Grassi and Rovelli showed that Dipylidium caninum
developed in fleas70. Three years later, they showed that Hymenolepis
diminuta developed in a variety of arthropod intermediate hosts 71.
Pieces were put into place partially or completely during this period for a
number of nematodes. In 187 6, Leuckart reported that when he had fed ova of
Trichuris affinis to a lamb and T. crenatus eggs to pigs, he was able to recover
subsequently adult worms 112 then Railliet in 1884 reported a simila r
phenomenon with dogs and T. depressiusuculus. This was applied to the
human parasite, T. trichiura, in 1886 when Calandruccio successfully infected
himself after swallowing eggs, the results being reported by Grassi 67. In the
same year, Calandruccio likewise i nfected a boy with Ascaris lumbricoides by
administering embryonated ova to him. This experiment was also reported by
Grassi67, who had claimed a similar result in a few years earlier 66, although that
claim must be viewed with considerable circumspection in view of th e
unusually short incubation period that he reported.
Similar attempts were made to transmit hookwor m infection. In 1878, Grassi
and his colleagues failed to infect humans b y ingestion of either hookworm ova
or larvae (presumably first-stage), nor could they infect a dog by administering
eggs orally69. In 1886, however, Leichtenstern undertook feeding experiments
and reported that he was able to infect humans by administering third-stag e
hookworm larvae orally 102, a feat which Wilms repeated in 1897 with th e
similar parasite, Strongyloides stercoralis 206. A far more important even t
occurred when the German, Looss, working in Egypt reported in 1898 tha t
infective larvae were able to penetrate the intact skin, migrate to the gut and
mature119. This was greeted with considerable scepticism, but several year s
later he was able to prove his point as will be described in the next section.
Meanwhile, a discovery of great significance was made in 1877 by th e

Englishman, Patrick Manson, working in China. The scene was set for hi s
epochal discovery by the finding in 1872 by Lewis that the embryonic forms
of the filarial parasite, Wuchereria bancrofti, circulated in the periphera l
blood. Manson puzzled about the fate of these larvae and tried to ascertai n
their destiny. He deduced that the most likely means of exit was via a
blood-sucking insect, and with a stroke of luck selected mosquitoes as th e
most likely candidate. He thereupon procured some mosquitoes and fed them
upon his gardener who happened to have a microfilaraemia. He then examined
the mosquitoes at daily intervals and found that the parasites metamorphosed
in the insects' abdomen 128. Manson was incredibly lucky in that he knew little
about mosquitoes and happened by chance to use a species that wa s
susceptible to infection. He was incorrect, however, in his surmise tha t
mosquitoes flew off to stagnant water to deposit their eggs and there died ,
releasing larvae which reached the human host via drinking water. Manson's
observations on the uptake and development of microfilariae in mosquitoe s
were soon confirmed by Lewis and S ilva Araujo, but it was not until 1900 that
the final link in the chain was put in place. Thomas Bancroft in Australi a
infected mosquitoes, that had been reared in the laboratory and were free o f
parasites, by allowing them to feed on an infected person then sent the spec-
imens to Manson in London. Manson passed them on to George Low wh o
prepared histological sections of the mouthparts and demonstrated th e
infective larvae in the proboscis 122. Almost immediately afterwards, Jame s
independently made similar observations 81.
THE FIRST QUARTER OF THE TWENTIETH CENTURY
At the turn of the nineteenth century, great interest centred on Looss's claim of
1898 that hookworm larvae could p enetrate the intact skin. As indicated in the
preceding section, this report was greeted with considerable scepticism. I n
order to prove his point, he applied filariform larvae to the skin of a thirteen
year old boy one hour before he was due to have his leg amputated. Immed-
iately following removal of the leg, the exposed skin was excised and histo -
logical sections disclosed larvae in the dermis. Looss reported his findings in
1901 120 , but disbelief was still rampant. He therefore persuaded an hospita l
attendant to allow himself to be infected ex perimentally. After ascertaining that
the person was not infected already, a drop of culture fluid containing infective
larvae was placed on his forearm; hookworm ova were found in his faeces 71
days later, thus proving that the life cycle of this parasite could be completed
in this manner 121.
These observations with hookworm were then applied to the similar parasite,
Strongyloides stercoralis. Van Durme showed with histological studies i n
1901-2 that Strongyloides infective larvae were able to invade the skin o f
guinea pigs50. Over ten years later, Fülleborn took the final step in experiments
with dogs and showed that larvae applied to the skin migrated through the lungs
and then were able to develop into adult worms in the intestines 62.
In 1905, Robert Leiper went to the Gold Coast (Ghana) to further in -
vestigate the life cycle of Dracunculus medinensis . First, he repeated
Fedchenko's experiments and examined the manner in which Cyclops were
infected. He then fed a monkey on bananas contaminated with copepods that
had been infected with guinea worm embryos five weeks earlier. Six months
later, he found five immature Dracunculus in the tissues at post-morte m
examination103. In 1913, Turkhud in India gave a small number of infecte d
Cyclops in water to five "volunteers". Just over one year later, one of thes e
persons developed a clinical infection, although whether this was as a result of
the experimental exposure or was acquired naturally cannot be determined with
certainty193.
By analogy with Wuchereria bancrofti, it seemed very likely that Loa loa
was also transmitted by some form of biting insect. In 1912, Leiper journeyed
to West Africa and fed many type s of arthropods on infected persons. He found
that development of microfilariae occurred in flies of the genus Chrysops 104 but
he did not publish details of the developmental changes. His results wer e
confirmed several years later by Kleine and then by Connal and his wife, th e
latter pair of investigators providing considerable detail 39,40.
Another question that burned in the minds of many helminthologists at this
time concerned the manner of transmission of schistosomiasis. As is discussed
in chapter 8, investigators fell into one of two camps - those that favoure d
direct transmission and those that believed that there must be an intermediate
host. The answer came not from a study of Egyptian schistosomiasis, but from
investigation of Schistosoma japonicum infection that had just been discovered
in Japan. In 1909, Fujinama and Nakamura showed by a series of experiments
using cows that infection was acquired via the skin rather than by the ora l
route 60,61. The events leading up to such infection were described by Miyair i
and Suzuki in 1913. They reported that they had collected snails of uncertain
identity (subsequently shown to belong to the genus Oncomelania) from a
roadside ditch, found that they were free of trematode infections, then exposed
them to S. japonicum miracidia hatched from eggs. They observed that th e
miracidia invaded the snails, developed into sporocysts then ultimatel y
produced and released cercariae. They then exposed the skins of mice t o
cercariae released from naturally-infected snails and a few weeks late r
recovered adult schistosomes from the portal veins of the infected mice 132,133.
These results were then soon confirmed by Leiper and Atkinson 107 and by
Yokogawa210.
In the light of these observations, Leiper then turned his attention t o
schistosomiasis in Egypt. After a rapid series of experiments, he was able t o
report in 1915 that he had infected Bulinus snails with miracidia derived from
terminal-spined eggs (S. haematobium), observed their development through
sporocysts to cercariae in the snails, then infected mice percutaneously an d

recovered adult worms 105. In the following year, he showed that miracidi a
derived from lateral-spined ova (S. mansoni) underwent development in snails
of the genus Biomphalaria 106.
Almost contemporaneously with these e vents, the life cycles of the liver fluke,
Clonorchis, and the lung fluke, Paragonimus, were elucidated. In 1911, th e
Japanese zoologist, Kobayashi, while working i n Korea, found that an immature,
encysted fluke occurred commonly in certain freshwater fish in an area where
clonorchiasis was endemic. He then fed flesh of fish containing these cysts t o
cats and recovered adult Clonorchis from the biliary system 88,89. The mode in
which fish became infected, however, remained a mystery although Kobayashi
suspected that snails may be involved. That this was so was proven by th e
Japanese pathologist, Muto, in 1918. He found a species of snail ( Bithynia, now
called Parafossarulus) naturally infected with several forms of cercariae. H e
used these molluscs to infect fish then fed these fish to dogs and eventuall y
found Clonorchis adults in the biliary tract 138,139.
Kobayashi's discovery stimulated his compatriot, Nakagawa, working in an
area of Taiwan where paragonimiasis was endemic , to search the local molluscs,
fishes, amphibia and insects for the intermediate stages of Paragonimus. In
1914 he found two sorts of en cysted trematodes in crabs of the genus Potamon.
He fed tissues from infected crabs to dogs and eventually recovered adul t
Paragonimus from their lungs 140,141. It was not until 1917, however, tha t
Yokogawa proved which form of encysted larva was the precursor of the adult
Paragonimus 211. Again the problem remained as to the manner in which crabs,
clearly a second intermediate host, became infected. Attempts to solve thi s
problem were confused initially by the uncertainty as to which form of encysted
larva in the crab was really Paragonimus. Independently, and at around th e
same time between 1917 and 1919, Ando 4, Kobayashi90 , Miyairi 131
,
142
Nakagawa and Yokogawa all concluded that snails of the genus Melania (=
Semisulcospira) were probably the first intermediate host.
Following his success with Clonorchis, Nakagawa turned his attention to the
intestinal fluke, Fasciolopsis buski. In 1920, he found that miracidia hatche d
from Fasciolopsis eggs invaded, then developed into sporocysts, rediae an d
cercariae in snails now known as Segmentina haemisphaerula 143. Furthermore,
he noted that the cercariae escaped from the snails and encysted on grass. H e
then infected a dog and pigs with these encysted worms and succeeded i n
recovering adult Fasciolopsis from the intestinal tract; these details wer e
published in 1922 144.
Similar success was achieved with Metagonimus yokogawai . In 1911 Yoko-
gawa showed that trout were the second intermediate host of this infection 209.
Six years later, Muto found that snails of the g enus Semisulcospira were the first
intermediate host of this parasite 137. In 1915, Onji and Nishio showed tha t
certain fish were the second intermediate host of the fluke, Heterophyes
heterophyes 154 but the first intermediate host remained obscure for a number
of years. In 1917, Ciurea found that certain species of fish were the secon d
intermediate host of Opisthorchis felineus 36, but again, the nature of the firs t
intermediate host remained unknown.
During this period, the missing link in the chain of transmission of the broad
tapeworm, Diphyllobothrium latum , was finally put into place. Janicki an d
Rosen in Switzerland attempted to infect fish directly with larvae hatched from
D. latum eggs. When this failed, Janicki examined the stomach contents o f
species of fish that were known to transmit the infection. He found by a process
of exclusion that all fish containing younger stages of the tapeworm ha d
copepods in their gut 82. Likewise, Rosen examined a number of potentia l
primary intermediate hosts without success until he turned his attention t o
copepods. In the body cavity of certain Cyclops, he found oncospheres typical
of D. latum 171. Both investigators came to this conclusion independently in June
1917. In order to complete the life cycle experimentally, Rosen infecte d
copepods by exposing them to tapeworm eggs then six weeks later placed trout
in the aquarium. When the fish were killed s ubsequently, he found plerocercoids
in the musculature 171.
In 1911, Nicholl and Minchin found t hat Hymenolepis nana, in addition to its
direct cycle of transmission, could also be acquired by ingestion of infecte d
fleas147.
THE REMAINDER OF THE TWENTIETH CENTURY
The only helminth infection of major human importance in which the life cycle
was still uncertain at the beginning of the seco nd quarter of the twentieth century
was Onchocerca volvulus. A number of investigators had studied a number of
potential intermediate hosts without success, and in 1917 Robles in Guatemala
had suggested on epidemiological grounds that blackflies of the genus Simulium
may be involved but he offered no definitive evidence. That these flies wer e
indeed the vector was proven by Blacklock in Sierra Leone. He reported i n
1926 that Onchocerca microfilaria were present in the gut of these insects and
he traced their development into infective larvae which migrated into th e
proboscis 17,18. Like most of the other filarial nematodes, this worm has neve r
been transmitted experimentally to humans.
The remainder of the century saw several small points in the life cycles of the
important human parasites tidied up and observations made upon the lif e
histories of a number of worms of lesser signifi cance. With respect to nematodes
of lesser importance for humans, Dyce Sharp showed in 1927 that Mansonella
perstans developed in Culicoides 51,52. Buckley reported in 1933 that insects of
the same genus were the vectors of Mansonella ozzardi 28,29. Likewise,
Culicoides were found by Chardome and Peel in 1949 to be the intermediat e
hosts of Mansonella streptocerca 35. In 1960, Edeson and his colleague s
reported that they had induced a patent infection in a human with Brugia
pahangi although they had failed to achieve this result with B. malayi 53. The
latter infection was transmitted success fully to monkeys by Orihel and Pachecho
in 1968157. Likewise, Cross and his colleagues reported in 1979 that they had
transmitted successfully Wuchereria bancrofti to monkeys44. Four years earlier,
Orihel and Moore had transmitted Loa loa to two species of subhuma n
primates156.
The details of the first and second intermediate hosts of Gnathostoma
spinigerum were described by Prommas and Daengsvang in in 1936 168. Mack-
erras and Sandars described the molluscan inte rmediate host of Angiostrongylus
cantonensis in 1955124 while Morera and Ash in 1971 described the slug vector
of Angiostrongylus costaricensis. Infection with Capillaria philippinensis was
shown to be by ingestion of infected fish by Cross and his colleagues in 1972 43.
With respect to trematodes of lesser human significance, Asada in 192 8
discovered the snail first intermediate host of Heterophyes heterophyes 7.
Cameron in 1931 showed that certain snails were the intermediate host o f
Dicrocoelium dendriticum 32, while Krull and Mapes later found that meta -
cercariae developed in ants 91. In 1933, Tubangui and Pasco identified the snail
intermediate hosts of Echinostoma ilocanum 192. In 1934, Vogel showed tha t
snails of the genus Bithynia were the first intermediate host of Opisthorchis
felineus 203. The first and second intermediate hosts of O. viverrini were
described by Wykoff and his colleagues in 1966 208.
Concerning cestodes of less importance for huma ns, Stunkard showed in 1940
that mites were the vector of Bertiella studeri 188.
OVERVIEW
In retrospect, it is clear that almost no progress in an understanding of the nature

of the origin and transmission of worms was achieved for most of recorde d
history. Spontaneous generation of helminths seemed a perfectly respectabl e
explanation and only began to be seriously questioned in the late seventeent h
century. Even then, it took nearly 200 years for the issue to be settled finally with
general acceptance that worms, like other living creatures, were produced from
gametes. This coincided with elucidation of the means by which parasiti c
helminths were transferred from one host to another. A landmark in theoretical
understanding was the publication of the theory of "Alternation of Generations"
by Steenstrup in 1842, but perhaps even more important was the popularization
by Küchenmeister beginning in 1851 of the use of experimental method i n
solving these problems. A veritable explosion of information and discovery then
followed, so that within three quarters of a century, the life cycles of all the major
human helminth infections were understood. Today's helminthologists ar e
attempting to apply all of these achievements to the control of these ubiquitous
parasites and prevention of infections in human populations.
REFERENCES
1. ABILDGAARD PC. Almindelige Betragtninger over Indvoldeorme, Bemaerkingner ve d

Hundstelens Baendelorm, og Beskrivelse med Figurer of nogle nue Baendeloreme. Skrivter
af Naturhistorie-Gelskabet, Kjøbenhavn 1: 26-64, 1790. German translation in Schriften der
Naturforschen der Gesellschaft, Köpenhagen 1: 24-59, 1793. Partly translated in 84
2. ALDROVANDI U. De animalibus insectis libri septem denuo impressum, Ferronius ,
Bononiae, pp 767, 1638. Cited in 77
3. AL-QAZWINI. Cited in 77
4. ANDO A. (The first intermediate host of Paragonimus westermani .) Tokyo Iji Shinshi Nos.
2175-2178, pp 21, 1920. In Japanese. Abstracted in Tropical Diseases Bulletin 17: 51, 1921
5. ANDRY N. De la génération des vers dans le corps de l'homme. Avec trois lettres sur les
sujets des vers, les deuxs premières.... par M Nicolas Hartsoeker et l'autre....par M Georges
Baglivi, Laurent d'Houry. Paris, pp 468, 1700. An account of the the breeding of worms in
humans bodies, etc., translated by H Rhodes and A Bell, London, pp 266, 1701
6. ARISTOTLE. Generation of animals, translated by AL Peck, Loeb Classical Library ,
Heinemann, London, 1953
7. ASADA J. (Determination of the first intermediate host of Heterophyes heterophye s
occurring parasitic in human body in Japan and an experimental investigation of it s
development.) Tokyo Iji Shinshi No. 2564, pp 6-12, 1928. In Japanese. Abstracted in Japan
Medical World 8: 134, 1928
8. AVICENNA. Libri in re medica omnes, qui hactenus ad nos perverene etc., V Valgrisius,
Venetiis, pp 966, 1564. Original Arabic version, "Al Canon fi Al Tib", c. 1000 AD. Partly
translated in 86
9. von BAELLSTADT A (ALBERTUS MAGNUS). De animalibus, written about 1260. In,
Beiträge zur Geschichte der Philosophie der Mittelalters, volumes 15 and 16, 1916 and 1920
10. von BAER KE. Beiträge zur Kenntnis der niedern Thiere. Nova Acta Academiae Ceasareae
Leopoldino-Carolinae Naturae Curiosorum, Vratislaviae etc 13: 523-762, 881-882, 1827
11. BAGLIVI G. Cited in 5
12. BASTIAN HC. The beginnings of life: being some account of the nature, modes of origin
and transformation of lower animals, MacMillan and Co., London, two volumes, pp 1115,
1872
13. van BENEDEN PJ. Les ver cestoïdes ou acolytes, considérés sous le rapport de leu r
classification, de leur anatomie et de leur développement. Extracted from Mémoires d e
l'Académie Royale de Belgique de Bruxe lles, volume 25, pp 190, 1850. Abstracted in British
and Foreign Medico-Chirurgical Review 10: 322-335, 1852
14. van BENEDEN PJ. Note sur des expériences relatives au développement des cysticerques.
Annales des Sciences Naturelles 1: 104, 1854
15. BERTOLUS G. Dissertation sur les métamorphoses des Cestoieds, Thèse de Montpellier,
1856
16. BIDLOO G. Brief van G Bidloo, aan Antony van Leeuwenhoek, wegens de dieren, welke
men zomtyds in de lever der schaapen en andere beesten vind, H van Kroonevelt, Delft, pp
34, 1698. Cited in 101
17. Blacklock DB. The development of Onchocerca volvulus in Simulium damnsosum . Annals
of Tropical Medicine and Parsitology 20: 1-48, 1926
18. BLACKLOCK DB. The further development of Onchocerca volvulus in Simulium
damnosum Theob. Annals of Tropical Medicine and Parasitology 20: 203-218, 1926
19. BLOCH ME. Abhandlung von der Erzeugung der Eingeweidewürmer und den Mittel n
wider dieselben. Eine von der königlich dänischen Societät der Wissenschaften z u
Copenhagen gekrönte Preisschrift, Sigismund Friedrich Hesse, Berlin, pp 54, 1782. Partly
translated in 55
20. BOERHAAVE H. Aphorismi de cognoscendis et curandis morbis in usum doctrina e

domesticae digesti. Editio Leydensis quarta auctior, S Leuchtmans et T Haak, Lugdun i
Batavorum, pp 350, 1728
21. BOJANUS LH. Kurze Nachricht über die Zerkari en und ihren Fundort. Isis (Okens's), Oder
Encyclopädische Zeitung, Jena, pp 729-730, 1818. Partly translated in 84
22. BRAUN M. Zur Frage des Zwischenwirthes von Bothriocephalus latus Brems.
Zoologischer Anzeiger 4: 593-597, 1881; 5: 39-43, 1882; 5: 194-196, 1882; 6: 97-99 ,
1883. Partly translated in 84
23. BRAUN M. Bothriocephalus latus und seine Herkunft. Archiv für pathologische Anatomie
und Physiologie und für klinische Medicin (Virchow) 92: 364-366, 1883
24. BRAUN M. The animal parasites of man. A handbook for students and medical men ,
translated by P Falcke, revised by LW Sambon and FV Theobald, John Bale, Sons an d
Danielsson, London pp 453, 1906
Aertze. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. Nebst eine m
Anhange über Pseudo-Helminthen, Carl Schaumburg und Comp., Wien, pp 248, 1819 .
Partly translated in 77
26 BRENDEL. Cited in 46
27. BROWNE T. Pseudoxia, 1645. Cited in 38
28. BUCKLEY JJ. Some observations on two West Indian parasites of man. Proceedings of
the Royal Society of Medicine 27: 134-135, 1933
29. BUCKLEY JJ. On the development in Culicoides furens Poey of Filaria (Mansonella)
ozzardi Manson, 1897. Journal of Helminthology 12: 99-118, 1934
30. BUFFON, Comte de (LE CLERC GL). Histoire naturelle, Sonnini-Dupont, Paris, 4 4
volumes, 1749-1804. Partly translated in 55
31. BULLOCH W. The history of bacteriology, Oxford University Press, London, pp 442 ,
1938
32. CAMERON TW. Experimental infection of sheep with Dicrocoelium dendriticum . Journal
of Helminthology 9: 41-44, 1931
33. CARDANUS. Cited in 77
34. CHAMISSO A. De animalibus qulbusdam e classe vermium Linneana, i n
circumnavigatione terrae annis 1815, 16, 17, 18 peracta observatis. Fasc. 1: De Salpa, F
Dümmlerum, Berolini, pp 24, 1819
35. CHARDOME M, PEEL E. La répartition des filaires dans la région de Coquilhatville et
la transmission de Dipetalonema streptocerca par Culicoides grahami . Annales de la
Société Belge de Médecine Tropicale 29: 99-119, 1949
36. CIUREA J. Die Auffindung der Larven von Opisthorchis felineus , Pseudoamphistomum
danubiense und Metorchis albidus und die morphologische Entwicklung dieser Larven zu
den geschlechstreifen Würmen. Zeitschrift für Infektionskrankheiten, parasitäre Krankheiten
und Hygiene der Haustiere 18: 301-333, 345-356, 1917
37. CLERICUS D (LE CLERC D). Historia naturalis et medica latorum lumbricorum intr a
hominem et alia animalia, nascentium etc., Fratres de Tournes, Genevae, pp 449, 1715. A
natural and medicinal history of worms bred in the bodies of men and other animals etc.,
translated by J Browne, printed for J Wilcox at the Green-Dragon, Little Britain, pp 436,
1721
38. COLE R. Francesco Redi (1626-1697), physician, naturalist, poet. Annals of Medica l
History 8: 347-359, 1926
39. CONNAL A, CONNAL SL. A preliminary note on the development of Loa loa (Guyot)
in Chrysops silacea (Austen). Transactions of the Royal Society of Tropical Medicine and
Hygiene 15: 131-134, 1921
40. CONNAL A, CONNAL SL. The development of Loa loa (Guyot) in Chrysops silacea
(Austen) and in Chrysops dimidiata (Van der Wulp). Transactions of the Royal Society of
Tropical Medicine and Hygiene 16: 64-89, 1922
41. CREPLIN FHC. Novae observationes de entozois, Berolini, pp 134, 1829
42. CREPLIN FHC. "Distoma". In, Allge meine Encyclopädie der Wissenschaften und Kunste,
JS Ersch und JP Grüber (Editors), Leipzig, Sect. 1. Part 29: 309-329, 1837. Partl y
translated in 84
43. CROSS JH, BANZON T, CLARKE MD, BASACA-SERVILLA V, WATTEN RH ,
DIZON JJ. Studies on the experimental transmission of Capillaria philippinensis in
monkeys. Transactions of the Royal Society of Tropical Medicine and Hygiene 66 :
819-827, 1972
44. CROSS JH, PARTONO F, HSU MK, ASH L R, OEMIJATI S. Experimental transmission
of Wuchereria bancrofti to monkeys. American Journal of Tropical Medicine and Hygiene
28: 56-66, 1979
45. DAVAINE CJ. Nouvelles re cherches sur le développement de la propogation de l'ascaride
lombricoide et du trichocéphale d e l'homme. Comptes Rendus Hebdomadaires des Séances
de l'Académie des Sciences, third series, 4: 261-265, 1862. Translated in 84
46. DAVAINE CJ. Traité des entozoaires et des maladies vermineuses de l'homme et de s
animaux domestiques, second edition, J B Baillière et fils, Paris, pp 1003, 1877
47. DOLOEUS J. De infantum et puerorum morbis. In, Encyclop. medicinae, Francofurti, 4:
10, 1684-1691. Cited in 46
48. DRUMMOND JL. Thoughts on equivocal generation of entozoa., Annals of Natura l
History 6: 101-108, 1841
49. DUJARDIN F. Histoire naturelle des helminthes ou vers intestinaux, Librairi e
Encyclopédique de Roret, Paris, pp 654, 1845
50. van DURME P. Quelques notes sur les embryons de "Strongyloides intestinalis" et leu r
pénétration par la peau. Thompson Yates Laboratories Report 4: 471-474, 1901-1902
51. DYCE SHARP NA. Development of microfilaria perstans in Culicoides grahami : a
preliminary note. Transactions of the Royal Society of Tropical Medicine and Hygiene 21:
70, 1927
52. DYCE SHARP NA. Filaria perstans: its development in Culicoides austeni . Transactions
of the Royal Society of Tropical Medicine and Hygiene 21: 371-396, 1928
53. EDESON JF, WILSON T, WHARTON RH, LAING AB. Experimental transmission of
Brugia malayi and B. pahangi to man. Transactions of the Royal Society of Tropica l
Medicine and Hygiene 54: 229-234. 1960
54. ESCHRICHT DF. Inquiries, experimental and philosophical, concerning the origin o f
intestinal worms. Edinburgh New Philosophical Journal 31: 314-356, 1841
55. FARLEY J. The spontaneous generation controversy (1700-1860): the origin of parasitic
worms. Journal of the History of Biology 5: 95-125, 1972
56. FEDCHENKO (FEDTSCHENCKO) AP. (Concerning the structure and reproduction of
the Guinea worm [Filaria medinensis L.]. Izvestiia Imperatorskago Obshchestva Liubitelei
Estestvoznaniia Antropologii i Ethnografii - Moskva, 8: columns 71-81, 1870. In Russian.
Translated in 84
57. de FILIPPI. Descrizione di nuovi entozoi trovati in alcuni molluschi d'aqua dolce .
Bibliotheca Italiana, an 22, 87: 333-340, 1837
58. FILLIOZAT J. La doctrine classique de la médecine Indienne, Imprimerie Nationale, Paris,
1949
59. FORBES D. Extracts from the half yearly reports of the diseases prevailing at Dharwar in
the 1st grenadier regiment, for the year 1836. N.I. for the year 1836. Transactions of the
Medical and Physical Society of Bombay 1: 215-225, 1838
60. FUJINAMI A, NAKAMURA H. (The mode of transmission of Katayama disease in the
Hiroshima prefecture, Japanese schistosomiasis, the development of its causative worm ,
and the disease in animals caused by it.) Hiroshima Iji Geppo 132: 324-341, 1909. I n
Japanese. Abstracted in 205
61. FUJINAMI A, NAKAMURA H. (Route of infection, development of the worm in the host
and animals in Katayama disease in Hiroshima Prefecture [Japanese blood sucking worm
disease - schistosomiasis japonica].) Kyoto Igaku Zasshi 6: 224-252, 1909. In Japanese.
Translated in 84
62. FÜLLEBORN F. Untersuchungen über den Infektionsweg bei Strongyloides und

Ankylostomum und die Biologie dieser Parasiten. Archiv für Schiffs- und Tropen-Hygiene
18: 26-80, 1914
63. GABUCINUS H. De lumbri cis alvum occupantibus, ac de ratione curande eos, qui ab illis
infestantur, Commentarius, H Scotus, Venetiis, pp 56, 1547
64. GALENUS CC. Works of, In, Medicorum Graecorum opera quae exstant, edited by KG
Kühn (Greek text with Latin translation), Leipzig, 20 volumes, 1821-1833
65. GOEZE JAE. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper,
PA Pope, Blankenburg, pp 471, 1782
66. GRASSI GB. Note intorno ad alcuni parassiti dell'uomo. III. Intorno all' Ascaris
lumbricoides. Gazzetta degli Ospitali, Milano 2: 432, 1881
67. GRASSI GB. Trichocephalus und Ascarisentwicklung. Preliminärnote. Centralblatt fü r
Bakteriologie und Parasitenkunde, Abteilung originale 1: 131-132, 1887
68. GRASSI GB. Entwicklungsc yclus der Taenia nana. Dritte Praliminärnote. Centralblatt für
69. GRASSI GB, PARONA C, PARONA E. Intorno all' Anchilostoma duodenale (Dubini).
Gazzetta Medica Italiana Lombardia 38: 193-196, 1878. Translated in 84
70. GRASSI GB, ROVELLI G. Embryolische Forschungen an Cestoden. Centralblatt fü r
Bakteriologie und Parasitenkunde, Abteilung originale 5: 370-377, 401-410, 1889
71. GRASSI GB, ROVELLI G. Ricerche embriologiche sui cestodi. Atti dell'Accademi a
Gioenia di Scienze Naturali, Catania, volume 4, memoir 2, 1892
72. HARTING P. Het mikroskoop, four volumes, 1848-1854; Das Mikroscop: Theorie ,
Gebrauch, Geschichte und gegenwärtiger Zustand desselben, translated by FW Theile, F
Vieweg und Sohn, Braunschweig, three volumes, 1866
73. HARTSOEKER N. Cited in 5
74. HARVEY W. Exercitationes de generatione animalium, 1651. The works of Willia m
Harvey, translated by R Willis, The Sydenham Society, London, 1847
75. HERBST M. Beobachtungen über Trichina spiralis. Nachrichten von der Georg-August
Universität, Göttingen. Königliche Gesellschaft der Wissenschaften, pp 260-264, 1851 .
Abstracted in Quarterly Journal of Microscopical Science 1: 209-211, 1853. Translated in
84
77. HOEPPLI R. Parasites and parasitic infections in early medicine and science, University
of Malaya Press, Singapore, pp 526, 1959
78. HOFFMANN FH. Opera omnia physico-medica et supplementa etc, Genevae, pp 508 ,
1740-1753
79 HUMBERT A. Cited in 15
80. HUXLEY TH. Biogenesis and abiogenesis (1870). In, Collected essays, MacMillan and
Co., London, nine volumes, 1894-1908
81. JAMES SP. On the metamorphosis of the Filaria sanguinis hominis in mosquitos.
Especially with reference to its metamorphosis in Anopheles rossi and other mosquitos of
the Anopheles genus. British Medical Journal ii: 533-536, 1900
82. JANICKI C. Observations sur quelques espèces de poissons afin d'arriver à connaître plus
à fond le contenu de leur estomac et pour trouver des stades encore inconnus d e
plerocercoïde. Bulletin de la Société Neuchâteloise des Sciences Naturelles 42: 22-29 ,
83. JOLLY J. Indian medicine, translated from the German and supplemented with notes by
CG Kashikar, Poona, 1951
84. KEAN BH, MOTT KE, RUSSELL AJ. Tropical medicine and parasitology. Classi c
investigations, Cornell University Press, Ithaca, pp 677, 1978
85. KERCKRINGIUS T. Spicilogium anatomicus etc, A Frisii, Amstelodami, pp 280, 1670.
Cited in 46
86. KHALIL M. An early contribution to medical helminthology translated from the writings
of Ibn Sina (Avicenna) with a short biography. Journal of Tropical Medicine and Hygiene
25: 65-67, 1922
87. KNOCH J. Vorläufige Mittheilung über den Bothriocephalus latus die Entwicklung
desselben, die Wanderung und endliche Uebertragung seines Embryo's in den Menschen.
Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (Virchow)
24: 453-461, 1862
88. KOBAYASHI H. (A preliminary report on the source of the human liver distome ,
Clonorchis endemicum (Bälz)(= Distoma spathulatum Leuckart.) Annotatione s
Zoologicae Japonenses 271-277, 1911. In Japanese, with English summary
89. KOBAYASHI H. A preliminary report on the source of the human liver distome ,
Clonorchis endemicum (Bälz) (Distomum spathulatum , Leuckart). Far Easter n
Association of Tropical Medicine: Transactions of the Second Biennial Congress, Hong
Kong, pp 108-112, 1912
90. KOBAYASHI H. Studies on the lung fluke in Korea. I. On the life-history an d
morphology of the lung fluke. Mittheilungen aus der medizinischen Fachschule zu Keijo
2: 97-115, 1918
91. KRULL WH, MAPES CR. Studies on the biology of Dicrocoelium dendriticu m
(Rudolphi 1819) Looss, 1899 (Trematoda: Dicrocoeliidae) including its relation to th e
intermediate host, Cionella lubrica (Muller). IX. Notes on the cyst, metacercaria, an d
infection in the ant, Formica fusca. Cornell Veterinarian 43: 389-409, 1953
92. KÜCHENMEISTER F. Vorläufige Mittheilung. Über Cysticercus pisiformis der Kanin-
chen. Zeitschrift für klinische Medicin (G unsburg) 2: 240, 1851. Translated by L Herzberg
93. KÜCHENMEISTER F. Einiges über den Übergang der Finnen in Taenien und über das
Digitalin. Zeitschrift für klinische Medicin (Gunsburg) 2: 295-299, 1851
94. KÜCHENMEISTER F. Ueber die Umwa ndlung der Finnen (Cysticerci) in Bandwuermer
(Taenien). Prager Vierteljahrsschrift für die Praktische Heilkunde 33: 106-158, 1852
95. KÜCHENMEISTER F. Über Cestoden im Allgemeinen und die des Mensche n
insbesondere etc., Zittau, 1853. Partly translated in 55
96. KÜCHENMEISTER F. Experimente über die Entstehung der Cestoden Zweiter Stuf e
zunächst des Coenurus cerebralis . Under Mitwirkung des Herrn Professor Haubner auf
Befehl und Kosten des hohen königliche sächsischen Staatsminsterii des Innern. Zeitschrift
für klinische Medicin (Gunsburg) 4: 448-451, 1853
97. KÜCHENMEISTER F. Offenes Sendschreiben an die k.k. Gesellschaft der Zertze z u
Wien. Experimenteller Nachweiss, da ssCysticercus cellulosae innerhalb des menschlichen
Darmkanales sich in Taenia solium umwandelt. Wiener medicinische Wochenschrift 5:
1-4, 1855. Translated in 84
98. KÜCHENMEISTER F. Erneuter Versuch der Umwandlung des Cysticercus cellulosae
in Taenia solium hominis . Deutsche Klinik 12: 187-189, 1860. Abstracted in Medica l
Times and Gazette ii: 414, 1860
99. KÜCHENMEISTER F, HAUBNER GC. Weitere Mittheilungen über die Entwicklung
der Band- und Blasenwürmer Nach den Versuchen von Dr. Küchenmeister und Dr .
Haubner. Magazin für die Gessamte Thierheilkunde 20: 366-368, 1854; 21: 100-118 ,
1855
100. van LEEUWENHOEK A. Part of a letter from Mr. Anthony van Leeuwenhoe k
concerning worms observ'd in sheeps' livers and pasture grounds. Philosophica l
Transactions of the Royal Society 24: 1522-1527, 1704
101. van LEEUWENHOEK A. The selec t works of Anthony van Leeuwenhoek containing his
microscopical discoveries in many of the works of nature, translated by S Hoole from the
Dutch and Latin editions, Henry Fry, London, 1798
102. LEICHTENSTERN O. Futterungsversuche mit An kylostomalarven. Ein neue Rhabditisart
in den Fäces von Ziegerlarbeitern: Berichtigung. Centralblatt für klinische Medicin 7 :
673-675, 1886
103. LEIPER RT. The etiology and prophylaxis of dracontiasis. British Medical Journal i :
129-132, 1907
104. LEIPER RT. Filaria loa. Cited in British Medical Journal i: 39-40, 1913
105. LEIPER RT. Report on the result s of the Bilharzia mission in Egypt, 1915. Journal of the
Royal Army Medical Corps 25: 1-55, 147-192, 253-267, 1915
106. LEIPER RT. On the relation between the terminal-spined and lateral-spined eggs o f
Bilharzia. British Medical Journal i: 411, 1916
107. LEIPER RT, ATKINSON EL. Observations on the spread of Asiatic schistosomiasis .
British Medical Journal i: 201-203, 1915
108. LEUCKART R. Die Blasenbandwürmer und ihre Entwicklung. Zugleich ein Beitrag zur
Kenntnis der Cysticercusleber, J Ricker, Giessen, pp 162, 1856
109. LEUCKART R. Expériences sur la trichina spiralis (le ver devient un trichocéphale dans
l'intestin du porc). Comptes Rendus Hebdomadaires des Séances de l'Académie de s
Sciences 49: 453-457, 1859
110. LEUCKART R. Der geschlechstreife Zustand der Trichina spiralis. Eine vorläufige
Mittheilung. Zeitschrift für rationale Medicin 8: 259-262, 334-335, 1860. Translated in
Quarterly Journal of Microscopical Science 8: 168-171, 1860
111. LEUCKART R. Die menschlichen Parasiten und die von ihnen herrührenden Krankheiten.
Ein Hand- und Lehrbuch für Naturforscher und Aertze, CF Winter'sche Verlagshandlung,
Leipzig, volume 1, pp 776, 1863
112. LEUCKART R. Die menschlichen Parasiten und die von ihnen herrührenden Krankheiten.
Leipzig, volume 2, pp 882, 1867-1876
113. LEUCKART R. Zur Entwickelungsgeschichte des Leberegels. Zoologischer Anzeiger 4:
461-464, 1881. Translated in 84
114. LEUCKART R. Zur Entwickelungsgeschichte des Leberegels ( Distomum hepaticum ).
Archiv für Naturgeschichte 1: 80-119, 1882
115. LEUCKART R. Zur Entwickelungsgeschichte des Leberegels. Zweite Mittheilung .
Zoologischer Anzeiger 5: 524-528, 1882
116. LEUCKART R. Die Parasiten des Menschen und die von ihnen herrührende n
Krankheiten. Ein Hand- und Lehrbuch für Naturforscher und Aertze, CF Winter'sch e
Verlagshandlung, Leipzig, volume 1, pp 1009, 1879-1886. The parasites of man and the
diseases which proceed from them, translated by WE Hoyle, Young J Pentland ,
Edinburgh, pp 771, 1886
117. LINNAEUS C. Cited in 24
118. von LIPPMANN E O. Urzeugung und Lebenskraft. Zur Geschichte dieser Probleme von
den ältesten Zeiten an bis zu den Anfängen des 20. Jahrhunderts, Julius Springer, Berlin,
pp 135, 1933
119. LOOSS A. Zur Lebensgeschichte des Ankylostoma duodenale . Centralblatt für
Bakteriologie und Parasitenkunde, Abteilu ng originale 24: 441-449, 483-488, 1898. Partly
translated in 84
120. LOOSS A. Ueber das Eindrigen der Ankylostomalarven in die menschliche Haut. Cen-
tralblatt für Bakteriologie und Parasitenkunde, Abteilung originale 29: 733-739, 1901
121. LOOSS A. The anatomy and life histo ry of Agchylostoma duodenale Dub. A monograph.
Part II. The development in the free state. Translated from the German by M Bernhard.
Records of the School of Medicine, Egyptian Ministry of Education, 4: 163-613, 1911.
Pp 252-277 reprinted in the Journal of Tropical Medicine and Hygiene 15: 155-157 ,
171-174, 182-185, 199-201, 235-238, 1912. Abstracted in Journal of the Royal Arm y
Medical Corps 19: 42-55, 1912
122. LOW GC. A recent observation on Filaria nocturna in Culex: probable mode of infection
in man. British Medical Journal i: 1456-1457, 1900
123. LUTZ A. Zur Lebensgeschichte des Distoma hepaticum . Centralblatt für Bakteriologie
und Parasitenkunde, Abteilung originale 11: 783-796, 1892. Partly translated in 84
124. MACKERRAS MJ, SANDARS DF. The life-history of the rat lung-worm ,
Angiostrongylus cantonensis (Chen) (Nematoda: Metastrongylidae). Australian Journal
of Zoology 7: 1-21, 1955
125. de MALEBRANCHE N. De la recherche de la verité, 1673. Malebranche's Search after

Truth, translated by T Taylor, London, two volumes, 1694
126. MALPIGHI M. De formatione pulli in o vo, 1673. In, Opera omnia, R Scott, Londini, two
volumes, 1686
127. MALPIGHI M. De ovo incubato, 16 75. In, Opera omnia, R Scott, Londini, two volumes,
1686
128. MANSON P. Further observations of Filaria sanguinis hominis . China Imperial Maritime
Customs, Medical Reports for the half year ended 30th September, 1877, 14th issue, pp
1-26, 1878. Reprinted without illustrations as "On the development of Filaria sanguinis
hominis and on the mosquito considered as a nurse." Journal of the Linnean Societ y
(Zoology) 14: 304-311, 1878
129. MEHLIS E. Novae observationes de entozois. Auctore Dr. Fr. Chr. H. Creplin. Isi s
(Oken's), Oder Encylopädische Zeitung, Jena, pp 68-99, 166-199, 1831
130. MERCURIALIS H. De internis puerorum morbis, Lugduni, 1623
131. MIYAIRI K. (A contribution to the knowledge and development of the lung fluke.) Sai
Kin Gaku Zasshi No. 281, 1919. In Japanese
132. MIYAIRI K, SUZUKI M. (On the development of Schistosoma japonicum .) Tokyo Iji
Shinshi No. 1836, pp 1-5, 1913. In Japanese. Abstracted in 205
133. MIYAIRI K, SUZUKI M. (Der Zwischenwirt des Schistosomum japonicum Katsurada.)
Mittheilungen aus der medizinischen Fakultät der kaiserlichen Universität Kysush u
Fukuoka 1: 187-197, 1914 Partly translated in 84
134. MOSLER KF. Ueber einen Fall von Helminthiasis. Archiv für pathologische Anatomie
und Physiologie und für klinsiche Medicin (Virchow) 18: 242-250, 1860
135. MOSLER KF. Helminthologisch e Studien und Beobachtungen, A Hirschwald, Berlin, pp
89, 1864
136. MÜLLER OF. Vermium terrestrium et fluviatilium, seu animalium infusorium ,
helminthocorum et testaceorum, non marinorum, succincta historia. Volume 1, Infusoria,
Havniae et Lipsiae, pp 135, 1773
137. MUTO M. (Biologische Studien über die Cercarien und die encystierten Cercarien de s
Metagonimus yokogawai.) Kyoto Igaku Zasshi 14: 79-100, 1917. In Japanese, wit h
German summary, pp 54-56
138. MUTO M. Ueber den ersten Zwischenwirt von Clonorchis sinensis . Verhandlungen der
japanischen pathologischen Gesellschaft, Tokyo 8: 151, 1918. Abstracted in Tropica l
Diseases Bulletin 17: 49, 1921
139. MUTO M. (On the primary intermediate host of Clonorchis sinensis .) Chuo Igakkai
Zasshi 25, No. 3, 49-52, 1918. In Japanese. Translated in 84.
140. NAKAGAWA K. (A preliminary report on the discovery of the intermediate host of the
human lung fluke.) Tokyo Iji Shinshi, No. 1910, 1915. In Japanese
141. NAKAGAWA K. The mode of infection in pulmonary distomiasis. Certain freshwate r
crabs as intermediate hosts of Paragonimus westermanii . Journal of Infectious Diseases
18: 131-142, 1916
142. NAKAGAWA K. Human pulmonary distomiasis caused by Paragonimus westermani .
Journal of Experimental Medicine 26: 297-323, 1917
143. NAKAGAWA K. On the life cycle of Fasciolopsis buski , Lankester. Kitasato Archives
of Experimental Medicine 4: 159-167, 1921
144. NAKAGAWA K. The development of Fasciolopsis buski (Lankester). Journal o f
Parasitology 8: 161-165, 1922
145. NAUNYN B. Ueber die zu Echinococcus hominis gehörige tänie. Archiv für Anatomie,
Physiologie und wissenschaftliche Medicin, pp 412-416, 1863. Translated in 84
146. NEEDHAM JT. Observations upon the generation, composition and decomposition o f
animal and vegetable substances. Phil osophical Transactions of the Royal Society, volume
44, 1750. Cited in 31
147. NICHOLL W, MINCHIN EA. Two species of cysticercoids from the rat flea ( Cerato-
phyllus fasciatus). Proceedings of the Zoological Society of London 1: 9-13, 1911
148. NITZSCH CL. Seltame Lebens- und Todesart eines kleinen bisher unbekannte n
Wasserthierchens. In, Kilian. Georgia, der Der Menschen im Leben und im Staate, p p
257-262, 281-286, 1807
149. NITZSCH CL. Beitrag zur Infusorienkunde, oder Naturbeschreibung der Zerkarien und
Bazillarien. Neue Schriften der naturforschenden Gesellschaft zu Halle 3: 1-128, 1817
150. von NORDMANN A. Mikrographische Beiträge zur Naturgeschichte der wirbellose n
Thiere, G Reimer, Berlin, two volumes, pp 268, 1832
151. OKEN LH. Cited and partly translated in 24
152. OKEN LH. Cited and partly translated in 181
153. OLIVER JH. Cited in Seventh Annual Report of the Sanitary Commissioner (1870) of the
Government of India, Calcutta, pp 82-83, 1871
154. ONJI Y, NISHIO K. (General observations on new intestinal flukes.) Igaku Chuo Zasshi
14: 875-883, 1915. In Japanese
155. ORIBASIUS. Cited in 2
156. ORIHEL TC, MOORE P JJ. Loa loa: experimental infection in two species of African
primates. American Journal of Tropical Medicine and Hygiene 24: 606-609, 1975
157. ORIHEL TC, PACHECHO G. Brugia malayi in the Philippine macaque. Journal o f
Parasitology 54: 1234-1235, 1968
158. PALLAS PS. Bemerkungen über die Bandwürmer in Menschen und Thieren. Neu e
nordische Beyträge Physikalische und Geographische Erd- und Vokerbeschriften 1 :
39-112, 1781. Partly translated in 116
159. PALLAS PS. Einige Erinnerungen die Bandwürmer bettrefend: in Beziehung auf da s
zwölfte und vierzehnte stück des Naturforschers. Neue nordische Beytrage Physikalische
und Geographische Erd- und Vokerbeschriften 1: 113-131, 1781
160. PARACELSUS. De natura rerum, liber primus de generationibus rerum naturalium .
Saemtliche Werke, K Sudhoff (Editor), München, 14 volumes, 1922-1923. Partl y
translated in 77
161. PARÉ A. Les oeuvres d'Ambroise Paré etc., Paris, 1561. Partly translated in 77
162. PASTEUR L. Mémoire sur les corpuscles organisés qui existent dans l'atmosphère .
Examen de la doctrine des générations spontanées, Société Chimique, Paris, 1861
163. PERRONCITO E. On the tenacity of life of the cysticercus in the flesh of oxen and on the
rapid development of the corresponding Taenia mediocanellata in the human body. The
Veterinarian 50: 817-818, 1877
164. PLANCK M. Wissenschaftliche Selbstbiographie, Johann Barth, Leipzig, 1955. Partl y
translated in 55
165. POUCHET FA. Hétérogonie, Paris, 1859. Partly translated in 31
166. POUCHET, VERRIER. Expériences sur l es migrations des entozoaires. Comptes Rendus
Hebdomadaires des Séances de la Académie des Sciences 54: 958-963, 1862. Translated
in Quarterly Journal of Microscopical Science 2: 171-175, 1853
167. POWER H, SEDGEWICK LW (Editors). The New Sydenhams Society's lexicon o f
medicine and the allied sciences, The New Sydenham Society, London, five volumes ,
1881-1894
168. PROMMAS C, DAENGSVANG S. Preliminary report of a study on the life-cycle o f
Gnathostoma spinigerum . Journal of Parasitology 22: 180-186, 1936
169. REDI F. Esperienze intorno alla generazione degl'insetti, Carlo Dati, Firenze, pp 177 ,
1668. Experiments on the generation of insects, translated from the 1688 edition by M
Bigelow, Opencourt Publishing Co., Chicago, pp 160, 1909
170. RHIND W. A treatise on the nature and cure of intestinal worms of the human body ,
Samuel Highley, London, pp 153, 1829
171. ROSEN F. Recherches expérimentales sur le cycle évolutif du Dibothriocephalus latus .
Bulletin de la Société Neuchâteloise des Sciences Naturelles 42: 29-49, 1917. Partl y
translated in 84
172. RUDOLPHI CA. Entozoorum sive vermium intestinalium historia naturalis, Treuttel et
Würtz, Paris, two volumes, pp 1370, 1808-1810
173. SCHREIBER. Cited in 25

174. von SIEBOLD CT. Helminthologische Beiträge. Archiv für Naturgeschichte 1: 45-84 ,
1835
175. von SIEBOLD CT. Zur Entwicklungsgechichte der Helminthen. In, Die Physiologie als
Erfahrungswissenschaft (KF Burdach, editor), 2 Aufl. v. 2, Buch 4, pp 183-213, 1837
176. von SIEBOLD CT. Bericht über die Leistungen im Gebiete der Helminthologie während
des Jahres 1842. Archiv für Naturgeschichte 9: 300-335, 1843
177. von SIEBOLD CT. Parasiten. In, Handwörterbuch der Physiologie mit Rücksicht au f
physiologische Pathologie, R Wagner (Editor), 2: 650-676, 1844
178. von SIEBOLD CT. Expérience sur la transformation des vers vésiculaires ou cysticerques
in taenia. Annales des Sciences Naturelles, series 3, 17: 377-381, 1852
179. von SIEBOLD CT. Ueber die Verwa ndlung des Cysticercus pisiformis in Taenia serrata.
Zeitschrift für wissenschaftliche Zoologie 4: 400-408, 1853. Translated in Quarterl y
Journal of Microscopical Science 2: 255-263, 1854
180. von SIEBOLD CT. Ueber die Verwan dlung der Echinococcus-brut in Taenien. Zeitschrift
für wissenschaftliche Zoologie 4: 409-425, 1853. Partly translated in 84
181. von SIEBOLD CT. Über die Band- und Blasenwürmer nebst einer Einleitung über di e
Entstehung der Eingeweidewürmer, W Engelmann, Leipzig, pp 115, 1854. On tape and
cystic worms, with an introduction on the origin of intestinal worms, translated by T H
Huxley, pp 88; bound with volume 2 of F Küchenmeister's "Manual of parasites", Th e
Sydenham Society, London, 1857
182. von SIEBOLD CT. Cited in 112
183. SINGER CT. A history of biology to about the year 1900, Abelard-Schuman, revise d
edition, London, pp 580, 1960
184. SPALLANZANI L. Saggio de osservazione microscopiche concernanti il sistema della
generazione de' Signori de Needham e Buffon, Modena, 1755. Also; Upuscoli de fisica
animale e vegetabile, Modena, 1766
185. SPIGELIUS A. De lumbrico lato liber etc., L Pasquati, Patavii, pp 88, 1618
186. STEENSTRUP JJ. Om Fortplantning og Udvikling gjennem vexlende Generation s
Raekker en saeregen Form for Opfostringen i de lavere Dyreklasser, CA Reitzel ,
Kjøbenhavn, pp 76, 1842. On the alternation of generations, or, the propogation an d
development of animals through alternate generations: a peculiar form of fostering th e
young in the lower classes of animals, translated by G Busk from the German version of
CH Lorenzen, The Ray Society, London, pp 132, 1845
187. von STEIN F. Beiträge zur Entwickelungsgeschichte der Eingeweidewürmer. Zeitschrift
für wissenschaftliche Zoologie 4: 196-214, 1852
188. STUNKARD HW. The morphology and life history of the cestode, Bertiella studeri.
American Journal of Tropical Medicine 20: 305-333, 1940
189. SWAMMERDAM J. Historia insectorum generalis etc., M van Dreunan, Utrecht, pp 49,
1669. Also; The Book of nature; or the history of insects....illustrated with coppe r
plates....with the life of the author by H Boerhaave, translated from the Dutch and Latin
original edition by T Flloyd, revised and improved by notes from Reamur and others, by
J Hill, London, 1758
190. THOMAS AP. Report on experiments on the development of the liver fluke ( Fasciola
hepatica). Journal of the Royal Agricultural Society of England 17: 1-28, 1881
191. THOMAS A P. Second report of experiments on the development of the liver fluk e
(Fasciola hepatica). Journal of the Royal Agricultural Society of England 18: 439-455,
1882. Abstracted in British Medical Journal ii: 1001-1002, 1882
192. TUBANGUI MA, PASCO A. The life history of the human intestinal fluke, Euparyphium
ilocanum (Garrison, 1908). Philippine Journal of Science 51: 581-603, 1933
193. TURKHUD TA. Report of the Bombay Bacteriological Laboratory for the year 1913 ,
presented by WG Liston, Government Central Press, pp 14-16, 1914
194. TYSON E. Lumbricus latus, or a discourse read before the Royal Society, of the joynted
worm, wherein a great many mistakes of former writers concerning it, are remarked; its
natural history from more exact observations is attempted; and the whole urged, as a
difficulty against the doctrine of univocal generation. Philosophical Transactions of th e
Royal Society 13: 113-144, 1683
195. TYSON E. The Lumbricus Latus (Abstract). Memoirs of the Philosphical Transactions
of the Royal Society pp 122-130. Abstract of 194
196. la VALETTE de ST. GEORGE A. Symbolae ad trematodorum evolutionis historiam ,
Berlin, pp 38, 1855
197. VALLISNERIUS (VALLISNIERI) A. Opera fisico-mediche stampate e manoscritte .
Raccolte da Antonio suo figliuolo, S Coleti, Venezia, three volumes, pp 1696, 1733 .
198. VILLANOVANUS (de VILLENEUVE) A. De lumbricus et ascaridibus. In, Opera omnia,
Basileae, 1585. Original edition c. 1300. Cited in 37
199. VIRCHOW R. Die Cellularpathologie in ihrer Begründung auf physiologische un d
pathologische Gewebelehre, A Hirschwald, pp 440, Berlin, 1858. 1859. Cellula r
pathology as based upon physiological and pathological histology, translated from th e
second edition by F Chance, J Churchill, London, pp 511, 1860
200. VIRCHOW R. Futterungsversuch mit Trichina spiralis. Deutsche Klinik 11: 430, 1859
201. VIRCHOW R. Recherches sur le développement de la trichina spiralis (Ce ver devien t
adulte dans l'intestin du chien). Comptes Rendus Hebdomadaires des Séances d e
l'Académie des Sciences 49: 660-662, 1859
202. VIRCHOW R. Helmintholgische Notizen. 3. Ueber Trichina spiralis. Archiv für
pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 18 :
330-345, 1860. Abstracted in British and Foreign Medico-Chirurgical Review 26 :
515-516, 1860
203. VOGEL H. Der Entwicklungszyklus von Opisthorchis felineus (Riv.) nebst Bemerkungen
über Systematick und Epidemiologie. Zoologica 33: 1-103, 1934
204. WAGENER H. Beiträge zur Entwickelungs-Geschichte der Eingeweidewürmer .
Naturkundige Verhandelingen van de Hollandsche Maatschapij der Weteschappen t e
Haarlem, pp 112, 1857
205. WARREN K S. Schistosomiasis: the evolution of a medical literature. M.I.T. Press ,
Cambridge, Mass., pp 1307, 1973
206. WILMS. Anchylostoma duodenale und Angullula intestinalis . Schmidt's Jahrbücher der
in-und ausländischen gesammten Medicin 256: 272, 1897
207. WOTTON E. Edoardi Wuottoni Oxoniensis, De differentiis animalium, Lutetia e
Parisiorum, 1552
208. WYKOFF DE, HARINASUTA C, JUTTIJUDATA P, WINN MM. Opisthorchis
viverrini in Thailand - the life cycle and comparison with O. felineus, Journal of
209. YOKOGAWA S. (A new parasite involving trout as its intermediate host and its ne w
generic name.) Okayama Igakkai Zasshi No. 279, 1912. In Japanese
210. YOKOGAWA S. (Schistosoma japonicum in Formosa, especially on its intermediat e
host.). Taiwan Igakkai Zasshi 149: 178-183, 1915. In Japanese. Abstracted in 205
211. YOKOGAWA S. (Paragonimus ringeri . Study of stages from the crab and points o f
difference distinguishing it from similar cysts occurring there.) Taiwan Igakukai Zasshi
No. 175, pp 298-307, 1917. In Japanese. Abstracted in Tropical Diseases Bulletin 12 :
173-174, 1918
212. ZENKER FA. Ueber die trichinen-Krankheit des Menschen. Archiv für pathologisch e
Anatomie und Physiologie und für klinische Medicin (Virchow) 18: 561-572, 1860 .
Translated in 84
Table 2.1. Landmarks in the understanding of the origin and transmission of worms
___________________________________________________________________
BC The spontaneous generation of certain animals was generally accepted

1668 Redi showed by experiment that maggots in rotten meat developed not b y
spontaneous generation but from eggs deposited by flies. He conceded, however,
that intestinal worms may be generated spontaneously
1673 Leeuwenhoek began to publish the results of his observations using a microscope
of the microbiological world
1698 Bidloo discovered eggs of Fasciola
1700 Andry in his textbook declared that all parasitic worms were bred by means of a
"seed" introduced from the external envi ronment. He believed that he had observed
the eggs of tapeworms
1750+ Buffon and Needham defended staunchly the theory of spontaneous generation
1766 Spallanzani showed that heated, sealed infusions were sterile and concluded that
"animalcules" were carried in by the air
1780 The Royal Academy of Science in Copenhagen set a prize essay on "The origins
of parasitic worms". First and second prizes were won by Bloch and Goeze ,
respectively, both of whom believed in spontaneous generation.
1781 Pallas injected Dipylidium caninum eggs into the abdominal cavity of a dog and
concluded erroneously that they developed into adult worms
1787 Linnaeus believed incorrectly that certain specific, parasitic worms develope d
from morphologically similar, immature free-living helminths that were ingested
in food and water. The principle, however, was correct
1790 Abildgaard fed stickleback fis h containing immature cestodes to a duck and found
them living in the gut three days later
c.1800 The discovery that many cysts were verminous in nature yet had no reproductive
organs seemed to support the idea of spontaneous generation
1810-19 Rudolphi (1810) and Bremser (1819) in their textbooks of helmintholog y
continued to support the theory of spontaneous generation
1817 Nitzsch noticed the resemblance between cercariae and flukes, and discerned the
encystation of cercariae
1818 Bojanus discovered that cercariae w ere generated within organisms (rediae) within
snails
1819 Chamisso described the alternation of generations of marine animals belonging to
the family, Salpae
1831 Mehlis observed larvae (miracidia) hatch from fluke eggs
1835 von Siebold observed rediae released from disintegrating miracidia in water
1835 von Siebold discovered larvae with hooklets within tapeworm eggs
1837 von Siebold found that certain cercariae encysted inside snails
1842 Steenstrup published his book on the "Alternation of Generations" in which h e
proposed a unifying hypothesis to explain the life cycles of certain trematodes and
other organisms
1851 Herbst found Trichinella spiralis larvae in dog muscles after feeding them with
infected badger flesh
1851 Küchenmeister fed Cysticercus pisiformis of the rabbit to foxes and recovere d
adult tapeworms (Taenia pisiformis ) from the gut
1852 Küchenmeister gave Cysticercus fasciolaris of mice to a cat and recovered adult
tapeworms (Taenia taeniaeformis )
1853 Küchenmeister reared adult tapeworms in dogs fed with cystic worms from sheep:
Taenia hydatigera from Cysticercus tenuicollis and T. multiceps from Coenurus
cerebralis
1853 von Siebold discovered Echinococcus granulosus adult worms in the intestines of
dogs after feeding hydatid cysts to them
1854 van Beneden generated Cysticercus cellulosae by feeding Taenia solium eggs to
pigs
1855 Küchenmeister reported the recovery of immature Taenia solium after feeding
Cysticercus cellulosae shortly before execution to a condemned murderer
1855 Humbert ingested Cycsticercus cellulosae and three months later began to pas s
Taenia solium proglottids in his stools
1855 la Valette de St. George showed that certain encysted cercariae but no t
non-encysted cercariae developed into adult flukes when ingested by birds o r
animals
1857 Wagener witnessed the metamorphosis of Distoma cygnoides miracidia into rediae
in snails
1857+ Pasteur showed that a bacterial ferment soured milk and that yeasts or mould s
were necessary for the making of wine from grapes
1859 Virchow discovered adult Trichinella spiralis in the gut of a dog after feeding it
with trichinous meat
1860 Zenker discovered adult Trichinella spiralis in the bowel at the post-morte m
examination of a young woman who had died of a typhoidal illness after recently
eating trichinous pork
1860 Küchenmeister repeated his experime nt on a condemned murderer. The incubation
period was several months and this time he recovered Taenia solium tapeworms
up to 1.5 m long
1861 Pasteur showed that air contained bacteria which caused putrefaction in steril e
infusions
1862 Leuckart fed Taenia saginata proglottids to calves and generated Cysticercus
bovis
1865 Leuckart and his students swallo wed Enterobius vermicularis eggs and developed
patent infections
1867 Leuckart generated hydatid cysts in pigs after feeding them with Echinococcus
granulosus ova
1870 Oliver may have produced a patent Taenia saginata infection in a human afte r
feeding Cysticercus bovis to a man
1870 Fedchenko reported that Dracunculus medinensis larvae developed with the body
of Cyclops (crustacean)
1877 Perroncito recovered an adult Taenia saginata from a human 4 months afte r
ingestion of Cysticercus bovis
1877 Manson discovered that Wuchereria bancrofti microfilariae metamorphosed i n
certain mosquitoes
1881 Thomas and Leuckart independently discovered that Lymnaea snails were the
intermediate hosts of Fasciola hepatica
1881-3 Braun showed that certain freshwater fish were the second intermediate hosts of
Diphyllobothrium latum by feeding infected fish to dogs and humans the n
recovering adult worms
1886 Calandruccio produced a patent infection with Trichuris trichiura in himself after
swallowing eggs
1886 Leichtenstern produced patent infections with hookworm in humans afte r
administering infective larvae orally
1887 Grassi showed that Hymenolepis nana could be transmitted directly from on e
definitive host to another
1889 Grassi and Rovelli reported that Dipylidium caninum larvae developed in fleas
1892 Grassi and Rovelli showed that Hymenolepis diminuta developed in a variety of
arthropod intermediate hosts
1892 Lutz fed Fasciola cysts to guinea pigs then recovered adult flukes
1897 Wilms infected a human by administering Strongyloides stercoralis larvae orally
1898 Looss first claimed that hookworm infective larvae penetrated the intact skin
1900 Low reported thatWuchereria bancrofti infective larvae were found in th e
mouthparts of mosquitoes that had been filariated by Thomas Bancroft
1901 Looss showed by histological examination of an amputated leg that hookwor m
larvae applied before amputation penetrated the skin
1901-2 van Durme showed that Strongyloides larvae penetrated the skin
1907 Leiper recovered immature Dracunculus medinensis from a monkey 6 month s
after feeding it water containing infected Cyclops
1909 Fujinami and Nakamura demonstrated that Schistosoma japonicum infection in
cows was acquired via the skin
1911 Looss reported the development of a patent hookworm infection 71 days afte r
percutaneous infection of a human
1911 Yokogawa discovered that trout were the second intermediate hosts o f
Metagonimus yokogawai
1911 Kobayashi recovered adult Clonorchis sinensis from the biliary system of cat s
after feeding them with fish infected with certain encysted, immature flukes
1913 Leiper reported that tabanid flies ( Chrysops) were the vectors of Loa loa
1913 Miyairi and Suzuki discovered that Oncomelania snails were the intermediat e
hosts of Schistosoma japonicum , described the larval stages of the parasite, and
recovered adult worms from mice infected percutaneously with cercariae released
from these snails
1913 One out of five persons given infected Cyclops to drink by Turkhud develope d
dracunculiasis one year later
1914 Fülleborn showed that Strongyloides stercoralis larvae applied to the ski n
developed into adult worms in the gut of dogs
1914 Nakagawa showed that crabs of the genus Potamon were the second intermediate
hosts of Paragonimus westermani
1915 Onji and Nishio found that certain fishes were the second intermediate hosts o f
Heterophyes heterophyes
1915 Leiper and colleagues showed that miracidia from terminal-spined egg s
(Schistosoma haematobium) developed in Bulinus snails, described the
intermediate stages, then recovered adult worms after infecting mic e
percutaneously with cercariae obtained from these mice
1916 Leiper proved that miracidia derived from lateral-spined eggs developed i n
Biomphalaria snails and were a different species ( S. mansoni)
1917 Muto reported that Semisulcospira snails were the first intermediate hosts o f
Metagonimus
1917 Ciurea discovered that certain fishes were the second intermediate hosts o f
Opisthorchis felineus
1917 Janicki and Rosen discovered that certain crustaceans ( Cyclops) were the first
intermediate hosts of Diphyllobothrium latum
1917-19 Ando, Kobayashi, Miyairi, Nakagawa and Y okogawa all concluded independently
that Melania (= Semisulcospira) snails were the first intermediate hosts o f
Paragonimus
1918 Muto showed that Bithynia (= Parafossarulus) snails were the primar y
intermediate hosts of C. sinensis
1921 Nakagawa reported that Segmentina snails were the first intermediate hosts o f
Fasciolopsis buski
1922 Nakagawa showed that Fasciolopsis cercariae escaped from the snails an d
encysted on grass, then fed them to dogs and recovered adult worms
1922 Connal and Connal provided detailed descriptions of the development of Loa loa
in Chrysops
1926 Blacklock discovered that Simulium blackflies were the vectors of Onchocerca
volvulus
1927 Dyce Sharp showed that Culicoides midges were the vectors of Mansonella
perstans
1928 Asada described the snail intermediate host of Heterophyes heterophyes
1931 Cameron observed that certain snails were intermediate hosts of Dicrocoelium
dendriticum
1933 Buckley found that Culicoides was the vector of Mansonella ozzardi
1934 Vogel found that Bithynia snails were the first intermediate hosts of Opisthorchis
felineus
1936 Prommas and Daengsvang described the first and second intermediate hosts o f
Gnathostoma spinigerum
1949 Chardome and Peel showed that Culicoides was the vector of Mansonella
streptocerca
1952 Krull and Mapes showed that Dicrocoelium dendriticum larvae encysted in certain
ants
1953 Edeson and his colleagues infected a human with Brugia pahangi using Mansonia
mosquitoes
1955 Mackerras and Sandars reported that slugs were the intermediate hosts o f
Angiostrongylus cantonensis
1966 Wykoff and colleagues described the first and second intermediate hosts o f
Opisthorchis viverrini
1968 Orihel and Pachecho produced patent infections in monkeys with B. malayi
1971 Morera and Ash described the slug vector of Angiostrongylus costaricensis
1972 Cross and his colleagues found that Capillaria philippinensis infection was
acquired by ingesting infected fish
1975 Orihel and Moore transmitted Loa loa to subhuman primates
1979 Cross and his colleagues successfully infected monkeys with Wuchereria
bancrofti
___________________________________________________________________
Chapter 3
THE DISCOVERY AND DEVELOPMENT OF

ANTHELMINTICS
TRADITIONAL REMEDIES
Men have undoubtedly tried to rid themselves of worms infecting their bodies
for almost as long as they have recognized them. As discussed elsewhere in this
book, only a very small number of parasitic helminths were known during most
of recorded history. These were certain visible worms that enjoyed a wide
geographical distribution and were extruded from time to time from the
gastrointestinal tract, i.e. tapeworm proglottids or segments (Taenia and
Diphyllobothrium species), the common roundworm (Ascaris lumbricoides)
and the pinworm or threadworm (Enterobius vermicularis). In addition, Guinea
worm (Dracunculus medinensis) was found in certain restricted localities but
its verminous nature was a matter of some controversy.
Most attention, therefore, was paid to the common intestinal worms. Plants
were the major therapeutic sources. Herbal products that were believed to have
specific vermicidal or vermifugal properties were often combined with
purgatives (to flush the worms out) and various sweeteners or diluents. In the
Egyptian Papyrus Ebers (c.1500 BC), for example, castor oil and senna were
recommended as purgatives and anthelmintics were often administered together
with honey, sweet beer or dates126. While it is true that certain preparations did
have some therapeutic efficacy, the coincident, spontaneous passage of
senescent worms often led to anthelmintic properties being ascribed erroneously
to many concoctions.
The development of herbal products depended upon the local botanical flora
with the result that different remedies tended to develop in different parts of the
world. Nevertheless, in some instances, the same or related plants were used
over wide geographical areas. Thus, the pomegranate (Punica granatum) was
utilized in countries ranging from Egypt to China. For convenience, however,
major traditional remedies are reviewed in relation to different regions of the
globe.
THE MEDITERRANEAN REGION
Many different anthelmintics were used in the countries abutting the Med-
iterranean Sea in the centuries before the birth of Christ. The Egyptian
75
Papyrus Ebers (c.1500 BC) mentions various purgatives such as castor oil,
colocynth and senna as well as specific vermifuges such as pomegranate 126.
Clay tablets found in the library of Asur-bani-pal (c.650 BC) in Assyria refer to
mint, coriander seeds, onion, colocynth, myrrh, turpentine, pomegranate and
cassia as anthelmintics79. These agents, as well as extracts of Artemisia, acacia
gum, anise seed, fennel, garlic, mulberry, olive oil, pepper, scammony seed,
spearmint and male fern root found their way into the materia medica of
ancient Greece and Rome. Extraordinarily complicated combinations of drugs
and directions for their administration were evolved. Thus, Celsus (c.25 AD)
wrote:
For the flat worms, there should be given as draughts, a decoction of lupins, or of
mulberry bark, to which may be added, after pounding, either hyssop or a vinegar
cupful of pepper, or a little scammony. Alternatively, on one day let him eat a quantity
of garlic and vomit, then on the next day take a handful of fine pomegranate roots,
crush them and boil them in a litre and a half of water down to one-third, to this add
a little soda, and drink it on an empty stomach. At three hours interval, let him take two
further draughts; but with the addition of half a pint of sea water or strong brine; then
on going to stool, sit over a basin of hot water. Again, for the roundworms...., both the
same remedies may be given and some milder ones, such as pounded-up seeds of
nettles or of cabbage or of cummin in water, or mint in the same of a decoction of
worm-wood or hyssop in hydromel or cress-seeds pounded up in vinegar. It is also of
service either to eat lupin or garlic, or administer into the lower bowel a clyster of olive
oil.28
Many of these drugs maintained their popularity over the next two thousand
years.
Pomegranate
The roots or bark of the pomegranate (Punica granatum) have been used as an
anthelmintic for millenia. Perhaps the earliest record is in the Egyptian Papyrus
Ebers:
to kill roundworm: root of pomegranate 5 ro (1 ro = 15 ml), water 10 ro, remains
during the night in the dew, is strained and taken in one day.126
Pomegranate continued to be popular with the physicians of ancient Greece and
Rome for the treatment of both roundworm and tapeworm infections and was
still being recommended around 1,000 AD by the Arabian, Avicenna6.
Nevertheless, pomegranate bark was little valued in northern Europe until the
beginning of the nineteenth century when the Englishman, Buchanan, introduced
it from the the East Indies. The alkaloid, pelleterine, was isolated as the active
principle26 and pomegranate decoctions remained a standard remedy until well
into the twentieth century.
Male fern (filix mas, oleoresin of Aspidium)
Male fern, otherwise known as filix mas or oleoresin of aspidium, is derived

Anthelmintics 77
from the powdered rhizomes of Dryoptera filix mas. These plants are spread
widely throughout the northern hemisphere. The efficacy of this extract in the
treatment of tapeworm infections was recorded long ago by the Greek,
Theophrastus of Eresus (370-c.285 BC) who wrote:
Of male fern, no part but the root is useful and it has a sweet astringent taste. It expels
the flat worm. It has no seed nor juice; and they say it is ripe for cutting in the
autumn.165
Likewise, the Roman, Pliny (23-79 AD), recommended powdered root of male
fern as an anthelmintic24. Filix mas has maintained its popularity in one form or
another for centuries. One classic example of its use was as the major
constituent of Madame Nouffer's "Tapeworm Cure" in the late eighteenth
century. The French king, Louis XVI, was somewhat peeved to find this in 1776
after he had handed over 18,000 francs for the formula. Madame Nouffer's
technique was described by Davaine46. Three drachms of the pulverized root in
four ounces of infusion were administered followed by a bolus of calomel,
scammony and gamboge after two hours. When vomiting occurred, the remedy
was repeated and strong coffee was given to prevent sickness. If the worm was
not fully expelled in four hours, an ounce of magnesium sulphate in warm water
was then drunk.
The general practice was to collect rhizomes of the plant in autumn, free them
from roots and dead parts, then soak them in ether for 48 hours. This was then
filtered out, leaving a dry, oily residue, oil of aspidium. Male fern was added to
the British Pharmacopoeia in 1863. Beginning with the work of Boehm in
1897 14 , a number of phloroglucinol compounds have been isolated as active
principles. The major anthelmintic constituent is filicic acid (= filicin)26. Male
fern remained popular in the treatment of tapeworm infections until more
effective and less toxic drugs became available in the middle of the twentieth
century.
Semen-contra-vermes (Santonin)
Semen-contra-vermes (semen against worms) is so-named because of its

fancied resemblance to semen. It consists of the dried, unexpanded flower heads
obtained from several species of the genus Artemisia (= Santonica), especially
A. cina. It was mentioned by the Roman, Dioscurides Anazarbeus, in the first
century AD as being indicated for the treatment of ascariasis and enterobiasis 50.
It remained popular for centuries and was mentioned by Avicenna (980-1036) 6.
According to Davaine in 186046, it was most effective against Ascaris,
moderately active against tapeworms, and less efficacious against Enterobius.
Semen-contra-vermes was added to the British Pharmacopoeia in 1863. The
active principle is santonin, a sesquiterpene lactone27. The drug was abandoned
in the early twentieth century when more effective and less toxic agents became
available.
Chrysanthemum
Flowers of Chrysanthemum have been used for centuries as anthelmintics. The

active constituents of pyrethrum powder obtained from these plants are
pyrethrins; these substances are also powerful insecticides. Modern studies have
given conflicting reports on the effectiveness of pyrethrins against cestodes26 and
there is some evidence that they are partially active against intestinal
nematodes27.
Tin
Metallic tin has been used to treat tapeworm infections for centuries. Their use
was praised by Paracelsus (1493-1541) 127 and tin filings were commonly
prescribed until the first half of the nineteenth century. This was somewhat
dangerous, however, as tin preparations often contained traces of lead or arsenic
that led to poisoning. "Cestodin", a combination of metallic tin, tin oxide and tin
chloride was used until recent years.
AFRICA
Anthelmintics used traditionally by people living along the Mediterranean

littoral have been described earlier. Little is known of practices in Africa south
of the Sahara. An important remedy in northeastern Africa, however, was
kousso.
Kousso (kosso)
Tapeworm infections have been particularly common for many years among
people living in Ethiopia as a result of the habit of eating raw beef. Con-
sequently, there was also considerable interest in that country in developing
taenicides. The most popular of these was kousso which was derived from the
blood-red flowers and seeds of the tree Hagenia abyssinica (= Banksia abyss-
inica = Brayera anthelmintica). One of the earliest records of its use is the
indication by a sixteenth century monk that Bitole, the fourth Golla chief,
adopted the habit of taking it during his term of office from 1546-1554 124.
The drug attracted the attention of Spanish and Portuguese Jesuit missionaries
in the early seventeenth century. They observed that it was prepared by steeping
a handful of seeds of flowers in two quarts of beer all night then the bitter potion
was drunk in the morning. Little interest in this preparation was shown in
Europe, however, until the Frenchman, Dr Brayer, publicized its effectiveness
in the 1820's125. In 1845, his compatriot, Rochet d'Héricourt brought enough
drug for 40,000 doses to Paris. Its effectiveness was confirmed by several
French medical authorities and it became popular not only in France but also in
Anthelmintics 79
Britain. A major problem initially was its expense but, with increasing
availability, its price fell. Kousso was finally given a place in the British
Pharmacopoeia in 1863. The active principles were identified as phloroglucinol
derivatives, kosin and kosotoxin, related to filicic acid of male fern26. Its
popularity waned in Europe in the latter part of the nineteenth century but it is
still widely used in Ethiopia today.
ASIA
As in the West, herbal remedies were popular in the Orient. Traditional

anthelmintics still in use in India at the beginning of the present century were
derived from the leaves of Clerodendrum infortunatum, fruits of Embelia ribes,
juice of the leaves or the head of the wild date palm (Phoenix dactylifera, and
from the leaves of Costus speciosus as well as the root of the pomegranate
(Punica granatum).
Likewise in China, there was little change in the products used over a period
of 2,000 years78. The most popular plants were "Lei-wan" (Mylitta lapidescens),
"Ho-shih" (Carpesium abrotanoides), "Shih-chun-tze" (Quisqualis indica),
"Ping-lang" (Areca catechu = betel nut), "Shih-liu-p'i" (Punica indica =
pomegranate) and Mallotus philippinensis (= kamala). In addition, a number of
substances of mineral and animal origin were used. Among the former were
included sulphur, lead, tin, mercury and arsenic. Animal products with supposed
vermifugal properties included chicken faeces, pig's blood, ash of human hair,
baked toad and snake skin. Several examples of Chinese anthelmintic
prescriptions are listed below.
a. For Ascaris: Han period (c.220 AD):
"Decoct 2 liang (1 liang = 36 gram) of Kan-ts'ao (= Glycyrrhiza glabra) in 3 sheng
(1 sheng = 1 litre) of water until 2 sheng of the fluid is left. Then discard the
sedimented particles and add to the fluid 1 liang Fen (lead carbonate) and 4 liang Mi
(honey). Stir thoroughly and decoct the mixture again to a solution like congee, 1
sheng of which taken warm, will effect an immediate cure."30
b. For Enterobius: T'ang dynasty (c.650 AD):
"Take one ball of human hair about the size of an egg burned into ashes. Mix the
above, after sifting, with bitter wine, and take the entire solution after rising in the
morning."159
c. For tapeworm: T'ang dynasty (c. 752 AD):
"Suan-shih-liu-ken, root of Punica granatum (pomegranate) one handful of its
branches directing eastwards, 3 liang Wu-i (Ulmus macrocarpa) and one half liang
powdered Ch'ien-niu-tzu seed (Ipomoea hederacea). Decoct the first two drugs in 6
sheng of water. Then filter and divide the total solution into three equal parts. Admix
the powder of the seed of Ipomoea when the drug is to be taken. Take successive
doses at intervals equal to the time required for a five-li walk. All the worms will be
killed and passed out.176
Betel nut (Areca)
Betel nuts are seeds of the palm, Areca catechu, which is widespread in
southern and eastern Asia. According to Liu102, the chewing of betel nut has
been practised for at least 1400 years and has built up a reputation as a
taeniafuge. It may also be administered in the form of a decoction obtained from
the dried, powdered nut. Such a technique is described by Sun Szu-Miao in the
T'ang dynasty (c.650 AD):
Grind 14 pieces of Ping-lang (Areca catechu) into powder and sift. Then boil the shells
of Ping-lang in 2.5 sheng of water until half a sheng of the liquid is left. After filtration,
put the powder into the liquid. Drink the solution from time to time and lie in bed and
keep warm. The worms will come out.159
The active principle is the alkaloid, arecoline26.
Kamala
Kamala is a resin derived from the glands and hairs covering the fruits of
Mallotus philippinensis (= Rotteria tinctoria) which is widespread in Asia and
has been used as a folk remedy for centuries. It became popular in Europe for
the treatment of tapeworm in the nineteenth century and was entered into the
British Pharmacopoeia in 1863, decoctions being prepared in alcohol. Like male
fern and kousso, the active constituents are ploroglucodins such as rottlerine
which paralyse the cestodes26. Its popularity waned with the appearance of more
efficient agents in the twentieth century.
THE AMERICAS
A number of plants have been held in some traditional regard as vermifuges.

These include a legume (Mucuna pruriens), the cebadilla (Spigelia
anthelmintica) in tropical America as well as Fucus helmintocorton, a seaweed
from the west of Argentina78. The most important American plant products,
however, were pumpkin seeds, oil of chenopodium and leche de higueron.
Pumpkin seeds
Pumpkin seeds, particularly Cucurbita pepo, have been used in tropical

America for centuries as a treatment for tapeworm infections. From there, the
popularity of this remedy spread to Europe. Tyson in England, for example,
recommended consumption of pumpkin seeds for taeniasis in 1683171. The seeds
were generally minced into a paste and swallowed. The active component,
cucurbitine, has been isolated and identified as an amino acid,
3-amino-3-carboxy pyrrolidin26.
Anthelmintics 81
Oil of chenopodium
The most widely used indigenous plant anthelmintic from the Americas is oil of
chenopodium derived from Chenopodium ambrosioides, popularly known as
American wormseed, Mexican teak, Jerusalem oak and "epazote" or "paico"89.
This aromatic herb is found as an annual weed in locations varying from
Argentina in the south to Canada in the north. Archaeological and ethnological
studies suggest that it has been used for many centuries. Wild plants have been
found growing in association with long-abandoned Pueblo ruins while the
pre-Columbian Maya of Yucatan in Mexico called it "lucum xiu" meaning
"worm-plant"139. The plant was illustrated in a sixteenth century codex
concerned with the Aztecs49. In the early eighteenth century, Peter Kalm
(1715-1779), a Swedish botanist and traveller, reported that it was used by both
the indigenous inhabitants as well as European settlers in the American colonies
for the treatment of Ascaris 83. In 1723, plants were taken to Europe, cultivated
widely, and were soon in common use. The leaves, seeds and flowering tops
have all been used to produce decoctions. The extracted oil of chenopodium,
usually prepared by boiling, became the common form of the drug throughout
the nineteenth century and during the first half of the twentieth century. The
active principle, ascaridol, a volatile terpene, was isolated and eventually
synthesized 27.
Although Baumler (1881) and Breton (1905) in the United States of America
had tried oil of chenopodium without success in ancylostomiasis, Bruning
began to use it successfully in 190917 then this was confirmed by Schüffner152.
In view of its easy availability and cheapness, oil of chenopodium was employed
with considerable success by the Rockefeller Foundation in hookworm
campaigns in the Dutch East Indies (Indonesia), Malaya (Malaysia) and Fiji in
the 1920's and then in Brazil in the 1930's. Toxic reactions including
gastrointestinal upsets, headache, deafness, tachycardia and rarely death were
recognized with increasing frequency, however, and this together with the
development of other safe, effective anthelmintics led to its official aban-
donment. Moreover, a recent study of traditional village use of Chenopodium
extracts has cast doubts on its efficacy89. Nevertheless, it continues to be used
by millions of urban and rural people in the third world for the treatment of
intestinal worm infections.
Leche de higueron
The inhabitants of equatorial South America and Central America have long
used the sap of the figs, Ficus glabrata and F. laurifolia, as an anthelmintic.
The milky fluid (latex) has been called leche de higueron or lait d'higueron.
Wucherer remarked in 1866 that it was effective in the treatment of hookworm
infection180 then in 1912 Berrio reported that it was useful for trichuriasis 12. The
active principle, ficin, is a protease related to papain27.
Table 3.1. Major anthelmintics listed by Rudolphi140

____________________________________________________________________
Mechanical irritants
Stannum purum et granulatum (tin)
Purgatives
Salina, Glaubers, ammonia etc. (Glaubers' salts etc)
Olea expressa
Olea ricina (castor oil from Ricinus species)
Oleum nucum
Scammoneum (scammony from Convolvulus scammonia)
Helleborum (hellebore from Helleborus species)
True anthelmintics
Stizolobium (from cowhage, Macuna pruriens)
Aqua frigida (ice water)
Oleum Chaberti (Chabert's oil)
Oleum animali Dippelis
Oleum terebinthicae (turpentine from Pistacia terebinthus)
Petroleum
Oleum cajeputi (from Melaleuca)
Camphora (from Camphora officinarum = Laurus camphora)
Artemisiae judaicae sive cinae semen (semen-contra-vermes)
Tanaceti vulgaris semina
Helminthocorton
Goeffroeae surinamensis cortex (bark of Geoffroea surinamensis)
Polypodii (Aspidii) filicis maris radix (root of male fern)
Spigelias
____________________________________________________________________
NINETEENTH CENTURY
When Clericus in Geneva reviewed human helminthology in his book in 1715,

he tabulated the substances believed to have an anthelmintic action that were
known in Europe at that time36. Of these, 379 were vegetable in origin, 27 were
derived from animal products, and 13 were minerals. Those that were
considered to be of greatest value were listed by Rudolphi at the beginning of
the nineteenth century (Table 3.1). He divided these agents into three groups -
"purgatives" which expelled helminths from the gut by increasing intestinal
secretions and stimulating peristalsis, "mechanical irritants" which were
supposed to cause the worms to relax their hold upon the gut mucosa so that
they could be expelled more readily by purgatives, and "true vermifuges" which
poisoned the parasite. Those substances that really were important anthelmintics
are all traditional remedies and have been described already.
Anthelmintics 83
FIRST QUARTER OF THE TWENTIETH CENTURY
One major advance in the chemotherapy of helminth infections was made during
the first quarter of the twentieth century. This was the discovery that antimony
compounds when administered intravenously were effective in the treatment of
schistosomiasis. In addition, a number of other compounds with some
anthelmintic efficacy were described.
Antimonials
In 1918, Christopherson reported that the antimony compound, tartar emetic

(antimony tartaratum, potssium antimony tartrate) was extremely effective in
human infections with Schistosoma haematobium and S. mansoni 31. His
serendipitous discovery of the use of this drug for schistosomiasis while
treating a patient with kala azar is detailed in chapter 8. Pentavalent anti-
monials were found to be ineffective in schistosomiasis but a number of trivalent
organic antimony compounds including sodium antimony tartrate, stibophen
(fouadin), lithium antimony thiomalate (anthiomaline), sodium antimony
gluconate (triostam) and sodium antimony dimercaptosuccinate (stibocaptate,
astiban), were developed. The relative advantages and efficacies of these
compounds are discussed further in chapter 8. Antimony therapy of
schistosomiasis was taken up enthusiastically and, despite some toxicity, re-
mained the cornerstone of treatment for these infections for the next forty to fifty
years.
Betanaphthol
Betanaphthol is a synthetic naphthalene derivative which was first used as a

treatment for hookworm by Bentley in 190411. Its side-effects, particularly in
causing haemolysis and renal damage, led to its falling into disfavour.
Bismuth
Bismuth carbonate was used by Loeper in 1921 for the treatment of enterobiasis
but did not enjoy wide favour104.
Carbon tetrachloride
In 1921, Hall reported that carbon tetrachloride was a useful anthelmintic in

animals with intestinal nematode infections70. Having swallowed some himself
without ill-effect, he suggested its use in the treatment of human hookworm
infection71. The effectiveness of this drug in ancylostomiasis was soon
confirmed7,99 and it was also reported to be useful in tapeworm infections143 .
Doubts soon arose about its toxicity when a number of people died of liver
failure158, however, and it fell rapidly into disuse.
SECOND QUARTER OF THE TWENTIETH CENTURY
The pace of discovery quickened considerably during the second quarter of the
twentieth century. These drugs influenced many helminth infections and ranged
from the introduction of tetrachlorethylene in the treatment of hookworm
infection to the use of lucanthone for the therapy of schistosomiasis and
diethylcarbamazine for filariasis.
Arsenicals
Arsenical compounds were introduced by Erlich for the treatment of trypan-

osomiasis and syphilis at the dawn of the twentieth century. In 1905, Blair had
claimed that sodium arsenite produced clinical improvement in dogs with
heartworm infection but produced no supporting parasitological details. Neo-
arsphenamine was soon tried in bancroftian filariasis with disappointing results.
In 1940, Hawking noted that phenyl arsenoxide derivatives were micro-
filaricidal in vitro but little attention was paid to this observation because of the
distractions of war74. A few years later, Otto and Maren noticed an action of
arsenicals against both adult worms and microfilariae of Litomosoides 121 and
Dirofilaria immitis 122. The most effective preparations were arsenamide and
several melarsen derivatives.
Arsenamide (thiacetarsamide) was used in humans infected with Wuchereria
bancrofti 166 amd Onchocerca volvulus 122. Melarsenoxide was used against W.
bancrofti by Culbertson 41 and found to be moderately effective but dangerous.
A soluble derivative, melarsenoxide potassium dimercaptosuccinate (Mel W)
was also tried in bancroftian filariasis106 and onchocerciasis 62 a few years later.
Unfortunately, these drugs may be highly toxic, particularly to the liver, kidney
and brain. They therefore fell into disrepute for the treatment of filarial diseases
since these conditions, although they may produce significant morbidity, rarely
cause death.
For similar reasons, arsenicals have been little used in intestinal nematode
infections although acetarsol was employed in enterobiasis by Perrin in 1927132
and diphetarsone was tried in trichuriasis by Junod83.
Cashew nut oil (oil of anacardium)
Cashew nut oil is obtained from Anacardium occidentale, a tree indigenous to

tropical America. The oil was shown to be effective in canine ancylostomiasis
then was used with some effect in human hookworm infection53.
Anthelmintics 85
Chloroquine
Chloroquine was introduced in the 1940's as an antimalarial agent. In 1949,

Basnuevo used it with some success in patients with fascioliasis 9. Subsequently,
Chung and colleagues claimed some value for the drug in the treatment of
paragonimiasis 32 while others believed it had a place in the management of
opisthorchiasis 142.
Diethylcarbamazine
In 1947, Hewitt and his colleagues showed that the piperazine derivative,
diethylcarbamazine, was active against Litomosoides carinii in cotton rats and
against Dirofilaria immitis in dogs76. This anthelmintic was the result of a
research programme initiated because of the large number of American veterans
who had acquired filariasis during World War II. Later in the same year,
Santiago-Stevenson described the use of diethylcarbamazine in humans with
bancroftian filariasis and noted that it produced a dramatic fall in the numbers
of circulating microfilariae144. Subsequent observations, however, revealed that
these effects were not sustained. Within a year or two, a number of investigators
reported that diethylcarbamazine produced some clinical improvement in
patients with loiasis154,156. The majority of these patients did not have
microfilaraemia, however, and it took some little time for it to become clear that
the reduction in microfilaraemia was transient. Likewise, the effects of
diethylcarbamazine in onchocerciasis were soon examined. In 1948, Mazzotti
and Hewitt found some reduction in the numbers of microfilariae in the skin
after diethylcarbamazine treatment but observed living adult worms in extirp-
ated nodules113. Mazzotti then noted that microfilarial numbers in the skin built
up again to pre-treatment levels over the next few months112. In contrast to all
of these conditions, Danaraj in 1958 observed that the ill-defined filarial
infection, tropical pulmonary eosinophilia, responded dramatically and perm-
anently to diethylcarbamazine treatment45.
Although diethylcarbamazine has been used primarily in filarial infections,
it has also been used for the treatment of gastrointestinal nematode infections.
Hewitt and colleagues in 1948 observed that it was effective in canine ascar-
iasis77 then in the following year Oliver-Gonzalez and others showed that it was
reasonably effective in humans infected with Ascaris lumbricoides 120. While
diethylcarbamazine was thought to be moderately valuable in ancylostomiasis 44,
it was noted to be ineffective in enterobiasis 105.
Gentian violet and related dye-stuffs
Gentian violet is a dye-stuff composed of a mixture of variable proportions of

the tetra-, para- and hexylmethyl derivatives of rosaniline. Kudiche showed in
1925 that the related compounds, crystal violet and fuchsin, killed Strongyloides
stercoralis infective larvae in vitro 91. In 1928, de Langen reported that oral
administration of gentian violet in conjunction with intravenous injection of
tartar emetic was effective in strongyloidiasis 97 but in the following year he
acknowledged that his patients had relapsed98. Faust, on the basis of exper-
iments in monkeys, believed that adult worms were killed in situ 56 then in 1932
claimed that 95% of patients were cured by oral gentian violet57. Palmer123 gave
gentian violet by slow intravenous injection in this condition then Schreiber 151
extolled its value when given by duodenal intubation. Nevertheless, the
preponderance of opinion was that the drug was of little value in the treatment
of strongyloidiasis.
Wright and Bray in 1938 used gentian violet for the treatment of entero-
biasis179 but much more effective drugs are now available.
Hexylresorcinol
Hexylresorcinol is a phenol which was shown by Lamson and his colleagues in

1931 to be effective in the treatment of ascariasis 95. Shortly afterwards,
Maplestone and Mukerji reported that it was active againt Taenia saginata 110.
It then became the treatment of choice for hymenolepiasis until recent times.
Likewise, hexylresorcinol has been used in fluke infections such as fasciol-
opsiasis108.
Lucanthone and hycanthone
Lucanthone (miracil D, nilodin) was the first schistosomicidal drug which was
metal-free and orally active. Its efficacy in experimental schistosomiasis was
first shown by Kikuth and colleagues during World War II2 then this was
reported several years later88. Experimental and clinical studies indicated that
it was most active against Schistosoma haematobium, less active against S.
mansoni and had little effect on S. japonicum. It was shown eventually by Rosi
and co-workers that the active form was an hydroxymethyl derivative now
known as hycanthone138. This drug was then used clinically as hycanthone
methanesulphonate (etrenol)35. Concern was expressed about possible muta-
genic effects, however, and it was eventually replaced by more effective and less
toxic agents.
Mepacrine (quinacrine, atebrin, atabrine)
Mepacrine was originally synthesized as an antimalarial compound in 1932. In

1939, Neghme reported that it was useful in the treatment of Taenia saginata
and T. solium infections118. Ruikka showed in 1951 that it was also effective in
diphyllobothriasis 141. Mepacrine became a very popular treatment for tapeworm
infections until the introduction of niclosamide.
Anthelmintics 87
Phenothiazine
The anthelmintic properties of phenothiazine were first recognized by Harwood

and colleagues who reported in 1938 that it eliminated ascarids from the
intestines of swine73. Manson-Bahr then showed in 1940 that it was effective in
humans infected with Enterobius vermicularis 109. However, less toxic agents
soon became available for the treatment of intestinal nematode infections.
Piperazine (diethylenediamine)
In 1942, Giroud noted that a patient infected with Enterobius was cured when
treated with piperazine. This observation was taken up by Mehrez who in 1947
confirmed its effectiveness 115. Two years later, Fayard described its efficacy in
ascariasis58. This drug was so superior to all previously available agents for the
treatment of ascariasis and enterobiasis that Bueding and Swartzwelder in
195718 considered its discovery to be one of the most important turning points
in development of the chemotherapy of helminthiasis. Piperazine was prepared
in a number of forms including the hydrate, citrate, adipate and phosphate
compounds. Piperazines were shown rapidly to be ineffective in the other major
intestinal nematode infections but they are still widely used in many countries
as inexpensive, popular anthelmintics.
Suramin (antrypol)
Suramin was introduced in 1921 for the treatment of trypanosomiasis. In 1945,

van Hoof and his colleagues, during experimental infections on trypanosomiasis
in volunteers, fortuitously discovered that it also acted upon Onchocerca
volvulus adult worms (cited in177). This action was then confirmed by Ashburn
and colleagues 4. Subsequently, Thooris showed that it killed Wuchereria
bancrofti adult worms as well170. It was observed, however, that this drug may
cause serious toxic effects, particularly to the kidney, and it has not found a
place in the treatment of filariasis and its role in the management of
onchocerciasis remains doubtful.
Tetrachlorethylene
Tetrachlorethylene was introduced by Hall and Shillinger in 1925 for the

treatment of hookworm infection72 four years after the advent of carbon tetra-
chloride. Its effectiveness was confirmed by Schapiro and Stoll148. In 1929,
Lamson and colleagues showed that this drug was significantly less toxic than
carbon tetrachloride 96. Although it still had significant toxicity, it remained a
very popular anti-hookworm therapy for several decades.
THIRD QUARTER OF THE TWENTIETH CENTURY
Wide ranging advances in anthelmintic therapy occurred in the third quarter of

the twentieth century. A number of new drugs were developed for the treatment
of schistosomiasis, niclosamide became available for the therapy of tapeworm
infections, and the benzimidazole series of anthelmintics appeared.
Bephenium
In 1958, Copp and his colleagues reported the discovery of quaternary ammon-
ium compounds effective against intestinal nematodes; of these, bephenium was
the most interesting37. In the same year, the drug was reported to be an effective
agent against Ancylostoma caninum and Toxocara canis in dogs and T. cati in
felines21 then was shown to be superior to tetrachlorethylene in the treatment of
human ancylostomiasis 66,184. Moreover, the drug was noted to be effective also
against Ascaris lumbricoides 66 and to be variably effective in
trichostrongyliasis 68 and heterophyiasis117 but ineffective in enterobiasis and
strongyloidiasis.
Bithiniol
Bithiniol was described originally as a bactericidal and antifungal agent but in

1957 Sawada reported that it was active against the chicken tapeworm
Raillietina kashiwarensis 147. It was then shown to expel Taenia saginata 183 and
Diphyllobothrium latum 116 from humans.
Dichlorophene
This halogenated hydroxyphenylmethane was shown in 1946 to be active

against tapeworms in dogs40. Its use in human Taenia saginata infections was
first suggested in 1956114,153.
Dithiazanine
Dithiazanine iodide is a dicarbocyanine dye which was demonstrated as having

anthelmintic properties in experimental animals by MacCowen and colleagues
in 1957107. They showed that it was effective against Ascaris, Ancylostoma and
Trichuris infections in cats and dogs. These actions in human intestinal
infections were confirmed in the same year. The distinctive feature of dithia-
zanine in contrast to earlier anthelmintics was that while it had limited activity
in ascariasis, ancylostomiasis and enterobiasis, it was active against Trichuris
trichiura 63,160 and Strongyloides stercoralis 160. Likewise, encouraging reports
appeared of its value in taeniasis175 and clonorchiasis 181. Unfortunately, at least
eight deaths due to dithiazanine administration occurred1,137,157 and the drug was
Anthelmintics 89
withdrawn from the market.
Hetol (chloxyl)
This chlorinated benzene derivative (1,4-bis trichloromethylbenzene) was

shown to be effective in the treatment of fascioliasis in various animal species
by Lämmler in 196094. Some success attended its use in human fascioliasis 133,
clonorchiasis 182, paragonimiasis 33 and opisthorchiasis 134.
Hexachlorophene
Hexachlorophene was tried in clonorchiasis with mixed success by Chung and

colleagues 34 and by Liu103.
Metrifonate
Metrifonate is an organophosphate compound. These substances have been used

as insecticides since the 1950's. Their use as anthelmintics in veterinary
medicine was first described by Levine and colleagues in 1958100. In 1960, Da
Cruz Ferreira and co-workers reported on its use in ancylostomiasis but it was
variably effective and caused some intolerance 43. Two years later, Cerf and
others showed that it was moderately effective against both Ascaris lumbri-
coides and Schistosoma mansoni 29. In 1963, Talaat and colleagues confirmed
this observation and also showed that metrifonate was active against S. haem-
atobium 163. Subsequent experience indicated that this drug was particularly
useful for S. haematobium infections and it was not used for other forms of
schistosomiasis 59.
Niclosamide
In 1960, Gönnert and Schraufstätter described a new molluscicide, niclosamide

(molluscicide Bayer 73). Screening studies showed that it was active against
Hymenolepis diminuta in rats65. World-wide clinical trials followed and it was
shown that it was active against practically all the tapeworms of man42,90.
Niclosamide remains one of the drugs of choice for the treatment of tapeworm
infections.
Niridazole
In 1964, Lambert reported that niridazole was active against Schistosoma

mansoni infections in mice92. In the following year, Lambert and Da Cruz
Ferreira showed that it was effective in humans with urinary schistosomiasis in
Portuguese Guinea (Guinea Bissau)93. Further observations revealed that in
humans, niridazole was more active against S. haematobium than S. mansoni
82
and least active against S. japonicum 145. Niridazole held pride of place in the
treatment of urinary schistosomiasis for a short period but has now been largely
displaced by less toxic drugs, especially praziquantel.
Oxamniquine
In 1973, Foster and colleagues reported that oxamniquine was active against
Schistosoma mansoni in rodents and monkeys although it was inactive against
S. haematobium and S. japonicum 60. In the same year, Katz and his colleagues
tested the efficacy of the drug when given by oral and intramuscular routes to
humans with schistosomiasis in Brazil and observed that the latter route was
preferable85. Subsequent studies indicated that oxamniquine was more active
against South American than African strains of S. mansoni 162.
Oxantel
Oxantel is an analogue of pyrantel that was shown to be effective in trichuriasis

by Lim in 1974101 but has little effect on ascariasis and hookworm infection. It
has therefore been used sometimes in combination with pyrantel.
Paromomycin
Paromomycin is an antibiotic with antibacterial and amoebicidal properties.

Ulivelli reported in 1963 that it was effective in humans with taeniasis172.
Pyrantel
In 1966, Austin and colleagues reported that pyrantel was an effective

broadspectrum anthelmintic in domestic animals5. Three years later, Bumbalo
and co-workers showed that it was useful in human enterobiasis 19 then in 1970
Desowitz and others found that it was effective in ascariasis and hookworm
infection but not in trichuriasis 48.
Stilbazium
The anthelmintic actions of stilbazium iodide in infected animals were first

escribed by Burrows and colleagues in 196122. In the following year, Swartz-
welder and co-workers reported that it was effective in humans infected with
Ascaris lumbricoides, Enterobius vermicularis and Trichuris trichiura but was
of little value in ancylostomiasis 161. This drug has not found a permanent place
in the therapeutic armamentarium.
Anthelmintics 91
Tetramisole and Levamisole
In 1966, Thienpont and his colleagues described tetramisole as a potent

broadspectrum veterinary anthelmintic 167. Later in the same year, Do Nasc-
imento and colleagues showed that it was effective in humans with ascariasis 51.
Subsequent observations, however, revealed that its activity was relatively poor
in hookworm infection, trichuriasis and strongyloidiasis. In 1969, Thienpont and
his collaborators showed that the levo-isomer of tetramisole, levamisole, was
more active against Ascaris lumbricoides than the racemate and was useful in
hookworm infection and possibly in strongyloidiasis but was not effective in
trichuriasis or enterobiasis 166.
Thiabendazole, Mebendazole, Albendazole and other Benzimidazoles
Thiabendazole was introduced in 1961 when Brown and his colleagues showed
that this agent had broadspectrum activity against intestinal nematodes in pigs
and horses15. Later that year, Gordon indicated that it was highly effective
against nematode infections of the gastrointestinal tract of sheep67. The drug was
then tried in human infections and was found to be variably effective in
ascariasis81, enterobiasis54 , ancylostomiasis81,173 and strongyloidiasis 61,173
but
inactive in trichuriasis.
Mebendazole was introduced in 1971 by Brugmans and colleagues who
showed that it was effective in enterobiasis16. It was soon noted to be also active
in ascariasis 64,129, trichuriasis64,129 , ancylostomiasis8,64 , trichostrongyliasis3 and
capillariasis 155 but to be of doubtful efficacy in strongyloidiasis. In addition,
mebendazole was shown to be of some value in intestinal taeniasis87,119. Sub-
sequently, experimental studies in animals suggested that it may be of value in
echinococcosis 75 then it was used with partial success in humans with hydatid
infections by Bekhti and colleagues in 197710.
The activity of albendazole against certain trematode, cestode and nematode
infections in animals was described by Théodoridès and colleagues in 1976164.
It was shown to be effective in a number of human gastrointestinal nematode
infections including enterobiasis, ascariasis, trichuriasis and ancylostomiasis by
Pene and co-workers in 1981130 but to be of variable effectiveness in
strongyloidiasis 38. More recently, it has been suggested that albendazole may be
better than mebendazole in the treatment of infections with Echinococcus
granulosus and E. multilocularis 128.
Cambendazole was used in strongyloidiasis with good effect by Martirani and
Rodrigues in 1976111 but the drug has since been withdrawn from the market.
Flubendazole, a fluorine analogue of mebendazole, was reported to have
similar activity to that compound by Schenone and colleagues 149.
Viprynium (Pyrvinium)
Viprynium pamoate is a cyanine dye. In 1953, both Hales and Welch69 and
Weston and others178 showed that it had anthelmintic activities in animals. It was
then shown in the same year to be of some value in human hookworm infection
by Perez-Santiago and colleagues131 but its main role came to be in the treatment
of enterobiasis.
FINAL QUARTER OF THE TWENTIETH CENTURY
The last quarter of the twentieth century is only halfway through but already
two valuable new drugs, ivermectin and praziquantel, have appeared.
Ivermectin
Studies on the fermentation broth of the actinomycete, Streptomyces aver-

mitilis, revealed that it was active against Nematospiroides dubius in mice. In
1978, Blair and Campbell reported that a purified product of this broth, iver-
mectin, was active against Ancylostoma caninum 13 and Dirofilaria immitis 25
in dogs. Subsequently, it was observed that ivermectin had extraordinary
potency against a wide range of nematodes and arthropods. In 1984, Coulaud
and colleagues reported that it was useful in the treatment of humans with
onchocerciasis 39.
Praziquantel
Praziquantel was identified from a group of heterocyclic pyrazino-isoquinolines

and found to have unusually broad anthelmintic activity. In 1975, Thomas and
his colleagues reported its efficacy against intestinal tapeworms 169. In 1977,
Espejo showed that it was valuable in the treatment of infections with
Hymenolepis, Taenia solium and Diphyllobothrium pacificum 55 while Bylund
and colleagues documented its use in D. latum infections23. In 1979, a number
of reports appeared describing its use in the three major schistosome infections
of man47,80,86,146. Subsequently, its value in clonorchiasis135 , fasciolopsiasis20 ,
fascioliasis 150 and paragonimiasis 136 was reported.
CONCLUSION
It is only fifty years since the sulphonamides first appeared then penicillin
ushered in the dawn of antibiotic therapy of bacterial infections. In that short
time, a variety of antibiotics have been developed for the treatment of the vast
majority of bacterial infections. In contrast, cures for worms have been sought
Anthelmintics 93
for millenia. Although remarkable advances have been made in recent times,
many helminthiases, particularly nematode and cestode infections of the tissues,
remain refractory to therapy. They offer a continuing challenge for
parasitologists, pharmacologists and physicians.
REFERENCES
1. ABADIE SH, SAMUELS M. A fatality associated with dithiazanine therapy. Journal of

the American Medical Association 192: 326-327, 1965
2. ANONYMOUS. Combined Intelligence Objectives Subcommittee File No. 25, volume 54,
1945. British Intelligence Objectives Subcommittee Final Report, volume 116, 1946
3. ARFAA F, FARAHMANDIAN I. Progress achieved in the chemotherapy of soil-trans-
mitted helminths. Chemotherapy 6: 11-22, 1976
4. ASHBURN LL, BURCH TA, BRADY FJ. Pathologic effects of suramin, hetrazan and
arsenamide on adult Onchocerca volvulus. Boletin del Oficina Sanitaria Panamericana 28:
1107-1117, 1949
5. AUSTIN WC, COURTNEY W, DANILEWICZ JC, MORGAN DH. Pyrantel tartrate, a
new anthelmintic effective against infections of domestic animals. Nature 212: 1273-1274,
1966
6. AVICENNA. Libri in re medica omnes, qui hactenus ad nos pervenere etc., V Valgrisius,
Venetiis, pp 966, 1564. Original Arabic version, "Al Canon fi Al Tib", circa 1,000 AD
7. BAIS WJ. Tetrachlorokoolstof als mijnwormmiddel. Geneeskundig Tijdschrift voor Neder-
landsch-Indië 62: 381-391, 1922
8. BANNERJEE D, PRAKASH O, KALIYUGAPERUMAL V. A clinical trial of meben-
dazole (R 17635) in cases of hookworm infection. Indian Journal of Medical Research 60:
562-566, 1972
9. BASNUEVO JG. Cloroquina y clonorchiasis. Revista Kuba de Medicina Tropical y Para-
sitologia 5: 105-110, 1949
10. BEKHTI A, SCHAAPS JP, CAPRON M, DESSAINT JP, SANTORO F, CAPRON A.
Treatment of hepatic hydatid disease with mebendazole: preliminary results in four cases.
American Journal of Tropical Medicine and Hygiene 24: 1047-1051, 1977
11. BENTLEY CA. Some notes on ancylostomiasis in Assam. Indian Medical Gazette 39:
135-136, 1904
12. BERRIO LP. Contribution à l'étude de la trichocéphalose et de son traitement par le latex
d'higueron. Revue de Médecine et d'Hygiene Tropicale 9: 178-184, 1912
13. BLAIR LS, CAMPBELL WC. Efficacy of avermectins against Ancylostoma caninum in
dogs. Journal of Helminthology 52: 305-307, 1978
14. BOEHM R. Beitrag zur Kenntnis der Filixsauregruppe. Archiv für experimentelle Path-
ologie und Pharmakologie 28: 305-307, 1897
15. BROWN HD, MATZUK AR, ILVES IR, PETERSON LH, HARRIS SA. Antiparasitic
drugs. N-2-(4'thiazolyl)-benzimidazole, a new anthelmintic. Journal of the American
Chemical Society 83: 1764-1765, 1961
16. BRUGMANS JP, THIENPONT DS, VAN WIJNGAARDEN I, VANPARIJS OF,
SCHUERMANS VL, LAUWERS HL. Mebendazole in enterobiasis: radiochemical and
pilot clinical study in 1,278 subjects. Journal of the American Medical Association 217:
313-316, 1971
17. BRUNING H. Zur Frage der Helminthiasis-Therapie in den Tropen. Archiv für Schiffs-
und Tropen-Hygiene 14: 733-738, 1910
18. BUEDING E, SWARTZWELDER JC. Anthelmintics. Pharmacological Reviews 9:
329-365, 1957
19. BUMBALO TS, FUGAZZOTTO DV, WYCAZLEK JV. Treatment of enterobiasis with
pyrantel pamoate. American Journal of Tropical Medicine and Hygiene 18: 50-52, 1969
20. BUNNAG D, RADOMYOS P, HARINASUTA T. Field trial on the treatment of fasciol-
opsiasis with praziquantel. Southeast Asian Journal of Tropical Medicine and Public Health
14: 216-219, 1983
21. BURROWS RB. The anthelmintic effect of bephenium on Ancylostoma caninum. Journal
22. BURROWS RB, HUNT GR, LILLIS WG. A new series of pyridines with anthelmintic
activity. Journal of Parasitology 47: Supplement, 35-46, 1961
23. BYLUND BG, BANG B, WIKGREEN K. Tests with a new compound (praziquantel)
against Diphyllobothrium latum. Journal of Helminthology 51: 115-119, 1977
24. CAIUS PLINIUS SECUNDUS. Historia naturalis, translated by J Bostock and H T Riley,
Bohn's Classical Library, six volumes, London, 1855-1857
25. CAMPBELL WC, BLAIR LS. Efficacy of avermectins against Dirofilaria immitis in dogs.
Journal of Helminthology 52: 308-310, 1978
26. de CARNERI I, VITA G. Drugs used in cestode diseases. In, International encyclopedia
of pharmacology and therapeutics, section 64, Chemotherapy of helminthiasis, R Cavier
and F Hawking (Editors), Pergamon Press, Oxford, volume 1, pp 145-213, 1973
27. CAVIER R. Chemotherapy of intestinal nematode diseases. In, International encyclopedia
of pharmacology and therapeutics, section 64, Chemotherapy of helminthiasis, R Cavier
and F Hawking (Editors), Pergamon Press, Oxford, volume 1, pp 215-436, 1973
28. CELSUS AC. De medicina, translated by WG Spencer, Loeb Classical Library, Hein-
emann, London, three volumes, 1948-1953
29. CERF J, LEBRUN A, DIERICH XJ. A new approach to helminthiasis control: the use of
an organophosphorus compound. American Journal of Tropical Medicine and Hygiene 11:
514-517, 1962
30. CHANG CHUNG-CHING. (Synopsis of the golden chest.) In, Chung-Ching's complete
work. About 217 AD. In Chinese, partly translated in 78
31. CHRISTOPHERSON JB. The successful use of antimony in bilharziasis administered as
intravenous injections of antimony tartaratum (tartar emetic). Lancet ii: 325-327, 1918
32. CHUNG HL, CH'EN C, HOU TC. Preliminary observations on efficacy of chloroquine in
treatment of paragonimiasis. Chinese Medical Journal 72: 1-14, 1954
33. CHUNG HL, K'O HY, TS'AO WC, HSU CP. Hexachloroparaxylol as a new specific
remedy for curing paragonimiasis in cats and man. Chinese Medical Journal 85: 756-759,
1965
34. CHUNG HL, TS'AO WC, HSU HC, KUO CH, K'O HY, MO PS, CHANG HY, CHUO
HT, CHOU WH. Hexachlorophene (G.11) as a new specific drug against Clonorchis
sinensis. Chinese Medical Journal 82: 691-701, 1963
35. CLARKE V de V, BLAIR DM, WEBER MC. Field trials of hycanthone (etrenol
Winthrop) in the treatment of urinary and intestinal bilharziasis. Central African Journal of
Medicine 15: 1-6, 1969
36. CLERICUS (LE CLERC) D. Historia naturalis et medica latorum lumbricorum intra hom-
inem et alia animalia, nascentia, Fratres de Tournes, Genevae, pp 449, 1715. A natural and
medicinal history of worms bred in the bodies of men and other animals etc., translated by
J Browne, printed for J Wilcox at the Green Dragon, Little Britain, pp 436, 1721
37. COPP FC, STANDEN OD, SCARNELL J, RAWES DA, BURROWS RB. A new series
of anthelmintics. Nature 181: 183, 1958
38. COULAUD JP, DELUOL AM, CENAC J, ROSSIGNOL JF. L'albendazole dans le
traitement de la strongyloidose. À propos de 66 observations. Bulletin de la Société de
Pathologie Exotique 75: 530-533, 1982
39. COULAUD JP, LARIVIÈRE M, AZIZ MA, GERVAIS MC, GAXOTTE P, DELUOL
A M, CENAC J. Ivermectin in onchocerciasis. Lancet i: 526-527, 1984
40. CRAIGE AH, KLECKER AL. Taenicical action of di-phentane-70. North American
41. CULBERTSON JT. Experimental chemotherapy of filariasis. Transactions of the Royal
Anthelmintics 95
Society of Tropical Medicine and Hygiene 41: 18-54, 1947

42. DA CRUZ FERREIRA FS, DE OLIVEIRA LECUONA M, LOPES DA CUNHA CS.
Ensaios terapeuticos con o Bayer 2353 (Yomesan) na teniase (T. saginata). Anais do
Instituto de Medicina Tropical 17: 1009-1015, 1960
43. DA CRUZ FERREIRA FS, LOPES DA CUNHA CA, CARVALHO RF. Ensaios
terapeuticos com o Bayer 2349 na ancilostomiase. Anais do Instituto do Medicina Tropical
17: 655-668, 1960
44. DANA R, SEBAG A, COHENS J, BORSINI G. Ankylostomose et accessoirement
ascaridiose par le diéthylcarbamyl-1-methyl-4-pipérazine. Tunisie Médicale 38: 875-879,
1950
45. DANARAJ T. The treatment of eosinophilic lung (tropical eosinophilia) with
diethylcarbamazine. Quarterly Journal of Medicine 27: 243-263, 1958
46. DAVAINE CJ. Traité des entozoaires et des maladies vermineuses de l'homme et des
animaux domestiques, JB Baillière et fils, Paris, pp 838, 1860
47. DAVIS A, BILES JE, WRICH AM. Initial experience with praziquantel in the treatment
of human infection due to Schistosoma haematobium. Bulletin of the World Health
Organization 57: 773-780, 1979
48. DESOWITZ RS, BELL TH, WILLIAMS J, CARDINES R, TAMARUA M. Anthelmintic
activity of pyrantel pamoate. American Journal of Tropical Medicine and Hygiene 19:
775-778, 1970
49. DIBBLE CE, ANDERSON AJ. General history of the things of New Spain (Florentine
Codex), translated by CE Dibble and AJ Anderson, School of American Research,
University of Utah, Museum of New Mexico, Santa Fe, 1963
50. DIOSCORIDES ANAZARBEUS. De medica materia libros quinque enarrantiones, W
Ribelius, Argentorati, pp 535, 1554
51. DO NASCIMENTO OB, HALSMAN M, ORIA H, CAMPOS JV. Ensaio terapeutico na
ascariase com doses unica de novo antihelmintico de sintese (tetramisole). Revista do
Instituto de Medicina Tropical de São Paulo 8: 143-147, 1966
52. EBBELL B. The Papyrus Ebers, the greatest Egyptian medical document, translated by B
Ebbell, Levin and Munksgaard, Copenhagen, pp 135, 1937
53. EICHBAUM FW, KOCH-WESER D, LEAO AT. Activity of cashew (Anacardium
occidentalis) nutshell oil in human ancylostomiasis. American Journal of Digestive
Diseases 17: 370, 1950
54. ESCOBAR AJ. Tiabendazole, un nueva antihelmintico de amplio espectro. Antioquia
Médica 14: 369-387, 1964
55. ESPEJO H. Tratamiento de infecciones por Hymenolepis nana, Taenia solium y Diphyll-
obothrium pacificum con praziquantel. Boletín Chileno de Parasitología 32: 39-40, 1977
56. FAUST EC. Human strongyloidiasis in Panama. American Journal of Hygiene 16:
203-211, 1931
57. FAUST EC. The symptomatology, diagnosis and treatment of Strongyloides infection.
Journal of the American Medical Association 98: 2276-2277, 1932
58. FAYARD C. Ascaridiose et pipérazine. Thèse Méd. (Paris), No. 889, 1949
59. FORSYTH DM, RASHID C. Treatment of urinary schistosomiasis. Practice and theory.
Lancet i: 130-133, 1967
60. FOSTER R, CHEETHAM BL, KING DF. Studies with the schistosomicide oxamniquine
(UK-4271). Activity in rodents and in vitro. Transactions of the Royal Society of Tropical
Medicine and Hygiene 67: 685-693, 1973
61. FRANZ KH. Clinical trials with thiabendazole against intestinal nematodes infecting
humans. American Journal of Tropical Medicine and Hygiene 14: 383-386, 1963
62. FRIEDHEIM EA. Quelques observations concernant le Mel W dans le traitement de la
filariose à O. volvulus et à W. bancrofti. Annales de la Société Belge de Médecine
Tropicale 41: 367-372, 1961
63. FRYE WW, SWARTZWELDER JC, LAMPERT R, ABADIE SH, CARSON CB. An
effective trichuricide suitable for oral administration. American Journal of Tropical

64. GATTI F, KRUBWA F, LONTIE M, VANDEPITTE J, THIENPONT D. Clinical exper-
ience with mebendazole, a new broad-spectrum anthelmintic. Advances in antimicrobial and
antineoplastic chemotherapy, Urban Schwarzenberg, 1972
65. GÖNNERT R, SCHRAUFSTÄTTER E. Experimentelle Untersuchungen mit N-(2'-
chlor-4'nitrophenyl)-5-chlorsalicylamid, einem neuen Bandwurmmittel. I. Mitteilung:
Chemotherapeutische Versuche. Arzneimittel-Forsch 10: 881-884, 1960
66. GOODWIN LG, JAYEWARDENE LG, STANDEN OD. Clinical trials with bephenium
hydroxynaphthoate (Alcopar) against hookworm in Ceylon. British Medical Journal ii:
1572-1576, 1958
67. GORDON H McL. Thiabendazole: a highly effective anthelmintic for sheep. Nature 191:
1409-1410, 1961
68. HAHN SS, KANG HY, HAHN YS. The anthelmintic effect of bephenium hydroxy-
naphthoate on intestinal helminths. Journal of Tropical Medicine and Hygiene 63: 180-184,
1960
69. HALES D, WELCH A. A preliminary study of the anthelmintic activity of cyanine dye 715
in dogs. Journal of Pharmacology and Experimental Therapeutics 107: 310-314, 1953
70. HALL MC. Carbon tetrachloride for the removal of parasitic worms, especially hook-
worms. Journal of Agricultural Research 21: 157-175, 1921
71. HALL MC. The use of carbon tetrachloride for the removal of hookworms. Journal of the
American Medical Association 77: 1641-1643, 1921
72. HALL MC, SHILLINGER J. Tetrachlorethylene, a new anthelmintic. American Journal
of Tropical Medicine 5: 229-237, 1925
73. HARWOOD PD, JERSTAD AC, SWANSON LE. The efficacy of phenothiazine for the
removal of ascarids from swine. Journal of Parasitology 24: Supplement, 16-17, 1938
74. HAWKING F. Chemotherapy of tissue nematodes. In, International encyclopedia of
pharmacology and therapeutics, section 64, volume 1, Chemotherapy of helminthiasis, R
Cavier and F Hawking (Editors), Pergamon Press, Oxford, pp 437-500, 1973
75. HEATH DD, CHRISTIE MJ, CHEVIS RA. The lethal effect of mebendazole on
secondary Echinococcus granulosus, cysticerci of Taenia pisiformis and tetrathyridia of
Mesocestoides corti. Parasitology 70: 273-285, 1975
76. HEWITT RI, KUSHNER S, STEWART HW, WHITE E, WALLACE WS, SUBBA-
ROW Y, Experimental chemotherapy of filariasis. Journal of Laboratory and Clinical
Medicine 32: 1293-1329, 1947
77. HEWITT RI, WALLACE WS, WHITE RE, SUBBAROW Y. The treatment of ascariasis
in dogs with 1-diethyl-carbamyl 4-methylpiperazine hydrochloride. Journal of Parasitology
34: 237-239, 1948
79. HORGAN ES. Medicine and surgery in the most ancient East-Babylonia and Egypt. Sudan
Notes and Records, volume 30, supplement pp 39-46, 1949. Cited in 78
80. ISHIZAKI T, KAMO E, BOELONE E. Double-blind studies of tolerance to praziquantel
in Japanese patients with Schistosoma japonicum infections. Bulletin of the World Health
81. ISHIZAKI T, KUTSUMI H, YASROKA K, HOSAKA Y. The anthelmintic effect of thia-
bendazole against ascaris, whipworm and hookworm infections in man. Japanese Journal
82. JORDAN P. Trial of ambilhar, a nitrothiazole derivative, in Schistosoma mansoni
infections in Tanzania. British Medical Journal i: 276-278, 1966
83. JUNOD C. Essai de traitement de la tricocéphalose par la diphétarsone. Bulletin de la
Société de Pathologie Exotique 58: 653-660, 1965
84. KALM P. Cited in 174
85. KATZ N, PELLEGRINO J, GRIMBAUM E, CHAUVES A, ZICKER F. Preliminary
trials with oxamniquine, a new antischistosomal agent. Revista do Instituto de Medicina
Anthelmintics 97
Tropical de São Paulo 15: 25-29, 1973

86. KATZ N, ROCHA R S, CHAVES A. Preliminary trials with praziquantel in human infect-
ions due to Schistosoma mansoni. Bulletin of the World Health Organization 57: 781-786,
1979
87. KATZ N, ZICKER F. Clinical trial with mebendazole in patients with taeniasis. Revista
da Sociedade Brasileira de Medicina Tropical 7: 225-229, 1973
88. KIKUTH W, GÖNNERT R. Experimental studies on the therapy of schistosomiasis.
Annals of Tropical Medicine and Parasitology 42: 256-267, 1948
89. KLIKS M M. Studies on the traditional herbal anthelmintic Chenopodium ambrosioides
L: ethnopharmacological evaluation and clinical field trials. Social Science and Medicine
21: 879-886, 1985
90. KNORR R. Bandwurmbehandlung mit Yomesan bei 36 Patienten. Medizinische Klinik 55:
560-570, 1960
91. KUDICHE R. Neue Verfahren zu Untersuchung und Prüfung von Wurmmiteln. Versuch
an Finnen und Strongyloideslarven. Archiv für Schiffs- und Tropen-Hygiene 29: 189-197,
1925
92. LAMBERT CR. Chemotherapy of experimental Schistosoma mansoni infections with a
nitro-thiazole derivative, CIBA 32,644-Ba. Annals of Tropical Medicine and Parasitology
58: 292-303, 1964
93. LAMBERT CR, DA CRUZ FERREIRA FS. Résultats de premier essai de traitement de
la bilharziose vésicale par le CIBA 32,644-BA. Bulletin of the World Health Organization
32: 73-82, 1965
94. LÄMMLER G. Chemotherapeutische Untersuchungen mit Hetol, einem neuenhochwirk-
sam Leberegelmittel. Deutsche tieraertzliche Wochenschrift 67: 408-413, 1960
95. LAMSON PD, CLADWELL EL, BROWN HW, WARD CB. Hexylresorcinol in the
treatment of human ascariasis. American Journal of Hygiene 13: 568-575, 1931
96. LAMSON PD, ROBBINS BH, WARC CB. The pharmacology and toxicology of tetra-
chlorethylene. American Journal of Hygiene 9: 430-444, 1929
97. de LANGEN CD. Anguillulosis en het ziektebeeld van de "idiopathische hypereos-
inophilie". Geneeskundig Tijdschrift voor Nederlandsch-Indië 68: 973-990, 1928
98. de LANGEN CD. Postscript about anguillulosis and eosinophilia. Mededeelingen van den
Dienst der Volksgezondheid in Nederlandsch-Indië 18: 310-314, 1929
99. LEACH CN. Carbon tetrachloride in the treatment of hookworm disease. Journal of the
100. LEVINE ND, KANTOR S, TAYLOR GD. Nematocidal activity of some organic
phosphorus compounds against horse strongyle larvae in vitro. American Journal of Veter-
inary Research 19: 299-303, 1958
101. LIM JK. Anthelmintic effect of oxantel pamoate against Trichocephalus trichiurus infect-
ion. Korean Journal of Pharmacology 10: 25-28, 1974
102. LIU HL. Betel nut as a useful taeniafuge. China Medical Journal 41: 134-141, 1936
103. LIU JW. Hexachlorophene in the treatment of clonorchiasis sinensis. Chinese Medical
Journal 82: 793-811, 1963
104. LOEPER. La guérison de l'oxyurose par le carbonate de bismuth. Union Pharm. 62: 8,
1921
105. LOUGHLIN EH, RAPPAPORT I, JOSEPH AA, MULLIN WG. Treatment of human
ascariasis with Hetrazan. Use of syrup containing 1-diethyl-carbamyl-4-methyl piperazine
dihydrogen citrate (Hetrazan). Lancet ii: 1197-1200, 1951
106. McCARTHY DD, SIMPSON E, ROBATI P. A new filaricidal agent. Report of a trial
using Mel W in the treatment of non-periodic type of Wuchereria bancrofti in Raratonga,
Cook Islands. New Zealand Medical Journal 61: 143-147, 1962
107. MacCOWEN MC, CALLENDER ME, BRANDT MC. The anthelmintic effect of dithia-
zanine in experimental animals. American Journal of Tropical Medicine and Hygiene 6:
894-897, 1957
108. McCOY OR, CHU TC. Fasciolopsis buski infection among schoolchildren in Shaohsing
and treatment with hexylresorcinol. China Medical Journal 51: 937-944, 1937
109. MANSON-BAHR P. Phenothiazine as an anthelmintic. Lancet ii: 808-809, 1940
110. MAPLESTONE PA, MUKERJI AK. Hexylresorcinol as an anthelmintic. Indian Medical
Gazette 67: 610-612, 1932
111. MARTIRANI PA, RODRIGUES LD. Ensaio clinico com o cambendazole, uma nova
droga na terapeutica anti-helmintica (nota previa). Revista do Instituto de Medicine
112. MAZZOTTI L. Estudio ucerca del tratamiento de la oncocercosis. Medicina, Mexico 29:
1-5, 1949
113. MAZZOTTI L, HEWITT R. Tratamiento de la oncocercosis por el cloruro de 1-dietil-
carbamil-4-metilpiperazine (Hetrazan). Medicina, Mexico 28: 39-42, 1948
114. MAZZOTTI L, MENDEZ D. El difentano-70 en el tratamiento de la teniases. Revista del
Instituto de Salubridad y Enfermedades Tropicales (Mexico) 16: 9-14, 1956
115. MEHREZ R. Les nouveaux traitements de l'oxyurose. Thèse Méd. (Paris) No. 546, 1947
116. NAGAHANA M, YOSHIDA Y, MATSUNO K, KONDO K. Treatment of Taenia
saginata and Diphyllobothrium latum infections with bithiniol. American Journal of
117. NAGATY HF, KHALIL HW. Bephenium hydroxynaphthoate against Heterophyes het-
erophyes infections. Journal of Tropical Medicine and Hygiene 64: 263, 1961
118. NEGHME RA. The effect of acridine (mepacrine) on tapeworms. Revista Chilena de Hist.
Nat. 43: 97-99, 1939
119. de OLIVEIRA GOMES ME. The treatment of taeniasis with mebandazole. Folha Médica
66: 87-95, 1973
120. OLIVER-GONZALEZ J, SANTIAGO-STEVENSON D, HEWITT R. Treatment of six
cases of ascariasis in man with 1-diethylcarbamyl 4-methylpiperazine hydrochloride.
Southern Medical Journal 42: 65, 1949
121. OTTO GF, MAREN TH. Filaricidal activity of substituted phenyl arsenoxides. Science
106: 105-107, 1947
122. OTTO GF, MAREN TH. Studies on chemotherapy of filariasis. American Journal of
Hygiene 50: 92-141, 1949
123. PALMER ED. A note on the treatment of strongyloidiasis with intravenous gentian violet.
124. PANKHURST R. The traditional taenicides of Europe. Journal of the History of Medicine
24: 323-334, 1969
125. PANKHURST R. Europe's discovery of the Ethiopian taenicide - kosso. Medical History
23: 297-313, 1979
126. PAPYROS EBERS. Das hermetische Buch über die Arzneimittel der alten Aegypter in
hieratischer Schrift. Herausgegeben, mit Inhalsangabe und Einleitung versehen von Georg
Ebers. Mit hieroglyphische-latineischen Glossar von Ludwig Stern, two volumes, Leipzig,
1875. The Papyrus Ebers, translated from the German version by CP Bryan, Geoffrey
Bles, London, pp 167, 1930
127. PARACELSUS. De natura rerum liber primus de generationibus rerum naturalium;
Saemtliche Werke, K Sudhoff (Editor), München und Berlin, 14 volumes, 1922-1923
128. PAWLOWSKI Z. Chemotherapy of human echinococcosis. Proceedings of XII
Congresco Internacional de Hidatologia, pp 346-347, 1985
129. PEÑA CHAVARRIA A, SWARTZWELDER JC, VILLAREJOS VM, ZELEDÓN R.
Mebendazole, an effective broad-spectrum anthelmintic. American Journal of Tropical
130. PENE P, VICENTELLI JM, SOULA G, BOURDERIOUX CH, ROSSIGNOL JF. Le
zentel (albendazole) dans le traitement des nématodoses intestinales. Étude multicentrique
en Afrique de l'Ouest. À propos de 390 observations. Médecine d'Afrique Noire 28:
483-485, 1981
131. PEREZ-SANTIAGO E, OLIVER-GONZALEZ J, THILLET CJ. The effect of cyanine
dye on infections with hookworm and trichuris in man. American Journal of Tropical
Anthelmintics 99
Medicine and Hygiene 2: 307, 1953

132. PERRIN M. Action anthelminthique du stovarsol. Biologie et Médecine 17: 436-438,
1927
133. PLOTNIKOV NN. (Treatment of human fascioliasis with chloxyle.) Meditsinskaya Para-
sitologiya i Parazitarn e Bolezni 35: 482-483, 1965. In Russian
134. PLOTNIKOV NN, OZERETSKOVSKAYA NN, KARNAUKHOU VK, ZALNOVA
NS, FAIBUSOVICH GM, KUTKA GI, ALEKSEEVA MI. (Specific therapy of human
opisthorchiasis with hexachloroparaxylene.) Meditsinskaya Parasitologiya i Parazitarn e
Bolezni 33: 678-681, 1964. In Russian
135. RIM HJ, LYU KS, LEE JS, JOO KH. Clinical evaluation of the therapeutic efficacy of
praziquantel (Embay 8440) against Clonorchis infection in man. Annals of Tropical
Medicine and Parasitology 75: 27-33, 1981
136. RIM JH, LYU KS, LEE JS, JOO KH, SUH WH, TSUJI M. Clinical evaluation of
praziquantel (Embay 8440: Biltricide) in the treatment of Paragonimus westermani.
Korean Journal of Parasitology 19: 27-37, 1981
137. RODRIGUEZ DE CURET H, DE PILAR MA. Dithiazanine intoxication, a case report.
Boletín de la Asociación Médica de Puerto Rico 55: 469-473, 1963
138. ROSI D, PERUZZOTTI G, DENNIS EW, BERBERIAN DA, FREELE H, ARCHER
S. A new active metabolite of Miracil D. Nature 208: 1005, 1965
139. ROYS RL. The ethnobotany of the Maya. Tulane University Department of Middle
American Research, New Orleans, 1931. Cited in 89
Würtz, Paris, three volumes, pp 1370, 1808-1810
141. RUIKKA I. Atebriini matolääkeenä. Duodecim (Helsinki) 67: 254-257, 1951
142. SADUN EH, CHAMNANKIT C, CHETANASEN S. Studies on the treatment of Opis-
thorchis viverrini in human infections with quinacrine hydrochloride and chloroquine
phosphate. American Journal of Tropical Medicine and Hygiene 4: 1080-1087, 1955
143. SANDGROUND JH. Newer drugs for the treatment of tapeworm infections. New
England Journal of Medicine 218: 298-304, 1938
144. SANTIAGO-STEVENSON D, OLIVER-GONZALEZ J, HEWITT RI. Treatment of
filariasis bancrofti with 1-diethyl-carbamyl-4-methylpiperazine hydrochloride
("Hetrazan"). Journal of the American Medical Association 135: 708-712, 1947
145. SANTOS AT, BLAS BL, NOSEÑAS JS, PORTILLO GF. Niridazole in the treatment
of schistosomiasis japonica. Journal of the Philippine Medical Association 47: 203-207,
1971
146. SANTOS AT, BLAS BL, NOSEÑAS JS, PORTILLO GF, ORTEGA DM, HAYASHI
M, BOEHME K. Preliminary clinical trials with praziquantel in Schistosoma japonicum
infection in the Philippines. Bulletin of the World Health Organization 57: 793-799, 1979
147. SAWADA I. On the experiment for the removal of the chicken tapeworm Raillietina
(Parionella) kashiwarensis. Japanese Journal of Parasitology 6: 8-11, 1957
148. SCHAPIRO L, STOLL NR. Preliminary note on the anthelmintic value of tetra-
chlorethylene based on egg counts before and after one treatment. American Journal of
Tropical Medicine 7: 193-198, 1927
149. SCHENONE H, GOLDAMES M, INZUNA E, JIMENEZ M, ROMERO E, BLOOM-
FIELD R. Flubendazole en el tratamiento de infecciones por nematodes intestinales en
niños. Boletín Chileno de Parasitologia 32: 85-86, 1977
150. SCHIAPACASSE RH, MOHAMMADI D, CHRISTIE AJ. Successful treatment of sev-
ere infection with Fasciola hepatica with praziquantel. Journal of Infectious Diseases 152:
1339-1340, 1985
151. SCHREIBER W. Intraduodenal therapy for tenia, hookworm and strongyloides infection.
Gastroenterology 37: 346-349, 1959
152. SCHÜFFNER W. Der Wert einiger Vermifuga gegenüber dem Ankylostomum mit
Bemerkungen über die Wurmkrankheit in Niederlandisch-Indien. Archiv für Schiffs- und
Tropen-Hygiene 16: 569-588, 1912
153. SEATON DR. A short way with Taenia saginata. Lancet i: 808-809, 1956
154. SHOOKHOFF HB, DWORK KG. Treatment of Loa loa infections with hetrazan.
155. SINGSON CN, BANZON TC, CROSS JH. Mebendazole in the treatment of intestinal
capillariasis. American Journal of Tropical Medicine and Hygiene 24: 932-934, 1975
156. STEFANOPOULO CJ, SCHNEIDER J. Essais de traitement de la filariose à F. loa par
la 1-diethylcarbamyl 4-methylpipérazine. Comptes Rendus Hebdomadaires des Séances
de l'Académie de Biologie 142: 930-931, 1948
157. STEMMERMAN GN, NAKASONE N. Strongyloides stercoralis infestation:
malabsorption defect with reaction to dithiazanine iodide. Journal of the American Medical
Association 174: 1250-1253, 1960
158. STRAUB M. Tetrachloorkoulstofvergiftigi ng in twaalf gevallen. Geneeskundig Tijdschrift
vor Nederlandsch-Indië 65: 624-645, 1925
159. SUN SZU-MIAO (One thousand golden prescriptions.) About 650 AD. In Chinese, partly
translated in 78
160. SWARTZWELDER JC, FRYE WW, MUHLEISEN JP, MILLER JH, LAMPERT R,
PEÑA CHAVARRIA AA, ABADIE SH, ANTHONY SO, SAPPANFIELD RW.
Dithiazanine, an effective broad spectrum anthelmintic. Journal of the American Medical
Association 165: 2063-2067, 1957
161. SWARTZWELDER JC, MILLER JH, LAMPERT R, PEÑA CHAVARRIA A, ABADIE
SH, FRYE WW, MUHLEISEN P, LIZANO C. Anthelmintic activity of stilbazium iodide
(monopar) against intestinal nematodes in man. Journal of Parasitology 48: 29-30, 1962
162. SYMPOSIUM DE OXAMNIQUINE. Rio de Janeiro, Brasil, Junho, 1973. Revista do
Instituto de Medicina Tropical de São Paulo 15, supplement, pp 1-175, 1973
163. TALAAT SM, AMIN N, EL MASRY B. The treatment of bilharziasis and other intestinal
parasites with dipterex. A preliminary report of 100 cases. Journal of the Egyptian
Medical Association 46: 827-832, 1963
164. THEODORIDES VJ, GYURIK RJ, KINGSBURY WD, PARISH RC. Anthelmintic
activity of albendazole against liver flukes, lung and gastrointestinal roundworms.
Experientia 32: 702, 1976
165. THEOPHRASTUS. Enquiry into plants, translated by A F Horst, Loeb Classical Library,
Heinemann, London, two volumes, 1948-1949
166. THETFORD ND, OTTO GF, BROWN HW, MAREN TH. The use of phenyl arsenoxide
in the treatment of Wuchereria bancrofti infection. American Journal of Tropical Medicine
28: 577-583, 1948
167. THIENPONT D, BRUGMANS J, ABADI K, TANAMAL S. Tetramisole in the treat-
ment of nematode infestations in man. American Journal of Tropical Medicine and
Hygiene 18: 520-525, 1969
168. THIENPONT D, VAN PARIJS OF, RAEYMAKERS AH, DEMOEN PH,
ALLEVWIJN FT, MARSBOOM RP, NIEMEGEERS CJ, SCHELLEKENS KH,
JANSSEN PA. Tetramisole (R.8299), a new potent broad spectrum anthelmintic. Nature
209: 1084-1086, 1966
169. THOMAS H, GÖNNERT R, POHLKE R, SEUBERT J. A new compound against adult
tapeworms. Proceedings of the Seventh International Conference of the World Association
for the Advancement of Veterinary Parasitology, Thessaloniki, Abstract No. 51, 1975
170. THOORIS GC. Le traitement expérimental de la filariose à Wuchereria bancrofti en
Océanie française par la suramine (naphuride de sodium). Bulletin de la Société de Path-
ologie Exotique 49: 311-317, 1956
worm etc. Philosophical Transactions of the Royal Society 13: 113-144, 1683
172. ULIVELLI A. Terapia antibiotica della teniasi (primi favorelli resulti del trattamento con
paromomicina). Revista di Clinica Pediatrica 72: 371-383, 1963
173. VILELA M de P, RODRIGUES LD, CAPELL JI, BRANDAO JA, MARTIRANI I,
ZACATO M. O emprego di tiabendazole no tratamento de estrongiloidiase de outras
Anthelmintics 101
parasitos humanas. Hospital, Rio de Janeiro 62: 691-710, 1962

174. VOGEL VJ. American Indian medicine, University of Oklahoma Press, Norman, 1970
175. WAGNER ED, LEMON FR, BURNETT HS. The use of dithiazanine in the treatment
of helminthiasis in Mexican farm labourers. Transactions of the Royal Society of Tropical
176. WANG T'AO (The private prescriptions of an official.) About 752 AD. In Chinese, partly
translated in 78
177. WANSON M. L'hetrazan dans la période d'invasion de l'onchocercose. Annales de la
178. WESTON J, THOMPSON P, REINERTSON J, FISKEN R, REUTNER T. Anti-
oxyuricid activity, toxicology and pathology in laboratory animals of cyanine dye 715.
Journal of Pharmacology and Experimental Therapeutics 107: 315-324, 1953
179. WRIGHT WH, BRADY FJ. Studies of oxyuriasis. A preliminary note on therapy with
gentian violet. Proceedings of the Helminthological Society of Washington 5: 5-7, 1938
180. WUCHERER OE. Sobre a molestia vulgarmente denominada oppilaçao ou cançaço.
Gazeta Medica da Bahia 1: 27-29, 39-41, 52-54, 63-64, 1866
181. YAMAGUCHI T, UEHARA K, SHINOTO M, MINEDA H. Dithiazanine iodide as a
new anthelmintic for treatment of Clonorchis sinensis. Japanese Journal of Parasitology
10: 697-704, 1961
182. YOKOGAWA M, KOYAMA H, YOSHIMURA H, TSAI CS. Chemotherapy of Clon-
orchis sinensis infection. Clinical observations on the treatment of patients with
1,4-bis-trichloromethylbenzol. Japanese Journal of Parasitology 14: 526-533, 1965
183. YOKOGAWA M, YOSHIMURA H, OKURA T, SAITO M. The treatment of Taenia
saginata with bithiniol. Japanese Journal of Parasitology 11: 39-44, 1962
184. YOUNG MD, JEFFERY GM, FREED JE, MOORHOUSE WG. Bephenium, a new drug
active against human hookworm. Journal of Parasitology 44: 611-612, 1958
Chapter 4
Fasciola hepatica and FASCIOLIASIS
SYNOPSIS
Common name: liver fluke; produces sheep liver rot

Major synonyms: Distoma hepaticum, Distomum hepaticum
Distribution: world-wide
Life cycle: The flat, leaf-like hermaphroditic worms, 30 mm long by 13 mm wide, live
in the biliary tract and produce eggs which are passed in the faeces. The ova develop
in water over two weeks or so, then each miracidium escapes and invades a snail
intermediate host of the genus Lymnaea. The miracidium becomes a sporocyst (an
elongated sac without suckers or alimentary canal) which in the course of four weeks
produces first-generation then second-generation rediae (characterized by the presence
of a single sucker and a simple sac-like alimentary canal) and cercariae. The cercariae
emerge from the snail, swim about in water, then encyst on aquatic vegetation. After
ingestion by a mammalian host, the enclosed metacercaria excysts in the duodenum,
migrates through the intestinal wall into the peritoneal cavity, penetrates the liver
capsule then migrates through the parenchyma to the biliary tree where it matures over
two to three months
Definitive hosts: sheep, goats, cattle, pigs, humans etc.
Major clinical features: fever, malaise, jaundice, abdominal pain, urticaria in heavy
infections
Diagnosis: demonstration of eggs in the faeces of patients with patent infections
Treatment: bithiniol, praziquantel
DISCOVERY OF THE ADULT WORM
IN ANIMALS
The name of the person who first found liver flukes and knowledge of when the
observation was made have been lost in the sands of time. The flukes wer e
probably found independently by numerous people in diverse places over many
years. The first recorded reference to these worms was made by a Frenchman,
Jean de Brie, in 1379. de Brie, who was known as "Le bon berger", meaning
"The good shepherd", had been commissioned by Charles V of France to write
a treatise on the proper management of sheep and the production of wool .
Although he did not describe the morphology of the parasite, was uncertain of
its precise nature, and appears to have been somewhat confused as to whether
the worms were the cause of, or the consequence of sheep rot, there is littl e
103
doubt that he recognized the worm we now know as Fasciola hepatica.

He believed that the consumption by sheep of a herbivorous leaf known locally
as "la dauve" (probably Ranunculus species) corrupted the liver to produce "a
type of worm which putrefaction does eat and destroy the entire liver of th e
animal"15.
The parasites were discussed again in 1523 by the English lawyer, Anthony
Fitzherbert (1470-1538), who, in the section on sheep rot in the book on ani-
mal husbandry traditionally ascribed to him, referred to "flokes" (flukes) in the
livers of afflicted animals 32. This name is thought to have been derived from the
old Anglo-Saxon word "floc", meaning a flounder (i.e. type of fish) 18. Twenty
four years later (1547), the Italian physician, Hieronymous Gabucinus, referred
to worms resembling pumpkin seeds that he had often found in the livers o f
sheep and goats 34. In 1551, Conrad Gesner mentioned "duva" or liver flukes in
his monumental book, Historia Animalium 36. They were discussed again by the
Dutchman, Cornelius Gemma, in his 1575 accoun t of an epidemic of fascioliasis
which had occurred in Holland in 1562 35. He was followed by Fromma n
(1663)33, Faber (1670), Leeuwenhoek (1679), Wepfer, Borel and others. The
worms were, of course, well-known to the butchers of the time, those i n
Florence referring to them as "Biscioule", those in Holland calling the m
"Bottiens", and those in Provence naming them "Dalbères". The afore -
mentioned authorities, however, were frequently as ignorant as th e
butchers, often considering the flukes to be leeches or cucurbitini (tapewor m
proglottids).
The first person to investigate and illustrate these parasites further was th e
Italian physician, Francisco Redi, when he recovered them from the liver of a
castrated ram in 1668 68. He encountered them again in 1684 in a hare whic h
also harboured large numbers of "hydatids" (pr esumably Cysticercus pisiformis )
in the mesentery and in the perit oneal cavity. He observed 18 worms swimming
in the bile and remarked that their shape resembled somewhat the fish calle d
sole. Because of the concurrence of the two forms, he wondered:
whether the aqueous swelling, shaped like the seeds of a melon or gourd could poss-
ibly be the embryos, so to speak, of the worms which dwell in the bile, and whether
they, upon growing and perfecting themselves, become such. However, I would not
affirm this with certainty.69
In order to test this possibility, he took fluid from the vesicles and boiled it .
Since it did not coagulate as did fluid in eggs found in the ovaries of quad -
rupeds, he concluded by this doubtful process of reasoning that this possibility
was unlikely.
A study of these worms was then taken up in earnest by the Dutchman ,
Godefridus Bidloo. In a letter dated 21 March 1698, he wrote to the celebrated
microscopist, Antony van Leeuwenhoek, detailing his findings; this wa s
published as a memoir in that year 8, then was included in the Dutch and English
editions of the Select works of A. van Leeuwenhoek . He provided illustrations
of the parasite, noted its size and shape (which he compared with sole an d
Fascioliasis 105
flounder), colour, the transparent skin and discussed its motion. He was rather
confused about parts of the internal anatomy, however, giving the wor m
non-existent eyes, liver, heart and circulatory system. Nevertheless, he di d
discern correctly a bowel, discovered eggs, and recognized that the creature s
were hermaphroditic. Concerning the ova, he recounted that he had found:
an innumerable quantity of oval particles, hundreds of which, taken together, are not
equal to the size of a grain of sand. They are of a pale red colour, and I take them to
be the spawn or eggs.8
and with respect to the sexuality of the flukes, he noted:
Notwithstanding my most diligent examination of these creatures, I could never
discover any difference of the sexes; and its seem to me most probable that they are of
that species called Hermaphrodites, or everyone equally prolifick. 8
Even though Fasciola had been known for many years, there was an imperfect
perception of its structure and confusion as to its zoological position. Thus ,
Gabucinus, Redi, Malpighi and Borel seem to have equated the fluke wit h
cucurbitini (Taenia), while Bonamicus, Fromann and Wepfer regarded it as a
kind of leech. In fact, Linnaeus appears at various times to have considered it as
a leech, a planarian, and a cestod e. More than 100 years were to pass before the
details of the fluke's anatomy were worked out correctly by a number o f
investigators including Mehlis (1831) 56, Emile Blanchard, Rudolf Leuckart ,
Sommer and Macé.
IN HUMANS
Although this fluke had been found many times in animals, infection wa s
rarely recognized in humans. Passing references to human infection wer e
made in the seventeenth century. According to Clericus, Pierre Borel noted
that he had seen flukes, which he called insects, in all sorts of animal s
including humans and pigs, writing, "mihi asseruit in omnibus animalibu s
insecta haec reperiri et se in hominibus, porcis etc., eos vidisse" 11. Similarly,
Marcus Malpighi claimed that cucurbitine worms occurred frequently in th e
livers of humans and animals, especially in cattle and wrote: "In hepat e
frequentes occurent vermus cucurbitini in homine et brutis, praesertim i n
bove"53. Again, Bidloo recalled having seen, in human livers, worms similar to
those commonly encountered in the livers of sheep and cattle 8, while Wepfer
claimed to have often found the bile ducts of humans filled with "hirudinibus"
(leeches).
The first person to clearly describe finding these flukes in a human, however,
was Pallas who in 1760 recounted observing worms in the hepatic ducts of a
female patient during an autopsy in Berlin 66. He was followed a century later by
Bucholz in Weimar who found a large number of flukes in the gallbladder of a
convict who had died from a "putrid fever" 17. Although Bucholz's case wa s
accepted by Davaine 24, Küchenmeister46 noted that Bremser had later examined
some of the worms which had been preserved and thought that they were really
Distoma lanceolata (= Dicrocoelium dendriticum ). Some years later, Chabert

claimed to expel great numbers of flukes from a twelve year old girl with the aid
of his empyreumatic oil 19.
NOMENCLATURE
Linnaeus at first regarded the fluke as a slug, but eventually created the genus
Fasciola in his group Intestina of his Class Vermes and named the parasit e
Fasciola hepatica in 175851. The generic name is derived from the Latin word
"fasciola" meaning "fillet" or "small b andage". Goeze believed that the organism
was a planarian and at one time called it Planaria latiuscula. In 1786, Retzius
needlessly changed the name of the genus to Distoma, meaning two openings
(as opposed to the Monostoma - worms with a single opening - and Polyostoma
- worms with multiple openings) 70,71, then Abildgaard designated the fluk e
Distoma hepatica 1. This nomenclature was followed by Zeder (1800) ,
Rudolphi (1808-1810) and Dujardin (1845), while Diesing (1849-1851) called
it Distomum hepaticum, with the result that the disease was known for man y
years as distomiasis. With the establishment of the law of priority i n
nomenclature in the early part o f this century, however, the Linnean designation
regained pride of place through Opinion 84 of the International Commission on
Zoological Nomenclature 41.
ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY

OF THE LARVAL STAGES AND SNAIL INTERMEDIATE HOSTS
Early students of Fasciola suggested all manner of means by which the worms
were produced and propagated, ranging from generation by putrified o r
decaying substances to the eff ects of excessive wetness or heat. Bidloo in 1698,
however, no doubt girded by his discovery of eggs in the flukes, asserted tha t
these suggestions were but "ideal tales" and "senseless imaginations". He laid:
it down as a certain truth, that these, as well as other small living creatures, are
produced from their like, by the means of eggs, seed or spawn, according to the nature
implanted in them at their first creation.8
Bidloo thought it most probable that the worms bred in moist earth then were
swallowed together with their eggs in water by herbivorous animals such a s
sheep, stags, calves and wild boars. He did not believe, however, that the adult
worms forced their way from the gut into the gall bladder and biliary system .
Rather, he reasoned that the eggs might be carried into the biliary passages ,
become fixed there, then nourish themselves on the bile and develop.
Bidloo's correspondence with Antony van Leeuwenhoek encouraged th e
Dutch microscopist to investigate the manner of transmission of this infection.
Being conversant with the general view that infection was acquired by animals
feeding on contaminated pastures, he examined green sods from the meadows
Fascioliasis 107
on which some infected sheep had fed seeking microscopical creatures re -

sembling the adult flukes. Sadly, he communicated his failure to find any such
animals to the Royal Society of Londo n, but being convinced that infection must
be acquired by ingestion, he speculated that when the worms reached:
the beginning of the guts, where the bladder of the gall doth empty itself, these animals
being pleased with the taste of the gall, swim against it. 47
and thus enter and lodge in the biliary system.
Both Bidloo and Leeuwenhoek were close to the truth, but nearly 200 years
were to pass before the life cycle of Fasciola hepatica was finally elucidated.
During this period, many author ities strayed far from the mark. As late as 1837,
Youatt in his book on sheep claimed that:
Rot is caused simply by the extrication of certain gases or miasmata during the
decomposition of vegetable matter, under the influence of moisture and air. 94
An understanding of the mode of development of Fasciola hepatica took so
long to achieve for several reasons. Not only was the life cycle of this parasite
extremely complex, but the concepts involved were unknown in the eighteenth
century and were appreciated only gradually during the nineteenth century .
Fasciola hepatica was the first fluke of human importance to be discovered, and
also the first one in which the life cycle was worked out. The way in which this
was achieved, however, can only be und erstood when viewed in a wider context
encompassing discoveries with various non-human parasites.
In 1773, OF Müller discovered microscopic organisms, which we now know
to be the larval stages of trematodes, living free in water 58. He regarded them as
independent adult creatures, consi dered them to be Infusoria, and gave them the
generic name, Cercaria. A study of these organisms was then taken up by CL
Nitzsch, a professor in Halle, (now East) Germany, in the early part of th e
nineteenth century. He noticed that many of these cercariae transformed into a
"pupa" or "encysted" on foreign bodies, but was of the opinion that this process
merely signified the termination of life 60. Nitzsch also recognized that cercariae
were not Infusoria, and came some way towards realizing that they wer e
trematodes. He noticed the resemblance of the anterior part of the body of a
cercaria to a fluke (Distomum). As a result of such observations, he concluded
in 1817 that a cercaria was a combination of a Distomum with a Vibrio which
he believed provided the characteristic tail of the cercaria 61.
The origin of these cercariae was a puzzle. They did not appear to have any
sexual organs so many authorities invoked the doctrine of spontaneous gener-
ation to explain their existence. In 1818, however, the Prussian, Ludwig Bojan-
us, a professor at Wilno (now Vilnius) in present-day Lithuania made a mom-
entous discovery. While dissecting some snails from a fresh-water pond, h e
noticed that cercariae crept out of s acs in the viscera of the snails and concluded
that they were probably generated within them. He called these sacs "roya l
yellow worms" (or "king's yellow worms"):
When the Lymnaea (snails) were taken from the dish, a large number of royal yellow,
living, but in movement very indolent, cylindrical worms (Distomata?) were found in
many of them....In the yellow worm one saw, under the microscope, active movement
which came from the enclosed winding animals....Some of the enclosed animals
succeeded, finally, at various places, in breaking through. All those that slipped out by
themselves had the appearance of the previously described cercariae. 10
These yellow royal worms were given the generic name Redia by de Filippi in
1837 in honour of Francesco Redi 30; de Filippi later accepted the view that the
redia was a larval stage and recommended that the name be no longer used to
designate a genus31. It caused much astonishment that cercariae were no t
derived from parents resembling themselves, but came from these peculiar ,
animated, worm-shaped sacs. Oken, in whose journal Bojanus published hi s
discovery, remarked that "observations of this kind make one dizzy" 64 and
added that "one might lay a wager that these cercariae are the embryos o f
distomes"63. This observation of Bojanus was confirmed by CE von Baer i n
1827.
The story was taken a stage further in 1831 when Karl Mehlis, a medica l
practitioner in Clausthal in (now West) Germany, not only discovered th e
operculum (lid) of each fluke ovum, but also saw an infusorian-like ciliate d
embryo slip out of many eggs of the flukes, Monostomum flavum and Distomum
hians 56. Several years later (1837) Friedrich Creplin (1788-1863), a medical
practitioner and zoologist in Greifswald, (now East) Germany, showed that the
eggs of Fasciola hepatica likewise hatched a ciliated larva 23. Again it caused
some surprise that the embryo, later to be called a miracidium, meanin g
"youthful person" by Braun 12 should be so different in appearance from th e
parent worm. The discovery of these motile worms led von Nordmann to point
out that the ability of the flukes' progeny to swim about in water suggested that
hosts were unlikely to become infected by passively ingesting eggs, but rather
that the swimming embryos might seek out their hosts themselves 62.
Nevertheless, it was not until Simonds showed in 1852 that not a single fluke
was found nor were any traces of liver rot present in sheep fed fluke eggs, that
the old hypothesis that infection was acquired by ingestion of eggs was finally
laid to rest 78.
Meanwhile, Carl von Siebold had linked the embr yos released from fluke eggs
with rediae and cercariae. While District Medical Officer in Heilsberg (no w
known as Lidzbark) in East Prussia (present-day Poland), he had occasion t o
examine large numbers of the fluke Monostomum mutabile which lived in the
orbital cavities of geese. He noted the hatching of ciliated larvae from the eggs
and watched them swimming around in the water. After a while, they died and
disintegrated, each one releasing from its interior a motile, cylindrical body with
two short lateral processes and furnished with a pharynx and simple gut. These
he recognized as being identical with certain cercaria-sacs that he had seen in
snails. Although he was not able to actually witness the process, he theorize d
that the adult trematode worms produce e ggs from which the larvae hatch, swim
around to find an appropriate snail, penetrate the tissues of the new host, then
die releasing cercaria-sacs (rediae) 75. This hypothesis was eventually prove n
correct when G Wagener observed the metamorphosis of the miracidium o f
Fascioliasis 109
Distoma cygnoides of the frog into a redia in 1857 88. The fate of the cercariae
thus produced remained uncertain although von Siebold reported in 1837 that
some cercariae such as C. echinata encysted in snails.
Despite the observations and hypotheses mentioned above, most authorities
held that Cercaria, Redia and Distoma were unrelated organisms, eac h
deserving and occupying separate generic sta tus in the schemes of classification.
To others, however, all these seemingly irregular phenomena constituted a
complete chaos which appeared to break down all the known laws of anima l
existence and propogation. It was at t his point that the Danish scholar, Johannes
Steenstrup, entered the scene. He succeeded in evolving a certain plan out o f
this confusion by the discovery of a hidden, underlying law of nature throug h
which all the phenomena that had seemed devoid of plan could be brought t o
order. He synthesized many reports in the literature with his own observations,
then in 1842 he published a book in which he promulgated his doctrine of the
"Alternation of Generations" 81. This term had already been used in 1819 by the
German poet and navigator, A von Chamisso, who had shown that in the Salpae,
a form of marine animal, free individuals and individuals bound together i n
chains alternated with one another in each successive generation. In his work,
Steenstrup gave an account of the evolution of coelenterates (Medusae an d
claviform polyps), of pelagic tunicates (Salpae), and of trematodes, and found
a phenomenon common to all of them that he summarized in the followin g
terms:
An animal bears young which are, and remain, dissimilar to their parent, but bring
forth a new generation, whose members either themselves, or in their descendants,
return to the original form of the parent animal. 81
Thus, just as the polyp originating from the eggs of a medusa represented a n
alternate generation, so did the royal yellow worm (cercaria or redia) derive d
from the ciliated embryo of a fluke. The consequences of this statement wer e
that cercariae were the progeny of trematodes, that these worms passed part of
their existence in a state of freedom, and that whole divisions of families must
be abolished because they included only undeveloped forms. Steenstru p
observed that in some of the Trematoda the latter generations remained within
the earlier forms until they attained their full development whereas other s
forsook them earlier to become free-swimming then underwent a complet e
metamorphosis. He conjectured fur ther that cercariae might penetrate into other
animals, lose their tails and become adult flukes. Steenstrup knew that C.
echinata encysted in snails so he extracted parasites from the cysts after various
periods and showed that they contained typical fluke-like forms. His view s
required both correction and completion, particularly in his supposition tha t
final maturation occurred in the body of the snail, but they provided a n
indispensable principle upon which the details of the life cycles, not only o f
trematodes but also of cestodes, could be fleshed.
Although some investigators such as von Siebold (1844) 76 and van Beneden
(1852) 7 seized upon this idea of alternation of generations, other authoritie s
remained obstinate. Thus, Diesing in his major work of 1849-1851, Systema

Helminthum, still considered cercariae to be adult trematodes and erected a
suborder for them25. Later (1858), he came to accept the larval nature o f
cercariae although he continued to use generic names for them 26.
Immediately after the appearance of Steenstrup's book, von Siebol d
expressed the opinion that encysted cercariae must migrate, i.e. needed to b e
transmitted with the bearers on or in which they were encysted into other hosts,
before they could mature 76. In this view he was supported by de Filippi31 , la
Valette de St. George87 and Pagenstecher 65. La Valette de St. George provided
important information when he showed that if tailed, non-encysted cercaria e
were administered to experimental animals, they failed to develop. He the n
went on to show, however, that when certain encysted cercariae wer e
ingested, the larvae escaped in the stomach and matured in the gut. Thus ,
Cercaria echinifera was converted very rapidly in the intestine of warm -
blooded animals and slowly in that of cold-blooded species into Distoma
echinifera, and C. flava became transformed into Monostomum flavum of
finches and sparrows 87.
When Küchenmeister came to review the probable life cycle of F. hepatica
in 1855 he speculated, therefore, that although it was still unknown how th e
miracidium became metamorphosed, into what redia it was converted, where the
rediae lived, whether their offspring were tailed or tail-less, or whether the y
encysted themselves, it seemed likely that herbivores and omnivores, including
humans, infected themselves with encysted worms by devouring infected snails
hidden in grass or vegetables, or possibly by drinking contaminated water 46.
These views were modified by the Ger man zoologist, David Weinland, in 1875.
During studies of the molluscan fauna of the Swabian Alps, he found rediae in
the livers of Limnea (= Lymnaea) truncatula. He noted further that whe n
cercariae were released they showed a strong inclination to leave the water and
climb up onto foreign objects. He speculated, therefore, that they might encyst
on grass in order to be ingested by sheep, and suggested that they could be the
intermediate forms of F. hepatica 91.
This was the scene in 1880 when the young Englishman, Algernon Thomas
turned his attention to the problem, and when Rudolf Leuckart in German y
finally began to have some success with his endeavours. For many years ,
Leuckart had tried in vain to infect the most frequently encountered local snails
with miracidia of F. hepatica. Near the end of the summer of 1879, he foun d
small snails which he thought were Limneus minutus (= L. truncatula) in the
Dresden Botanical Gardens. A few days after placing them in his breedin g
vessels, he found that some snails were cover ed with small parasites which were
also to be found in the viscera, especially in the lungs. They had the form o f
small tubes, but without cilia, and had two eye spots and a head sucker, while
their contents consisted of clear cells which were beginning to proliferate. He
thought that there was little doubt that these organisms were related to F.
hepatica miracidia. Unfortunately, he ran out of snails with which to continue
Fascioliasis 111
his experiments, and a paucity of the molluscs plagued him again in th e

following year. In the interim, however, he convinced himself that the snail s
were really young L. pereger which he had already failed to infect wit h
F. hepatica when they were half-grown or mature. This led him to the idea that
F. hepatica miracidia might only be able to develop in very young snails of
this species. He believed this t o be proven in the summer of 1881 when he was
able to infect hundreds of young snails thought to be L. pereger with F.
hepatica. He traced the development of miracidia into rediae containing 5- 8
offspring, but by the time of his report in December 1881, he had been unable
to characterize them in any detail 48. In fact, he at first believed incorrectly that
F. hepatica rediae contained tail-less larvae 49. He then realized his mistakes,
and in 1882 detailed the development of F. hepatica in L. truncatula, his final
paper being published in October of that year 50, almost simultaneously wit h
Thomas's second report in the Journal of the Royal Agricultural Society o f
England.
Concurrently with Leuckart and quite independently of him, Thomas was re-
searching the life cycle of F. hepatica in England. A major outbreak of liver rot
in 1879-1880 had killed more than three million sheep in Britain. The Roya l
Agricultural Society of England provided funds for an investigation of th e
problem, particularly regarding t ransmission of the infection. George Rolleston,
professor of anatomy and physiology at Oxford University, who had earlie r
postulated that the black slug, Arion ater, was the intermediate host, wa s
approached to investigate the problem. He declined because of ill-health bu t
recommended instead that his former pupil, Thomas, who had just bee n
appointed demonstrator in biology at the University Museum be given the task.
Thomas took up the challenge and showed first that eggs of F. hepatica would
not develop when maintained at internal body temperature (37 oC) or at the
lower temperatures obtaining during an English winter. When the eggs wer e
kept at 23-26 oC, however, the miracidia developed fully within two to thre e
weeks, although some eggs continued to hatch over weeks or even months 83. He
observed, further, that the released miracidia lived for only about eight hours in
water. Thomas was aware that similar embryos of Distoma nodulosum and D.
trigonocephalum developed in the snails Bithynia tentaculata and Paludina
species, respectively. In these hosts, the former worm metamorphosed into a
sporocyst, and the latter helminth changed into a redia, both ultimately giving
rise to cercariae. He assumed, therefore, that a species of mollusc was likely to
be the intermediate host of F. hepatica. Consequently, he expose d
experimentally "Arion ater, Limax agrestia, Arion hortensis, Limax cinereus,
Planorbis marginatus, Succinea amphibia, Limnaeus pereger and Limnaeus
truncatulus"83 as well as some small crustacea to F. hepatica miracidia, but
without success. Thereupon, he decided to tackle the problem from anothe r
angle, and so began to visit a large number of farms near Oxford where there
had been severe outbreaks of fascioliasis in 1879-1880. There he examined the
fauna, particularly the snails, in great detail in the middle of 1880. The results
were tantalizing but inconclusive. On 22 December 1880 he found in a field at

Wytham, a tiny L. truncatula which was infected with a redia containin g
peculiar tadpole-shaped cercariae. Since no-one at that time knew what th e
cercariae of F. hepatica looked like, the identity of these worms remaine d
uncertain. The only way to be sure was by experimental infection of snails,
but by this time, Thomas's source of snails had dried up and such researche s
had to await the next season. Nevertheless, he was able to observe the habits
of these cercariae. He found that they encysted on surroundings objects ,
especially plants, and speculated that sheep might be infected wit h
F. hepatica by ingestion of grass contaminated with these cysts. Th e
following year (1881) proved to be one of intense disappointment. Despit e
scouring the countryside, no appropriate snails could be found. Never -
theless, the absence of an epidemic of liver rot in sheep near Oxford that year
consoled him somewhat and convinced him that he must be on the right track.
In the meantime, he had reasoned that two species of snails likely to be inter-
mediate hosts were Lymnaea pereger and L. truncatula. These molluscs were
two of the eight species of snails on the Faroe Islands where fascioliasis wa s
very common, and L. pereger was the only aquatic pulmonate snail on th e
Shortland Islands where liver fluke also occurred. Accordingly, he tried onc e
more to infect these snails experimentally. In July of 1882, floods in the rive r
Isis (Thames) at Oxford result ed in the appearance of vast numbers of L. trunc-
atula. He exposed them to F. hepatica miracidia and was immediatel y
successful:
The snails were speedily found to have afforded a suitable place for the further
development of the embryos, and of those examined up to the present time all have
proved to be infected, often containing as many as 80 embryos. 84
Thomas was then able to follow the devel opment of larvae within the snails. He
observed that once in the snail:
the embryo undergoes a metamorphosis. It loses the external layer of ciliated cells and
changes from the conical to an elliptical shape.84
This organism was not a redia, but a sporocyst or brood-sac in which redia e
would be formed. Within the sporocy sts, which Thomas found in the pulmonary
membrane of the mollusc, balls of cells multiplied and were transformed int o
rediae, each with its own pharyn x and intestine. He found that when a redia was
fully formed:
it breaks through the wall of the sporocyst, and the wound caused by its forcible exit
immediately closes up, and there remaining germs continue to develop. 84
These rediae were much more dangerous to the snail than the rather iner t
sporocysts, for they were very activ e and migrated from the pulmonary chamber
to various tissues, especially the liver, upon which they fed. By 31 days afte r
infection, the rediae were approximately 1 mm long by 0.2 mm in width an d
contained up to a score of "germs" or " spores" in various stages of development,
although it was still not clear what form they would take. By seven weeks ,
however, he could find cercariae within the rediae. In contrast to Leuckart' s
Fascioliasis 113
assertion of the previous year, each cer caria was endowed with a long tail. What
was more, these cercariae and rediae appeared to be identical with those he had
seen in the snail collected from the farm at Wytham two years before. H e
concluded that:
There can be no doubt that the cercariae I found really belong to the liver fluke. The
rediae in which they occurred were closely similar to those I have found throughout
this examination of the snails I have infected with embryos, and in the same snail with
these rediae were sporocysts, still recognisable by the eye-spots and papilla as
belonging to F. hepatica. Moreover, all the specimens of L. truncatulus which I have
infected have proved to contain larval trematodes, clearly belonging to one and the
same zoological species, and as a preliminary precaution a number of snails of the
same gathering as those submitted to infection were examined, and all were completely
free from larval trematodes.84
Furthermore, Thomas observed that rediae sometim es did not produce cercariae,
but generated rediae instead. Indeed, he found as many as four generations o f
larval F. hepatica within the same snail, and calculated that a single fluke might
give rise to over 1,000 cercariae. He ended his paper by indicating that it was
still necessary to elucidate the manner in which sheep were infected wit h
cercariae. He noted that this could occur either by consumption of mollusc s
containing cercariae, as Leuckart favoured, or as he believed more likely ,
cercariae might swim about, encyst on grass and then be ingested. Thomas' s
second report84 and Leuckart's final paper50 both came out in October 1882 .
Thomas then wrote two further papers 85,86 reviewing his findings and comparing
them with those of Leuckart.
Despite Thomas's confident anticipation that he would soon be able to pro-
vide the answer to the last-posed question, another ten years were to elaps e
before the Brazilian, Adolfo Lutz, proved that infection was acquired by in -
gestion of cysts containing metacercariae. In t he interim, Leuckart had also tried
to infect rabbits but was unable to find any worms. The reasons for his apparent
lack of success were not apparent until Ssinitzin discerned the pathway o f
migration in the body of young worms in 1914. Lutz was working in Hawai i
where he was the Director of the Leper Hospital in Honolulu. Although h e
published his findings as referring to F. hepatica, it has since been suggested
that the species he studied was in fact F. gigantica 2. Be that as it may, the
findings are equally applicab le. Lutz observed in 1892 that snails infected with
Fasciola only liberated cercariae when they were damaged or dead. Thes e
cercariae encysted rapidly as soon as they found support, whether a plant o r
some other material, and remained viable for up to two months. He infected a
kid, a piglet and three guinea pigs with numerous cysts of different ages. The
kid died within 20 hours of feeding, probably because it was weaned too early,
and worms could not be found in the piglet bec ause its stomach was too full. He
had more luck with his guinea pigs. The f irst animal was infected on 23, 24 and
27 December 1891 with about 60 cysts. It was found dead one month later and
autopsy revealed numerous small cavities filled with blood clot in the live r
parenchyma: 29 flukes ranging in size from 5-9 mm were recovered from this
organ. In the second guinea pig, which had been fed with about 20 cysts, 1 8
flukes were recovered 32 days later, one of them being in the liver and the rest
being located in the peritoneal cavity. Similar findings were obtained with the
third guinea pig 52. Finally, Shirai eventually proved that not only were cercariae
non-infective, but the cysts were not either until a period of at least twelv e
hours had elapsed after encystment 74.
Thus, the mode of transmission of the parasite from excretion of eggs in the
faeces to ingestion of metacercariae had been determined. What remained to be
demonstrated was the route of migration and the processes of maturation o f
worms in the definitive host.
STUDIES OF THE MIGRATION AND DEVELOPMENT OF LARVAE

AND PATHOLOGICAL REACTIONS IN THE DEFINITIVE HOST
Initial conceptions as to the genesis of disease were confused. Jean de Bri e

(1379) ascribed a major role to the herb, "la dauve":
La dauve is of such a nature that it adheres to and lives in the liver of the sheep or
other beasts. And this bad herb does not rise, does not return to the throat of the
animal as do other herbs but....corrupt(s)....the liver. 15
de Brie believed that this damage was then compounded by the worms which
were generated and ultimately destroyed the entire liver. He found it necessary
to explain that the reason why sheep died was because "the liver is one of the
three principal places where life lies....therefore the sheep cannot live" 15.
Fitzherbert (1523) described the morbid anatomy of infected sheep ver y
graphically. Moreover, he comprehended the connection between flukes, liver
disease, jaundice and ascites:
whane thou hast kylde a shepe his belly woll be full of water yf he be sore rotten: and
also the fatte of the flesshe wolle be yellowe if he be rotten and also and thou cut the
lyver therin wyll be lytell quykena lyke flokes and also the lyver will be full of knotts
and whyte blysters yf he be rotten.32
Many persons believed that the flukes were situated in the portal veins. John
Faber in 1670 was apparently the first to state that liver flukes were located in
the bile ducts28. Willius in 1674, in describing an epidemic in cattle in Zeeland,
wrote that not only were the worms in the branches of the portal veins, but that
large numbers of flukes were also present in the biliary and hepatic ducts 92.
Redi emphasized the biliary location of worms further in 1684 69 as did Bidloo
in 1698. The latter wrote that they are found:
only (in) the vessels, tubes and channels wherein the gall is formed and collected,
though most commonly in the liver, and here they may be said to swarm, producing
grievous swellings, callosities, contortions and sinuses in the part: and cavities which
will be often found an inch and a half in diameter. In these parts the noxious animals
are found in heaps and the places where they lie become hard and cartilaginous. In the
small gall-ducts they lie longitudinally, and sometimes rolled or curled up together. 8
Fascioliasis 115
Bidloo further realized that the numbers of worms varied enormously: in one
liver he recovered 870 worms plus ma ny fragments, whereas in other livers he
found but ten or twelve flukes. He postulated a number of mechanisms b y
which they might cause ill-effects, including distension, destruction an d
inflammation of the biliary passages following obstruction of the biliar y
circulation by worms and their products, inf lammation and necrosis of the liver
by worm toxins, and competition by the worms with the organs for nutrien t
juices.
Once the location of worms in the biliary tree was identified correctly, the
logical assumption seemed to be that they reached that site via the opening of
the bile duct into the duodenum. For over 200 years this remained accepte d
dogma. In 1880, Thomas made an observation which could have put him on
the right path, but he failed to interpret it properly. In September of that year,
he was sent a liver which contained over 2 00 small, immature flukes. He noted
that:
no flukes of any kind could be found in the larger ducts. By far the largest number
were in the smaller branches of the bile ducts or in centres of destroyed hepatic
tissue. They occurred especially near the surface of the liver. The young fluke on
entering the liver by the duct appears to push its way onwards into smaller ducts
where some remain whilst others penetrate the walls of the ducts and crawl forwards
to the surface, causing the destruction of the parenchyma as they proceed. Arrived
at the surface of the liver, they may pass along beneath the peritoneum, or....pierce
the peritoneum and set up perihepatitis.83
Furthermore, Thomas had seen flukes in the peritoneal cavity of a rabbit and
had been told of worms in the mesentery and uterus of a sheep that had died
of the rot. Thus, Thomas made the correct observations, but his interpretation
was exactly opposite to the actual route of migration. Leuckart made similar
observations and also arrived at the same misconception. Lutz (1892) made
the same mistake. In one of his experimental guinea pigs, the vast majority of
young flukes were in the peritoneal cavity, but he concluded erroneously that:
the invading flukes soon go to the periphery of the liver and when the normal bile
passages become too narrow, they burrow further....through the soft parenchyma.
Having reached the surface, they perforate the capsule and thus can reach the
peritoneal cavity where they live perhaps for some time, but probably do not reach
full development.52
It fell to Dimitry Ssinitzin (also known as Sisintsin) in Moscow in 1914 to
demonstrate what is generally accepted as being the true pathway of migration.
He put the reasoning behind his experiment in a very entertaining fashion a
few years later:
I am now a cercaria which has just emerged from its cyst and has found itself in the
intestinal tract....On me are poured smart, biting fluids from the digestive glands and
I wish nothing more than to escape this horrib1e place....What am I to do? If I were
smaller, I should penetrate into a blood vessel but I am too big for that. Dr. Leuckart
advises me to look for the opening of the gall duct in the duodenum, but while I am
listening to him I am transported far behind this opening and how can I, in such a
spacious hollow filled with moving food, find that commended spot? I do not accept
this advice; I hasten to conceal myself in any place; I work my way into the bottom,
between the folds of the epithelium and penetrate through the intestinal wall. 79
Ssinitzin infected rabbits with metacercariae and found that the young worms
had escaped from the cyst walls within two to three hours of reaching th e
intestine. He then observed that they penetrated the intestinal wall and passed
into the peritoneal cavity where they remained for up to two weeks. They then
attached themselves to the surface of the liver by the mouth suction cap, pen-
etrated into the liver parenchyma with the aid of hard, pointed spines, the n
passed further into the biliary passages every day. He noticed that they fed on
erythrocytes during their travels and emphasized the large haemorrhages they
left in their tracks behind them. Final ly, they reached the larger branches of the
biliary system and mature worms bega n to pass eggs two months or more after
infection80.
Ssinitzin's findings were confirmed in guinea pigs by Shirai in 1927 74 and
then in rabbits by Krull and Jackson in 1943. Suzuki in 1931 provide d
confirmation in another manner. He freed young worms from their cysts b y
artificial digestion then inject ed them directly into the abdominal cavity, portal
vein and bile duct of goats, rabbits and guinea pigs. He claimed success for the
portal but not the biliary routes. Nevertheless, he did not believe that th e
former pathway was really relevant in natural infections, considering instead
that some of the young worms penetrated the intestinal wall to enter th e
abdominal cavity 82.
The duration of infection is uncertain, but three patients have been reported
with longlasting infections, suggesting that in humans, worms may live for at
least nine years 3.
RECOGNITION OF THE CLINICAL FEATURES
IN ANIMALS
Fitzherbert provided a masterly description of the clinical manifestations of

liver rot in sheep, paying particular attention to jaundice (best noted in th e
eye), the appearance of the sk in and the condition of the wool. To Sir Anthony
Fitzherbert, a judge of the Court of Common Pleas, has traditionally bee n
ascribed authorship of A Boke of Husbondrye published in 1523 but it wa s
probably written by his brother, John:
Take both your hands and twyrle upon his eye: and if it be ruddy and have reed
strands in the whyte of the eye than he is sounde. And if the eye be whyte lyke
talowe; and the strindes darke coloured than he is rotten: and also take the shepe and
upon the wole on the syde and if the skynne be ruddy colour and drie thane he is
sounde: and if he be pale coloured and watry than he is rotten....take a lytell of the
wole between thy fynger and thy thombe and pull it a lytell and yf it stycke fast he
is sounde and yf it come lightly of he is rotten.32
Fascioliasis 117
This description has hardly been improved upon since.
IN HUMANS
One of the earliest detailed descriptions of subacute fascioliasis was recorded

during the severe epidemic of sheep rot in Britain in 1879-1880. I n
November, 1879, a 52 year old labourer at Corfe Castle in Dorset, Englan d
complained of vomiting and upper abdominal pain of two months' duration .
Examination revealed that his abdomen was distended with gas and that h e
was intensely tender in the epigastrium. Soon after admission to hospital, he
became febrile and developed increasing pain in the right hypochrondrium ,
diarrhoea, and began to cough. His rectum became blocked transiently, bu t
was cleared and he passed a stinking slough 3x5 inches in size per rectum .
Fistulous abscesses developed around the rectum and he died four month s
later. At post-mortem examination, the upper rectum was thickened and nar-
rowed, with sinus tracks opening into it. The liver was greyish-red and tense;
the hepatic ducts were considerably thickened and enlarged and contained 26
fully developed F. hepatica 40.
Despite the severe complications which could occur, as in this patient, it was
recognized that many infected people were either asymptomatic or had onl y
minor symptoms. Perhaps unexpectedly in view of the fact that flukes live in
the bile ducts, jaundice was not a common feature, occurring in only three of
sixteen patients reported up to 190227. This was confirmed during a small out-
break of fascioliasis in six patients in England in 1958, none of whom wer e
jaundiced29, and in a subsequent epidemic involving 44 people a few year s
later in the same country39. The dominant features in these patients were mal-
aise, fever, weight loss and right upper quadrant pain and tenderness of th e
abdomen. Many of them had transient episodes of urticaria, but the liver was
rarely much enlarged.
Very infrequently, immature flukes have been found in ectopic sites. One of
the earliest recorded examples of this concerns a woman who presented i n
1848 with a painful sole which she had had for several months; surgica l
exploration revealed the presence of an immature F. hepatica 37. Naturally
enough, this experience (in 1848) suggested to some commentators that fasc-
ioliasis might be acquired by migration of cercariae through the skin 46. In
1895, the case was described of a French naval officer who after three weeks
of a pulmonary illness which included pain at the base of his right lung ,
paroxysmal coughing and slight haemoptysis, finally coughed up a living F.
hepatica 38. This was said to be the first recorded case in which the parasite
had been lodged in the lungs, but as will be discussed later, some subsequent
commentators have believed that this worm was really F. gigantica.
Finally, adult F. hepatica has been said to cause "halzoun" or oedema of the
buccopharyngeal mucosa by becoming attached to the lining of the oral cavity

when ingested45. Nevertheless, Azar was unable to reproduce this when he fed
infected raw liver to 92 volunteers 6.
DEVELOPMENT OF DIAGNOSTIC METHODS
For many years, a diagnosis of fascioliasis was difficult to prove. The rar e
patient passed flukes in the faece s or brought them up in the vomitus. The first
person who considered the diagnosis in and proved it in a living patien t
appears to have been Dr. San Pedro Marti n de la Calle in the late 1880's (cited
in4 ). His patient remained undiagnosed for four months until it suddenl y
occurred to Martin de la Calle that many sheep had been dying for the past few
months from a disease called locally "con vulia", and that these sheep had many
signs somewhat reminiscent of those present in his patient. He examined the
carcasses of some of these sheep and found flukes in the biliary system. The
clue being thus obtained, he set abo ut looking for flukes in the patient's faeces;
nothing was found at first, but eventually an adult fluke was passed after the
patient had been treated with castor oil.
Surprisingly, no attempt was apparently made to examine the faeces micro-
scopically for ova, despite the fact that it was well-known to veterinarians that
eggs were common in the faeces of infected shee p. Indeed, the first person who
diagnosed a patient in this way seems to have been Ward in 1911 89. Martin and
his collaborators found eggs in the bile in 1944 54; it is likely that this will
become more common now that upper gastrointestinal endoscopy is bein g
practised widely.
A clue to the infection may be provided by finding an eosinophilia; this was
also first recorded by Ward 89. The possibility of diagnosing fascioliasis sero-
logically by a complement fixation test was first demonstrated in sheep b y
Weinberg in 1909 90, then this assay was improved and used in a human patient
by Servantie in 1921 73. Skin tests, both by scratch testing and by intradermal
injection, were used by Morenas with the former technique being mor e
accurate57.
THE SEARCH FOR EFFECTIVE TREATMENT
It is only in recent times that effective therapy for fascioliasis has becom e
available. Many years ago, Chabert claimed to effect the passage of flukes with
his empyreumatic oil 19. Küchenmeister (1855) despaired of treatment, bu t
recommended that calomel and mineral waters or oil of turpentine with sulph-
uric ether be tried 46. Subsequent putative remedies included extract of mal e
fern, antimony compounds, carbon tetrachloride and thymol, but evidence for
Fascioliasis 119
the efficacy of these drugs was lacking.

Kouri and Arenus introduced treatment with emetine in 1932 45 and this be-
came adopted widely even though no controlled trials verified its efficacy .
Subsequently, chloroquine was evaluated, but it failed to cure the infection 29.
Bithiniol was thought to be of value by Yoshida and his collaborators (1962)
who used it in two patients 93. This drug was also claimed to be effective b y
Ashton and colleagues, although convincing evidence for this was not pre -
sented5. Again, good results were claimed i n a small number of patients treated
with metronidazole 59. Recently, it has been shown that praziquantel is effective
in fascioliasis 72.
UNDERSTANDING THE EPIDEMIOLOGY
Jean de Brie in the fourteenth century made an epidemiological observation of

the profoundest importance by linking the acquisition of infection to feeding
animals on certain types of pasture at particular times of the year:
The good shepherd should be extremely careful in the month of March not to lead
his animals to pasture in marshy regions that are low and damp for there grows a
very dangerous herb with a small, round, green leaf that is called la dauve, which the
sheep like very much to eat, but which is very harmful and damaging to them. 15
These points were expounded 150 yea rs later by Fitzherbert, who, having des-
cribed several grasses called "sperewort", "penny grasse" and "myldew e
grasse" remarked that "All manner of grasse that the lande flode ronneth over
is yll for shepe" 32.
In 1562, a very severe epidemic of sheep rot broke out in Holland. This was
described by the Dutch physician and astronomer, Cornelius Gemma wh o
ascribed it to a manifestation of divine justice as were earthquake, flood and
pestilence35. This episode was followed by a large outbreaks in Holland i n
167492 and again in Germany in 168 3. The problem was so widespread and so
well-known that Shakespeare alluded to it in his play "Titus Andronicus" (Act
4 Scene 4):
I will enchant the old Andronicus
With worms more sweet, and yet more dangerous,
Than baits to fish, or honey-stalks to sheep,
When as the one is wounded with the bait,
The other rotted with delicious feed.
It gradually became clear that infection was most likely to occur when sheep
and other animals were fed on moist ground in warm weather. This was most
probable in low-lying marshes and swamps, but could happen upland if there
was sufficient moisture. In his studies on the transmission of fascioliasis ,
Thomas (1881-1882) made a number of observations which helped to clarify
the epidemiology of this infection. Firstly, he defined the environmenta l
conditions necessary for ripening of the eggs. Secondly, he showed that eggs
continued to hatch over weeks or months, thus prolonging the period of trans-
mission. Thirdly, he indicated that outbreaks of fascioliasis in sheep wer e
associated with similar epidemics in rabbits and that these animals greatl y
facilitated the dispersion of ova. Fourthly, he confirmed that Weinland' s
observation of cercarial cyst formation on grass 92 was applicable to F. hepat-
ica, and thus helped to explain the mod e of acquisition of infection 83,84. Finally,
his and Leuckart's discovery that certain speci es of snails were the intermediate
host made the epidemiology of fascioliasis comprehensible. The potentia l
magnitude of transmission was emphasized by their calculations that eac h
fluke produced at least 40,000 eggs, and that a single miracidium might gen-
erate over 1,000 cercariae. Militating against this, however, was the fact that
environmental conditions generally prevented the majority of miracidia an d
cercariae from finding their intended hosts. It was now clear that epidemic s
were common in wet years because moisture both enhanced the development
of F. hepatica eggs and favoured the multiplication of molluscan intermediate
hosts. Sheep were likely to be infected by eati ng grass contaminated with cysts,
perhaps by ingesting infected snails, and possibly by drinking adulterate d
water. During this century, studies have defined the species of Lymnaea and
related genera that are intermediate hosts of this parasite in different regions
of the world.
Despite the ravages of rot in sheep, it was recognized that fascioliasis was
rare in humans 4. Indeed, by 1915, it was said that only 28 cases had been re-
corded in the literature up to that time, although it must be said that man y
hundreds of such infections have since been reported. There was considerable
discussion for many years as to whether it was safe for humans to eat the flesh
of sheep with this infection. With the demonstration of Simonds (1850) that
feeding F. hepatica eggs did not result in infection, and with the delineation
of the life cycle by Thomas and Leuckart (1 881-1882), it became apparent that
the dangers of such a practice were not at all that great. Nevertheless, thi s
possibility was in the back of t heir minds when Humble and Lush in 1881 dis-
cussed how their patient had become infected. After discounting this as a
possibility, for the patient had not been in the habit of eating sheep's livers ,
they remarked that "we can throw no light on the question, how the patien t
contracted the disease" 40 but did mention that "he frequently ate th e
watercress" 40.
It subsequently became accepted that infection could be acquired by eating
plants contaminated with cysts, particularly watercress ( Nasturtium
officinale), or by drinking polluted water. The role of the former wa s
emphasized when a small outbreak of fascioliasis occurred in six patients in
Hampshire, England in 1958-1959; all of them were in the habit of eatin g
watercress frequently29. It was shown even more dramatically in a larg e
outbreak in Monmouthshire, England in 1968-1969 in which 44 patients were
infected, all of whom admitted to have eaten watercress from the same be d
Fascioliasis 121
which also was located near some infected cattle and sheep 39.
THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES
The possibility of preventing fascioliasis in sheep has been known for mor e
than 600 years. de Brie in 1379 concluded his dissertion on rot in sheep b y
reminding his readers that "the s hepherd should take care not to lead his sheep
near marshy places where la dauve grows all summer long" 15. Fitzherbert
(1523) emphasized this, recommending that the sheep "may nat well be lette
out of the fold tyll the sonne have domynacion to drie them away" 32.
Thomas amplified preventive measures by recommending that infecte d
sheep be destroyed, infected livers disposed of, and manure from infecte d
sheep be collected and eggs hindered from developing by the addition of coal
tar or by being spread over, dry, well-drained ground. Further, he emphasized
the value of draining the land and destroying snails with a dressing of lime or
with salt83. To these measures were added during this century, adequat e
chemotherapy of infected animals and t he introduction of newer molluscicides.
Understanding the epidemiology and the frequent incrimination of water -
cress as the vehicle by which human infections were acquired, led to repeated
calls for education of the public concerning the dangers of eating wild water-
cress, and recommendations that watercress be grown commercially unde r
controlled conditions.
OTHER SPECIES OF FASCIOLA
F. GIGANTICA
The adult fluke was discovered in the liver of a giraffe and named Fasciola
gigantica by Spencer Cobbold in 1855 21. The life cycle of this parasite and the
pathology and clinical features it induces parallel those of F. hepatica, but
different species of snails are the intermediate hosts.
In 1895, de Gouvêa in Rio de Janeiro, Brazil published an account of a
French naval officer who had recently been in Senegal and who had presented
with fever and haemoptysis, then had coughed up a fluke 2.5 cm long 38. There
have been differences of opinions as to the identity of this parasite. According
to Brumpt16, Railliet considered that it was the liver fluke, F. hepatica var
augusta while Raphael Blanchard identified it as F. gigantica. In 1927,
Pigoulewsky described F. gigantica infection in a child in Tashkent, USSR.
The diagnosis was based only upon the appearances of eggs found in th e
faeces67. The first clearcut case of fascioliasis gigantica was reported b y
Codvelle and his colleagues in 1928 22.
REFERENCES
1. ABILDGAARD PC. Almindelige Betragtninger over Involde-Orme, Bemaerkninger ved

Hundsteilens Baendelorm, og Beskrivelse med Figurer af nogle nye Baendelorme. Skrivter
af Naturhistorie-Selskabet Kjøbenhavn 1: 26-64, 1790
2. ALICATA JE. Observations on the life history of Fasciola gigantica, the common liver fluke
of cattle in Hawaii, and the intermediate host, Fossaria ollula. Bulletin 80 of the Hawaii
Agriculture Experimental Station, pp 22, 1938
3. d'ALLAINES F, LAVIER G, GANRILLE. Une petite epidémie de distomatose hépatique à
Fasciola hepatica. Diagnostiquée rétrospectivement. La Presse Médicale 50: 738-739, 1942
4. ANONYMOUS The rot in sheep. Lancet i: 924, 1880
5. ASHTON WL, BOARDMAN PL, D'SA CJ, EVERALL PH, HOUGHTON AW. Human
fascioliasis in Shropshire. British Medical Journal ii: 500-502, 1970
6. AZAR JE. An unsuccessful trial on production of parasitic pharyngitis (Halzoun) in human
volunteers. American Journal of Tropical Medicine and Hygiene 13: 582-583, 1964
7. van BENEDEN PJ. Mémoires sur les vers intestinaux. Supplement to Comptes Rendus
Hebdomadaires des Séances de l'Académie des Sciences, Tome II, Paris, pp 376, 1858
(written, 1852; couronné par l'Institut, 1853)
8. BIDLOO G. Brief van G Bidloo, aan Antony van Leeuwenhoek, wegens de dieren, welke
men zomtyds in de lever der schaapen en andere beesten vind, H van Kroonevelt, Delft, pp
34, 1698. In, The select works of Anthony van Leeuwenhoek containing his microscopical
discoveries in many of the works of nature, translated by S Hoole from the Dutch and Latin
editions, Henry Fry, London, 1798
9. BLANCHARD E. Recherches sur l'organisation des vers. Annales des Sciences Naturelles,
Zoologie, Series 3, 7: 87-149, 271-341, 1847
10. BOJANUS LH. Kurze Nachricht über die Zerkarien und ihren Fundort. Isis (Oken's), Oder
Encyclopädische Zeitung, Jena, pp 729-730, 1818 Partly translated in 43
11. BOREL P. Cited in 20
12. BRAUN M. Vermes. In, Klassen und Ordnungen des Tierreichs, HG Bronn (Editor), CF
Winter'sche Verlagshandlung, Leipzig, volume 4, pp 209-925, 1879-1893
13. BRAUN M. The animal parasites of man: a handbook for students and medical men, third
edition, translated by P Falcke and brought up to date by LW Sambon and FV Theobald,
John Bale, Sons and Danielsson, London, pp 453, 1906
14. BRAUN M, SEIFERT O. Die Tierischen Parasiten des Menschen, Verlag von Cürt
Kabitzsch, Würzburg, volume 1, pp 559, 1915
15. de BRIE J. Le bon berger ou le vray régime et gouvernement des bergers et bergères. Com-
posé par le rustique Jehan de Brie le bon berger (1379), Isidor Liseux, Paris, pp 160, 1879
(reprinted from the edition of 1541). Partly translated in 43.
16. BRUMPT R. Précis de parasitologie, Masson et Cie, éditeurs, Libraires de l'Académie de
Médecine, Paris, pp 1011, 1913
17. BUCHOLZ. Cited in 42
18. CAMERON TW. The internal parasites of domestic animals, A&C Black Ltd., London, pp
292, 1934
19. CHABERT JX. Another case of tapeworm "about 30 yards long" associated with specimens
of Distoma hepaticum. Boston Medical and Surgical Journal 47: 173, 1853
20. CLERICUS D (LE CLERC). Historia naturalis et medica latorum lubricorum intra hom-
inem et alia animalia, nascentium. Ex variis auctoribus propriis observationibus, Fratres De
Tournes, Genevae, pp 449, 1715. A natural and medicinal history of worms bred in the bod-
ies of men and other animals etc., translated by J Browne, printed for J Wilcox at the Green-
Dragon, Little Britain, pp 436, 1721
21. COBBOLD T S. Description of a new trematode worm (Fasciola gigantica). Edinburgh
New Philosophical Journal, new series, 2: 262-267, 1855
22. CODVELLE, GRANDCLAUDE, VANLANDE. Un cas de distomatose humaine à
Fasciola gigantica (Cholécystite aigue distomienne avec lésions particulières de la paroi
Fascioliasis 123
vésiculaire). Bulletins et Mémoires de la Société Médicale des Hôpitaux de Paris 52:

1180-1185, 1928
23. CREPLIN FC. "Distoma". In, Allgemeine Encyklopädie der Wissenschaften und Künste,
JS Ersch und JP Gruber (Editors), Leipzig, Sect. 1, Part 29: 309-329, 1837 Partly translated
in 43
24. DAVAINE CJ. Traité des entozoaires et des maladies vermineuses de l'homme et des ani-
maux domestiques, second edition, J-B Baillière et fils, Paris, pp 1003, 1877
25. DIESING CM. Systema helminthum, Wilhelmum Braumüller, Vindobonae, two volumes,
pp 1267, 1849-1851
26. DIESING CM. Berichtigungen und Zusätzen zur Revision der Cercarien. Sitzsungsberichte
der Akademie der Wissenschaften in Wien. Mathematische-naturwissenschaftliche Klasse
31: 239-290, 1858
27. DUFFEK E. Distomum hepaticum beim Menschen. Wiener klinische Wochenschrift 15:
772-776, 1902
28. FABER J. Note in G J Sach's Scholium to T. Bartholin's "Sanguis verminosus", Lipsiae, p
147, 1670
29. FACEY RV, MARSDEN PD. Fascioliasis in man: an outbreak in Hampshire. British
Medical Journal ii: 619-625, 1960
30. de FILIPPI F. Descrizione di nuovi entozoi trovati in alcuni molluschi d'aqua dolce. Biblio-
theca Italiana, an 22, 87: 333-340, 1837
31. de FILIPPI F. Mémoire pour servir à l'histoire génétique des trématodes. Memorie della
Reale Accademia delle Scienze de Torino, second series, 15: 331-358, 1854
32. FITZHERBERT A. The boke of husbondrye. Here begynneth a newe tracte or treatyse
moost profytable for all husbande men: and very frutefull for alle other persons to rede, pp
65, 1523. Formerly attributed to Sir Anthony, but really written by John, his brother
33. FROMMAN JC. De verminoso in ovibus et juvencis reperto hepate. Miscellanea Curiosa
Sive Ephemeridum Medico-Physicarum Germanicarum Academiae Naturae Curiosorum
(1675-1676), pp 245-252, 1688
34. GABUCINUS H. De lumbricis alvum occupantibus, ac de ratione curande eos, qui ab illis
infestantur, commentarius, H Scotus, Venetiis, pp 56, 1547
35. GEMMA C. De naturae divinis characterismis seu raris et admirandis spectaculis, causis,
indiciis, proprietatibus rerum in partibus singulis universi, Antverpiae, pp 225, 1575
36. GESNER C. Historiae animalium liber I. Qui est de quadrupedibus viviparus, Tiguri, pp
1104, 1551-1558
37. GIESKER, FREY H. Helminthologische Beitrag. Mittheilungen der naturforschenden
Gesellschaft in Zurich 2: 89-95, 1850
38. de GOUVÊA H. La distomatose pulmonaire par la douve du foie, L Bataille et Cie, Paris,
pp 46, 1895. Abstracted in British Medical Journal i: 932, 1895
39. HARDMANN EW. Fascioliasis - a large outbreak. British Medical Journal ii: 502-505,
1970
40. HUMBLE WE, LUSH WV. A case of Distoma hepaticum (liver-fluke) in man. British
41. INTERNATIONAL COMMITTEE ON ZOOLOGICALNOMENCLATURE. Trematode,
Cestode and Acanthocephala names placedin the official list of generic names (Opinion 84),
Smithsonian Miscellaneous Collections, Smithsonian Institution, Washington, DC,
Publication 2830, 73: 11-12, 1925. Also, Nature 117: 414, 1926
42. JÖRDENS JH. Entomologie und Helminthologie des menschlichen Körpers etc., GA Grau,
Hof, pp 473, 180-1802
43. KEAN BH, MOTT JE, RUSSELL AJ. Tropical medicine and parasitology. Classic invest-
igations, Cornell University Press, Ithaca, two volumes, pp 677, 1978
44. KHOURY A. Le halzoun. Archives de Parasitologie 9: 78, 1905
45. KOURI P, ARENAS R. La distomatosis par Fasciola hepatica L. en Cuba. Especial refer-
encia sobre so tratamiento. Possible accion especifica de la emetine. Vida Nueva 28:
553-579, 1932
46. KÜCHENMEISTER F. Die in und am dem Körper des lebenden Menschen Vorkommenden
pflanzischen Parasiten des Menschen, two volumes, BG Teubner, Leipzig, pp 486, 1855.
On animal and vegetable parasites of the human body. A manualof their natural history,
diagnosis and treatment. Volume 1. Animal parasites belonging to the group entozoa, trans-
lated by E Lankester, The Sydenham Society, London, pp 452, 1857
47. van LEEUWENHOEK A. Part of a letter from Mr. Antony van Leeuwenhoek concerning
worms observ'd in sheeps livers and pasture grounds. Philosophical Transactions of the
Royal Society 24: 1522-1527, 1704
48. LEUCKART R. Zur Entwickelungsgeschichte des Leberegels. Zoologischer Anzeiger 4:
641646, 1881. Translated in 43
49. LEUCKART R. Zur Entwickelungsgeschichte des Leberegels (Distomum hepaticum).
Archiv für Naturgeschichte 1: 80-119, 1882
50. LEUCKART R. Zur Entwickelungsgeschichte des Leberegels. Zweite Mittheilung. Zool-
ogischer Anzeiger 5: 524-528, 1882
51. LINNAEUS C. Systema naturae, per regna tria naturae, secundum, classes, ordines, genera,
species, cum characteribus differentiis, synonymis, locis, tenth edition, L Salvii, Holmiae,
two volumes, pp 823, 1758
52. LUTZ A. Zur Lebensgeschichte desDistoma hepaticum. Centralblatt für Bakteriologie und
Parasitenkunde, Abteilung originale 11: 783-796, 1892. Partly translated in 43
53. MALPIGHI M. Opera posthuma. Quibus praefixa est vita, a seipso scripta, A et J Churchill,
Londini, pp 187, 1698
54. MARTIN R, LE ROY, SUREAU B, BABOUOT P, BOURCART N. Un nouveau cas de
distomatose hépatique: diagnostic précoce par le tubage duodénal. Bulletin de la Société de
55. MARTIN de la CALLE SP. Abstracted in, Distomiasis in man, Lancet ii: 1340-1341, 1890
56. MEHLIS CF. Novae observationes de entozois, auctore Dr Fr Chr H Creplin. . . Angezeigt
und mit Bemerkungen begleiter von Dr E Mehlis. Isis (Oken's), Oder Encyclopädische
Zeitung, Jena, pp 68-99, 166-199, 1831
57. MORENAS L. Les réactions d'allergie cutanée dans la distomatose humaine àFasciola
hepatica: cuti et intra-dermo-réaction. Comptes Rendus Hebdomadaires des Séances et
Mémoires de la Société de Biologie 137: 563-565, 1943
58. MÜLLER OF. Vermium terrestrium et fluviatilium, seu animalium infusorium,
helminthocorum et testaceorum, non marinorum, succincta historia. Vol. 1, Infusoria,
Havniae et Lipsiae, pp 135, 1773
59. NIK-AKHTAR B, TABIBI V. Metronidazole in fascioliasis. Report of four cases. Journal
of Tropical Medicine and Hygiene 80: 179-180, 1977
60. NITZSCH CL. Seltsame Lebens- und Todesart eines kleinen bisher unbekanntnen Wasser-
thierchens. In, Kilian. Georgia, oder Der Menschen im Leben und im Staate, pp 257-252,
281-286, 1807
61. NITZSCH CL. Beitrag zur Infusorienkunde, oder Naturbeschreibung der Zerkarien und
Bazillarien. Neue Schriften der naturforschenden Gesellschaft zu Halle 3: 1-128, 1817
62. von NORDMANN A. Mikrographische Beiträge zur Naturgeschichte der wirbellosen
Thiere, G Reimer, Berlin, two volumes, pp 268, 1832
63. OKEN L. Cited in 13
64. OKEN L. Cited in 77
65. PAGENSTECHER HA. Trematodenlarven und Trematoden, Helminthologischer Beitrag,
Heidelburg, pp 56, 1857
66. PALLAS PS. Dissertatio medica inauguralis de infestis viventibus intraviventia, Lugduni
Batavorum, 1760
67. PIGOULEWSKY SW. (Un cas de Fasciola gigantica Cob chez un enfant Usbék en Vieux
Tashkent. Pensée Médecine d'Usbekistane.) In Russian, pp 59-61, French summary, p 131,
1927. Republished in German in Archiv für Schiffs- und Tropen-Hygiene 32: 511-512,
1928
68. REDI F. Esperienze intorno alla generazione degl'insetti, Carlo Dati, Firenze, pp 177, 1668.
Experiments on the generation of insects translated from the 1688 edition by M Bigelow,
Opencourt Publishing Co., Chicago, pp 160, 1909
69. REDI F. Osservazioni intorno agli animal viventi che si trovano negli animali viventi, Piero
Fascioliasis 125
Matini, Firenze, pp 244, 1684. Partly translated in 43.

70. RETZIUS AJ. Lectionibus publicae de vermibus intestinalibus imprimis humanis quas
habuit in musaeo rev. nat. acad. Ludensis d. xviii Martii et seq., 1784, Holmiae, pp 55, 1786
71. RETZIUS AJ. Lectionibus publicae de vermibus intestinalibus, imprimis humanis, quas
habuit in musaeo rev. nat. acad. Ludensis d. xviii Martii et seq. 1784. In. J P Frank,
Delectus oposculorum medicorum, Ticini, 9:1-92, 1790
72. SCHIAPPACASSE RH, MOHAMMADI D, CHRISTIE AJ. Successful treatment of severe
infection with Fasciola hepatica with praziquantel. Journal of Infectious Diseases 152:
1339-1340, 1985
73. SERVANTIE L. Recherche de la déviation du complement dans la distomatose humaine.
Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 84:
699, 1921
74. SHIRAI M. The biological observation on the cysts ofFasciola hepatica and the route of
migration of young worms in the final host. Scientific Reports of the Government Institute
of Infectious Diseases, Tokyo, 6: 511-523, 1927
75. von SIEBOLD CT. Helminthologische Beiträge. Archiv für Naturgeschichte 1: 45-84, 1835
76. von SIEBOLD CT. Parasiten. In, Handwörterbuch der Physiologie mit Rücksicht auf
physiologische Pathologie, R Wagner (Editor), Braun Schweig, 2: 650-676, 1844
77. von SIEBOLD CT. Über die Band- und Blasenwürmer nebst einer Einleitung über die
Entstehung der Eingeweidewürmer, W Engelmann, Leipzig, pp 115, 1854. On the tape and
cystic worms with an introduction on the origin of intestinal worms, translated by TH
Huxley, pp 88, bound with volume 2 of F Küchenmeister's Manual of Parasites, The
Sydenham Society, London, 1857.
78. SIMONDS JB. The rot in sheep; its nature, causes, treatment and prevention, fifth edition,
John Murray, London, pp 100, 1880
79. SISINTSIN DF. Methods I have followed in my research. Journal of Parasitology 13:
84-86, 1926
80. SSINITZIN DF. Neue tatsachen über die Biologie der Fasciola hepatica L. Zentralblatt für
Bakteriologie, Parasitenkunde und Infektionskrankheiten, Abteilung originale 74: 280-285,
1914
81. STEENSTRUP JJ. Om Fortplantning og Udvikling gjennem Vexlende Generations
Raekker, en saeregen Form for Opfostringen i de lavere Dyreklasser, CA Reitzel,
Kjøbenhavn, pp 76, 1842. On the alternation of generations, or, the propogation and
development of animals through alternate generations: a peculiar form of fostering the young
in the lower classes of animals, translated from the German version of CH Lorenzen by G
Busk, The Ray Society, London, pp 132, 1845
82. SUZUKI S. (Researches into the life history of Fasciola hepatica and its distribution in
Formosa, especially on the determination of the first intermediate host and some experiments
with larvae freed from their cysts artificially.) Taiwan Igakkai Zasshi volume 30, no 12. In
Japanese, with English summary 30: 97-100, 1931
83. THOMAS AP. Report on experiments on the development of the liver fluke (Fasciola hep-
atica). Journal of the Royal Agricultural Society of England 17: 1-28, 1881
84. THOMAS AP. Second report of experiments on the development of the liver fluke
(Fasciola hepatica). Journal of the Royal Agricultural Society of England 18: 439-455,
1882. Abstracted in British Medical Journal ii: 1001-1002, 1882 and Lancet ii: 849, 1882.
85. THOMAS AP. The rot in sheep, or the life history of the liver fluke. Nature 26: 606-608,
1882
86. THOMAS AP. The life history of the liver fluke (Fasciola hepatica). Quarterly Journal of
Microscopical Science, new series, 23: 99-133, 1883
87. la VALETTE de St. GEORGE A. Symbolae ad trematodum evolutionis historiam, Berlin,
pp 38, 1855
88. WAGENER GR. Beiträge zur Entwickelungs-Geschichte der Eingeweidewürmer. Natur-
kundinge Verhandelingen van de Hollandsche Maatschapij der Wetenschappen te Haarlem,
pp 112, 1857
89. WARD GR. Hepatic distomiasis (sheep rot) in man. British Medical Journal i: 931-935,
1911
90. WEINBERG. Recherches des anticorps spécifiques dans la distomatose et la cysticercose.

219-221, 1909
91. WEINLAND D. Die Weichthierfauna der schwäbischen Alp, Stuttgart, p 101, 1875
92. WILLIUS JV. Vernichtung des Viehstandes auf Abrahamstrup in Seeland durch Blasen-
würmer. In, Th. Bartholinus, Acta medica et philosophica, Hafniansa, Library of Useful
Knowledge, London, 5 volumes, 1673-1680
93. YOSHIDA Y, MIYAKE K, NAKANISHI Y, NISHIDA K, YAMASHIKI Y, ISHIKAWA
T, FUJISAKA K, TANAKA A, EBARA S. (Two cases of human infection withFasciola
sp. and the treatment with bithiniol). Japanese Journal of Parasitology 11: 411-420, 1962.
In Japanese
94. YOUATT W. Sheep, their breeds, management, and diseases, London, pp 568, 1837
Table 4.1. Landmarks in fascioliasis

_________________________________________________________________
1379 First recorded reference to worms in sheep by de Brie, who also linked
infection with feeding animals in certain types of pastures at particular times
of the year
1523 Fitzherbert gave an accurate clinical description of fascioliasis in infected
sheep
1670 Faber observed that worms were located in the biliary tree
1690 Bidloo discovered eggs and recognized that the worms were hermaphroditic
1758 Linnaeus named the worm Fasciola hepatica
1760 Pallas gave the first detailed account of human infection (earlier allusions had
been made by Borel, Malpighi and Bidloo)
1882 Leuckart and Thomas described independently the development of miracidia
through to cercariae in the snail, Lymnaea truncatula
1892 Lutz demonstrated that adult worms developed after ingestion of encysted
metacercariae
1911 Ward diagnosed human fascioliasis by finding eggs in faeces
1914 Ssinitzin demonstrated the pathway of migration of flukes in the definitive
host
1985 Schiappacasse and colleagues reported that praziquantel was effective in
human fascioliasis
___________________________________________________________________
Chapter 5
Fasciolopsis buski and FASCIOLOPSIASIS.
SYNOPSIS
Common name: giant intestinal fluke

Major synonyms: Distoma crassum, Distoma Buskii
Distribution: Asia, especially eastern Asia
Life cycle: The elongate-ovoid hermaphroditic worms, 20-75 mm in length, 8-20 mm
in breadth and 0.5-5 mm in thickness live in the small intestinal lumen attached to the
duodenal and jejunal mucosa. They produce eggs which are passed in the faeces. The
ova develop in water over 3-7 weeks then each miracidium escapes and invades snail
intermediate hosts of the genera Segmentina and Hippeutis. The miracidium becomes
a sporocyst which passes through first and second generation rediae to produce
cercariae after a few weeks. The cercariae emerge from the snail and encyst on
aquatic vegetation including caltrop and water chestnut. People become infected by
peeling off the outer covering of the plants with their teeth before swallowing the raw
nut. The metacercariae excyst in the duodenum, attach to the small intestinal wall and
mature in about three months.
Definitive hosts: humans, pigs, (dogs)
Major clinical features: diarrhoea, abdominal pain and urticaria in heavy infections
Diagnosis: demonstration of eggs in faeces
Treatment: hexylresorcinol, dichlorophen, praziquantel
While performing in 1843 an auto psy on a Lascar (i.e. a sailor from the eastern
part of India) who had died in the naval hospital Dreadnought in Greenwich,
England, the English surgeon, George Busk, found 14 flukes in the duodenum.
This finding was not reported until 1852 when, based upon informatio n
supplied by Busk, it was described briefly by George Budd in his book ,
Diseases of the Liver. It was noted that these flukes, which were not present in
the gall bladder or bile ducts:
were much thicker and larger than those of the sheep, being from an inch and a half
to near three inches in length. They resembled the Distoma hepaticum in shape, but
were like the Distoma lanceolatum in structure; the double alimentary canal, as in the
latter variety, being not branched, and the entire space between it towards the latter
part of the body being occupied by the uterine tube. 8
This discovery was cited again in 1857 by ER Lankester in appendix B to his
translation of Küchenmeister's textbook, On animal and vegetable parasites
127
of the human body. After speculating about the possible life cycle of th e
parasite, he went on to say that:
In the absence of any other distinguishing name for this species, I have called it, after
the name of its discoverer, Distoma Buskii.19
Busk, however, objected to this designation. M oreover, Cobbold considered the
name invalid on the ground that Lankester had not provided a sufficien t
description of the parasite. Cobbold therefore asked Busk to suggest a ne w
name, and the latter thereupon proposed the appellation, Distoma crassum
(derived from the Latin "crassus" meaning "thi ck" or "gross"). This was adopted
by Cobbold when he redescribed the worm in his Synopsis of the Distomidae
communicated to the Linnean Society in London in June 1859 and published
in its journal in the following year10. This was to cause confusion subsequently,
with some authors calling the worm D. crassum Busk and others referring to
it as D. crassum Cobbold. Cobbold himself used the former term in his original
description. To complicate matters more, the name Distoma crassum had
already been used in 1836 by von Siebold for a fluke found in a house martin.
This nomenclature was rejected by C obbold for the same reason that he had set
aside D. buskii, i.e. the naming was not accompanied by an adequat e
description. Cobbold's redescription w as based on one of Busk's original flukes
which had been kept in the museum of the Royal College of Surgeons i n
London. He subsequently sent the worm to Leuckart who concurred wit h
Cobbold's view and described it as D. crassum in his textbook in 1863 23.
Weinland and also Davaine14, however, were misled by the inaccurate original
description of the uterine coils and transferred the worm to the genu s
Dicrocoelium.
The parasite was not recognized again until the northern spring of 1874. A
missionary and his wife who had been resident in China for about four year s
consulted Dr George Johnstone in London concerning persistent diarrhoea .
They were referred to Cobbold who treated them with aloes and asafoetid a
without any improvement. Eventually, however, twelve worms were expelled
spontaneously. When Cobbold showed them to Busk, "he at once recognised
them as referrable to the species he had long ago discovered" 11.
Meanwhile, Dr JG Kerr, the founder of the Hospital for the Insane i n
Canton, China, had sent another worm to Professor Gross in the Unite d
States of America, remarking that it had been vomited by a 15 year ol d
Chinese boy. He added that at one time, a four year old English girl ha d
passed nine of these worms. The parasite passed into the hands of Josep h
Leidy who exhibited it at the Academy of Natural Science in Philadelphia i n
October 1873. Leidy described its external morphology but said nothing of its
internal organization and misdi agnosed it as Fasciola hepatica 20. He corrected
the error 18 years later, merely to commit another when he equated it with F.
magna 21.
In 1887, J Poirier began the fashion of giving new specific names to variant
specimens of F. buski when he described the worm passed by a 35 year ol d
Fasciolopsiasis 129
Chinese woman at the Catholic Mission in Zi-kawei, China, and which ha d

been sent to him by Father Rathouis in Shanghai. Since the woman had a
chronic liver complaint, Poirier concluded that the parasite must have come
from the bile ducts and named it D. rathouisi 33. At the outset, Leuckart was
sceptical and considered that it was probably identical with the D. crassum of
Busk24. He was supported in this view by Odhner 30 but contradicted by Ward 38
and by Railliet and Henry34. Ward's opinion was based on a study of 11 spec-
imens obtained from two cases by FW Goddard in 1907 and forwarded to him
by Dr WH Jeffreys of Shanghai. Included in this batch of worms were fiv e
helminths that had minor morphological differences: Ward named these F.
goddardi 38. In 1908, an eight year old girl in Hong Kong vomited a fluke; it
was brought to DM Heanley by Dr Kwan King-Hung. Heanley thought tha t
this was an undescribed species and it be came known as Kwan's fluke 16. Leip-
er later showed that it was merely F. buski that had been macerated by th e
action of gastric juices before being vomited 22. In 1909, another Laskar from
Calcutta was admitted to the Seaman's Hospital in Hamburg, Germany, with
a provisional diagnosis of typhoid fever. He passed several flukes in his faeces,
and E Rodenwaldt, considering them to be a new species, named it F. fülle-
borni 35. Finally, Brown in 1917 examined 118 specimens preserved i n
alcohol that had been collected in Shaohsing, and believing erroneously that
F. buski did not have cuticular spines, proposed naming those with spines F.
spinifera 7.
All this confusion and proliferation of names was brought to an end in 1919
by FW Goddard of the Christian Hospita l in Shaohsing, China. He studied 433
specimens then cut histological sections from 17 worms that conformed to the
description of F. buski, F. rathouisi and F. goddardi. He concluded that:
the parasite showed great variation in morphology but withal such gradation in
variation as to justify including the forms now described as F. rathouisi and F. god-
dardi in the species F. buski. On account of the close similarity of F. fülleborni it
would appear desirable to subject this species also to further investigations. 15
Meanwhile, this species had been transferred to another genus by Odhner in
190230. He examined flukes in the Zoological Museum in Copenhagen tha t
were contained in two glass jars dated Dec. 20, 1890 and Jan. 1, 1891. They
had been obtained by Dr Deuntzer in Bangkok f rom a 13 year old boy who had
had a typhoid fever-like illness and had expelled flukes after the administration
of calomel. Odhner improved on the description of the worm and transferred
it to the genus Fasciolopsis that had been erected by Looss in 1899 25. This
name is derived from a combination of th e Latin "fasciola" meaning "fillet" and
the Greek (OPSIS) "meaning resemblance", to indicate the similarity of
this worm to F. hepatica. Odhner named the worm Fasciolopsis buski,
spelling the specific name with one "i" 30 instead of with two (buskii) as in the
original of Lankester; it has generally retained this designation since that time,
although some authors have labelled it as F. buskii.

OF THE LARVAL STAGES AND SNAIL INTERMEDIATE HOSTS
When he named the parasite F. buski in 1857, Lankester speculated about the
life cycle of this worm. He surmised that the usual host was probably som e
species of lower animal living in the tropics and that humans were likely t o
acquire the infection in a fashion similar to the way in which they becam e
infected with F. hepatica 19. The means by which the latter worm was trans-
mitted was not known at that time, although speculation that snails wer e
involved was rife. When this was confirmed by Thomas and Leuckart in 1882
(see chapter 4), it gave credence to the idea that fasciolopsiasis was trans -
mitted likewise. Lankester's suppositions were substantiated further when i t
was discovered that pigs in certain endemic areas were infected not infre -
quently with F. buski. The only other observation of significance that wa s
made during the nineteenth century was the discovery of the operculum of the
F. buski egg. Although Cobbold had desc ribed the appearance and dimensions
of these ova in 1875 11, he apparently failed to see the operculum. This wa s
eventually discovered by an anonymous commentator who examined a spec-
imen submitted to the British Medical Journal by JH Walker in Sandakar ,
North Borneo in 1891 1.
This, therefore, was the background when Koa n Nakagawa in Formosa (Tai-
wan) in 1915 turned his attention from the study of the life cycle of Para-
gonimus westermani to investigate that of F. buski. Human infections with the
parasite were almost unknown on that island, but fasciolopsiasis was ver y
common in pigs, so he obtained his specimens from that source. He pursued
his experiments over five years, finally publishing his results in 1921 28 and
again with more details in the following year 29. He noted that when eggs were
deposited in water during the warmer months, they developed over the nex t
two to three weeks, then hatched miracidia which swam about freely in th e
water. He incubated these miracidia with a number of species of snail s
collected from local ponds and brooks but obtained either negative o r
confusing results. Realizing that he had to have snails that were free of an y
naturally-acquired infection (there being at least 17 different forms of cercariae
present on Taiwan), he tried to raise s nails artificially from eggs in aquaria. He
finally succeeded in cultivating what he considered to be two species of snail,
Plan-orbis coenosus and Segmentina largillierta (now both known as
Segmentina hemisphaerula ). These snails proved susceptible to infection, for
when he placed them with F. buski miracidia in an aquarium in April 1920,
the snails:
were soon found covered by swarming miracidia which tried to bore into the head,
foot, tentacles, mantle etc. They left their ciliated coats as they penetrated into the
snail.28
In the tissues of the snails, he observed that the miracidia transformed int o
sporocysts, grew and migrated, especially into the mantle and walls of the ali-
Fasciolopsiasis 131
mentary canal. By the seventh day of infection, rediae could be seen in th e

sporocysts, and by 35 days, young cercariae could be discerned within th e
rediae. Moreover, in some instances, daughter rediae (second generatio n
rediae) developed within parent redi ae. He then noticed that after the cercariae
were liberated from the snail 38 days or so after infection, they soon attached
themselves to grass and encysted. Furthermore, the cercariae were identical in
appearance to those he had seen in 1918 in naturally infected snails collected
from a small pond near Shinchiku where fasciolopsiasis in pigs was ver y
common. Nakagawa thus:
concluded that the intermediate hosts of Fasciolopsis buski are Planorbis coenosus
Benson and Segmentina largillierta Dkr. in Formosa28
Nakagawa then attempted to infect experimental animals with these cysts. On
19 June 1920, he infected a young dog with 40 cysts, then three days later he
gave it another 50 encysted cercariae. The animal was killed on 16 July 1920
and 59 young distomes 2-3 mm long were found squirming around in th e
duodenum and jejunum. Thereupon, he repeated the experiment with a young
pig and returned similar results. A third experiment was then undertaken with
another pig being infected on June 1920 then killed 90 days later; in thi s
animal, 23 worms, definitely F. buski, 13-15 mm in length, were found in the
small intestine. Nakagawa had thus completed the life cycle and conclude d
that:
the mode of infection with F. buski is very simple. The only means of being infected
is to eat raw water plants, which carry the encysted cercariae, or to drink the water
containing them.29
The next person to apply his mind to the problem of fasciolopsiasis wa s
Claude Barlow, an American missionary at Shaohsing Christian Hospital i n
Chekiang Province, China. He reported the results of some of his invest -
igations in a number of journals over several years, then brought all th e
available information together in a monograph of nearly 100 pages published
in 19255. Fasciolopsiasis was a common and serious problem in the are a
around Shaohsing, occurring frequently in humans but almost never in pigs,
the opposite situation to that pertaining in Taiwan. Thus, Barlow's observ -
ations were made on F. buski derived from human sources.
Before the life cycle of F. buski was understood, Barlow swallowed egg s
(late 1918) and living adult flukes (early 1920) in order to establish the time
required for stools to become free of ova after treatment and to determin e
whether infection could be acquired by ingesting adult worms. When he swall-
owed eggs in gelatine capsules, they appeared in the faeces on either the same
day or on the following day, then disappeared within eight days; they did not
seem to be damaged in the process. On the first occasion that he swallowe d
living adult worms, eggs were not seen at any time. He then ingested thre e
more flukes, one of which lodged in t he intestines with the result that ova were
discovered in the stools 28 hours later. Fertile eggs continued to be excreted
by this single fluke until it was expelled by an anthelmintic one year later 2.
In 1922, following publication by Nakagawa of the details of the life cycle

of F. buski, Barlow reported in a preliminary note that human infection wa s
acquired by eating water chestnut ( Eliocharis tuberosa) and water caltrop
(Trapa natans) on which the cercariae encysted. The red water caltrop wa s
particularly incriminated, with as many as 40 cysts being found on a single nut.
Furthermore, he indicated that no cases of infection in pigs had been discov-
ered, even in the areas of greatest infection of humans around Shaohsing, thus
suggesting that there may be differences be tween the porcine and human forms
of the parasite3. These findings were then reported in greater detail in th e
following year when he also recorded the results of his next experiment .
Barlow had determined to confirm that Nakagawa's observations on the inf-
ection of pigs and dogs exposed to pig-derived F. buski were also applicable
to humans infected with cercariae emanating from human sources. Secondary
objectives were to characterize the species of snail susceptible to the loca l
strain of the parasite and to discern the symptoms induced by infection.
Initially, Barlow developed the procedu res necessary for establishing the life
cycle of the parasite in the laboratory. He found that two species of aquati c
snails that were commonly associated with the water caltrop, Planorbis
schmakeri (now known as Hippeutis cantori) and Segmentina nitidellus (= S.
hemisphaerula), were susceptible to infection. He reared the snails in th e
laboratory and followed the course of infection when they were exposed to F.
buski miracidia hatched from eggs in human faeces. Like Nakagawa, he ob-
served the transformation of miracidia i nto sporocysts and the growth of rediae
within them, then noted the escape of rediae from ruptured sporocysts ,
beginning eight days after infection. In fact, he continued to see rediae being
released for as long as 254 days after infection of the snail, and thought tha t
this probably indicated multiple generations of rediae. He found that cercariae
formed within daughter rediae began to emerge between 25 and 30 days after
infection of the snail, but that instead of leaving the host immediately through
the mantle or pulmonary orifice, they usually remained in the liver or in th e
lymph space around the heart for from a few hours to a couple of days while
completing their maturation. He descri bed the process of encystation carefully,
indicating that it began within a few min utes of the cercariae coming in contact
with plants, and was completed within one to three hours.
Now that he had a sure and defined source of F. buski cysts, this intrepid
investigator was ready to enter the n ext phase of his investigation. On 27 Nov-
ember 1922, having first ascertained that his stools were free of eggs, Barlow
swallowed 98 cysts collected from water caltrop in the fields nearby. Th e
following day, he ingested another 35 cysts obtained from aquarium-reare d
snails. Thirty one days after the initial infection, ova appeared in his faeces. On
23 February 1923, following the administration of an anthelmintic (carbo n
tetrachloride), he passed a total of 124 ad ult F. buski in his stools 4. His graphic
account of the clinical manifestations induced by infection will be recounted
shortly.
Fasciolopsiasis 133
RECOGNITION OF THE CLINICAL FEATURES AND VIEWS O N

PATHOGENESIS
An association between infection with F. buski and diarrhoea was moote d

early. This symptom was the major complaint of the missionary and his wife
who were treated by Spencer Cobbold on their return from China. Whethe r
coincidentally or not, the diarrhoea resolved when the flukes were expelled ,
and Cobbold was left in no doubt as to there being a causal relationshi p
between the two events. Nevertheless, he had a remarkably naive and immat-
ure view of the symptomatology of this infection, for when discussing th e
condition several years later, he commented that:
Savages of the untutored races in the matter of symptoms, suffer much less from the
presence of intestinal worms than their civilised fellow-men do. 12
Several of the first reported patients had a typhoid fever-like illness an d
passage of the worms was associated with resolution of the complaint. Thi s
led, naturally enough, to speculation that the febrile state was a consequence
of the fluke infection, but it was realized subsequently that the worms wer e
merely co-existent and that the unfav ourable environment induced by the fever
caused them to be expelled.
That fever was not a feature of fasciolopsiasis was recognized in 1919 b y
Goddard who described three phases in the clinical picture 15. During the per-
iod of latency, a few flukes generally caused no inconvenience except for a
mild asthenia. The period of diarrhoea was characterized by persistent passage
of frequent, offensive stools containing poorly-digested food material, plus a
profound anaemia. The final phase was the period in which severe anaemi a
was complicated by the appearance of massive oedema beginning in the ab-
domen and genitals, then progressing t o involve the whole body. Although this
description was based upon observation of many patients, the study was un-
controlled, and it is difficult to disentangle the role of F. buski in engendering
these features from the multitude of other infectious agents and non-infectious
conditions which might produce similar effects in people with coinciden t
F. buski infections.
The clinical features of fasciolopsiasis were placed on a more defined basis
when Barlow infected himself with F. buski 5, although even here, they must
be viewed with some circumspection since t he possible causes of diarrhoea for
someone living in China at that time were legion. Barlow noticed no particular
ill-effects when the infection became patent 31 days after he had swallowe d
132 cysts. Two weeks later, however, he began to develop increasing hunger
and epigastric pain before meals. Nearly ten weeks after infection, he started
having symptoms even more reminiscent of duodenal ulceration:
hypogastric pain became severe and lasted from four o'clock in the morning till food
was taken. It was griping in nature and continued for half an hour after eating then
subsided entirely. It was of daily occurrence and came on only in the early morning. 5
At the same time, he became troubled with diarrhoea, there being mucus but
no blood in his stools. On 13 February 1923, 77 days after infection:

a severe diarrhoea, with six movements during the 24 hours, began and lasted till the
20th of February, with from four to six movements daily, accompanied with severe
griping pain which was irregularly intermittent all day long. The pain was confined
to the hypogastrium and seemed to be caused by an increased peristalsis and a large
quantity of gas. The pain was so intense that lying on the abdomen was the only way
to get relief. During the periods of diarrhoea, there was a marked aversion to food. 5
These problems then subsided somewhat and on 27 February he treated him-
self with 90 minims (7.5 ml) of carbon tetrachloride in water at 7.30 a.m. At
midday, he passed a large, loose stool containing 20 flukes and one ascarid:
There was a constant and nauseating eructation of carbon tetrachloride gas and the
whole treatment was accompanied by weakness, dizziness, nausea and tinnitus....(the
drug) made me feel decidedly ill, but after four stools, this feeling subsided and a
comfortable night was passed.5
These four stools contained a further 73 flukes, then another 33 worms were
passed on the following day. There was little doubt, therefore, that infectio n
with F. buski resulted in diarrhoea, and the absence of anaemia or oedem a
could be explained easily enough on the basis that the infection was of either
insufficient intensity or duration to induce these effects. Barlow went on t o
note that diarrhoea was absent in many patients with this infection, and re -
marked that anaemia was infrequent. Indeed, he implied that anaemia wa s
merely a dilutional consequence of the fluid overload causing ascites an d
peripheral oedema. He believed that these complications were most likely to
arise if the patient was small and undernourished and at the same time wa s
infected heavily. He described such a patient: she was a nine year old gir l
suffering from oedema who passed 3,721 flukes after treatment wit h
betanaphthol 5.
Barlow also described the location of flukes in the small intestine:
(They) were all in the duodenum and all fastened to the mucous membrane by their
suckers or were buried in mucous secretion. None were loose in the bowel....They
may remain attached to the mucosa till little reddened spots appear. 5
It was not surprising that such lesions should induce pain with many of th e
features reminiscent of those seen in duodenal ulceration. A number of early
authors subscribed to the view that many of the symptoms and signs o f
fasciolopsiasis were due to toxins produced by the flukes 5,13,15. If oedema and
these other effects are indeed a feature of severe fasciolopsiasis and are due to
the liberation of toxins by flukes in the bowel, the toxin or toxins whic h
produce them have not yet been identified nor have the mechanisms by which
they produce these ill-effects been clarified.
Initially, many authors 13,15 took an alarmist view of fasciolopsiasi s
considering that the infection "may be fatal unless the parasites are expelled
by art or accident" 13. This was based upon the often false assumption that F.
buski infection was the cause of the patients' trouble. Thus, Cole wrote that:
I had one death....within twenty four hours of admission for bowel troubles, in which
the typical ova were demonstrated before death.13
Fasciolopsiasis 135
Nevertheless, it became clear gradually that the severity of infection wa s

dependent upon the worm burden and might be grave only in those with ex-
tremely heavy infections if left untreated.
More recently, the clinical features in 28 infected persons were compared
with those in an equal number of uninfe cted control subjects living in the same
endemic area of Thailand. No significant differences in symptomatology ,
growth and development, haematological parameters or screening tests fo r
malabsorption were found between the two groups, and it was concluded that
F. buski was not responsible for overt clinical disease unless the parasite was
present in massive numbers 32.
It is perhaps remarkable that wh en Cobbold in 1875 found that his patient had
fasciolopsiasis, this diagnosis was made only because adult flukes wer e
passed in the stools. Apparently he was not in the habit of examining micro-
scopically the faeces of patients whom he suspected of having an helmint h
infection, even though such a technique had been described nearly 20 year s
earlier. Even had he done so, however, he would not have arrived at the cor-
rect diagnosis, as the eggs of F. buski were not described at that time. Never-
theless, observation of their presence would have alerted him to the existence
of some intestinal worm in the gastrointestinal tract.
The first person to find F. buski eggs in the faeces was JH Walker in British
North Borneo in 1891. In a 22 year old Chinese male with beriberi:
microscopic examination of the faeces showed that they contained....very numerous
eggs of a kind I could not find described in any books at my disposal. 37
He then went on to describe the eggs and provided a figure illustrating one .
Walker attempted to ascertain the the adult worm producing these eggs b y
treating the patient with a combination of anthelmintics and purgatives; th e
patient pronounced himself cured but failed to bring the parasites to th e
hospital. He had more luck with a second patient in whose faeces he foun d
similar eggs; anthelmintic therapy resulted in the recovery of an adult fluk e
which he identified as Distoma crassum.
Microscopical examination of the faeces then became standard practice ,
particularly in the heavily endemic area around Shaohsing in China, wit h
Barlow remarking that:
in diagnosing fasciolopsiasis there are only two pathognomonic signs; the finding of
ova in stool and the vomiting of live flukes. Only in cases of massive infestation does
the latter occur, while it is almost impossible to overlook ova in the stool when but
one fluke is harboured because of a large number of ova discharged by one adult. 5
although he also claimed that "fluke-harboring individuals are easil y
recognized on the streets after one has seen many cases clinically" 5.
Stoll and his colleagues took this diagnostic procedure one step further and
showed that quantification of the number of eggs in the stools was a valuable
index of the number of adult worms with which a person was infected. They
further demonstrated that each fluke produce d between 15,000 and 48,000 ova
per day36.
Walker in 1891 showed that a combination of thymol and santonin togethe r

with calomel and senna purgatives was effective against F. buski 37. A trad-
itional Chinese remedy which had some measure of success was areca nu t
combined with cathartics. Turpentine and carbon tetrachloride enjoyed trans-
ient popularity but they were soon abdandoned because of severe damage to
the kidneys and liver, respectively 6. Experience in China then showed tha t
betanaphthol was the best available drug, although it had to be given i n
repeated small doses in order to reduce the frequency and severity of depress-
ion as a side-effect 6,15. In 1937, McCoy and Chu introduced therapy wit h
hexylresorcinol. They treated 129 children with this drug and found that when
the faeces were re-examined two to three weeks later, that 54% of them were
cured and that most of the remainder had a reduction of 80% or more in egg
counts26. Tetrachlorethylene also enjoyed som e transient favour. In more recent
times dichlorophen has been shown to be relatively effective 17,27. In 1983,
Bunnag and his colleagues reported that praziquantel (see chapter 3) wa s
effective; they treated 85 children with small doses and all of them wer e
cured9. This anthelmintic is likely to become the drug of choice for th e
treatment of fasciolopsiasis.
Despite the initial paucity of reports, fasciolopsiasis was found to be common

in various regions of South and Eastern Asia. One of the most heavily infected
areas was the Shaohsing region of China, where Barlow believed that i t
occasioned greater economic loss than did hookworm and schistosom e
infections put together 5. Between 40 and 50% of the hospital patients were inf-
ected, while in some villages, all of the inhabitants carried the fluke.
The discovery by Nakagawa of the snail intermed iate host of F. buski and his
realization that infection was acquired by ingesting metacercariae encysted on
water plants immediately shed light on the epidemiology of fasciolopsiasis .
This was extended by Barlow who not onl y confirmed the life cycle of F. buski
by deliberate infection of a human, but identified two major types of plants ,
water chestnut and water caltrop, as the final vehicle of infection to humans.
He expounded the reasons why caltrop was so important in transmission:
The caltrop is a most acceptable feeding ground for the snails. It has a broad, soft,
Fasciolopsiasis 137
spongy leaf on a fibrous, cellular petiole and the root-stalk is spindle-shaped and
cellular. The air cells keep the plant supported on the water, and the rootlets get their
food largely from the water, although there is a root which is sent down to the
bottom, even though the depth may be 12 or 15 feet. These plants are usually alive
with little snails, feeding on the tender skin on the stems, petioles, leaves and nuts.
It is not unusual to find more than 20 on a single nut. This obliterates distance for the
emerging cercariae and brings encystment where it is more efficacious and
dangerous.5
Water caltrop and water chestnut were grown in shallow ponds and infection
was enhanced by fertilizing with human night soil. Surveys of these plant s
showed that there was an average of 17 cysts for every caltrop nut.
Barlow then went on to examine the durability of cysts and found that they
were not very resistant to drying, being unable to withstand one day in the hot
sun. For this reason, vegetables which were grown on dry soil were not inf -
ected, even though they were located near ponds containing many infecte d
snails.
Subsequent experience in other endemic regions indicated that F. buski
cercariae were not fastidious but could live on almost any kind of water plant
growing in stagnant water near infected snails. Thus, cysts were described on
the roots and leaves of lotus, water bamboo, Salvinia natans and Lemna
polyrhiza 18. The most common way in which humans acquired infection was
by peeling off the outer covering of each nut with teeth, before swallowing the
raw food.
Likewise, the important snail intermediate hosts in various regions wer e
characterized. These snails were somewhat difficult to identify and there was
considerable confusion initially. Segmentina hemisphaerula (identical with
Nakagawa's S. largillierta and his Planorbis coenosus and synonymous with
Barlow's S. nitidellus) and Hippeutis cantori (= Planorbis schmakeri of Bar-
low) were found to be the major molluscan hosts in eastern Asia, whil e
S. trochoideus was identified as the most important vector in northeaster n
India.
The interaction between the pig and human cycles also caused some con -
sternation at first. Nakagawa noted that porcine fasciolopsiasis was common
in Taiwan, whereas human infe ction was prevalent around Shaohsing. Barlow
showed that pigs could be infected with cerca riae derived from human sources,
although the parasite appeared to be somewhat smaller 5.
Once he had discovered the life cycle of F. buski, Nakagawa was quick to
list various measures designed to reduce the transmission of infection. H e
indicated that the eating of raw water pl ants and the drinking of unboiled water
should be prohibited, while the consumption of uncooked freshwater fish and
molluscs which sometimes contain encysted cercariae should be avoided, as

should the washing of table utensils in ditches and rivers. Furthermore, h e
recommended that faeces contaminated with eggs should be dis -infected ,
infected domestic waste should be disposed of, and that the intermediate hosts
should be destroyed 28.
While these measures were simply stated, easy to recommend, and ought to
be effective, they were difficult to p ut into practice. In echoing these measures,
Barlow noted that:
the possibility of control is fairly simple and easily accomplished. With laws effective,
living conditions regulated, and customs subordinated, the disease could be blotted
out in one season.5
But he was not sanguine about the likely outcome, declaring that:
with things as they are, looking with optimism on the problem of control, one may
predict that it will take from 10 to 20 years to reduce the disease to the point at which
it will cease to be a menace, and 50 years or more to stamp it out completely, unless
Chinese officialdom and the common people cooperate in a common plan with the
control-man to eradicate it. This is a desideratum hardly to be contemplated. 5
Unfortunately, even this forecast was too optimistic, and in many regions ,
fasciolopsiasis is still a problem.
REFERENCES
1. ANONYMOUS. A rare parasite. British Medical Journal ii: 1224-1225, 1891
2. BARLOW CH. Experimental ingestion of the ova of Fasciolopsis buski : also the
ingestion of adult Fasciolopsis buski for the purpose of artificial infestation. Journal of
3. BARLOW CH. Life cycle of Fasciolopsis buski : discovery of the means of infestation
of human beings. China Medical Journal 36: 546, 1922
4. BARLOW CH. Life cycle of Fasciolopsis buski (human) in China. China Medica l
Journal 37: 453-472, 1923
5. BARLOW CH. The life cycle of the human intestinal fluke Fasciolopsis busk i
(Lankester). American Journal of Hygiene Monograph Series, No 4, pp 99, 1925
6. BARLOW CH. The treatment of fasciolopsiasis. China Medical Journal 41: 253-265 ,
1927
7. BROWN NW. The Fasciolopsinae of China. A study of two species from Chekian g
Province. Johns Hopkins Hospital Bulletin 28: 322-329, 1917
8. BUDD G. Diseases of the liver, John Churchill, London, second edition, pp 486, 1852
9. BUNNAG D, RADOMYOS P, HARINASUTA T. Field trial on the treatment o f
fasciolopsiasis with praziquantel. Southeast Asian Journal of Tropical Medicine an d
Public Health 14: 216-219, 1983
10. COBBOLD TS. Synopsis of the Distomidae. Journal of the Linnean Society, London,
Zoological Division 5: 1-56, 1860
11. COBBOLD TS. On the suppos ed rarity, nomenclature, structure, affinities and source of
the large human fluke (Distoma crassum Busk). Journal of the Linnean Society 12 :
285-296, 1875
12. COBBOLD TS. Parasites: a treatise on the entozoa of man and animals including some
accounts of the ectozoa, J&A Churchill, London, pp 508, 1879
13. COLE AF. Five cases of Fasciolopsis infection, with remarks. Transactions of the Royal
Fasciolopsiasis 139
14. DAVAINE C, Traité des entozoaires et des maladies vermineuses, de l'homme et de s

animaux domestique, J-B Baillière et fils, Paris, pp 838, 1860
15. GODDARD FW. Fasciolopsis buski , a parasite of man as seen in Shaohsing, China .
Journal of Parasitology 5: 141-163, 1919
16. HEANLEY CM. A large fluke of man probably not hitherto described; Fasciolopsis buski
as a parasite of man in Hongkong; its usual host probably the pig. Journal of Tropica l
17. IDRIS M, RAHMAN KM, MUTTALIB MA, AZAD KHAN AK. The treatment o f
fasciolopsiasis with niclosamide and dichlorophen. Journal of Tropical Medicine an d
Hygiene 83: 71-74, 1980
18. KUANG WU. Deux nouvelles plantes pouvant transmettre le Fasciolopsis buski . Revue
générale. Annales de Parasitologie Humaine et Comparée 15: 458-464, 1937
19. LANKESTER ER. Appendix B. In, F. Küchenmeister's "On animal and vegetabl e
parasites of the human body. A manual of their natural history, diagnosis and treatment.
Volume 1. Animal parasites belonging to the group entozoa", translated by E Lankester,
The Sydenham Society, London, pp 452, 1857
20. LEIDY J. On Distoma hepaticum . Proceedings of the Academy of Natural Sciences ,
Philadelphia 25: 364, 1873
21. LEIDY J. Notice of entozoa. Proceedings of the Academy of Natural Sciences ,
Philadelphia, pp 234-236, 1891
22. LEIPER RT. On Kwan's fluke and the presence of spines in Fasciolopsis. Journal of
23. LEUCKART R. Die menschlichen Parasiten und die von ihnen herrührende n
Krankheiten. Ein Hand- und Lehrbuch für Naturforscher und Aertze, C F Winter'sch e
Verlagshandlung, Leipzig, volume 1, pp 776, 1863
24. LEUCKART R. Die Parasiten des Menschen und die von ihnen herrührende n
Verlangshandlung, Leipzig, volume 2, pp 897, 1886-1901
25. LOOSS A. Weitere Beiträge zur Kenntnis der Trematoden-Fauna Aegyptens zugleic h
Versuch einer naturlichen Gliederund des Genus Distomum Retzius. Zoologische
Jahrbücher. Abtheilung für Systema 12: 521-784, 1899
26. McCOY OR, CHU TC. Fasciolopsis buski infection among school children in Shaohsing
and treatment with hexylresorcinol. Chinese Medical Journal 51: 937-944, 1937
27. MUTTALIB MA. Dichlorophen in the treatment of Fasciolopsis buski . Bangladesh
Medical Journal 7: 45, 1978
28. NAKAGAWA K. On the life cycle of Fasciolopsis buski , Lankester. Kitasato Archives
of Experimental Medicine 4: 159-167, 1921
29. NAKAGAWA K. The development of Fasciolopsis buski (Lankester). Journal o f
30. ODHNER T. Fasciolopsis buski (Lank.) (= Distomum crassum Cobb.) ein bisher wenig
bekannter Parasit des Menschen in Ostasien. Centralblatt für Bakteriologie ,
Parasitenkunde und Infektionskrankheiten, Abteilung originale 31: 573-581, 1902
31. ODHNER T. Was is Distomum rathouisi ? Archives de Parasitologie 12: 573-581, 1909
32. PLAUT AG, KAMPANART-SANYAKORN C, MANNING GS. A clinical study o f
Fasciolopsis buski in Thailand. Transactions of the Royal Society of Tropical Medicine
and Hygiene 63: 470-478, 1969
33. POIRIER J. Note sur une nouvelle espèce de Distome parasite de l'homme le Distomum
rathouisi. Archives de Zoologie Expérimentale et Générale 5: 203-211, 1887
34. RAILLIET A, HENRY R. Helminthes du porc receuillis par M. Bauche en Annam .
Bulletins de la Société de Pathologie Exotique et de ses Filiales 4: 693-699, 1911
35. RODENWALDT E. Fasciolopsis füllebor ni n. sp. Centralblatt für Bakteriologie, Parasit-
enkunde und Infektionskrankheiten, Abteilung originale 50: 451-461, 1909
36. STOLL NR, CORT WW, KWEI WS. Egg-worm correlations in cases of Fasciolopsis
buski with additional data on the distribution of this parasite in China. Journal o f
37. WALKER JH. Two cases of beri-beri asso ciated with Distomum crassum , Anchylostoma
duodenale and other parasites. British Medical Journal ii: 1205, 1891
38. WARD HB. Fasciolopsis buskii, F. rathouisi and related species in China. China Medical
Journal 24: 1-10, 1909
Table 5.1. Landmarks in fasciolopsiasis

___________________________________________________________________
1843 George Busk discovered the adult worm

1857 Lankester named the worm Distoma Buskii
1891 Walker diagnosed fasciolopsiasis by finding eggs in faeces
1918 Barlow experimentally swallowed eggs
1920 Nakagawa hatched miracidia from pig-derived eggs, observed development
through to the cercarial stage in snails, noted encystation on plants, then
recovered adult worms from experimentally infected pigs
1920 Barlow swallowed adult worms and developed a persistent infection
1922 Barlow swallowed cysts and developed a patent infection
1937 McCoy and Chu introduced treatment with hexylresorcinol
1983 Bunnag and colleagues demonstrated the efficacy of praziquantel
__________________________________________________________________
Chapter 6
Clonorchis sinensis and CLONORCHIASIS
SYNOPSIS
Common name: Chinese liver fluke

Major synonyms: Distoma sinense, D. spathulatum, D. endemicum
Distribution: eastern Asia
Life cycle: The flat, transparent and spatulate hermaphroditic worms, 10-22 mm long
and 3.5 mm wide live in the biliary passages attached to themucosa. They produce
eggs which are passed in the faeces. The miracidium hatches only after ingestion
of the egg by a suitable species of operculate snail (Alocima, Bulimus, Melanoides,
Parafossarulus, Semisulcospira). The miracidia develop into sporocysts then in
turn become rediae which produce cercariae. The cercariae emerge from the snail,
swim about in the water until they encounter certain freshwater fish (at least 80
species, mostly of the family Cyprinidae are susceptible), attach to the surface, lose
their tails, penetrate under the scales, encyst in the skin or flesh, and develop over
3-4 weeks at summer temperatures. When raw, infected fish is eaten by humans,
the metacercariae excyst in the duodenum, enter the common bile duct through the
ampulla of Vater and ascend to the small biliary passages where they mature in one
month
Definitive hosts: humans, dogs, cats
Major clinical features: fever, jaundice, pain and tenderness in the right
hypochondrium, hepatomegaly in heavy infections
Diagnosis: demonstration of eggs in the faeces or duodenal aspirate of patients with
patent infections
Treatment: praziquantel
On 8 September 1874, a 20 year old Chinese carpenter was admitted in a

moribund condition to the Medical C ollege Hospital in Calcutta, India. He had
been febrile for two weeks and died several hours after admission. A post -
mortem examination was performed later that morning by James McConnell,
professor of pathology and resident physician, who noted that the patient was
jaundiced and that:
the liver was dark, swollen and tense;....the bile ducts (were) particularly
distinct from their large size, and distension with thick yellow bile. O n
incising the liver in different directions, it was noticed that small, dark ,
vermicular-looking bodies escaped onto the table, and on more carefu l
141
examination these were clearly seen to protrude from the bile ducts, which,
on being dissected, were found more or less obstructed by and containing
them in large numbers, some lying fr ee, others coiled up and either solitary
or in groups of twos or threes within the biliary ducts; all were dead....No
distomata were found in the gall-bladder, nor were any ova discovered on
microscopical examination of the bile and lining membrane of this sac .
Numerous ova and shreds of epithelium were found in the biliary canals. 45
McConnell concluded that the flukes in the bile ducts caused degeneration of
the liver, and that the "cholaemic condition" induced by obstruction of th e
biliary channels was the immediate cause of death. He then went on to des-
cribe the external and internal morphology of the flukes, which were nearl y
one inch in length, then compared them with the two flukes well-known i n
Europe, Distoma hepaticum (Fasciola hepatica) and Distoma lanceolatum
(Dicrocoelium dendriticum), as well as discussing them in relation to Fasc-
iolopsis buski found in China by Kerr and wrongly identified by Leidy a s
F. hepatica (see chapter 5). This led McConnell to the conviction that th e
flukes that he had found in the liver "not only differ from the ordinary live r
fluke (Dist. hepaticum) but constitute an entirely new species" 45. His paper
was published in The Lancet on 21 August 1875 then four weeks late r
Spencer Cobbold wrote to the editor of that journal remarking that:
without doubt the species is new to science, and ought to have som e
distinctive name by which it may be recognised amongst th e
trematodes. I propose to call it Distoma sinense.11
This name was presumably intended to indicate its discovery in the body of a
Chinese person. In the following year, however, Leuckart, in his textbook ,
labelled the parasite Distoma spathulatum 43.
The parasites were encountered again in 1877 by William McGregor i n
Port Louis, Mauritius. Eight Chinese persons were suffering from a paralytic
illness, and he found the flukes in the three patients who died. Naturall y
enough, but quite wrongly, he ascribed the pa ralysis to these worms 47. In 1878,
McConnell again found the parasites in a Chinese cook from Hong Kong 46. In
the same year, Ishizaka discovered the infection in a farmer in Okayam a
Prefecture in Japan31, then Erwin Baelz recovered the worms during th e
autopsy of a patient in Tokyo University Hospital in 1883. Baelz recognized
two forms of the fluke: he regarded the smaller form as being pathogenic and
named it Distoma hepatis endemicum sive perniciosum and the larger type as
being nonpathogenic, calling it Distoma hepatis endemicum sive innocuum 3.
Ijima, however, believed them to be identical and shortened the name of the
parasite to Distoma endemicum 30.
In 1895, Raphael Blanchard erecte d the genus Opisthorchis and placed D.
sinense in it6. In 1907, however, Arthur Looss created the genus Clonorchis
for this oriental liver fluke with branched instead of lobed testes, the nam e
being derived from the Greek words (CHLON) and (ORCHIS)
meaning "branch" and "testis", respectively 44. He recognized two species ,
Clonorchiasis 143
Clonorchis sinensis, a larger form that he believed was found more commonly
in China, and C. endemicus, a smaller worm which was thought to be found
mainly in Japan and Indochina. In addition, Looss believed that the shapes of
the eggs differed between the two forms of the worm. Kobayashi (1912) ,
however, considering that the size of the adult worm depended upon the nature
and size of the host and upon the in tensity of infection, and believing that there
were no significant differences in the shape of the eggs, concluded that there
was only one species, C. sinensis 36,38.

OF THE LARVAL STAGES AND INTERMEDIATE HOSTS
When McConnell described the adult fluke in 1875, he also described an d

illustrated the eggs that he found in the bile. His epidemiological observations
allowed him to speculate on the nature of the life cycle of the parasite. H e
recalled seeing several patients with clinically enlarged livers who may have
been similarly infected. Since these people were Chinese, he surmised tha t
they might have become infected by ingestion of certain contaminated fishes
or vegetables since:
Chinese....are well known to be 'filthy feeders' delighting in putrid messes
of half-raw fish, &c; they are bound by no caste prejudices (as the natives
of India are) to abstain from any kind of 'flesh, fish or fowl'; they partake,
moreover, of all kinds of 'vegetable food'. The sources from whence th e
larvae of such parasites may be deri ved are therefore not far to be sought. 45
This idea received further support when M cGregor found the infection in more
Chinese, and suggested that the vehicle might be a species of snail, th e
"bêche-de-mer" 47 and was reinforced when McConnell found the parasite in
yet another Chinese person 46.
In 1885, Isao Ijima began to investigate the life cycle of C. sinensis 30.
Using those flukes whose life cycle had already been worked out, particularly
Fasciola hepatica (see chapter 4) as an analogy, he fixed his attention o n
molluscs. He dissected a large number of aquatic snails including species of
Anodonta, Corbicula, Cyclas, Lymnea, Melania, Paludina and Planorbis but
failed to discern any trace of sporocyst, redia or cercaria in any one of thes e
snails. He did, however, describe the appearance of miracidia forced out o f
their shells by tapping coverglasses sharply. These embryos were non-motile,
and he was unable to hatch them artificial ly, despite keeping them for over five
months and placing them in an incubator. This difficulty hindered experimental
attempts to investigate the life cycle in the same way that Thomas and Leuckart
had recently done for F. hepatica. In noting that he was carrying out suc h
experiments, Ijima remarked "I have no expectation of bringing them soon to
a close" 30. He then canvassed four possible ways in which humans migh t
acquire infection, including drinking of ditch water, ingestion of infecte d
snails, consumption of vegetables contaminated with cysts, and by eatin g

undercooked second intermediate hosts such as shrimps and fishes" 30.
The inability to hatch eggs continued to be a bugbear. Saito (1898) devel-
oped a mechanical method for expressing the m iracidia and claimed to observe
larvae exit from ova spontaneously 63, but this was not the general experience
and did not provide sufficient numbers of miracidia for experimental purposes.
Similarly, all attempts by Heanley (1908) to hatch eggs failed. He even caused
many molluscs to ingest eggs but they were passed in the excreta unhatched.
These frustrations led Heanley to adopt the view that:
the easiest way of finding out something of the life history of O. sinensis
will be to feed animals with food eaten raw by Cantonese....There is a dish
frequently eaten which contains uncooked vegetables and fish. Th e
freshwater snail (Paludina sinensis) is also eaten more or less cooked, and
I was told, sometimes raw. 20
Heanley followed his own advice and fed several dogs with various types of
food but failed to achieve any positive result.
DISCOVERY OF THE FISH SECOND INTERMEDIATE HOSTS
Heanley's approach was adopte d with success several years later, however, by
the Japanese zoologist Harujiro Kobayas hi, while working in Korea. He exam-
ined a variety of molluscs, fishes and aquatic arthropods while looking fo r
trematode larvae. He found a number of fo rms of cercariae and encysted young
flukes, but noted that one particular kind of immature, encysted fluke wa s
common in certain freshwater fish that came from the same regions wher e
human clonorchiasis was freque nt. Since cats were known to be often infected
naturally, he used these animals for experimental studies. They were firs t
shown to be uninfected by repeated examination of the faeces then given the
flesh of fish containing these cysts. Kobayashi then fed them exclusively on a
diet of boiled rice and disinfected milk. Nine kittens and two cats were fed on
the fishes Pseudorasbora parva and Leucogobia guntheri. They either died
or were killed at varying intervals; all were found to be infected wit h
C. sinensis (Kobayashi called the worm C. endemicus) in the bile duct, hepatic
ducts, gall bladder, pancreas and duodenum. These findings were first reported
by Kobayashi in the form of a short note in Japanese in 1911 35, then appeared
in English the following year 37.
In 1913, Houghton, a western physician, also claimed to have determined
the life cycle of C. sinensis 25. While making some observations in 1910 o n
parasites present in foodstuffs commonly eaten in Shanghai, China, where he
was working, Houghton noticed the practically constant presence of a larval
trematode free in the intestine of a species of fish of the genus Notropis. In
view of the possibility that these larvae might parasitize humans or some other
mammalian host, he fed them to kittens. In the first experiment, two suckling
kittens were fed, one with raw fish, boi led rice and tinned milk, while the other
Clonorchiasis 145
received rice and milk only. On killing the animals two months later, he found
that the animal fed with fish was infected with C. sinensis whereas the control
cat was not. The experiment was repeated and similar results were returned,
with hundreds of Clonorchis being recovered. On the third attempt, bot h
kittens died of an intercurrent illness after o ne month. Houghton concluded that
although his data were scanty, it seemed likely that clonorchiasis was acquired
by ingestion of undercooked, sma ll cyprinidine fish. Nevertheless, his findings
must be viewed with some scepticism, since the larvae he saw were lying free
in the intestines, not encysted in the flesh, nor did subsequent investigator s
give any credence to his work. Indeed, Leiper and Atkinson in 1914 made a
similar finding in fish near Shanghai and concluded that it had nothing to do
with the life cycle of Clonorchis 42. Despite Houghton's claim that th e
intestinal larvae were the only trema todes found either in the gut or in the flesh
of the fish, it is possible that C. sinensis cysts were present conincidentally in
the skin, thus causing him to misinterpret the relationship between th e
intestinal larvae and the adult worms that he reared.
Meanwhile, Kobayashi continued his studies using cats, dogs, rabbits ,
guinea pigs and rats, describing his findings in Japanese in 1912 36 and in
English in a German journal published on 15 January 1915 38. He observed that
cysts were abundant both in the subcutaneous tissues and in the muscles o f
fish, particularly in the more superficial parts. In these papers, he showed that
another ten species of freshwater fi shes also acted as intermediate hosts. Later,
Kobayashi and other workers found further species of freshwater fishes tha t
were vectors of C. sinensis, so that by 1965, approximately 80 such species
had been identified 40, although only a dozen or so were important sources of
human infections 78.
Thus, although Kobayashi had demonstrated conclusively tha t
experimental animals, and therefore almost certainly humans, acquire d
infection with C. sinensis by ingestion of infected fish, the mode of infection
of the fish remained unknown. Kobayashi thought it highly likely that a
mollusc was involved and suspected Melania species as prime candidates.
DISCOVERY OF THE SNAIL FIRST INTERMEDIATE HOSTS
The Japanese pathologist, Masatomo Muto (also known as Shochi Muto) ,

skirted around the difficulty of obtaining miracidia and solved the riddle of the
primary intermediate hosts of C. sinensis in an ingenious manner. Previously,
he had been investigating parasites in s nails and had shown that the river snail,
Thiara (=Melania) libertina (which Kobayashi had proposed as the likel y
intermediate host of C. sinensis) was the primary intermediate host o f
Metagonimus yokogawai. Muto thought it unlikely that this species of snai l
was also the primary intermediate host of C. sinensis, but while pursuing this
line of investigation, came across a new species of snail in Lake Biwa, Koshu,
Japan. This snail harboured three species of cercariae. In order to determine
whether one of these forms was C. sinensis, he used these naturally-infected

molluscs to infect experimental, cyst-free fish which were in turn fed t o
uninfected mammalian definitive hosts. In his first experiment, he fed tw o
small dogs with the fish Pseudorasbora parva which had been incubated in
a tank with the snails; C. sinensis ova appeared in the dogs' faeces 18 and 20
days later, then large numbers of adult C. sinensis were found at autopsy. As
a control, he fed a third dog with P. parva which had been incubated with T.
libertina; Metagonimus but not Clonorchis was recovered from this animal.
He repeated this experiment with four guinea pigs, two of which were fed with
P. parva incubated with the snails in question, and two of which were given
uninfected P. parva to eat; C. sinensis was found in the first two animal s
whereas the second two remained uninfected. He summarized his finding s
thus:
I collected a species of snail ('mametani shi')....and discovered three species
of cercaria in the shell. I succeeded in infecting uninfected P. parva with
one of these species. After a certain period , I fed the P. parva to small dogs
and guinea pigs and confirmed th e existence in these animals of parasitism
by C. sinensis. In this way, I proved that the primary intermediate host of
C. sinensis is 'mametanishi' - Bulimus striatula var japonica Pilsbury.52
Muto's findings were first presented to the eighth meeting of the Japanes e
Pathological Association in April 1918; in this paper, the snail was identified
as Bithynia striatula var japonica 51. In his more definitive paper reported later
that year, the snail was referred to as Bulimus striatula var japonica52. In
1948, Abbott proposed that the Bithynia striatula of Japan and China should
be incorporated into the species Parafossarulus manchouricus which is
distributed widely in China, Japan, Korea, Taiwan and probably in Indochina 1.
There was little doubt that these sna ils were the primary intermediate hosts
of C. sinensis. In order to substantiate this conclusion, however, Muto visited
a number of endemic areas and showed that there was a strong correlatio n
between the prevalence of clonorchiasis in humans and the presence of these
snails. Furthermore, he demonstrated that fishes were a necessary stage in the
development of the parasite, for when he infected a rabbit with cercaria e
obtained from snails (rabbits having been shown by Kobayashi to be suscept-
ible to infection) adult worms were not found. Finally, Muto obtained a
miracidium of C. sinensis and infected a snail with it; when he examined the
snail three weeks later, he found a sp orocyst and wrote: "This corroborated my
conviction and the results of my experiment" 52.
Other species of molluscs were then shown to be intermediate hosts o f
C. sinensis in various regions. Melania hongkongensis was found in 1924 to
be the vector around Shaohsing, China where cats but not humans were com-
monly infected12. Faust and Khaw (1927) regarded Bithynia fuchsiana (= Bul-
imus fuchsianus) as the major vector of C. sinensis in northern China and
considered that Bithynia longicornis (= Alocima longicornis) was a less
important potential vector 16. The susceptibility of this latter species to infection
Clonorchiasis 147
with C. sinensis was confirmed experimentally b y Hsu and Li in 1940 27. Mean-
while, Galliard (1938) found that Bithynia chaperi and Melania tuberculata
were the major intermediate hosts of the infection in Vietnam 18.
Attempts continued meantime to persuade miracidia to hatch from eg g
shells. A variety of mechanical stimuli such as placement of ova in runnin g
water34 were deemed to be ineffective. It was eventually shown by Hsu and Li
in 1940 that miracidia hatch only in the alimentary canal of susceptibl e
snails28. These authors showed that when eggs were ingested by Bithynia
fushsiana, miracidia hatched within one hour then penetrated the gut wall to
become sporocysts within four hours of infection. The sporocysts the n
migrated into the lymph spaces surrounding the intestine and rectum. There,
they produced rediae which in turn migrated primarily into the liver, but also
into other regions such as the foot and mantle, and produced cercariae within
them.
Discovery of the snail intermediate host permitted observation of the fate
of these cercariae. After escaping from the snail and having a brief free -
swimming existence, the cercaria e became attached to the fish, discarded their
tails, penetrated under the scales and encysted in the subcutaneous tissues or
in the muscles. Three or four weeks were required for complete development
into metacercariae at temperatures occurring during summer.

AND THE PATHOLOGICAL RESPONSES OF THE DEFINITIV E
HOST
When Kobayashi discovered that the infection was acquired by ingestion

of infected fish, he devised some experiments to ascertain the route by which
the parasites migrated in the definitive host. Cats were fed with fish meat con-
taining C. sinensis cysts, then dissected at various intervals. Three hours after
ingestion, some of the cysts were found to be empty and the young flukes were
creeping about with the aid of their suckers in the gut lumen. Kobayashi was
of the opinion that the metacercariae bur st through the cysts walls by their own
exertions rather than that the walls were digested by the gastric juices for two
reasons. Firstly, the cysts remained undissolved in the gastrointestinal contents
for many hours after exit of the parasites. Secondly, when fish flesh wa s
crushed and soaked in water, many flukes managed to escape. When two cats
were dissected 15 and 24 hours after infection, worms were found both in the
gall bladder and in the bile duct. Kobayashi interpreted these results in th e
following manner:
It is quite natural to infer that after they reach this part they go into th e
hepatic duct and in it they cease to travel and grow. 38
The next person to investigat e the route of migration was Takayuki Muko-
yama in Japan50. He fed encysted larvae to rabbits, dogs and guinea pigs .
Young flukes were found in the bile duct as early as six hours after infection
(the earliest time at which he looked). The only places in which worms were
ever seen were the biliary system, duodenum and stomach. Furthermore, when
the bile ducts were ligated, worms were found in the duodenum, but not in the
biliary tree, liver or abdominal cavity. Finally, when young flukes were placed
directly into the peritoneal cavity of rabbits, the worms failed to migrate to the
liver and bile ducts during the three and a half weeks of observation. Thus ,
Mukoyama concluded that young fluke s were unable to penetrate the intestinal
mucosa but migrated directly along the bile duct. Similar conclusions wer e
reached several years later by Faust and Khaw who observed that whe n
animals swallowed cysts, young flukes attached themselves to the duodena l
mucosa, massed in the region of the opening of the common duct, then by 48
hours after infection had all migrated into the biliary tree 15. Since that time,
however, some investigators have cast some doubt upon this route o f
migration. Nevertheless, the weight of evidence favours the direct lumina l
route.
Once flukes have reached the biliary system, they may live there for many
years. Although Muto found that most worms in infected dogs died during the
space of two to three years 53, there are reports of Chinese emigrants continuing
to pass eggs after long periods of residence in non-endemic areas, wherea s
concomitant infections with other worms such as Ascaris, Trichuris and
hookworm disappeared spontaneously. Thus, one person who had live d
continuously in Costa Rica for 25 years retained his infection with C. sin-
ensis49. Similarly, C. sinensis ova were found in the bile of a Vietnamese who
had lived in New Caledonia for 24 years7 and another Chinese patient still had
clonorchiasis after living in Panama for over 40 years 9. Nevertheless, these
reports must be viewed with some circumspection, since it is possible tha t
infection could have been acquired for example, by ingestion of undercooked
fish which had been imported from China.
While the route of migration was of great interest to parasitologists, th e
consequences of infection were of mor e concern to pathologists and clinicians.
When he first found the flukes, McConnell believed that they had played a
major part in causing the deat h of his patient 45, and McGregor thought that the
flukes produced a paralysis of reflex origin 47. McConnell had doubts abou t
this, however, when he reported his second case in 1878 46, and this was
echoed a number of years later by Heanley in Hong Kong when he wrote that:
The literature of tropical medicine abounds with instances of commo n
parasites being mistaken for causes of disease until further investigatio n
has shown the parasite to be as common in the healthy population as in the
sick.20
Heanley, in fact, reported the first major series of patients with clonorchiasis.
He examined 300 unselected livers at autopsy during an 18 month period and
found that 109 of them were infected, the number of flukes present rangin g
between one and 350, with the average burden in adult persons being of the
order of 40-50 worms. He was not impressed by the damage produced b y
these worms, remarking that:
Clonorchiasis 149
After doing more than 3,000 post mortems in Cantonese, I am still unable
to say whether C. sinensis ever produces disease in them, although I a m
inclined to think that it in very old people the enlargement of the bile ducts
may help in the production of gall-stones. 20
and adding as an addendum to the title of his paper on clonorchiasis, the words
"its small pathological importance" 20.
Nevertheless, it gradually became clear that serious damage could b e
caused by C. sinensis, particularly in heavy infections. Perhaps the mos t
massive infection on record is that described by Sambuc and Beaujean i n
which 21,000 flukes weighing approximately 300 g were recovered from the
liver and biliary system65. In 1920, Mebius gave a detailed pathological study
of clonorchiasis seen in Chinese in Indonesia 48. The worms were shown t o
induce an epithelial proliferation and crypt formation in the extrahepatic bile
ducts, luminal enlargement and thickening of the walls of the intrahepati c
ducts, periportal lymphocytic infiltration and fibrosis, and atrophy of live r
parenchymal cells. These features were interpreted as indicating hyperplastic
cholangitis with chronic fibrosing hepatitis. Similar changes were also noted
by Hoeppli (1933) in a series of 66 patients 21. In all of these individuals, the
infection was discovered incidentally at autopsy, most patients having die d
accidentally, and the conclusion was drawn that bodily damage may b e
considerable even though symptoms were abs ent or slight. More recent studies
such as those of Hou 23 have defined the incidence of gall-stones, biliar y
obstruction, cholangitis and cirrhosis in clonorchiasis, but the absence o f
controls has not allowed adequate evaluation of the role of Clonorchis in the
genesis of these conditions.
Although flukes generally live in the bile ducts, worms have occasionally
been found in the pancreatic ducts, the first such patient being described b y
Sambuc in 191364. Attempts have been made from time to time to associat e
clonorchiasis with cancer. Watson-Wemyss in 1919 reported the coexistence
of carcinoma of the liver and clonorchiasis in a Chinese soldier 72, but this
association was almost certainly coincidental since both conditions are ver y
common in eastern Asia. There may, however, be more substance in the sug-
gestion of a causal relationship between clonorchiasis and carcinoma of th e
bile ducts 17.
Although the first patient reported with clonorchiasis had features clearl y
referrable to the hepato-biliary system, having both fever and jaundice 45, these
signs could also have arisen as a result of complications of the Clonorchis
infection or from a co-existent illness. When he described his second cas e
three years later, McConnell remarked that:
I am inclined to believe that there do not exist any special symptoms o f
liver infection by these flukes - nothing by which the disease can b e
recognised during life. 46

The question of the clinical manifestations of C. sinensis infection was taken
up by Oldt in 1927 in a paper entitled "Is clonorchiasis a health menace i n
China?"55. Although he considered that cholelithiasis, Banti's disease, carc -
inoma and liver disease with ascites were m ore common in patients with Clon-
orchis infections, particularly in those wi th heavy worm burdens, he concluded
from his clinical studies that the presence of flukes did not ordinarily excit e
symptoms, and felt that there was no group of symptoms that could properly
be called typical of clonorchiasis. Indeed, after considering all the factors, he
believed that clonorchiasis was less harmful than ascariasis.
Berkowitz working in Korea (1931) believed that the commonest features
of clonorchiasis were indigestion and an enlarged liver, but provided no data
to support this contention. He also suggested that flukes might cause nigh t
blindness, for when flukes were removed by drainage with duodenal tubes left
in situ for days, this symptom resolved 5. While it is conceivable that biliar y
obstruction by flukes could impede the absorption of vitamin A and thus pro-
duce night blindness, it is perhaps more likely that an improved diet while in
hospital may have replenished a deficiency of the vitamin.
A massive outbreak of clonorchiasis occurred in 1946 in Shanghai, China
when 20-30% of 20,000 Jew ish refugees became infected after eating pickled
fish. One group was observed from soon after exposure then during the pro-
dromal and acute phases. The onset of illness was variable, with fever some-
times beginning abruptly, sometimes insidiously. This was associated in some
patients with enlargement of a tender liver, slight jaundice, splenomegaly and
an eosinophilia in 10-40% of them. Eggs were found three to four weeks after
exposure39. While these manifestations may have been a consequence of clon-
orchiasis, there are a multitude of other infectious agents, particularly vira l
hepatitis, which occur commonly in refugee camps and could have accounted
for most of these effects, and concurrent inf ection with other helminths is likely
to have caused an eosinophilia.
It certainly seems likely that chronic Clonorchis infection does not cause
significant symptoms, particularly if the worm burden is not high. This view
is supported by the observations of Strauss w ho compared symptoms in 58 inf-
ected Orientals and 48 infected Caucasians in San Francisco, USA, with those
in a similar number of uninfected control subjects of both racial groups; n o
significant differences were found between infected and uninfected persons 69.
The diagnosis of clonorchiasis was made initially at autopsy. The passage of

eggs in the faeces provides a simple method of arriving at the diagnosis. It is
not clear who first made use of this technique in the living patient, althoug h
Roux and Tardieux (1912) appear to have been amongst the earliest 61. Ova
can also be recovered from the upper gastrointestinal tract. Thus, C. sinensis
eggs were found in the bile at cholecystostom y71 and in duodenal fluid obtained
Clonorchiasis 151
by duodenal intubation 5.
Immunodiagnosis has not been of great value. Kuwabara and Muto in 1921
found that the complement fixation reaction was positive in a patient wit h
longstanding clonorchiasis but negative in a patient with recent infection 41. In
the following year, Ryuji extended these observations in both humans and exp-
erimental animals and concluded that the established methods of faeca l
examination for ova were both more reliable and easier 62.
Radiological investigations such as oral cholecystography and intravenous
cholangiography, although not providing an aetiological diagnosis, may give
a picture of structural damage consequent upon the infection 57. Functional
damage may be indicated by liver function tests, particularly in patients with
heavy infections or bacterial complications, but these tests are usually normal
in persons with light infections. Choi and his colleagues, for example, found
no significant differences between asymptomatic infected persons an d
uninfected control subjects 10.
Initial attempts to treat clonorchiasis were based upon the principle of firstly
stimulating liver secretions (hopefully) by the administration of such agents as
calomel, urotropin and sodium salicylate in order to expel the parasites from
the bile duct mechanically, then secondly, obtaining their removal from th e
intestines by prescription of purgatives and enemata 61. Needless to say, these
measures were not particularly effective. Direct surgical intervention wit h
flushing out of flukes by drainage of the gall bladder was also tried o n
occasion54,71. Similarly, Bercowitz proposed prolonged duodenal intubatio n
and suction in order to remove a dult worms, but the side-effects of such a pro-
cedure were somewhat severe 5.
A number of specific anthelmintics have been advocated. Some efficac y
has been claimed for tartar emetic 8, arsphenamine66 , gentian violet 14,56
,
68 58 29 4 32,59
neostibnal , gold , fouadin , chloroquine , hexachloroparaxylol , and
hetol76,77 but the effectiveness of these drugs left a lot to be desired and their
toxicity was a serious problem. The recent introduction of praziquantel (see
chapter 3) has provided a safer and more effective drug. Although Wang and
his colleagues compared praziquantel, amoscanate and hexachloroparaxylol
in 98 patients in China and concluded that hexachloroparaxylol was the drug
of choice70, subsequent workers have found that praziquantel to be the most
effective. Thus, Rim and his colleagues treated 35 patients with three doses of
praziquantel on a single day and cured 30 of them; the remaining five patients
were cured by a second course of treatment and there were few side-effect s
apart from headache and dizziness 60. Similar results have been reported b y
other investigators 2,22.
The major factors underlying the epidemiology of clonorchiasis were discerned

only gradually. In 1887, Ijima first demonstrated that there was an anima l
reservoir of infection when he dissected three cats in Tokyo and foun d
C. sinensis in two of them. He concluded that "It thus stands beyong doubt that
Dist. endemicum infests not only the human liver but also cats" 30.
Subsequently, Kobayashi showed tha t a wide range of carnivorous animals
was susceptible to infection 36,38. The importance of cats and dogs in th e
maintenance of the life cycle was revealed when it was shown that these ani-
mals were heavily infected in central China and that approximately 30% o f
them were so infected in northern China 13. Nevertheless, the distribution o f
clonorchiasis in animals and humans did not always coincide, the infectio n
being infrequent in humans in central China and unknown in northern China,
whereas it was common in southern China. The explanation of this phenom-
enon was furnished by Kobayashi's discovery in 1911 of fish being the second
intermediate host of C. sinensis 35, for only in southern China was it the custom
of humans to eat fish raw or undercooked. Oldt analysed the prevalence o f
infection in this region in detail and showed that 20-30% of humans were inf-
ected whereas cats and dogs were only slightly infected55. This was because the
price of fish was so high as to preclude its being fed to these animals. For the
same reason, the infection was mo re common in the wealthier business people
because the poorer classes could not afford to buy the food. The infection was
common, however, in the farmers who raised the fish in fresh-water ponds .
Amongst towns-people, it was more prevalent in males than in females be -
cause raw fish were usually eaten in restaurants that women did not patronize.
Similarly, custom favoured infection in Vietnam where 1-40% of humans,
11% of dogs and 33% of cats were infected. The Vietnamese commonly ate
fish raw. The larger kinds were scaled, cleaned, filletted, cut into pieces 1-4
cm long, carefully dried between two bits of paper, dipped into an acid, salty
or sugary sauce, sprinkled with rice or grated sesame, mixed with powdered
ginger, wrapped in some aromatic leaf an d eaten. Small fish such as Carassius
auratus, however, were placed in a bowl and allowed to swim about, then the
feaster when he felt so disposed, f ished for it with a scoop, seasoned it, and ate
the fish while it was still wriggling 24.
Hsu and Chow investigated the prevalence and intensity of infection with
C. sinensis in various species of fish frequently eaten in Canton, the majo r
endemic area in China. They found that the number of cysts ranged from none
to as many as 300 per fish 26.
Finally, when Muto (1918) found the missing link in the chain b y
discovering that Bithynia striatula was the first intermediate host, an d
subsequent workers defined several other susceptible species of molluscs in
limited geographical areas, the restricted distribution of C. sinensis became
understandable and fears that clonorchiasis might be introduced and spread in
Clonorchiasis 153
new regions were assuaged.
The possibility of preventing clonorchiasis was apparent immediately Kobay-

ashi discovered that fish were the vehicle by which the worm was conveyed to
humans. Kobayashi realized this and observed the effects of preparing fish in
the standard Japanese ways on the vitality of the enclosed cysts. When whole
fish were roasted over live charcoals or boiled in water for 15 minutes an d
then fed to cats and rabbits, infection failed to develop, but when the fish were
cooked in water at 50-70 oC for 15 minutes, the worms remained viable .
Kobayashi found that larvae remained alive for several days when fish wer e
refrigerated, but if the fish were kept at room temperature, the young fluke s
died when their host became putrid 38. A few years later, Faust also showed that
worms survived immersion in strong brine for 54 hours and drying for a
similar period 13.
It was clear that the infection could be prevented by proper cooking of fish,
and many authorities recognized the need for intensive health educationa l
campaigns to persuade the populace to reform their eating habits. Thus, one
author suggested that public places and schools should be placarded wit h
humorous posters24, while in Okayama prefecture, Japan, a leaflet was dis -
tributed urging that for the good name of the prefecture, river fish should not
be eaten unless fully cooked and that no unboiled water be used 67. Other con-
trol measures have been suggeste d such as sanitary disposal of human faeces 16
and attempts at snail control 67, but for a variety of reasons, these have not been
very successful.
Finally, officials of the United States government became concerned about
the possibility of importation and spread of clonorchiasis in the USA whe n
20% of Chinese immigrants arriving at San Francisco during World War I
were found to be infected 19. Consequently, aliens with clonorchiasis wer e
excluded from Hawaii, the condition being classified as a "loathsome an d
contagious disease". Since the infection did not spread to humans in th e
mainland USA or in Hawaii, and as experiments failed to incriminate native
snails as intermediate hosts 73, this restriction on immigration was relaxed i n
1927.
REFERENCES
1. ABBOTT RT. Handbook of medically important mollusks of the Orient and Wester n
Pacific. Bulletin of the Museum of Comparat ive Zoology, Harvard College 100: 245-328,
1948
2. AMBROISE-THOMAS P, GOUVILLIER A, WEGNER DG. Le praziquantel dans le
traitement des distomatoses hépatiques extrême-orientales à Clonorchis sinensis ou
Opisthorchis viverrini. Bulletin de la Société de Pathologie Exotique 74: 426-433, 1981
3. BAELZ E. Über einige neue Parasiten des Menschen. Berliner klinische Wochenschrift
20: 234-238, 1883
4. BASNUEVO JG. Cloroquina y clonorchiasis. Revista Kuba de Medicina Tropical y
Parasitologia 5: 105-110, 1949
5. BERCOWITZ Z. Clinical studies of human infestations with the liver fluke ( Clonorchis
sinensis). American Journal of Tropical Medicine 11: 43-60, 1931
6. BLANCHARD R. Animaux parasites (Notice préliminaire). Bulletin de la Sociét é
Zoologique de France 20: 217, 1895
7. BORDES FP, CAVALLO A, VAILLANTA, MARTIN M. Distomatose hépatiqu e
évoluant plus de vingt ans après l'infestation. Médecine Tropicale 23: 139-142, 1963
8. BRUG SL. Un cas grave de clonorchiase traité par l'émétique. Bulletins de la Société de
Pathologie Exotique et de ses Filiales 14: 161-162, 1921
9. CALERO MC. Clonorchiasis in Chinese residents of Panama. Journal of Parasitolog y
53: 1150, 1967
10. CHOI DW, KIM JW, PARKS SB. Laboratory findings in symptomless clonorchiasis.
Korean Journal of Parasitology 8: 8-12, 1970
11. COBBOLD TS. The new human fluke. Lancet ii: 423, 1875
12. FAUST EC. Notes on larval flukes from China. II. Studies on some larval flukes from
the central and south coast p rovinces of China. American Journal of Hygiene 4: 241-301,
1924
13. FAUST EC. Some recent aspects of the epidemiology of Clonorchis infection in China.
China Medical Journal 39: 287-296, 1925
14. FAUST EC, KE-FANG Y, KHAW O K, YUNG-AN C. Experimental therapy i n
Clonorchis infections. Proceedings of the Society for Experimental Biology and Medicine
23: 607-608, 1926
15. FAUST EC, KHAW OK. Excystment phenomena in Clonorchis sinensis . Proceedings
of the Society for Experimental Biology and Medicine 23: 245-248, 1925
16. FAUST EC, KHAW OK. Studies on Clonorchis sinensis (Cobbold) with a consideration
of the molluscan hosts of Clonorchis sinensis (Cobbold) in Japan, China and southeastern
Asia and other species of molluscs closely related to them. American Journal of Hygiene
Monograph Series, Number 3, pp 284, 1927
17. FLAVELL DJ. Liver fluke infection as an aetiological factor in bile duct carcinoma of
man. Transactions of the Royal Society of Tropical Medicine and Hygiene 75: 814-824,
1981
18. GALLIARD H. Recherches sur l'étiologie de la distomatose hépatique au Tonkin .
Annales de l'École Supérieure de Médecine et de Pharmacie Indochine 2: 96-103, 1938
19. GUNN H. Clonorchis sinensis in Orientals arriving in the United States. Journal of the
20. HEANLEY CN. The age incidence of 109 cases of Opisthorchis sinensis infection in
Cantonese: its small pathologica l significance. Journal of Tropical Medicine and Hygiene
2: 38-39, 1908
21. HOEPPLI R. Histological changes in the liver of thirty-six Chinese infected wit h
Clonorchis sinensis . Chinese Medical Journal 47: 1125-1141, 1933
22. HORSTMANN RD, FELDHEIM W, FELDMEIER H, DIETRICH M. High efficacy
of praziquantel in the treatment of 22 patients with Clonorchis/Opisthorchis infections.
Tropenmedizin und Parasitologie 32: 157-160, 1981
23. HOU PC. The pathology of Clonorchis sinensis infection of the liver. Journal o f
Pathology and Bacteriology 70: 53-64, 1955
24. HOUDEMEYER E. Au sujet d'une coutume favorisant l'infestation des Indochinois par
Clonorchis sinensis (Cobbold, 1875). Bulletins de la Société de Pathologie Exotique et
de ses Filiales 27: 21-23, 1934
25. HOUGHTON HS. Notes on the life cycle of Clonorchis. China Medical Journal 27 :
168-171, 1913
26. HSU HF, CHOW CY. Studies on certain problems of Clonorchis sinensis . II.
Clonorchiasis 155
Investigation in the chief endemic centre of China, the Canton area. Chinese Medica l
Journal 51: 341-356, 1937
27. HSU HF, LI SY. Studies on ce rtain problems of Clonorchis sinensis . VIII. Experimental
proof of Bithynia longicornis as the first intermediate host of C. sinensis. Chinese
Medical Journal, Supplement 3: 241-243. 1940
28. HSU HF, LI SY. Studies on certain problems of Clonorchis sinensis . IX. The migration
route of its larval stages in the snail, Bithynia fuschsiana . Chinese Medical Journal ,
Supplement 3: 244-254, 1940
29. HUECK O, WEN HH. Zur Fuadinbehandlung bei Opisthorchis sinensis . Archiv für
Schiffs- und Tropen-Hygiene 42: 25-27, 1938
30. IJIMA I. Notes on Distoma endemicum , Baelz. Journal of the College of Science ,
Imperial University, Tokyo 1: 47-59, 1886
31. ISHIZAKA K. Igaku Zasshi (40): 20-26, 1878. In Japanese
32. JOHN L, WANG CN, TSENG FJ, FAN KC, TU CC, CHANG TF, SUN KJ, CHI N
CM, TU SF. Hexachloroparaxylol in the treatment of clonorchiasis sinensis. Chines e
Medical Journal 84: 8-16, 1963
33. KEAN BH, MOTT JE, RUSSELL AJ. Tropical medicine and parasitology. Classi c
investigations, Cornell University Press, Ithaca, two volumes, pp 677, 1978
34. KHAW OK. The hatching pheno mena of Clonorchis ova. Proceedings of the Society for
Experimental Biology and Medicine 22: 564-566, 1925
35. KOBAYASHI HARUJIRO. (A preliminary report on the source of the human live r
distome, Clonorchis endemicus [Bälz][=Distoma spathulatum Leuckart]). Annotationes
Zoologicae Japonenses 271-277, 1911. In Japanese, with English summary
36. KOBAYASHI HARUJIRO. Saikingo Zasshi No. 202, pp 1-66, 1912. In Japanese
37. KOBAYASHI HARUJIRO. A preliminary report on the source of the human live r
distome, Clonorchis endemicum (Bälz)(Distomum spathulatum , Leuckart). Far Eastern
Association of Tropical Medicine: Transactions of the Second Biennial Congress, Hong
Kong, pp 108-112, 1912
38. KOBAYASHI HARUJIRO. On the life history and morphology of Clonorchis sinensis .
Centralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten, Abteilun g
originale 75: 299-317, 1915
39. KOENIGSTEIN RP. Observations on the epidemiology of infections with Clonorchis
sinensis. Transactions of the Royal Society of Tropical Medicine and Hygiene 42 :
503-506, 1949
40. KOMIYA Y. Clonorchis and clonorchiasis. Advances in Parasitology 4: 53-106, 1966
41. KUWABARA S, MUTO M. (Is immunization possible in liver distomiasis?) Chu o
Igakkai Kw. Zasshi Nagoya pp 34-45, 1921. In Japanese. Abstracted in Japanese Journal
of Medical Science 1: 145, 1922
42. LEIPER RT. Report on an exp edition to China to study the trematode infections of Man.
Unpublished report to the Colonial Office, pp 4, 1915. Abstracted in Tropical Diseases
Bulletin 6: 295-296, 1915
43. LEUCKART R. Die menschlichen Parasiten und die von ihnen herrührende n
Verlagshandlung, Leipzig, volume 2, pp 882, 1867-1876
44. LOOSS A. On some parasites in the museum of the School of Tropical Medicine ,
Liverpool. Annals of Tropical Medicine and Parasitology 1: 123-152, 1907
45. McCONNELL JF. Remarks on the anatomy and pathological relations of a new species
of liver-fluke. Lancet ii: 271-274, 1875
46. McCONNELL JF. "Distoma sinense" (McConnell). Lancet i: 406, 1878
47. McGREGOR W. A new form of paralytic disease associated with the presence of a new
species of liver parasite. Glasgow Medical Journal 9: 3-15, 1877
48. MEBIUS J. Clonorchiosis hepatis, cirrhosis parasitaria en typische groei van het galgang-
epitheel. Geneeskundig Tijdschrift voor Nederlandsch-Indië 60: 224-294, 1920
49. MOORE D. Note on the longevity of Clonorchis sinensis . Public Health Reports 39 :
18021803, 1924
50. MUKOYAMA T. (Experimental study on the transmigration route of the liver distome
in the body of the final host). Aichi Igakkai Zasshi 29, No. 2, 1922. In Japanese .
Abstracted in Japan Medical World 2: 243, 1922
51. MUTO M. Ueber den ersten Zwischenwirt von Clonorchis sinensis . Verhandlungen der
japanischen pathologischen Gesellschaft, Tokyo 8: 151, 1918. Abstracted in Tropica l
52. MUTO M. (On the primary intermediate host of Clonorchis sinensis ) Chuo Igakkai
Zasshi 25, No. 3: 49-52, 1918. In Japanese. Translated in 33
53. MUTO M. On the duration of life of Clonorchis sinensis infecting the animal body. Japan
Medical World 2: 224-226, 1922
54. NARDONE PM. La distomiasis sinense. Contributo allo studio delle sindromi d a
"Clonorchis sinensis" nell'esturio dello Yangtzekiang e nella zona di Shanghai (Cur a
chirugica con fistola biliare terapeutica). Annali di Medicina Navale 53: 59-78, 1948
55. OLDT F. Is clonorchiasis a health menace in China? China Medical Journal 41: 185-204,
1927
56. OLIVIER PH, KANDOU R. De behandeling van Clonorchiasis sinensis me t
Gentiaanviolet Grübler. Geneeskundig Tijdschrift voor Nederlandsch-Indië 67: 59-63 ,
1927
57. OTTO JH. Zur Frage der röntgenolo gischen Erkenbarkeit krankhafter Veränderungen am
Magen-Darmkanal bei Patienten mit Opisthorchis sinensis . Archiv für Schiffs- un d
TropenHygiene 41: 296-302, 1937
58. OTTO JH, TSCHAN TJ. Ueber de Behandlung der menschlichen Infektion mi t
Clonorchis sinensis (Kobbold) mit Goldeinspritzungen. Archiv für Schiffs- un d
59. PLOTNIKOV NN, SINOVICH LI. (Experimental therapy of clonorchiasis wit h
hexachloroparaxylol. Preliminary communication). Meditsinskaya Parasitologiya i
Parazitarn e Bolezni, pp 301-302, 1964. In Russian, with English summary
60. RIM HJ, LYU KS, LEE JS, JOO KH. Clinical evaluation of the therapeutic efficacy of
praziquantel (Embay 8440) against Clonorchis sinensis infection in man. Annals o f
Tropical Medicine and Parasitology 75: 27-33, 1981
61. ROUX, TARDIEU. Un cas de distomatose hépatique ( Opisthorchis sinensis ) chez une
Européene. Bulletin de la Société Médico-Chirurgicale de l'Indochine 3: 528-532, 1912
62. RYUJI S. (Diagnostic value of complement fixation in distomiasis). Okayama Igakkwai
Zasshi No. 384, 1922. In Japanese. Abstracted in Tropical Diseases Bulletin 19: 651 ,
1922
63. SAITO S. (The internal organs of Clonorchis sinensis ova and the morphology of th e
miracidium). Tokyo Igakkai Zasshi 12: 579-587, 1898. In Japanese. Partly translated in
33
64. SAMBUC E. Distomatose pancréatique. Bulletin de la Société Médico-Chirurgicale de
l'Indochine 4: 331-333, 1913
65. SAMBUC E, BAUJEAN R. Un cas de cachexie aqueuse chez l'homme (distomatos e
hépatopancréatique) avec syndrome pseudo-béribérique. Bulletin de la Sociét é
Médico-Chirurgicale de l'Indochine 4: 425-429, 1913
66. SHATTUCK GC. Results of treatment for clonorchiasis. American Journal of Tropical
Medicine 3: 475-494, 1923
67. SHIMUZU K, KAWADA T. Prevention of distomi asis hepatis as carried out in Okayama
prefecture. Journal of the Public Health Association of Japan 13: 1-4, 1937
68. SHIRAI M. Studies on the tr eatment of experimental liver distomiasis with "Neostibnal".
Scientific Reports of the Government Institute of Infectious Diseases 5: 633-645, 1926
69. STRAUSS WG. Clinical manifestations of clonor chiasis - a controlled study of 105 cases.
70. WANG QN, LIU JB, LIU YH, CHEN RX, QIU ZD, QU ZG. Comparison o f
praziquantel, amoscanate and hexachloroparaxylol in clonorchiasis sinensis. Chines e
Clonorchiasis 157

71. WATSON FC. Clonorchis sinensis infection of the gall bladder and biliary passages -
with report of a case. Proceedings of the Medical Association of the Isthmus Canal Zone
10: 130135, 1917
72. WATSON-WEMYSS HL. Carcinoma of the liver associated with infection b y
Clonorchis sinensis . Edinburgh Medical Journal 22: 103-104, 1919
73. WAYSON NE. An investigation to determi ne whether clonorchiasis may be disseminated
on the Pacific slope. American Journal of Tropical Medicine 3: 461-473, 1923
74. WAYSON NE. Spontaneous hatching of Clonorchis ova. A preliminary note on th e
investigation to determine whether clonorchiasis may be disseminated on the Pacifi c
Slope. Public Health Reports 39: 861-862, 1924
75. WYKOFF DE, LEPES TJ. Studies on Clonorchis sinensis . I. Observation on the route
of migration in the definitive host. American Journal of Tropical Medicine and Hygiene
6: 1061-1065, 1957
76. YOKOGAWA M. Chemotherapy of Clonorchis sinensis . II. Clinical observations on the
treatment of clonorchiasis patients with 1,4-Bis-Trichloromethylbenzol. Japanese Journal
77. YOKOGAWA M, KOYAMA H, YOSHIMURA H, TSAI CS. (Chemotherapy o f
Clonorchis sinensis infection. I. Chemotherapy with 1,4-Bis-Trichloromethylbenzo l
[Hetol] for animals infected experimentally with Clonorchis sinensis .) Japanese Journal
of Parasitology 14: 233242, 1965. In Japanese, with English summary
78. YOSHIMURA H. The life cycle of Clonorchis sinensis : a comment on the presentation
of the seventh edition of Craig and Faust's Clinical Parasitology. Journal of Parasitology
51: 961966, 1965
Table 6.1. Landmarks in clonorchiasis

_________________________________________________________________________
1874 McConnell discovered adult worms in the bile ducts of a human

1887 Ijima found the parasite in cats
1911 Kobayashi discovered the second intermediate host by feeding cyprinidine fis h
infected with certain cysts to cats then recovering adult worms
1912 Roux and Tardieu diagnosed cl onorchiasis in a living patient by finding eggs in the
faeces
1915 Kobayashi suggested that larvae migrated from the gut directly into the biliar y
system
1918 Muto discovered the first intermediate host by incubating naturally infected snails
with fish then feeding the fish to dogs then finally recovering adult worms
1918 Muto infected a snail with a miracidium and found a single sporocyst
1920 Mebius emphasized the possible pa thological consequences of C. sinensis infection
1922 Mukoyama confirmed the larval migration route suggested by Kobayashi
1940 Hsu and Li showed that miracidia hatch only in the alimentary canal of susceptible
snails and described their development in molluscs
1981 Various investigators report ed that praziquantel was the most effective drug for the
treatment of clonorchiasis
_________________________________________________________________________
Chapter 7
Paragonimus westermani and PARAGONIMIASIS
SYNOPSIS
Common name: lung fluke

Major synonyms: Distoma ringeri, D. pulmonale, D. westermani
Distribution: eastern Asia (related species are found in West Africa)
Life cycle: the ovoid flukes, 7-12 mm long by 4-6 mm wide and thick, live in cavities
in the lungs and produce eggs which are coughed up in the sputum. The ova develop
in water over two weeks then each miracidium escapes and invades snail
intermediate hosts of the genera Semisulcospira and Brotia. The miracidium
becomes a sporocyst which produces rediae then cercariae. The emergent cercariae
invade the gills then the muscles of a number of freshwater crabs and crayfish where
they encyst. On ingestion by a human, the enclosed metacercariae excyst in the
duodenum, migrate through the intestinal wall to the peritoneal cavity then pass
through the diaphragm and the pleural spaces to the lungs where they mature in cysts
or "capsules" over two to three months
Definitive hosts: humans, cats, dogs, mongoose etc
Major clinical features: fever, cough, sputum, dyspnoea, abdominal discomfort
and epilepsy in heavy infections
Diagnosis: demonstration of eggs in sputum, pleural aspirates or faeces
Treatment: bithiniol, praziquantel
In June 1879, a Portuguese resident of Tamsui, Formosa (Taiwan) die d

suddenly from a ruptured aneurysm of the ascending aorta. Since he was a
foreigner, the local physician, Dr BS Ringer, was able to perform a post -
mortem examination without incurring the wrath of the Chinese who wer e
extremely prejudiced against mutilating the human body after death. A t
autopsy, Ringer found, in addition to the aneurysm, a parasite in the lungs .
Since the dead man had been a patient of Patrick Manson's in Amoy, Chin a
during November and December of the previous y ear, Ringer wrote to Manson
detailing his findings. With respect to the worm, he wrote:
After making a section I found the parasite lying on the lung tissue - it might have
escaped from a bronchus. Whilst alive a number of young (microscopic) escaped
from an opening in the body. There were some small deposits of tubercle, no cavities,
and, if I remember aright, slight congestion of the lungs. 104
On 24 April of the following year (1880), a 35 year old Chinese man, who
was a secretary in a mandarin's office, consulted Manson about an eczematous
159
eruption on his face and legs. While the patient was speaking, he was seized
by a fit of coughing and expectorated small quantities of reddish sputum .
Manson (who at that time was trying to find the daytime location of periodic
microfilariae) placed some of this material on a microscope and was astounded
to find that instead of the anticipated microfilariae, it:
contained, besides ordinary blood and mucus corpuscles, large numbers of bodies
evidently the ova of some parasite. These bodies were oval in form, one end of the
oval being cut off by an operculum, granular on the surface, bloodstained, measuring
on an average 1/300" x 1/500". Firm pressure on the covering glass caused them to
rupture and their contents to escape, the shell being left empty and fractured at the
opercular end....No distinctly organised embryo could be made out in the uninjured
ovum, but when the contents were expressed, they resolved themselves into oil
masses, and granular matter having very active molecular movements. 69
Concerned that there might be a parent worm in the mouth or throat, Manson
examined the oral cavity caref ully but failed to find such a parasite. In order to
exclude accidental introduction of ova in food, he obtained a fresh specimen
of sputum two days later and confirmed the presence of eggs. He wrote in his
diary at this time that "I cannot but think that the parent of the ova and th e
haemoptysis are associated as cause and effect" 72. Several years later he
recalled that "I concluded that a parasite must reside somewhere below th e
vocal cords, probably in the lungs, and that I had stumbled on a new disease." 71
Further enquiry revealed that the patient had o nly been in Amoy for one year.
He was a native of Foochow in China but fifteen years previously he had gone
to Taiwan to live and had remained there for nearly ten years. Moreover, the
attacks of haemoptysis had begun after he had been on that island for about a
year. He had lived in a town called Tacktc ham, a place about two days' journey
from Tamsui, and this reminde d Manson of the parasite discovered by Ringer.
Accordingly, he wrote to Ringer who s ent him the solitary specimen preserved
in "spirit of wine". Manson placed a little of the sediment in the spirit under a
microscope and "found in it several ova of the same shape, colour, an d
dimensions as those I had some time before found in the Chinaman' s
sputum."69
The parent parasite was light brown in colour, of a firm, leathery texture, and
measured nearly half an inch in length. Manson realised that it was a
trematode, but being unsure of whether or not it was a new species, sent it to
Spencer Cobbold in London together with a covering letter dated 4 May 1880
saying:
I could not find in your 'Parasites' a worm to correspond, and as I have some idea that
the worm is not an unfrequent cause of haemoptysis in Chinese, I turn to you for
more information. I send the worm - evidently a fluke - and also a sample of the
Chinaman's sputum.68
Cobbold communicated news of the discovery to the meeting of the Quekett
Microscopical Club on 25 June 1880, and there announced his intention t o
name the fluke Distoma ringeri after its discoverer. The first notice of thi s
event appeared in an abstract in The Lancet of 3 July 1880 13 then Manson's
Paragonimiasis 161
letter to Cobbold was published in the Journal of the Quekett Microscopical

Club the following month 68. In an Appendix to this paper, Cobbold added that
he had now viewed the worm sent to him by Manson:
I satisfied myself that the fluke was new to science and accordingly I propose to call
it Distoma ringeri after the discoverer. Though mutilated, the oral sucker was well
shown, as also were traces of an organ which I regarded as the remains of the ventral
acetabulum. When flattened on a glass slide, the capsules of the vitellarium were well
seen, and occupied fully four-fifths of the body, lying deep under the dermal surface.
The worm reminds me very much of the Distoma compactum, which many years
ago I detected in the lungs of an Indian ichneumon, but it is much larger and
evidently a distinct species.36
Manson's detailed account of the ova and clinical aspects of the case appeared
in the Medical Reports of the Imperial Maritime Customs (China) 69, was
reproduced in the Medical Times and Gazette in 1881 69, and was retold in The
Lancet in 1883 71.
Meanwhile, the same eggs had been seen in 1878 in Tokyo, Japan, by Erwin
Baelz, although he failed initially to recogniz e their true nature. Baelz had gone
to Japan from Germany in 1878 as a lecturer at the Imperial University i n
Tokyo. Soon after his arrival, he became in terested in a respiratory disease that
had been mistaken previously for tuberculosis. In September 1880, Bael z
reported that he had seen 19 patients with haemoptysis in whose sputum h e
had found parasites. He described these organisms as being of two forms:
(1) as intensive yellow-brown, oval bodies, 0.13 mm in length and 0.07 mm in
width. They have an sharp, doubly refractile shell, 0.02 mm thick, which shimmers
greenish or reddish....At the blunt end a kind of cover is often found; here the cyst
of the "egg" opens. The contents consist of a viscous gelatin in which three to five
(most often four) lumps are embedded....(2) motionless balls ....having no shell and
measuring 0.01 to 0.04 mm in diameter.16
He believed that the larger bodies were psorosperm cysts and that the smaller
balls were immature psorosperms. Since psorosperms were thought at tha t
time to be a stage in the development of gregarines (i.e. protozoa), Baelz in his
first publication stated that he:
wish(ed) to name this disease Gregarinosis pulmonum and the parasite Gregarina
pulmonalis, or perhaps also, because of its color, Gregarina fusca.16
Soon afterward, Baelz sent specimens containing these bodies to Leuckart in
Germany who pronounced them to be eggs of a trematode. In the meantime,
Baelz, while awaiting Leuckart's reply, had come to the same conclusio n
himself, as is indicated in his letter to Manson quoted below.
An abstract of Baelz's report appeared in The Lancet of 2 October 1880 13.
Manson read this and recognized the likely connection between the eggs h e
was studying and the parasite found by Bael z. He therefore wrote to Baelz who
sent him some sputum containing the bodies, together with an accompanying
letter dated 19 February 1881 (publ ished in Manson-Bahr and Alcock 74 where
it is misdated as 1880, and in Manson-Bahr 73):
Dear Dr. Manson, - First of all I have to apologize for not having written to you
earlier. I always waited for a good case of the Haemoptöe parasitica, to send you a
specimen. At last I have got a prominent one, and trust you will be able to compare
the eggs in the sputa with those which you found in the lung of a patient affected
with distoma. It is not at all improbable that you will find them identical. I had called
them Gregarinae, because they are exactly what is described as such, but now when
I send my first notice of them to Europe, I saw some cases what seem to me to prove
that the oval bodies must be eggs of some worm, and if so, there could hardly be
question of another than distoma. I wrote this to Leuckart, and he too is of the same
opinion....
P.S. I ask your pardon for my bad English, I have not much practice in writing the
language, and feel only too well that I always make mistakes. 18
When Manson examined the specimens sent to him by Baelz, he found that the
bodies were identical in every respect with those coughed up by his ow n
patient and with those expressed from Ringer's fluke 70. It was now clear that
Baelz's Gregarina pulmonalis were none other than ova of the fluke named
D. ringeri by Cobbold.
Near the end of 1880, the Japanese investigator, Nakahama, who had been
a medical student at Tokyo Imperial University and a pupil of Baelz, went to
Okayama in Japan to study the disease. He surveyed patients who came to the
clinic of the Okayama Prefectural Hospital between November 1880 an d
October 1882, and found 52 cases of the infection. In November 1881 in the
same hospital, Drs Kiyono, Suga and Yamagata performed their first autopsy
on a patient with parasitical haemoptysis and found about 20 cysts, each con-
taining one or two worms. Nakahama tried to study the morphology of these
worms but they had shrunk so badly in alcohol that it was impossible t o
discern details of their structu re. Nevertheless, he sent several worms to Baelz
in Tokyo with the suggestion that they be named Distoma pulmonalis. In
March 1883, Nakahama and Suga carried out a second autopsy and obtained
several more worms. Nakahama published his findings in four parts between
February and September 1883 94, then Baelz prepared a report (published in
a German journal) in which he named the species D. pulmonale 17, even
though he must have known that Cobbold had called the same parasite D.
ringeri.
Before all these events occurred, however, a royal tiger had died in th e
Amsterdam Zoological Gardens in Holland in September 1877. At autopsy,
worms thought to be a species of Distoma were found in the lungs. These hel-
minths were sent by the director of the zoo, Dr CF Westerman, to the Dutch
zoologist Coenraad Kerbert for further identificaton. Kerbert described th e
worms, which were nearly one centimetre long, as being:
found, always in pairs, inside rather thick, fibrous capsules, which, because of the
somewhat blue color, were noticed immediately on the outer surface of the lungs. 49
Since flukes had already been found in the lungs of an otter by Natterer an d
described by Diesing in 1850 (D. rude) and in an Indian mongoose by Cob-
bold in 1859 (D. compactum), Kerbert thought that this trematode migh t
prove to be one of those species. Detailed examination revealed that this was
not so, and Kerbert recorded the discovery in 1878, naming the worm afte r
Paragonimiasis 163
Westerman and wrote: "I feel justified, therefore, in introducing this unknown
worm to zoologists as Distoma westermanni, n. sp"49.
Three years later, another tiger died in the Zoological Gardens in Hamburg,
Germany, and a similar parasite was found in its lungs. This material was also
forwarded to Kerbert, enabling him to undertake an intensive morphological
study50.
The specimens studied by Kerbert were re-examined later by Leuckart and
Nakahama (who had gone from Japan to study parasitology in Germany with
Leuckart), and they compared them with the Japanese flukes. Nakahama, inc-
identally, later returned to Japan and was awarded the degree of doctor o f
medicine by Tokyo Imperial University. Much was expected of him as he was
the first Japanese to receive such an extensive parasitological training, but he
soon abandoned this vocation and took up a position as chief of the medical
section of the Nippon Life Insurance Company. In 1889, Leuckart wrote that
in his and Nakahama's opinion, the European and Japanese forms of th e
worms were identical 64. This view became accepted and Stiles and Hassa l
voiced the general opinion when they stated that the human parasite "though
originally supposed to represent a new species, is now generally admitted to
be identified with Kerbert's form from the tiger. 107.
Since Kerbert's description had priority, Cobbold's name of D. ringeri and
Baelz's D. pulmonale lapsed, and the parasite became known as D. wester-
manni, although there were pleas to the contrary, such as that written by Paul
in Japan:
'Distoma pulmonale' is the best name; it raises no question as to priority of discovery,
and by its affinity with the names 'distoma haematobium' and 'distoma hepaticum' it
aids the memory and pleases an orderly mind.101
There was considerable confusion over the correct spelling of the specifi c
name, however, with the forms westermanni, westermanii and westermani all
being used by different authors, and even by the same author; eventually the
last description became generally accepted even though Kerbert had first des-
cribed it as westermanni.
A number of authors realized that the morphological features of this fluke
were so distinctive that it should not be retained in the genus Distoma. In
1899. Max Braun erected the genus Paragonimus for the mammalian lung
flukes, making P. westermani (Kerbert) the type species 21. The name
Paragonimus was derived from the Greek words (PARA) meaning "by
the side of" and µ (GONIMOS) meaning "gonad" or "genitalia". Later
in the same year, and unaware of Braun's revision, Arthur Looss gave a
detailed description, which was the most accurate and complete that wa s
available for many years, of the parasite. He established the genus Polysarcus
for the mammalian lung flukes 66, but because of its slightly later appearance,
this name was relegated to synonymy.

OF THE LARVAL STAGES AND THE INTERMEDIATE HOSTS
Manson concluded his paper of 1880 by remarking that the questions of the
existence and identity of the intermediate host or hosts of the parasite offered
a very interesting field for further investigation 69. Almost 40 years were t o
pass, however, before the life cycle of P. westermani was finally determined.
As soon as he first saw the ova, Manson realized that their contents wer e
undeveloped. For about 18 months after his discovery of the eggs, he scrut -
inized sputa of about 150 persons in a fruitless search for more ova; he hoped
that these would enable him to observe t he development of the larva within the
egg and characterize the conditions under which it hatched. He deduced that
the infection was not endemic in Amoy, and eventually obtained some fres h
infected sputum from Taiwan which permitted him to continue hi s
experiments. He placed some phlegm in water jars in his laboratory, the n
examined them daily for the first fortnight or so, but the ova refused to hatch.
He then forgot about the specimens for six weeks or so until his wife com -
plained of an odour emanating from the laboratory. The smell was comin g
from the decomposing sputum on which fungi of all descriptions wer e
growing. When he examined this material, Manson found that miracidia had
developed and escaped from the ova by way of the opercula 70. He reasoned
that the intermediate host must be an inhabitant of fresh water, common t o
Japan and Taiwan where parasitic haemoptysis appeared to be endemic, but
rare on the Chinese mainland around Amoy. With great foresight, h e
considered the possibility of a snail being the intermediate host. He wrote to
R Hungerford, a conchologist in Hong Kong for further information .
Hungerford replied on 21 October 1881 and with remarkable prescience put
his finger on the correct species:
My dear Manson, Your discoveries about the lung fluke are decisively interesting,
and any help I can give you in this matter is very much at your service. I know of one
fresh water species which I think answers all your requirements of 16 shells of which
I am sending you from my collection in the mail. Let me know if you would like to
have a few specimens in spirit and I will write to a friend in Nagasaki to send them
down. The shell I speak of is Melania libertina (Gould)....It occurs in Japan
at....places widely apart....I have found none of this species in China, however,....On
the whole I think M. Libertina must be your friend, he is a hardy beast and will reach
you from Tamsui alive....It will be something in favour of my hobby, if it helps clear
up a doubtful point in the natural history of flukes. 38
The full significance of Manson's perspicacity is displayed when it is recalled
that it was not until 1882 that Thomas and Leuckart demonstrated that Fasc-
iola hepatica was transmitted by molluscs (see chapter 4). Unfortunately, the
lack of potentially appropriate snails and the difficulty in obtaining a con -
tinuing supply of ova prevented Manson from pursuing the matter further.
Manson's observations on the development and hatching of miracidia were
confirmed by Nakahama in 1885, but no further significant advances wer e
Paragonimiasis 165
made until the Japanese physician, Koan Nakagawa, reported his discoveries
in 1915.
DISCOVERY OF THE CRAB SECOND INTERMEDIATE HOSTS
The discovery by Kobayashi that freshwater fishes were the second inter -
mediate host of Clonorchis sinensis (see chapter 6) encouraged Nakagawa ,
who had been appointed head of the public hospital in Shinchiku, Taiwa n
where parasitic haemoptysis was endemic, to seek the intermediate host o f
P. westermani. He knew that an intermediate host was necessary for he ha d
shown earlier that miracidia were incapable of developing in the definitiv e
host. In October 1913, he had both fed puppies with miracidia and immersed
them in water containing miracidia but had failed to find flukes in the dog s
45-100 days later90. He therefore collected and examined all the molluscs ,
fishes, amphibians and insects that he could find. In September 1914, he cap-
tured a crab that was of type he had not seen before in a rivulet near Kalapai
village. He identified this creatu re as Potamon obtusipes, although it was later
shown to be P. rathbuni 53. In the liver of this crustacean, Nakagawa foun d
numerous encysted larvae, 0.2 mm in diameter, which were unmistakabl y
half-grown trematodes, but the specific identity of which was uncertain .
Continued searching, however, revealed the worms that he had been seeking:
as a result of further investigation I found in the gills full-grown ones with all the
morphologic structures peculiar to the distome of the human lung. 89
The second form of encysted larvae measured 0.3-0.4 mm in diameter, had a
short, thick, straight body and an oval sucker with a spine. Nakagawa at that
time believed that both the large and the small cysts belonged to P. wester-
mani, with the smaller variety being merely younger stages of the larger. Sub-
sequently, he found both kinds of metacercariae in P. dehaani, and occasion-
ally in another crab, Eriocheir japonicus.
Nakagawa was convinced on morphological grounds that the larger cysts at
least, were stages in the life cycle of P. westermani, but in order to prove the
point, he had to raise adult worms from them. He therefore fed the liver, gills
and other organs of a crab harbouring numbers of encysted larvae to two pup-
pies that had been obtained fr om an area where paragonimiasis was unknown.
One of the dogs died 60 days later; post-morte m examination showed the lungs
to have a large number of cysts. Within each cyst, two or three P. westermani
were present, although they were insufficiently mature to produce eggs. The
second dog died 90 days after eating infected crab. At autopsy, the lungs of the
dog were found to contain numerous cysts enclosing adult flukes ready t o
discharge ova. He then repeated the experiment with three more puppie s
brought from a nonendemic area; two were fed with a large quantity of th e
internal organs of infected crabs while the third was left as a control. The first
two dogs died about seven weeks later and were found to be infected wit h
Paragonimus, while the control puppy remained uninfected. These result s

were first published in Japanese in 1915 87 then appeared in English in the fol-
lowing year 89. In that paper, Nakagawa summarized his findings thus:
In conclusion, I may say that of the three species of freshwater crabs, the encysted
larvae of the human lung distomes are found in the first and second species, the
occurrence in the third being problematical.89
This discovery was soon confirmed by Ando, Hisao Kobayashi, Matsui, S
Yokogawa and Yoshida, all of whom reported their experiences in the same
year (1915). Yoshida found that in Japan, the species of crabs that were th e
second intermediate hosts of P. westermani were Potamon dehaani, Sesarma
dehaani and E. japonicus; cysts were found in the gills, muscles and liver of
the crustaceans, the exact distribution depe nding upon the species of crab 132,133.
He fed cysts to three cats and a dog and eventually recovered adult P. wester-
mani. In Korea, Harujiro Kobayas hi found that in addition to E. japonicus, the
crayfish Astacus (Cambaroides) similis was also an intermediate host of P.
westermani 54,55.
In 1917, Sadamu Yokogawa argued that the two forms of cysts found in the
crab by Nakagawa belonged to distinct species, with the larger one being the
intermediate stage of the lung fluke 127. Yokogawa based this conclusion upon
the observation that the smaller cysts were sometimes found in regions where
paragonimiasis was not endemic. Furthermore, the smaller cysts could b e
reared, at least partially, in mice and the resultant immature worms inhabited
the bile duct and did not have a spine on the oral sucker. As will be discussed
later, Nakagawa in 1917 accepted that Yokogawa's views were correct.
The precise mode by which humans and animals became infected wit h
P. westermani was a matter of some debate. While infection could clearly be
acquired by eating undercooked crabs, a number of investigators realized that
paragonimiasis sometimes occurred in regions where people did not take crabs
as food134 or else they always cooked them thoroughly first 40 . This led to the
assumption that infection may result from contamination of food and water by
freeliving cysts discharged from infected crabs.
DISCOVERY OF THE SNAIL FIRST INTERMEDIATE HOSTS
It is difficult, if not impossible, to pinpoint precisely who first described th e

primary intermediate host of P. westermani and the time when this was done.
As described earlier, Hungerford in 1881 suggested that M. libertina was a
likely species, purely on the basis of circumstantial evidence. Subsequen t
investigators added experiment to hypothesis, but the details of most of their
experiments were unclear, imprecise or incomplete.
The first person after Hungerford to close in on the molluscan intermediate
hosts was Nakagawa. Indeed, before he discovered cysts in the crab, he had
made an extensive study of freshwater molluscs obtained from ponds an d
Paragonimiasis 167
streams in the region. He found 17 different kinds of cercariae, but could not
distinguish those of the lung fluke. He therefore put various snails in wate r
containing P. westermani miracidia in order to see which kinds of molluscs the
miracidia would infect:
It resulted that they infected Melania libertina Gould and M. oblique-granosa Smith
most abundantly. From this it may be assumed that these two species of fresh water
molluscs are the first intermediate hosts of the lung distomes. 89
Nakagawa tried to keep the snails alive in an experimental pond but they all
died within a few weeks and no fully-developed cercariae could be seen. He
did find, however, that all the M. libertina living in the creeks of a highl y
endemic area contained sporocysts in the liver and a particular cercaria which
he then described. He wrote in 1916 that "it may not be unreasonable to con-
clude that these cercariae are tho se of the lung distome. However, we have not
yet any experimental proof" 89.
In 1917, Nakagawa added new data to his earlier observations and indicated
that M. tuberculata was also a likely vector. He published a detailed des -
cription of the development of larvae in the snails, but it is unclear whethe r
these snails were infected experimentally with miracidia derived from human
P. westermani ova or whether they were naturally-infected snails. It is prob-
able that he was dealing with the latter case since he justified his assertion that
the resultant cercariae were P. westermani on a number of grounds, including
the resemblance between the cercariae and the small type of cyst he ha d
described in the livers of crabs. Further, he attempted to establish the link in
the life cycle between molluscs and crabs by infecting crabs with cercaria e
derived from snails. He had considerable difficulty in obtaining crabs free of
flukes, but finally secured 50 P. obtusipes and 20 P. dehaani. He put these
together with Melania snails in a stream on 4 September 1915 but was re -
warded with only scant success. Again, it is uncertain whether the snails were
infected experimentally or naturally. It seems likely that they were the latter,
in which case the identity of the parasites is doubtful. When Nakagaw a
examined the crabs 36 days later, he found none of 20 P. obtusipes and only
one of 20 P. dehaani infected. When the remaining 30 crabs were dissected
after a further three weeks, he could find only three infected animals .
Nakagawa was uncertain why it was so difficult to infect the crustacean s
experimentally. Indeed, the few crabs found to have been infected may wel l
have acquired their infection naturally in the wild. Nevertheless, Nakagaw a
was convinced that he had demonstrated the life cycle of P. westermani, and
in 1917 published his findings in the Journal of Experimental Medicine 90.
As mentioned earlier, Yokogawa in 1917 showed that the two types of cysts
found by Nakagawa in crabs represented different species of flukes. Thi s
confuses further the validity of the observations just described. Nakagaw a
recognized he veracity of Yokogawa's assertions and admitted that the forms
taken by him to be developmental stages of P. westermani belonged to some
unknown fluke. He thereupon published a new series of illustrations of th e
various stages in the development of the larvae which form large cysts 91,92 to
replace the earlier series which had depicted both forms of larvae. The smaller
cysts were subsequently identified as belonging to a previously undescribe d
fluke, Stephanolecithus parvus 92,93.
Inconclusive attempts to passage P. westermani through M. libertina were
also made by Kakami 40. In 1918, Kobayashi working in Korea, showed tha t
under experimental conditions, P. westermani miracidia attacked M. gott-
schsei, M. nodiperda var. quinaria and M. extensa vigorously. He concluded
cautiously that the genus Melania was probably concerned in the metamorph-
osis of Paragonimus 55. He then examined the effects of infecting M. pauci-
cincta with P. westermani miracidia reared from human sputum. Th e
miracidia penetrated the skin readily and gave rise to sporocysts localized near
the surface. Within each sporocyst, a single redia was formed. The redia e
migrated into the deeper parts of the snail's body and formed secondgeneration
rediae which in turn migrated into the liver and produced cercariae 56. Similar
experiments were performed and results obtained at almost the same time by
K Miyairi78,79.
In a new attempt to prove that snails were the intermediate host of P. west-
ermani, A Ando (also known as R Ando) took cercariae isolated from (prob-
ably) naturally-infected Melania and introduced them through the mouth, gills,
genital openings and wounds on the surface of crabs, but the cercariae failed
to develop or else the crabs died. He therefore put P. dehaani into a pool with
snails heavily infected with cercariae; the snails had been obtained from a n
area that was highly endemic f or paragonimiasis. Many crabs became infected
subsequently with P. westermani, and some of the parasites were induced to
develop into adult Paragonimus when the infected crabs were fed to youn g
dogs6 . Ando also showed that a second intermediate host was necessary fo r
maturation, for when cercariae obtained from s nails were fed to or injected into
experimental definitive hosts, they failed to develop 8.
Although Ando later contended that he had proved definitely that Melania
libertina was the intermediate host of P. westermani 14, S Yokogawa and
Wakeshima in 1934 still believed that there was no conclusive proof that Mel-
ania species were involved, for experimental infections had never been carried
through from the miracidial through the cercarial and cystic to the adult stages
using defined worms obtained from infected individuals 130. It was not until
1934 that the complete life cycle of any Paragonimus (P. kellicotti) was
carried through experimentally 3. Finally, in 1952, M Yokogawa succeeded in
infecting experimentally P. dehaani, E. japonicus and P. clarkii with P.
westermani by feeding the crabs with cercariae in the digestive glands of M.
libertina121. This technique was necessary because Yokogawa had found that
cercariae were rarely shed from the snails under natural conditions. H e
concluded, therefore, that the second intermediate hosts were infected b y
eating snails containing mature cercariae.
The snail intermediate hosts of P. westermani all belong to the family
Paragonimiasis 169
Thiaridae which contains several hundred species of large, operculate snails

that live in fresh or brackish water. Fo r many years, the members of this family
that served as intermediate hosts for trematodes were assigned to the genu s
Melania. In 1948, Abbott revised the nomenclature of these snails 1; since that
time, Melania libertina, for example, has been known as Semisulcospira
libertina.

AND PATHOLOGICAL REACTIONS IN THE DEFINITIVE HOST
For a number of years, the route o f migration of P. westermani larvae from the
mouth to the lungs was in doubt. Otani (1887) favoured the haematogenous
route100, while Yamagiwa (1890) believed that direct migration from th e
peritoneal cavity across the diaphragm to the pleural space and lungs wa s
more likely119. Once the final part of the life cycle was discovered by Naka -
gawa, however, the pathway of migration of larvae was determined independ-
ently and with incredible speed by f ive investigators, with Ando 4, Hisao Koba-
yashi60, Nakagawa88,89 and Sadamu Yokogawa 125,126 first reporting their results
in 1915 and Yoshida 134 doing likewise in the following year. Each of thes e
persons reported similar findings, so it is impossible to assign priority to any
particular individual. The most accessible of these papers, however, are those
of Nakagawa89 and Yoshida134 . In the experiments performed by these tw o
investigators, dogs and cats were fed upon infected crab flesh then killed after
varying periods. Once the larvae had escaped from the cysts, they penetrated
right through the intestinal wall, usually that of the jejunum, and entered the
peritoneal cavity, mostly within 48 hours. They then crossed the abdomina l
cavity and perforated the diaphragm to reach the pleural spaces after several
days. The larvae then travelled beneath the visceral pleura before burrowing
into the lung parenchyma where cysts were formed and the worms matured.
As Yokogawa remarked:
metacercariae....don't instantly penetrate the parenchyma, but rather they penetrate
the visceral pleura; from that point, they form the tiny vacuoles or tunnels. Even if
they move into the parenchyma, the young larvae penetrate freely into the tissues of
the lung and form petechiae in many places there. 126
In the lungs, the larvae developed into adult worms and often persisted fo r
many years. Ando and Tsuyuki recorded the case of a patient who still ha d
eggs in his sputum 20 years after leaving an endemic area 10.
Sometimes the migrating flukes took aberrant paths such as into th e
abdominal wall where they moved about in the muscles and connective tissue
planes, or through the mediastinal connective tissues, particularly via th e
perivascular sheaths, to the neck and head. Under these circumstances ,
however, they failed to complete their development. Thus, Nakagawa wrote:
These parasites can bore through various tissues and may reach other organs than the
lungs, where they form their regular cysts, but the lungs seem to be the most
favourable place for their development and the laying of their eggs. In other organs,
they can never reach the perfect growth.89
These views were echoed by S Yokogawa:
metacercariae....are able to live and grow in connective tissues such as the
mediastinum, the greater omentum, subcutaneous connective tissue, orbit, eyelids,
the scrotum and brain. They don't have means of discharging eggs or ovulation.
What is more a mechanical stimulation causes suppurative inflammation in the area,
thus the larvae might be destroyed by lack of nutrition. In contrast to the above fact,
those parasites which reside in the lungs easily produce ova when the nutrients are
provided; thus they stay there longer and produce those symptoms which initially
attracted my attention to them as parasites.126
Subsequent studies, however, showed that this was not always true. Fo r
example, Kimuri found large numbers of eggs in the neighbourhood of cysts
in the brain 52, and Choy and Ludlow noted ova in a mass in the anterio r
abdominal wall 28.
In order to determine whether resistance to reinfection could be induced in
paragonimiasis, Ando fed cysts repeatedly to dogs that were already infected
with adult flukes. He found that the number of flukes which matured declined
progressively. Furthermore, when puppies born of infected bitches were chal-
lenged, flukes failed to develop in the lungs. Thus, Ando concluded that a n
effective immunological response was mounted 9.
Pathological reactions in the definitive host were studied in experimenta l
animals and in humans that came to autopsy, with attention being focused on
both the worms in the lungs and those in aberrant sites. S Yokogawa 126 and
other early investigators found that migrating larvae caused little reaction .
Sometimes, petechiae were noticed in the intestinal wall where larvae ha d
presumably penetrated and a m ild inflammatory reaction in the serous cavities
was evoked occasionally. Similarly, helminths migrating through the body not
infrequently left small haemorrhages marking their tracks. Kau and Wu studied
the histopathology of the lungs of cats infected experimentally and note d
collapse, congestion, oedema and leucocytic infiltration which culminated in
the formation of a fibrous cyst wall around worms 45. Ova surrounded by
chronic granulomatous inflammation were seen in the walls of cysts, in th e
bronchial mucosa and submucosa, and in the hilar lymph nodes. Simila r
changes were described in infected human lungs 37,86,100. Cysts about 1 cm in
diameter were found more commonly in the deeper parts of the lungs, with a
matrix of small blood vessels in the capsule and with openings into th e
airways, thus allowing egress of ova and any blood surrounding the worms. In
ectopic locations, chronic inflam mation produced granulomatous tubercle-like
lesions which sometimes suppurated.
Paragonimiasis 171
The major symptom of paragonimiasis, haemoptysis, was first described b y

Baelz in 1880. He recognized that in contrast to that other prevalent cause of
spitting blood, tuberculosis, the afflicted individuals were generally otherwise
completely well:
the disease manifests itself in that otherwise completely healthy individuals cough up
blood-containing sputum for a long time, very often for many years either frequently
or intermittently....The patients show absolutely no symptoms except for occasional
throat irritation and a completely untroublesome cough. 16
This was also appreciated in the same year by Manson who described his first
patient, Tso-tong in detail:
When he was 22 years of age, he first spat blood. Everyday for 19 days he brought
up from an ounce to half an ounce of blood; he emaciated slightly, but had very little
cough. Haemoptysis returned about six months later, smaller in quantity, but, as in
the former attack, the blood at first was pure, unmixed with mucus, and of a bright
red colour; this second attack lasted for a few days only. Since then, he says he has
spat blood for two or three days at a time, in small quantities, every second or third
month. He has never had much cough, and he says that the blood is always mixed
with mucus after the first mouthful....Though rather thin, he enjoys good health. I
could discover no signs of lung disease on auscultation. 69
Manson's next two patients, who were servants of a friend of his on Taiwan,
had similar symptoms, one having recurrent haemoptysis for 11 years and the
other for four years 71. Manson realized that recurrent bleeding might induc e
anaemia in certain persons and expo sed them to the possibility of a dangerous,
sudden, profuse lung haemorrhage. Nevertheless, he remarked
I am not in a position to assign to this parasite its exact share among the causes of
grave disease, but I have no doubt that in time it will be found to operate prejudicially
on the populations of the countries in which it is endemic. 71
Clinical studies over the years have generally confirmed these observation s
with the additional realization that secondary infection may be a distressin g
complication of pulmonary paragonimiasis 20. In a recent series, Lu and col -
leagues found that a productive cough, a t times streaked with blood, chest pain
and night sweats were the most common symptoms, but that no characteristic
signs were present on clinical examination 67.
Clinical manifestations of ectopic paragonim iasis, however, were recognized
gradually over the years in a small proportion of infected patients. Masse s
were observed in the abdomi nal wall and complicating abscess formation was
seen28 . Migration of parasites through the peritoneal cavity was thought t o
sometimes cause abdominal pain and tenderness. Most importantly, Otani in
1887 found cysts as well as eggs of P. westermani in the frontal and occipital
lobes of the brain during the post-mortem examination of a man who had suf-
fered from recurrent epileptic attacks; cysts were also observed in the liver ,
intestinal wall, peritoneum, diaphragm, mesentery and cervical glands 100. The
importance of paragonimiasis as a cause of Jacksonian epilepsy was the n
emphasized by Yamagiwa 119,120, although according to Katsurada 44, Yamagiwa
subsequently concluded that the eggs that he had seen were really those o f
Schistosoma japonicum. Nevertheless, Kawamura and his colleagues late r
claimed that Paragonimus infection may be a significant cause of centra l
nervous system disease 46,47. In one village of 686 inhabitants, 11 cases of brain
complications were found among the children, so me of whom died. An autopsy
was performed on only one of these children, however; it disclose d
Paragonimus eggs in caseous cysts in the brain. The outstanding clinical feat-
ures were described as follows:
It begins with sudden severe headaches with vomiting and dizziness. In many cases,
there are epileptic attacks....These attacks are repeated several times and may last
from one to two hours or as long as ten or fifteen days. Various symptoms at the time
of the onset disappear gradually....mentality is weakened in some cases and in worst
cases they become idiotic.47
In other patients, spastic paraplegia followed infection, most commonly when
it involved the lower thoracic area with extradural deposits of worms 98, the
first such patient being reported in 1917 by Moriyasu 85.
Paragonimiasis is one of the helminthic infections in which the method o f

diagnosis was established before the adult worm itself was defined. As des -
cribed earlier, Baelz found ova in the sputum of patients while he was looking,
presumably, for tubercule bacilli 16 and Manson saw them in sputum whil e
looking for microfilariae 69. Microscopical examination of the sputum ha s
remained the diagnostic method of choice since that time, although eggs are
sometimes seen only in the faeces, when sputum is swallowed 61.
Spasmodic attempts have been mad e to develop immunoassays for the diag-
nosis of paragonimiasis, beginning with Ando in 1919 who showed tha t
complement fixing antibodies were present in the sera of infected humans and
dogs5. An intradermal test was introduced by Nunogami in 1930 95.
Ando and Yamada in 1916 were the first to report on the possibility of using
chest radiography in the diagnosis of paragonimiasis 11. In 1937, Wang and
Hsieh showed that structural damage to the lung could be demonstrated b y
chest radiography, although aetiological diagnosis was not possible 113.
In contrast, ectopic paragonimiasis has b een much more difficult to diagnose
and this has depended upon finding either ova or worms in biopsy or autopsy
material.
When Manson found Paragonimus ova in the sputum of his patients, he nat-
urally turned his attention towards trying to cure them and made many attempts
of dislodge the parasites. With consi derable ingenuity, he introduced a number
Paragonimiasis 173
of potentially parasiticidal agents, including quassia, kousso, santonin ,

turpentine and sulphurous acid into the airways via a steam spray, but success
did not attend his efforts71. Efficacy was claimed for pills containing a mixture
of quinine, ergot and opium by Lara 63, but the apparent effectiveness of thi s
therapy was probably merely associated with periodical waxing and waning
of the disease.
Stibnal was said to be of value when tried in 19 patients by Kondo 62, but
tartar emetic was not deemed to be very effective 75. Claims were made by
many observers for the value of emetine, although its effectiveness in man y
cases could hardly be called dramatic. In 19 15, Ikeda reported that he was able
to cure three patients with 12-33 injections of emetine hydrochloride 39. Three
years later, Kikuiko and Imamura described favourable results following the
subcutaneous or intravenous inj ection of emetine daily for up to one week, but
noted that patients with longstanding disease were more prone to develo p
untoward side-effects from the drug51. Some patients required prolonged ther-
apy to effect a cure, Martin, for example, inst ancing one individual who needed
70 injections; he believed, however, that concurrent use of mercurochrom e
shortened greatly the duration of emetine treatment 75.
In 1939, S Yokogawa and Ro investigated the effect of combining emetine
with the sulphonamide, prontosil, in experimentally infected dogs and thought
that it brought about a rapid and radical cure 129. Eggs disappeared from th e
sputum and examination of the lungs disclosed dead, degenerating worm s
which then became atrophic and calcificied. In control dogs which had been
given emetine alone, there was only a partial reduction in egg numbers an d
little killing of adult worms in the lungs. A combination of emetine an d
prontosil was therefore tried by Yokogawa and his colleagues in nine human
patients with paragonimiasis. Of the nine patients so treated, seven could be
followed up; four had no recurrence of symptoms, one died of an unrelate d
disease, and two relapsed with severe haemoptysis 131.
Encouraging results with chloroquine were reported in 1954 by Chung and
colleagues who treated three patients with paragonimiasis 29. In 1961, however,
bithiniol was introduced and this became the drug of choice for nearly tw o
decades. Following in vitro experiments and animal trials, Yokogawa and his
collaborators used bithionol to treat 13 patients, most of whom had bee n
unsuccessfully treated previously with emetine and a sulphonamide. All o f
them were cured after 5-15 doses given on alternate days; eleven had transient
side-effects, the most frequent bei ng diarrhoea 124. Katamine and his colleagues
gave bithionol in various schedules to 22 patients. When the largest dose was
used, sputum and stool specimens became negative in all patients 3-15 days
after beginning treatment, and there were no parasitological relapses after a
period of up to four months. Haemoptysis ceased in four of the five patient s
who had been troubled with that symptom, and the chest X-ray appearances
improved in four persons 43.
Two new drugs have been shown recently to be highly effective. In 1975 ,
Rim and his colleagues showed that niclofolan was effective in cats and dogs
infected with P. westermani 102. In the following year, menichlopholan ( =
niclofolan) was shown to give a cure rate of between 73% and 90% in humans
infected with P. uterobilateralis in Nigeria97. Ripert and colleagues then exam-
ined the efficacy of a single dose of niclofolan in Cameroon and obtained a
cure rate of 100% 105. Finally, praziquantel (see chapter 3) has been shown to
be highly effective. In 1981, Rim and co-workers in Korea reported that up to
100% effectiveness could be obtained, depending upon the dose of prazi -
quantel used103. In contrast to niclofolan, however, praziquantel had negligible
side-effects. Thus, this agent seems destined to become the standard agent for
the therapy of paragonimiasis.
As the mode of transmission between first and second intermediate hosts was
clarified and as the various reservoir hosts of the adult worms were identified,
the epidemiology of paragonimiasis gradually began to be understood. Th e
first advance was the discovery of infection in Potamon obtusipes (= P.
rathbuni) and then in P. dehaani and Eriocheir japonicus by Nakagawa. This
was followed by the demonstration by various investigators that in addition to
Potamon and Eriocheir, other genera of crabs, including Potamiscus,
Parathelphusa and Siamthelphusa, were important in transmission in some
countries. Furthermore, the cr ayfish, Cambaroides and Procambarus, and the
shrimp, Palaemon, were also found to be vectors of infection. Similarly, the
realization that a snail, Melania (= Semisulcospira) libertina was the first
intermediate host of P. westermani was followed by the discovery that species
of Brotia were also susceptible to infection. It became appreciated tha t
different species of both primary and secondary intermediate hosts ha d
different habitats, some living in mountain streams, whereas others inhabited
delta regions.
Transmission of infection, however, depended upon the presence of defin-
itive hosts excreting P. westermani ova into the environment. In addition t o
humans and the tigers originally shown to be infected by Kerbert, a wide range
of vertebrates, including dogs, cats, pigs, panthers, wolves and foxes, wa s
shown to be infected in nature 58,59. Railliet in 1890 was apparently the firs t
person to report the occurrence of P. westermani in dogs, the specimen being
shown in the Japanese veterinary exhibit at the Paris exposition and bein g
named by him "Metagonimus pulmonalis , or better M. ringeri, or better still,
M. westermanni". In 1892, Janson reported that Tokishige found the lung fluke
in dogs and pigs in Japan, while the parasite was found in cats by Inouye and
Katsurada in 1893 (cited in 128).
For humans to acquire infection, however, cysts have to be ingested in a
viable state. The dietary habits and methods of preparing crustaceans var y
Paragonimiasis 175
from place to place. In China, the eating of crabs dates back at least 3,00 0
years118. The dish may be well- or slightly-cooked, or eaten uncooked ,
depending upon the preference of the consumer. Sometimes the crabs ar e
merely immersed in millet or rice wine, so that these "drunken" crabs are still
living when devoured. In some areas, the crab juice is a domestic remedy for
such ailments as whooping cough a nd measles 77, while Koreans commonly eat
fresh crabs as an antipyretic and an tidiarrhoeal remedy 57. Famine may increase
the consumption of crabs and thus precipitate an outbreak of paragonimiasis,
as happened in eastern Nigeria du ring the Nigerian Civil War of 1967-1970 96.
Finally, infection may occur even without eating crabs as was indicated by the
disease occurring in American soldiers who were presumed to have drun k
contaminated water 106.
Although paragonimiasis has been found most commonly in eastern Asia,
infection was recognized gradually amongst th e indigenous inhabitants of other
regions, including Central America 63, South America19 , Central Africa65 and
Melanesia35. Even though some of these infections may have been acquired as
a result of transmission via immigrant carriers from endemic regions, as may
have happened, for example, with the Peruvian engineer who was a patient of
Barton19, it is now realized that in some of these foci, infections are caused by
species of Paragonimus other than P. westermani (see differentiation of
species).
Even without knowing anything of the life cycle of P. westermani, Manson was
able, by the use of elementary epidemiological principles, to indicat e
accurately the means by which human infection could be prevented:
It is only necessary to boil or filter water, and never to eat uncooked vegetables or
other uncooked food.71
The validity of these views was established when the life cycle wa s
determined, with particular attention being paid to avoiding uncooked crabs
and other potentially-infected crustaceans. If these measures were adopted ,
paragonimiasis could be eliminated in human populations. To this end, health
education campaigns have been carried out in several heavily endemic areas,
but it is difficult to change the entrenched habits of a population.
Attempts to break the life cycle of Paragonimus by attacking one of the
intermediate hosts are difficult. Extermination of crabs is next to impossible,
even if desirable, owing to their hiding in deep holes and under stones in river
beds57. Similarly, control of molluscs is often not practicable, although chem-
ical agents and natural predators such as ducks and carp have been tried 7.
DIFFERENTIATION OF SPECIES
Speciation in the genus Paragonimus has long been a subject of confusion and
controversy. As discussed earlier, Baelz classsified the human parasite no w
known as P. westermani as two separate species, but this view was no t
generally accepted. For a number of years, the lung flukes found in variou s
animal species were also equated with P. westermani. This seemed not unreas-
onable because it appeared until 1894, that all of these animals could hav e
been infected in areas in which human paragonimiasis was endemic.
In 1894, Henry Ward described a lung fluke obtained from a cat in Michi-
gan, USA. Although differences were m entioned between this worm and those
described by Kerbert in tigers and by Leuckart and others in humans, th e
parasite was nevertheless assigned tentatively to the species, P. westermani,
especially as there was a possibility that the host had been brought as a pe t
from the Orient114. Exotic infection seemed less likely, however, when Kelli-
cott later that year discovered worms in the lungs of a dog in Columbus, Ohio;
these parasites were sent to Ward and he identified them as being identica l
with those reported earlier by him from the cat 116. No doubt remained tha t
paragonimiasis was endemic in the USA when Stiles and Hassal in 1900 re-
corded the discovery made two years earlier by AJ Payne of many lung flukes
in pigs in Cincinatti, Ohio, this parasite also being given the tentativ e
designation, P. westermani 107. In 1908, however, Ward reached th e
conclusion that the lung fluke found in cats, dogs and pigs in the United States
was undoubtedly a distinct species, and to this he gave the name, P.
kellicotti 115. In 1915, Ward and Hirsch compared Kerbert's original specimens
from the tiger with animal material from the USA and human flukes fro m
eastern Asia. On the basis of the structure and distribution of the cuticula r
spines, they concluded that these flukes represented three separate specie s
which they named P. westermani, P. kellicotti and P. ringeri, respectively 117.
Kobayashi, on the other hand, believed that there was but one species, for
when he examined flukes from a variety of both natural and experimental hosts
in Korea, he found great variation in the cuticular spines 56. Ameel in 1934
reached the view that differentiation of species on the basis of cuticular spines
was very doubtful, but found that there was a clearcut difference between P.
kellicotti and P. westermani in the anatomy of the digestive tract 3. Despite the
difficulties in establishing the systematic position of new isolations, a number
of new species have been described in the last two decades. By 1975 ,
Yokogawa was able to list 31 species of Paragonimus but recognized that
some of them were not or may not be valid 122. At least nine species ar e
believed cause to disease in man, although some of them may be synonymous.
Paragonimiasis 177
OTHER SPECIES OF PARAGONIMUS
P. AFRICANUS
This fluke was found in the mongoose and dog and was first described by
Voelker and Vogel in 1965 in West Africa 111. The snail and crab inter-
mediate hosts are probably Potadoma freethii and Sudanautes species,
respectively. Later in the same year, Vogel and Crewe identified P. afric-
anus eggs in sputa from 30 patients 112.
P. ECUADORIENSIS
This species was found in 1979 by Voelker and Arzube in a coati in Ecua-
dor109. The crab host is Hypoloberca aequatoralis but the first inter-
mediate host is as yet unknown. The same authors identified eggs in th e
sputum of two patients in Ecuador as P. ecuadoriensis.
P. HETEROTREMUS
This fluke was first reported in rats by Ch'en and Hsia in 1964 27. It was
described later in the same year as P. tuanshanensis by Chung and col-
leagues30. Tricula gregoriana and Potamon species were shown to be the
first and second intermediate hosts, respectively. It was first found i n
humans in the subcutaneous tissues of the chest of a 13 year old boy i n
Thailand by Miyazaki and Harinasuta in 1966 81, then in the lungs of 39
year old Laotian male 80.
P. HUEITUNGENSIS
Immature forms of this worm were first found in biopsy of migratory sub-
cutaneous nodules from two children in China and colleagues in 1977 ,
then the adult worms were recovered from rats, cats and dogs infecte d
experimentally32. The snail host is Tricula cristata and the crab hosts are
species of Siropotamon and Isalopotamon.
P. KELLICOTTI
As discussed earlier, this worm was described as a separate species i n

North America by Ward in 1908115. Pomatiopis lapidaria and Cambarus
are the first and second intermediate hosts, respectively. Human infection
has been reported only once 2.
P. MEXICANUS
This species was found in opossums in 1968 by Miyazaki and Ishii 83.
P. peruvianis, reported by Miyazaki and colleagues from Peru in 1969 82,
is now thought to be a synonym. Miyazaki and Ishii 83 also identified the
eggs in the lungs of a 35 year old Mexican, and which had been described
as P. westermani by Martinéz Báez and Jiménez Galán in 1961 76, as being
those of P. mexicanus. Details of the life cycle were described by Brenes
and collaborators in 1980 22.
P. MIYAZAKII
This fluke was first recovered from a cat which had been infected with
a crab by Kamo and colleagues in Japan in 1961 42. Bythinella species41
and P. dehaani 108 were shown to be the first and second intermediat e
hosts, respectively. Human infections have also been described 123.
P. SKRJABINI
This worm was recovered from Paguma larvata (Viverridae) by Ch'en in

195923, then described more fully by the same author two years later 24 . A
parasite recovered from cats, and described as P. szechuanis by Chung and
Tsao in 196233, is generally considered to be a synonym. Infection i n
humans was described by Ch'en25 and by Chung and colleagues 34 in 1962.
It commonly occurs in ectopic locations, especially in subcutaneous nod-
ules. Assiminea lutae 26 and Tricula gregoriana 31 are the first and second
intermediate hosts, respectively.
P. UTEROBILATERALIS
This trematode was recovered from a swamp mongoose in West Africa and
described by Voelker and Vogel in 1965 111. The crab hosts are species of
Sudanonautes. Human infection with this parasite was first describe d
under this name by Onuigbo and Nwako in Nigeria in 1974 99 then by
Voelker and Nwokola in 1977 110. Praziquantel was shown to be effective
in treatment by Monson and colleagues in 1983 84.
REFERENCES
1. ABBOTT RT. Handbook of medically important mollusks of the Orient and Western Pacific.
Bulletin of the Museum of Comparative Zoology, Harvard College 100: 245-328, 1948
2. ABEND L. Ueber Haemoptysis parasitäria. Deutsches Archiv für klinische Medizin 100:
501-511, 1910
Paragonimiasis 179
3. AMEEL D. Paragonimus, its life history and distribution in North America and its taxonomy
(Trematoda: Troglotrematidae). American Journal of Hygiene 19: 279-317, 1934
4. ANDO A. (Investigation on Paragonimus westermani.) Chugai Iji Shinpo Nos. 847, 851,
856, 1915. In Japanese
5. ANDO A. Komplementablekung bei der Distomiasis pulmonum. Verhandlungen der
japanischen pathologischen Gesellschaft, Tokyo 7: 128, 1917. Also: (Complement fixation
test of paragonimiasis) Nihon Byori Gakkai 7: 633, 1917. In Japanese
6. ANDO A. (The first intermediate host of Paragonimus westermani.) Tokyo Iji Shinshi Nos.
2175-2178, pp 21, 1920. In Japanese. Abstracted in Tropical Diseases Bulletin 17: 51, 1921
7. ANDO A. (A supplementary notice on the prevention and elimination of pulmonary
distomiasis.) Nippon Biseibutsakkwai Gakka Zasshi 15: 43-56, 1921. In Japanese.
Abstracted in Japan Medical World 1: 19, 1921
8. ANDO A. (Morphologische und biologische Untersuchung ueber die Zerkaria vonPara-
gonimus westermani.) Chugai Iji Shinpo 41: 286-297, 1921. In Japanese. Abstracted in
Tropical Diseases Bulletin 21: 538, 1924
9. ANDO A. (Can immunisation be obtained by the infestation of Paragonimus westermanii?)
Iji Shinbun No. 1070, 1921. In Japanese. Abstracted in Tropical Diseases Bulletin 20:
209-210, 1923
10. ANDO A, TSUYUKI A. (On the endemic of pulmonary distomiasis in Tokigun, Gifu
prefecture.) Iji Shinbun No. 1136, pp 327-337, 1924. In Japanese
11. ANDO A YAMADA M. Chuo Igaku Zasshi No. 128, pp 1-11, 1916. In Japanese. Also
published as ANTO R, YUMATA R (X-ray diagnosis of pulmonary lesions of Paragonimus
westermani.) Taiwan Igakukai Zasshi No. 169, pp 934-935, 1916. In Japanese. Abstracted
in Tropical Diseases Bulletin 10: 109, 1917
12 ANONYMOUS. Microfilariae. Lancet ii: 25, 1880
13. ANONYMOUS. Parasitical haemoptysis. Lancet ii: 548-549, 1880
14. ANONYMOUS. In, 406th Medical General Laboratory. Annual Historical Report 1951.
Professional Section, Tokyo, pp 304, 1952. Cited in 128
15. ARCE J. La paragonimiasis en El Peru. Crónica Médica, Lima 32: 249-254, 1915
16. BAELZ EO. Ueber parasitäre hämoptoë (Gregarinosis pulmonum). Centralblatt für die
medicinischen Wissenschaften 18: 721-722, 1880. Translated in 48. Abstracted in Lancet ii:
548-549, 1880
17. BAELZ EO. Ueber einige neue Parasiten des Menschen. Berliner klinische Wochenschrift
20: 234-238, 1883
18. BAELZ EO. Cited in 73 and 74
19. BARTON. Cited in 15
20. BERCOWITZ Z. Clinical studies on human lung fluke disease (endemic haemoptysis)
caused by Paragonimus westermani infestation. American Journal of Tropical Medicine 17:
101-122, 1937
21. BRAUN MG. Über Clinostomum Leidy. Zoologischer Anzeiger 22: 489-493, 1899
22. BRENES R, ZELEDÓN R, ROJAS G. Biological cycle and taxonomic position of a Costa
Rican Paragonimus and the present status of Paragonimus from the New World. Brenesia
18: 353-366, 1980
23. CH'EN HT. (New species of lung flukes and note on Paragonimus species in China as
related to human infections.) 1958 Annual Report of the Chungshan Medical College, p 152,
1959. In Chinese
24. CH'EN HT. Taxonomic consideration of Paragonimus, including morphological notes on
P. skrjabini. Acta Zoologica Sinica 12: 27-36, 1960
25. CH'EN HT. The etiologic agent of human paragonimiasis in China. Chinese Medical Journal
81: 345-353, 1962
26. CH'EN HT. Paragonimus, Pagumogonimus and a paragonimus-like trematode in man.
Chinese Medical Journal 84: 781-791, 1965
27. CH'EN HT, HSIA TK. (A preliminary report on a new species of Paragonimus.) Zhongshan
Daxue Wuebo 2: 236-238, 1964. In Chinese, with English summary
28. CHOY PD, LUDLOW AI. Ova ofParagonimus westermani encysted in the abdominal wall.
China Medical Journal 40: 326-328, 1926
29. CHOY HL, CH'EN CH, HOU TC. Preliminary observations on efficacy of chloroquine in
treatment of paragonimiasis. A report of 3 cases. Chinese Medical Journal 72: 1-14, 1954
30. CHUNG HL, HO LY, CHENG LT, TS'AO WC. The discovery in Yunnan Province of two
new species of lung flukes Paragonimus tuanshanensis sp. nov. and Paragonimus
menglaensis sp. nov. Part I. Studies on morphology and life history with discussion on
possible pathogenicity to man. Chinese Medical Journal 83: 641-659, 1964
31. CHUNG HL, HO LY, TS'AO WC, HSING PH, TUNG YC, MU SH. The discoveryof a
minute freshwater snail, Tricula sp. as the first intermediate host of Paragonimus
szechuanensis. Chinese Medical Journal 82: 712-717, 1963
32. CHUNG HL, HSU CP, HO LY, KAO PC, LAN S, CHIU FH. Studies on a new pathogenic
lung fluke - Paragonimus heit'ungensis sp. nov. Chinese Medical Journal 3: 379-394, 1977
33. CHUNG HL, TS'AO WC. Paragonimus westermani (Szechuan variety) and a new species
of lung fluke - Paragonimus szechuanensis. Part I. Studies on morphological and life history
of Paragonimus szechuanensis. Chinese Medical Journal 81: 354-378, 1962
34. CHUNG HL, TS'AO WC. Paragonimus westermani (Szechuan variety) and a new species
of lung fluke - Paragonimus szechuanensis. Part II. Studies on clinical aspects of
paragonimiasis szechuanensis - a new clinical entity. Chinese Medical Journal 81: 419434,
1962
35. CILENTO RW, BACKHOUSE TC. Paragonimiasis: its first recorded occurrence in the
Territory of New Guinea. Medical Journal of Australia i: 79-81, 1927
36. COBBOLD TS. Note by the President. Journal of the Quekett Microscopical Club 6: 139-
140, 1880
37. DIACONITA GH, GOLDIS G. Investigations in pathomorphology and pathogenesis of
paragonimiasis. Acta Tuberculosea Scandinavica 44: 51-75, 1964
38. HUNGERFORD R. Cited in 73
39. IKEDA M. (Report on treatment of lung fluke disease with emetine hydrochloride.) Namman
Igukkwai Zasshi 3: 120-126, 1915. In Japanese
40. KAKAMI. (Paragonimus westermanii, investigation of the lung distoma in South Ham
Kyung Province, Korea.) Chosen I Ho No. 12, pp 151-156, 1916. In Japanese. Abstracted
41. KAMO H, HATSUSHIKA R, MAEJIMA J. Studies on Paragonimus miyazakii Kamo,
Nishida, Hatsushika et Tomimura 1961. I. Snail intermediate host and intrasnail stages.
Yonago Acta Medica 11: 26-34, 1967
42. KAMO H, NISHIDA H, HATSUSHIKA R, TOMIMURA T. On the occurrence of a new
lung fluke, Paragonimus miyazakii n. sp. in Japan (Trematoda: Troglotrematidae). Yonago
Acta Medica 5: 43-52, 1961
43. KATAMINE D, MURAKAMI F, MOTOMURA K, NIKISHUBO K, AJISAKA S,
TAKATSO H. (Treatment of human paragonimiasis with bithionol). Endemic Diseases
Bulletin, Nagasaki University 3: 130-138, 1961. In Japanese, with English summary
44. KATSURADA F. Schistosoma japonicum, a new human parasite which gives rise to an
endemic disease in different parts of Japan. Journal of Tropical Medicine and Hygiene 8:
108-111, 1905
45. KAU LS, WU K. Preliminary report on histopathology of paragonimiasis in cats in China.
Chinese Medical Journal Supplement 1: 101-105. 1936
46. KAWAMURA R, ISHIBARA C, YAMAGUCHI S. (Paragonimus westermanii infection
in children, with invasion of the brain.) Tokyo Iji Shinshi No. 2064, pp 449-454, 1918. In
Japanese. Abstracted in Tropical Diseases Bulletin 16: 130, 1920
47. KAWAMURA R, YAMAGUCHI M. On the pulmonary distomiasis which caused brain
symptoms in children. Japan Medical World 1; No. 4: 1-7. 1921
48. KEAN BH, MOTT KE, RUSSELL AJ. Tropicalmedicine and parasitology. Classic investig-
ations, two volumes, Cornell University Press, Ithaca, pp 677, 1978
49. KERBERT C. Zur Trematoden-Kenntnis. Zoologischer Anzeiger 1: 271-273, 1878. Partly
translated in 48
50. KERBERT C. Beitrag zur Kenntnis der Trematoden. Archiv für mikroskopische Anatomie
und Entwicklungsmechanik 19: 529-578, 1881
51. KIKUIKO M, IMAMURA H. (Paragonimus westermanni infection, treatment by emetine
hydrochloride.) Chu Gai Iji Shimpo No. 908, 1918. In Japanese. Abstracted in Tropical
Diseases Bulletin 15: 214-215, 1920
Paragonimiasis 181
52. KIMURI O. A case of cysts in the brain caused by Paragonimus westermani. Mittheilung
aus der pathologischen Institut der kaiserlich-japanischen Universität zu Sendai, Japan 1:
375-384, 1921
53. KOBA K. Revision of the specific name of a crab as a second intermediate host ofParagon-
imus westermani in Formosa. Science Reports of the Tokyo Bunrika Daigaku 39: 201-207,
1936. Abstracted in Tropical Diseases Bulletin 34: 397, 1937
54. KOBAYASHI HARUJIRO. (A crayfish as one of the intermediate hosts ofParagonimus
westermanii) Chosen Igakukai Zasshi No. 19, pp 65-69, 1917. In Japanese. Abstracted in
55. KOBAYASHI HARUJIRO. Studies on the lung fluke in Korea. I. On the life-history and
morphology of the lung fluke. Mittheilungen aus der medizinischen Fachschule zu Keijo 2:
97-115, 1918
56. KOBAYASHI HARUJIRO. Studies on the lung fluke in Korea. II. Structure of the adult
worm. Mittheilungen aus der medizinischen Fachschule zu Keijo 3: 16-36, 1919. Abstracted
in Tropical Diseases Bulletin 14: 139-140, 1919
57. KOBAYASHI HARUJIRO. On the development of Paragonimus westermanni and its pre-
vention. Japan Medical World 1: 14-17, 1921
58. KOBAYASHI HARUJIRO. On the animal parasites in Korea. Japan Medical World 5: 9-16,
1925
59. KOBAYASHI HARUJIRO. Lung-fluke disease in Chosen. Mittheilungen aus der medizin-
ischen Akadamie zu Keijo 9, Nos. 3 & 4, pp 3, 1926
60. KOBAYASHI HISAO. (The migratory course of the lung fluke in the body of the final host.)
Tokyo Iji Shinshi Nos. 1925 & 1930, 1915. In Japanese
61. KOMIYA Y, YOKOGAWA M. The recovery of Paragonimus eggs from stools of patients
by AMS III centrifuging technic. Japanese Journal of Medical Science and Biology 6:
207-211, 1953
62. KONDO K. (Antimony treatment of paragonimiasis.) Tokyo Iji Shinshi Nos. 2383-2385,
1924. In Japanese. Abstracted in Tropical Diseases Bulletin 22: 474, 1925
63. LARA A. Hemoptysis endemica de los Paises tropicales. Revista de Medicina de Yucatan 9:
1-5, 1913
64. LEUCKART R. Die parasiten des Menschen und die von ihnen herrhührenden Krankheiten.
Ein Hand- und Lehrbuch für Naturforscher und Aertze, C F Winter'sche Verlagshandlung,
Leipzig, Abtheilung 2, volume 1, pp 897, 1886-1901
65. LIBERT C. A case of paragonimiasis. West African Medical Journal 5: 51-52, 1932
66. LOOSS A. Weitere Beiträge zur Kenntnis der Trematoden-Fauna Aegyptens zugleich
Versuch einer naturlichen Gliederund des Genus Distomum Retzius. Zoologische Jahrbücher
Abteilung für Systema 12: 521-784, 1899
67. LÜ CH et al. Clinical observations of195 cases of Paragonimus in children. Chinese Journal
of Pediatrics 8: 143-146, 1957
68. MANSON P. Further observations on microfilariae, with descriptions of new species, com-
municated (with a prefatory note) by the President. Journal of the Quekett Microscopical
Club 6: 130-140, 1880
69. MANSON P. Distoma ringeri. China Imperial Maritime Customs. Medical Reports for the
half year ended 30th September 1880. 20th issue, pp 10-12, 1881. Reprinted in Medical
Times and Gazette ii: 8-9, 1881
70. MANSON P. Distoma ringeri and parasitical haemoptysis. China Imperial Maritime
Customs. Medical reports for the half yearended 30th September 1881. 22nd issue, pp 55-62,
1882. Reprinted in Medical Times and Gazette ii: 42-45, 1882
71. MANSON P. On endemic haemoptysis. Lancet i: 532-534, 1883
72. MANSON P. Cited in 73
73. MANSON-BAHR P. Patrick Manson as aparasitologist. A "critical review". In International
Review of Tropical Medicine, D R Linicombe (Editor), Academic Press, New York, pp
77-129, 1961
74. MANSON-BAHR PH, ALCOCK A. The life and work of Sir Patrick Manson, Cassell,
75. MARTIN SH. Paragonimiasis and its treatment. China Medical Journal 41: 457-460, 1927
76. MARTINÉZ BAELZ M, JIMÉNEZ GALÁN A. Un cas de trematodiasis pulmonar reg-
istrado en Mexico. Revista del Instituto de Salubridad y Enfermedades Tropicales 21: 101-
114, 1961
77. MINAMI S, SATO T. Hautgeschwülste durch Lungen distoma (Paragonimus westermani).
Arbeiten aus der medicinischen Universität zu Okayama 2: 78-88, 1930
78. MIYAIRI K. (A contribution to the knowledge and development of the lung fluke). Sai Kin
Gaku Zasshi No. 281, 1919. In Japanese
79. MIYAIRI K. Beitrag zur Kenntnis der Entwicklung für Paragonimus westermanii. Mittheil-
ungen aus der medizinischen Fakultät der kaiserlichen Universität Kyushu Fukuoka 6:
313-319, 1922. Abstracted in Tropical Diseases Bulletin 21: 539, 1924
80. MIYAZAKI I, FONTAN R. Mature Paragonimus heterotremus found from a man in Laos.
Japanese Journal of Parasitology 19: 109-113, 1970
81. MIYAZAKI I, HARINASUTA T. The first case of human paragonimiasis caused by
Paragonimus heterotremus Chen et Hsia, 1964. Annals of Tropical Medicine and Para-
sitology 60: 509-514, 1966
82. MIYAZAKI K, IBANEZ N, MIRANDA H. On a new lung fluke found in Peru. Para-
gonimus peruvianus sp. n. (Trematoda: Troglotrematidae). Japanese Journal of Parasitology
18: 123-130, 1969
83. MIYAZAKI I, ISHII Y. Studies on the Mexican lung flukes with special reference to a des-
cription of Paragonimus mexicanus (Trematoda: Troglotrematidae). Japanese Journal of
84. MONSON MH, KOENIG JW, SACHS R. Successful treatment with praziquantel of six
patients infected with the African lung fluke, Paragonimus uterobilateralis. American
Journal of Tropical Medicine and Hygiene 32: 371-375, 1983
85. MORIYASU R. (A case of myelitis caused by parasitism of Paragonimus westermani in
the vertebral canal.) In Japanese. Cited in 128
86. MUSGRAVE WE. Paragonimiasis in the Philippine Islands. Philippine Journal of Science
B 2: 15-63, 1907
87. NAKAGAWA K. (A preliminary report on the discovery of the intermediate host of the
human lung fluke.) Tokyo Iji Shinshi No. 1910, 1915. In Japanese
88. NAKAGAWA K. (On the migratory course of the lung fluke in the body of the final host).
Tokyo Iji Shinshi No. 1923, 1915. In Japanese
89. NAKAGAWA K. The mode of infection in pulmonary distomiasis. Certain freshwater crabs
as intermediate hosts of Paragonimus westermanii. Journal of Infectious Diseases 18:
131-142, 1916
90. NAKAGAWA K. Human pulmonary distomiasis caused by Paragonimus westermanni.
91. NAKAGAWA K. (Description of the cysts and young developing worms ofParagonimus
westermanii.) Taiwan Igakukai Zasshi No. 176, pp 366-368, 1917. In Japanese. Abstracted
92. NAKAGAWA K. (A new species of lung fluke infesting the pond crabs, Potamon dehaani,
of Kalapai as an intermediate host.) Juzankai Zasshi 23: 1-2, 1918. In Japanese
93. NAKAGAWA K. Further notes on the studyof the human lung distome Paragonimus west-
ermani. Journal of Parasitology 6: 39-43, 1919
94. NAKAHAMA T. (Ueber den Bau des Distomum pulmonis.) Tokyo Iji Shinshi Nos. 254,
261, 282 and 283, 1883. In Japanese
95. NUNOGAMI M. (Skin reaction in paragonimiasis.) Kumamoto Igakkwai Zasshi 6: 513,
1930. In Japanese
96. NWOKOLO C. Outbreak of paragonimiasis in eastern Nigeria. Lancet i: 32-33, 1972
97. NWOKOLO C, VOLKMER KJ. Single dose therapy of paragonimiasis with meni-
chlopholan. American Journal of Tropical Medicine and Hygiene 26: 688-692, 1977
98. OH SJ. Spinal paragonimiasis. Journal of Neurological Science 6: 125-140, 1968
99. ONUIGBO WI, NWAKO FA. Discovery of adult parasites of Paragonimus uterobilat-
eralis in human tissue in Nigeria. Zeitschrift für Tropenmedizin und Parasitologie 25: 433-
436, 1974
100. OTANI S. (Cysten des Gehirns mit Eiern von Distomen sonst in der Leber, Darmwand,
Peritonäen, Lymphdrüsen.) Tokyo Igakkwai Zasshi 1: 458-460, 1887. InJapanese, with
German summary. Also, with the same title, Zeitschrift für medicinischen Gesellschaft,
Paragonimiasis 183
Tokyo 1: 8-9, 1887

101. PAUL ME. Distoma pulmonale. Lancet ii: 1789, 1896
102. RIM HY, KIM S, HA JH, CHANG DS. Experimental chemotherapeutic effects of niclo-
folan (Bayer 9015, Bilevon) on the animals infected withParagonimus westermani or P.
iloktuensis. Korean Journal of Parasitology 14: 140-146, 1976
103. RIM HJ, LYU KS, LEE JS, JOO KH, SUH WH, TSUJI M. Clinical evaluation of prazi-
quantel (Embay 8440; Biltricide [R]) in the treatment of Paragonimus westermani. Korean
104. RINGER BS. Cited in 69
105. RIPERT C, CARRIE J, AMBROISE-THOMAS P, BAECHERE R, KUM NP, SAME-
EKOBO A. Étude épidemiologique et clinique de la paragonimose au Cameroun. Résultats
du traitement par le niclofolan. Bulletin de la Société de Pathologie Exotique 74: 319-331,
1981
106. ROQUE FT, LUDWICK RW, BELL JC. Pulmonary paragonimiasis: a review with case
reports from Korea and the Philippines. Annals of Internal Medicine 38: 1206-1221, 1953
107. STILES CW, HASSALL A. The lung fluke (Paragonimus westermanii) in swine and its
relation to parasitic haemoptysis in Man. Annual Report of the Bureau of Animal Industry
16:560-611, 1900
108. TOMIMURA T, MORIBANI M, TERAUCHI J, TAKEYAMA K. (Observations on the
incidence of encysted larvae of Paragonimus miyazakii in Potamon dehaani in Rokuroshi,
Iwakuni City, Yamaguchi Prefecture.)Japanese Journal of Parasitology 13: 204-214, 1964.
In Japanese, with English summary
109. VOELKER J, ARZUBE RM. Ein neuer Lungenegel aus der Küstenkordillere von Ecuador:
Paragonimus ecuadoriensis sp. n. (Paragonimidae: Trematoda). Tropenmedizin und
Parasitologie 30: 249-263, 1979
110. VOELKER J, NWOKOLO C. Human paragonimiasis in Eastern Nigeria caused byPara-
gonimus uterobilateralis. Zeitschrift für Tropenmedizin und Parasitologie 24: 323-328,
1973
111. VOELKER J, VOGEL H. Zwei neue Paragonimus-Arten aus West-Afrika:Paragonimus
africanus und Paragonimus uterobilateralis (Troglotrematidae: Trematoda). Zeitschrift
für Tropenmedizin und Parasitologie 16: 125-148, 1965
112. VOGEL H, CREWE W Beobachtungenüber die Lungenegel-Infektion in Kamerun (West-
afrika) Zeitschrift für Tropenmedizin und Parasitologie 16: 125-148, 1965
113. WANG SH, HSIEH CK. Roentgenologic study ofparagonimiasis of lungs. Chinese Medical
Journal 52: 829-842, 1937
114. WARD HB. Ueber das Vorkommen von Distoma westermanii in den Vereinigten Staaten.
Centralblatt für Bakteriologie und Parasitenkunde, Abteilung originale 15: 362-364, 1894
115. WARD HB. Data for the determination of human entozoa. II. Transactions of the American
Microscopical Society 28: 177-202, 1908
116. WARD HB. Cited in 117
117. WARD HB, HIRSCH EF. The species of Paragonimus and their differentiation. Annals of
118. WU K. The epidemiology of paragonimiasis in China. Far Eastern Association of Tropical
Medicine. Comptes-Rendus Dixième Congrès, Hanoi 2: 689-713, 1938
119. YAMAGIWA K. Beitrag zur Aetiologie der Jacksonischen Epilepsi. Archiv für patholog-
ische Anatomie und Physiologie und für klinische Medicin (R Virchow) 119: 447-460,
1890
120. YAMAGIWA K. Ueber die Lungen-distomen-Krankheit in Japan. Archiv für pathologische
Anatomie und Physiologie und für klinische Medicin (R Virchow) 127: 446-456, 1892
121. YOKOGAWA M. Studies on the biological aspects of the larval stages ofParagonimus
westermanii, especially the invasion of the second intermediate hosts. Japanese Journal of
Medical Science and Biology 5: 221-237, 501-515, 1952
122. YOKOGAWA M. Paragonimus and paragonimiasis. Iranian Journal of Public Health 4:
42-51, 1975
123. YOKOGAWA M, ARAKI K, SAITO K, MOMOSE T, KIMURA K, SUZUKI S, CHIBA
N, KUTSUMI H, MINAI M. Paragonimus miyazakii infections in man first found in Kanto
District, Japan - especially, on the methods of immuno-serodiagnosis for paragonimiasis.

124. YOKOGAWA M, YOSHIMURA H, OKURA T, SANO M, TSUJI M, IWASAKI M,
HIROSE H. Chemotherapy of paragonimiasis with bithionol. II. Clinical observations on
the treatment with bithiniol. Japanese Journal of Parasitology 10: 317-327, 1961
125. YOKOGAWA S. (On the migratory course of the lung fluke in the body of the final host.)
Tokyo Iji Shinshi Nos. 1920, 1922, 1934; Year 1915. In Japanese
126. YOKOGAWA S. (On the route of migration of Paragonimus westermani in the definitive
host.) Taiwan Igakkai Zasshi No. 152, pp 685-700, 1915. In Japanese. Translated in 48
127. YOKOGAWA S. (Paragonimus ringeri, Study of stages from the crab and points of differ-
ence distinguishing it from similar cysts occurring there.) Taiwan Igakukai Zasshi No. 175,
pp 298-307, 1917. In Japanese. Abstracted in Tropical Diseases Bulletin 12: 173-174, 1918
128. YOKOGAWA S, CORT WW, YOKOGAWA M. Paragonimus and paragonimiasis.
Experimental Parasitology 10: 81-137, 139-205, 1960
129. YOKOGAWA S, RO M. Studies on the treatment of paragonimiasis. Part I. Experimental
treatment and efficacy on dogs harbouring lung flukes (Paragonimus westermanii). Acta
Japonica Medica Tropica 1: 1-18, 1939
130. YOKOGAWA S, WAKESHIMA T. (Cercariae in Semisulcospira libertina collected from
the endemic area of paragonimiasis, Shinchuku Province, Formosa.) Taiwan Igakkwai
Zasshi 33: 875-876, 1934. In Japanese
131. YOKOGAWA S, WAKISAKA K, SO K. Studies on the treatment of paragonimiasis. Part
II. On the efficacy of prontosil in combination with emetine against lung flukes during
treatment. Acta Japonica Medica Tropica 2: 23-54, 1940
132. YOSHIDA S. (On the intermediate host of the lung fluke in Tokushima Prefecture.) Tokyo
Iji Shinshi No. 1936, 1915. In Japanese
133. YOSHIDA S. On the intermediate hosts of the lung distome, P. westermani Kerbert. Journal
134. YOSHIDA S. Some notes on the encysted larva of the lung distome. Journal of Parasitology
2: 175-180, 1916
Paragonimiasis 185
Table 7.1. Landmarks in paragonimiasis

__________________________________________________________________
1877 Kerbert discovered adult worms in the lungs of a tiger and named the
parasite Distoma westermanni
1879 Ringer discovered an adult worm in the lung of a human
1880 Baelz and Manson discovered independently eggs in the sputum of
humans and recognized that haemoptysis was the main symptom with the
patients being otherwise usually well
1880 Manson observed that eggs needed to incubate for several weeks before
miracidia were released
1881 Manson postulated that a snail may be the first intermediate host and
Hungerford suggested that Melania libertina was a likely candidate
1887 Otani found parasites in the brain
1913 Nakagawa showed that miracidia were not infective to dogs
1914 Nakagawa found encysted larvae which resembled adult Paragonimus in
the gills of a crab which could be a second intermediate host
1915 Nakagawa reported that adult worms developed in dogs fed these cysts
1915 Ando, Kobayashi, Nakagawa and Yokogawa determined independently the
pathway of migration of larvae in the definitive host
1916-22 Nakagawa, Yokogawa, Kobayashi, Miyairi and Ando all concluded
independently that snails of the genus Melania (= Semisulcospira) were
probably the first intermediate host
1939 Yokogawa proposed a combination of emetine and prontosil for treatment
1961 Bithiniol was shown to be an effective treatment
1965 P. africanus infections were identified in humans by Vogel and Crewe
1974 P. uterobilateralis infections were identified in humans by Onuigbo and
Nwako
1975 Niclofolan was shown in experimental animals to be an effective treatment
1981 Rim and colleagues showed that praziquantel was a very effective drug
___________________________________________________________________
Chapter 8
Schistosoma haematobium and SCHISTOSOMIASIS

HAEMATOBIA
SYNOPSIS
Common name: vesical blood fluke; causes vesical or urinary schistosomiasis or

bilharziasis
Major synonyms: Distoma haematobia, Bilharzia haematobia
Distribution: Africa, Middle East, (Portugal, India)
Life cycle: The adult worms are unisexual. The male worm, 12 mm in length by 1 mm
in breadth, carries a slender female worm, 20x1 mm in size, in its gynaecophoric
canal. The adult worms live in the portal venous system, especially in the vesical
plexus, and produce eggs, some of which are transported through the bladder wall
and are passed in the urine. On dilution in water, the ova soon hatch miracidia
which invade snail intermediate hosts of the genus Bulinus (Ferrisea and
Planorbarius in small foci in Portugal and India, respectively). Each miracidium
becomes a sporocyst which in the course of 6-8 weeks produces second generation
sporocysts, then cercariae. The cercariae emerge from the snail, swim about in
water, then penetrate the skin of persons immersed in that water, lose their tails to
become schistosomula, then migrate through the bloodstream via the lungs to the
portal venous system where they mature over three months
Definitive hosts: humans (monkeys, baboons, chimpanzees)
Major clinical features: haematuria; obstructive uropathy and secondary bacterial
infections in heavy infections
Diagnosis: demonstration of eggs in the urine
Treatment: hycanthone, metrifonate, niridazole, praziquantel
DISCOVERY OF THE ADULT WORMS
Before Theodor Bilharz went to Cairo, Egypt in 1850, he sought the advice of
his erstwhile teacher and mentor, Carl von Siebold, as to which branch o f
natural science he should particularly direct his attention. Von Siebol d
recommended that he concentrate on h uman helminths, as it seemed likely that
the "strange country" would provide a fruitfu l field for such investigations. And
so it did. Bilharz was astonished at the variety and numbers of worms ,
especially intestinal nematodes, that he encountered during the course o f
performing some 200 post-mortem examinations. In early 1851, whil e
carrying out an autopsy on a young man, he made a discovery that astounded
him. He found a worm, which not only had he never seen before, but whic h
187
was located in the blood vessels, a location hitherto unrecognized in humans.

He appreciated that this blood-dwelling worm, or haematozoon as he called
it, was a trematode, but at first was misled by his initial failure to realize that
the specimens that he was examining were all male worms. Bilharz's confusion
is not at all surprising since all species of flukes known at that time wer e
hermaphroditic. In some excitement, he wrote a letter, dated 1 May 1851, to
von Siebold in Breslau, Germany (now Wroclaw, Poland), recounting hi s
discovery:
Soon after my attention had been directed to the liver and its associated structures,
I found in the blood of the portal vein a number of long, white helminths which,
with the naked eye, I considered to be nematodes, but soon recognized as
something new. A look into the microscope revealed a splendid Distomum with a
flat body and a spiral tail at least ten times as long as the body....the tail....was a
continuation of the flat body of the worm itself, rolled sideways towards the
stomach surface in a half canal; the forked blind end of the intestinal canal
extended into it very plainly....I found no mature sexual organs. 32
He concluded his description by asking the question:
What then is this animal? In spite of its long tail, it probably cannot be called a
cercaria, which is completely different, histologically and morphologically. 32
It was not long, however, before he was able to shed some light on tha t
question himself. He discovered that these helminths were unisexual and that
he had been looking at the male worms. In another letter to von Siebold dated
28 August 1851, he explained how he had made this observation:
I have not yet reported to you the new stages of my portal vein worm. It did not, as
I had expected, develop into a wonderful old wives' tale but into something more
wonderful, a trematode with divided sex. The worm I described in my last letter
was a male. When I searched the intestinal veins more carefully (and more
expediently by holding the undamaged mesentery against the light), I soon found
specimens of the worm which harboured a gray thread in the groove of their tail.
You can imagine my surprise when I saw a trematode protruding from the frontal
opening of the groove and moving back and forth; it was similar in shape as the
first, only much finer and more delicate. Instead of the groove-shaped tail, it had a
ribbonlike posterior end which was completely enclosed in the groove-shaped half
canal of the male posterior, similar to a sword in a scabbard. The female was easily
pulled out of the male's groove and was recognized most clearly by its internal
structure.32
He then went on to describe the anatomy of both male and female worms. In
a third letter to von Siebold in December 1851 he enclosed preserve d
specimens of the parasites and provided illustrations and a definitiv e
description, including coining of the term "gynaecophoric canal" to denote the
rolled ventral surface of the male worm which surrounded the filiform female
worm. Furthermore, he named the worm Distomum haematobium, the specific
name presumably derived from a combination of the Greek words µ
(HAIMA, HAEMA) [combini ng form µ - (HAIMAT-)] meaning "blood"
and (BIOS) meaning "life, course or way of living", to indicate that these
worms lived in the bloodstream. V on Siebold announced Bilharz's discoveries
to the Congress of Naturalists in Gotham, then published Bilharz's letters ,
Schistosomiasis haematobia 189
together with his own annotations, in Zeitschrift für wissenschaftlich e

Zoologie which both he and Kölliker edited 32. Bilharz's discovery was soo n
confirmed by a number of pathologists including Griesinger, Reinhard an d
Lautner, all of whom found worms in the portal veins and its tributaries in the
mesentery and bladder.
CONTROVERSIES OVER NOMENCLATURE
On 4 December 1857, T Spencer Cobbold found a similar bisexual fluke in

the portal vein of a sooty monkey (Cercopithecus fuliginosus ) which had died
in the Zoological Society's menagerie in Lon don. Cobbold at the time believed
it was a new species and on 20 January 1859 presented his findings to th e
Linnean Society, naming the worm Bilharzia magna. Thus, he erected a new
genus, named in honour of Bilharz, to encompass these distinctive distomes,
and gave it the specific epithet, magna, to denote its large size 54. He was
eventually to agree with Leuckart that the fluke found in the monkey and that
described by Bilharz were identical and that bo th worms should thus be termed
Bilharzia haematobia. During the period between Cobbold's discovery of the
worm and the formal publication of his finding, Diesing communicated to the
Vienna Academy his Revision der Myzelminthen in which he placed the fluke
in a new genus, Gynaecophorus, to indicate the characteristic gynaecophoric
canal71. Both Cobbold's and Diesing's designations were ultimately to laps e
because of the law of priority in nomencla ture, however. Even earlier, in 1858,
Weinland had used the name Schistosoma to describe this parasite in a list of
all the worms that had thus far been found in man 202. This latter term was
derived from the Greek words (SCHISTOS) meaning "split" an d
µ (SOMA) meaning "body". All of these authorities were agreed on one
thing, - the extraordinary unisexual character of these flukes required thei r
separation from the genus Distoma. Subsequently, Moquin-Tandon proposed
the name Thecosema for the genus, since Saint-Hilaire had used the nam e
Schistosoma previously to describe a particular form of monster 164.
Moquin-Tandon's suggestion never met with any acceptance, but the names
Schistosoma and Bilharzia both continued to be used for many years.
In October 1863, a resident of the Cape of Good Hope, South Africa ,
consulted by mail John Harley, assistant physician to King's College and the
London Fever Hospital, concerning the slight haematuria with which he had
been afflicted for many years. He also noted that many people in certain parts
of the Cape were affected similarly and sent a number of samples of his urine
to Harley. In all of these specimens, Harley found eggs of a worm. One o f
these eggs hatched to reveal a "minute, ciliated animalcula" 102. Furthermore,
Harley secured urine specimens from the tw o sons, who had also suffered from
haematuria, of a South African colleague, Dr Dunsterville; in both instances,
he was able to demonstrate the characteristi c eggs. Harley recognized the close
similarity between these eggs and those of S. haematobium described by

Bilharz and Griesinger in Egypt (see next section), and presented his findings
to a meeting of the Royal Medical and Chirurgical Society in London on 2 6
January 1864. Since the eggs that he had found differed in certain respect s
from those described by Bilharz, however, Harley felt obliged to place them
in a separate species which he named Distomum capense 102. In the subsequent
discussion, Cobbold declared that there was no doubt that the eggs described
by Harley were identical to those of Bilharzia haematobia, and therefore, that
the name of Distomum capense should not stand 56. Harley's reported response
to this is incomprehensible circumlocution:
He had referred to it as a new species, because, after careful comparison with Gries-
inger's figures and description, and Leuckart's review of them in his recently
published work, he could hardly refer the ciliated embryo he had described to
Gynaecophorus haematobium. On the other hand, the resemblances were so close
and so many that it was probable that they were identical; but from a bare
comparison with the figures, he could not justly infer that they were actually so. 102
Again, in 1870, his assertions are not clear, but it is apparent that he was then
troubled by the absence of a lateral spine in any of the ova that he had found:
I have never had much doubt of the identity of the North and South African
parasites; still I can only deal with facts, and my position with regard to the question
is pretty much the same as it was seven years ago....both Bilharz and Griesinger
describe and figure two forms of eggs, the one with a terminal and the other with
a lateral spine. In all my own cases I can say positively that only one form of egg
has existed, viz. that with a terminal spine. I have never seen any egg with even a
tendency to the formation of a side spine.104
In fact, as discussed in chapter 9, he was correct and Bilharz and Griesinger
were mistaken, for S. haematobium ova do not posssess a lateral spine, as was
clearly shown by Leiper when he demonstrated the life cycle of S.
haematobium many years later. Thus, B. capense became synonymous with
S. haematobium.
More vexed was the question of the name of the genus. Cobbold ardently
defended his name Bilharzia against both Gynaecophorus and Schistosoma 57.
With respect to Diesing's Gynaecophorus he wrote:
but, when it was subsequently found that the title Bilharzia had been proposed by
myself some six months before Diesing communicated his paper to the Vienna
Academy, the choice of several systematists and others fell upon my title, which
had the additional advantage of handing down the true discoverer's name to
posterity.57
Laudable though the latter objective may have been, Cobbold does not seem
to have been entirely accurate in his facts, for his nomenclature was no t
presented publicly until after that of Diesing. Concerning Weinland' s
Schistosoma he wrote:
In a letter which I received from Dr. Weinland (dated September 6th, 1861) that
able helminthologist willingly abandoned the claims of Schistosoma, remarking
that 'the generic term Bilharzia has the preference'.57
In 1931, Senn put forward Bilharzia von Hemsbach 1856 as the valid name
of the genus, that name being adopted earlier than either Schistosoma
Weinland 1858, Gynaecophorus Diesing 1858 or Bilharzia Cobbold 1859 183.
In the same year, Leiper also tried to beat off the term Schistosoma by again
drawing attention to the use o f the word for nearly a century by teratologists to
denote a fairly common type of monstrosity in domesticated animals 140.
Nevertheless, the International Commission on Zoological Nomenclature by
Opinion 77 in 1922 placed Schistosoma on the Official List of Generi c
Names 113. Thus, the valid names for the organism and the disease ar e
Schistosoma and schistosomiasis, respectively.
DISCOVERY OF THE EGG AND MIRACIDIUM
In his second communication to vo n Siebold in August 1851, Bilharz reported

that he had seen eggs in the oviduct and uterus of female worms, and note d
their characteristic morphological features - the terminal spine writing, "th e
eggs are oval and pointed at one end" 32. In the following year, he found these
same eggs in the bladder mucosa and observed that they contained activ e
embryos which escaped from the egg shells: "Many of these eggs containe d
mature, actively motile embryos: next to them lay broken, empty egg shells" 32.
He then went on to recount the manner in which these larvae escaped fro m
their constraints:
(the) embryos....moved briskly in all directions, now contracting spherically, now
stretching out, and finally tearing the egg shell: in this process they stretch out to
their full length and tear the shell with a strong sideways pull. 32
Bilharz then described the appearances of the free embryos (now known a s
miracidia):
The organism that emerged had a long, cylindrical cone-shaped form which was
thicker anteriorly and more rounded posteriorly, with a proboscis-like protruberance
anteriorly. It was completely covered with rather long cilia which enabled it to swim
around in the water with a lively, rotating motion. 32
He then examined the behaviour of these organisms and found that they swam
around in the water for an hour or so, developed blister-like bulges on thei r
surfaces, assumed a mulberry shape, then finally lost their motility and dis -
integrated. Bilharz was uncertain as to the fate of the embryos. In 1851, he had
noted calcified areas in the liver along with S. haematobium eggs: "strange
bodies provided with spines, approximately similar to those eggs in size" 32.
These were probably empty egg shells of S. mansoni (see chapter 9), but
Bilharz did not recognize them as such. He found them again in the following
year and put forward the hypothesis that they were capsules representing a
further stage in the development, perhaps a kind of pupal covering to protect
the embryos when newly emerged from the eggs. Since these bodies wer e
found in patients with old, healed dysentery, he speculated that the healin g
process had prevented the embryos from making their normal egress, and that
they prematurely went through a phase of development that normally occurred
outside the human body.

Following Bilharz, a number of investigators including Harley 104,
Cobbold57, Sonsino186, Brock37 and Looss141 studied the anatomy and behaviour
of S. haematobium miracidia.
THEORIES ON THE MODE OF TRANSMISSION
Soon after the discovery of schistosomes, Griesinger speculated on the ways

in which infection might be acquired. Since he was about to leave Egypt, he
was unable to investigate the question himself, but with considerabl e
disingenuousness, thought that the problem should not present too muc h
difficulty:
Had I remained longer in Egypt, I would have set myself two large practical tasks.
First, I would wish to discover the ways in which these entozoa penetrate the body.
This is relatively easy considering the simple food of the people. 100
Little did Griesinger realise that more than 60 years of confusion, concoction
and controversy would have to pass before light dawned on this problem. He
pointed a finger of suspicion at three main potential culprits: impure Nil e
water, contaminated bread or grain and/or dates, and the half-rotten fish that
were beloved by the fellaheen. He believed that patient investigation ough t
eventually to disclose eggs, larvae or mature worms in one or other of these
vehicles.
It is perhaps surprising that neither Bilharz nor Griesinger appear to have
paid any serious attention to the possibility that infection might be transmitted
by snails, or that von Siebold did not make this suggestion in hi s
correspondence with Bilharz. This is more understandable in the case o f
Griesinger, for although he made major contributions to parasitology ,
particularly schistosomiasis and hookworm disease, his major interests lay in
the field of psychiatry, and it was for that reason that he was about to return to
Germany. Bilharz, however, was a pupil of von Siebold's and knew of th e
latter's work on the relationship between miracidia of the trematode ,
Monostomum mutabile, a parasite of geese, and certain cercaria-sacs found in
snails, and he must surely have known of Steenstrup's theory of th e
"Alternation of Generations" (see chapter 4). In their defence, however, it must
be admitted that 30 years were to p ass before Thomas and Leuckart elucidated
the life cycle of Fasciola hepatica, that many authorities in the early 1850's did
not accept a connection between cercariae an d distomes, and that schistosomes
were very unusual flukes in that they were unisexual.
Spencer Cobbold in London, however, was on the right track. He was an
experienced and widely read helminthologist, and in his textbook of 1864 on
the human entozoa, he wrote that:
it is more probable that the larvae in the form of cercariae, rediae and sporocysts,
will be found in certain gasteropod molluscs, proper to the localities from whence
the adult forms have been obtained.55
Cobbold thought that human infection was probably acquired either b y

swallowing the snails themselves, or by drinking unfiltered water into which
the larvae had escaped.
These views were echoed in the same year by Harley who wrote that:
it may safely be assumed that between the ciliated embryo....and the adult sexual
animal there are probably two distinct forms which serve to complete the chain of
metamorphosis connecting these two extremes of development. What these forms
are, and what are their transmigrations, are questions which require careful
elucidation. The ciliated embryo is adapted for an aquatic existence. Swimming
freely about, these minute organisms probably come in contact with certain
molluscs and become developed within them into what have been called cercaria
sacs.102
Harley later put this idea to the test by examining some fresh-water molluscs
(Unio kaffre) sent to him by Dr Dunsterville from an endemic area in South
Africa but failed to detect any schistosomes 103. Nevertheless, he also kept his
options open for as well he canvassed the possibility that the parasite migh t
develop directly from ova introduced into the human body. He then examined
this possibility in 1870 by attempting to infect experimental animals directly.
He fed large numbers of S. haematobium eggs to two rabbits and two dogs in
their food. Three animals were killed, one each at two, three and six months
after infection, but no trace of schistosomes could be found 104.
Meanwhile, Cobbold in the same year, had indicated to a meeting of th e
British Medical Association meeting in Liverpool, that he had undertake n
some experiments in order to trace the development of the worm i n
invertebrate intermediate hosts. The results of these studies were published in
1872, together with the outcome of his attempts to infect various species o f
fish. He used ova obtained from patients infected in South Africa and:
tried to induce the ciliated embryos to enter into the bodies of a great variety of
animals, such as gammari, dipterous larvae, entomostraca, limnei, paludinae,
different species of Planorbis, and other fresh-water molluscs, but neither in them
nor in sticklebacks, roach, gudgeon, or carp, did they seem inclined to take up their
residence.57
However, Cobbold quite rightly qualified his findings by indicating that h e
may not have reproduced the conditions obtaining in endemic areas:
These experiments, however, are by no means conclusive, since the conditions
under which the experiments were made departed in several respects from those
that are presumably essential to success in the ordinary course of Nature. 57
These two approaches, the direct infection experiment of Harley's and the
search for a molluscan intermediate host by Harley and Cobbold, formed the
basis for subsequent attempts to elucidate the life cycle of schistosomes .
Unfortunately, the debate on this subject ofte n sank into the depths of acrimony
and vituperativeness. Cobbold, in his usual dogmatic way, began this with an
attack on Harley in 1872. Having criticized him for his erection of B. capense,
Cobbold remarked that he doubted whether Harley had looked carefully into
the writings of other investigators and then wrote:
On what grounds....Dr John Harley could possibly expect to rear Bilharzia by
feeding dogs and rabbits with ova, I am at a loss to understand; and his apparent
suspicion that parasites 'may increase in the (human) body from the development
of eggs' in a direct manner, is to me a mere haphazard conception, and one which
virtually sets at nought the well established experiences of every original
experimenter whose name is known in connexion with the advancement of
helminthology in its ontogenic bearings. Throughout the whole of Dr Harley's
remarks on this head - and I confess to have the greatest difficulty in
comprehending the purport of many passages - the generally received opinion as
to the necessity of an intermediate host amongst the Trematoda seems to me to
have been altogether overlooked, and therefore to that extent utterly ignored. So far
as Dr Harley is concerned in this particular relation, the teachings of Leuckart,
Pagenstecher, Guido Wagner, Siebold, van Beneden and especially Filippi, are
altogether a dead letter.57
This was an unjust criticism for Harley had in fact been much more scientific
in his approach than the cocksure Cobbold. As already intimated, Harley, as
early as 1864, had suggested on general grounds than an intermediate hos t
might be necessary, and had actually looked for schistosomes in snails before
Cobbold had. But he realized, as Cobbold himself had remarked in justifying
separate generic status for Bilharzia, that schistosomes were so different from
other flukes that it did not necessarily follow that were transmitted in the same
way. It was not only reasonable, but necessary, that direct infection should be
proven or disproven by experiment.
Permeating both the "direct" and "snai l" theories was the widely held belief
that water was intimately concerned in the transmission of infection. Ther e
were, however, two views as to the way in which infection was acquired from
water. As early as 1864, Cobbold declared that it was quite clear to him that
people in Africa were infecte d when they drank unfiltered waters 56. Two years
later, Dr Rubidge of Port Elizabeth, South Africa, put forward a novel ide a
based upon perspicacious epidemiological and clinical observations when he
wrote to Harley in London in response to the latter's request for information on
endemic haematuria. Harley quoted Rubidge in his second communication on
the subject to the Royal Medical and Chirurgical Society:
Pretty extensive enquires lead me to believe that bathing in rivers has something
to do with the production of the disease. I have never met with a case in boys who
do not frequently bathe in the Zwarlkojss or Booker's River. On the other hand,
those few boys in the families of my patients who are free from the disease, bathe
in the sea only. My impression is that the parasite gains entrance into the skin while
the individual is bathing in the river and I may mention that the lad W. Jones . .
described a sort of urticarious eruption attended with great irritation, as a frequent
result of bathing in Booker's River....Females are rarely affected, if at all. I have not
myself observed a single wellmarked case in this sex. 179
Following on from this, Harley in 1870 put forward the hypothesis that ov a
may be inserted into the skin while bathing, perhaps by being injected by the
ovipositor of a minute, leech-like animal 104.
In 1882, attention was focused again on water as the vehicle of infection
when a dozen staff of the Eastern Telegraph Company at Suez were attacked
with schistosomiasis after drinking water from the Sweet Water Canal while
walking or shooting nearby12. In the same year, Allen also noted that in Natal,
South Africa, the infection was most common in natives and in the mal e
children of white settlers, then put forward the following observation:
The reason is very evident; they are the largest consumers of unfiltered water. It is
not so often in girls, they staying at home more can as a rule get filtered water; boys
and natives, living much in the veldt and drinking copiously from the first stream
they come across, soon imbibe it.4
In this view, Allen was supported by Lyle, al so of Natal 150, Sonsino in Egypt 188,
and Castle in East Africa 40. While agreeing that infection was much mor e
common in males, Guillemard (1883) was not so sure that drinking infected
water was the correct explanation. He referred to Sonsino's patients in th e
Zagazig where not a single female case occurred, yet only unfiltered water was
available. He favoured the possibility that infection occurred while bathing in
contaminated water:
The mode of infection, so far from being evident, is extremely obscure; but the
supposition that river-bathing, which is but seldom indulged in by women, is in
some way connected with the acquirement of disease seems the most tenable. 101
Allen later (1888) came around to this notion, remarking that:
Nearly all the youths bathing in the Umdimdusi and Drop Spruit are infected, while
the girls, who do not bathe, remain free of the disease. 6
and suggested that an unknown larval stage might enter the body through the
skin. In 1894, Brock supported this view strongly. After stating that "it i s
among boys, who are fondest of swimming, that the symptoms earliest make
their appearance." 38 and that females were rarely affected, he remarked that:
other things being equal, the chances of infection occurring will be greater from the
large quantity of water which must come in contact with the body in bathing, than
from the comparatively small amount conveyed into the stomach by drinking; so
that granting the larvae to have the power of penetrating the body by some means,
we should expect to meet with a much larger proportion of cases among bathers
than among those who only drink the infective water. 38
In contrast, Bronte Elgood (1908) examined the relationship between the
prevalence of schistosomiasis and water contact in schoolgirls and in female
hospital patients in Cairo. She found that i nfection was common in young girls,
even in those who did not bathe in the Nile, but was rare in adult women. She
concluded that infection was unlikely to be due to bathing, was possibly a
consequence of faulty storage of water, or was a result of the consumption of
raw vegetables or fruit that had been washed in dirty canals or rivers 73. Looss
acidly replied that Dr Elgood's conclusions "appear deficient in lucidity ,
disconnected, contradictory" 145, for he considered it impossible that miracidia
could live under the conditions suggested. In fact, Leiper was later to show that
Cairo had two water supplies; in addition to piped filtered water for drinking,
there was a separate supply of unfiltered water direct from the Nile fo r
gardens, and suggested that it was via this route that the girls acquired thei r
infection137. Elgood and Cherry later disputed the significance of Leiper' s
observation, however, for they found vector snails in public ponds an d

fountains and in private gardens in Cairo 74.
A novel but logical suggestion for the acquisition of urinar y
schistosomiasis was publicized by Norman Moore at a meeting of th e
Pathological Society of London in 1882. He quoted a patient of his, a doctor
who had practised in Africa, as telling him that the indigenous inhabitants of
Central Africa believed that the parasite (or at least the cause of th e
haematuria) entered the body via the urethra. Consequently, they tied up the
penile orifice before they crossed a river 163. It has also been suggested tha t
further evidence for such a belief is provided by the penile covers or condoms
that are present on several ancient Egyptian statues and reliefs. In any event,
the idea was sanctioned in a leading article in The Lancet (1900) in which
infection via the oral and urethral routes was compared:
It is by no means improbable that the parasite may enter the body by both of these
methods, although haematuria would probably only follow invasion by the urinary
route.16
This notion was espoused by Allen who wrote:
There can be no doubt but that the prepuce plays a most important part in the entry
of the parasite into the urethra. During the act of bathing the sac formed by the
prepuce becomes filled with water, and if the distoma enters with it, it is obvious
it would be guided almost immediately to the mouth of the urethra and sustained
until it effected entry.7
He then went on to advocate universal, enforced circumcision as a contro l
measure in every country where schistosomiasis was prevalent 8. Similarly, it
was also suggested that infection might be ac quired per anum while bathing 180,
but this idea was uniformly laughed out of court, Manson, for exampl e
remarking that "Apes and the like do not practise ablutions - ergo thei r
schistosomes could not be acquired in that way, and neither could those o f
man"154.
Following Harley's and Cobbold's negative but pioneering studies i n
Britain, attention turned to experimental investigation of the transmission of
infection in endemic areas. The first major contribution came from Sonsino in
Egypt in 1884187, but he could not solve the problem. Nearly ten years later,
three special missions visited North Africa between 1893 and 1894 in search
of a solution: Sonsino, then a lecturer in parasitology at the University of Pisa
went to Tunisia, Lortet and Vialleton were sent by the French government to
Egypt, and Leuckart's assistant, Looss, went from the University of Leipzig to
Alexandria, Egypt. Finally, Leiper led a team to Egypt in 1915. As mentioned
earlier, these studies fell into two broad groups.
DIRECT INFECTION EXPERIMENTS
Despite Harley's failure to infect rabbits and dogs with S. haematobium ova,
this idea was not given up and was examined repeatedly by a number o f
investigators. Mantey made some experiments in 1880 but his results wer e
negative157, In 1882, Hatch in India failed to infect puppies by feeding the m
with S. haematobium eggs in urine mixed with milk 108. In 1894, Lortet and
Vialleton failed in all attempts to produce infection directly; they passed eggs
into the stomach of guinea pig s through a tube, injected ova intravenously into
rabbits, and fed Macacus monkeys with eggs in their food 149. Lortet even kept
sheep with shaven, lightly excoriated legs plunged in water containing many
S. haematobium miracidia for three months, but found no trace of adult worms
at post-mortem examination 148. He had chosen sheep as the host as many sheep
in Sicily were infected naturally with Bilharzia crassa, a parasite closely
related to S. haematobium. Yet as Milton later justly remarked, thi s
experiment would have been more meaningful if Lortet had used B. crassa
miracidia instead 161.
Also in 1894, Looss gave various species of monkeys (since Cobbold had
shown that they were susceptible to infection) water containing miracidia to
drink repeatedly for six to eight weeks; again the results were negative 142.
Despite his failure to prove infection by this means, Looss championed th e
notion that transmission did not require an intermediary host, albeit h e
accepted eventually that infection occurred through the skin. The former tenet
was held because he failed to find an infected intermediate host, as will b e
detailed shortly. Looss explained the rea soning upon which the latter statement
was based to the Egyptian Medical Congress in 1905. His argument wa s
centred principally upon his demonstration that miracidia could not survive in
stomach juice or hydrochloric ac id; perforce, they must travel through the skin
as he had already shown was the case with hookworm larvae. He regretted ,
however, that he did not have any proof, despite repeated attempts to confirm
his thesis:
Unfortunately I still cannot furnish you with the indisputible proof by experiment.
I have already made some trials for introducing larvae into the animals, but these
experiments, fewer than the rest, and being conducted without system, did not give
decisive results.143
Other investigators also kept trying. Wolff in German East Africa (1911)
failed to infect a cat immersed for half an hour in water swarming wit h
miracidia204. Bour in Mauritius (1912) was unable to infect two cynomolgous
monkeys, either orally or percutaneously 36, while Joyeux in French Wes t
Africa was unable to infect a Cercopithecus ruber monkey by bathing it in
urine containing miracidia 117. In 1914, Conor carried out an extensive series
of experiments in Tunis, administering miracidia orally, percutaneously an d
subcutaneously to monkeys, sheep, rabbits, guinea pigs and rats, all wit h
negative results61. Finally, Fülleborn, Leiper and some of Looss's ow n
colleagues in unpublished studies 134 failed to achieve infection directly. Bu t
Looss remained obstinate, explain ing all these failures with the claim that man
was the only known host for S. haematobium 147.
THE SEARCH FOR AN INTERMEDIATE HOST
The first major attempt to investigate transmission in an endemic area wa s

made by Prospero Sonsino, an Italian physician who had been appointed i n
1873 to the Khedividial laboratories in Cairo and had access to Kasr-El-Aini
Hospital where he was able to examine patients and perform autopsies. Ten
years after his arrival, he turned his attention to examining the life cycle of S.
haematobium by following the approach already taken by Cobbold. Perhaps
stimulated by the successful determination of the life cycle of Fasciola
hepatica by Thomas and by Leuckart in 1882, Sonsino concentrated on snails
as being the most likely intermediate hosts. His studies were divided into two
parts. Firstly, he tried to infect experimentally snails kept in an aquarium .
Species of Cleopatra, Melania, Physa and Vivipara were exposed to S.
haematobium miracidia, but infection failed to develop. Secondly, local snails
including species of Cleopatra, Corbicula, Limnea, Melania, Physa,
Planorbis, Unio and Vivipara were examined while searching for evidence of
natural infection with schistosomes, but again he met with no success. H e
concluded:
It is probable that Bilharzia, owing to several other peculiarities, differs from other
genera of distomes and presents this peculiarity: that it possesses as intermediary
host animals belonging to classes different from those which serve as carriers to
other Distomidae. Moreover, this peculiarity invests to this end all its life-history,
in part free in water, and in part parasitic in a single definitive host, and surely
through alternating generations.187
Sonsino's work was regarded highly, with a special correspondent to th e
British Medical Journal writing in December 1884:
Dr Sonsino is continuing his researches....into the life history of parasitic trematode
worms. In this way, it is to be hoped that he will discover the intermediate host of
Bilharzia haematobia.13
Six months later, however, a further note appeared in the same journa l
regretting Sonsino's departure for Italy. The correspondent then went o n
optimistically:
There is now a clear field for an investigator to find the intermediate host of
Bilharzia haematobia. After Mr. Thomas's successful search in the case of
sheep-rot, it should be much easier to set this question at rest. It would be
worthwhile for the B.M.A. to select a man and set apart funds for research. The
Khedividial laboratory....offers every facility; and there is good reason to hope that
by working along the lines of Mr. Thomas, a successful result might be brought
about in one or two years.14
Nothing happened. Eight years later in June 1893, Sonsino returned to North
Africa to recommence his studies into this question. He went to Tunisia and
found some patients who provided him w ith ova in sufficient numbers to allow
him to rear miracidia in association with freshwater molluscs and arthropods.
He believed that he had discovered that a small crustacean was th e
intermediate host. Mysteriously, he d id not publish his results but sent a sealed
letter dated 3 August 1893, i ndicating the nature of his discovery and when he
had made it, to the secretary of the Societa To scana di Scienze Naturali in Pisa.
Perhaps he was not sure of his facts, but was afraid that Lortet and Vialleton
would beat him to the mark. In the event, he changed his mind and wrote to
The Lancet, his paper appearing on 9 Se ptember 1893. Without providing any
details of the experiments, he proclaimed:
After many experiments I succeeded with a small crustacean (amphypoda) and
obtained evidence that this same crustacean is an effective intermediary host of
bilharzia, and so discovered the secret of the life history of the African parasite. 189
Sonsino then amplified his conclusions, indicating that S. haematobium
resembled a holostome rather than a digenetic trematode and underwen t
metamorphosis but neither alternation nor asexual generation in a smal l
crustacean. He stated that the free-swimming miracidia penetrated th e
crustacean at its head, then encysted. Human infection was acquired b y
ingesting these infected crustaceans in contaminated drinking water. He then
went on to say that his further researches had revealed that larvae of several
kinds of aquatic insects were also efficient vectors. This report was received
with acclamation in an accompanying Lancet editorial15, but in the following
year further work indicated that these conclusions were completely untenable
and forced Sonsino to withdraw them entirely 190. It must be admitted though,
that this withdrawal was less public than it might have been - it was published
in the Pisa Society's proceedings but not in The Lancet! Nevertheless,
Sonsino's idea was adopted tentatively by Balfour in Khartoum, Sudan, i n
1904 when he wondered whether the minute crustaceans (probabl y
Ostracoda) obtained from a school well and which took up miracidia might
not be the long sought for intermediate host 24. Nothing came of this suggestion
either.
At around the same time as Sonsino (1894), Lortet and Vialleton reported
that they were unable to infect a number of species of molluscs (includin g
Corbicula, Lanistes, Melania, Physa, Unio and Vivipara), aquatic arthropods,
or water plants with S. haematobium 149. Lortet then continued thi s
experimental work in Lyon, France with local species of Lymnaea, but again
without luck 148.
Simultaneously, Looss in Egypt embarked upon the trail. Initially (1893),
like Cobbold and Sonsino, he predicted that molluscs would be vectors, so he
searched for natural infections amongst local molluscs:
Naturally, the most likely course and that which one expected a priori was for the
embryo after escaping from the egg-case to penetrate, in a manner similar to that
observed in other species of distoma, into some intermediate host appertaining to
the class of mollusca. In my experiments in this connexion, I repeated those of
Cobbold and Sonsino, but with the like absolutely negative results. 142
Even when he dissected snails from the most notorious foci of human infection
in the Nile delta, he failed to find any evidence of schistosomal infection. This
led him to state categorically in 1894:
It is more particularly these latter negative experiences that induce me now
definitely to exclude mollusca as the intermediate hosts of our parasite. 142

In like manner, he failed to infect crustacea, insect larvae, small worms an d
fish. This led him to the conclusion which he maintained stolidly, tenaciously
and immovably for the next 20 years or so:
The above described behaviour of the embryos towards other animals was in the
main what led me finally to the definite conviction that probably no transference
of the embryos by means of an intermediate host appertaining to the classes of the
lower animals takes place. Hence the only possible solution that remained was that
the embryo reached man directly, and develops into a sporocyst in the human host,
the offspring of the cyst being subsequently distributed to its host. 142
He reiterated this view in 1905 143 and again in 1908144 , 1909145 and 1910146 .
Even after Japanese investigators succeeded in infecting a variety of animals
with S. japonicum by immersing them in flooded fields in endemic areas, but
failed to do so when they were immersed in water full of miracidia, Loos s
pontificated as late as 1914:
It is remarkable that the Japanese authors do not appear to be able to come to any
clear concept as to the nature of the invading form. Bilharzia japonica must differ
essentially in its development from B. haematobia, for it seems a priori difficult
to understand how an intermediate host that lives in water can participate in the
spread of B. haematobia in the towns of Egypt.147
Nevertheless, there were dissenters, including Blanchard 35 and Manson 155 in
their textbooks, although it mus t be admitted that their views were based upon
theoretical considerations rather th an personal, practical experience. Such was
the authority and vociferousness of Looss, however, that his dogmati c
statements effectively inhibited the search for an intermediate host for 2 0
years. One commentator remarked:
Hitherto, the scientific world had listened to the teaching of Looss, and any attempt
at upsetting the classical research of the great authority was considered to be
well-nigh sacrosanct.17
It was not until Looss was banished from Egypt by the British at the outbreak
of World War I, that the way was left open for Leiper to make his epocha l
discoveries.

OF THE LARVAL STAGES AND THE SNAIL INTERMEDIAT E
HOSTS.
At the outbreak of war in 1914, British authorities became concerned about

the potential deleterious effects of schistosomiasis on British troops in Egypt.
This concern was founded upon their e xperiences with schistosomal infections
in British soldiers in South Africa during the Boer War, and had been given
deeper expression by Lord Kitchener, the British administrator of Egypt, in his
annual report in 1913 in which h e emphasized that "It is high time that serious
steps should be taken to prevent the continuity of infection that has been going
on so long in the country"129. British authorities were receptive, therefore, to

Leiper's submission that he be allowed to study the problem of th e
transmission of schistosomiasis in Egy pt. Robert Leiper had just returned from
Eastern Asia where he and At kinson had been investigating the life cycle of S.
japonicum and was familiar with the recent discoveries by Japanese workers.
Consequently, Leiper and Drs RP Cockin and JG Thomson, who were to assist
him, were given temporary commissions and sent to Egypt by the British War
Office to "Investigate bilharzia disease in that country and advise as to th e
preventive measures to be adopted in connection with the troops" 134.
The mission arrived in Egypt on 8 February 1915 and was beset wit h
difficulties almost from the start. Within a month of their arrival, Cockin fell
sick and had to be invalided home. Leiper himself was afflicted with scarle t
fever and was admitted to hospital. The influx of the wounded from th e
Gallipoli campaign in May brought pressure for closure of the study. Finally,
when experimentally infected animals were eventually obtained, Leipe r
realized that it was imperative that he had expert pharmacological advice in
the matter of testing anthelmintics; he returned to England on 15 July 191 5
leaving behind Thomson who had joined the general service of the Roya l
Army Medical Corps. Neverthel ess, during this brief period and working with
incredible speed, the team made discoveries of immense importance. Thei r
findings were reported in three instalments in the Journal of the Royal Army
Medical Corps, beginning in July 1915 134. Leiper continued his observations
in England and again in Egypt on his subsequent return there in Novembe r
1915, and brought out two further pa rts of his report in 1916 135 and in 1918 137.
By a stroke of irony, Leiper and his colleagues set up headquarters i n
Looss's vacated laboratories in the Cairo School of Medicine. Leiper ha d
reviewed the literature well and realized that of the 50 species of freshwater
molluscs that had been described thus far in Egypt, only ten had bee n
examined by the combined efforts of Sonsino, Lortet, Vialleton and Looss .
Furthermore, his studies of S. japonicum cercariae while in Japan ha d
convinced him that he could distinguish s chistosome cercariae, including those
of S. haematobium from cercariae of the other distomes on morphologica l
grounds, in particular, the absence of a muscular pharynx 137. Consequently,
Leiper had his team set about the collec tion and identification of all the species
of freshwater molluscs that they could find in the province of Qaliub, a highly
endemic area a few miles north of Cairo, then dissected them in order to look
for any larvae which showed morphological characteristics of schistosomes.
In addition, snails were collected from ponds in the Botanical and Zoological
Gardens at Giza. The second phase of the plan was to ascertain if schistosome
miracidia exhibited chemotactic behaviour towards any species of mollusc .
Thirdly, if cercariae could be found in snails, experimental animals were to be
infected with them and the route of infection determined. Fourthly, if all o f
these were successful, it was planned to assess the efficacy of variou s
chemotherapeutic agents. Finally, th e bionomics of the molluscan intermediate
host, if found, were to be studied.

Attention finally focused on a village called El Marg, nine miles north of
Cairo, which was the home of an Arab attendant in the Department o f
Parasitology of the Cairo School of Medicine; 15 species of molluscs wer e
recovered from this site. Altogether, almost 30 species of snails from various
locations were examined. Four species, Bullinus (now known as Bulinus)
species, Limnaea truncatula, Planorbis boissyi (now known as Biomphalaria
alexandrina) and Pyrgophyla forskali were found to be chemotactic fo r
miracidia hatched from schistosome ova. On dissection of wild snails, thre e
forms of cercariae of the schistosome type were found in four species of snails
from El Marg and the Gardens. Le iper wondered whether they represented the
three species of Schistosoma that were supposed to occur in Egypt: S.
haematobium of humans, S. bovis of cattle and Bilharziella polonica of ducks.
The first form of cercaria, which was distinctive and which he thought wa s
probably the avian form, was found in Planorbis mareoticus, P. boissyi and
Melania tuberculata. The second type of cercaria was discovered in P. boissyi
and M. tuberculata, while the third form was seen in P. boissyi and a species
of Bullinus. Cercariae from these snails were used to infect a calf, a lamb ,
mice, rats, geese, ducks, chickens, crows and wagtails percutaneously. All the
experiments on birds were negative but on 13 June 1915, a young rat which
had been exposed on 4 May was found to be infected, as was on 24 June a
mouse that had been infected on 2 May . Schistosome worms were found in the
liver and mesenteric veins, but since they had not reached maturity ,
differentiation between S. haematobium and S. bovis was difficult.
Encouraged with this success, Leiper infected with cercariae from P.
boissyi or Bullinus, four mice, 26 white rats, 16 desert rats, two guinea pigs
and four mangaby monkeys, and took them back with him to England .
Examination of these animals when they arrived in England disclosed that all
of them had enormous numbers of schistosomes with "characteristic eggs" in
the portal system. Further, he was able to show that the incubation period of
the infection was approximately 6-8 weeks. Leiper used the monkeys t o
compare the percutaneous and oral routes of infection. Three monkeys were
infected percutaneously and one was infected orally. All eventually died o f
heavy schistosome infections, but Leiper thought it most likely that the las t
animal was infected by cercariae penetrating the oral mucous membrane.
While in Egypt, Leiper and his associates also studied the development of
larvae in susceptible species of snails and found that miracidia gave rise t o
sporocysts which in turn produced daughter sporocysts that migrated into the
digestive gland. Cercariae developed within these sporocysts, and thes e
eventually ruptured releasing the cercariae which were then discharged int o
the water. Furthermore, they showed that each cercaria lost its bifid tail o n
penetration of the skin of the final host.
Thus, in 1915, Leiper was in no doubt that certain species of snails were
the required intermediate hosts of the worm or worms that caused huma n
schistosomiasis. Enough was known for a general understanding of th e

epidemiology of the infections, and to devise effective control measures .
However, it was still a matter of debate whether there were one or two species
of schistosomes, and if the latter was the case, which snails were the vectors
of which species. The studies which Leiper undertook in London and on his
return trip to Egypt are detailed in chapter 9. Suffice it to say here, that th e
upshot was that there were indeed two species, and that S. haematobium with
the terminal-spined eggs was transmitted by snails known to Leiper a s
Bullinus contortus, B. dybowski and B. innesi.
Leiper and many of the other early investigators spelled the generic name
of the snail intermediate host as Bullinus. Annandale 10 pointed out that the
genus was described originally from a West African specimen by Adamson in
1757 who spelled it with a single "l" even though the word was derived from
"bulla". Consequently, Oken in 1815 changed the name to Bullinus. The
taxonomy of these snails was confused further when Ehrenberg in 183 0
erected the genus Isidora for certain Egyptian and Syrian forms. Many South
African authors used this designation, although Annandale considered that it
was synonymous with Bulinus 10, and other scholars treated it as a subgenus
of Bulinus. Furthermore, Annandale in 1922 wrote that B. contortus, B.
dybowski and B. innesi were all synonyms of each other and, moreover, that
they were also synonymous with Physa truncata; since the latter specific
designation had precedence, the correct name for the snail was Bulinus
contortus 11. In 1927, Pilsbury and Bequaert declared that Isidora, amongst
other names, was synonymous with Bulinus 173. It was not until 1931 whe n
Baylis28 reiterated these points, howeve r, that the nomenclature of B. truncatus
became accepted generally.
Leiper's results were confirmed by Manson-Bahr and Fairley who studied
schistosomiasis between 1916 and 1918 in Imperial troops of the Egyptia n
Expeditionary Force. They recovered S. haematobium adults from monkeys
infected experimentally with cercariae from Bulinus then infected Bulinus
snails with S. haematobium miracidia and confirmed that Planorbis was
resistant to these miracidia 156.
Concurrently with Leiper's work in Egypt, and being stimulated by th e
recent discoveries concerning the life cycle of S. japonicum in the Orient, FG
Cawston turned his attention to determining the mode of transmission of the
terminalspined S. haematobium in South Africa. In collaboration with Dr E
Warren, Director of the Natal Government Museum, snails were taken from
a swimming pool, which was believed to be the source of schistosomiasis in
Pietermaritzburg, then mixed with urine containing S. haematobium eggs.
After three to four weeks, cercariae with bifid tails, generally resembling those
seen with S. japonicum, were found encysted within the liver of one of th e
snails identified as Physopsis africana (now known as Bulinus [Physopsis]
africanus), but not in Limnea (= Lymnaea) natalensis exposed similarly. Dr
Watkins-Pitchford, Director of the South African Institute of Medica l
Research, first communicated these results in July 1915 198, even though
Warren looked upon these observation s as merely tentative and deprecated the
drawing of definite conclusions, particularly as the snails could have bee n
infected naturally and as there was no proof that they were the cercariae of S.
haematobium. Publication of Leiper's discoveries prompted a flurry of activity
by Cawston. He exposed a mouse and a guinea pig to washings obtained from
infected snails, but the mouse escaped and schistosomes could not be found in
the guinea pig at autopsy six months later. Nevertheless, Cawston the n
indulged in what was to become a favourite hobby of his, publishing these in-
determinate findings in three different journals 41. In the following year (1916),
he recorded finding "bilharzia forms of cercariae" in 17.4% of 533 specimens
of P. africana42. Cawston had made a quite unwarranted assumption an d
Leiper condemned this when reviewing the paper for the Tropical Diseases
Bulletin:
The use of the term 'Bilharzia forms' for cercariae with bifid tails is exceedingly
misleading. The presence of a bifid tail is no indication that a cercaria belongs to
any special systematic group. In Egypt, 9 out of 27 recorded species of cercaria
have 'bifid tails'.136
A multitude of papers flowed from Cawston's pen over the next several years,
much to the exasperation of Leiper who wrote "There is no evidence that the
various forms so loosely and repeatedly termed 'Bilharzia cercariae' in thi s
author's numerous papers are actually such" 138 and "The subject matter ha s
already been repeatedly reviewed in this Bulletin, and the present pape r
contains nothing new" 139.
In fact, one of these so-called cercaria of S. haematobium finally turned out
(when sent to Leiper for identification) to be that of S. bovis43. In 1920,
however, Annie Porter showed by infecting experimental animals that P.
africana was naturally-infected with both S. haematobium (commonly) and
S. mansoni (occasionally), and that Lymnaea natalensis rarely harboured
cercariae of S. haematobium174. Porter was later to remark that cercariae of at
least 22 different species has been found in P. africana 175. Cawston finally had
a modicum of luck when he succeeded eventually in infectin g
laboratory-reared P. africana with S. haematobium miracidia and obtained
cercariae six weeks later 44.
Several years later, Blacklock an d Thompson in Sierra Leone also infected
Physopsis with miracidia from S. haematobium ova, obtained cercariae from
these snails, infected monkeys and guinea pigs, then recovered S.
haematobium adult worms 33.
In 1921, 17 autochthonous cases of schistosomiasis were found i n
Portugal. França investigated the attraction of various species of local snails
for miracidia of S. haematobium and opined that Planorbis corneus var
metidjensis (now known as Planorbarius metidjensis ) was likely to be the
intermediate host 88; in this, he was later proven to be correct 29.
A focus of infection with S. haematobium was found in a village nea r
Bombay, India in 1952 by Gadgil and Shah 92, then it was shown by Gadgil in
1963 that the local vector was the limpet, Ferrisea tenuis 91.
CORRELATION OF INFECTION WITH PATHOLOGY
In the patient in whom he found flukes, Bilharz apparently recognized no

partcular pathology, for he made no comment on this subject in his first letter
about this infection to von Siebold. In March of the following year (1852) ,
however, he and Griesinger fou nd evidence of bladder involvement when they
performed an autopsy on a boy who had died from meningitis. When the y
opened the bladder, they found:
lentil- to pea-size, soft, spongy excrescences....They were ecchymotic and often
encrusted with urinary salts. In the older lesions, we observed dark gray, leatherlike
areas of mucosa covered with salt crusts; in the earlier lesions we saw areas
surrounded by varicose capillaries coated with mucus and blood. 32
When some of the larger lesions were cut into, it became apparent that some
of them were dilated blood vessels containing adult schistosomes. Earl y
lesions on the other hand, harboured large numbers of S. haematobium eggs,
either singly or in clumps. The same eggs had been noted previously in th e
bladder by one of their colleagues, Dr Lautner, but he had not been able t o
explain their nature. One week later, Bilharz had a second case in which there
were not only bladder tumours, but also extensive dysenteric changes in th e
intestine. In this patient, the bladder excrescences contained no worms bu t
eggs in spherical heaps were embedded in the mucosa.
In May of that year (1852), Bilharz again wrote to von Siebold stating his
view that S. haematobium was the cause of extensive damage to the urinary
tract:
I no longer have any doubt that the worms cause the changes in the bladder, ureter
and the seminal vesicle and so on. I, therefore, believe that the worm is related to
a large extent to the frequency of bladder ailments, calculi and also certain renal
diseases.30
Bilharz also noted that this worm may be related to disease of the large bowel
and indicated that eggs had been found in dysenteric intestines, but the n
qualified this remark by adding that cadavers of such patients were rare .
Although he considered it likely that the pathological processes in the bladder
and the gut were identical, and was convinced that the presence of worms in
the bladder was a prerequisite for urinary disease, he was less certain abou t
their role in dysentery, for he had two patients with this latter condition i n
whom eggs could not be found. This led him to ask:
Is my ineptness to be blamed or is the worm attracted by the initiation of primary
disease of the intestine or is the worm the direct and immediate cause of the disease
- but not solely responsible. I have not been able to reach a decision concerning
these important questions.30
It is quite possible that Bilharz was sometimes dealing with cases of amoebic
or bacillary dysentery, for neither of these conditions nor their causative agents
were recognized at that time. What is less clear is how many of the eggs in the
intestines that he saw were those of S. haematobium and how many were S.
mansoni, for he did not differentiate between the two, labelling them all a s
eggs of S. haematobium. It seems most likely that those patients with intestinal
schistosomiasis as well as vesical schistosomiasis were infected concurrently
with both S. haematobium and S. mansoni.
In 1854, Bilharz's colleague, Griesinger, published a classic report on his
findings in the 117 cases of schistosomi asis that he had encountered during the
course of 363 autopsies. He descri bed the various changes that could be found
in the bladder. In the mildest cases, there were simply:
foci of hyperaemia....containing many fine extravasations of blood. The mucosa
was somewhat swollen....and often....covered either with viscous mucus or with a
soft grayishyellow, hemorrhagic exudate. In these secretions, the eggs of the
Distoma were found, en masse.100
He noted that the urine in the bladder of these patients was generally light and
clear. In more advanced cases, he described "polypoid patches of the mucosa
which were....discolored....(and) often....showed a brittle crust on th e
surface"100.
Bilharz believed that these changes could be attributed to inflammation an d
extravasation of blood consequent upon invasion of the small blood vessels by
schistosomes and deposition of their eggs. He also recognized a third type of
lesion:
In some instances solitary clusters of pea-to-bean size, yellowish or ecchymotic
papillomata or vegetations one to three lines high were found on the mucosa. They
were wart-like or fusiform.100
There were countless transitional forms or intermediate stages between these
tumours and the diffuse lesions, so he concluded that the former simply rep-
resented more advanced degrees of same process.
Griesinger also noted that all these changes were often seen in the ureteric
mucosa and sometimes even in the renal pelvis. He realized that th e
consequences of the ureteric lesions were much more serious:
Deposits on the mucosa and frequent thickening of the submucosa caused stricture
of the ureter; in addition, there may be spindle-shaped or sac-like dilation of the
lumen, muscular hypertrophy, and/or urinary retention with its complications. In
cases where these changes had been present a longer time, fatty degeneration,
pyelitis, hydronephrosis and complete atrophy of the kidney parenchyma were
found.100
In the same manner as Bilharz, Griesinger connected vesical schistosomiasis
with the urinary lithiasis endemic in Egypt "In addition, large urinary stones
often formed in the kidneys, ureters and bladder with serious consequences" 100.
Griesinger understood that these disturbances in the function of the urinar y
tract sometimes led to a generalized chroni c disease, culminating in death from
debilitation, pneumonia, dysentery and anaemia. Like Bilharz, he realized that
urinary schistosomiasis was sometimes associated with intestinal disease ,
having found that 50 of his 117 cases with urinary schistosomiasis had acute
or chronic dysentery. Similarly, 20 of the pe rsons had died of "bilious typhoid",
so he remarked cautiously that there was not necessarily a direct link between
schistosomiasis and dysentery or typhoid fever. He suggested that an y
relationship between schistosomiasis and both hepatic abscess and live r
atrophy was worthy of investigation. Finally, his discovery of schistosome ova
in the blood of the left side of the heart caused him to remark that "th e
transportation of the worms or at least their eggs into the general circulation
and to essential organs must be kept in mind" 100.
In 1856, Bilharz published a lengthy paper on the relationship between S.
haematobium and pathological changes in the urinary system 31. He classified
the pathological changes in the urinary system into four groups: catarrha l
inflammation of the bladder and ureters, induration and calcification of th e
mucosa, polypoid growth of the mucosa, and mucosal ulceration. All of these
changes Bilharz attributed to the presence of eggs in the mucosa. H e
postulated that male worms carrying a pregnant female in the gynaecophoric
canal migrated against the flow of blood to the small vessels of the vesica l
venous plexus and that the female worms then deposited ova in a gelatinous
substance. He suggested that the adult worms and eggs blocked blood flo w
causing rupture of the vessels and extravas ation of eggs, either into the mucosa
itself, or directly into the lumen of the urinary tract. If trapped in the tissues,
the eggs acted as foreign bodies and stimulated an inflammatory reactio n
which resulted in the lesions seen.
These descriptions of the gross morbid anatomical changes in urinar y
schistosomiasis have hardly been improved upon since. Following thes e
pioneering studies, the histopathological changes of chronic inflammation and
fibrosis around eggs were described by a number of investigators e.g .
Zancarol205. The pathogenesis of these lesions is similar to that which occurs
in S. mansoni infection and is described in the next chapter.
Urinary schistosomiasis is sometimes complicated by the development of
neoplasia. This was first suggested by Harrison in Liverpool in 1889; h e
reported that four out of five specimens of bladder schistosomiasis sent to him
from Alexandria by Mackie were complicated by the presence of squamou s
carcinoma106. He acknowledged that further investigations were needed t o
determine whether the worms were merely an irritant in persons predisposed
to cancer or whether there was a direct aetiological relationship between the
worm infection and cancer. A similar case was reported by Albarran an d
Bernard in 1897 3. In 1911 Ferguson set the association on a firmer foundation
when he described a series of 40 cases of malignant neoplasia, usuall y
carcinoma, in the bladder of patients with schistosomiasis. He wrote: "I have
no hesitation in affirming that cancer of the urinary bladder is the irritatio n
cancer of Egypt." 83 To underscore his point, Ferguson went on to contrast this
with intestinal schistosomiasis, remarking that he had not been able to trac e
any relationship between schistosomiasis and cancer of the anus, rectum o r
sigmoid colon.
The behaviour of S. haematobium adult worms in blood vessels wa s
studied in anaesthetized monkeys by Fairley 78,80. He observed that the adul t
worms moved with a peristalsis-like action of the body and with the aid of the
ventral sucker. When the time for egg-laying was at hand, the female worms
left their male partners and retrogressed against the portal bloodstream to the
small venules. By a process of elongation , each worm then worked the anterior
truncated part of its body into a vessel of smaller diameter than its own, then
ejected an ovum, with the spine pointing backwards into the current of blood.
The adult worm then withdrew slightly and the overdistended venul e
contracted down upon the egg, and so the process was repeated. Fairle y
believed that the spine engaged the vessel wall, then rent a tear in it under the
forces of the bloodstream, and was thus extruded into the perivenous tissue.
This view was disputed later by Brumpt who could see no role for the spine 39.
With respect to the location of the adult worms, Fairley showed tha t
although they could be found in the portal and inferior mesenteric veins, the
largest numbers were present in the vesical and uterine venous plexuses. I n
this situation they may live for many years; one well-known English zoologist
and physician was infected whilst on a naturalist expedition between th e
Limpopo and Zambesi rivers in 1878, and continued to pass eggs for at least
another 28 years 51.
The pathological changes in the liver and lungs in S. haematobium
infections broadly resemble those caused by S. mansoni ; the recognition of
these effects is described in chapter 9.
It must have been clear to Bil harz and Griesinger when they first found ecchy-
moses and blood clots in the blad der of a boy with vesical schistosomiasis that
passage of blood in the urine would be a promi nent feature of schistosomal inf-
ection. This, in fact, was the sign which gave Bilharz the clue to the diagnosis
of schistosomiasis when later that year, he first found eggs in the urine of a
living patient. In his review of urinary schistosomiasis in Egypt, Griesinge r
listed haematuria, pyelitis, enlargement of the kidney, septicaemia and acute
exacerbation of various obscur e and undiagnosed bladder and kidney ailments
as the ways in which patients with the infection could present clinically 100.
Bilharz later re-emphasized these points, making particular mention of a
feeling of pressure and tenderness in the lower abdomen, increasing o n
occasion to vehement burning or colicky pain, frequency of micturition ,
passage of mucus in the urine, and haematuria, the last being usually only a
slight admixture of blood, but long-lasting and recurring frequently. Lik e
Griesinger, he also thought that infection predisposed to urolithiasis, especially
to stones in the ureter 31.
These symptoms were similarly well-described by Harley in London i n

1864 in connection with his patient with the "endemic haematuria of the Cape
of Good Hope". His patient complained that after micturition, a little blood ,
never exceeding a teaspoonful , or some dark "veins" (presumably blood clots)
appeared with the last half ounce of urine. In this person, the urine itself was
never bloody, but sometimes the "veins" would block the urethra and caus e
obstruction for a few minutes. Moreover, he had occasional twinges of pain in
the loins102. Harley later came to realise though that many robust person s
(colonists) in South Africa were infected with the parasite without an y
apparent detriment to their health 105.
Once the clinical manifestations of S. haematobium infection were defined,
it became possible to recognize earlier descriptions of schistosomiasis. Many
Egyptologists have concluded tha t the - - disease mentioned in ancient texts
such as the Kahun papyrus (c.1900 B.C.) and in the Papyrus Ebers (c.1500
B.C.)168 referred to haematuria, undoubtedly of schistosomal origin 2,109
,
although the Egyptians were probably no t familiar with the worms themselves.
Indeed, haematuria was so common that it was mentioned some fifty times in
papyri known by 1951 185. Moreover, description of the use of a basket to cover
the penis as a protective measure against this affliction has been found in the
Papyrus Ebers172. Formal proof that the ancient Egyptians played host to S.
haematobium was provided when Ruffer found large numbers of calcified ova
in the kidneys of two mummies dating from between the XVIII and X X
Dynasties (1250-1000 BC) 181. It has even been postulated that urinar y
schistosomiasis was the basis of Joshua's curse and the cause of th e
abandonment of ancient Jericho 111.
Similarly, it became clear that the epidemic which afflicted Napoleon' s
troops in Egypt at the turn of the century before Bilharz discovered the worm
and which was described graphically by Renoult was none other tha n
schistosomiasis haematobia:
A most stubborn haematuria....manifested itself among the soldiers of the French
Army ....the continual and very abundant sweats diminished the quantity of urine,
the latter becoming thick and bloody. Often even, the last drops are pure blood. The
sickness gives sharp pains in the regions of the bladder, the last contractions of the
bladder are accompanied by the most lively and piercing pains. 176
These symptoms and signs were again well-recognized in British troops i n
South Africa during the Boer War and in Imperial soldiers in Egypt durin g
World War I. For example, 75 troopers of the Australian light horse wer e
infected by bathing whilst stationed at Serapeum and at Tel-el-Kebir in 1916.
The clinical manifestations were divided into two phases. The early toxaemic
stage occurred four to ten weeks after infection in more than half of th e
soldiers and was characterized by fevers, rigors, sweats, headache, myalgia,
urticaria and emaciation lasting from t wo to five weeks. A later stage appeared
three months after infection; in 60% of the patients, the earliest symptom was
a burning urethral pain on micturition, then terminal haematuria supervened
after another one to four weeks 77.

The kinetics of infection and the consequences of urinary schistosomiasis
were particularly well-illustrated by a self-inflicted infection with S.
haematobium. On 31 May 1944, Claude Barlow (who had earlier infecte d
himself with Fasciolopsis buski), infected himself by applying eight cercariae
from eight different specimens of B. truncatus to the skin of his forearm. On
the following day, he placed eight more cercariae from the same snails around
his umbilicus. Two weeks later, many cercariae from another six snails were
again applied near the navel; 147 sma ll red papules were seen on the next day,
thus confirming his previous observation that dermatitis may occur i n
schistosomiasis haematobia 26. After a further week, more cercariae wer e
similarly placed and 61 papules were seen 24 hours later. Barlow estimated
that he was infected with a minimum of 224 cercariae. Eleven weeks after the
major exposure on 14 June, he developed a mild fever, spermatozoa wer e
found in his urine, and schistosome eggs were seen in the seminal fluid and in
a plug of mucus in his stool. Ova ap peared in the urine on the 106th day. After
20 weeks, a nodule which discharged eggs appeared on the scrotum; further
nodules developed and one was excised, revealing a pair of adul t
schistosomes. Eggs continued to be excreted in the urine and faeces, wit h
20,000-30,000 being passed daily in the urine alone. An evening pyrexi a
persisted and Barlow felt ill and prostrate. Micturition was frequent an d
painful and blood, pus and shreds of m ucosa were seen in the urine. Blood and
mucus appeared regularly in the stools. Barlow's blood eosinophil level was
increased, ranging between 6% and 16%. Ten months after infection, he was
treated with fouadin, this caused a fever, nausea, wheeze and cough. Th e
numbers of eggs excreted were reduced greatly, although the drug did no t
eradicate the infection completely 27.
The amount of blood lost in the urine in patients with schistosomiasi s
haematobia has been investigated on several occasions. Gerritsen and hi s
colleagues showed in 1953 that between 1.3 and 6.1 ml of blood was lost per
day in African males 94. A rather greater blood loss was estimated by Farid and
his colleagues who used red blood cells radiol abelled with 59Fe: they calculated
that between 2.6 and 126 ml of blood were lost each day in infecte d
Egyptians82.
While mild or moderate symptoms were the rule, it was realized that very
intense infections may cause severe disease. Thus, Maddern described th e
possible devastating consequences:
He has constant micturition, really an incontinence and dribbling, with pain in the
penis and deep down in the perineum near the rectum. He very often carries his
scrotum in his hand, feeling that the support affords him some alleviation of his
pain. A very small quantity of water is voided at a time, which is very offensive,
dark brown in colour . . and turbid....On examining the abdomen, a hard mass may
be felt in the suprapubic region, which is not at all tender, is very irregular and
stony, and may extend as far as the umbilicus and to any extent laterally. One or
both kidneys will be found enlarged and tender, and the much dilated and thickened
ureters may be felt through the usually thin abdominal wall. On rectal examination,
the bladder will be felt firm and contracted, and bimanually the great thickening of
and around the bladder will be well appreciated. On introducing a sound, it can
often only be passed just beyond the neck of the bladder into a very much
contracted cavity.153
In addition, Maddern noted that urethral fistulae and a destructive, distorting
false elephantiasis of the scrotum and perineum might supervene 153.
With respect to prognosis, Bilharz recognized that the disease may last for
many years, thus indicating that either the worms lived for a long time, or that
reinfection was common. On the whole, he thought that the latter was more
likely. Nevertheless, he did not reject the possibility that spontaneous cur e
might occur, for he often encountered pigmented, leathery areas of bladde r
mucosa which contained innumerable calcified ova but no living adult worms
or fresh eggs31. Both Bilharz and Griesinger thought that death was ofte n
caused by intercurrent illness, and this view was supported by practitioners in
South Africa who claimed that they had never seen anyone die fro m
schistosomiasis 4,150. Cobbold was among the first to realize that the severity of
clinical manifestations bore some relation to the worm burden. He contrasted
'slight' and 'excessive' invasions thus:
In cases of the former kind not more than a dozen or so of the parasite's eggs will
be passed at each act of micturition, whereas in the latter it is not uncommon for
the patient to pass fifty, or for that matter, a hundred dozen bilharzia eggs at a time.
In severe cases the daily average of evacuated ova greatly exceeds this estimate. 59
Nevertheless, Cobbold went on to suggest that:
the severity of the symptoms and consequent dangers are, as a rule, more
dependent upon associated disorders than upon the actual number of parasites
present.59
Infections in British troops in the South African war revealed that the disease
was more prolonged than had hitherto been believed. Symptoms persisted for
between five and thirteen years, often intermittently, but it was concluded that
mortality arising from infection did not exceed 1% in the 466 soldier s
studied107.
In 1852, Bilharz made a provisional diagnosis of vesical schistosomiasis i n

one living patient and proved the diagnosis in another. In the former case, he
felt a rough surface in the bladder which he was able to palpate between his
finger in the rectum and a catheter i n the bladder; unfortunately, he was unable
to examine the urine of this patient. In another patient, however, he told von
Siebold in a letter dated 2 August 1852 "I found fresh eggs in the urine of a
young man who had moderate haematuria of unknown aetiology" 30.
Griesinger later referred to this epochal observation:
The eggs of the Distoma were found by Dr Bilharz while microscopically
examining the urine of a boy who developed haematuria during convalescence

from typhoid fever. The diagnosis can be established with this finding alone 100.
Many investigators believed that eggs could be found most frequently in the
terminal urine, although this has been dispu ted by others. In more recent times,
a rapid concentration technique using filters has been developed for rapi d
quantification of eggs in the urine 171.
An alternative but more complex method of making the diagnosis whe n
facilities became available was by endoscopic biopsy of lesions in the bladder.
This technique does, however, have the advantage of delineating the natur e
and severity of damage to the blad der. Minet in 1915 appears to have been the
first person to examine the bladder cystoscopically. He investigated tw o
soldiers, one of whom had a light infe ction, while the other suffered from more
severe disease. In the latter patient, he noted three types of lesions; smal l
yellow granulations likened to grains of millet, infiltrated swellings of th e
mucosa, and fungating vegetations of the mucosa 162.
Structural damage to the urinary system can on ly be outlined radiologically.
In 1917, Diamantis and Lotsy showed calcification of the left ureter an d
bladder due to deposition of eggs in a plain x-ray of the abdomen 70.
Intravenous pyelography provides a much more sensitive and complet e
definition of the urinary tract and has been used in the last few decades 85,166.
An increased number of eosinophils in the peripheral blood was found in
a single patient by Coles 60 in 1902 then the presence of eosinophilia wa s
confirmed in a series of patients by Douglas and Hardy 72. Many attempts have
been made to diagnose schistosomiasis by immunological methods. In 1919,
Fairley reported the development of a complement fixation test fo r
antischistosomal antibodies 79 then he and Williams described an intradermal
test for the infection 81.
The early investigators recognised the need for effective anthelmintics to cure
schistosomiasis. Griesinger suggested that calomel and oil of turpentine might
be effective, and that perhaps certain foods such as onions and garlic migh t
exert a beneficial effect 100. Bilharz indicated that local pains usuall y
disappeared rapidly after the use of opium, but he was less sanguine abou t
prospects for eradication of the worms, for he thought it would be difficult for
drugs to reach them in their domicile in the veins. He tried on a couple o f
occasions to poison worms in diseased specimens with calomel, but wit h
inconclusive results 31.
In 1870, Harley reported the effects of his treatment for endemi c
haematuria. He found that general therapy with potassium iodide and henbane
was of little use, but that local injections of emulsions of oil of male fern o r
potassium iodide in a strong infusion of wormwood or quassia into the bladder
via a catheter were beneficial 104.

A few years later (1882), Cobbold classified treatment into thre e
categories. In the "heroic plan", medications such as a saturated alcoholi c
solution of santonin were injected into the bladder. He remarked wryly tha t
since patients did not return after this agonizing treatment, the proponent o f
this therapy concluded that the treatment was successful 4. The "do-nothing
plan" was based upon the assumption that the patient would outgrow th e
disease. The so-called "rational plan" (presumably Cobbold's) consisted o f
general support by way of a nutritious diet and the administration of iron and
quinine 58. Cobbold's comments drew a vociferous reply from the injured J F
Allen, the exemplar of the "heroic" system:
Those who may have to treat cases of this kind must not be deterred from using
injections into the bladder by Dr. Cobbold's describing the treatment as heroic; he
is, I fear, so timid and ultra-conscientious that he would consider it heroic to use
enemata in the treatment of ascaris vermicularis in the rectum. Injections into the
bladder are more painful, more difficult, and followed by cystitis, but they are
efficacious in the one case as in the other. It is to these injections Dr Cobbold
objects so much, but as experience and common sense both point to their use, it is
to be hoped that even he may be induced to adopt them. 5
In the interim, Cobbold's views had been supported by FH Guillemard wh o
wrote from Japan expressly to dissuade the adoption of Allen's regimen. H e
lamented the lack of any concrete evidence given by Allen for the efficacy of
local treatment, then emphasized the toxicity of such therapy:
Dr Allen allows that acute cystitis is a common result, and in a case with which I
am unfortunately only too well acquainted, cystitis, acute nephritis with secondary
pericarditis, and probable life-long ill-health have been the unlucky
consequences.101
Cobbold's "rational" treatment also met with criticism. Harley remarked that
he could see no reason why the parasite should not flourish all the more when
the host was healthy, so he hardly thoug ht that improving the general condition
of the patient was likely to result in cure 105. Sonsino then reviewed thes e
arguments and concluded: "as yet, we have no means of curing the infection
of Bilharzia better than it is done by nature" 188.
In 1888, Fouquet in Cairo claimed that extract of male fern was beneficial
in fifteen of his patients 87. In 1906, Stock suggested, on the basis of a couple
of coincidental observations, that antityphoid serum may be of use 191.
Salvarsan enjoyed a vogue after being introduced in 1911 by Dr Nicola s
Joannidès, a physician in Cairo, then given wide publicity by Erlich, th e
famous chemist115. Many observers were not convinced of its efficacy ,
however. For example, Day and Richards (1912) in Cairo assessed th e
effectiveness of the drug in patients with urinary and/or intestina l
schistosomiasis and found it wanting 66. Similarly, Schrecker had fou r
longstanding and four recent cases, and in only two of them did the numbers
of ova in the urine diminish even transiently 182. Thymobenzone was advocated
in 1916177, but proved to be of little use. T hus, none of these drugs was of great
value, and an eminent surgeon in Cairo wrote in April 1917: "Until now there
is no curative treatment for schistosomiasis, and I think it is far from possible

to find one in the near future" 18.
He was wrong. In the following year, JB Christopherson reported that the
antimonial compound, tartar emetic (antimonium tartaratum, potassiu m
antimony tartrate) was of great value in the therapy of both urinary an d
intestinal schistosomiasis 47,48. Christopherson, who was principal medica l
officer at the Civil Hospital in Khartoum, Sudan, had treated a patient wit h
kala azar (visceral leishmaniasis) with antimony. He noted that during thi s
course of treatment, those symptoms that were due to schistosomiasis (wit h
which the patient was concurrently infected), were alleviated. Christopherson
followed up this serendipitous observation in other patients, and found tha t
after intravenous injection of tartar emetic, the schistosome ova becam e
shrivelled, dark-coloured and failed to hatch miracidia in water. After a fe w
weeks, the eggs disappeared completely from the urine or faeces. He described
his technique as follows:
A 10 ccm. record syringe, with a fine needle was used. The injection was given into
one of the conspicuous veins at the bend of the elbow. The patient lay down for an
hour on a bed after the injection, or longer if symptoms intervened. The solution
used was tartar emetic, 1/2gr to 20m aq. distill., and diluted with 2 vols of aq.
distill. at the time of use. The injection was repeated and the dose increased by
1/2gr every other day until 2gr was reached and this was continued until 30gr had
been injected.47
Christopherson also noted that it was essential to watch for signs of acute to
chronic poisoning. Altogether, approximately 30 grains (O.46mg) given over
15-30 days were necessary to achieve a "killing dose". Further experienc e
showed him that the drug was not only able to kill the adult worms, but also
the embryos in the ova in the tissues 50. So convinced of the efficacy of th e
treatment was Christopherson, that he wrote that it may be possible to rid the
scourge of schistosomiasis from Egypt, so that the people would become a
"clear-complexioned, rosy-faced race" 49.
Christopherson's regimen was taken up enthusiastically by a number o f
physicians, including Cawston (1919), Fairley (1919), Low and Newha m
(1919), Innes (1919) and Taylor (1919) who also reported encouraging results
in small series of patients. By 1921, Day was able to report an analysis o f
toxicity and effectiveness of the drug in 1,000 persons treated as outpatients
in a tent-annexe at the Kasr-el-Aini Hospital in Cairo: 88% of these patients
had urinary schistosomiasis. He found that 13gr was the smallest curativ e
amount, but that 24gr or more were usually needed. Day also noted that after
the first weeks of intensive treatment, results appeared excellent, but that two
to three months later, ova reappeared. Since it was thought unlikely tha t
reinfection had occurred, these data were interpreted as indicating that th e
primary effect of the drug was the destruction of ciliated embryos within their
shell, the parent worm requiring a larger dose to achieve a lethal effect 65. The
effectiveness of the drug was confirmed by Lasbrey and Coleman in Cairo in
the same year, also with a series of 1,000 cases. Of those who finished th e
course (20gr), 70% were pronounced cured and they remarked that:
the successful treatment of complications dependent upon bilharziasis, such as
urinary fistulae and rectal papillomata, is enormously facilitated by the elimination
of the causative factor.133
The effectiveness of the drug was demonstrated amply by Shaw in 1921 who
studied the cystoscopic appearances in 23 patients with schistosomiasis who
were undergoing treatment. In half of these persons, there had been activ e
nodules present before therapy, and these disappeared after administration of
tartar emetic. Similarly, infiltrations and signs of subacute cystitis subsided ,
and even the fibrotic areas appeared to improve and become pink 184.
Not surprisingly, when an effective drug was promulgated, others tried to
cash in on the credit. In the week following Christopherson's paper, a lette r
was published by JE McDonagh in which he recalled that he had use d
antimony in 1911 and had eliminated ova from the urine in 23 cases; h e
claimed that he had used the drug empirically because of its effectiveness in
some other disease caused by animal parasites 151. He reiterated this claim two
years later, quoting from the 1915 edition of his book Biology and treatment
of venereal diseases :
I should like to mention that I have had great success in treating cases of
bilharziasis with intravenous injections of antimony. 152
This drew forth the riposte that although it was the earliest record of the use
of antimony in bilharziasis, it could not have been more effectivel y
pigeon-holed. Similarly, but more in the nature of an anecdote, Wiley wrote
that a case of urinary schistosomiasis had been treated in a like manner at the
Australian Dermatological Hospital in Cairo in 1916 203.
Following the introduction of tartar emetic, a number of other trivalen t
organic antimonials were developed, pentavalent antimonials being found to
be ineffective in schistosomiasis. Sodium antimonyl tartrate (SAT) wa s
claimed by some to be better tolerated than the potassium salt, but this view
was not accepted universally. The advent of st ibophen (fouadin, neoantimosan)
in 1929 was hailed as a considerable advance because it could be given b y
intramuscular injection and as it was at first thought to have higher cure rates
and less toxicity that tartar emetic 124,125. Lithium antimony thiomalat e
(anthiomaline) was introduced in 1935 and could also be given b y
intramuscular injection. Sodium antimonyl gluconate (triostam) given b y
intravenous injection had variable effectiveness 75. Sodium antimonyl
dimercaptosuccinate (TWSB, stibocaptate, astiban) was introduced b y
Friedheim and colleagues in 1954 for schistosomiasis mansoni 90, and was then
used in schistosomiasis haematobia in 1956 89. Unfortunately, these
compounds, though less toxic, were less effective than tartar emetic.
A major problem with the antimonials was the severe, sometimes fata l
toxicity associated with their use. In 1936, Khalil estimated that antimon y
killed about 2,000 persons in Egypt each year122. This appalled Diamantis who
considered such therapy monstrous, seeing that the infection would not have
killed the patients in that time, and that had they kept to certain rules, the y
might have looked for a natural cure 69.

In 1946, Alves and Blair introduced "intensive therapy" with antimonials.
They treated 100 patients with S. haematobium and S. mansoni infections with
full doses of sodium antimonyl tartrate frequently within a period of only two
days. The therapeutic results were excellent and the apparent absence o f
toxicity was remarkable 9.
These problems with toxicity led to a continuing search for safer and more
effective schistosomicides. The first major competitor for the antimonials was
emetine. In fact, at almost the same time as tartar emetic was introduced, the
virtues of emetine in the treatment of schistosomiasis were sung, particularly
by continental European workers. In 1917, Diamantis reported that emetine
was of value in a series of patients with schistosomiasis 68. In the following
year, Mayer treated a case of urinary and intestinal schistosomiases b y
subcutaneous injection of emetine and found that blood disappeared from the
urine and stools, and the patient showed great improvement 158. In 1919, Erian
reported that he had used large doses of e metine in 50 patients with both forms
of schistosomiasis and claimed to have no failures 76. In 1921, Tsykalas, after
declaiming the use of antimony as barbarous, promulgated the use of emetine.
He indicated that 90% of 2,000 patients showed a complete and lasting cure,
provided that the emetine was given in a total dose of 1.0-1.2 grams injected
intravenously in aliquots over 10-12 days 193.
As with antimony, controversy then ensued as to who first introduce d
emetine therapy. The article by Tsykalas stimulated a letter from Mayer who
claimed priority in the use of the disease, saying that he recommended it and
gave it subcutaneously in 1915. Nevertheless, Mayer considered the drug to
be inferior to antimony 159. Tsykalas responded to this by stating that he himself
had given it intravenously in 1914, but that Tsamis of Alexandria had in fact
used it as early as 1913 194.
In order to facilitate administration of the drug, oral preparations wer e
developed. In 1926, Gordon showed that emetine periodide was effectiv e
when given orally 99. Nevertheless, emetine in its various forms did not achieve
the long lasting popularity of the antimonials as it was generally considered to
be both less effective and too toxic for outpatient use.
In the middle of the 1930's, there was a spasm of interest in th e
anti-schistosomal properties of acriflavine 84, but this proved to be
short-lived 126.
At the end of the Second World War, it became known that Dr H Mauss
in Germany had synthesized a new series of compounds known as miracils .
One of these preparations, miracil D (nilodin, lucanthone) was shown b y
Kikuth and Gönnert to be active against S. mansoni in mice and in monkeys
when given orally19, but because of the political circumstances, they were not
able to publish details of their experiments until subsequently 127,128. Clinical
trials were then carried out in Southern Rhodesia (Zimbabwe) and in Egypt,
and it was found that S. haematobium was more susceptible to the drug than
was S. mansoni 34.

In 1967, another miracil derivative, hycanthone, was reported to be active
against schistosomes in experimental monkeys 169. Later that year, Katz an d
Pellegrino showed that it was effective in patients with schistosomiasi s
mansoni118, then in 1969 it was reported to be active against human S.
haematobium infections as well 53.
Meanwhile, in 1964, Lambert had reported that a new drug, niridazol e
(ambilhar) was active in mice infected with S. mansoni 131. In the following
year, its efficacy in urinary schistosomiasis was reported following a clinical
trial in Portuguese Guinea (Guinea-Bissau). The drug was given orally an d
was well-tolerated 132. Subsequent studies showed that the agent was als o
effective against S. mansoni but less so than against S. haematobium 116.
Thus, by the early 1970's there were three major therapeutic agents used
in urinary and intestinal schistosomia sis - antimony, hycanthone and niridazole
- each with its supporters and opponents. The consensus of opinion was that
tartar emetic was the most effective drug in bringing about a parasitological
cure, but it needed to be given intravenously, the course was long, and th e
toxicity was sometimes severe. Niridazole had the advantage of ora l
administration and was effective, but was prone to provoke neuropsychiatric
complications, particularly if there was hepatic insufficiency. Hycanthon e
could be given by a single injection, but eradicated the infection in onl y
50-65% of patients, and was sometimes toxic to the liver 21.
There was, however, a fourth drug which was useful in urinar y
schistosomiasis. In 1962, Cerf and colleagues indicated that th e
organophosphate compound, dipterex (trichlorophone, metrifonate) wa s
effective in patients with schistosomiasis haematobia 45. This observation was
confirmed by a number of investigators 86,192, but the drug was shown to b e
inactive against S. mansoni 110.
In the late 1970's, a pharmaceutical company collaborated with the World
Health Organization to assess, in a uniform manner, the effectiveness an d
toxicity of new agent, praziquantel (biltricide, droncit) against all three of the
major schistosome species infecting humans 64. This drug had been identified
in 1972 from a group of heterocyclic pyrazino-isoquinoline derivatives an d
was found to have unusually b road anthelmintic activity. In 1977, a number of
investigators reported that it was active against S. haematobium, S. mansoni
and S. japonicum in experimental animals 97,114,170,201. This drug had the added
advantages that it could be given orally and in a single dose. Subsequen t
clinical studies showed that it was highly active against both S. haematobium
in Zambia63 and against S. mansoni in Brazil119 . Moreover, it had very littl e
toxicity. Praziquantel promises to become the drug of choice in the treatment
of all forms of schistosomiasis.
Occurring concurrently with these medical developments were changes in
the surgical management of urinary schistosomiasis. Improvements in surgery
and anaesthesia facilitated surgical intervention where necessary. In 1897 ,
Curtis described partial resection of bladder for a vesical ulcer caused b y

schistosomal infection 62. In 1903, Milton reviewed the surgical management
of schistosomiasis haematobia and recommended that cystitis be treated b y
bladder washouts with mild antiseptics such as quinine, lithotomy for th e
removal of calculi, drainage of the bladder by perineal puncture for acut e
retention of urine or in very late stages of the disease, plus removal o f
schistosomal tissue if possible, and excision of fistulae 160. In 1918, Desnos
investigated the effects of cystoscopic high frequency diathermy o f
papillomatous and epitheliomatous gro wths of the bladder wall, and found that
the procedure not only cauterized the lesions but also appeared to kill egg s
infiltrating the bladder wall 67. The introduction of effective chemotherapy ,
however, has reduced greatly the need for surgical intervention.
S. haematobium sometimes occurs in subhuman primates, as was first shown

when Cobbold found the parasite in a monkey in London 54. It has been
suggested that human schistosomiasis may have evolved at the same time as
there was a shift in human populations from hunter-gatherer economies t o
societies based upon domestic agriculture, since this parasitism requires a
stable relationship between parasite a nd host. It is thought that schistosomiasis
may have first evolved around the great lakes of East Africa, then sprea d
together with the vector snails along the Nile and out into the Middle East via
the trade routes 167.
Some of the initial ideas on the epidemiology of schistosomiasis have been
discussed earlier in relation to the various theories on the transmission o f
infection. In particular, the geographical distribution of urinary schistosomiasis
was recognized, the increased prevalence in males and the young was realized,
and the association with water was commented upon. Nevertheless, failure to
understand the life cycle led to a number of incorrect assumptions about the
epidemiology of infection. This especially flowed from the view espoused by
Looss that direct infection with miracidia without the mediation of a vecto r
takes place. The consequences of this idea were the beliefs that transien t
collections of water were dangerous if contaminated whereas large bodie s
were not liable to be infective (because of dilution), infection could occur in
both towns and in rural areas if puddles were contaminated, water woul d
become safe automatically after 30 hours if the local population was removed
(because miracidia have only a limited life span), autoinfection could occur for
example in household baths, and infection could spread to any part of th e
globe144.
These concepts underwent a radical revision when Leiper showed in 1915
that infection only occurred via a mollus can intermediate host 134. In view of the
time required for cercariae to develop, it became obvious that transient water
collections were quite safe whereas permanent collections were potentiall y

dangerous if the vector was present, infection in towns was possible if there
was a supply of unfiltered water from contaminated water sources, prevention
of urinary or faecal contamination of water would have no effect for som e
months, autoinfection was impossi ble, and infection could only spread to parts
of the globe where susceptible snails were present.
Much effort was then expended on determining the prevalence an d
intensity of infection in various endemic areas, the age and sex distribution of
the infection, and the prevalence and density of vector snails. The frequency
of infection ranged from near zero to 100% in different localities, but th e
increased prevalence and intensity in males and in children was generall y
confirmed. Urinary schistosomiasis was not a static process, however, fo r
infection increased in some areas and fell in other. These fluctuation s
depended upon changes in water resou rces93. Many examples of these changes
have been recorded; several will be cited here.
Before building the Sennar dam across the Blue Nile to irrigate the Gezira
Province of Sudan in 1925, schistosomiasis haematobia was almos t
non-existent in that part of Africa. Within two years, however, Bulinus species
were present in all the waterways of the system and infection, introduced by
Egyptian labourers, was spreading 112. In Egypt, the introduction of perennial
as opposed to basin irrigation, i.e. irrigation only at the flood of the Nile ,
increased the infection rate between four- and forty-fold in a number o f
villages in the three years from 1934 to 1937 123. In more recent years, a
number of great man-made lakes in Africa including Lake Volta in Ghana ,
Lake Nasser in Egypt and Sudan, and Lake Kariba in Zambia, have bee n
constructed to enhance economic development by improving water supplies
and generating electricity. Unfortunately, scant regard was paid to the potential
health hazards, and the occurrence of schistosomiasis has increase d
enormously, in some places reaching epidemic proportions 23. Not only have
changes occurred around the lakes themselves but along the Nile the pattern
of schistosomiasis has altered downstream; in one village surveyed in 193 5
and again in 1979, schistosomiasis haematobia, which was once commo n
(74% of the population infected), had almost disappeared (2.2%), but th e
prevalence of schistosomiasis mansoni had shown an almost reciprocal effect,
rising from 3.2% to 73%. These effects were ascribed to changes in th e
densities of the respective vector snails consequent upon the changes in th e
water-flow pattern of the Nile following construction of the Aswan High Dam
and creation of Lake Nasser 1.
In the final analysis, though, the habits of the human population are o f
crucial importance, for there is no significant animal reservoir of infection .
Urination in water sources by infected persons and contact with that water ,
whether for economic, social, domestic or recreational reasons, are essential
for maintenance of the life cycle of the parasite and play a major part i n
determining the prevalence and intensity of infection in a given population 196.
The association of schistosomiasis with water was so strong that an editorial

writer in the British Medical Journal of 1882 was able to suggest correctl y
effective control measures, despite an inadequate understanding of the lif e
cycle of the parasite. The editorial followed a minor epidemic o f
schistosomiasis among the staff of the Eastern Telegraph Company at Suez,
and remembering the affliction of French tr oops by endemic haematuria during
the expedition of 1799 to Egypt, the writer was concerned that a similar fate
might befall British troops then situated in that country:
If drinking directly from the canals, or bathing much in muddy water be avoided,
and water well-boiled or well-filtered....be alone used for drinking purposes, the
disease may be prevented. The Mediterranean troops have, it seems, been left
unprovided with any filters, and it is certainly greatly to be hoped that the
authorities will immediately adopt measures to save our troops from so formidable
and painful a disease as haematuria.12
This was good advice, but hardly applicable to the indigenous populatio n
living along the banks of the Nile and in similar endemic areas, for many o f
whom daily contact with water was necessary for survival. Methods for th e
control of infection among the general population hinged upon whether or not
infection was direct or occurred via an intermediate host. Irrespective of the
mode of transmission, Looss was correct when he said:
Infected persons should never evacuate urine or faeces into water, for this is the
only way in which the latter becomes populated with dangerous germs. 146
This was easier said than done, however, and eradication depended upon educ-
ation and complete sanitary control throughout the country, with the sustained
cooperation of every individual being essential. This was and is an almos t
impossible task. The demonstration of transmission through snails, however,
provided a link in the chain which could be attacked without the cooperation
of infected individuals. Further, it was now clear that large bodies of wate r
rather than transient pools should be avoided.
When Leiper worked out the life cycle of schistosomiasis in 1915, h e
turned his attention to a consideration of both personal prophylaxis (wit h
particular reference to troops) and control of the infection in general. Wit h
respect to the former, he studied various physical and chemical measure s
designed to kill cercariae and concluded t hat unfiltered water was safe if stored
for 48 hours, water heated to 50 oC or treated with sodium bisulphate was safe,
that filtration through sand was untrustworthy, and that personal contact with
any kind of unfiltered water was risky 134,135. Concerning control of infection in
the country as a whole, he noted that practically all the water in Egypt came
from the Nile, and that if this fact were properly exploited, it could lead to the
eradication of the disease in the course of a few years. He suggested tha t
appropriate measures included periodical drying of waterways in agricultural
areas to kill snails by drying, and storage of water before supplying it t o
towns134. This approach was only partially successful, however, for Barlo w
showed in field experiments that when the waterways were dried, the Bulinus
snails took up a position with the shell-opening facing down and secreted a
protective coat of slime, with the result that 50% of the snails survived 25.
Nevertheless, snail eggs were killed by these physical measures.
An alternative approach was to kil l the snails with chemical molluscicides.
In 1920, Chandler showed in labora tory experiments that snails were killed by
immersion in a 1 in 1,000,000 solution of copper sulphate 46, then Khalil in
1927 demonstrated in a field experiment that all the Bulinus in an oasis were
killed by this measure and that none were alive six months later 121. In 1932,
Humphreys reported that carbolic acid in a strength of 1 in 20,000 killed all
the snails in the irrigation system in the Gezira region of the Sudan 112, but
copper sulphate remained the mainstay of intervention. In 1941, Mozle y
indicated that malachite green (mineralized basic copper sulphate) was just as
effective and much less expensive 165. These molluscicides were in tur n
followed in 1957 by sodium pentachlorophenate 130 then in 1959 by
niclosamide (Bayer 73, Bayluscide) 96,98. Nevertheless, it was concluded i n
1962 that this approach had been unfruitful, largely because of the grea t
expense involved, the difficulty in providing adequate teams to distribute the
molluscicides, aestivation (similar to hibernation) of the snails, and toxicity of
the molluscicides for aquatic fauna 20. More recently, a mood of optimism has
returned, with Webbe writing in 1981:
There is ample evidence that area-wide mollusciciding is now successfully
controlling snails in major control programmes - for example, in Egypt and China
- and that control of transmission based on the essential focality of transmission in
many areas (St. Lucia, Ghana, Yemen and Saudi Arabia) is also being successfully
prosecuted by killing snails and surveillance.200
A third technique of control is by the mass treatment of infected persons.
This was hailed with enthusiasm following the introduction of specifi c
treatment with tartar emetic in 1918. Christopherson himself wrote:
It is in mass treatment in schools and villages where the hope to eradicating the
disease lies....My own view is that there is more hope of successfully dealing with
the schistosomiasis problem by the symptomatic treatment of individual cases
wherever they are met than by attempting to eliminate the disease by destruction
of snails which can only be a practicable proposition in limited areas. 52
In Egypt, a large number of treatment centres w ere set up in an effort to control
the infection but less than 5% of the total number of infected persons wer e
treated each year. In 1933, Rose reviewed the effectiveness of this programme
and wrote:
complete unanimity exists among all Egyptian specialists. No influence on the mere
occurrence of the disease has been obtained by the present methods. But on the
contrary, no doubt exists that....the grave cases of urinary fistulae, the pyo- and
hydronephroses, the numerous urinary calculi, all these serious complications of
Egyptian schistosomiasis have greatly diminished in number. 178
Control based upon mass chemotherapy lay in the doldrums for man y
years. Recently the outlook has changed because of two factors. Firstly, more
effective and less toxic drugs have appeared. Secondly, it has been realize d
that among infected individuals in a population, a small number of person s

harbour a large number of worms, and it is these people who are at most risk
of developing disease and who make the greatest contribution to th e
contamination of the environment with miracidia. This has led to th e
introduction of "targeted mass treatment" in which only the heavily infecte d
persons are treated. This has been eva luated in schistomiasis mansoni 197; it has
the twofold aim of curing diseased persons and of reducing transmission ,
although the efficacy of the latter is yet to be proven.
Another approach was to attempt to improve sanitation. A major project
was undertaken by the Rockefeller Foundation and the Egyptian government
between 1928 and 1937 in which bore-hole latrines were introduced to rural
houses, but this measure alone had little effect.
All these measure are more likely to be succes sful if used concurrently with
health educational control programmes. Indeed, the best results are obtained
when there is integration of chemotherapy, snail control and propagand a
campaigns. Nevertheless, even th e most optimistic must doubt that these tech-
niques are likely to control, let alone eradicate, schistosomiasis in the nea r
future. Although the prospects of control by immunization have been touted 22,
the problem of schistosomiasis seems unlikely to go away unti l
socio-economic conditions improve to such an extent that provision of saf e
water supplies and constant usage of reliable waste disposal systems become
the norm in endemic areas.
REFERENCES
1. ABDEL-WAHAB MF, STRICKLAND GT, EL-SAHLY A, EL-KADY N, ZAKARIA S,

AHMED L. Changing patterns of schistosomiasis in Egypt 1939-1975. Lancet ii: 242-244,
1979
2. ADAMSON PB. Schistosomiasis in antiquity. Medical History 20: 176-188, 1976
3. ALBARRAN J, BERNARD L. Sur un cas de tumeur épithéliale due à la Bilharzia
haematobia, contribution à l'étude de la pathologie du cancer. Archives de Médecine
Expérimentale et d'Anatomie Pathologique 9: 1096-1123, 1897
4. ALLEN JF. Remarks on Bilharzia. Lancet ii: 51-53, 1882
5. ALLEN JF. Bilharzia haematobia. Lancet i: 660-661, 1883
6. ALLEN JF. Parasitic haematuria, or bloody urine. Practitioner 40: 310-320, 1888
7. ALLEN JF. Bilharzia haematobia and circumcision. Lancet i: 1317-1320, 1909
8. ALLEN JF. Bilharziosis and how to prevent it. Lancet ii: 375-376, 1910
9. ALVES W, BLAIR DM. Schistosomiasis: intensive treatment with antimony. Lancet i: 9-12,
1946
10. ANNANDALE N. Freshwater snails from Mesopotamia. Records of the Indian Museum 15:
No. 20. Abstracted in Tropical Diseases Bulletin 13: 200-201, 1919
11. ANNANDALE N. Notes on the genera Bullinus and Physa in the Mediterranean Basin
(Mollusca Pulmonata). Indian Journal of Medical Research 10: 482-491, 1922
12. ANONYMOUS. Endemic haematuria in Egypt. British Medical Journal ii: 275, 1882
13. ANONYMOUS. Special correspondence, Cairo. British Medical Journal ii: 1264, 1884
14. ANONYMOUS. British Medical Journal i: 916, 1885
15. ANONYMOUS. A newly differentiated parasite. Lancet ii: 640-641, 1893
16. ANONYMOUS. Endemic haematuria. Lancet i: 249-250, 1900
17. ANONYMOUS. The intermediate host in Bilharzia. Journal of Tropical Medicine and
Hygiene 18: 232-234, 1915
18. ANONYMOUS. Cited in 95
19. ANONYMOUS. Combined Intelligence Objectives Subcommittee File No. 25, vol. 54, 1945.
British Intelligence Objectives Subcommittee Final Report, vol. 116, 1946
20. ANONYMOUS. A century of schistosomiasis. Lancet i: 1223-1224, 1962
21. ANONYMOUS. Chemotherapy in schistosomiasis. British Medical Journal i: 128-129, 1972
22. ANONYMOUS. Immunological control of schistosomiasis. British Medical Journal ii:
366-367, 1972
23. ANONYMOUS. Menace of Man-made lakes. British Medical Journal i: 62-63, 1973
24. BALFOUR A. Endemic haematuria (Bilharzia). Wellcome Research Laboratory Report 1:
51-52, 1904
25. BARLOW CH. The effect of the "winterrotation" of water upon snails involved in the spread
of schistosomiasis in Egypt, 1930-1931 and 1931-1932. American Journal of Hygiene 17:
724-742, 1933
26. BARLOW CH. Is there dermatitis in Egyptianschistosomiasis? American Journal of Hygiene
24: 587-599, 1936
27. BARLOW CH, MELENEY HE. A voluntary infection with Schistosoma haematobium.
28. BAYLIS HA. The names of some molluscan hosts of the schistosomes parasitic in man.
29. BETTENCOURT A, BORGES I. Le Planorbis metidjensis, hôte intermédiaire du
Schistosoma haematobium au Portugal. Confirmation expérimentale. Comptes Rendus
Hebdomadaires des Séances et Mémoires de la Société de Biologie 87: 1039-1040, 1922
30. BILHARZ T. Fernere mittheilungen über Distomum haematobium. Zeitschrift für wissen-
schaftliche Zoologie 4: 454-456, 1853. Partly translated in 120
31. BILHARZ T. Distomum haematobium und sein Verhältniss zu gewissen pathologischen
Veränderungen der menschlichen Harnorgane. Wiener medizinische Wochenschrift 6: 49-65,
1856. Abstracted in 195
32. BILHARZ T, von SIEBOLD CT. Ein Beitragzur Helminthographia humana, aus brieflichen
Mittheilungen des Dr. Bilharz in Cairo, nebst Bermerkungen von Prof. C. Th. von Siebold
in Breslau. Zeitschrift für wissenschaftliche Zoologie 4: 53-76, 1852-1853 (distributed2
September 1852). Partly translated in 120
33. BLACKLOCK DB, THOMPSON MG. Human schistosomiasis due toS. haematobium in
Sierra Leone. Annals of Tropical Medicine and Parasitology 18: 211-234, 1924
34. BLAIR DM, HAWKING F, ROSS WF. The effect of Miracil D on human schistosomiasis.
Lancet ii: 911-912, 1947
35. BLANCHARD R. Traité de zoologie médicale. J-B Baillière et fils, Paris, 2 volumes, pp
1689, 1885-1890
36. BOUR FE. On numerous cases of oedema of the legs and albuminuria occurring in a
reformatory, with a contribution to the study of bilharziosis. Journal of Tropical Medicine and
Hygiene 15: 148150, 1912
37. BROCK GS. Anatomy and physiology of the Bilharzia ovum. Lancet ii: 622-625, 1893
38. BROCK GS. On the Bilharzia haematobia. Journal of Pathology and Bacteriology 2: 52-74,
1894
39. BRUMPT E. La ponte des schistosomes. Annales de Parasitologie Humaine et Comparée 8:
263297, 1930
40. CASTLE RF. Haematuria in East Central Africa. Lancet i: 931-932. 1891
41. CAWSTON FG. Schistosomiasis in Natal. Journal of Tropical Medicine and Hygiene 18:
257-258, 1915; Bilharziosis in Natal. British Medical Journal ii: 746,1915; Bilharziosis.
Lancet ii: 1427, 1915
42. CAWSTON FG. Report on the examination of 1,000 molluscs in Natal. Medical Journal of
South Africa 11: 197, 1916
43. CAWSTON FG. Schistosomes of man andbeast in Natal. South African Medical Record 18:
264, 1920
44. CAWSTON FG. Experimental infestation of freshwater snails. Transactions of the Royal
Society of South Africa 9: 301-303, 1921

45. CERF J, LEBRUN A, DIERICH XJ. A new approach to helminthiasis control: the use of an
organophosphate compound. American Journal of Tropical Medicine and Hygiene 11:
514-517, 1962
46. CHANDLER A C. Control of fluke diseases by destruction of the intermediate host. Journal
of Agricultural Research 20: 193-208, 1920
47. CHRISTOPHERSON J B. The successful use of antimony in bilharziosis administered as
intravenous injections of antimonium tartaratum (tartar emetic). Lancet ii: 325-327, 1918
48. CHRISTOPHERSON JB. Intravenous injections of antimonium tartaratum in bilharziosis.
British Medical Journal ii: 652-653, 1918
49. CHRISTOPHERSON JB. Antimony in bilharziosis. Lancet i: 79, 1919
50. CHRISTOPHERSON JB. Bilharzia disease: the sterilization of the ova during the course of
cure by antimony (tartrate). Journal of Tropical Medicine and Hygiene 23: 165-167, 1920
51. CHRISTOPHERSON JB. Longevity of parasitic worms: the term of living existence of
Schistosoma haematobium in the human body. Lancet i: 742-743, 1924
52. CHRISTOPHERSON JB. In, Forward to, Schistosomiasis vel bilharziasis, by C G Sharp, J
Bale, London, 1925
53. CLARKE V de V, BLAIR DM, WEBER MC. Field trial of hycanthone (Etrenol Winthrop)
in the treatment of urinary and intestinal bilharziasis. Central African Medical Journal 15:
1-6, 1969
54. COBBOLD TS. On some new forms of entozoa. Transactions of the Linnean Society of
London 22: 363-366, 1859
56. COBBOLD TS. Discussion of 102. Lancet l: 157, 1864
57. COBBOLD TS. On the development of Bilharzia haematobia together with remarks on the
ova of another urinary parasite (the so-called Trichina cystica of Dr. Salisbury) occurring in
a case of haematuria from Natal. British Medical Journal ii: 89-92, 1872
58. COBBOLD TS. Discussion of 150. British Medical Journal 11: 1000, 1882 and Lancet ii:
848, 1882
59. COBBOLD TS. Endemic haematuria in Egypt. Lancet ii: 272, 1882
60. COLES AC. The blood in cases affected with filariasis and Bilharzia haematobia. British
Medical Journal i: 1137-1138, 1902
61. CONOR A. Essais de transmission de la Bilharziose. Archives de l'Institut Pasteur, Tunis 9:
39-42, 1914, and Bulletins de la Société de Pathologie Exotique et de ses Filiales 7: 202-206,
1914
62. CURTIS BF. Partial resection of the bladder for ulcer caused by the Distoma haematobium.
63. DAVIS A, BILES JE, ULRICH AM. Initial experiences with praziquantel in the treatment
of human infections due to Schistosoma haematobium. Bulletin of the World Health
64. DAVIS A, WEGNER DH. Multicentre trials of praziquantel in human schistosomiasis:
design and techniques. Bulletin of the World Health Organization 57: 767-771, 1979
65. DAY HB. The out-patient treatment of bilharziasis, with an analysis of 1,000 cases. Lancet
i: 525529, 1921
66. DAY HB, RICHARDS O. The treatment of bilharziasis by salvarsan. Lancet i: 1126-1127,
1912
67. DESNOS E. Bilharziose vésicale traitée par les cautérisations diathermiques (haute
fréquence). Bulletin de l'Académie de Médecine 82: 37-40, 1918
68. DIAMANTIS. Sur un nouveau traitement de l'hématurie bilharzienne en Égypte. Journal
d'Urologie Médicale et Chirurgicale 7: 17-25, 1917
69. DIAMANTIS A. Considérations sur la chimiothérapie antibilharzienne en Égypte à propos
du "Fouadin Tolerance Test" du Prof. Khalil Bey. Journal of the Egyptian Medical
Association 21: 45-56, 1938
70. DIAMANTIS, LOTSY Bilharziose urétéro-vésicale precoce. Diagnostiquée par la
radiographie. Journal d'Urologie Médicale et Chirurgicale 7: 59-63, 1917
71. DIESING KM. Revision der Myzhelminthen. Abtheilung: Trematoden. Sitzungsberichte der
kaiserlichen Akademie der Wissenschaften in Wien. Mathematisch-naturwissenschaftliche
Classe 32: 307-390. 1858
72. DOUGLAS SR, HARDY FW. Some remarks on 50 cases of Bilharzia disease with special
reference to the characters of the white corpuscles found in the blood and urine. Lancet ii:
1009-1012, 1903
73. ELGOOD BS. Bilharziasis among women and girls in Egypt. British Medical Journal ii:
1355-1357, 1908
74. ELGOOD BS, CHERRY T. Bilharziasis: its incidence and eradication. Lancet ii: 636-637,
1919
75. ERFAN M, TALAAT S. Trivalent sodium antimony gluconate in the treatment of
schistosomiasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 44:
123-126, 1950
76. ERIAN A. The treatment of bilharziosis by massive doses of emetine. Practitioner 103:
391-393, 1919
77. FAIRLEY NH. Observations on the clinical appearances of bilharziasis in Australian troops
and the significance of the symptoms noted. Quarterly Journal of Medicine 12: 391-403,
1919
78. FAIRLEY NH. Bilharziasis: some recent advances in our knowledge. Lancet i: 1016-1021,
1919
79. FAIRLEY NH. The discovery of a specific complement fixation test for bilharziasis and its
practical application to clinical medicine. Journal of the Royal Army Medical Corps 32:
449-460, 1919
80. FAIRLEY NH. A comparative study of experimental bilharziasis in monkeys contrasted
with the hitherto described lesions in Man. Journal of Pathology and Bacteriology 23:
289-314, 1920
81. FAIRLEY NH, WILLIAMS FE. A preliminary report on an intradermal reaction in schisto-
somiasis. Medical Journal of Australia ii: 811-818, 1927
82. FARID Z, BASSILY S, SHULERT AR, ZEIND AS, McCONNELL E, ABDEL WAHAB
MF. Urinary blood loss in Schistosoma haematobium infection in Egyptian farmers.
Transactions of the Royal Society of Tropical Medicine and Hygiene 62: 496-500, 1968
83. FERGUSON AR. Associated bilharziasis and primary malignant disease of the urinary
bladder, with observations on a series of forty cases. Journal of Pathology and Bacteriology
16: 76-94, 1911
84. FISHER AC. The treatment of schistosomiasis with acriflavine. Lancet i: 897, 1934
85. FORSYTH DM, BRADLEY DJ. Irreversible damage by Schistosoma haematobium in
schoolchildren. Lancet ii: 169-171, 1964
86. FORSYTH DM, RASHID C. Treatment of urinary schistosomiasis. Practiceand theory.
Lancet i: 130-133, 1967
87. FOUQUET. Note sur le traitement des accidents produits chez l'homme par la présence dans
l'organisme de la Bilharzia. La France Médicale i: 667-680, 693-696, 1888
88. FRANÇA C. Bilharziose em Portugal. Medicina Contemporanea 39: 273-275, 1921
89. FRIEDHEIM EA. Le traitement de la bilharziose urinaire à S. haematobium par le
dimercaptosuccinate d'antimoine (TWSb). Bulletin de la Société de Pathologie Exotique 49:
1247-1252, 1956
90. FRIEDHEIM EA, da SILVA JR, MARTINS AV. Treatment of schistosomiasis mansoni
with antimony-a,a'-dimercapto-potassium succinate (TWSb). American Journal of Tropical
91. GADGIL RK. Human schistosomiasis in India. Indian Journal of Medical Research 51:
244-251, 1963
92. GADGIL RK, SHAH SN. Human schistosomiasis in India. Discovery of an endemic focus
in Bombay State. Indian Journal of Medical Science 6: 760-763, 1952
93. GAUD J, JAUBERTIE R. Rôle des facteurs humains dans la répartition géographique des
bilharzioses en Afrique. Annales de Parasitologie Humaine et Comparee 26: 420-439, 1951
94. GERRITSEN J, WALKER AR, de MEILLON B, YEO RM. Longterm investigation of
blood loss and egg load in urinary schistosomiasis in adult African Bantu. Transactions of
the Royal Society of Tropical Medicine and Hygiene 47: 134-140, 1953
95. GIRGES R. Schistosomiasis (bilharziasis), John Bale, Sons and Danielsson, London, pp
527, 1934
96. GÖNNERT R. Results of laboratory and field trials with the molluscicide Bayer 73.
Bulletin of the World Health Organization 25: 483-501, 1961
97. GÖNNERT R, ANDREWS P. Praziquantel, a new broadspectrum antischistosomal agent.
Zeitschrift für Parasitenkunde 52: 129-150, 1977
98. GÖNNERT R, SCHRAUFSTÄTTER E. A new molluscicide: Molluscicide Bayer 73.In,
Proceedings of the Sixth International Congress of Tropical Medicine and Malaria, Lisbon,
1958. Abstracts of the papers, Lisbon, Instituto de Medicina Tropical, vol. 2, p. 197, 1959
99. GORDON RM. Emetine periodide in the treatment of S. haematobium infections amongst
West African children. Annals of Tropical Medicine and Parasitology 20: 229-237, 1926
100. GRIESINGER W. Klinische und anatomische Beobachtungen. Über die Krankheiten von
Egypten. Archiv für Physiologie Heilkunde 13: 528-575, 1854. Partly translated in 120
101. GUILLEMARD FH. Bilharzia haematobia. Lancet i: 151, 1883
102. HARLEY J. On the endemic haematuria of the Cape of Good Hope. Medico-Chirurgical
Transactions 47: 55-72, 1864. Abstracted in Lancet i: 156-157, 1864
103. HARLEY J. A second communication on the endemic haematuria of the Cape of Good
Hope. Medico-Chirurgical Transactions 52: 379-387, 1869
104. HARLEY J. Third communication on the endemic haematuria of the southeastern coast of
Africa, with remarks on the topical medication of the bladder. Medico-Chirurgical
Transactions 54: 47-62, 1871. Abstracted in British Medical Journal ii: 641-642, 1870
105. HARLEY J. Discussion of, Cases of haematuria due to Bilharzia by TS Cobbold, presented
to the Royal Medical and Chirurgical Society. British Medical Journal i: 1097, 1885;
Lancet i: 985, 1885
106. HARRISON R. Specimens of Bilharzia affecting the urinary organs. Lancet ii: 163, 1889
107. HARRISON WS. The prognosis in bilharziasis. Journal of the Royal Army Medical Corps
21: 385-388, 1913
108. HATCH WK. Endemic haematuria. British Medical Journal ii: 737, 1882
109. HOEPPLI R. Morphological changes in human schistosomiasis and certain analogies ni
ancient Egyptian sculpture. Acta Tropica, Supplement 30: 1-11, 1973
110. HUGGINS D. Ineficácia do K-7505 (Ronnel) no tratamento da esquistossomíase
mansônica. Revista de la Sociedad Brasileira de Médica Tropica 2: 221-224, 1968
111. HULSE EV. Joshua's curse and the abandonment of ancient Jericho: schistosomiasis as a
possible medical explanation. Medical History 15: 376-386, 1971
112. HUMPHREYS RM. Vesical schistosomiasis in the Gezira irrigated area of the Sudan.
113. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. Thirty five
generic names in Protozoa, Coelenterata, Trematoda, Cestoda, Cirrepoda, Tunicata and
Pisces placed in the official list of generic names (Opinion 77), Smithsonian Miscellaneous
Collections, Smithsonian Institution, Washington, D C, Publication 2657, 73: 71-73, 1922
114. JAMES C, WEBBE G, NELSON GS. The susceptibility to praziquantel of S. haematobium
in the baboon (Papio anubis) and of S. japonicum in the vervet monkey (Cercopithecus
aethiops). Zeitschrift für Parasitenkunde 52: 179-194, 1977
115. JOANNIDES NZ. Die Wirkung des Salvarsans auf dieBilharzia. Deutsche medizinische
Wochenschrift 37: 1551, 1911
116. JORDAN P. Trial of Ambilhar, a nitrothiazole derivative, in S. mansoni infections in
Tanzania. British Medical Journal i: 276-278, 1966
117. JOYEUX C. Note sur quelques cas de bilharziose observés à Kouroussa (Guinea Française).
118. KATZ N, PELLEGRINO J. Ensaio laboratorial e clínico com hycanthone nôvo agente
esquistossomicida. Revista de la Sociedad Brasileira de Médica Tropica 1: 219-230, 1967
119. KATZ N, ROCHA RS, CHAVES A. Preliminary trials with praziquantel in human
infections due to Schistosoma mansoni. Bulletin of the World Health Organization 57:
781-785, 1979
120. KEAN BH, MOTT KE, RUSSELL AJ. Tropical medicine and parasitology. Classic

121. KHALIL M. The eradication of bilharziasis: a successful attempt in an endemic area. Lancet
ii: 1235, 1927
122. KHALIL M. Individual variation in the excretion of drugs as an important factor in their
therapeutic results. A practical method for detecting the schistosomiasis cases with so-called
idiosyncrasy to antimony to avoid fatalities and complications. Journal of the Egyptian
123. KHALIL M, AZIM MA. Further observations on the introduction of infection with
Schistosoma haematobium through irrigation schemes in Aswan Province. Journal of the
Egyptian Medical Association 21: 95-101, 1938
124. KHALIL M, BETACHE MH. Treatment of bilharziasis with a new compound "Fouadin".
Report on 2041 cases. Lancet i: 234-235, 1930
125. KHALIL M, NAZMI M, PETER FM, EL DIN MS, EL BETASH MH. Die Behandlung
der Schistosomiasis mit intramuskulären "Fuadin"-Injektion. Deutsche medizinische
Wochenschrift 55: 1125-1126, 1929
126. KHALIL M, SALAH, M. Treatment of schistosomiasis with acridine compounds. Lancet
ii: 862863, 1934
127. KIKUTH W, GÖNNERT R. Experimental studies on the therapy of schistosomiasis. Annals
of Tropical Medicine and Parasitology 42: 256-267, 1948
128. KIKUTH W. GÖNNERT R. Experimentelle Untersuchungen und Erfahrungen mit dem
neuen Schistosomiasismittel Miracil. Zeitschrift für Tropenmedizin und Parasitologie 1:
234-258, 1949
129. KITCHENER, LORD. Cited in 134
130. KLOCK JW, GERHARDT CE, ILDEFONSO V, SERRANO JM. Characteristics of
sodium pentachlorophenate used against Australorbis glabratus in Puerto Rico. Bulletin
of the World Health Organization 16: 1189-1201, 1957
131. LAMBERT CR. Chemotherapy of experimental Schistosoma mansoni infections with a
nitrothiazole derivative, CIBA 32,644-Ba. Annals of Tropical Medicine and Parasitology
58: 292-303, 1964
132. LAMBERT CR, FERREIRA FS. Résultats du premier essai de traitement de la bilharziose
vésicale par le CIBA 32,644-Ba. Bulletin of the World Health Organization 32: 73-82,
1965
133. LASBREY FO. COLEMAN RB. Notes on one thousand cases of bilharziasis treated by
antimony tartrate. British Medical Journal i: 299-301, 1921
134. LEIPER RT. Report on the results of the Bilharzia mission in Egypt, 1915. Journal of the
Royal Army Medical Corps 25: 1-55, 147-192, 253-267, 1915
Royal Army Medical Corps 27: 171-190, 1916
136. LEIPER RT. Tropical Diseases Bulletin 8: 610, 1916
140. LEIPER RT. Schistosome worms and schistosome monsters. British Medical Journal i: 817,
1931
141. LOOSS A. Beobachtungen über die Eier und Embryonen derBilharzia. In, Parasiten des
Menschen, R Leuckart (Editor), CF Winter'sche Verlagshandlung, Leipzig, volume 2, pp
521-528, 1893
142. LOOSS A. Bemerkungen zur Lebensgeschichte der Bilharzia haematobia. Centralblatt für
Bakteriologie und Parasitenkunde, Abteilung originale 26: 286-292, 340-346, 1894. Partly
translated in 134
143. LOOSS A. Histoire naturelle de la Bilharzia. Premier Congrès Égyptien de Médecine,
Comptes Rendus ii, Chirurgie, pp 3-18, 1905. Partly translated in 95
144. LOOSS A. What is Schistosomum mansoni Sambon 1907? Annals of Tropical Medicine
and Parasitology 2: 153-191, 1908
145. LOOSS A. Bilharziosis of women and girls in Egypt in the light of the "skin-infection
theory". British Medical Journal i: 773-777, 1909

146. LOOSS A. The life-history of the Bilharzia worm. Cairo Scientific Journal 4: 134, 1910
147. LOOSS A. Würmer und die ihnen hervorgerufenen Erkrankungen. In, Handbuch der
Tropenkrankheiten, second edition, C Mense (Editor), J A Barth, Leipzig, volume 2, pp
148. LORTET A. Expériences nouvelles sur le développement et le mode de pénétration du
Bilharzia haematobia. Premier Congrès Égyptien de Médecine, Comptes Rendus ii,
Chirurgie, pp 129-131, 1905
149. LORTET, VIALLETON. Étude sur le Bilharzia haematobia et la bilharziose. Annales de
l'Université de Lyon 9: 1-118, 1894
150. LYLE V. On the endemic haematuria of the southeast coast of Africa, with an introduction
by John Harley. Medico-Chirurgical Transactions 66: 113-132, 1883. Abstracted in British
Medical Journal ii: 1000, 1882; Lancet ii: 848, 1882
151. McDONAGH JE. Antimony in bilharziosis. Lancet ii: 371, 1918
152. McDONAGH JE. The treatment of bilharziasis with antimony. Journal of Tropical
153. MADDERN FC. The incidence of bilharziosis in Egypt and its clinical manifestations.
154. MANSON P. Discussion of 73. British Medical Journal ii: 1357, 1908
155. MANSON P. Tropical diseases. A manual of the disease of warm climates, fifth edition,
Cassell and Co., London, pp 922, 1914
156. MANSON-BAHR P, FAIRLEY N H. Observations on bilharziasis amongst the Egyptian
Expeditionary Force. Parasitology 12: 33-71, 1920
157. MANTEY. Distomum haematobium. Die durch dasselbe hervorgerufenen Krankheiten und
deren Behandlung. Dissertation, Jena, pp 30, 1880
158. MAYER M. Behandlung der Bilharziakrankheit mit Emetin. Münchener medizinische
159. MAYER M. Zur Behandlung der Bilharzia-Krankheit mit Emetin. Wiener klinische
160. MILTON F. Bilharziosis surgically considered. Lancet i: 866-869, 1903
161. MILTON F. Speculations on the life-history of Schistosomum haematobium. Journal of
162. MINET H. Deux cas de bilharziose vésicale provenant de l'Afrique septentrionate française.
Annales des Maladies Vénériennes 10: 385-396, 1915
163. MOORE N. Discussion of 205. British Medical Journal i: 13, 1882 and Lancet i: 16, 1882
164. MOQUIN-TANDON A. Elements of medical zoology, translated by R T Hulme, Baillière,
165. MOZLEY A. Malachite in the control of bilharzia. British Medical Journal i: 511, 1941
166. NABAWY M, GABR M, RAGAB MM. Visceral bilharziasis in childhood: a
clinico-radiological study. Journal of Tropical Medicine and Hygiene 64: 314-318, 1961
167. NELSON GS, TEESDALE C, HIGHTON RB. The role of animals as reservoirs of
bilharziasis in Africa. In, Bilharziasis, Ciba Foundation Symposium, GE Wolstenholme and
M O'Connor (editors), Little Brown, Boston, pp 127-148, 1962
168. PAPYROS EBERS. Das hermetische Buch über die Arzneimittel der alten Aegypter ni
hieratischer Schrift Herausgegeben, mit Inhaltsangabe und Einleitung versehen von Georg
Ebers. Mit hieroglyphisch-lateinischem Glossar von Ludwig Stern, Leipzig, two volumes,
1875. The Papyrus Ebers, translated from the German version by C P Bryan, Geoffrey Bles,
169. PELLEGRINO J, KATZ N, SCHERRER JF. Oogram studies with hycanthone, a new anti-
schistosomal agent. Journal of Parasitology 53: 55-59, 1967
170. PELLEGRINO J, LIMA-COSTA FF, CARLOS MA, MELLO RT. Experimental
chemotherapy of schistosomiasis mansoni. XIII. Activity of praziquantel, an
isoquinoline-pyrazino derivative, in mice, hamsters and Cebus monkeys. Zeitschrift fur
Parasitenkunde 52: 151-168, 1977
171. PETERS PA, MAHMOUD AA, WARREN KS, OUMA JH, SIONGOK TK. Field studies
of a rapid accurate means of quantifying Schistosoma haematobium eggs in urine samples.

172. PFISTER F. Über die - - Krankheit der Papyri Ebers und Brugsch. Archiv für Geschichte
der Medizin 6: 12-20, 1912
173. PILSBRY HA, BEQUAERT J. The aquatic molluscs of the Belgian Congo. With a
geographical and ecological account of Congo malacology. Bulletin of the American
Museum of Natural History 53: 69-602, 1927
174. PORTER A. The experimental determination of the vertebrate hosts of some South African
cercariae from the molluscs Physopsis africana and Limnaea natalensis. Medical Journal
of South Africa 15: 128-133, 1920
175. PORTER A. Some flukes bred from cercariae recurring in Schistosoma-transmitting
molluscs in South Africa. Proceedings of the Royal Society of Medicine 18: 56-57, 1925
176. RENOULT AJ. Sur l'hématurie que les Européens éprouvent en Égypte. Journal Général
de Médecine de Chirurgie et de Pharmacie 17: 366-370, 1803. Partly translated in Medical
Times, New York 90i: 447-452, 1962
177. ROBERTSON W. Thymobenzene in bilharziosis. Lancet i: 698, 1916
178. ROSE G. Schistosomiasis in Egypt and its bearing on the schistosomiasis problem in China.
Chinese Medical Association Special Report Series No. 2, pp 86, no date. Abstracted ni
Tropical Diseases Bulletin 34: 864-866, 1937
179. RUBIDGE. Cited in 103.
180. RUFFER MA. Discussion of 73. British Medical Journal ii: 1356, 1908
181. RUFFER MA. Note on the presenceof "Bilharzia haematobia" in Egyptian mummies of the
twentieth dynasty (1250-1000 B.C.). British Medical Journal i: 16, 1910
182. SCHRECKER. Ueber Salvarsanbehandlung bei Bilharziosis. Archiv für Schiffs- und
TropenHygiene 19: 149-150, 1915
183. SENN E. Theodor Bilharz. Ein deutsches Forserchleben in Ägypten 1825-1862. Schriften
des Deutschen Ausland-Instituts Stüttgart. Reihe D: Biographien und Denkwurdigkeiten.
Ausland und Heimat Verlags-Aktiengelleschaft, Stüttgart, Band 5, pp 76, 1931. Abstracted
184. SHAW CG. Cystoscopic appearances in bilharziosis. Medical Journal of Australia i: 85-86,
1921
185. SIGERIST HE. A history of medicine. Volume 1. Primitive and archaic medicine. Oxford
University Press, New York, pp 564, 1951
186. SONSINO P. Ricerche intorno alla Bilharzia haematobia in relazione colle ematuria
dell'Egitto e nota intono ad un nematoidea. &c. Rendiconti della Reale Accademia di Napoli
6: 71-83, 305321, 1874. Partly translated in 95
187. SONSINO P. Ricerche sullo sviluppo della Bilharzia haematobia. Giornale della Reale
Accademia di Medicina di Torino 32: 380-395, 1884. Partly translated in 95
188. SONSINO P. The treatment of Bilharzia disease. British Medical Journal ii: 1197-1198,
1885
189. SONSINO P. Discovery of the life history of Bilharzia haematobia (Cobbold). Lancet ii:
621-622, 1893
190. SONSINO P. Aggiunta alla precedente nota sulla sviluppo della Bilharzia haematobia.
Processi Verbali della Società Toscana di Scienze Naturali in Pisa, January 21, pp 10-14,
1894
191. STOCK PG. Endemic haematuria. Lancet ii: 857-858, 1906
192. TALAAT SM, AMIN N, EL MASRY B. The treatment of bilharziasis and other intestinal
parasites with dipterex. A preliminary report on 100 cases. Journal of the Egyptian Medical
Association 46: 827-832, 1963
193. TSYKALAS. Neue Wege in der Behandlung der Bilharziakrankheit in Aegypten. Wiener
klinische Wochenschrift 34: 579-580, 1921
194. TSYKALAS. Erwiderungen auf obige Bemerkingen des Prof. Martin Mayer. Wiener
klinische Wochenschrift 35: 60, 1922
195. WARREN KS. Schistosomiasis. The evolution of a medical literature: selected abstracts and
citations, 1852-1972, MIT Press, Cambridge, Massachussetts, pp 1307, 1973
196. WARREN KS. Regulation of the prevalence and intensity of schistosomiasis in man:
immunology or ecology? Journal of Infectious Diseases 127: 595-609, 1973
197. WARREN KS, MAHMOUD AA. Targeted mass treatment: a new approach to the control
of schistosomiasis. Transactions of the Association of AmericanPhysicians 89: 195-204,
1976
198. WATKINS-PITCHFORD W. Note on schistosomiasis. Medical Journal of South Africa 10:
226, 1915
199. WATSON JM, ABDEL AZIM M, HALAWANI A. Investigations on the antibilharzial
actions of Miracil D (Nilodin). Transactions of the Royal Society of Tropical Medicine and
Hygiene 42: 37-54, 1948
200. WEBBE G. Schistosomiasis: some advances. British Medical Journal ii: 1104-1106, 1981
201. WEBBE, G, JAMES A. A comparison of the susceptibility to praziquantel of S.
haematobium, S. japonicum, S. mansoni, S. intercalatum and S. mattheei in hamsters.
202. WEINLAND DF. Human cestoides. An essay on the tapeworms of man giving a full
account of their nature, organization, and embryonic development; the pathological
symptoms they produce, and the remedies which have proved successful in modern practice.
To which is added an appendix, containing a catalogue of all species of helminthes hitherto
found in man, Metcalfe and Co., Cambridge, Massachussetts, pp 93, 1858
203. WILEY CJ. The treatment of bilharziosis by intravenous injections of tartar emetic. British
204. WOLFF. Ueber Bilharzia in Deutsch-Ostafrika. Archiv für Schiffs- und Tropen-Hygiene
13: 167, 1909
205. ZANCAROL G. A specimen of Bilharzia haematobia, with ova in the tissues of the bladder
and large intestine. Transactions of the Pathological Society of London 33: 410-412, 1882.
Abstracted in British Medical Journal i: 13, 1882; Lancet i: 16, 1882
Table 8.1. Landmarks in schistosomiasis haematobia

___________________________________________________________________
1851 Bilharz discovered adult worms

1852 Bilharz and Griesinger identified urinary lesions
1852 Bilharz diagnosed urinary schistosomiasis in a living patient by finding eggs
in the urine
1866 Rubidge suggested on clinical and epidemiological grounds that infection was
acquired by bathing in certain rivers
1889 Harrison suggested a relationship between vesical schistosomiasis and
bladder cancer
1915 Leiper discovered that certain species of snails were chemotactic for S.
haematobium miracidia, observed development of the parasite through the
sporocyst to the cercarial stage in these molluscs, and produced patent
infections in rodents and monkeys with cercariae derived from naturally
infected snails that were collected in an area heavily endemic for
schistosomiasis
1916 Leiper confirmed the differentiation of S. haematobium and S. mansoni
1917 Diamantis reported the value of emetine in treatment
1918 Christopherson reported the efficacy of tartar emetic
1944 Barlow produced a patent infection in himself after placing cercariae on his
skin
1940's Kikuth and Gönnert showed that miracil D had schistosomicidal activity in
experimentally infected animals
1947 Blair, Hawking and Ross reported that miracil D was effective in humans
1962 Cerf, Kebrun and Dierich reported that metrifonate was effective
1964 Lambert and Ferreira reported that niridazole was active
1969 Clarke, Blair and Weber showed that hycanthone was effective
1977 Various investigators reported that praziquantel was effective against
schistosomes in experimental animals
1979 Davis, Biles and Ulrich reported that praziquantel was effective in humans
__________________________________________________________________
Chapter 9
Schistosoma mansoni and SCHISTOSOMIASI S

MANSONI
SYNOPSIS
Common name: intestinal blood fluke; causes intestinal schistosomiasis or bilharziasis

Major synonyms: Distoma haematobia, Schistosoma haematobia
Distribution: Africa, South America, Caribbean islands
Life cycle: Similar to S. haematobium except that the vectors belong to the genus
Biomphalaria and eggs are excreted in the intestines
Definitive hosts: humans (baboons, monkeys)
Major clinical features: rash followed by urticaria, dysentery and hepatosplenomegaly
in early, heavy infections; hepatosplenomegaly, ascites and oesophageal varices in
chronic, heavy infections
Diagnosis: demonstration of eggs in faeces, rectal mucosa or liver biopsy
Treatment: hycanthone, niridazole, oxamniquine, praziquantel
ATTEMPTS TO DIFFERENTIATE SCHISTOSOMA MANSONI FROM

S. HAEMATOBIUM
In 1851, soon after he had discovered the adult forms of S. haematobium

and had seen their ova with the charact eristic terminal spines, Theodor Bilharz
found near S. haematobium eggs in calcified areas of a liver "strange bodies
provided with spines, approximately similar to those eggs in size" 13. Although
the illustration he provided is har dly recognizable as that of an S. mansoni egg
shell, his accompanying description leaves little doubt that the bodies he was
seeing were remnants of S. mansoni ova, for he wrote:
They seemed to me to be long, yellow-brown bodies rounded on both ends. On one
side, near the more rounded end was a conical appendage, directed obliquely toward
the pointed end. No content was recognizable in these strange bodies. 13
In March of the following year, he found the same structures in a portion o f
dysenteric large intestine removed from t he body of a boy who also had vesical
schistosomiasis and had died from meningi tis. They were scattered through the
mucosa and submucosa as well as being embedded in bloody mucus on th e
surface of the mucosa. Bilharz's description of these bodies again indicates that
these were S. mansoni eggs: "These bodies, compressed from all sides, ar e
biconvex with a sharp edge from which the conical appendage protrudes" 13.
233
These structures were empty apart from a few granules massed against th e
inner edge. A few days later, however, Bilharz's colleague, Wilhel m
Griesinger found the same bodies in a piece of large bowel, but on thi s
occasion, they contained living o rganisms which crawled out and swam about,
resembling S. mansoni miracidia. This naturally led Bilharz to put th e
question: "Therefore, how should we regard these bodies. Are they a second
type of egg or a kind of pupal covering assumed by the organism after leaving
the egg?"13
As discussed in chapter 8, Bilharz came down in favour of the latte r
proposition. There were two reasons for this. Firstly, he found S. haematobium
eggs and these bodies intermingled in the tissues. Secondly, and mor e
importantly, Bilharz believed that he had seen the same structure within a n
adult female S. haematobium:
Last summer I found one of these bodies in one of the first female specimens of
Distomum haematobium that I studied. It was in the front part of the oviduct, the
posterior of which contained the usual egg. I made a drawing of that specimen at that
time.13
Since he had seen this phenomenon only once, he surmised that the specimen
in the oviduct had metamorphosed abnormally early. This erroneou s
observation was to set the scene for confus ion and controversy for the next half
century as to whether there were one or two species of schistosomes tha t
infected humans in Egypt. Bilharz, in forthright terms, left no doubt as to his
views:
That these shells belong to the developmental stages of Distomum haematobium
and not to another organism seems indubitable to me. I not only found them
intermixed with eggs of Distomum haematobium in the calcified areas within the
liver, in the submucosa, and in the mucosa of the large intestine in acute dysentery,
but also, although only once, in the oviduct of a female worm which also contained
ordinary eggs.13
Proof that the bodies which occ upied Bilharz's mind were indeed egg shells of
S. mansoni was, in retrospect, provided in 1853. In a letter to von Siebol d
dated 4 January of that year, Bilharz included a drawing of a "capsule" which
is clearly the shell of a lateral-spined S. mansoni ovum12. Griesinger accepted
Bilharz's contention completely, for in the legend accompanying an illustration
in his paper of a typical S. mansoni egg, he wrote:
saclike bodies provided with a lateral spike (eggs? pupal coverings?); in any case,
belonging to the developmental cycle of the Distoma haematobium, since such a
body was once found in the fallopian tube of the organism. 43
As mentioned in the previous chapter, Harley in 1864 was so struck by the
complete absence of lateral-spined ova in the urine of patients with endemic
haematuria in South Africa that he was induced to name the parasite in tha t
region Distoma capense 44. Sonsino then suggested that schistosomiasis was
caused by two different species of worms, each producing characteristic ova
which differed in the position of their spine, but later abandoned this thesis in
favour of the postulate that one f orm of egg developed into a male worm while
Schistosomiasis mansoni 235
the other became a female schistosome.

It gradually became clear to invest igators in Egypt that different types of egg
were associated with different dise ases. Thus, in 1882, Dr Zancarol, a surgeon
at the Greek Hospital in Alexandria, demonstrated to the Royal Medical and
Chirurgical Society in London microscopical sections of vegetations from the
large bowel of an Arab who had suffered from dysentery and noted that "as is
usual when occurring in this situation, (the ova) were each provided with a
large lateral spine" 124. He also exhibited sections from the bladder of another
patient and remarked that "each ovum was provided with a spine, but here its
situation was terminal and not lateral" 124. Even so, both conditions wer e
attributed to infection with S. haematobium.
Zancarol's views were supported in the same year by James Mackie ,
surgeon to the British consulate and Dea conesses' Hospital in Alexandria, who
wrote:
in my own experience the ova found in the rectum have in nearly all cases the spike
placed laterally differing from those generally found in the urine, which have the
spike at the extremity.78
Spencer Cobbold was not convinced, however, fo r when he presented 13 cases
to the Royal Medical and Chirurgical Society in 1885, he attributed no path-
ological or clinical significan ce to the remarkable variations in the appearance
of schistosome eggs 19.
For many years, it was believed that schistosomiasis was restricted to Africa
and adjacent regions. In 1902, however, Patrick Manson in England reported
that a 38 year old British patient of his had contracted the infection in the West
Indies where he had lived for 15 ye ars. The patient complained of vague aches
and pains, and since he looked anaemic, Manson examined his stool s
expecting to find hookworm eggs, but instead found schistosome ova. Further-
more, he remarked that "In this ca se, as so often happens in bilharzia ova from
the alimentary canal, the spine is placed laterally" 81. Microscopical
examination of the urine disclosed no ova.
Thus, whereas schistosomiasis in Egypt was hopelessly intermingled with
urinary and intestinal pathology and eggs with terminal or lateral spines, there
were now cases on record exemplifying the two poles of the spectrum -
patients with urinary schistosomiasis and terminal-spined eggs as describe d
by Harley, and patients with intestinal eggs with lateral spines as shown b y
Manson. In fact, Manson in this paper made no great play about the egg s
having a lateral spine; rather, he was concerned to suggest that a mollusc or
arthropod common to both African and American regions might be the long
sought for intermediate host. In the following year, however, he put forward
the suggestion that:
possibly there are two species of Bilharzia, one with its lateral-spined ova, depositing
its eggs in the rectum only, the other haunting bladder or rectum indifferently. 82
Impetus to the idea that there may be more than one species of schistosome
infecting humans was given by the discovery of S. japonicum by Katsurada in
Japan in 1904 (see chapter 10). Manson's view was then championed by Louis
Sambon, a lecturer at the London School of Tropical Medicine. Putting al l
these thoughts together, he proposed at a meeting of the Zoological Society of
London on 19 March 1907 that the worm producing lateral-spined eggs b e
named Schistosomum mansoni 102. He so named the parasite in recognition of
Manson's earlier suggestion that there may be two species of Africa n
schistosomes: "In appreciation of this, one of his many genial intuitions, th e
new Trematode is dedicated to him"103. Sambon justified his creation of a new
species on the grounds of difference s in the morphology of the eggs, variations
in the clinical manifestations, and dissimilar geographical distributions o f
infection:
the ova of the new species have a large, curved, lateral spine which distinguishes
them from those of the old classic species with a short, straight spine at their posterior
extremity....S. mansoni ova are eliminated solely by way of the intestine....The
patients harbouring this parasite suffer from a haemorrhagic enteritis, but they never
present haematuria....S. mansoni has a wide distribution throughout Africa....It is
found also in the West Indies....and very likely in other places within the Tropics. 103
Sambon reiterated these points later in the year in a further communication ,
remarking on this occasion that although adult schistosomes of humans an d
cattle were very similar in general appearance, with the exception of the male
S. japonicum, he had no doubt that a minute comparative anatomical study of
these worms would bring out info rmation about many structural differences 104.
To further support his argument, Sambon drew attention to the report in July
of that year by Holcomb of a large number of cases of schistosomiasis wit h
lateral-spined eggs in the Caribbean, including no less than 167 cases i n
Puerto Rico, yet endemic haematuria was completely unknown 47.
Sambon's new species met with a vitriolic blast from Looss in a 39 pag e
paper entitled "What is Schistosomum mansoni Sambon 1907?". He
introduced his paper by remarking that:
if Dr. Sambon's view were correct, all of us who have devoted attention to the
subject, would have indeed been wandering in the dark since the time of Bilharz
himself, fiftyseven years ago.73
And indeed, some of them, with Looss amongst them, were. Looss was th e
arch protagonist of two controversial theories - the direct infection hypothesis
and the single species stance - both of which he was destined to lose. Afte r
bemoaning the fact that no notice had been taken of the (vague an d
unspecified) cautionary "hints" that he had "dropped" while in London tw o
years earlier (but precisely to wh om he could not remember), Looss castigated
Sambon's credentials saying:
Among scientific workers, it is a good custom that anyone who believes he has made
a new discovery also takes the trouble to prove it; it is not customary among scientists
to assert something then call for the help of others to establish it. 73
He then launched into an attack on Sambon's propositions. Looss's arguments
were centred on the following b ases. Firstly, he insisted that the differentiation
of species could only be made on the morphology of the adult worms, not on
the appearance of the eggs. The foun dation stone of Looss's faith was Bilharz's
statement that he saw both types of eggs in one worm. He then adde d
sarcastically:
This observation is now fifty seven years old and might have been known to Dr.
Sambon if he had studied of those authors who he accuses of having failed to
recognise an obvious fact.73
Looss then remarked that if his memory did not fail him, he had seen several
similar female worms during the course of the years, and regretted that h e
could not produce them. Nevertheless, to let it be absolutely clear where h e
stood, he reiterated:
The occurrence of terminal-spined and lateral-spined eggs in one and the same
individual worm is one of the fundamental facts on which my views rest; I wonder
how Dr. Sambon will explain it by his theory.73
Looss thought that the position of the spine depended upon the position of the
egg during the process of its formation in the ootype. Extrapolating from his
observations on a number of trematodes, Looss deduced that lateral-spine d
eggs were abnormal and were probably produced by unfertilized femal e
worms. He explained the presence of a miracidium in some of these eggs as
being the result of a process of parthenogenesi s. Secondly, Looss dismissed the
differing clinical and pathological pictures associated with the two forms o f
eggs on the basis of variations in the habits of the human host and th e
conditions of the country. He produced an amazing and intricate hypothesi s
based upon the supposition that mirac idia were infective directly, and that they
developed into sporocysts in the liver. He postulated that when the infecting
dose of miracidia was high, there would be plenty of male worms present to
carry the females off to the vesical venous plexus where they produce d
terminal-spined eggs and caused urinary schistosomiasis. In contrast, h e
suggested that when the infecting dose was low, solitary females sometime s
developed, that these spinsters produced lateral-spined eggs, and that thes e
lonely worms sometimes migrated as far as the large intestine. Moreover ,
Looss believed that there was not a sharp line of demarcation between these
two responses. Finally, Looss contended feebly that the differences i n
geographical distribution of the two forms of parasite and disease cited b y
Sambon were based "upon a peculiarly one-sided interpretation of th e
literature" 73. Looss concluded his lengthy paper:
there is no possible doubt....that this species....must produce the same two shapes of
eggs as does the Sch. haematobium....If, therefore, Dr. Sambon wishes to maintain
that there is an independent "Sch. mansoni"....the entire proof of its existence
remains to be given.73
In January of the following year (1909), Sambon replied to Looss' s
criticisms in a long article with the same title as that used by Looss 105. He
began by saying that he ought to have refuted Looss's "critical", "violent" and
"ill-considered" paper at once, but he had delayed in the hope that someon e
would be able to describe distinctive morphological features for adul t
S. mansoni. Since this had not yet been done, he now found it necessary t o
reply lest his silence be interpre ted wrongly. Sambon let it be clear that he had
the utmost regard for the eminent scientist who had studied helminthology in
Egypt during the previous 25 years, but tempered this by remarking that :
"Respect for authority is one thing, slavish submission to authority i s
another"105. Sambon then proceeded to counter Looss's arguments point b y
point. He insisted that the marked differences in the morphology of the eggs
were quite sufficient to estab lish a new species, quoted precedents established
by zoologists, and asserted that Looss himself had subscribed to new species
on much flimsier grounds. Conce rning Bilharz's alleged discovery and Looss's
vague confirmation of two forms of egg within the one adult worm, Sambon
declared:
Until he can show me an actual specimen I am bound to place the worm capable of
producing the two kinds of eggs with the phoenix, the chimaera and other mythical
monsters.105
He then demolished Looss's dismissal of the different clinico-pathologica l
effects associated with the two forms of worms, demonstrating that Looss' s
views were a: "multitude of surmises and conjectures more or les s
improbable"105 and adding nastily: "But Professor Looss has a theory, an d
theories often require a careful selection of the facts" 105. Sambon then
re-emphasized the different geographical distributions of S. mansoni and
S. haematobium. He noted that large numbers of patients in certain region s
passed vast numbers of lateral-spined eggs, yet not a single terminal-spine d
ovum could be found, and questioned how this could possibly be consisten t
with Looss's idea that they were a product of unfertilized female worms - there
would have to be an entire absence of ma le schistosomes. Further, he reasoned
that explaining all these lateral spines on the basis of abnormality an d
parthenogenesis bordered on absurdity. Next, Sambon showed that he had not
distorted the literature; rather, it was likely that the several patients wit h
urinary schistosomiasis in America that Looss had referred to, had acquire d
their infection in Africa, and there was no doubt that urinary schistosomiasis
alone occurred in southern Africa. Finally, he stood his ground and declared:
I never for a moment placed myself on the same level in the latter respects (as a hel-
minthologist) with the celebrated professor of Cairo, but at the same time I would say
that I have paid some attention to the subject, and cannot abandon my independence
of judgement, or my right to give expression to my views. 105
Two years later (1911), stung by Sa mbon's objections, Looss returned to the
debate. He had concluded on the basis of further observations that it was not
necessary to invoke parthenogenesis. Instead, he postulated that unfertilized
eggs are laterally spined, and that after fertilization, there is a "transitio n
period" following which the eggs become terminally spined. He had th e
impression that once the production of normal (terminal-spined) eggs ha d
begun, the others (lateral-spined) were usually evacuated quickly, bu t
reiterated: "that the females of S. haematobium can, and do, produce two
forms of eggs is beyond question, even now" 74.
While all this was going on, a number of workers, particularly in th e

Americas, had embarked upon a search for characteristic morphologica l
features of worms producing lateral-spined eggs which would allow definite
distinction of S. mansoni from S. haematobium. Holcomb, an assistant
surgeon with the US Navy, in 19 07 examined material from patients in Puerto
Rico and thought that the male worms were more brown in colour and had a
larger ventral sucker 47. In the following year (1908), Pirajá da Silva in Brazil
recovered 24 worms, including both sexes, from the portal venous system of
a single cadaver; all these worms produced only lateral-spined eggs. Pirajá da
Silva, who was an assistant in internal medicine at the Santa Isabel Hospital
in Bahia, described a number of features of the adult worms which he thought
were distinctive. These included differences in the outlines of the anterior end
of the male worm and the posterior end of female schistosomes, less salien t
spinous papillae, a more distal location of the caecum, and subtle differences
in the structure of the female reproducti ve organs when compared with Looss's
figures of S. haematobium. He first published these opinions in Portuguese in
190892, then amplified them in English 93 and in French 94 in the following year.
Also in 1908, Leiper studied material from Uganda and thought that ther e
were differences in the shape of the testes 69, although in a letter to Pirajá d a
Silva in February 1909 he wrote:
I regret that so far I have not been able to separate the Schistosomum haematobium
from the Sch. mansoni in the specimens I have received from abroad and I cannot
therefore send you types of each. Both forms occur in Egypt and we in Europe get
the worms from the portal veins and these may be one or the other of the two forms
and so far we know no way of differentiating them. 70
In fact, at that stage, Leiper lea ned towards Looss's unitarian view, for he went
on to say:
There is a good deal too much theory alike in Looss' as in Sambon's position. I mean
they require more facts. I studied for a year under Professor Looss and saw enough
of his work to feel more reliance on his observations than on those of Dr. Sambon
but I have not yet made up my mind finally on the subject. 70
Similarly, Flu (1911) thought that there were differences in the formation of
the anterior part of the gynaecophoric canal of the two parasites 36.
To all of this, Looss replied that each and every one of these features could
be seen in in Egypt. Pirajá da Silva received the full force of Looss's wrat h
when he wrote vitriolically:
Thus Pirajá da Silva's 'proof' of the existence of a 'second species' of Schistosomum
becomes reduced to a combination of several very elementary mistakes; what the
conclusions based on such evidence are worth scientifically, every reader is at liberty
to decide for himself. But am I to be blamed if I urge that authors, before they write
on parasitological questions, should make themselves acquainted with the parasites
they deal with.74
Moreover, Looss tried to ridicule da Silva by claiming that the ova that h e
described were nothing more than concretions. In April 1912, Pirajá da Silva
presented his findings to the German Society of Tropical Medicine i n
Hamburg. The subsequent discussion has been published by de Cerquier a

Falção who has championed da Silva's cause in a paper entitled "Professo r
Pirajá da Silva, incontestable discoverer of 'Schistosoma mansoni'" 18.
Parenthetically, it ought to be re marked that while it is true that Pirajá da Silva
did discover S. mansoni adult worms in Brazil, de Cerqueira Falção ha s
ignored the fact that Holcomb e had described adult S. mansoni in Puerto Rico
before Pirajá da Silva, and that many observers had doubtless seen S. mansoni
adults in Africa, although they did not recognize them as such. But returning
to Pirajá da Silva in Hamburg:
"Pirajá faced with courage and firmness the giant Looss stating....'I was afterwards
contested with energy by Prof. Looss: the eggs I observed in the uterus of the female
Schistosoma were considered by him as mere concretions, although he had never
seen my slides. Gentlemen: I am not a zoologist but I have for many years dealt
exclusively with helminths; being a physician, I based myself on my own
observations. A wrong interpretation of the microscopic aspect of my slides might
have occurred. However, in spite of Looss's authority, I am not ready to admit such
a mistake to have been made. I have now the pleasure to emphasize that in the course
of careful and repeated investigations on some 100 cases of bilharziasis in Bahia, I
could never find one single egg bearing a terminal spine....Our best clinicians are
unable to report on any bladder affection as being due to Schistosoma....In Bahia,
bilharziasis is a disease affecting exclusively the lower portion of the intestines,
extending into the liver.95
It is with these last remarks that Pirajá da Silva probably put his finger on the
deficiency in Looss's armamentarium that prevented him from seeing the truth.
Both Sambon and Pirajá da Silva were physicians and were impressed by the
marked pathological, clinical and diagnostic differences between urinary and
intestinal schistosomiasis. When put together with the variations in th e
morphology of the eggs and in the geographical distributions of the two forms
of schistosomiasis, there was no doubt in their minds that there were tw o
species of schistosomes. Looss, on the other hand, was not a clinician an d
failed utterly to appreciate th e completely different responses of humans to the
two species of parasites. Thus, an impasse was reached, and it remained for
Leiper in his studies of the life cycle of schistosomes to prove beyond all doubt
that the two species were separate.

HOST AND PROOF OF THE EXISTENCE OF S. MANSONI
By the middle of 1915, Leiper was convinced that schistosomiasis in Egypt,

whether due to one or two species, was transmitted by the mediation of certain
snail intermediate hosts. The events that led up to this discovery have bee n
described in chapter 8. Furthermore, it was this achievement which enabled
him to differentiate definitively between S. mansoni and S. haematobium.
Shortly before Leiper left Egypt for Europe in July 1915, a mouse which had
been infected with cercariae from Planorbis boissyi (now known as
Biomphalaria alexandrina) died. This mouse was infected with adult schisto-
somes, and although only two or three eggs were seen, they were all laterally
spined. According to Looss's later theory, they were abnormal products in the
transitional phase of young sexually matu re worms of S. haematobium, where-
as according to Sambon, they indicated that the adult worm was S. mansoni.
On Leiper's reaching London, he found that four monkeys, also infected with
cercariae from P. boissyi, also began to pass lateral-spined eggs in August, but
they died within a fortnight from an overwhelmingly intense infection .
Similarly, in rats infected with P. boissyi-derived cercariae, only laterall y
spined eggs were found. Leiper had also infected some animals very lightl y
with cercariae from Bulinus (known to Leiper as Bullinus) snails in the hope
that some of these animals would live long enough to permit the testing o f
potential anthelmintics. Unfortunately, the infection was so light that no worms
were found in any of these animals.
In October of that year, Leiper reviewed the position and realized that h e
needed to infect animals lightly with cercariae from P. boissyi so that they
would survive for several months and thus enable the female schistosomes to
pass through Looss's hypothetica l "transition period". Secondly, another group
of animals had to be infected heavily with cercariae from Bulinus in order to
establish the specific nature of this form of parasite. Accordingly, he returned
to Egypt in November 1915 and infected monkeys orally and mice, rats and
monkeys percutaneously. The smaller animals were killed weekly in order to
assess the mode of development. Worms were first recovered 17 days afte r
infection from a mouse infected with cercariae obtained from Bulinus;
although the parasites were immatur e, they showed differences in the structure
of the gut when compared with with those obtained from mice infected with
P. boissyi-derived cercariae. Egg production began during the ninth week. He
published his findings and conclusions in a preliminary report in the British
Medical Journal in March 1916:
By submitting individual mice, each on one occasion only, for a limited period to
infection with the cercariae from single infected molluscs, it has been possible to
demonstrate that those developing in the Bullinus molluscs always produce bilharzia
worms which give rise solely to terminal-spined eggs, while those which have
developed in Planorbis boissyi always become worms which produce solely
lateral-spined eggs.71
He then turned his attention to experiments with monkeys. Two monkeys taken
from London to Egypt were infected orall y on the same day, one with cercariae
from Planorbis and the other with cercariae from Bulinus. The former monkey
began to pass lateral-spined eggs after six weeks and died from dysentery on
the sixtieth day. The other monkey had no eggs in the urine or faeces and was
killed six weeks after infection; worms were found in the liver and in th e
mesenteric veins but no eggs were seen. Meanwhile, a third monkey had been
infected orally with cercariae from Bulinus. Confusingly, it began to pas s

terminal-spined eggs in the faeces after 12 weeks and died five weeks later; at
autopsy, no eggs were found in the urine or bladder. At this point, Leiper had
determined that cercariae derived from Planorbis produced only
terminal-spined eggs. He explained the restriction of infection to the intestine
in monkeys as being due to differences in the venous connections of th e
bladder in this host. In order to cl inch the matter completely, rats and monkeys
were infected lightly with P. boissyi cercariae and kept alive for nine months,
i.e. well past Looss's transition period; lateral-spined eggs only were produced
during that time. Leiper concluded that:
The terminal-spined and lateral-spined eggs found in bilharzial infections are,
therefore, the normal and characteristic products of two distinct species, B.
haematobium and B. mansoni, and are spread by different intermediary hosts.72
Thus, at one stroke, Leiper confirmed the differentiation of Egyptia n
Schistosoma into two species, S. haematobium and S. mansoni, and at the
same time demonstrated that Bulinus species were the intermediate hosts of
the former worm and Planorbis boissyi (Biomphalaria alexandrina ) was the
vector of the latter schistosome. Leiper went on to remark that he ha d
examined the only remaining fragment of a male schistosome found in 1857
by Cobbold who had called it B. magna, but was unable to identify whether it
was S. haematobium or S. mansoni. Consequently, there was no difficulty in
the names of S. haematobium and S. mansoni standing for the worms causing
urinary and intestinal schistosomiasis, respectively 72.
Shortly afterwards, Manson-Bahr and Fairley studied intestina l
schistosomiasis in British Em pire troops of the Egyptian Expeditionary Force.
They confirmed Leiper's findings by infecting monkeys with cercariae fro m
Planorbis snails then subsequently recovering adult S. mansoni. They infected
Planorbis molluscs with S. mansoni miracidia, and confirmed that Bulinus
species were resistant to that para site83. Following this, Porter showed in 1920
that in southern Africa that Planorbis pfeifferi (= Biomphalaria pfeifferi ) was
a vector of S. mansoni 97.
Within a year or two of the publication of Leiper's discoveries, two Sout h
Americans working independently confirmed his findings with respect to S.
mansoni. In December 1916, Adolpho Lutz reported that certain species o f
local Planorbis snails were intermediate hosts of S. mansoni in Brazil. He
experimented with five species of Planorbis and found that P. olivaceus = P.
bahiensis (now known as Biomphalaria glabrata ) was the species most
susceptible to infection with miracidia obtained from laterally spined ova ,
although development also took place but to a lesser extent in P. ferrugineus
and P. tenagrophilus. Cercariae developed after five weeks or so in the same
manner as Leiper had described, but he observed that the rate was dependent
upon the temperature 75. In the following year, he completed the cycle o f
development by infecting guinea pigs and rabbits with cercariae from thes e
snails then subsequently recovering S. mansoni adult worms 76. Lutz also
pointed out that the cercariae of S. mansoni had in fact been seen, but no t
recognized as such, by Pirajá da Silva as early as 1912 when the latte r
described them and named them Cercaria Blanchardi. Finally, Lutz showed
that P. olivaceus was infected naturally with S. mansoni cercariae, and
re-examined in detail the kinetics of inf ection in experimentally infected snails.
He found that miracidia penetrated the molluscs within 10-15 minutes, th e
most usual site of attack being the antenna. Sporocysts were apparent within
three to four days then secondary sporocysts were seen migrating into th e
visceral sac 20 days after infection. Mature cercariae were found about fiv e
weeks after exposure 77.
In Caracas, Venezuela, Juan Iturbe (1917) infected P. guadelupensis (now
known as Biomphalaria glabrata ) with miracidia obtained from S. mansoni
ova51. He observed the transformation of miracidia into sporocysts then th e
production of secondary sporocysts then the appearance of cercariae after six
to seven weeks. White mice, guinea pigs and newborn puppies were infected
percutaneously with these cercariae; two months later, adult S. mansoni were
recovered from the portal vein of two mice. Iturbe found, however, that th e
most constant success was obtai ned when experimental animals were fed food
contaminated with livers of P. guadelupensis containing large numbers o f
cercariae. He then found many naturally infected snails of this species in the
city. Finally, Ampullaria luteostoma and P. cultratus were infected under
laboratory conditions, but he did not regard these as being vectors in nature.
Also from South America, Cardoso in 1923 reported that Planorbis
centrimetralis was the common intermediate host of the parasite in Sergip e
State, Brazil 16.
The cycle of transmission was again invest igated by Faust and his colleagues
in the early 1930's. They infected the snail they called Heliosoma
(Planorbina) guadaloupense (= Biomphalaria glabrata ) with S. mansoni
miracidia then produced patent infec tions in a variety of experimental animals.
With respect to development of the parasite in the snails, they first identified
sporocysts on the eighth day. Cercariae began to emerge after 24-35 days ,
depending upon the season and continued to be discharged for four months ,
producing altogether about 100,000 cercariae from a single miracidium 31,32.
The taxonomy of the snail vectors of S. mansoni has been a matter of some
controversy. Planorbis boissyi described by Potiez and Michaud in 1838 was
shown to be identical with Planorbis alexandrinus described by Ehrenberg in
1831; this latter name therefore had priority. A number of other genera were
raised, however, to house intermediate hosts of S. mansoni; these included, in
addition to the genus Planorbis described by Geoffoy in 1767, Biomphalaria
raised by Preston in 1910 98, Tropicorbis enunciated by Pilsbry and Brown in
1914, Afroplanorbis of Thiele, 1931, and Australorbis erected by Pilsbry in
1934. A World Health Organiz ation study group in 1954, however, noted that
it had long been recognized that the known species of snails which serve a s
intermediate hosts for S. mansoni are generically the same, and that they al l
have probably been derived from the same stock. They recommended that the
name Biomphalaria should be used for all the snail intermediate hosts o f
S. mansoni 99. In 1965, the International Commission on Zoological Nomen-
clature confirmed this view and ruled that the correct generic name for th e
following snail vectors of S. mansoni, Armigerus, Planorbina and Taphius,
was Biomphalaria 50. In an annotation on an abstract concerning this decision,
Wright noted that it had not been necessary to consider Australorbis and
Tropicorbis since they were both junior synonyms of Biomphalaria 123. The
correct names for the major African vectors of schistosomiasis mansoni ar e
therefore Biomphalaria alexandrina and B. pfeifferi.
Concerning the South American molluscan vectors, Martins in 193 8
considered that Planorbis centrimetralis , P. guadaloupensis, P. immunis, P.
nigricans, P. olivaceus and perhaps P. peregrinus were all synonyms given
to members of a variable species properly known as Australorbis glabratus
85
. As already noted, the proper name for Australorbis is Biomphalaria,
therefore the correct name for the major South American vector o f
schistosomiasis mansoni is Biomphalaria glabrata .
MIGRATION OF WORMS IN THE DEFINITIVE HOST
In 1919, Iturbe and Gonzalez in Venezuela studied the migration of S. man-

soni through the tissues of experimental animals and found that the event s
were similar to those that had already been described for S. japonicum ( see
chapter 10). They observed that cercariae penetrated the skin within fiv e
minutes, lost their tails in the process, then the resultant schistosomula passed
via the bloodstream through the hea rt and lungs to the liver. Male worms were
found in the portal veins 18 days after infection, but female worms were not
identified until one month after exposure 52.
In the same year, Fairley repor ted his observations in monkeys infected with
S. mansoni. He observed that the worms inhabited chiefly the inferior an d
superior mesenteric veins and tributaries of the portal vein in the liver. Fairley
then went on to describe the mechanism of egg-laying by female worms in the
distal tributaries of the portal venous system; this was the same as has already
been recounted for S. haematobium (see chapter 8).
A few years later, Faust and his colleagues re-investigated the route an d
kinetics of migration in rats, rabbi ts and monkeys infected experimentally with
a Puerto Rican strain of S. mansoni. They noted that schistosomula had left the
skin within 16-20 hours of infection, and pas sed mainly via the veins but partly
through the lymphatics to the lung capillaries where they were first seen at 20
hours. By the third day. they had reached the systemic circulation, and on the
fourth day, they were discovered within the hepatic radicles of the portal vein
where they were believed to feed for the first time. Larvae were found in the
lungs up to 19 days after infection, and peak numbers of worms in the live r
were reached on the thirteenth day. Mature worms were first seen in th e
colonic venules 35-40 days after infection 32,33.
Adult worms may live in the portal venous syst em of humans for many years.
One patient has been recorded who, at least 26 years after infection, was still
passing eggs containing living miracidia 116. Epidemiological evidence ,
however, suggests that the average life span for these worms is between five
and ten years 120.
CORRELATION OF INFECTION WITH PATHOLOGY AND

INVESTIGATIONS OF PATHOGENESIS
The pathological changes in schistosomiasis mansoni were described b y

Bilharz and Griesinger soon after the discovery of S. haematobium, although
neither of these investigators realized that the pathological changes they saw
in the large bowel were caused by S. mansoni infection. On 15 March 1852,
Bilharz and Griesinger performed an autopsy on a boy who had died fro m
meningitis. In addition to urinary sch istosomiasis, disease of the intestinal tract
was discovered:
From the middle of the transverse colon to the anus, the mucosa was somewhat
swollen and delicate; it was markedly congested and covered with reddish mucus. In
the region of sigmoid colon and in the rectum were superficial erosions....Between
these hyperemic, inflamed areas were both more coarsely congested and almost or
completely normal stretches of mucosa.13
As has been discussed earlier, Bilharz found clumps of eggs as well as eg g
shells which he thought were S. haematobium "capsules" in this intestine .
Several days later, Griesinger discovered eggs with lateral spines containing
miracidia in dysenteric large intestine:
In a black-pigmented large intestine showing scars of healed ulcerations and many
warts and spines, I found (19 March 1852) an enormous number of Distoma shells
(eggs?) (sic) provided with a lateral spine. I was fortunate enough to see massive
hatching of the organisms.43
When Griesinger found a number of such patients, he wondered whether these
trematodes might not be the cause of both the acute and chronic diseases of the
large intestine that abounded in E gypt. Against this, however, was the fact that
during the short time that he had left in the country, Griesinger did not always
find eggs in cases of dysentery, despite the most assiduous searching .
Consequently, he reached the conclusion that most of the dysenteries aros e
from causes other than schistosomiasis, but that "distomiasis of the larg e
intestine.... is only one, but nevertheless a highly important complication o f
these diseases" 43. He did, however, add a caveat:
But I do consider it possible that, in some cases, Distoma alone can effect changes
in the large intestine which, at least to the naked eye, seem very similar to those of
true dysentery.43
These changes were then studied in more detail in histological sections .

Thus, Zancarol (1882) demonstrated that colonic vegetations, which in th e
fresh state had the appearance of internal haemorrhoids, were in fact folds of
mucous membrane which were stuffed wi th schistosome eggs 124. Several years
later, Belleli described the histological characteristics of a tumour, the size of
a small apple, removed from the rectum of a patient in Egypt; it had th e
appearance of an ordinary ad enomatous polyp, but groups of ova were seen in
the connective tissues 8. This gave rise to speculation that irritation by parasites
may play a part in tumour formation 3, but Ferguson was later to remark that the
rarity of malignant neoplasia in intestinal schistosomiasis stood out in contrast
with that seen in the urinary infection 34. These polyps were recognize d
frequently in Egyptian schistosomiasis but rarely elsewhere. Thei r
manifestations and the resulting complications were described by Maddern:
The most common seat of infection is the lower part of the small intestine and the
large intestine generally. The most common lesion in the intestinal tract is the
presence of papillomata of varying sizes and characters along the whole length of the
intestine from the ileum to the anus, sometimes thickly scattered or again sparsely
distributed throughout the mucous membrane....Over quite extensive areas of certain
parts of the large intestine, the papillomata have necrosed and separated off at their
pedicles, resulting in ulcers of dysenteric appearance....Sometimes, again, certain
lengths of the large intestine become infiltrated, together with their peritoneal
attachments, with hard bilharzial tissue. There is an enormous thickening of the walls
of the gut, a dense packing of its interior with papillomata, and deposits of bilharza
tissues in the appendices epiploicae and on the serous surface of the gut, and a fixing
of the intestine with massive deposits behind it and between the layers of its
peritoneal attachments.79
Although Bilharz originally found adult s chistosomes in the portal vein close
to the liver, S Kartulis in 1885 was the first person to report the deposition of
eggs in the liver55. As his patient suffered from both urinary and intestina l
schistosomiasis, it is not now possible to be certain whether Kartulis saw ova
of S. mansoni, S. haematobium or both. In 1904, William St. Clair Symmers
published the results of his observations on liver pathology during a five year
period in Cairo. From time to time, he had n oticed that the liver had an unusual
appearance:
On section, the liver presents a remarkable appearance due to an enormous increase
of the fibrous tissue (Glisson's capsule) which normally surrounds the portal canals....
When a portal canal is cut transversely, the mouths of the contained vessels and bile
ducts are seen embedded in the centre of a circular or slightly oval area of white
connective tissue, the diameter of the mass being....from a sixth to a quarter of an
inch; whereas, longitudinal sections of the canals reveal elongated masses of similar
appearance and thickness, so that the cut surface of the liver looks as if a number of
white clay-pipe stems had been thrust at various angles through the organ. 110
Microscopical examination of six of these livers revealed that this periportal
firosis was associated with the presence of schistosome ova:
Among this tissue are seen ova of the Bilharzia haematobia, often in considerable
numbers. ...A small blood vessel may often be seen running up to, and widening into,
such a mass of concentrically arranged young fibrous tissue, and lying in the centre
of the newly formed mass, as if it had become impacted in the vessel, and had by its
presence produced the proliferation of tissue which resulted in cirrhosis, an ovum. 110
Although he entitled his paper "Note on a new form of liver cirrhosis due to
the presence of the ova of Bilharzia haematobia", it is clear that he was
visualizing eggs of S. mansoni, for he remarked that most of the ova wer e
laterally spined. Most of the eggs were dead with merely the shell remaining
and were surrounded by fibrou s tissue, but he occasionally observed fresh ova
which were filled with a mass of inflammatory cells. Symmers thought that all
of these changes were indicative of a cirrhosis of the liver caused b y
schistosome ova.
Cirrhosis of the liver and splenomegaly with ascites have long bee n
recognized as being frequent in Egypt. Indeed, an attempt has been made to
link the abdominal distension and gy naecomastia seen on several reliefs on the
tomb of Mehou, a notable of the VIth Dynasty, to hepatic involvement i n
schistosomiasis 46. Certainly, this form of liver disease accounted for 4% of the
admissions to the medical wards of the Kasr-el-Aini Hospital in Cairo during
the early part of this century. In 1909, Day and Ferguson reported thei r
experience with this problem and concluded that it was not due t o
schistosomiasis 23. Fifteen years later, however, Day changed his position when
ova were discovered at liver biopsy in a series of patients subjected t o
splenectomy. He regarded splenomeg aly as an early and often transient feature
of S. haematobium infection, but concluded that progressive and lastin g
splenomegaly may accompany hepatic schistosomiasis mansoni, even whe n
infection of the intestinal tract was slight. Day believed that there were tw o
types of "cirrhosis". If the numbers of eggs were small, a diffuse multilobular
cirrhosis was established, but if they were numerous, the dense periporta l
(pipestem) fibrosis of Symmers was found 22.
The paucity of eggs in the liver and the recovery of male worms alone from
the portal vein, however, led Girges in his review to conclude that:
Egyptian splenomegaly is a disabling endemic parasitic syndrome caused by male
Schistosoma mansoni infestation of the liver and portal vein....It presents an
absolutely different picture from the ordinary type of schistosomiasis mansoni. There
is very little or no alimentary disturbance or implication of the gut, the brunt of the
infection being inflicted upon the viscera.40
Subsequently, the view was promulgated that these features were very similar
to Banti's syndrome and "before falling back on this obscure diagnosis in the
future, the question of schistosomiasis....will have to be considered" 4.
Nevertheless, the genesis of these liver changes remained a matter o f
controversy for many years. Thus, in 1959, Carter and Shaldon wrote:
the importance and extent of the infiltration of the liver by ova, and the nature and
causes of the fibrosis found in the livers of patients with schistosomiasis, are still
disputed.17
Experimental studies, however, eventually placed beyond any doubt tha t
when splenomegaly and ascites were due to schistosomiasis of the liver, they
were the result of presinusoidal hypertension caused by obstruction to blood

flow as a result of granulomas around the eggs. Thus, infections with worms
in the portal system but without eggs in the liver failed to induce significan t
changes in the haemodynamics of the portal venous system in experimenta l
animals. Further, the eggs themselves were calculated to contribute less than
5% of the obstruction, the great proportion of obstruction being generated by
granulomas117. Progressive understanding of the genesis and evolution of these
lesions led to a solidification of the concept that the condition described b y
Symmers was not cirrhosis, as defined by liver parenchymal cell death, nodular
regeneration and sclerosis, but a simple hepatic fibrosis. Thus, in retrospect,
it is apparent that schistosomiasis with heavy egg deposition and subsequent
granulomatous inflammation may cause portal hypertension, splenomegaly ,
ascites and oesophageal varices. It is now clear that in those instance s
described by the early investigators in which cirrhosis was associated with a
minimal number of eggs, the patients had cirrhosis resulting from one of the
many other causes, known and unknown, of that condition together wit h
coincidental light schistosome infections.
Griesinger's postulate that eggs might sometimes be carried in th e
circulation to organs outside of the portal venous system was borne out when
Belleli7 reported the finding by Mackie in 1885 of numerous small, fibrosing
abscesses containing schistosome eggs in the lungs of a man who had die d
from the complications of urinary schistosomiasis. In 1905, Symmer s
described the recovery of a pair of copulating worms from the left lung of a 35
year old person who had died from intestinal schistosomiasis 111. Pulmonary
schistosomiasis was then investigated intensively by Shaw and Ghareeb who
examined 282 cadavers of persons with schistosomiasis mansoni an d
schistosomiasis haematobia in Egypt and found that in 2%, death was du e
directly to lung damage caused by these parasites. Moreover, one third of all
these patients had schistosomal pulmonary emboli; 10% of these emboli were
due to the adult worms themselves, whereas the rest were due to eggs. The ova
caused necrosis of the vessel walls and passed into the alveolar spaces an d
were associated with a chronic inflammatory re action, sometimes accompanied
by endothelial thickening of the arterioles, resulting in cor pulmonale 107.
Following delineation of the pathology of schistosomiasis, attempts wer e
made to comprehend the genesis of these changes. Crucial to such a n
understanding was the realization that the primary inflammatory reactio n
around schistosome worms and eggs in the tissues was of a non-suppurative
nature. Fairley in 1919 described "tubercles" containing many eosinophili c
leucocytes around eggs in monkeys infected experimentally with S.
haematobium and S. mansoni 26,29. Hutchinson in 1928 detailed thi s
phenomenon more clearly, showing that ova were at first surrounded b y
fibroblasts and foreign body giant cells to form a granuloma which he called
a "bilharzial pseudotubercle" 48. This was echoed by Koppisan who described
the pseudotubercle as the fundamental histopathological unit o f
schistosomiasis mansoni. He also portrayed an evolutionary process in which

an infiltration of eosinophils and neutrophils around ova in the tissues wa s
followed by the appearance of ep ithelioid cells which were in turn replaced by
fibrosis65. Eventually, KS Warren and a number of other investigators showed
that these granulomas were the consequence of cell-mediated immun e
reactions to schistosome egg antigens 117,119.
Whether or not resistance to reinfection is generated by prior exposure t o
infection has been a vexed and controversial topic. Reductions in frequenc y
and intensity of infection in older age groups have been put forward as a n
indication of the acquisition of such resistance, but Warren, in his majo r
review118, concluded that these effects were more probably explained o n
ecological grounds, particularly behavioural influences on contact wit h
contaminated water.
The dysenteric symptoms of schistosomiasis were emphasized by Mackie in

Alexandria in 1882. He noted that many Egyptians suffering from thi s
condition complained of a feeling of a constant weight and discomfort about
the rectum, pain in the hypogastrium, and a frequent desire to defaecate, but
that straining at stool resulted only in the passage of a little mucus and blood.
These symptoms had often been present for months. The patients wer e
sometimes emaciated, and rectal ex amination disclosed firm nodules about the
size of a small bean in the rectal mucosa 78. These features were reiterated by
Maddern, also in Egypt, a few years later. He wrote that the most commo n
lesions in the intestinal tract were papillomas in the large bowel associate d
with symptoms ranging from minimal to diarrhoea, tenesmus, and passage of
blood and mucus, as in dysentery 79.
The early manifestations of infection w ere reported by Lawton in 1917, soon
after the differentiation of S. mansoni as a separate entity by Leiper in 1916.
Lawton described the clinical features of a group of 24 Australian soldiers who
had been infected at a freshwater canal at Tel-el-Kebir during World War I.
Several of the men had noticed itching when coming out of the water afte r
bathing. The incubation period was uncertain, but between four weeks an d
three months later, there was a gradual onset of anorexia, headache, myalgia,
dizziness, cough, fever, rigors, sweats and abdominal pain. Generalize d
urticaria was always present, usually during the second and third week of the
clinical illness, and lasted for 12-48 hours. Diarrhoea was only an occasional
and transitory feature. Examination revealed abdominal tenderness, partic -
ularly in the right upper quadrant and over the descending colon, as well a s
enlargement of the liver and spleen 67.
In 1922, Girges reviewed the clinical aspects of schistosomiasis on the basis
of his observations of 4,000 cas es of S. mansoni infection at Tanta on the Nile
delta40. He divided them into two types - the intestinal and hepatic. Intestinal
schistosomiasis was in turn divided into four phases following "Baoonah itch"
(indicating cercarial invasion) and a laten t period: (1) febrile or toxaemic stage
lasting three to six weeks - this was seen in 3% of his patients and was marked
by the sudden or insidious onset of fever, hepatosplenomegaly, occasiona l
urticaria, indigestion, diarrhoea and tendern ess in the right hypochondrium; (2)
dysenteric stage lasting two to three years - this was seen in nearly three fifths
of his patients and coincided with the ap pearance of eggs in the faeces and was
characterized by exacerbations of dysentery every 15-20 days associated with
fever; (3) intestinal or papillomatous stage - this was seen in one third of his
patients and was typified by thickening of the lower bowel which was ofte n
palpable through the abdominal wall, and the appearance of papillae in th e
rectum. (4) final stage or "stage of repair" was seen in only 0.2% of hi s
patients - Girges considered it the terminal stage of infection with marke d
sclerosis and contraction of the tissues and with only a few atrophie d
papillomata left. The manifestations of hepatic schistosomiasis (which Girges
considered as being synonymous with Egyptian splenomegaly) were initially
the same as those in intestinal schistosomiasis. The second stage was marked
by the appearance of an enlarged, hard, o ften tender liver and spleen. The third
stage was indicated by the appearance of ascites. Ova were typically absen t
from the stools. As already indicated, it is now probable that this conditio n
frequently had nothing whatever to do with schistosomiasis.
Similar syndromes to these were described a few years later by Pons i n
Puerto Rico96. They were reiterated again by Gelfand in Southern Rhodesi a
(Zimbabwe) who recognized three clinical varieties: (1) an acute phase o f
fever and urticaria, often associated with malaise, anorexia and cough; (2 )
chronic abdominal pain and periodic mild diarrhoea with occasional blood and
mucus in the stools; (3) a late form with cirrhosis and splenomegaly 39.
In many endemic areas, not only is polyparasitism present, but infection s
with gastrointestinal bacterial and viral pathogens are common. Thi s
frequently makes it difficult to discern which features are due to schisto -
somiasis and which are due to other pathogens. In recent years, a number of
community studies have shed some light on this problem by relating th e
clinical manifestations to the int ensity of infection. A controlled study by Cook
and his colleagues of schistosomiasis in the West Indian island of St. Luci a
showed that gastrointestinal symptoms were no more frequent in infected than
in non-infected individuals, but that hepatomegaly and splenomegaly wer e
more common in the moderately and heavily infected children, as defined by
the numbers of eggs excreted in the faeces 20. Similar observations were then
made in Kenya 109 and in Brazil 68.
These findings confirmed views on the prognosis in schistosomiasi s
mansoni. Although severe and sometimes fatal infections with S. mansoni
were well-described in the nineteenth century, it was recognized that such an
outcome was uncommon. Before elucidation of the life cycle, there was some
speculation that autoinfection might occur, and that this could influence th e
prognosis. When it was realized that infection was acquired from infecte d
snails and that adult worms did not multiply in the human host, it seeme d
probable that continuing exposure was necessary for the development o f
severe disease. This concept was supported by the observation that expatriate
troops infected during World War I did not develop progressive disease when
they were removed from the endemic areas 27.
In the last several decades, some longitudinal studies of the effects o f
schistosomiasis have been carried out, although they have tended to con -
centrate on the more heavily infected individuals. Thus, Katz and his col -
leagues in Brazil followed up 112 patients fo r ten years; two patients died from
haematemesis, seven had evolved towards hepatosplenomegaly, but most of
the others showed little progres s in the severity of the disease 58. Rather similar
results were reported by Kloetzel, also in Brazil, who observed 105 patients
infected with S. mansoni for five years and found that only seven had died 63.
Thus, schistosomiasis mansoni, although it may be a cause of considerabl e
morbidity, is not a major cause of death.
Although Bilharz and Griesinger discover ed that urinary schistosomiasis could

be diagnosed in life by finding eggs in the uri ne, and were aware that ova could
be found in the intestinal mucosa at post-mortem examination, they do no t
appear to have paid much attention to diagnosing schistosomiasis by finding
eggs in the stools. It is true that Bilharz did write to von Siebold in Augus t
1852; "I have also found eggs in the stool of a patient with acute dysentery" 12.
This was almost a throw-away line, however, and neither Bilharz no r
Griesinger developed the idea that this phenomenon could be utilized i n
diagnosis. This presumably devolved from thei r failure to differentiate between
laterally and terminally-spined eggs, their belief that urinary schistosomiasis
was of greater importance, and the relative ease of examining urine compared
with faeces. This concept was accepted by various commentators in thei r
textbooks; they all recommended examining the urine in order to make th e
diagnosis.
Thirty years after Bilharz disc overed the worms, Mackie reported that rectal
nodules common in Egyptians with schistosomiasis could be twisted off with
haemorrhoidal forceps, then the characteristic ova could be demonstrate d
microscopically. He even added that no ova could be seen in the urine despite
careful and repeated micoscopical examination, but made no mention of any
similar examination of the faeces 78. As late as 1903, Milton, in an extensiv e
review of schistosomiasis which encompassed clinical and therapeutic aspects
of both urinary and intestinal forms of the disease, discussed diagnosis b y
examination of the urine for eggs, but omitted any reference to a simila r
examination of the stools 87.

It is uncertain who first began routine microscopical examination of th e
faeces in order to diagnose schistosomiasis mansoni, although it is clear that
Manson in 1902 serendipitously found laterally-spined eggs while looking for
hookworm ova in the stools 81; indeed, it was this discovery which, as already
described, initiated the debate that led to the delineation of S. mansoni as a
separate species. Following this report, however, examination of the faece s
became a frequent, then a standard, inves tigation in both clinical situations and
in epidemiological studies. Much attention then turned to developin g
laboratory techniques for maximizing the chances of detecting ova in th e
stools6,30,100,106,115,122. With the realization that it was important to determine the
intensity of infection, however, these techniques largely fell out favour an d
were replaced by quantitative methods, the most important of which is th e
Kato technique, originally described by Kato and Miura in 1954 57, then mod-
ified by Komiya and Kobayashi 64, adapted for quantitative diagnosis by Martin
and Beaver84, simplified by several workers 14,59, then developed into a "Quick
Kato Smear" suitable for rapid quantification of schistosome eggs under field
conditions 91.
The introduction of the proctoscope and sigmoidoscope provided a tool for
visualizing the intestinal lesions induced by S. mansoni. Thus, Bercowitz and
his colleagues examined proctoscopi cally 155 Puerto Rican army recruits who
had eggs in the faeces, and found that two thirds of them had small, sharpl y
demarcated ulcers, pinpoint or linear in shape and up to several millimetres in
width10. Subsequently, Greany in the Sudan sigmoidoscoped 38 patients with
schistosomiasis and found that the most frequent lesions were yellow-whit e
pinhead dots; hyperaemia and friabil ity were common, ulcers were seen in one
third, and polyps were rarely met 42. Da Cunha and his colleagues sigmoid -
oscoped over 2,000 patients with schistosomiasis in Brazil and found tha t
congestion was the commonest lesion, rectal polyps were rare, yellowis h
nodules of ova could be visualized, and varices were frequent in patients with
hepatosplenic schistosomiasis 21.
Even though polyps containing eggs were rare in regions outside of Egypt,
it was found that eggs could often be found in biopsies of rectal mucosa 45.
Similarly, eggs may be found in the liver in schistosomiasis; thus in one study,
ova were seen in liver biopsies in 21 out of 45 cases 25.
Structural damage to the large intestine can be displayed by radiographi c
barium enema examination24. Similarly, effects on the liver and portal venous
system can be investigated radiologically, manometrically, and using nuclear
medicine techniques 1,5,88,89. In most instances of hepatic schistosomiasis, it was
found that liver function tests were only mildly or moderately impaired 89,101.
There have been many efforts to develop immu nological assays for the diag-
nosis of schistosomiasis mansoni. Fairley described the employment of a
complement fixation assay for antischistosomal antibodies in 1919 28, while
Taliaferro and his colleagues described a precipitation reaction 113 and an
intradermal test114, but immunoassays have remained much less useful tha n
parasitological diagnostic techniques.
The anthelmintic therapy of schistosomiasis mansoni is broadly similar to that

of schistosomiasis haematobia and has been detailed in chapter 8. There are,
however, some differences. As already indicated, niridazole was shown to be
less effective against S. mansoni than against S. haematobium and metrifonate
was found to be of no value at all. On the other hand, oxamniquine is a useful
addition to the therapeutic armamentarium in schistosomiasis mansoni. This
drug was shown by Foster and coll eagues in 1973 to be active against S. man-
soni in rodents and in monkeys, but had no effects on S. haematobium or S.
japonicum 37. In the same year, Katz and co-workers tested oral and intra -
muscular administration of the drug i n 24 adults in Brazil with schistosomiasis
mansoni and found that the latter route was preferable 60. Subsequent studies
confirmed the efficacy of the drug against S. mansoni, although it appeared to
be more useful against the South American than the African strains of th e
parasite112.
In 1903, Milton reviewed the surgic al management of schistosomiasis of the
rectum. He recommended enemas of starch and opium or copper sulphate in
the early stages. He advised removal of polyps, but this was frequently no t
possible because they were either too numerous or were too high in th e
rectum. He found that excision of the rectum was rarely necessary 87.
Splenectomy was undertaken for "Egyptian splenomegaly" in the earl y
1920's, and this was said to be sometimes attended by considerable improve-
ment22. Noya Benitez performed 22 splenectomies in patients with schisto -
somiasis and reported in 1947 that it may relieve portal hypertension i f
undertaken before liver damag e was excessive 90. Ligation of the hepatic artery
had its advocates 49,62 but sometimes had devastating consequences and did not
find lasting recognition. Various shunt procedures such as portocaval anast-
omosis and lieno-renal anastomosis were assessed from time to time 38,54,89,108.
It was thought initially that patients with schistosomal portal hypertensio n
were not likely to develop po rtosystemic encephalopathy as liver function was
held to be relatively undisturbed. There were reports, however, that hepati c
dysfunction did supervene 121 and the operation gradually lost favour with many
surgeons.
An ingenious procedure for removal of adult worms from the portal venous
system by extracorporeal filtration of blood was described by Goldsmith and
colleagues in 1965 41. They removed 148 to 800 worms from three patients, but
the technique did not live up to expectations and was abandoned.
Early ideas concerning the epidemio logy of schistosomiasis before S. mansoni

and S. haematobium were distinguished have been recounted in chapter 8 .
Central to the understanding of the epidemiology of schistosomiasis mansoni
was the demonstration by Leiper that this infection was transmitted by certain
species of snails. This was followed by the delineation of the geographica l
distribution of S. mansoni, with the realization that this infection but no t
S. haematobium infection also occurred in the Western Hemisphere. This was
followed by the identification o f the various species of snail intermediate hosts
of the parasite in different parts of the world. Over the next few decades, much
effort was expended on defining the frequency of the infection and severity of
disease in a large number of endemic areas. Although humans have proven to
be the major reservoir of infection, S. mansoni infection in nonhumans wa s
first reported by Cameron in 1928 after he found that monkeys on the Wes t
Indian island of St. Kitts were infected naturally 15. Subsequently, the
occurrence of natural infections in rodents in Egypt 66 and in South America 86
was shown.
As with schistosomiasis haematobia, the main determinants of the prev -
alence and intensity of infection are the presence and density of vector snails,
and the behavioural habits of the human population which determine both the
contamination of water sources with infected faeces and the exposure t o
cercaria-laden water. Like schistosomiasis haematobia, schistosomiasi s
mansoni has been spreading wit h the advent of new irrigation systems and has
increased in frequency along the Nile downstream from the Aswan High Dam
(see chapter 8).
INTRODUCTION OF SCHISTOSOMA MANSONI INTO THE

WESTERN HEMISPHERE
In 1902, Manson wrote that with the exception of Mesopotamia, Cyprus and
Mauritius, schistosomiasis had hitherto been supposed to be peculiar to Africa.
He then reported the instance of an Englishman who had been infected with
schistosomes producing laterally spined eggs while residing in the Wes t
Indies. Its occurrence in a white man suggested to Manson that the infection
must be not uncommon among the indigenous inhabitants. He then dre w
attention to the parallels betwee n schistosomiasis and another African disease,
Guinea worm infection, which had been at one time prevalent in parts o f
Central and South America, and noted that the latter condition had no w
disappeared. Although he did not specifical ly say so, Manson implied that both
of these infections had been introduced from Africa, and with remarkabl e
precision and foresight wrote: "It is evident that the distribution of this an d
similar parasitic diseases depends on the presence or absence of the efficient
intermediaries" 81.
This form of schistosomiasis wa s indeed found to be common in parts of the
Americas. In 1908, Pirajá da Silva wrote that the worm was probabl y
introduced into the New World from Af rica by West African slaves, beginning
in 1550. Infection was particularly common in the environs of Bahia, Brazil
from where da Silva was writing. That city was at one time one of the mai n
entry ports during the times of the slave trade. He postulated that these people
were the carriers of schistosomes from Africa, and that the schistosome eggs
found climatic conditions in America favourable for development 92. More
recently, it has been suggested that Recife in Brazil may have been the most
important entry point, particularly during the Dutch administratio n
(1630-1654), since the Dutch brought in an in ordinately high number of slaves
during this period 2.
Although laterally spined eggs were common in South America in the early
parts of this century, haematuria and terminally spined eggs were not, eve n
though the latter disease was frequent in parts of Africa and may have been at
some time in the past in the Western Hemisphere. This became explicabl e
when Leiper proved that S. mansoni and S. haematobium were different
species and required different molluscan vectors. Snails susceptible t o
S. mansoni were found in various regions of the Americas, although they were
usually different species from those seen in Africa, but snails susceptible t o
S. haematobium were absent. While indigenous American snails wer e
susceptible to S. mansoni and are most important in transmission, there may
also have been a small-scale introduction of African vectors. For example ,
Biomphalaria alexandrina pfeifferi and Bulinus tropicus were found in the
municipal gardens and in ditches about the city of São Paulo, Brazil. It wa s
suggested that these species may have been introduced in water barrel s
brought from Africa during the slave trade times, and had been left behin d
when the barrels were washed out and refilled with fresh water 9. Further
support for the slave trade theory was provided by the demonstration tha t
infection was common in those places where slaves from endemic areas o f
Africa had been imported, such as northe astern Brazil. This infection may now
be becoming zoonotic, for Martins in Brazil in 1958 found that natura l
infections were common in wild and domestic rodents 86.
While it is the view of the vast majority of investigators that S. mansoni was
introduced from Africa, a few workers believe that this worm was autochth-
onous in Brazil. Magalhães and Dia s, for example, reached this opinion on the
basis of reports of a disease with symptoms similar to that seen in schisto -
somiasis mansoni which was said to have existed along the rivers before the
arrival of the Portuguese 80.
Measures for the prevention and control of intestinal schistosomiasis ar e

similar in many respects to those used in S. haematobium infections. The
development of such techniques has already been outlined in chapter 8. The
greatest success has attended a multidisciplinary approach. For example ,
Biaggi reported forty years ago that the prevalence of S. mansoni infection in
a rural area of Puerto Rico had been reduced from 44.6% to 4.5% by a
combination of treatment, installation of efficient latrines, improvements i n
water supply and attempts at biological control of snails, but he commente d
that these measures were too expensive to be applied to the whole island 11.
Similarly, schistosomiasis was once common in St. Kitts, West Indies, with the
prevalence of infection as late as 1932 being estimated to be as high as 25%.
The infection has now disappeared, presumably as a result of unplanne d
environmental improvements 35.
Various methods for the control of schistosomiasis mansoni have bee n
assessed in various parts of the world, but perhaps the most elegant of these
studies were carried out on the West Indian island of St. Lucia by Jordan and
his colleagues. The efficacies of different control techniques including snai l
control, chemotherapy and provision of safe water supplies were investigated.
Although all methods produced similar results, it was concluded that chemo-
therapy (hycanthone plus or minus oxamniquine) was the cheapest and most
rapidly effective method of achieving transmission control and also provided
disease control. Snail control (with Bayluscide), however, did not requir e
either population cooperation or a stable community. Installation of safe water
supplies was the costliest technique and required education and cooperation
of the population, but provided other social and medical benefits 53. These
techniques are being used in varying combinations, as far as practicable and
economically feasible, in various parts of the world.
REFERENCES
1. ALMEIDA FC, LUZ FF. Direct operative portography in hepatosplenic schistosomiasis

mansoni. Gazeta Médica da Bahia 70: 1-15, 1970
2. ALMEIDA MACHADO P. The Brazilian program for schistosomiasis contro l
1975-1979. American Journal of Tropical Medicine and Hygiene 31: 76-86, 1982
3. ANONYMOUS. Parasites and tumours. Lancet ii: 300, 1885
4. ANONYMOUS. Schistosomiasis or Banti's Syndrome? Lancet i: 642, 1937
5. ARAFA MA, BIBAWA E, RAFAAT A. The portal pressure in hepatic fibrosi s
associated with bilharziasis. American Journal of Tropical Medicine and Hygiene 6 :
108-113, 1957
6. BELL DR. A new method for counting Schistosoma mansoni eggs in faeces. Bulletin of
the World Health Organization 29: 525-530, 1963
7. BELLELI. Les oeufs de Bilharzia, &c., dans les poumons. Union Médicale d'Egypt e
Nos. 22-23, pp 1-3, 1885

8. BELLELI V. Du rôle des parasites dans le développement de certaines tumeurs ;
fibro-adénome du rectum produit par les oeufs du Distomum haematobium . Progrès
Médical 13: 54-56, 1885
9. BEQUAERT JC, de LUCENA DT. Introdução no Brasil de duas espécies africanas de
caramujos transmissores da e squistossomose - Bulinus tropicus (Krauss) e Biomphalaria
alexandrina pfeifferi (Krauss). Revista Brasileira Medica 8: 167-170, 1951
10. BERCOWITZ ZT, RODRIGUEZ-MOLINA R, HARGRAVE D W, DICKE JD, GREEN
CE. Studies on human Schistosoma mansoni infections. I. Proctoscopic picture i n
asymptomatic schistosomiasis mansoni infections. Journal of the American Medica l
Association 125: 961-963, 1944
11. BIAGGI N. The fight against schistosomiasis. Puerto Rico Journal of Public Health and
12. BILHARZ T. Fernere Mittheilungen über Distomum haematobium . Zeitschrift für
wissenschaftliche Zoologie 4: 454-456, 1853. Partly translated in 61
13. BILHARZ T, von SIEBOLD CT. Ein Beitrag zur Helminthographia humana, au s
brieflichen Mittheilungen des Dr. Bilharz in Cairo, nebst Bemerkungen von Prof. C. Th.
von Siebold in Breslau. Zeitschrift für wissenschaftliche Zoologie 4: 53-76, 1852 Partly
translated in 61
14. BORDA CE, PELLEGRINO J. An improved st ool thick-smear technique for quantitative
diagnosis of Schistosoma mansoni . Revista do Instituto de Medicine Tropical de Sã o
Paulo 13: 71-75, 1971
15. CAMERON TW. A new definitive host for Schistosoma mansoni . Journal of
Helminthology 6: 219-222, 1928
16. CARDOSO E. Contribuição ao estudo da schistosome no Estado de Sergipe. Brazi l
Medico ii: 239-240, 1923
17. CARTER RA, SHALDON S. The liver in schistosomiasis. Lancet ii: 1003-1008, 1959
18. de CERQUEIRA FALÇÃO E. Professor Pirajá da Silva, incontestable discoverer o f
"Schistosoma mansoni". Zeitschrift für Tropenmedizin und Hygiene 10: 146-153, 1959
19. COBBOLD TS. Cases of haematuria due to Bilharzia. British Medical Journal i :
1096-1097, 1885
20. COOK JA, BAKER ST, WARREN KS, JORDAN P. A controlled study of morbidity
of schistosomiasis mansoni in St. Lucian children, based on quantitative egg excretion.
21. da CUNHA AS, CANCADO J R, PELLEGRINO J, de OLIVERIA CA. Valor oograma
para a seleção e avaliação de medicamentos da esquistossomose mansoni. Revista d o
22. DAY HB. The etiology of Egyptian splenomegaly and hepatic cirrhosis. Transactions of
23. DAY HB, FERGUSON AR. An account of a form of splenomegaly with hepati c
cirrhosis endemic in Egypt. Annals of Tropical Medicine and Parasitology 3: 379-394,
1909
24. di EGIDIO M. Osservazione radiologiche sulla bilharziosi intestinale nello Yemen .
Archivio Italiano di Scienze Mediche Tropicali e Parassitologia 38: 311-327, 1957
25. ERFAN M, TALAAT S. Demonstration of Schistosoma ova in the liver by biopsy .
Journal of the Royal Egyptian Medical Association 30: 663-664, 1947
26. FAIRLEY NH. Bilharziasis: some recent advances in our knowledge. Lancet i :
1016-1021, 1919
27. FAIRLEY NH. Observations on the clinical appearances of bilharziasis in Australia n
troops, and the significance of the symptoms noted. Quarterly Journal of Medicine 12:
391-403, 1919.
28. FAIRLEY NH, The discovery of a specific complement fixation test for bilharziosis and
its practical application to clinical medicine. Journal of the Royal Army Medical Corps
32: 449-460, 1919
29. FAIRLEY NH. A comparative study of experimental bilharziasis in monkeys contrasted

with the hitherto described lesions in Man. Journal of Pathology and Bacteriology 23 :
289-314, 1920
30. FAUST EC, D'ANTONI JS, ODOM V, MILLER MJ, PERES C, SAWITZ W ,
THOMEN LF, TOBIE J, WALKER JH. A critical study of clinical laboratory technics
for the diagnosis of protozoan cysts and helminth eggs in feces. American Journal o f
31. FAUST EC, HOFFMAN WA, JONES CA. Life history of Manson's blood fluk e
(Schistosoma mansoni). I. Extramammalian phase of the cycle. Proceedings of th e
Society of Experimental Biology and Medicine 31: 474-476, 1934
32. FAUST EC, HOFFMAN WA, JONES CA. Life history of Manson's blood fluk e
(Schistosoma mansoni). II. The mammalian phase of the cycle. Proceedings of th e
Society of Experimental Biology and Medicine 31: 476-478, 1934
33. FAUST EC, JONES CA, HOFFMAN WA. Studies on schistosomiasis mansoni in Puerto
Rico. III. Biological studies. 2. The mammalian phase of the life cycle. Puerto Ric o
Journal of Public Health and Tropical Medicine 10: 133-196, 1934
34. FERGUSON AR. Associated bilharziasis and primary malignant disease of the urinary
bladder, with observations on a series of forty cases. Journal of Pathology an d
Bacteriology 16: 76-94, 1911
35. FERGUSON FF, RICHARDS CS, SEBASTIAN CT, BUCHANAN IC. Natura l
abatement of schistosomiasis mansoni in St. Kitts, British West Indies. Public Health 74:
261-265, 1960
36. FLU PC. Beitrag zur Lösung der Frage, ob Schistosomum mansoni , identisch ist mit
Schistosomum haematobium. Centralblatt für Bakteriologie, Parasitenkunde un d
Infektionskrankheiten, Abteilung originale 61: 389-403, 1911
37. FOSTER R, CHEETHAM BL, KING DF. Studies with the schistosomicide oxamniquine
(UK-4271). I. Activity in rodents and in vitro. Transactions of the Royal Society o f
38. GARCÍA-PALMIERI MR, RAFFUCI FL, DÍAZ-BONNET LA, BERNAL-ROSA JF.
Shunt surgery for portal hypertension due to Schistosoma mansoni . Evaluation and
management in fortyone cases. Journal of the American Medical Association 171 :
268-271, 1959
39. GELFAND M. The clinical features of intestinal bilharziasis ( S. mansoni). Clinical
Proceedings, Cape Town 1: 247-252, 1942
40. GIRGES R. The aetiology of "Egyptian spleno megaly". Journal of Tropical Medicine and
Hygiene 35: 86-90, 99-105, 1929
41. GOLDSMITH EI, LUZ FF, PRATA A, KEAN BH. Surgical recovery of schistosomes
from the portal blood. Treatment of parasitization in man. Journal of the America n
42. GREANY WH. Schistosomiasis in the Gezira irrigated area of the Anglo-Egyptia n
Sudan. II. Clinical study of schistosomiasis mansoni. Annals of Tropical Medicine and
43. GRIESINGER W. Klinische und anat omische Beobachtungen. Über die Krankheiten von
44. HARLEY J. On the endemic haema turia of the Cape of Good Hope. Medico-Chirurgical
Transactions 47: 55-72, 1864. Abstracted in Lancet i: 156-157, 1864
45. HERNÁNDEZ MORALES F, MALDONADO JF, PRATT CK. The diagnosis o f
schistosomiasis by a rectal biopsy technique. American Journal of Tropical Medicine 26:
811-820, 1946
46. HOEPPLI R. Parasitic disease in Africa and the Western Hemisphere. D. Helmint h
infections. Acta Tropica, Supplement 10: 111-150, 1969
47. HOLCOMB RC. The West Indian bilharziosis in its relation to the Schistosomum
mansoni (Sambon 1907), with memoranda on ten cases. United States Naval Medica l
Bulletin 1: 55-80, 1907
48. HUTCHINSON HS. The pathology of bilharziasis. American Journal of Pathology 4 :

1-16, 1928
49. IBRAHIM H. Combined ligation of hepatic and splenic arteries in Egyptia n
splenomegaly. Journal of the Egyptian Medical Association 40: 253-269, 1957
50. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. Opinion
735. Biomphalaria Preston, 1910 (Gastropoda): Grant under the plenary powers o f
precedence over Planorbina Haldeman, 1842, Taphius H. and A. Adams, 1855, an d
Armigerus Clessin, 1884. Bulletin of Zoological Nomenclature 22: 94-99, 1965
51. ITURBE J. Intermediate host of Schistosoma mansoni in Venezuela. Journal of Tropical
52. ITURBE J, GONZALEZ E. Quelques observations sur les cercaires de la vallée d e
Caracas (Première partie). Laboratorio Iturbe, pp 18, 1919. Abstracted in Tropica l
53. JORDAN P. Schistosomiasis - research to control. American Journal of Tropica l
54. JUSTINIANO RT. Portocaval shunt in the treatment of bleeding esophageal varices due
to schistosomiasis. (preliminary report). Boletín de la Asociación Médica de Puerto Rico
55: 266-270, 1963
55. KARTULIS S. Ueber das vorkommen der Eier des Distomum haematobium Bilharz, in
den Unterleibsorganen. Archiv für pathologische Anatomie und Physiologie und fü r
klinische Medicin (Virchow) 99: 139-145, 1885
56. KARTULIS S. Bilharzia. Lancet ii: 364, 1885
57. KATO I, MIURA M. Comparative examin ations. Japanese Journal of Parasitology 3: 35,
1954
58. KATZ N, BRENER Z. Evolução clínica de 112 casos de esquistossomose manson i
observados após 10 anos de permanência em focos endêmicos de Minais Gerais. Revista
do Instituto de Medicina Tropical de São Paulo 8: 139-142, 1966
59. KATZ N, CHAVES A, PELLEGRINO J. A simple device for quantitative stoo l
thick-smear technique in schistosomiasis mansoni. Revista do Instituto de Medicin a
60 KATZ N, PELLEGRINO J, GRINBAUM E, CHAVES A, ZICKER F. Preliminary trials
with oxamniquine, a new antischistosomal agent. Revista do Insituto de Medicin a
61. KEAN BH, MOTT JE, RUSSELL AJ. Tropical medicine and parasitology. Classi c
62. KHAIRY M. Hepatic artery ligature for liver cirrhosis in Egypt. Journal of the Egyptian
63. KLOETZEL K. Mortality in chronic splenomegaly due to schistosomiasis mansoni :
follow-up study in a Brazilian population. Transactions of the Royal Society of Tropical
64. KOMIYA Y, KOBAYASHI A. Evaluation of Kato's thick smear technic with a
cellophane cover for helminth eggs in feces. Japanese Journal of Medical Science an d
Biology 19: 59-64, 1966
65. KOPPISAN E. Studies on schistosomiasis in Puerto Rico. VI. Morbid anatomy of th e
disease as found in Puerto Ricans. Puerto Rico Journal of Public Health and Tropica l
Medicine 16: 395-455, 1941
66. KUNTZ RE. Natural infection of an Egyptian gerbil with Schistosoma mansoni .
Proceedings of the Helminthological Society of Washington 19: 123-124, 1952
67. LAWTON FB. The early symptoms following infection by Schistosoma mansoni .
Medical Journal of Australia ii: 247-250, 1917
68. LEHMAN JS, MOTT KE, MORROW RH, MUNIZ TM, BOYER MH. The intensity
and effects of infection with Schistosoma mansoni in a rural community in northeas t
Brazil. American Journal of Tropical Medicine and Hygiene 25: 285-294, 1976
69. LEIPER RT. Half yearly report to the Colonial Office, May 1908. Cited in 72
70. LEIPER RT. Letter to P. da Silva (February 1909). Cited in 18

71. LEIPER RT. On the relation between the terminal-spined and lateral-spined eggs o f
Bilharzia. British Medical Journal i: 411, 1916
73. LOOSS A. What is "Schistosomum mansoni" Sambon 1907? Annals of Tropica l
74. LOOSS A. Some notes on the Egyptian Schistosoma haematobium and allied forms.
75. LUTZ A. Observações sobre a evolução do Schistosomum mansoni . Nota previa. Brazil
Medico 30: 385-387, 1916
76. LUTZ A. Observações sobre a evolução do Schistosomum mansoni . Brazil Medico 31:
81, 89, 1917
77. LUTZ A. O Schistosomum mansoni e schistosomose segundo observações feitas n o
Brazil. Memorias do Instituto Oswaldo Cruz 11: 121-155, 1919
78. MACKIE J. Bilharzia haematobia in connexion with a form of dysentery in Egypt .
British Medical Journal ii: 661, 1882
79. MADDERN FC. The incidence of bilharziosis in Egypt and its clinical manifestations.
80. MAGALHÃES BF, DIAS CB. Esquistossomose de Manson. Estudo Memorias d o
Instituto Oswaldo Cruz 41: 363-446, 1944
81. MANSON P. Report of a case of Bilharzia from the West Indies. British Medical Journal
ii: 18941895, 1902
82. MANSON P. Tropical diseases. A manual of the disease of warm climates. third edition,
Cassell and Co., pp 756, 1903
83. MANSON-BAHR P, FAIRLEY NH. Observations on bilharziasis amongst the Egyptian
Expeditionary Force. Parasitology 12: 33-71, 1920
84. MARTIN LK, BEAVER PC. Evaluation of Kato thick-smear technique for quantitative
diagnosis of helminth infections. Ameri can Journal of Tropical Medicine and Hygiene 17:
382-391, 1968
85. MARTINS A V. Contribuçã o ao estudo do gênero Australorbis Pilsbry 1934. Memórias
do Instituto Ezequiel Dias 2: 5-61, 1938
86. MARTINS AV. Non-human vertebrate hosts of Schistosoma haematobium and
Schistosoma mansoni . Bulletin of the World Health Organization 18: 931-944, 1958
87. MILTON F. Bilharziosis surgically considered. Lancet i: 866-869, 1903
88. MOUSA AH, EL-GAREM A, SAIF M, EL-ABDIN AZ. The significance of estimating
the hepatic blood flow in hepatosplenic bilharzial cases by the radiogold clearance and
uptake methods and its value in determining the extent of porta-systemic collaterals .
89. NEL CJ, HONIBALL PJ, VAN WYK FA. Portal hypertension in schistosomiasis. South
African Journal of Surgery 12: 233-239, 1974
90. NOYA BENITEZ J. Splenectomy in schistosomiasis. Preliminary report. Puerto Ric o
Journal of Public Health and Tropical Medicine 23: 247-255, 1947
91. PETERS PA, EL ALAMY M, WARR EN KS, MAHMOUD AA. Quick Kato smear for
field quantification of Schistosoma mansoni eggs. American Journal of Tropical Medicine
and Hygiene 29: 217-219, 1980
92. PIRAJÁ da SILVA M A. Contribução para o estudo da schistosomiasis na Bahia. Brazil
Medico 22: 281-283, 441-444, 451-454, 1908. Partly translated in 61
93. PIRAJÁ da SILVA M A (cited as da SILVA P). Contribution to the study o f
schistosomiasis in Bahia, Bra zil. Journal of Tropical Medicine and Hygiene 12: 159-163,
1909
94. PIRAJÁ da SILVA M A. La schistosomose à Bahia. Archives de Parasitologie 13 :
283-302, 1909
95. PIRAJÁ da SILVA M A. Cited in 18
96. PONS JA. Studies on schistosomiasis mansoni in Puerto Rico. V. Clinical aspects o f
schistosomiasis in Puerto Rico. Puerto Rico Journal of Public Health and Tropica l
Medicine 13: 171-254, 1937
97. PORTER A. The invertebrate (molluscan) hosts of Schistosoma mansoni and Fasciola
hepatica in South Africa. Medical Journal of South Africa 16: 75-76, 1920
98. PRESTON. Annals and Magazine of Natural History 6: 535, 1910
99. REPORT OF A STUDY GROU P. Bilharzia snail vector identification and classification
(Equatorial and South Africa). World Health Organization Technical Report Series, No.
90, pp 1-22, 1954
100. RITCHIE LS. An ether sediment ation technique for routine stool examinations. Bulletin
of the United States Army Medical Department 8: 326, 1948
101. RODRIGUEZ HF. Schistosomal hepa tosplenomegaly. Boletín de la Asociación Médica
de Puerto Rico 48: 393-403, 1956
102. SAMBON LW. Descriptions of some new species of animal parasites. Proceedings of
the Zoological Society of London. No. 19, pp 282-283, 1907
103. SAMBON LW. New or little known African entozoa. Journal of Tropical Medicine and
Hygiene 10: 117, 1907
104. SAMBON LW. Remarks on Schistosomum mansoni . Journal of Tropical Medicine and
Hygiene 10: 303-304, 1907
105. SAMBON LW. What is "Schistosomum mansoni" Sambon 1907? Journal of Tropical
106. SCOTT JA. Dilution egg counting in comparison with other methods for determining
the incidence of Schistosoma mansoni. American Journal of Hygiene 25: 546-565, 1937
107. SHAW AF, GHAREEB AA. The pathogenesis of pulmonary schistosomiasis in Egypt
with special reference to Ayerza's disease. Journal of Pathology and Bacteriology 46:
401-424, 1938
108. SHIROMA M, OKUMURA M, MEIRA JA, FERREIRA JM. Cirurgia da hipertensão
portal na esquitossomose mansônica hepatosplênica. Avaliação clínica de 150 casos de
anastomose espleno-renal. Revista do Hospital das Clínicas; Faculdade de Medicina ,
Universidade de São Paulo 22: 309-337, 1967
109. SIONGOK TK, MAHMOUD AA, OUMA JH, WARREN KS, MULLER AS ,
HANOKA AK, HOUSER HB. Morbidity in schistosomiasis mansoni in relation t o
intensity of infection: study of a community in Machakos, Kenya. American Journal of
110. SYMMERS WStC. Note on a new form of liver cirrhosis due to the presence of ova of
Bilharzia haematobia . Journal of Pathology and Bacteriology 9: 237-239, 1904
111. SYMMERS WStC. A note on a case of bilharzial worms in the pulmonary blood in a
case of bilharzial colitis. Lancet i: 22, 1905
112. SYMPOSIUM DE OXAMNIQUINE. Rio de Janeiro, Brasil, Junho, 1973. Revista do
Instituto de Medicina Tropical de São Paulo 15: Supplement, pp 1-175, 1973
113. TALIAFERRO WH, HOFFMAN WA, COOK DH. A precipitin test in intestina l
schistosomiasis. Journal of Preventive Medicine 2: 395-414, 1928
114. TALIAFERRO WH, TALIAFERRO LG. Skin reactions in persons infected wit h
Schistosoma mansoni. Porto Rico Journal of Public Health and Tropical Medicine 7 :
23-35, 1931
115. TOMB JW, HELMY MM. The diagnosis of in testinal schistosomiasis by sedimentation.
Transactions of the Royal Society o f Tropical Medicine and Hygiene 25: 181-185, 1931
116. WALLERSTEIN RS. Longevity of Schistosoma mansoni: observations based on a case.
117. WARREN KS. The immunopathogenesis of schistosomiasis: a multidisciplinar y
approach. Transactions of the Royal Society of Tropical Medicine and Hygiene 66 :
417-434, 1972
118. WARREN KS. Regulation of the prevalence and intensity of schistosomiasis in man:
immunology of ecology? Journal of Infectious Diseases 127: 595-609, 1973
119. WARREN KS. The pathology, pathobiology and pathogenesis of schistosomiasis .

Nature, London 273: 609-612, 1978
120. WARREN KS, MAHMOUD AA, CUMMINGS P, MURPHY DJ, HOUSER H B .
Schistosomiasis mansoni in Yemeni in California: duration of infection, presence o f
disease, therapeutic management. American Journal of Tropical Medicine and Hygiene
23: 902-909, 1974
121. WARREN KS, REBOUÇAS G, BAPTISTA AG. Ammonia metabolism and hepati c
coma in hepatosplenic schistosomiasis: patie nts studied before and after portacaval shunt.
Annals of Internal Medicine 62: 1113-1133, 1965
122. WELLER TH, DAMMIN GJ. The acid-ether centri fugation and the zinc sulfate flotation
techniques as methods for the recovery of eggs of Schistosoma mansoni . American
Journal of Tropical Medicine 25: 367-374, 1945
123. WRIGHT CA. Tropical Diseases Bulletin 63: 862, 1966
124. ZANCAROL G. A specimen of Bilharzia, &c., with ova in the tissues of the bladder and
large intestine. Transactions of the Pathological Society of London 33: 410-412, 1882.
Abstracted in British Medical Journal i: 13, 1882 and Lancet i: 16, 1882
Table 9.1. Landmarks in schistosomiasis mansoni

__________________________________________________________________
1851 Bilharz saw but did not recognize adult worms

1882 Zancarol and Mackie remarked that in Egyptian schistosomiasis, eggs found
in the bladder had terminal spines while those in the bowel had lateral spines
1882 Mackie emphasized the dysenteric symptoms of many patients with Egyptian
schistosomiasis
1885 Kartulis described schistosome eggs in the liver
1902 Manson reported a patient with schistosomiasis acquired in the Western
Hemisphere; the eggs were in the stools, not in the urine, and had lateral
spines
1904 Symmers described clay-pipe stem fibrosis of the liver
1907 Sambon gave the name Schistosoma mansoni to the worm producing
laterally spined eggs
1916 Leiper discovered the molluscan vectors of Egyptian schistosomiasis and
proved the specific identities of S. mansoni and S. haematobium
1918 Christopherson reported the efficacy of tartar emetic
1940+ Kikuth and Gönnert showed that miracil D had schistosomicidal activity in
experimentally infected animals
1947 Blair, Hawking and Ross introduced therapy with miracil D
1964 Lambert and Ferreira reported that niridazole was active
1967 Pellegrino, Katz and Scherrer showed that hycanthone was effective
1973 Oxamniquine was reported by various workers to be effective in treatment
1977 Praziquantel was reported by various investigators to be effective in
experimental animals
1979 Katz, Rocha and Chaves reported that praziquantel was effective in humans
__________________________________________________________________
Chapter 10
Schistosoma japonicum and SCHISTOSOMIASI S

JAPONICA
SYNOPSIS
Common name: Oriental blood fluke, causes Oriental schistosomiasis

Major synonyms: Bilharzia japonica, Schistosoma cattoi
Distribution: China, Philippines, Indonesia, (Japan)
Life cycle: similar to S. mansoni except that the vectors belong to the genus
Oncomelania
Definitive hosts: humans, dogs, cats, rodents, water buffalo, pigs, horses, sheep
Major clinical features: similar to schistosomiasis mansoni; also epilepsy
Diagnosis: demonstration of eggs in faeces, rectal mucosa, or liver biopsy
Treatment: niridazole, praziquantel, (tartar emetic)
DISCOVERY OF THE EGG
Ova of the parasite now known as Schistosoma japonicum were first dis-
covered in 1888 by Tokuho Majima (pen-name, Naganori) in Japan when he
made a postmortem examination of a man who had been suffering with ascites
and peripheral oedema. Majima noted that the spleen of this patient wa s
enlarged to five times the normal weight but that the liver was shrunken an d
contracted. The liver, moreover, had granular nodules both on its surface and
in the parenchyma amongst thickened connective tissue. When histologica l
sections of the liver were prepared:
It was found most surprisingly and unexpectedly that with the thickened interlobular
tissue there were countless parasite eggs, and these were located only in the
connective tissue....these eggs were oval....in shape and varied in size from 0.065 to
0.06 mm in length and 0.05 to 0.04 mm in diameter. The shells of the eggs did not
possess small covers (opercula). There were two kinds of eggs; the first type was pale
yellow in color with contents of a granular nature streaked with brownish-black
pigment....The second type had only the egg shell with no contents and were,
therefore, colorless and transparent.72
Majima wondered where the eggs came from, and with excellent logic bu t
miserable luck, opened the bile duct and the portal vein in the hope of finding
adult worms. He was unsuccessful - if he had been, he would have anticipated
the discovery of S. japonicum by 16 years. Majima was not able to examine the
faeces of this patient but predicted that eggs might have been found there .
263
Finally, he explained why he had reported this case:

I have set down my experience in the hope that in a parasite-ridden country like Japan,
a summary of the microscopic observations and clinical record might be useful to
students in the future.72
Similar eggs were found subsequently by Yamagiwa (1890) 119, Kurimoto
(1893)55, Kanamori (1898) and Fujinami (1904) in various organs, especially
the liver, of patients who had died in parts of Japan where an illnes s
characterized by hepatosplenomeg aly, diarrhoea, anaemia, wasting, ascites and
peripheral oedema was common. Some of these authors believed that the ova
played a role in the genesis of this disease, as did Kawanishi (pen-name Kasai),
who in 1902 was the first to find eggs in the faeces of patients 52.
In April 1904, Fujiro Katsurada, professor of medicine at Okayama Medical
College in Japan went to Yamanashi Prefecture Hospital and examined twelve
patients with this syndrome. In five of these persons, he found ova of th e
parasite now known as S. japonicum in the faeces. Although he is quoted a s
saying in one paper "Until now, the eggs have been unknown to the medica l
world"49 this appears to be a mistranslation for two reasons. Firstly, later in the
same paper, he refers to earlier discoveries of the same kind of eggs b y
Yamagiwa and Kanamori. Secondly, in a subsequent paper and translated by
a different person, the following passage appears:
Yamagiwa, Kurimoto, Fujinami and others observed cases in which in several
organs....in cadavers from infected areas, numerous eggs of a hitherto unknown
parasite were found.50
In any event, Katsurada described the eggs in detail, noting that they were oval
in shape, gave their dimensions, commented upon a transparent membran e
inside the shell, mentioned that the egg shells were devoid of any spine similar
to that seen in S. haematobium eggs, and described the miracidium which was
often seen within an egg. In one paper, he stated that the egg had a n
operculum 49, but later corrected this error 50.
In an attempt to find ova with morphological characteristics similar to those
of these eggs, Katsurada reviewed e very known parasite and concluded that the
most similar eggs were produced by the trematode, S. haematobium, but
realized that the eggs he had found were shorter and had no spine. When h e
studied the miracidia from his specimens and compared them with th e
descriptions given for the miracidia of S. haematobium, he could discern little
difference between the two parasites, except that he could find no evidence of
the two large gland cells in the anterior part of the body of the miracidium that
were said by Looss to be typical of S. haematobium. Consequently, Katsurada
wrote "therefore, I cannot but help conclude that the egg which I discovere d
and that of Bilharzia haematobium are similar, but not exactly the same" 49.
For a number of years it was thought that, in contradistinction to th e
terminally spined ova of S. haematobium and the lateral-spined eggs of S.
mansoni, S. japonicum ova did not have a spine. In 1910, however, Leipe r
examined 50 eggs from four human cases and three infections in dogs an d
Schistosomiasis japonica 265
discovered by rolling them around on a micr oscope slide that a small, knob-like
projection was always present 60.
Evidence of the antiquity of schistosomiasis ja ponica in eastern Asia has been
provided recently by finding typical eggs in human tissue. In 1971, a corps e
which had been buried 2,100 years pr eviously in Hunan Province of China was
exhumed and characteristic S. japonicum eggs were recovered from digested
liver. Four years later, eggs were found similarly in a corpse which had been
buried 100 years earlier than the previous one 75.
DISCOVERY OF THE ADULT WORMS
Following his initial observations, Katsurada hypothesized that, since thes e

eggs were not found in the faeces of every patient with the endemic syndrome,
and as greater numbers of eggs were recovered from purged stools, it wa s
unlikely that the adult worms dwelt within the gastrointestinal tract or an y
lumen connected directly with it. It was more probable that the worms resided
in the walls of the gut or in the visc era connected closely with it. It was obvious
to him that the only way to find these parasites and clarify the pathology of the
infection was to perform an autopsy on a patient with the endemic disease .
Unfortunately, Katsurada had no opportunity to undertake such a post-mortem
examination, but he was able to review specimens of three livers and on e
intestine obtained at autopsy a few years earlier by Drs. Shimohira ( =
Shimodaira) and Muramatsu. In this material, he found similar eggs. Thi s
evidence, together with the observations of earlier investigators, particularl y
Kanamori who had found similar ova in a rectal tumour and in a cirrhotic liver,
left Katsurada in little doubt that not only was this parasite the cause of th e
syndrome, but that it was most likely that the adult worms lived in the porta l
venous system.
As Katsurada knew that some ot her trematodes endemic in humans in Japan,
such as Clonorchis sinensis and Paragonimus westermani, could also be found
in cats and dogs, he killed a cat an d two dogs obtained from one of the endemic
areas. He noted nothing relevant in the dogs, but in the cat, killed on 9 Apri l
1904, Katsurada found two kinds of parasitic eggs in the liver, one of whic h
was the same as he had seen in human faeces an d in the specimens of liver from
three human autopsies. But in addition to the ova, he found adult worms:
white pieces of parasites were found in the large branch of the portal vein in the portal
system. After being suitably prepared, these worms were studied microscopically.
They were males, probably of the Bilharz's Schistosoma haematobia (or belonging
to the same genus) and had not been seen in Japan before. 49
In June 1904 Katsurada published all his f indings to that time. He described the
eggs and the male worms, and concluded tha t the eggs and worms were directly
related, as a child to its parent 48.
This view was disputed by a scholar of the subject, so Katsurada obtained a
second cat from the same village (Okamada in Yamanashi Prefecture) an d

found 24 male and eight female adult worms in the portal and mesenteric veins
of this animal. He then described both sexes of the worm in detail, including the
appearances of the eggs within the female worms, and emphasized th e
differences between the parasite that he had found and S. haematobium. These
results appeared in his second paper published in August 1904. At this time,
he called the parasite Schistosoma haematobium japonicum : "for the time
being, I want to call the parasite that I discovered, and which belongs to th e
genus Schistosoma, 'Schistosoma haematobium japonicum'" 49. In October
1904, he wrote a third account, which was also published in German i n
December 1904 then translated into English in April of the following year, the
worm on this occasion being labelled Schistosoma japonicum 50.
Katsurada's discovery was confirmed later in the same year by other Japanese
workers. In May 1904, Fujinami in Hiroshima (who had earlier found eggs in
the viscera of the first fatal case of Katayama disease that he had encountered),
discovered a partly damaged female worm in a branch of the portal vein of a
second patient who had died. He regarded this worm as a Distoma
haematobium and apparently believed initially that it was the first suc h
specimen to be found in Japan. In this patient, he also found the characteristic
ova in the liver, intestinal wall, mesenteric glands and pancreas 33. Soon
thereafter, Tsuchiya in Yamanashi found the parasite in cats, dogs an d
humans109.
These observations were all either unpublished or inaccessible to him in the
Japanese literature when the Englishman, John Catto, discovered worms of the
same type in 1904. Catto was res ident medical officer at St. John's Island quar-
antine station in Singapore when cholera broke out on a passenger ship from
China. One of the travellers, a man from Fukien, died from cholera, but wa s
noted during life to have hepatosplenomegaly. At autopsy, the rectovesica l
pouch was almost obliterated by adhesions, the mesentery was thickened and
contained enlarged lymph nodes, the l iver was enlarged and cirrhotic, the colon
was thickened with the mucosa being swollen, hyperaemic, friable an d
ulcerated, and the spleen was pigmented. Portions of the liver, mesenteri c
lymph nodes and bowel were preserved and histol ogical sections were prepared
in Singapore by Dr Finlayson and at the Kuala Lumpur Research Institute by
Dr Daniels. These disclosed "numerous small, oval bodies having a smooth ,
stout capsule"17 but opinions differed as to whether they were coccidia or the
ova of some unknown parasite. In the event, the case was published in th e
Journal of the Malaya Branch of the British Medical Association as one of
human coccidiosis. Catto then returned to England and re-examined th e
material at the London School of Tropical Medicine. This time, it becam e
evident that there were not only ova but also filariform larvae (? Strongyloides
- author) in the large intestinal mucosa. The sections were shown at th e
Medical Research Club in London but no definite conclusion was reached, so
samples were sent to an eminent German authority who considered that the y
were neither coccidia nor trematode ova, but the eggs of a nematode o f
unrecognizable species. At Patrick Manson's suggestion, Catto began to section
systematically all the preserved tissues. He found nematode larvae in smear s
prepared from the large intestine, a minute adult nematode in an artery of the
mesorectum, and a nematode larva in a mesenteric lymph node. Stimulated by
these observations, and no doubt misled by the German opinion, Manson and
Catto presented the case to a meeting of the British Medical Association i n
Oxford in July 1904 as that of an infection with a new nematode: "The parasite
would seem to be an oviparous nematode of minute dimensions and o f
unknown species" 74.
Catto continued his dissections and eventually found male and female adult
trematode worms in the mesenteric vessels, although neither he nor exper t
pathologists could be certain whether they were arteries or veins. Within th e
bodies of the female worms Catto now saw ova corresponding to the ova l
bodies in the viscera and realized that he was dealing with concomitan t
nematode and trematode infections. Manson then sent specimens to the Inter-
national Zoological Congress at Berne, Swi tzerland, where they were examined
by Blanchard, Looss, Ward, Stiles, Grassi and others, all of whom agreed that
the parasite was a schistosome and new to science. Catto then presented a n
updated version of his findings, describing both the autopsy features and th e
adult worms, to a meeting of the Pathological Society of London on 1 5
November 190416. Blanchard subsequently named the parasite Schistosoma
cattoi in Catto's honour, then Catto published a detailed record of the parasite
under that name in the British Medical Journal of 7 January 1905 17.
Further investigations revealed the identity of this parasite with the on e
described by Katsurada so, by the law of priority, Katsurada's designation ,
Schistosoma japonicum, stands as the correct name for this helminth. Thus, the
worm was discovered independently by several workers. Faust and Melene y
have placed these events in perspective well:
As has frequently been the case in many important contributions to science, several
workers attack the same problem contemporaneously, but without knowledge of each
other's investigations. Only the circumstance of time gives one the honor which the
other quite equally deserves. Such is the case with Schistosoma japonicum
Katsurada.29
Katsurada in Yamanashi attacked the problem logically and systematically; he
began with patients with a particular clinical syndrome, found eggs in thei r
stools, confirmed their presence in the viscera of other patients, surmised that
adult worms must live in the portal veno us system, found the male worm in that
position in a naturally-infected cat, then pursued the quest relentlessly until he
found female worms in another animal. Fujinami in Hiroshima, having earlier
found the eggs in another of his patients, was beaten to the punch by a mer e
month or so, but was without doubt t he first to find the female adult worm, and
the first to find an adult schistosome in a human being. Finally, Catto i n
Singapore and England, and completely unaware of the Japanese discoveries,

was tenacious enough, after meandering dow n several false alleys, to eventually
find adult worms a matter of several months after the Japanese researchers .
Furthermore, although the exact time sequence is unclear, it is probable tha t
Catto, or possibly Tsuchiya in Japan, was the first person to find male adul t
schistosomes in a human being.
DISCOVERY OF THE PERCUTANEOUS ROUTE OF INFECTION
When the adult forms of S. japonicum were discovered, it was clear that th e
infection must be transmitted in a fashion similar to that of S. haematobium.
But, as already discussed in chapter 8, the life cycle of that parasite too wa s
quite obscure, with protagonists of the direct infection theory and th e
intermediate host school each ardently defend ing their own particular view. The
speed with which the Japanese investigators worked out the life cycle of S.
japonicum is little short of remarkable, considering that it took only nine years
from Katsurada's discovery of the adult worms until Miyairi and Suzuk i
demonstrated transmission through snail intermediate hosts. This contrast s
starkly with the 64 years between Bilharz's discovery of S. haematobium and
Leiper's elucidation of the life cycle of that worm - and that largely followed the
precedent set by the Japanese. In defence of the European investigators ,
however, it must be remarked that two factors worked in favour of the Oriental
scientists. Firstly, Miyairi and Suzuki found snails susceptible to infection and
naturally infected with S. japonicum at almost their first attempt, whereas a
number of European investigators examined many different species with a
conspicuous lack of success. Secondly, although animals can be infecte d
experimentally with S. haematobium and S. mansoni, occidental schisto-
somiasis in nature is principally a disease of humans. Oriental schistosomiasis,
on the other hand, is a major zoonosis with humans and animals being equally
infected; this was known as early as 1847 for Fujii then wrote that even th e
cattle and horses were not immune to the affliction 32. This facilitated research
enormously for simple animal models were th erefore available for experimental
elucidation of the life cycle. Fujinami recognized this when he looked back on
the early years of schistosomiasis research in Japan:
animal experiments have been easily carried on, as the subjects of the experiment
could be infected by immersing them in water of the ditches in the endemic area. The
animal experiments have led to the solution of many interesting problems in the
pathology of the disease.34
Animal experimentation was indeed the key to success, but the key had first
to be found. It was Fujinami himself, in collaboration with Nakamura, a n
assistant professor of pathology at Kyoto Unive rsity, who made the fundamental
discovery. Because the adult schistosomes lived in the portal venous syste m
and were often found in the intestinal wall, many Japanese investigators thought
it likely that infection was acquired via the gastrointestinal tract, possibly by the
ingestion of worms in contaminat ed water. On the other hand, the development
of leg rashes and subsequent disease in farme rs working in rice fields suggested
that infection might occur through the skin.
Fujinami and Nakamura therefore devised an experiment to test the various
hypotheses. They decided to use cows since these animals were not onl y
susceptible to infection, but they were also large and docile enough to be made
to stand in water with only the hooves be ing soaked and without water touching
the anus and genitalia, thus avoiding the possibility of infection via the mucous
membranes of these organs. They used 17 cows up to one year of age an d
which had been obtained in Hiroshima ci ty where the infection was absent. The
experiment was begun on 7 June 1909 with the beasts being divided into a
number of groups. The first gr oup of six calves was given only boiled food and
water, and except on these occasions, th eir mouths remained covered. Each day
they were taken out of the barn and stood in water, three of them in the mud of
a rice paddy and the other three in a river which received great volumes o f
water from the rice fields. All of these animals became infected with S.
japonicum, but much larger numbers of adult worms were found in the cows
that had been allowed into the rice fields. A second group of seven calves had
their legs washed with soap and alcohol, then oiled and covered wit h
water-proof, protective leg bags. Four o f these animals ate and drank in the rice
fields, while three of them were taken to the river banks to feed. Six of these
cows remained uninfected, and a solitary worm pair was recovered from th e
seventh animal. A third group of two cows was fed and watered like the first
group. One cow was confined to the barn; no infection developed. The other
animal was placed in an irrigation canal for nearly five and a half hours on one
day only, nevertheless, it became infected with 31 worms. Finally, no special
measures were taken for a fourth group of two cows which were permitted to
roam freely; both animals became infected. Fujinami and Nakamura therefore
concluded that infection was acquired by penetration of the skin 35,36:
The great difference between the findings for group A and B is obvious - like snow
and charcoal - and we feel that the problem of the mode of entry of the infection,
which has vexed scientists for so long, has at last been incontrovertibly solved" 35
Further, they deduced that infection could be acquired easily in a short space
of time by contact with contaminated water, but that the risk of infection was
greater in the stagnant waters of the paddy fields and small irrigation canal s
than in the fast-flowing waters of the rivers.
The two researchers found schistosome s in different stages of growth in most
animals. One cow, however, had been exp osed on only one occasion, and when
it was killed 26 days later, small mal e and female worms were found in copula.
Although no eggs were detected, this observation led Fujinami and Nakamura
to write that: "the time required for the parasite to grow is comparativel y
short"36.
This conclusion was verified by experiments which they undertoo k
concurrently with dogs. These animals were kept secluded in cages an d

provided with uncontaminated food and water. At various intervals, they were
allowed outdoors into the rice fields and river. They were killed 23 or 54 days
later. In the dog killed after 23 days, small (4-5 mm) but mature male an d
female worms in copula were found, but again, no eggs were seen. In the dog
killed 54 days after infection, schistosomes 1 .0-1.3 cm long were recovered and
the female worms contained eggs. Similar results were obtained with rabbits,
and when the results from the three spec ies were compared, it became apparent
that ova were first produced five to six weeks after exposure, with egg s
appearing in the faeces shortly thereafter.
Thus, Fujinami and Nakamura proved that infection occurred via the skin ,
but they recognized that how it happened, and the nature of the antecedent and
subsequent events still remained unclear:
The life cycle before they (adult worms) are found in the portal circulation is not yet
known. The connection between the small worm (miracidium) which during the
warm season leaves the egg shell which had been deposited in the soil and water and
the very young, immature worms in the portal vein must await serious study in the
future.36
The demonstration by Fujinami and Nakamura that infection was effected by
penetration of the skin was confirmed later that year by Katsurada an d
Hasegawa who, in another district of Japan, infected a dog and a cat. It was also
demonstrated unexpectedly by Matsuura who had the misfortune to becom e
infected accidentally while wading in foul water. As will be discussed later ,
microscopical confirmation of t he direct penetration of the skin by schistosome
larvae, albeit of uncertain specificity, was provided in 1912 by Miyagawa 81.

HOSTS
The answer to the part of Fujinami and Nakamura's question concerning th e

events leading up to percutaneous infection was provided four years later b y
Keinosuke Miyairi and Masatsagu Suzuki, both of Kyoto University. They pub-
lished their results first in Japanese in 1913 86 (an English abstract of this paper
appeared in the March 1914 issue of the Tropical Diseases Bulletin ), then a
German version was published in 1914 87.
It had been known for a number of years that when eggs hatched, miracidia
were released. In 1904, Kawanishi had reported that when:
provided with a little warmth, it (the larva) immediately comes out of its shell....When
they first leave the shell, the larvae look like wine bottles. After one day they become
larger and assume many different shapes.52
Consequently, Miyairi and Suzuki began wi th the question as to what happened
to schistosome ova deposited in animal and human excrements in the open air.
They found a small ox infected with schistosomes which provided a constant

source of material for their exper iments. First, they observed the motions of the
miracidium within each egg, then they studied the hatching of the larva. At a
village called Kisi-mura of Miyoki-gun in Saga Prefecture, they found S.
japonicum eggs in human faeces left on the roadside. They therefore searched
carefully in the surrounding area and eventually:
succeeded in finding a certain species of snail in a little ditch by a rice field in the
village. The snail which apparently had no lungs had a brownish yellow shell which
was very smooth on the surface and was turning in a clockwise direction. The shell
could be easily crushed and had seven whorls....As amateurs, we couldn't tell the exact
name of the snail.86
Miyairi and Suzuki collected these snails and kept them alive in receptacle s
containing fresh water and cabbage leaves. They then took young snails which
proved to be free of naturally-acquired infect ion and mixed them in a basin with
miracidia freshly prepared from S. japonicum ova. They described graphically
the subsequent course of events: The way a fresh miracidium rushes up to its
host can be compared to that of a hungry tiger coming out his cage to hunt for
something to eat" 86. The miracidia attached themselves to the free body surface
of the snails then penetrated to the interior:
the animal (miracidium) makes its head sucker as thin as possible, pushes it between
the snail's epidermal cells, and stretches its cylindrical body as long as possible. With
a jerk it pulls itself together so that the base of the inserted proboscis cone and the
epidermal slit becomes wider. Repeated efforts, alternate stretching and contraction
of the body, push the cone further and further inside. 87
Miyairi and Suzuki were uncertain how each miracidium lost its ciliar y
covering but noted that the larvae tended to congregate in the gills, the wall of
the digestive organ, the salivary glands and near the nerves. The parasites then
became immobile and transformed in to small, spherical sporocysts which grew
daily. By twelve days after infection, Miyairi and Suzuki found secon d
generation sporocysts (they called them rediae) within the primary sporocysts:
the redia is a strange animal which, in open movement, can stretch out then contract
again into an oval form....Its head is thickly covered with fine spines. The mouth is
often wide open as though the animal intended to bite something. Very little can be
seen of the digestive tract. The entire abdominal content consists of rather large, pale
cells which, in the course of time, divide to form large and small cell aggregates. 87
The secondary sporocysts migrated into the liver where they grew lengthwise.
Seven weeks after infection of the snails, Miyairi and Suzuki found cercariae
within the secondary sporocysts. They wrote that "a cercaria is provided with
a powerful caudal tail and this is split, in its distal third, into two parts. Th e
body and the caudal tail are covered with spines" 87. then went on to provid e
details of the anatomical organization of the cercaria.
The next step was to complete the life cycle of the worm by infecting mice
with these cercariae. Attempts to infect mice with cercariae raised in snails in
the laboratory were unsuccessful, so Miyairi and Suzuki used older, naturally-
infected molluscs. These snails had three types of cercariae, one of whic h
resembled those raised in laboratory snails exposed experimentally to S. jap-

onicum miracidia. A mouse was placed together with the snails for three hours
each day for three days. Three weeks later, the mouse was killed by anothe r
mouse, but on examination, the investigators found male and female schist -
osomes in its internal organs. This experiment was repeated on a number o f
occasions with more mice, and they were always found to be infected.
Thus, Miyairi and Suzuki were able to demonstrate that a certain species of
mollusc was naturally infected with the larval stages of a worm which matured
into adult S. japonicum in experimental mice. Further, they were able to infect
clean snails with miracidia obtained from S. japonicum eggs and produce these
same larval forms. Although they did not complete the whole life cycle with the
same worms under laboratory conditions, there was nevertheless no doubt that
Miyairi and Suzuki had found an intermediate host and had described th e
various stages of metamorphosis and reprod uction of larval S. japonicum. They
were unable to identify the snails exactly, but concluded that the mollusc s
probably belonged to the family Hydrobiidae, remarking that precise species
identification must be left to the specialist.
At the same time as Miyairi and Suzuki were ca rrying out their studies, Miya-
gawa was working independently on the same prob lem. By a series of exclusion
experiments, he identified in snails the fork-tailed cercariae which developed
into adult schistosomes in experimental animals. Moreover, he demonstrated
the much closer morphological relationship between these latter two stages of
the parasite than between the miracidium and the cercariae 81-83.
It has been remarked that Miyairi received none of the international honours
he deserved89, but the same cannot be said, on this occasion at least, for Robert
Leiper. On 20 February 1914, Leiper and Staff Surgeon Edward Atkinson of
the Royal Navy left London for eastern Asia accompanied by an editoria l
fanfare in the Journal of Tropical Medicine and Hygiene :
The departure of the expedition....is an event which must prove of considerable
scientific importance....The primary object of the expedition is to ascertain the mode
of spread of the trematode diseases of man.3
Leiper and Atkinson arrived in Shanghai at the end of March and were granted
good laboratory facilities. This site had the added advantage of providing them
with ready access by road and water to endemic areas of schistosomiasis. They
investigated a number of parasites including Clonorchis, Metagonimus,
Diphyllobothrium, Echinochasma, Metorchis, Fasciolopsis and Ancylostoma,
but their main attention was centred on S. japonicum 61. Their first objective
was to find a patient with schistosomiasis who could provide them with a
steady source of eggs for experiments, but despite travelling 1,000 miles b y
boat, train and rickshaw over the space of three months, they failed to find a
suitable and cooperative person. By this time, unfortunately, the two principal
players, Leiper and Atkinson, had fallen out. Nelson, in his entertaining review
of this affair, quotes passages of letters written by Atkinson to Cherry-Garrard,
a zoologist who was to have worked with them:

I don't really think old chap that you can fully realise how perfectly damnable this man
can be.
This fellow has really been too damnable for words.
I ought to give him a sound thrashing, tell him what he is for the good of his soul and
then leave him.5
In the event, Leiper and Atkin son gave up their search for infected humans and
borrowed a dog, the faeces of which were loaded with S. japonicum eggs, from
a customs officer in Yanchow. They used miracidia hatched from these eggs to
infect all the available local snails, an experiment which they termed th e
"blunderbuss method". None of the molluscs, however, were attractive to the
larvae. Impatient with the tardiness of their progress, Leiper set off for Japan
where he first visited Fujinami, then journeyed to Katayama and collected a
batch of snails to take back with him to Shanghai. On his return to China, he
tested the snails with S. japonicum miracidia and found that one species, the
same as that of Miyairi and Suzuki, showed an extraordinarily marke d
attraction for the miracidia. This snail was identified subsequently by G C
Robson of the British Museum as a species of a new genus of hydrobii d
mollusc which he named Katayama nosophora 95. Furthermore, Leiper an d
Atkinson found the liver of these snails "ramified with long intertwinin g
delicate tubes bluntly rounded at the extremities and containing cercariae with
bifid tails"63. They believed that these tubes were not rediae but secondar y
sporocysts. Encouraged by this success, Leiper returned to Katayama an d
collected another supply of these molluscs. Many died on the return journey ,
but sufficient survived to provide cercaria e with which to infect laboratory-bred
mice. Meanwhile, however, World War I had b roken out, so the expedition was
aborted and Leiper and Atkinson returned to Britain with their specimens. Most
of the mice died before Hong Kong was reached, but in one putrescent animal,
a single male schistosome was found. At Aden, the few remaining snails were
sacrificed and used to infect the last remaining mouse. One month later, male
and female worms in copula were found in the portal vessels at autopsy i n
London. This led Leiper and Atkinson to conclude in their report published in
January 1915:
The marked attraction of the mollusc for the miracidium, the peculiar morphological
characters of the cercaria and the successful infection of a laboratory-bred mouse from
cercariae obtained from Katayama molluscs after several weeks' captivity at sea leave
no room for doubt that the schistosome has a life-cycle similar to that of other
trematodes.63
It has been suggested that one of Atkinson's main quarrels with Leiper was
over scientific priority. Nelson has postulated that the publication of tw o
papers, with Leiper as senior author, on t he parasites that Atkinson had brought
back from Antarctica may have started the row between the tw o
parasitologists 89. Similarly, Atkinson may have felt that Leiper gave insufficient
credit to the pioneering work of the Japanese scientists with inadequat e
reference to them in his publications. Thus, in their paper of January 191 5

(which was probably written largely if not entirely by Leiper as Atkinson was
on active service), there is only a sketchy outline of the Japanese discoveries
and no specific references are given. Concerning Miyairi and Suzuki's work,
it is merely recorded that there is a note in a paper by Katsurada in December
1913 "to the effect that he is informed in a private letter from a colleague that
Mr. Miyairi of Kiushu had just found a reproductive stage of Schistosoma in a
Lymnaeus species"63. Indeed, the paper concludes:
It would appear that the above results confirm Miyairi's main conclusion as to the
transmission of Schistosoma japonicum. Unfortunately, his paper is
inaccessible....The only information at present available to workers is an annotation
by Kumagawa in the Tropical Diseases Bulletin for March 30th, 1914. 63
Nelson has written that it must have been a great shock to Leiper when h e
visited Fujinami in Japan and the latter revealed to him the full details of th e
work of Miyairi and Suzuki. It seems quite likely, however, that Leiper knew
more about this work, even bef ore he left for the Far East, than he let on. In the
Tropical Diseases Bulletin of March 1914 (p. 290), Leiper provided a n
abstract of the paper by Katsurada of December 1913 in which Miyairi an d
Suzuki's work is alluded to. More imp ortantly, the preceding abstract, prepared
by Fleet Surgeon Kumagawa of the Tokyo Naval Medical College, wa s
concerned with Miyairi and Suzuki's definitive paper written in Japanese; this
abstract was referred to with the words "see above" in the text of Leiper' s
abstract (although it is possible that the comment was inserted in an editorial
capacity by someone else). Further, Leiper in the 1915 paper with Atkinso n
made no mention of the German version of Miyairi and Suzuki's pape r
published in 191487; it seems inconceivable that he did not know of it s
publication, particularly as he had discussed the Japanese investigators '
observations with Fujinami who would have known of its imminent or actual
publication. Finally, no ment ion at all was made of the Japanese studies among
the 532 references on schistosomiasis that Leiper published in 1915 i n
connection with his studies of the life cycle of S. haematobium. Leiper may
have been stung by such complaints as those attributed to Atkinson, for three
years later, in the final part of his report on his studies of S. haematobium in
Egypt, he harked back to his Japanese experience and took some pains t o
emphasize what he then felt had been his main contribution and the guidin g
principle behind the establishment of the expedition to the East:
a morphological clue might be established by which the bulk of cercariae of unknown
origin could be excluded microscopically; thus bringing the experimental use of
monkeys (for infection with S. haematobium) within practical limits.62
This morphological clue, he suspected, might be the absence of a muscula r
pharynx in schistosome cercariae compared w ith cercariae of most other flukes,
for adult schistosomes, in contrast to these trematodes, had no pharynx. In this
surmise Leiper was right, and he then went on to acknowledge the work o f
Miyairi and Suzuki (but, again, without giving a reference), and reiterated the
importance of the morphology of the cercaria for his own studies of the lif e
cycle of S. haematobium:
In the meantime, however, Miyairi and Suzuki....had succeeded by another method
of approach in tracing the metamorphosis in a closely allied, if not identical, snail in
the South Island of Japan. My own observations therefore confirmed generally the
results of these workers, apart from establishing my chief, ulterior object, which was
to provide a simple and reliable means of attacking the complex problems of B.
haematobia.62
The life cycle of S. japonicum was then confirmed in another geographical
area by S. Yokogawa. In February 1914, adult schistosomes were found in a
pig in Taiwan, then subsequent surveys disc losed them in dogs, pigs, goats, and
cattle. Yokogawa therefore collected snails and examined them for cercaria e
resembling those described by Miyairi. Eventually he succeeded in finding an
infected snail, obtained the cercariae and rubbed them on to the skin of a rabbit.
Eighteen days later, he killed the animal and recovered young schistosomes 5
mm long from the portal venous system 122. Many years later, Hsü and Hs ü
showed with human volunteers that the Formosan strain of S. japonicum is a
non-human, zoophilic strain wh ich develops for a short period in the viscera of
humans but does not reach maturity 42.
Attention then turned to China when Faust and Meleney investigated schisto-
somiasis and its transmission on the Chinese mainland. Their first step was to
obtain some snail vectors, known at that time as Blanfordia nosophora , from
S Yoshida in Osaka, Japan. In February 1922, they showed that these snail s
were susceptible to S. japonicum miracidia from a Chinese patient whereas the
usual molluscs in the Peking area, including Viviparus, Planorbis and
Lymnaea species could not be infected. Fa ust and Meleney therefore postulated
that the same or a similar species of mollusc must be the intermediate host in
China. In August 1922, Meleney found some similar snails near Soochow in
the lower Chang Jiang (Yangtze) Valley on river banks near the water's edge
and on water grass stalks. When dissected in the hospital laboratory, 28% of
these snails (which were identified subsequently as Oncomelania (Hemibia)
hupensis by Bryant Walker of Detroit, Michigan, USA) contained schistosome
cercariae. These cercariae were then used to infect laboratory mice and S.
japonicum adult worms were eventually obtained 78. Another batch of snails
which was not naturally infected was infected under experimental conditions
with S. japonicum miracidia of Chinese origin and the metamorphoses of the
larvae were observed. Cercariae, which were produced nine weeks afte r
exposure of the snails, were used to infect experimental dogs 28. Finally, O.
hupensis was infected successfully with S. japonicum of Japanese origin 27.
In 1932, Tubangui demonstrated that a snail identified by J Bequaert o f
Harvard University as Blanfordia quadrasi (now known as Oncomelania
quadrasi) was the intermediate host of S. japonicum in the Philippines 111.
Meanwhile, in an appendix to Faust and Meleney's monograph o n
schistosomiasis japonica which appeared in 1924, Nelson Annandale of th e
Zoological Survey of India and the Indian Museum, Calcutta, had reviewed the
status of the molluscan intermediate hosts of S. japonicum. He concluded that
there were three species which transmitted the worm, nosophora, formosana
and hupensis, all of which belonged to the genus Oncomelania Gredler 1881,
which was quite distinct from the genus Blanfordia 2.
Once Fujinami, Nakamura and others had shown that infection was acquired
by the percutaneous route, Yoneji Miyagawa turn ed his attention to both tracing
the route of migration of the worms from the skin to the portal venous system,
and determining the structures of the various developmental forms. He went to
Yamanashi province of Japan in the summer of 1911. Initially, he looked for
worms in the portal venous blood. Experimental animals, especially dogs and
rabbits, were immersed in water in areas where the disease was rampant, then
he collected blood between two and twenty four hours later. In these samples,
Miyagawa managed to find schistosomula. He then identified similar worms in
the skin and concluded that they had penetrated the skin partly directly an d
partly via the hair follicles, then entered the vascular system and possibly the
lymphatics, and were carried to the portal veins. He examined the anatomy of
these skin worms in detail and compared them with adult worms in the portal
vein and free-living miracidia, and found that they resembled adul t
schistosomes more than miracidia. This led him to conclude (before Miyair i
and Suzuki's proof) that the change in appearance must have occurred in a n
intermediate host:
On comparing the youngest described worms with the miracidia originating from
eggs, I found a considerable difference. I assume, therefore, that S. japonicum very
probably has an intermediate host.81
In a subsequent study, Miyagawa reported that he had found schistomula i n
thoracic duct lymph of infected dogs and in the draining lymph nodes. Because
of the paucity of numbers of worms in the lymph, however, he believed tha t
most worms passed directly via the bloodstream 82. Soon afterwards, Ogat a
made use of Miyairi and Suzuki's discovery t o confirm Miyagawa's findings. He
applied cercariae to the skin of experimental animals and observed thei r
passage through the integument via the bloodstream to the lungs 91.
Two schools of thought then arose as to the means by which worms reached
the portal system from the lungs. Narabayashi proposed that the parasite s
entered the pleural space then passed through the diaphragm to the liver and
portal circulation 88. He was supported in this view by Suyeyasu who studie d
serial sections of mice 104, but Miyagawa and Takemoto contended tha t
schistomula left the lungs via the systemic arterial circulation and were carried
to the gastrointestinal tract where they then found their way to the porta l
venules. Miyagawa and Takemoto based this view on their failure to fin d
worms penetrating the diaphragm or in the liver parenchyma, wherea s
parasites were seen in the intr ahepatic blood vessels of experimentally infected
animals84.
Shortly thereafter, Cort examined the development of these worms in detail.
He noted that soon after penetrating the skin, the tail of the cercaria was los t
and the cephalic glands dege nerated. By the twelfth day, the majority of worms
had reached the liver. There was little increase in size until the larvae reached
this organ, although the digestive system became more organized and the oral
sucker assumed its adult character. Cort was unable to distinguish between the
sexes in the earliest liver stages, but began to discern differences when the y
reached 0.3-0.4 mm in length. Growth continued after sexual maturity but at a
slower rate. As growth continued, he observed that the body of th e
female worms became rounded on cross-section while that of the male worms
flattened gradually and the sides grew up to form the gynaecophoric canal. Pari
passu with these events, the suckers grew and the digestive system becam e
horse-shoe shaped and distended with food. Differentiation of th e
reproductive organs came relatively late and they only became clearl y
distinguishable when the male and female worms attained lengths of 1.5 an d
2.0 mm, respectively 22.
A year or two later, Meleney and Faust re-examined both of these aspects .
They observed the process of invasion by cerca riae, noting that during invasion,
if not before, the tail of the organism dropped off, and determined that invasion
might be effected within several hours but could take up to two days. Within
two to three days of exposure of e xperimental animals, most schistosomula had
reached the lungs. Although a few worm s were side-tracked in heavy infections
and reached the pleural cavity where they degenerated, most larvae passe d
through the lungs into the systemic circulation. Meleney and Faust agreed with
Miyagawa's contention, for they recovered worms at this stage of the infection,
not only from mesenteric artery, but also from the renal, splenic and a variety
of peripheral arteries79. They found that those worms which reached the portal
venous system were able to grow and develop, with sexual differentiatio n
occurring as early as the seventeenth day, although sexual maturity was no t
reached until after four weeks. By this time, the worms had migrated retrograde
from the liver to the distal mesenteric venules where they laid eggs 28,29.
In 1932, Goto attempted to settle the argument over the two routes of migra-
tion. He found that washing out of the organs and tissues of dogs infected with
S. japonicum supported the systemic arterial migration theory of Miyagawa and
Takemoto while serial sections of decalcified mice indicated direct migration
as espoused by Narabayashi and Suyeyasu. Consequently, Goto concluded that
the results obtained depended upon the technique used 39.
Once within the portal system, worms may live for many years, continuing
infections being reported 32 years 76 and 47 years40 after the last possible
exposure.
The pathological changes produced by S. japonicum were recognized by

Majima simultaneously with his discovery of the eggs in 1888. The gros s
morbid anatomical changes he found have already been alluded to, as has his
description of the ova. In addition, however, Majima provided a luci d
exposition of the histological appearances, emphasizing that the eggs occurred
only in the portal tracts and not within the lobules, discussing the inflammatory
infiltration, and remarking upon the interlobular fibrosis:
these parasite eggs....were in peculiar locations in the connective tissues, mostly with
great numbers of eggs in large groups. Around the ends of these groups of eggs....a
marked infiltration of round cells was observed....There were indications in various
places of a new interlobular connective tissue; in these areas with increased
interlobular connective tissue there was marked round cell infiltration as well as
swelling and proliferation of the bile ducts....Because of the pressure by the new
connective tissue, atrophy was seen likewise in a small number of cells. 72
Katsurada in 1904 described the pathological consequences of infection in
both the liver and intestine, and remarked upon the absence of lesions in th e
rectum. He concluded that female worms released eggs which embolized t o
several organs where they excited inflammation and fibrotic reactions. Wit h
respect to the liver, he wrote: "In consequence of this the liver sooner or later
shrinks, and a kind of cirrhosis results, whereby the capsule of the live r
becomes granular, thickened and irregular" 50 and concerning the bowel ,
Katsurada remarked:
in most cases, eggs are found in the intestinal mucosa and submucosa, especially in
the large intestine. The deposition of eggs induces more or less severe inflammation,
which leads in parts to tissue disturbance, in parts to tissue growth; infiltration in the
bowel wall follows, and that frequently terminates in ulceration of the mucous
membrane.50
These features were reiterated by Catto who described deposition of ova, not
only in the liver and large intestine, but also in the gall bladder, mesentery and
small bowel, and wrote that "Where ova accumulate they provoke at certai n
places a small-celled infiltration, wh ich gives place later to a great proliferation
of fibrous tissue" 17.
In 1924, Faust and Meleney reviewed the p athological anatomy 29. They noted
that the invading cercariae produced a local reaction in the skin characterized
histologically by oedema, congestion and leucocytic infiltration. In thei r
passage through the lungs and later i n the gut, the chief lesions produced by the
young worms were haemorrhages. In massive infections, there was hepati c
parenchymal cell necrosis and degeneration of the convoluted tubules of th e
kidneys, presumably as a result of released toxins. Polymorphonuclea r
leucocytes, and particularly eosino phils, congregated around eggs in the tissues
and abscesses formed; these tended to break outwards by small openings into
the intestinal mucosa. Thrombosis of the lar ger mesenteric and portal veins was
frequently seen in later cases. In the liver, there was, in addition to th e
inflammatory lesions produced by degeneration of eggs, a general pipeste m
fibrosis. The spleen varied in size, but was sometimes hypertrophie d
enormously. Faust and Meleney were unimpressed by lung lesions, but noted
that eggs might sometimes be seen in the brain.
Japanese clinicians became aware gradually of a syndrome characterized b y

hepatosplenomegaly, diarrhoea, anorexia, gen eralized oedema and anaemia that
was endemic in certain parts of the country. It was particularly prevalent in a
village named Katayama, and was, on that ac count, sometimes known as Katay-
ama disease, the villagers ascribing the condition to a lacqueur said to hav e
been released from a ship wrecked nearby in a storm years before.
The first recorded clinical description of schistosomiasis was by a physician,
Dairo Fujii (pen name, Yoshinao), who visited the region in 1847 and wrote a
report which remained largely unknown for man y years. It was eventually found
in the possession of a descenda nt, Yaekichi Fujii, and Fujinami arranged for its
publication. Fujii did not know what type of disease it was, but described the
initial cutaneous manifestations, considered the onset as being not unlike that
of consumption (wasting disease, tuberculosis, although that infection was not
yet defined bacteriologically), and concluded that in its terminal stages, th e
condition was really an "abdominal swelling":
the native people who waded in the water to till the fields developed on their lower
legs small papules which were extremely pruritic....the clinical manifestations in
severe cases - pallor, sunken yellow facies, night sweats with muscle wasting, a rapid
and feeble pulse - were similar to those of consumption. Some people had watery
diarrhea and some had tenesmus. Others had a bloody or mucoid diarhhea. Later
wasting of the extremities occurred and the abdomen became swollen, like a drum.
Below the breasts the abdominal veins were dilated and the umbilicus herniated
outward. In advanced cases, the abdominal skin became shiny, even reflective,
anasarca usually ensued and the patient died.32
In the early 1880's, Erwin Baelz, a German professor at the Imperia l
University of Tokyo, visited the endemic area at Okayama. He found that 20%
of the population were afflicted with hepatosplenomegaly, bloody diarrhoea ,
anaemia, fever, ascites and oedema. Baelz attributed these findings t o
Clonorchis sinensis 6, although it now seems much more likely that he wa s
dealing with schistosomiasis japonica.
Nearly sixty years after Fujii's visit, and being aware of his memoir, Kenj i
Kawanishi (Kasai) visited Katayama. He too was familiar with the skin rashes,
and noted that cows and horses were also affected, writing "Persons who g o
into the mud immediately develop red rashes; the associated pruritis (sic) i s
said to be unbearable" 52. He then went on to state that the signs of Katayam a
disease were "(an) enlarged liver and spleen, sometimes abdominal ascites ,
anaemia and bloody stools" 52.
Although the relationship betwen schistosomiasis japonica and skin rashes
was fairly striking, there were some dissenters. For example, Miyagawa (1913)
discounted the association on a number of grounds, including variations i n
geographical distribution of the two conditions, differences in the histological
appearances of the skin, and the absence of eggs in the faeces of many patients
with dermatitis 83.
In various parts of China, a syndrome of fever with urticaria had been recog-
nized from time to time. This condition was known as Yangtze Fever, Hankow
Fever, Kiukang Fever and Urticarial Fever, dep ending upon the region in which
it was observed. In 1910, Houghton at Wuhu Hospital in China associated this
syndrome with S. japonicum infection69, then this opinion was supported b y
other observers. In 1913, Edgar gave an excellent description of the syndrome
which usually afflicted children or young men who bathed in creeks or waded
in marshy ground in the Chang Jiang (Yangtse) valley; the condition wa s
particularly well-recognized in foreign seamen. According to Edgar, malaise
was followed by headache, myalgia and fever which was remittent in character
and lasted for three to six weeks. Half of the cases had transient or persistent
urticaria, and many complained of cough and transitory diarrhoea whic h
sometimes developed into dysentery. The illness usually settled down withi n
two to three weeks 26.
This description was reiterated in the following year by Laning wh o
described two further stages in the evolution of the disease 56, a classification
which was also adopted by Mann 73. The next stage of illness was associate d
with hepatosplenomegaly, dysentery, marked eosinophilia, and the passage of
S. japonicum eggs in the stools. A terminal stage which may or may no t
supervene was typified by a:
cirrhotic liver, sometimes enlarged, sometimes shrunken, ascites, oedematous
extremities, marked emaciation, anaemia, weakness, passage of blood and mucus in
the stools.56
Interest in the clinical manifestations of schistosomiasis japonica by Western
clinicians was rekindled when a number of troops became infected during the
invasion of Leyte island in the Philippines in 1944. A number of series o f
patients were reported, and these descriptions generally followed the patter n
described thirty years earlier in China 30,45,107
With respect to prognosis, it had been apparent from the early times that the
severity of illness seemed to be dependent upon the intensity of infection. Long-
term observations of expatriates infected in China before and around Worl d
War I, and of Allied troops infected in Southe ast Asia during World War II, and
who were then removed from the endemic area, indicated that the prognosi s
was probably good in the absence of reinfection. Whether or not significan t

resistance to reinfection develops is uncertain, although Vogel and Minning in
1953 reported that complete resistance to reinfection could be built up i n
experimental monkeys infected repeatedly with S. japonicum 116.
The simplest means of diagnosing schistosomiasis japonica, that is the demon-

stration of the pathognomonic eggs in the stool, was discovered before th e
causative agent was found. Thus, in late 1902, or possibly in early 1903 ,
Kawanishi discovered what he regarded as a new type of egg in the faeces of
a patient from near Katayama. This patient had the typical syndrome common
in that area:
In the stools.....I found oval-shaped light brown colored eggs, 0.1-0.08 mm in length
and 0.077-0.05 in width.....an operculum is not found. The eggs vary in content. 52
Kawanishi therefore went back to the endemic area in March 1903 and found
several more patients excreting the same eggs. The value of this diagnosti c
technique was confirmed by Katsurada 49,50 in 1904 when he found eggs in the
faeces of five such patients and then went o n to discover the adult worms. Since
that time, considerable attention has been paid to improving techniques fo r
demonstrating and quantifying eggs in faeces (see chapter 9).
The introduction of sigmoidoscopy provided a means of assessing structural
damage to the large bowel and permi tted an alternative method of finding eggs.
Thus, Johnson and Berry (1945) reported that small yellow nodular lesion s
could be seen on sigmoidoscopy, particularly at the rectosigmoid junction, and
that biopsy of these lesions revealed the presence of the characteristic eggs 45.
Diagnosis of schistosomiasis japonica by liver biopsy, which also provides an
assessment of structural damage in the live r, appears to have been first reported
by Stransky and Pesigan in 1953 101. Later, Kurata showed that liver functio n
tests may provide an index of hepatic damage 54.
Many attempts have been made to dev elop immunodiagnostic procedures for
use in schistosomiasis japonica. In 1910, Yoshimoto was probably the firs t
person to introduce a complement fixation assay 123, while Miyairi and Imai in
1928 described a precipitin test 85. In 1936, Kan described an intradermal test 46.
Details of the development of drugs which have been used in the therapy o f
schistosomiasis japonica have been described in chapter 8. Initially, quinine 110
and arsenicals were tried, particula rly in Japan, but these drugs did not pass the
test of time and proved of little use. In 1913, Hutcheson reported that emetine
was useful in patients with dysentery 43. In view of the efficacy claimed for the
drug in other forms of schistosomiasis, there may have been some activit y
against S. japonicum, but it is also possible that the patients had concurren t
amoebic dysentery which responded to the drug. There was dispute over th e
effectiveness of emetine during the next few years 51,94,112, but interest in it
largely waned in favour of tartar emetic.
Following the introduction of antimonials for the treatment of schistosomiasis
in Africa, the drug was tried in Chin a and Japan against S. japonicum. In 1921,
Sanders and Priston reported that intravenous injection of antimony was effic-
acious in three patients; there was a great reduction in the numbers of ov a
excreted and those that were present in the faeces were not viable 97. On the
other hand, Libby, in a small series of cases, found that tartar emetic was not
particularly active and this led to suggestions that this drug was less effective
in schistosomiasis japonica than in other forms of human schistosomiasis 65. In
a later and more extensive study, the same author concluded that while tartar
emetic was useful in mild and moderate cases, it was of little value for patients
with severe infections where there was hepatosplenomegaly 66. Nevertheless,
Meleney and his colleagues regarded the drug as curative when a total dose of
1.5-2.0 grams of antimony was given over a period of 18-20 days 29,80.
Moreover, Nishi investigated the actions of the drug in experimentally infected
dogs and found that sodium antimony tartrate was able to kill youn g
schistosomes and affected eggs in tissues 90.
In 1951, Pesigan and his colleagues showed that lucanthone, when used in
doses recommended for other forms of schistosomiasis, was ineffective in the
treatment of S. japonicum infections93. Likewise, metrifonate and oxamniquine
were found to be inactive. At a symposium on niridazole held in Lisbon i n
1965, there were suggestions that this drug may be less effective i n
schistosomiasis japonica than in the treatment of S. mansoni and S. haem-
atobium infections. This question was investigated further by Santos and hi s
colleagues in the Philippines; they found that the cure rate in 106 patient s
treated with various regimens of niridaz ole ranged between 48% and 85% 98. Sy
then treated 237 persons and managed to follow up just over half of them one
month later; 55% were cured, the egg count wa s reduced in 18%, and there was
no response in the remaining 27% of patients 105. Praziquantel now looks to be
the drug of choice in the treatment of schistosomiasis japonica. Th e
introduction of this drug has been described in chapter 8. Suffice it to say here
that Santos and his colleagues studied the effects of different dosage regimens
in 128 Filipino patients and found that praziquantel was very effective; onl y
24% of patients treated for three days and reviewed 12 months later were still
passing ova in the faeces 99.
The syndrome known as Katayama disease and w hich turned out to be caused
by S. japonicum, was associated with water long before the causative agent was
identified. Thus, Fujii in 1847 related the condition to wading in the padd y
fields, and by making use of the appearance of a rash on the legs, was able to
pinpoint the time of the year at which infection was acquired to the seaso n
between spring and summer 32. The same connection between working in rice
fields and Katayama disease was recognized by Kawanishi who, in 1904 ,
provided a concise description of the locale. At that time, Katayama was a
village of 190 inhabitants and 36 houses situated at the foot of a hill 80 fee t
high. The paddy fields were several feet lower than the level of the river, thus
making it very difficult to drain the stagnant water, particularly during th e
prolonged rainy season, and it was in these fields that workers developed the
erythematous eruption on their legs 52. Furthermore, it was in these people that
Kawanishi found S. japonicum eggs, thus bringing the nature of the affliction
closer to clarification.
Fujii also recognized the focal nature of the condition, the locations an d
boundaries of which were gradually extended by a number of Japanes e
clinicians over the next sixty years. The discoveries by Catto in 1904 o f
S. japonicum in a man from Fukien province of China16,17, and in an 18 year old
male in Hunan province, China, by Logan in the following year 68 widened
knowledge of the geographical distribution considerably, as did the report by
Wooley in 1906 of schistosomiasis japonica in the Philippines 118. Many years
later (1937), Brug and Tesch discovered an endemic focus of infection i n
Sulawesi, Indonesia12. From time to time, weather conditions led to epidemics
of schistosomiasis in new areas as, for example, occurred when the summe r
floods in the Chang Jiang (Yangtse) valley in 1931 brought the infection from
the upper part of the system down to the delta 47, or when major floods occurred
in China in 1954 67.
The reason for the association with water fell into place, of course, with the
discovery that certain species of snails were the vectors of infections. Attention
then turned to investigating the behaviour and ecology of these long, narrow,
operculated snails. The amphibious snails were most numerous in wet, moist
soil near water and thick grass. The population was densest along irrigatio n
ditches and became progressively thinner on the banks of rivers and canals, in
rice beds, and in paddy fields. It was shown that they were most active at night,
but crawled only at a rate of about three metres a month. If the surface of the
earth became dry, the snails dug down into the deeper, wetter reaches, and by
closing the operculum, survived for three months or so, although infecte d
molluscs tended to die earlier. Mating was found to occur throughout the year,
but was at a maximum in the spri ng and early summer and at a minimum in the
early winter, with many snails hibernating during the depths of winter. Th e
average life span was determined at around five years or so, wit h
newly-hatched snails taking up to a year to reach maturity 21,29,103.

Finally, it was realized from the beginning that this form of schistosomiasis
was an extensive zoonosis, for a wide range of animals were found to b e
infected in nature, beginning with Katsurada's discovery of adult worms in cats
in 190449,50. These included dogs, rats, mice, cattle, water buffalo, pigs, horses,
sheep and goats.
Hopes for the control or, better, the eradication of schistosomiasis have been
held for many years. Over a century ago, Fujii left a memoir expressing thi s
desire:
I recently read my manuscripts and found the script of 'Katayama Memoir'. Thirty
years have passed....By knowing (what causes it), we can treat it. In this way, the
mysterious disease which has existed for many years can be eliminated easily. This
would be good for the people.32
Once Fujinami and Nakamura had shown that infection was acquired whe n
parasites penetrated the skin , they were able to suggest several means whereby
the infection could be contained:
(1) the faeces which contain the eggs must be disinfected. (2) in order to prevent the
growth of the causative agent, constructions on land and water must be renovated; (3)
in order to prevent the causative agents penetrating the body, contact with
contaminated water should be avoided.36
The first of these points was overvalued to some extent, for it took no account
of the excretion of eggs by infect ed animals, while the last proposal was clearly
impossible for the many peasants whose livelihood depended upon working in
the paddy fields. The discovery of the snail intermediate host by Miyairi an d
Suzuki, however, provided another point at which the cycle of transmissio n
could be attacked. This seemed the simplest approach, so attention in Japa n
centred upon the evaluation of various molluscicides. Of all the chemical s
tested, lime was found to be the surest and most economical agent 34,37. This
chemical was available readily in Japan and the farmers used it for fertilizing
the rice fields. Lime was therefore spread on the banks of infested canals and
drainage ditches, and in the water contained in them. Alternatively, Fujinami
and Fukutuni showed that burying the snails in wet, but not dry, soil kille d
them.
In 1928, Todokoro reported on the effectiveness of a combination o f
measures in Hiroshima prefecture in Japan. These included the destruction of
snails with lime, the installation of pit latrines, the replacement of cattle b y
horses (which are less susceptible to infection 34) for ploughing, the repression
of wild rats, and educating the local inhabitants about the dangers of immersing
skin in water. The results were highly encouraging, with the incidence of skin
rashes decreasing and the prevalence of infection in cattle and the numbers of
snails dropping markedly 108. Since that time, and occurring pari passu with
improving economic conditions, as well as the introduction of specifi c
measures such as the cement lining of irrigation ditches and the availability of
more effective molluscicides, the infection has almost disappeared i n
Japan120,121.
Similar excellent results have not been achieved in the Philippines o r
Indonesia where the paucity of economic resources has militated agains t
attempts to control the infection.
The situation in China is somewhat less clear. In 1924, after reviewing the
biological and technical problems in volved, Faust canvassed some of the social
and political factors that would affect control measures:
One more fact must be kept in mind in considering such an undertaking so intimately
concerning the native farming class - namely, their suspicion that only harm can result
from any stranger tresspassing on their domain. Coupled with this is the improbability
of securing any government cooperation at the present time in China. 27
Then, with truly prophetic foresight, he went on to add:
In spite of these unpleasant facts, the problem of eradicating schistosomiasis from
China is a hopeful one. One must bear in mind that China is an ancient country, that
she moves slowly and deliberately, but that she moves surely. The next fifty years will
bring much in the way of reorganization and development in China. It seems not too
much to expect that public health and preventive medicine will follow closely upon
the steps of improved agriculture and commerce, and that in this scheme of affairs,
schistosomiasis will not long be allowed to remain an uncontrolled infection in the
heart of the country.27
Schistosomiasis was regarded in China as a serious parasitic disease with a
major economic impact. By the middle of the 1950's, a nationwide contro l
scheme was evolved and put into operation. Maegraith visited the country a
year or two after the inititiation of this programme and has recorded hi s
impressions 71. The extent of infection at that time was not fully known, but it
was estimated that over 11 million people were infected in the fertile region of
the Yangtse valley. The three major components of the control scheme wer e
mass treatment of overt infections (with the two-fold aim of bringing clinical
relief and a reduction in the contamination of the environment with eggs) ,
preventing the pollution of water by infected human and animal faeces, an d
destruction of the snail intermediate hosts. Schistosomiasis centres wer e
established for the purpose of mass treatment, propaganda and administrative
control, while the actual field work was done by local farming and villag e
communities. The year 1970 was set as the target for effective control. Th e
most commonly used anthelmintic was sodium or potassium antimony tartrate,
given intravenously, initially in seven or 20 day courses, but later in a three day
regimen of treatment. Educational campaigns were set up to limit promiscuous
defaecation; arrangements were made to collect and store faeces for one week
in order to allow the ammonia that was generated to destroy the ova whic h
otherwise would survive for several months, but problems were encountered
in dealing with animal faeces. Snail control with molluscicides was instituted
with Paris green or calcium arsenate being used most commonly at first, bu t
later sodium pentachlorophenate be came the most popular chemical; they were
sprayed on land within two metres of the water level. Physical methods were
also employed; these included burning of grass in summer and the manua l
removal and burial of snail-containing mud in winter.
In 1977, an American delegation visited China in order to assess the impact
of these various measures on the prevalence of schistosomiasis 4. The members
of the delegation noted that by 1959, 25,000 communal health units concerned
with schistosomiasis control had been set up. Between 1958 and 1962 ,
5,000,000 people were treat ed with schistosomicides. The campaign to reduce
the numbers of Oncomelania hupensis , however, was the most importan t
feature of the control efforts. The delegation considered that there had been a
reduction by two thirds in the prevalence of human schistosomiasis. Th e
success of the programme was ascribed to China's economic, social an d
political organization which permitted disciplined mass participation, a n
approach which would be very difficu lt for any other nation to emulate. Finally,
it was also concluded that in addition to the effects of the various specifi c
control measures, the reduction in schistosomiasis transmission was probably
also consequent upon a general improvement in socio-economic conditions.
SCHISTOSOME DERMATITIS (SWIMMER'S ITCH, BATHER' S

ITCH)
Cases of dermatitis of unknown aetiology had occurred for a number of years

in persons wading in the freshwater Douglas Lake in Michigan, USA, whil e
collecting biological specimens for the Michigan Biological Station. Simila r
cases had also occurred in people at several holiday resorts in the region. I n
1928, WW Cort, while collecting molluscs, ( Lymnaea emarginata-angulata )
discovered accidentally that cercariae of a non-human schistosome, Cercaria
elvae (now known as the cercaria of Trichobilharzia ocellata ), produced a
severe, prickly sensation on the wrists and that this was followed by th e
appearance of papules which evolved into a pustular eruption with intens e
itching within 48 hours 23.
Soon afterwards, Christenson and Greene confirmed this observation a t
several lakes in Minnesota, finding C. elvae in Lymnaea stagnalis opressa 20.
Later that year, a similar outbreak occurred in people bathing in an artificia l
lake in Cardiff, Wales, and this was shown to be due to the same parasite 77. In
1930, Taylor and Baylis pointed out that C. elvae was identical with
C. ocellata. They further remarked that although the adult form was not known,
the cercariae resembled closely Bilharziella polonica which inhabited the
mesenteric veins of ducks 106. This was confirmed in the following year b y
Brumpt who placed four ducks in a vessel containing C. ocellata then recov-
ered subsequently eggs and adult forms of B. polonica 14. In 1940, Brackett
(who had been exposed naturally on many occasions) infected himself delib-
erately with C. stagnicola and C. ocellata then excised the lesions 29 and 50
hours later, respectively; no cercariae were seen but intense inflammation was
noted11. Subsequently, similar cases of dermatitis caused by cercariae o f
Trichobilharzia, Gigantobilharzia and Ornithobilharzia species, the definitive
hosts being birds and the vectors including species of Chilina, Physa,
Planorbis, Polypis and Stagnicola were reported from many parts of the world.
A second form of cercarial dermatitis acquired in fresh water was shown to
be due to penetration of human skin by cercariae of schistosomes whic h
develop in mammals other than man. This was first reported by Buckley i n
1938 who found that dermatitis in workers in paddy fields was a consequence
of infection with S. spindale cercariae15. Similar effects have since bee n
recognized as being caused by S. bovis 9, S. douthitti 24, S. mattheei 1 Hetero-
bilharzia americana 58 and Orientobilharzia turkestanicum 96.
Finally, cercarial dermatitis may also be acquired while bathing in salt water,
as was first reported by Penner in 1950. Seabirds serve as the definitive hosts
while marine molluscs are the vectors of the worms. Penner described a new
avian schistosome larva, Cercaria littorinalinae from the marine snail,
Littorina planaxis, found on the coast of southern California 92. Two years later,
Stunkard and Hinchcliffe described a s imilar affliction on the beaches of Rhode
Island, USA102. Parasites now known to cause this condition include Bilharzia
variglandis 102 and Gigantobilharzia huttoni 59.
OTHER SPECIES OF SCHISTOSOMA
S. BOVIS
This species was first described in 1876 by Sonsino when he recovered th e

worms from cattle in Egypt100. The eggs are longer and narrower than those of
S. haematobium, thus facilitating delineation of the species. Bulinus species are
molluscan intermediate hosts. There have been isolated but doubtful reports the
occurrence of this worm in humans.
S. INCOGNITUM
The distinctive eggs of this parasite were recovered from the faeces of tw o
human patients by Chandler in 1926. He proposed the name S. incognitum as
the parent worms were unknown 18. Later, the adult worms were found in pigs
and dogs in India8, then subsequently in rodents in southeast Asia. The egg s
have a short, pointed, terminal spine.
S. INTERCALATUM
In 1908, GC Low stated that when he was in Uganda, schistosomiasis wa s

almost entirely of the intestinal form, yet he only found terminal-spined ova in
the stools70. A similar observation was made in 1923 by CC Chesterman in the
Belgian Congo (Zaire) 19. In 1934, also in Zaire, AC Fisher found severa l
hundred such cases and erected a new species, S. intercalatum, to designate
this parasite31. Like S. haematobium, Bulinus species of snails are the
intermediate hosts of this worm. It resembles S. haematobium morphologically
and may be merely a strain of that helminth.
S. MARGREBOWIEI
This schistosome was discovered in ruminants by Le Roux in 1933 64. The egg
has a small, terminal spine. A human infection was reported by Lapierre and
Hien in 1973 57.
S. MATTHEEI
This schistosome was originally described in a sheep by Veglia and Le Roux

in 1929113. The eggs are terminally spined and Bulinus species of snails are the
intermediate hosts. The first definitive report of the occurrence of the infection
in humans was by Blackie in 1932 following a survey in Southern Rhodesi a
(Zimbabwe) 10.
S. MEKONGI
The first case of human schis tosomiasis of southeast Asian origin was reported
in 1957 not from Asia but from Paris when Vic-Dupont and colleagues dis -
covered the condition in an 18 year old Eurasian with hepatosplenomegaly and
haematemesis; the early part of the patient's childhood had been spent o n
Khong island in the Mekong river between Laos and Cambodia 114. Between
1963 and 1966, Barbier, also in Paris, saw four more Indochinese students who
were infected similarly; enquiry revealed that they had all lived on Khon g
island7. Alerted by these observations, a World Health Organization team was
sent to the island and found that schistosomiasis was endemic there 44.
Subsequent surveys indicated that the infection was endemic in some regions
of Thailand. Shortly thereafter, the intermediate host was identified as a n
aquatic, not amphibious mollusc, Lithoglyphopsis aperta 41, now known as
Tricula aperta 25. In 1978, Voge and her colleagues erected a new species, S.
mekongi, for this parasite, on the grounds that the eggs were smaller, th e
prepatent period in mice was l onger, and the intermediate host was different 115.
S. RODHAINI
This parasite of African wild rodents was described by Brumpt in 1931 13. The
eggs have a subterminal spine. It is transmit ted by Biomphalaria snails. Human
infection was reported in Zaire in 1954 by Gillet and Wolfs 38.
REFERENCES
1. ALVES W. Experimental cercarial dermatitis in man due to cercariae of Schistosoma

mattheei. Transactions of the Royal Society of Tropical Medicine and Hygiene 47: 272, 1953
2. ANNANDALE N. Supplement on the molluscan hosts of the human blood fluke in China and
Japan and species liable to be confused with them. In, Studies on schistosomiasis japonica, by
EC Faust and HE Meleney, American Journal of Hygiene Monograph Series, No. 3, pp 361,
1924
3. ANONYMOUS. Helminthological investigations. Journal of Tropical Medicine and Hygiene
17: 84-85, 1914
4. ANONYMOUS. Report of the American schistosomiasis delegation to the People's Republic
of China. American Journal of Tropical Medicine and Hygiene 26: 427-462, 1977
5. ATKINSON EL. cited in 89
6. BAELZ E. Ueber einige neue Parasiten des Menschen. Berliner klinische Wochenschrift 20:
234238, 1883
7. BARBIER M. Détermination d'un foyer de bilharziose artério-veineuse au sud-Laos (Province
de Sithadone). Bulletin de la Société de Pathologie Exotique 59: 974-983, 1966
8. BHALERAO G. On the occurrence of Schistosoma japonicum Katsurada in India. Indian
Journal of Veterinary Science and Animal Husbandry 4: 148-151, 1934
9. BIOCCA E. Osservazione sulla morfologia e biologia del ceppo sardo di schistisome bovis e
sulla dermatitie umana da esso provocato. Parassitologia 2: 47-54, 1960
10. BLACKIE WK. A helminthological survey of southern Rhodesia. Memoir Series of the
London School of Hygiene and Tropical Medicine, No. 5, pp 1-91, 1932
11. BRACKETT S. Pathology of schistosome dermatitis. Archives of Dermatology and Syphilis
42: 410-418, 1940
12. BRUG SL, TESCH JW. Parasitaire wormen aan het Lindoe Meer (Ou. Paloe, Celebes).
Geneeskundig Tijdschrift voor Nederlandsch-Indië 77: 2151-2158, 1937
13. BRUMPT E. Description de deux bilharzies de mammifères africaines, Schistosoma
curassoni sp. inquir. et Schistosoma rodhaini n. sp. Annales de Parasitologie Humaine et
Comparée 9: 325-338, 1931
14. BRUMPT E. Cercaria ocellata déterminant la dermatite des nageurs provient d'une bilharzie
des canards. Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences 193:
612-614, 1931
15. BUCKLEY JJ. On a dermatitis in Malaya caused by the cercariae ofSchistosoma spindale
Montgomery, 1906. Journal of Helminthology 16: 117-120, 1938
16. CATTO J. A new blood fluke of man. Transactions of the Pathological Society of London 56:
179189, 1905. Abstracted in Lancet ii: 1499, 1904
17. CATTO J. Schistosoma cattoi, a new blood fluke of man. British Medical Journal i: 11-13,
1905
18. CHANDLER AC. A new schistosome infection in man, with notes on other human fluke
infestations in India. Indian Journal of Medical Research 14: 179-183, 1926
19. CHESTERMAN CC. Note sur la bilharziose de la région de Stanleyville (Congo Belge).
Annales de Société Belge de Médecine Tropicale 3: 73-75, 1923
20. CHRISTENSON RO, GREEN WP. Studies on biological and medical aspects of "swimmers
itch". Schistosome dermatitis in Minnesota. Minnesota Medicine 11: 573-575, 1928
21. CORT WW. On the resistance to dessication of the intermediate host of Schistosoma
japonicum Katsurada. Journal of Parasitology 6: 84-88, 1919

22. CORT WW. The development of the Japanese blood-fluke, Schistosoma japonicum
Katsurada, in its final host. American Journal of Hygiene 1: 1-38, 1921
23. CORT WW. Schistosome dermatitis in the United States (Michigan). Journal of the American
24. CORT WW. Studies on schistosome dermatitis. American Journal of Hygiene 52: 251-307,
1950
25. DAVIS GM. Snail hosts of African Schistosoma infecting Man: evolution and co-evolution.
In, The Mekong schistosome, JI Bruce and S Sornmani (Editors), Whitmore Lake, Michigan,
Malacological Review Supplement 2: 195-238, 1980
26. EDGAR WH. Yangtze fever. Journal of State Medicine 21: 542-553, 1913
27. FAUST EC. Schistosomiasis in China: biological and practical aspects. Lancet i: 21-24, 1924
28. FAUST EC, MELENEY HE. The life history of Schistosoma japonicum Katsurada. China
29. FAUST EC, MELENEY HE. Studies on schistosomiasis japonica. American Journal of
Hygiene Monograph Series No. 3, pp 326, 1924
30. FAUST EC, WRIGHT WH, McMULLEN DB, HUNTER GW. The diagnosis of
schistosomiasis japonica. I. The symptoms, signs and physical findings characteristic of
schistosomiasis japonica at different stages in the development of the disease. American
Journal of Tropical Medicine 26: 87-112, 1946
31. FISHER AC. A study of schistosomiasis in the Stanleyville district of the Belgian Congo.
32. FUJII D (pen name, YOSHINAO). (An account of a journey to Katayama.) Chugai Iji Shinpo
No. 691, pp 55-56, 1909. (Originally published in 1847). In Japanese. Translated in 53, 117
33. FUJINAMI A. (Ueber die pathologische Anatomie, und ueber den bom Verfasser entdeckten
weiblichen Parasiten des Schistosomum japonicum.) Kyoto Igakkai Zasshi 1: No. 1, 1904.
In Japanese, with German summary
34. FUJINAMI A. Historical review of scientific investigations on the pathology of
schistosomiasis in Japan, and efforts for the eradication of this disease. Japan Medical World
6: 304-308, 1926
35. FUJINAMI A, NAKAMURA H (The mode of transmission of Katayama disease of Hiroshima
Prefecture, Japanese schistosomiasis, the development of its causative worm, and the disease
in animals caused by it.) Hiroshima Iji Geppo 132: 324-341, 1909. In Japanese. Abstracted
in 117
36. FUJINAMI A, NAKAMURA H. (Route of infection, development of the worm in the host and
animals in Katayama disease in Hiroshima Prefecture [Japanese blood sucking worm disease
- schistosomiasis japonica].) Kyoto Igaku Zasshi 6: 224-252, 1909. In Japanese. Translated
in 53.
37. FUJINAMI A, SUYEYASU Y. (Prophylaxis in schistosomiasis japonica.) Nishin Igaku
(special number), November-December 1919. In Japanese.
38. GILLET J, WOLFS J. Human schistosomiasis in the Belgian Congo and in Ruanda-Urundi.
39. GOTO T. Beiträge zur Kenntnis der Migrations-route von Schistosoma japonicum in den
Endwirten. Fukuoka Ikwadaigaku Zasshi 25, No, 3, 1932. In Japanese; German summary pp
11-13
40. HALL SC, KEHOE EL. Prolonged survival of Schistosoma japonicum. California Medicine
113: 75-77, 1970
41. HARINASUTA C, SORNMANI S, KITIKOON V,SCHNEIDER CR, PATHAMMAVONG
O. Infection of aquatic hydrobiid snails and animals with Schistosoma japonicum-like
parasites from Khong Island, Southern Laos. Transactions of the Royal Society of Tropical
42. HSÜ H F, HSÜ S Y. On the infectivity of the Formosan strain ofSchistosoma japonicum in
Homo sapiens. American Journal of Tropical Medicine and Hygiene 5: 521-528, 1956
43. HUTCHESON AC. Results in thirteen casesof dysentery treated with emetine. China Medical
Journal 27: 243-245, 1913
44. IJIMA T, GARCIA EG. Preliminary survey for schistosomiasis in South Laos. World Health
Organization Document, WHO/BILH/67.64, 1967

45. JOHNSON AS, BERRY MG. Asiatic schistosomiasis: clinical features, sigmoidoscopic
picture and treatment of early infections. War Medicine 8: 156-162, 1945
46. KAN HC. Intracutaneous test with Schistosoma japonicum antigen. Chinese Medical Journal
Supplement 1: 387-393, 1936
47. KASTEIN J. Beobachtungen von gehäuftem Auftreten von "Schistosomum japon-
icum"-Erkrankungen in Shanghai. Archiv für Schiffs- und Tropen-Hygiene 36: 1-4, 1932
48. KATSURADA F. (Ueber eine endemische Krankheit in der Provinz Yamanashi.)
Mittheilungen aus der medizinischen Gesellschaft zu Okayama No. 173, 1904. In Japanese,
with German summary.
49. KATSURADA (The etiology of a parasitic disease.) Iji Shimbun No. 669, pp 1325-1332,
1904. In Japanese. Translated in 53
50. KATSURADA F. Schistosomum japonicum, ein neuer menschlicher Parasit, durch welchen
eine endemische Krankheit in verschiedenen Gegenden Japans verusacht wird. Annotationes
Zoologicae Japonenses 5: 146-160, 1904. Translated as, Schistosomum japonicum, a new
human parasite which gives rise to an endemic disease in different parts of Japan. Journal of
51. KAWAMURA R, KAZAMA Y, TANAKA S. (On the therapeutic treatment of
schistosomiasis japonica.) Saikingaku Zasshi Nos. 336-337, 1924. In Japanese. Abstracted
in Japan Medical World 4: 132-133, 1924
52. KAWANISHI K (pen name Kasai). (A report on a study of the "Katayama disease" in Higi-
no-kuni. Tokyo Igakkai Zasshi, 18 (3): 31-48, 1904. In Japanese. Partly translated in 53.
53. KEAN BH, MOTT JE, RUSSELL AJ. Tropical medicine and parasitology. Classic
54. KURATA M. Pathological physiology of schistosomiasis japonica. Kurume Medical Journal
10: 137-161, 1963
55. KURIMOTO T. (Ueber die Eier eines neuen Parasiten.) Mittheilungen aus der medizinischen
Gesellschaft zu Tokyo 7 (22): 1-6, 1893. In Japanese, with German summary
56. LANING RH. Schistosomiasis on the YangtzeRiver, with report of cases. United States Naval
Medical Bulletin 8: 16-36, 1914
57. LAPIERRE J, HIEN TV. Un cas de triple infestation bilharzienne àSchistosoma mansoni,
S. haematobium et Rhodobilharzia margrebowiei? Annales de Parasitologie Humaine et
Comparée 48: 301-306, 1973
58. LEE HF. Susceptibility of mammalian hosts to experimental infection withHeterobilharzia
americana. Journal of Parasitology 48: 740-745, 1962
59. LEIGH WH. The morphology of Gigantobilharzia huttoni (Leigh, 1953), an avian
schistosome with marine dermatitis-producing larvae. Journal of Parasitology 41: 262-269,
1955
60. LEIPER RT. Note on the presence of a lateral spine in the eggs ofSchistosoma japonicum.
61. LEIPER RT. Report on an expedition to China to study the trematode infections of man.
Unpublished report to the Colonial Office, pp 4, 15 January 1915. Abstracted in Tropical
63. LEIPER RT, ATKINSON EL. Observations on the spread of Asiatic schistosomiasis. British
64. LE ROUX PL. A preliminary note on Bilharzia margrebowiei - a new parasite of ruminants
and possibly of man in Northern Rhodesia. Journal of Helminthology 11: 57-62, 1933
65. LIBBY WE. Tartar emetic in schistosomiasis japonica. China Medical Journal 37: 158-166,
1923
66. LIBBY WE. A further study in schistosomiasis japonica. China Medical Journal 38: 376-388,
1924
67. LIU J, CHENG WJ, HUANG MH,P'AN JS, CHIANG SC, HSÜ CY, HSÜ PY, T'ANG CY.
Acute schistosomiasis japonica. Chinese Medical Journal 76: 229-242, 1958
68. LOGAN OT. A case of dysentery in Hunan province caused by the trematode,Schistosoma
japonicum. China Missionary Medical Journal 19: 243-245, 1905

69. LOGAN OT. Schistosomiasis (japonicum) and "urticarial fever". A disclaimer of the priority
of suggesting that these diseases were identical. China Medical Journal 26: 240-241, 1912.
70. LOW GC. Discussion on "The part played by metozoan parasites in tropical pathology" by
L W Sambon. Transactions of the Society of Tropical Medicine and Hygiene 2: 45, 1908
71. MAEGRAITH BG. Schistosomiasis in China. Lancet i: 208-214, 1958
72. MAJIMA T (pen name Naganori). (A strange case of liver cirrhosis caused by parasitic ova).
Tokyo Igakkai Zasshi 2 (17): 898-901, 1888. In Japanese. Translated in 53.
73. MANN WL. Some practical aspects of schistosomiasis as found in the Orient. Journal of the
74. MANSON P, CATTO J. A new nematode. Lancet ii: 615, 1904
75. MAO SHOU-PAI, SHAO BAO-RUO. Schistosomiasis control in the People's Republic of
China. American Journal of Tropical Medicine and Hygiene 31: 92-99, 1982
76. MARKEL SF, LOVERDE PT, BRITT EM. Prolonged latent schistosomiasis. Journal of the
77. MATHESON C. Notes on Cercaria elvae Miller as the probable cause of an outbreak of
dermatitis at Cardiff. Transactions of the Royal Society of Tropical Medicine and Hygiene 23:
422-424,. 1930
78. MELENEY HE, FAUST EC. The intermediate host of Schistosoma japonicum. I. Its
discovery in the Soochow region. II. Its distribution in China. China Medical Journal 37:
541-554, 1923
79. MELENEY HE, FAUST EC. The route of migration of Schistosoma japonicum in the body
of its final host. Proceedings of the Society of Experimental Biology and Medicine 20:
397-398, 1923
80. MELENEY HE, FAUST EC, WASSEL CMcA. A study of intensive antimony therapy ni
schistosomiasis japonica. Journal of Tropical Medicine and Hygiene 15: 153-165, 1925
81. MIYAGAWA Y. Ueber den Wanderungsweg des Schistosomum japonicum von der Haut bis
zum Pfortadersystem und über die Körperkonstitution der jüngsten Würmer zur Zeit der
Hautinvasion. Centralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten,
Abteilung originale 66: 406-417, 1912. Partly translated in 53; Abstracted in 117.
82. MIYAGAWA Y. Ueber den Wanderungsweg des Schistosomum japonicum durch
Vermittlung des Lymphgefässystems des Wirtes. Centralblatt für Bakteriologie,
83. MIYAGAWA Y. Beziehungen zwischen Schistosomiasis japonica und der Dermatitis, unter
Berücksichtigung der Methode der Auffindung von Parasiteneiern in den Faeces, und Beiträge
zur Kenntnis der Schistosomum-Infektion. Centralblatt für Bakteriologie, Parasitenkunde und
84. MIYAGAWA Y, TAKEMOTO S. (The mode of infection of Schistosomum japonicum and
the principal route of its journey from the skin to the portal vein in the host.) Iji Shimbun No.
1839, 1918. In Japanese. Also, The mode of infection of Schistosomum japonicum and the
principal route of its journey from the skin to the portal vein in the host. Journal of Pathology
and Bacteriology 24: 168-174, 1921
85. MIYAIRI S, IMAI B. Serologische Studien bei Schistosomiasis japonica. Centralblatt für
Bakteriologie, Parasitenkunde und Infektionskrankheiten, Abteilung originale 106: 237-246,
1928
86. MIYAIRI K, SUZUKI M. (On the development of Schistosoma japonicum.) Tokyo Iji
Shinshi No. 1836, pp 1-5, 1913. In Japanese. Abstracted in 117
87. MIYAIRI K, SUZUKI M. Der Zwischenwirt des Schistosomum japonicum Katsurada.
Mittheilungen aus der medizinischen Fakultät der kaiserlichen Universität Kyushu Fukuoka
1: 187-197, 1914. Partly translated in 53; Abstracted in 117
88. NARABAYASHI F. (Contribution to the life history of Schistosomum japonicum. The
course in the final host from the skin to the portal vein.) Kyoto Igakai Zasshi 22 (3): 1-63,
1916. In Japanese
89. NELSON GS. A milestone on the road to the discovery of the life cycles of the human
schistosomes. American Journal of Tropical Medicine and Hygiene 26: 1093-1100, 1977
90. NISHI M. Experimental study of the treatment of schistosomiasis japonica with tartar emetic.
Clinical observation, histological investigation and pathological changes on animal

intoxicated with tartar emetic. Scientific Reports from the Government Institute for Infectious
Diseases, Tokyo 2: 485-501, 1923
91. OGATA S. Ueber den anatomischen Körperbau der Cercarien des Schistosomum japonicum
und die Uebertragungsweise derselben auf Tiere. Verhandlungen der japanischen
pathologischen Gesellschaft 48: 121-122, 1914
92. PENNER LR. Cercaria littorinalinae sp. nov., a dermatitis-producing schistosome larva
from the marine snail Littorina planaxis Philippi. Journal of Parasitology 36: 466-472, 1950
93. PESIGAN TP, PANGALINAN MV, SANIEL VF, GARCIA EG, BANZON TC, PUTONG
PB. Field studies on the treatment of schistosomiasis japonica with nilodin. Journal of the
Philippine Medical Association 27: 242-247, 1951
94. REED AC. Schistosomiasis japonica. American Journal of Tropical Diseases and Preventive
Medicine 3: 250-273, 1915
95. ROBSON GC. Note on "Katayama nosophora". British Medical Journal i: 203, 1915
96. SAHBA GH, MALEK EA. Dermatitis caused by cercariae of Orientobilharzia
turkestanicum in the Caspian Sea area of Iran. American Journal of Tropical Medicine and
Hygiene 31: 779-784, 1982
97. SANDERS AA, PRISTON JL. Notes on treatment of some cases of schistosomiasis. Journal
of the Royal Naval Medical Service 7: 290-292, 1921
98. SANTOS AT, BLAS BL, NOSEÑAS JS, PORTILLO GP. Niridazolein the treatment of
schistosomiasis japonica. Journal of the Philippine Medical Association 47: 203-207, 1971
99. SANTOS AT, BLAS BL, NOSEÑAS JS, PORTILLO GP, ORTEGA OM, HAYASHI M,
BOEHME K. Preliminary clinical trials with praziquantel in Schistosoma japonicum
infections in the Philippines. Bulletin of the World Health Organization 57: 793-799, 1979
100. SONSINO P. Intorno ad un unovo parasito del Buc Bilharz a bovis. Rendiconti della Reale
Accademia di Scienze Fisiche e Matematiche de Napoli 15: 84-87, 1876
101. STRANSKY E, PESIGAN NE. Liver damage in schistosomiasis in children. Preliminary
report. Journal of Tropical Medicine and Hygiene 56: 261-266, 1953
102. STUNKARD HW, HINCHCLIFFE MC. The morphology and life history of Microbilharzia
variglandis (Miller and Northrup, 1926), Stunkard and Hinchcliffe, 1951, avian
blood-flukes whose larvae cause "swimmers-itch" of ocean beaches. Journal of Parasitology
38: 248-265, 1952
103. SUGIURA S. (Studies on the prevention ofschistosomiasis japonica). Mittheilungen aus dem
pathologischen Institut der medizinischen Fakultät, Niigata, Japan No. 29, pp 10, 1933. In
Japanese, with English summary
104. SUYEYASU Y. (Invasionsweg des Schistosomum japonicum innerholb des Körpers des
Wirtes.) Kyoto Igakai Zasshi No. 1: 43-60, 1920. In Japanese, with German summary
105. SY FS. Niridazole in the treatment of schistosomiasis japonica. Journal of the Philippine
106. TAYLOR EL, BAYLIS HA. Observations and experiments on a dermatitis-producing
cercaria and on another cercaria from Limnaea stagnalis in Great Britain. Transactions of
107. TAYLOR HM, GAGE DP. Symptomatology of early schistosomiasis japonica. Bulletin of
the United States Army Medical Department 4: 197-202, 1945
108. TODOKORA K. History of Japanese schistosomiasis (Katayama Disease) and its prevention
in Hiroshima prefecture. Journal of the Public Health Association of Japan 4: 1-9, 1928
109. TSUCHIYA I. (Yamanishi disease.) Tokyo Iji Shinshi No. 1375, 1904. In Japanese
110. TSUCHIYA I. Clinical, pathological-anatomical, pathogenic, prophylactic and therapeutic
study of the schistosomiasis japonica. Sei-i-Kwai Medical Journal 32: 107-109. Abstracted
111. TUBANGUI MA. The molluscan intermediate host in the Philippines of the Oriental blood
fluke Schistosoma japonicum Katsurada. Philippine Journal of Science 49: 295-304, 1932
112. TYAU ES. Treatment of Asiatic schistosomiasis. National Medical Journal of China 8:
83-85, 1922
113. VEGLIA F, LE ROUX PL. On the morphology of a schistosome (Schistosoma mattheei sp.
n.) from the sheep in Cape Province. Fifteenth Annual Report, Director of Veterinary Service,
Union of South Africa, pp 335-346, 1929

114. VIC-DUPONT, BERNARD E, SOUBRANE J, HALLÉ B, RICHIR C. Bilharziose à
Schistosoma japonicum à forme hépato-splénique révélée par une grande hématémèse.
Bulletins et Mémoires de la Société des Hôpitaux de Paris 73: 933-941, 1957
115. VOGE M, BRUCKNER D, BRUCE JI.Schistosoma mekongi sp. n. from man and animals,
compared with four geographical strains of Schistosoma japonicum. Journal of Parasitology
64: 577584, 1978
116. VOGEL H, MINNING W. Über die erworbene Resistenz vonMacacus rhesus gegenüber
Schistosoma japonicum. Zeitschrift für Tropenmedizin und Parasitologie 4: 418-505, 1953
117. WARREN KS. Schistosomiasis. The evolution of a medical literature. M.I.T. Press,
Cambridge, Mass., pp 1307, 1973
118. WOOLEY PG. The occurrence of Schistosoma japonicum vel cattoi in the Philippine
Islands. Philippine Journal of Science 1: 83-89, 1906
119. YAMAGIWA K. (Eggs of an unknown parasite in the human liver.) Mittheilungen der
medizinischen Gesellschaft zu Tokyo 4: No. 22, 1890. In Japanese, with German summary
120. YOKOGAWA M. Review of prevalence and distribution of schistosomiasis in Japan.
Southeast Asian Journal of Tropical Medicine and Public Health 7: 137-143, 1976
121. YOKOGAWA M. Programme of schistosomiasis control in Japan. Southeast Asian Journal
of Tropical Medicine and Public Health 7: 322-329, 1976
122. YOKOGAWA S. (Schistosoma japonicum in Formosa, especially on its intermediate host.)
Taiwan Igakkai Zasshi 149: 178-183, 1915. In Japanese. Abstracted in 117
123. YOSHIMOTO M. Ueber die Komplementbindungsreaktion bei der Schistosoma-krankheit
in Japan. Zeitschrift für Immunitätsforschung 5: 438-445, 1910
Table 10.1. Landmarks in schistosomiasis japonica

__________________________________________________________________
1847 Fujii described the clinical syndrome of Katayama disease

1888 Majima found ova now known to be those of S. japonicum in human liver
and described the pathological appearances
1903 Kawanishi found eggs in human faeces
1904 Kawanishi described hatching of miracidia from eggs
Katsurada found male adult worms in the portal vein of a cat (April), then later
found male and female worms in another cat, and described the pathological
changes in the bowel
Fujinami found a female worm in the portal vein of a human (May)
Tsuchiya found adult worms in cats, dogs and humans
Catto found adult worms in the mesenteric veins of a human and described
the pathological appearances
1909 Fujinami and Nakamura showed by experiments with cows that infection was
acquired by organisms penetrating the skin
1912 Miyagawa demonstrated schistosomula in histological sections of skin and in
blood and lymph
1913 Miyairi and Suzuki described infection of Oncomelania snails with miracidia
and the development of miracidia through sporocyst stages to cercariae, then
recovered adult worms from mice exposed to cercariae obtained from
naturally infected snails
1919 Fujinami controlled the molluscan vectors with lime
1921 Sanders and Priston indicated that tartar emetic may be of some value in
treatment
1971 Niridazole was shown to be of value in therapy by Santos and colleagues
1977 Praziquantel was reported to be effective in experimental animals
1979 Praziquantel was shown to be highly effective in humans by Santos and
colleagues
__________________________________________________________________
Chapter 11
TREMATODE INFECTIONS OF LESSER

IMPORTANCE
INFECTION WITH ACHILLURBANIA SPECIES
A. NOUVELI
This Paragonimus-like fluke was discovered by Dollfus in 1939. He found

the worm in an orbital abscess i n a malayan panther (Panthera pardus) which
was being kept in a zoo in France 46. In humans, the parasite has bee n
recovered from a nodule behind the e ar of a ten year old girl in China by Ch'en
in 196537.
A. RECONDITA
This fluke was found in the maxillary sinuses of a Brazilian opossu m

(Didelphus marsupialis) by Travassos in 1942 135. Eggs identified as probably
those of A. recondita were found in peritoneal granulomas in a 19 year ol d
Honduran male16. The life cycle of both of these worms is not well understood.
INFECTION WITH ALARIA SPECIES
Flukes of this genus are found in the intestines of birds and mammals, no t
including man. Snails are the first intermediate host. Cercariae penetrate the
skin of a fish or tadpole then move about f reely in the tissues as mesocercariae.
In 1973, an unidentified mesocercaria was observed in the retina of a woman,
in Ontario, Canada, who had often prepared frogs' legs for eating 125. A
disseminated fatal infection with mesocercariae of A. americana occurred in
1976 in Ontario in a young man who had eaten inadequately cooked frogs '
legs51. Finally, A. marcianae mesocercariae were removed from the skin of a
man, in Louisiana, USA, who had eaten baked raccoon 17.
DICROCOELIASIS
DICROCOELIUM DENDRITICUM
This parasite was confused with the common liver fluke, Fasciola hepatica,
297
for many years. The worm is a common parasite in the biliary passages o f
sheep, deer and other herbivorous and omnivorous animals in many parts of
the world. It was named Fasciola lanceolata by Rudolphi in 1803 115, then
Fasciola dendritica by him in 1819116. In 1899, Looss transferred the worm
to the genus Dicrocoelium erected by Dujardin in 1845 47, this name being
derived from the Greek words (DIKROOS, DICROOS) and
(KOILIA, COELIA), meaning double and cavity, respectively; the parasit e
thus became known as D. dendriticum 83.
It took many years to elucidate the complete life cycle of D. dendriticum.
The eggs are embryonated when passed in the stools, but do not hatch i n
water. When ingested by appropriate land snails, metamorphosis occurs with
two generations of sporocysts being formed and the eventual production o f
cercariae. Many species of land snails act as the first intermediate host ,
depending upon the geographical region. Cercariae of this worm had in fact
been seen and labelled Cercaria vitrina by von Linstow in 1887, but thei r
relationship with D. dendriticum was not appreciated at that time.
In 1929, two papers appeared in Germany giving accounts of attempts t o
solve the problem of the source of this infection. Both investigations wer e
based upon intensive epidemiological inves tigations in several heavily infected
parts of that country. W. Nöller found that the snail, Zebrina detrita, was
heavily parasitized with C. vitrina. Since the distribution of the snail an d
dicrocoeliasis did not quite coincide, however, he considered that either C.
vitrina may not be the cercaria of D. dendriticum, or else that Z. detrita was
not the normal host of the worm. Further searching showed that Torquilla
frumentum was host to the same cercaria, and that its distribution did correlate
with the presence of infected sheep 97. In another area, Vogel found that Z.
detrita and Helicella candidula were infected with von Linstow's cercaria, and
he thought it very likely that the latter mollusc might be the intermediate host
of D. dendriticum 139. This view was proven to be correct two years later when
Cameron infected Helicella by feeding these snails with Dicrocoelium eggs,
then raising adult flukes in sheep infected with the cercariae obtained fro m
these snails 31.
Cercariae of Dicrocoelium aggregate in slime balls and are left on the grass
as the snail moves along. In 1952 and 1953, Krull and Mapes in the US A
showed that metacercariae develop in the ant, Formica fusca, and that
infection of the mammalian host resulted from ingestion of infected ants 70,71.
This was confirmed by Vogel and Falção in Germany 142, then the ants, F.
cinerea and F. picea, were shown to be the intermediate hosts in the USSR 105.
The first description of human infection with this parasite is shrouded i n
controversy. The patients described by Bucholz in Germany and Chabert i n
France might have been infected with F. hepatica or D. dendriticum (see
chapter 4). The same might be said for the nine year old daughter of a
shepherd in Bohemia described by Dr Kirchner of Kaplitz and recounted by
Miscellaneous Trematode Infections 299
Cobbold39; in this girl, 47 mature worms were found in the gall bladder a t
autopsy. This uncertainty flows from the difficulty those observers had i n
establishing the identity of the adult fluke. The diagnosis is usually made ,
however, by finding the distinctive eggs in the faeces. Many of these cases ,
though, are spurious. Strom showed in 1927 that they result from the ingestion
of liver heavily contaminated with eggs 132; in such patients, the excretion o f
eggs in the stools is transient compared with patients with true dicrocoeliasis.
Most of the infections with this parasite have been reported from the USSR 93.
Success has been claimed for thymol and stibophen in the treatment o f
dicrocoeliasis121, but subsequent experience has shown that these drugs are not
always reliable. Praziquantel may prove to be effective.
D. HOSPES
This species occurs commonly in cattle in Africa. A number of spuriou s

human infections have been encountered, but two genuine human cases have
been reported from Ghana by Odei 98.
INFECTION WITH ECHINOCHASMA PERFOLIATUS
This species was first described as Echinostomum perfoliatum by von Ratz

in 1908111 after he had found it in the small intestine of cats and dogs i n
Hungary. Later, it was renamed Echinochasma perfoliatus by Dietz in 1910 45,
the generic name being derived from the Greek words (ECHINOS)
and µ (CHASMA) meaning "spine" and "hiatus", respectively. Th e
worm is a common parasite of cats and dogs in many parts of the world. I n
1922, Tanabe infected himself experimentally by ingesting cercariae in th e
gills of freshwater fish 134, then Hirasawa recorded a natural human infection 55.
INFECTION WITH ECHINOPARYPHIUM RECURVATUM
This cosmopolitan parasite of the intestine of birds and mammals wa s

described by von Linstow in 1873 80, the generic name being derived from the
Greek words (ECHINOS) AND (PARYPHE) meaning
"spine" and "border", respectively. Infections of humans have been reported
a number of times; the first was by Morishita, who named it E. koidzunis, in
Taiwan in 192992. Since then, the parasite has been found in humans i n
Indonesia and in Egypt. Snails are the first intermediate host and metacercariae
encyst in tadpoles and frogs. E. paraulum, a probable synonym of E.
recurvatum, was described in a human in the USSR by Skrjabin in 1938 126.
ECHINOSTOMIASIS
E. HORTENSE
This parasite was first described by Asada in 1926 11. It was placed in the genus
Echinostoma of Rudolphi (1809) and emended by Dietz in 1910 45; the name
was derived from a combination of the Greek words (ECHINOS) and
µ (STOMA) meaning "spine" and "mouth", respectively. In 1976 ,
Arizono and his colleagues descr ibed infections in four people who ate loaches
(Misgurnus anguillicaudatus). Subsequently, loaches were collected from the
same restaurant in which two of the patients had eaten; parasites wer e
recovered from the soft tissues adjacent to the gills and a puppy was fed with
40 metacercariae and two humans ingested 10 metacercariae each. Egg s
appeared in the faeces after two weeks and the volunteers developed abdominal
pain lasting for several days about one month after infection. The dog wa s
necropsied after 33 days and five adult worms were recovered from its small
intestine9.
E. ILOCANUM
Eggs of this fluke were first found in the faeces of prisoners in Manila, Phil -
ippines by Garrison in 1907. He l ater recovered 21 adult worms, 2-6 mm long,
after administration of oleoresin of aspidium to one person. Since the prisoner
came from the Ilocano region of the Philippines, in 1908 he named i t
Fascioletta ilocanum 53. In 1911, Odhner transferred this helminth to the genus
Echinostoma 99. The parasite was found subsequently in various parts o f
southeast Asia, with first Tubangui (1 931) showing that rats, then Chen finding
that dogs, were reservoirs of infection.
In 1933, Tubangui and Pasco described the life cycle of the parasite (which
they called Euparyphium ilocanum); miracidia penetrated the snails Gyraulus
convexiusculus and Hippeutis umbilicus, metamorphosed into rediae, the n
produced daughter rediae and cercariae, the latter being liberated and encysting
on freshwater molluscs which may be eaten raw 137. G. prashadi was shown
subsequently to be the primary intermediate host in India. Worms attach to the
intestinal wall and may cause diarrhoea. Recently, Radomyos and colleagues
have shown that praziquantel is effective in the treatment of this infection 107.
E. LINDOENSE
This species was first reported as E. ilocanum by Brug and Tesch in 1937 in
the Celebes (Sulawesi), Indonesia 28, but was re-described as E. lindoense by
Sandground and Bonne in 1940 119. The parasite was named after the Lak e
Lindoe region of Central Celebes where human infection was common, with up
to 96% of the inhabitants being infected. The molluscan intermediate host s

were shown by Bonne to be Anisus sarasinorum and A. convexiusculus, with
mussels being important second intermediate hosts 24. He also reported that
diarrhoea was induced in experimental human infections. In recent years, the
worm has become less prevalent as a result of changes in the eating habits of
the population32. The parasite has also been found in Brazil wher e
Biomphalaria glabrata is the vector 78.
E. MACRORCHIS AND E. CINETORCHIS
The metacercariae of these parasites, which were first described by Ando and
Ozaki in 19238, encyst in the tissues of tadpoles and frogs. Majima found 66
adult E. macrorchis in the intestines of a boy in Japan in 1927 90. Since then,
occasional infections of humans by both species have been reported fro m
various parts of southeast Asia 25.
E. MALAYANUM
This parasite was first found in two Tamil coolies in Singapore and Kual a
Lumpur, and was named E. malayanum by Leiper in 1911 74. Species of
Lymnaea and Indoplanorbis were shown to be the first intermediate host by
Rao110 and then by Lie and Virik 79.
E. REVOLUTUM
This fluke, which is normally a parasite of t he intestine of various small animals

and birds such as musk rats, ducks, geese and fowl, was first described by von
Froelich in 1802 as Fasciola revoluta 52, then renamed E. revolutum by Looss
in 189983. The first intermediate hosts a re a number of species of snails, and the
second intermediate hosts on which encystation occurs are molluscs an d
tadpoles. The first infection found in humans was reported by Anazawa i n
1929; he recovered adult worms from the faeces of a Taiwanese woman who
had been treated with oleoresin of aspidium 7.
INFECTION WITH EUPARYPHIUM MELIS
This fluke, described originally as Fasciola melis by Schrank in 1788 122, is

normally a parasite of badgers, hedgehogs and dogs. It was recovered by Leon
in 1916 from the stools of a Rumanian patient who had been in Jassy, Iran ;
Leon and Ciurea named the worm Echinostoma jassyense in 192276. Hsu57
found two worms in the intestines of a Chinese who had died of chroni c
myeloid leukaemia and concluded that they were identical with the wor m
described by Schrank. That parasite, meanwhile, had been transferred to th e

genus Euparyphium. Snails are the first intermediate host and cercariae encyst
on tadpoles.
INFECTION WITH EURYTREMA PANCREATICUM
This fluke is a common parasite of the pancreatic ducts of cattle, buffalo ,

sheep, goats and hares in Asia and other parts of the world. It was discovered
in Japan and became first known to Europeans during the Paris Exhibition of
1889 when Janson from the A gricultural School of Komaba in Japan exhibited
a series of parasites, among which was a Distoma pancreaticum from the
pancreatic duct of a sheep. The new parasite was referred to in subsequen t
years by Railliet (1890) 109 and by Janson (1893) 58 in papers which dealt with
the anatomy and pathological significance of the worm, respectively. It wa s
then transferred to the genus Eurytrema by Looss in 1907 84. The generic name
is possibly derived from a combination of the Greek words (EURYS)
and µ (TREMA) meaning "broad" and "hole", respectively. The life cycle
of this parasite was determined in 1965 by Basch who fed sporocysts from a
snail, Bradybaena similaris, to grasshoppers, Conocephalus maculatus , in
which they grew to mature metacercariae; these in turn developed into adul t
worms in the pancreas of goats15. Castellani and Chambers in 1919 recorded
the presence of eggs of this tr ematode in the faeces of a Chinese coolie 33. Adult
worms were found in the pancreatic duct of a 22 year old Chinese man a t
autopsy by Chang and Li in 1964 34
INFECTION WITH GASTRODISCOIDES HOMINIS
This fluke was first found in the caecum of an Indian patient and designate d
Amphistomum hominis by Lewis and McConnell in 187677. Subseqently, it was
called Gastrodiscus hominis by Sonsino (1896) 128, then was redescribed i n
1913 by Leiper who renamed it Gastrodiscoides hominis 75. The generic name
is derived from the Greek words (GASTER ) and (DISKOS,
DISCOS) meaning "belly" and "disc", respectively, with the suffix
(EIDOS) indicating "like" or "similar". The worm is common in parts o f
northeastern India where more than 40% of the population may be infected 29,
but it is also found in other parts of Asia. Pigs are a common reservoir host but
various species of monkeys have also been found to be infected. The life cycle
is uncertain, but the snail, Helicorbis coenosus, has been infected
experimentally 48. Humans may be infected with large numbers of thes e
helminths, which are approximately 1 cm long and almost as much wide; 999
worms were recovered from one individual, simply by the administration o f
soap and water enemas29. Parasites generally attach to the large bowel and the
infection may cause diarrhoea. Mechanical t herapy with soap and water enemas
is often successful, as is treatment with thymol or tetrachlorethylene. Th e

efficacy of praziquantel needs to be evaluated.
INFECTION WITH HAPLORCHIS SPECIES
H. pumilio, described by Looss in 1896 82, H. tachui, described by Nishigori in

1924, and H. yokogawai, described by Katsuta in 1932, have all been reported
in humans in the Philippines2,3. H. tachui infections have also been reported in
Thailand67. The generic name is derived from a combination of the Gree k
words (HAPLOOS) and (ORCHIS) meaning "single" an d
"testis", respectively.
INFECTION WITH HETEROPHYES SPECIES
H. HETEROPHYES
This fluke was discovered in 1851 in Cairo by Theodor Bilharz. He wrote to

von Siebold in Breslau in Germany (now Wroclaw, Poland) on 1 May 185 1
recounting his discovery:
A short while ago, on 26 April, I discovered, in the intestine of a boy' s
cadaver a large number of small red dots which, under the microscop e
proved to be beautiful fully developed Distoma 1 mm in length and 0.3 mm
in width. The red color was due to the red-brown mature eggs which were
visible through the body of the worm. 20
In the following year, von Sie bold published Bilharz's letter and added his own
comments in which he named the parasite Distoma heterophyes 20. The specific
name was derived from a combination of the Gree k words (HETEROS)
and (PHYE) meaning "different" and "shape", respectively. The worm s
were seen on another occasion by Bilharz, but little more was heard of thi s
fluke until Blanchard in 1891 21 then Looss in 1894 81
once again directed
attention to its presence in Egypt.
In 1866, Cobbold placed the worm in a distinct genus and named it Hetero-
phyes aegyptiaca, to reflect both the specific name given to it by von Siebold
as well as the land of its discovery 40. In 1900, Stiles and Hassal renamed it ,
according to the nomenclatural law of priority, H. heterophyes 131.
In 1915, Onji and Nishio in Japan de scribed a fluke found in human intestine
which resembled H. heterophyes but which they believed represented a
different species. They called this worm H. nocens 101. Their paper was
published in Japanese but Cor t and Yokogawa brought it to the attention of the
English-speaking world in 1921 42. The distinction between the two species was
based upon small differences in size. This was criticized by Lane in 1922 who
noted that all the observed changes could be accounted for by muscula r
contraction 73. Lane concluded that H. nocens was a synonym of H.

heterophyes, a view which has become accepted generally.
The second intermediate host of H. heterophyes was identified before the
first intermediate host. Onji and Nishio sh owed in 1915 by feeding experiments
that cercariae of Heterophyes encysted in the fish, Mugil cephalus (mullet);
this observation was not generally appreciated, however, until the appearance
of Cort and Yokogawa's translation of Onji and Nishio's work in 1921. Thi s
was then soon confirmed for H. heterophyes in Egypt by Harujiro Kobayashi
and Mohammed Khalil, working independently. While returning to Japan after
a visit to Europe, Kobayashi purchased some Egyptian mullet in Port Said and
found in them metacercariae resembling youn g Heterophyes 69. That these were
indeed Heterophyes was proven by Khalil who fed encysted cercariae in Mugil
cephalus, from Lake Menzaleh near Port Said, to cats then recovered adul t
worms eight days later64. He found subsequently that Tilapia nilotica was also
infected65, and other investigators showed that Aphanius in Egypt and
Acantogobius in Japan were other second intermediate hosts.
In 1928, Asada in Japan discovered that a brackish-water snail ,
Tympanotonus microptera (= Cerithidea cingulata) was the first intermediate
host of Heterophyes. He showed that cercariae from these snails encysted i n
saltwater fishes but did not complete their development in freshwater fishes .
Asada completed the life cycle of Heterophyes by obtaining adult worms after
feeding fish, which had been infected in this way, to dogs 12. Subsequently,
Khalil in Egypt showed in 1933 t hat cercariae from the snail, Pirenella conica,
would encyst in the muscles of the fish, Gambusia affinis, and that when they
were fed to a dog, adult H. heterophyes were obtained 65. In addition to humans,
H. heterophyes infection has since been found in other mammals includin g
cats, dogs and foxes.
Heterophyiasis was diagnosed in life for the first time in 1899 in a girl who
was a patient of FM Sandwith in Kasr-el-Aini Hospital in Cairo. Adult worms
and eggs were both seen when faeces we re being examined microscopically for
schistosome ova120. Sandwith also noted that she had no particular symptoms
that could be attributed to the infec tion. Nevertheless, the parasite may produce
diarrhoea, sometimes associa ted with bleeding from the gastrointestinal tract 65.
The parasites occasionally lodge in ect opic locations, for example, adult worms
have been found in the brain 43.
Filix mas and tetrachlorethylene have been used in the past for the treatment
of this condition.
H. KATSURADAI
This fluke, closely related to H. heterophyes, was described by Ozaki an d

Asada in Japan in 1925. The parasites were recovered from humans treate d
with thymol. The infection was t ransmitted experimentally from the fish, Mugil
cephalus, to a dog102.
INFECTION WITH HIMASTHLA MUEHLENSI
This fluke, described by Vogel in 1933 and named by him after it s

discoverer, Mühlens, is a para site of gulls and other birds 140. The generic name
is derived from the Greek word µ (HIMASTHLE) meaning "thong" or
"strap". The infection has been described in humans only once; Mühlen s
obtained five specimens from a German patient who had lived in Colombia for
six years, but who may have acquired the infection after eating raw clams i n
New York. Marine snails are the first intermediate host and metacercaria e
encyst on bivalves such as Mytilus and Mya.
INFECTION WITH HYPODERAEUM CONOIDEA
This fluke, first recognized in 1782 by Bloch who named it Distoma conoid-
eum 23, and renamed by Dietz in 1909 44, is a common parasite of birds such as
ducks, geese and fowl. The intermediate hosts are Planorbis and Lymnaea
snails. The infection is common in some parts of Thailand, where more tha n
half of the population may be infected 148.
METAGONIMIASIS
The causative agent of this infection, Metagonimus yokogawai , a fluke about

1-2.5 mm long, was first found by H Kobayashi in 1908, but he did not publish
his report of the discovery until 10 October 1912, at which time he named it
Loxotrema ovatum 68. Not only was the name Loxotrema preoccupied by a
genus of the Mollusca, but the designation for the species was pre-empted by
Katsurada. In 1911 in Taiwan, S. Yokogawa had found this parasite in humans
and in cats and dogs infected experimentally with cysts from the trout ,
Plectoglossis altivelis. Yokogawa's discovery was reported to the Japanes e
Pathological Association by Katsurada at which time he gave the fluke th e
name Heterophyes yokogawai; this was duly published on 31 May 1912 60. In
the following month (30 June 1912), Katsurada erected a new genus ,
Metagonimus, in which to place the worm, thus naming it Metagonimus
yokogawai 61. Unaware of these publications in Japanese, Leiper, later i n
1913, erected the genus Yokogawa for this parasite 75, then Ciurea in 1915
designated it Loossia. The correct name, Metagonimus yokogawai , was used
for the first time in the non-Japanese literature by Yokogawa in Decembe r
1913150. The generic name, Metagonimus, is derived from a combination of the
Greek words µ (META) and µ (GONIMOS) meaning "posterior"
and "genitalia", respectively.
The piscine second intermediate host of M. yokogawai was discovered before
the molluscan first intermediate host. In 1912, Yokogawa reported tha t
encysted cercariae occurred in the freshwater trout, Plectoglossis altivelis, and

that eggs appeared in the faeces within one week of the parasites being fed to
experimental animals149,150. Subsequent investigations revealed tha t
Odontobutis obscurus and Salmo perryi were also vectors of infection.
In 1917, Muto demonstrated that Melania (= Semisulcospira) libertina was
the first intermediate host. He found that miracidia developed through a
sporocyst stage then two generations of rediae. Muto took cercariae from the
liver of infected snails and showed that direct infection of experimenta l
definitive hosts could not be induced. He then exposed goldfish and carp to the
cercariae and proved that they penetrated the skin of the fish and becam e
infective after about 20 days. The encysted metacercariae in fish were then fed
to cats, with the result that eggs of M. yokogawai appeared in the faeces 1 2
days later95,96.
As mentioned earlier, Yokogawa had discovered in 1911 that dogs could be
infected experimentally with this parasite. Kobayashi in 1912 68 reported that
dogs in Japan were infected with Metagonimus, then Leiper and Atkinso n
found that natural infections were common in dogs in Shanghai. Subsequently,
other investigators found that many species of fish-eating mammals wer e
reservoirs of infection.
Clinical studies have indicated that infection occasionally produces diarrhoea
particularly if the infection is heavy 123. Yokogawa in 1913 indicated that thymol
was effective in the treatment of metagonimiasis 150. Tetrachlorethylene has also
been used, while more recently, R im showed that niclosamide was often effect-
ive112. Praziquantel may well prove to be a valuable addition to the therapeutic
armamentarium.
OPISTHORCHIASIS
OPISTHORCHIS FELINEUS
This fluke, about 1 cm long, was discovered in the biliary passages of a cat by
Rivolta in 1884 and named Distomum felineum by him113, the specific desig-
nation reflecting the host in which it was found. In 1895, R Blanchard erected
the genus Opisthorchis and placed this fluke in it, the worm thus being known
as O. felineus 22. The generic name was derived from a combination of th e
Greek words (OPISTHON) and (ORCHIS) meaning
"posterior" and "testis", respectively.
Several years earlier (1892) in Tomsk, in the Siberian region of the USSR,
Winogradoff first reported this infection in humans. He found the parasite i n
nine patients and named it Distomum sibiricum 143. Subsequently, Kholo-
kowsky diagnosed the infection in a peasant from near Leningrad but who had
travelled extensively in Siberia 66. Askanazy then discovered the worm in five
people living in the East Prussian district of Heydekrug. Further studie s
revealed that a wide range of mammals including dogs, cats, foxes, pigs, rats,
rabbits and seals were infected in cent ral and eastern Europe and adjacent parts
of the USSR 49.
The life cycle of O. felineus was elucidated in fits and starts. Askanazy i n
1905 believed that he had shown that the fishes Idus melanotus (chub) and
Leuciscus rutilus (roach) were the intermediate hosts 14. Lühe then indicated
that the details of the development of the parasite were known only meagrely,
and suggested that an encysted larval worm found in Prussia in the flesh o f
L. idus and L. rutilus could be the metacercarial stage and that an earlier phase
perhaps passes in the body of a small bivalve mollusc, Dreissena polymorpha
86
. In 1917, Ciurea stated that he believed that Askanazy had been in error and
had probably been working with holostomes 38. Ciurea isolated encyste d
cercariae from the fishes Tinca tinca and Idus idus, then recovered mature
O. felineus twelve days after feeding the parasites to cats and dogs. Subsequent
studies by a number of investigators demonstrated that other freshwater fishes
of the genera, Abramis, Barbus, Blicca, Cyprinus, and Scardinius, were also
hosts of the larval stage of O. felineus.
The nature of the first intermediate host of the fluke remained obscure until
1934 when Vogel showed that development of the parasite occurred in th e
snail, Bithynia leachi 141. He found that eggs hatched after they were ingested
by the snails, then the miracidia mig rated into the tisssues, metamorphosed into
first then second generation sporocysts, then produced rediae in which th e
cercariae developed after about two months. B. leachi is the only species of
snail which has been shown to be susceptible to infection with this parasite .
Vogel observed that when cercariae enco untered the fish, they became attached
to the scales, dropped their tails, then penetrated into the tissues.
Vogel also investigated the route of migration of the worms in the definitive
host. He showed that like Clonorchis, but unlike Fasciola, metacercariae of
O. felineus excysted in the duodenum, then migrated through the ampulla o f
Vater to the distal bile passages wh ere they became attached to the mucosa and
matured, beginning the laying of e ggs about three to four weeks after ingestion.
Worms in the bile passages may induce inflammation and subsequent fibrosis
leading to biliary obstruction and secondary bacterial infection an d
cholelithiasis. Clinical studies indicated that the likelihood of significan t
damage depended upon the number of worms present. Patients with 50 or so
worms usually had no ill-effects, but people with many hundreds of worm s
sometimes had severe biliary and hepatic disease.
The diagnosis is made by finding eggs in the faeces or duodenal fluid. Hexa-
chloroparaxylol (chloxyl) was claimed to be partially effective in Russia n
patients with opisthorchiasis103. Praziquantel has been shown to be effective in
the treatment of O. viverrini infections and is presumably also active against O.
felineus.
O. VIVERRINI
This fluke was first found in a civet cat (Felis viverrus) by Poirier in 1886 and
named Distoma viverrini by him104. It was transferred to the genus Opisth-
orchis of Blanchard 22 by Stiles and Hassal in 1896 131
. Nevertheless, it is
possible that the correct name for this parasite is O. tenuicollis, reflecting the
Distoma tenuicollis described by Rudophi in 1819 116.
Most early reports of this infection in southeast Asia referred to this parasite
as O. felineus 63,106, although Leiper (1911) made a provisional diagnosis of O.
viverrini for some flukes from two prisoners in Chiengmai gaol in Thailand that
had been sent to him by Dr. Kerr 74. Differentiation between the two species is
extremely difficult; Wykoff and colleagues in 1965 could not distinguis h
between them on the basis of the appearances o f the adult worms or of the eggs,
but found differences in the patterns of the flame cells in the cercariae 146. The
infection is now recognized as being common in Thailand, with up to half of the
population being infected in some areas 54.
The life cycle of this parasite was studied in Thailand by Wykoff and hi s
colleagues; they showed that the snail intermediate hosts were Bithynia
goniomphalus, B. funiculata and B. laevis, while the most important fis h
intermediate hosts were species of Cyclocheilichthys, Hampala and
Punteus 146.
Early clinical studies suggested a high frequency of diarrhoea, abdomina l
pain and jaundice in patients with opisthorchiasis, but these studies were not
well-controlled 54,117. Subsequently, Wykoff and co-workers compared th e
clinical and biochemical findings in 921 infec ted persons with those in a similar
number of uninfected persons in Thailand, and could find no significant dif -
ferences between the two groups 145. On the other hand, Upatham and col -
leagues have shown more recently in a study of a village with 309 inhabitants
that right upper quadrant abdominal pain was more common in those persons
with heavy infections 138. It is possible that there is an association betwee n
opisthorchiasis and carcinoma of the bile duct; for example, 5896 worms were
found an autopsy of a man who died from this neoplasm 54.
The diagnosis is usually made by findi ng eggs in the faeces. Upatham and his
collaborators have defined recently the relationship between intensity o f
infection and faecal egg excretion138. A number of drugs have been proposed
as a treatment for opisthorchiasis viverrini. Partial responsiveness t o
dehydroemetine was shown by Muangmanee and co-investigators in 1974 94.
Niclofolan was thought to be of some value in patients with light infections 6.
Bunnag and Harinasuta showed in 1980 that the infection responded well t o
praziquantel; 23 out of 26 patients were cured by a two day course of treatment
and toxicity was minimal 30.
O. NOVERCA
This fluke, which is a common parasite of dogs and pigs in India, was firs t
found in these animals in that country by Lewis and Cunningham in 1872; i t
was named O. noverca by Braun in 1902 26. It has been recorded twice i n
humans, on both occasions by McConnell in India. McConnell, like Lewis and
Cunningham, considered it to be identical with Distoma conjunctum
discovered by TS Cobbold in the liver of an American red fox in 1858. Th e
first patient was a Muslim who died in Calcutta in 1876; post-morte m
examination revealed small flukes in dilated intrahepatic bile ducts 87.
McConnell encountered another patient i n 1878 and on this occasion noted that
the flukes were somewhat larger than those described by Cobbold 88.
O. GUAYAQUILENSIS
Rodriguez, Gomez and Montalvan in Ecuador in 1949 found this parasite in a

number of humans and dogs114. According to Artigas and Perez 10, this worm is
identical with Amphimerus pseudofelineus described in cats by Ward in 1901.
INFECTION WITH PARYPHOSTOMUM SUFRARTYFEX
This worm was first obtained from an eight year old girl in Assam, India and
named Artyfechinostomum sufrartyfex by Lane in 1915 72. It was later re-
described and transferred to the genus Paryphostomum of Dietz (1909) by
Bhalerao in 193119. The generic name is derived from the Greek word s
(PARAPHYE) and µ (STOMA) meaning "fringe" and "mouth",
respectively. The details of the life cycle are uncertain, but A. mehrai, which is
probably a synonym of P. sufrartyfex, utilizes the snail, Indoplanorbis exustus
108
. It is also possible that this species is synonymous with Echinostoma
malayanum described by Leiper in 1911.
INFECTION WITH PHILOPHTHALMUS
Worms of the genus Philophthalmus mainly parasitize the conjunctival sac of

the eyes of birds. The generic name is derived from the Greek words -
(PHILO-) and µ (OPHTHALMOS) meaning "like" and "eye" ,
respectively. Parasites of this genus develop in a snail intermediate host and do
not require a second intermediate host 4. Human ocular infection was firs t
described by Markovic in Belgrade in 1939 91.
PLAGIORCHIASIS
The genus Plagiorchis was raised by Lühe in 1899 85. It is derived from the
Greek words (PLAGIA) and (ORCHIS) meaning "oblique" and
"testis", respectively. The species of Plagiorchis normally occur in the
intestines of a wide range of vertebrates. Snails are the intermediate host s

although aquatic mussels may also serve as second intermediate hosts.
P. PHILIPPINENSIS
Africa and Garcia first found this fluke in 1935 during the autopsy of a man
from Ilocano, Philippines, but they left it un-named 1; it was given its curren t
name by Sandground in 1940 118. That first patient was also infected wit h
Echinostoma ilocanum and Spelotrema brevicaeca . People in this region o f
the Philippines were in the habit of eating grubs of certain species of insect s
which may be the second intermediate hosts.
P. JAVENSIS
Sandground in 1940 first found this worm in a Javanese who also had a heavy
infection with Echinostoma ilocanum 118.
P. MURIS
Tanabe described this fluke in 1922 133,134. McMullen in 1937 infected himself
experimentally89. A natural infection in a human has been reported only once;
it was found in a Japanese patient who was being treated for a heavy ,
concurrent infection with Metagonimus yokogawai 13.
INFECTION WITH POIKILORCHIS CONGOLENSIS
This fluke was described by Fain and Vandepitte in 1957 after they had found
it in a retroauricular cyst removed from a boy in Central Africa 50. Eggs similar
to those produced by this parasite had been removed previously from near the
ear of a man by Yarwood and Elmes in 1943 147. This genus is closely related
to, or may be identical with, Achillurbania 16. The generic name is derived from
a combination of the Greek words (POIKILOS) and
(ORCHIS) meaning "many" or "various" and "testis", respectively.
INFECTION WITH PYGIDIOPSIS SUMMA
Onji and Nishio described this fluke in 1915 101. It has been reported in humans
in Korea124. The generic name is derived from a combination of the Gree k
words (PYGIDION) and (OPSIS) meaning "posterior" o r
"rump" and "sight", respectively.
INFECTION WITH SPELOTREMA BREVICAECA
This fluke was first reported a s Heterophyes brevicaeca in 1935 by Africa and
Garcia who found it in the intestine of a Filipino male 1. It was renamed
Spelotrema brevicaeca by Tubangui and Africa in 1938 136. The complete life
cycle is unknown, but encysted metacercariae have been found in the crab ,
Carcinus maenas 56. In humans, eggs have been observed in the centra l
nervous system 2 and in the heart 3.
INFECTION WITH STELLANTCHASMUS FALCATUS
This fluke, described by Onji and Nishio in 1915 101, has been reported in
humans in Japan, Taiwan and Hawaii 5,59.
INFECTION WITH TROGLOTREMA SALMINCOLA
This worm, which lives in the intestinal wall of a number of carnivorou s

animals on the northern borders of the Pacific ocean, was described in 1926 by
Chapin who named it Nanophyes salmincola 35. It was then renamed
Nanophyetus by him in the following year 36. Bennington and Pratt showed in
1960 that the mollusc, Oxytrema silicula, is the first intermediate host 18. The
free-living cercariae encyst in the kidneys of certain species of fish, particularly
salmon and trout. In lower animals, the worm is a vector of a rickettsia which
often produces a fatal, febrile illness
In 1931, Skrjabin and Podjapolskaja found that a number of men inhabiting
the Amur and Usuri regions of the US SR were infected with a fluke which they
named Nanophyetus schikhobalowi 127. In the following year, however ,
Witenberg concluded that this fluke was identical with the N. salmincola of
Chapin, and transferred the parasite to the genus, Troglotrema, of Odhner 100,
the parasite thus being designated T. salmincola 144. The generic name is
derived from the Greek words (TROGLE) and µ (TREMA)
meaning "sunken" and "orifice", respectively.
Thymol was found to be effective in the original patients described b y
Skrjabin and Podjapolskaja 127. Praziquantel may be more active.
INFECTION WITH WATSONIUS WATSONI
This parasite was discovered in the intestine of a Nigerian by Watson and sent
to Conyngham in London. The flukes were pronounced a new species b y
Blanchard, then Conyngham named it Amphistomum watsoni in 190441. The
parasite was renamed Watsonius watsoni by Stiles and Goldberger in 1910 129.
It has been recovered from a human only this once. The life cycle is unknown.
REFERENCES
1. AFRICA CM, GARCIA EY. Plagiorchis sp., a new parasite of the human intestine. Papers
on helminthology: 30th jubilee of the activities of KJ Skrjabin, Moscow, pp 9-10, 1935
2. AFRICA CM, LEON W de, GARCIA EY. Heterophyidiasis: V. Ova in the spinal cord of
man. Philippine Journal of Science 62: 393-399, 1937
3. AFRICA CM, LEON W de, GARCIA EY. Heterophyidiasis: VI. Two more cases of heart
failure associated with the presence of eggs in sclerosed valves. Journal of the Philippine
Islands Medical Association 17: 605-609, 1937.
4. ALICATA JE. Life cycle and developmental stages of Philophthalmus gralli in the
intermediate and final hosts. Journal of Parasitology 48: 47-54, 1962
5. ALICATA JE, SCHATTENBURG OL. A case of intestinal heterophyidiasis in man ni
Hawaii. Journal of the American Medical Association 110: 1100-1101, 1938
6. AMBROISE-THOMAS P, WEGNER DH, GOULLIER A, DESGEORGES PT,
BILLIAULT X. Essais de traitement des opistorchiases humaines par le niclofolan (Bay
9015). À propos de 51 cas. Bulletin de la Société de Pathologie Exotique 73; 293-301, 1980
7. ANAZAWA K. (First instance of Echinostoma revolutum found in man and its course of
infection.) Taiwan Igakkai Zasshi No. 288, pp 221-224, 1929. In Japanese
8. ANDO A, OZAKI Y. (On four new species of trematodes of the genus Echinostomata).
Dobutsu Gaku Zasshi 34: 108-119, 1923. In Japanese
9. ARIZONO N et al. (Studies on Echinostoma hortense Asada, 1926 with special reference to
its human infection.) Japanese Journal of Parasitology 25: 36-45, 1976. In Japanese, with
English summary
10. ARTIGAS PdeT, PEREZ MD. Considerações sôbre Opisthorchis pricei Foster, 1939, O.
guayaquilensis Rodriguez, Gomez et Montalvan, 1949 e O. pseudofelineus Ward, 1901.
Descrição de Amphimerus pseudofelineus minutus n. subsp. Memorias do Instituto Butantan
30: 157-166, 19601962
11. ASADA J. (On a new species of trematode belonging to the Echinostoma family). Tokyo Iji
Shinshi No. 2447, p 1633, 1926. In Japanese
12. ASADA J. (Determination of the first intermediate host of Heterophyes heterophyes
occurring parasitic in human body in Japan and an experimental investigation of its
development.) Tokyo Iji Shinshi No. 2564, pp 6-12, 1928. In Japanese. Abstracted in Japan
13. ASADA J, OTAGAKI H, MORITA D, TAKEUCHI T, SAKAI Y, HONISHI T,
OKAHASHI K. A case report on the human infection with Plagiorchis muris, Tanabe 1922,
in Japan. Japanese Journal of Parasitology 11: 512-516, 1962
14. ASKANAZY M. Weitere Mittheilungen über die Quellen der Infektion mit Distomum
felineum. Schriften der physikalisch-oekonomischen Gesellschaft zu Königsberg 46: 127-131,
1905-1906
15. BASCH PF. Completion of the life cycle of Eurytrema pancreaticum (Trematoda:
Dicrocoeliidae). Journal of Parasitology 51: 350-355, 1965
16. BEAVER PC, DURON RA, LITTLE MD. Trematode eggs in the peritoneal cavity of a man
in Honduras. American Journal of Tropical Medicine and Hygiene 26: 684-687, 1977
17. BEAVER PC, LITTLE MD, TUCKER CF, REED RJ. Mesocercaria in theskin of man in
Lousiana. American Journal of Tropical Medicine and Hygiene 26: 422-426, 1977
18. BENNINGTON E, PRATT I. The life history of the salmon-poisoning fluke,Nanophyetus
salmincola (Chapin). Journal of Parasitology 46: 91-100, 1960
19. BHALERAO GD. Trematode parasites of pigs in Bengal. Records of the Indian Museum 33:
475482, 1931
20. BILHARZ T, von SIEBOLD CT. Ein Beitrag zur Helminthographia humana, aus brieflichen
Mittheilungen des Dr. Bilharz in Cairo, nebst Bemerkungen von Prof. C. Th. von Siebold in
Breslau. Zeitschrift für wissenschaftliche Zoologie 4: 53-76, 1853. Partly translated in 62
21. BLANCHARD R. Note préliminaire sur le Distoma heterophyes, parasite de l'homme en

Égypte. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie,
new series, 3: 791, 1891
22. BLANCHARD R. Animaux parasites. Notice préliminaire. Bulletin de la Société Zoologique
de France 20: 217, 1895
23. BLOCH ME, Abhandlung von der Erzeugung der Eingeweidewürmer und den Mitteln wider
dieselben. Eine von der königlich danischen Societät der Wissenschaften zu Copenhagen
gekrönte Preischrift, pp 54, 1782
24. BONNE C. Eenige verdere waarnemingen over echinostomiasis. Geneeskundig Tijdschrift
voor Nederlandsch-Indië 80: 537-548, 1940
25. BONNE C, BRAS G, LIE K J. Five human echinostomes in the Malayan region. Medisch
Maandblad 23: 456-465, 1948
26. BRAUN M. Die thierischen Parasiten des Menschen. Ein Handbuch für Studirende und
Aertze. 3. Vermehrte und Verbesserte, Würzburg, pp 360, 1903. Abstracted in Zoologisches
Centralblatt 9: 835-836, 1902
27. BRAUN M. The animal parasites of man: a handbook for students and medical men,
translated by P Falcke and brought up to date by LW Sambon and FV Theobald, third edition,
John Bale, Sons and Danielsson, London, pp 453, 1906
28. BRUG SL, TESCH JW. Incidence of intestinal parasites in region of Lindoe Lake (Celebes).
29. BUCKLEY JJ. Observations on Gastrodiscoides hominis and Fasciolopsis buski in Assam.
30. BUNNAG D, HARINASUTA T. Studies on the chemotherapy of human opisthorchiasis in
Thailand. Clinical trial of praziquantel. Southeast Asian Journal of Tropical Medicine and
Public Health 11: 528-531, 1980
31. CAMERON TW. Experimental infection of sheep with Dicrocoelium dendriticum. Journal
32. CARNEY WP, SUDOMO M, PURNOMO. Echinostomiasis: a disease that has disappeared.
Tropical and Geographical Medicine 32: 101-105, 1980
33. CASTELLANI A, CHALMERS AJ. Manual of tropical medicine, third edition, Baillière,
Tindall and Cox, London, pp 2436, 1919
34. CHANG Y, LI K. Human infection of Eurytrema pancreaticum. Report of a case with
autopsy findings. Acta Academia Medica Primae Shanghai 2: 393-395, 1964
35. CHAPIN EA. A new genus and species of trematode, the probable cause of salmon-poisoning
in dogs. North American Veterinarian 8: 36-37, 1926
36. CHAPIN EA. Society proceedings, Helminthological Society of Washington. Journal of
Parasitology 14: 60, 1927
37. CH'EN HT. Paragonimus, Pagumogonimus and Paragonimus-like trematode in man.
38. CIUREA J. Die Auffindung der Larven von Opisthorchis felineus, Pseudamphistomum
danubiense und Metorchis albidus und die morphologische Entwicklung dieser Larven zu
den geschlechtsreifen Würmen. Zeitschrift für Infektionskrankheiten, parasitäre Krankheiten
und Hygiene der Haustiere 18: 301-333, 345-356, 1917
40. COBBOLD TS. Tapeworms (human entozoa), their sources, nature and treatment, London,
pp 83, 1866
41. CONYNGHAM HF. A new trematode of man (Amphistomum watsoni). Journal of Tropical
42. CORT WW, YOKOGAWA S. A new human trematode from Japan. Journal of Parasitology
8: 66-69, 1921
43. DESCHIENS R, COLLOMB H, DEMARCHI J. Distomatose cérébrale à Heterophyes
heterophyes. Abstracts of the Sixth International Congress of Tropical Medicine and Malaria,
p 265, 1958
44. DIETZ E. Der Echinostomiden der Vögel. Zoologischer Anzeiger 34: 180-192, 1909
45. DIETZ E. Echinostomiden der Vögel. Zoologische Jahrbucher. Abteilung für Systematik,
Oekologie und Geographie der Tiere, Jena, Supplement 12: heft 3, 265-512, 1910
46. DOLLFUS R. Distome d'un abcès palpébro-orbitaire chez une panthère. Possibilité d'affinités
lointaines entre ce distome et les Paragonimidae. Annales de Parasitologie Humaine et
Comparée 17: 209-235, 1939
47. DUJARDIN F. Histoire naturelle des helminthes ou vers intestinaux, Librairie Encyclopédique
48. DUTT SC, SRIVASTAVA HD. The intermediate host and the cercaria ofGastrodiscoides
hominis (Trematoda: Gastrodiscidae). Journal of Helminthology 40: 45-52, 1966
49. ERHARDT A, GERMER WD, HORNING B.Die Opisthorchiasis, hervorgerufen durch dem
Katzenleberegel Opisthorchis felineus (Riv.). Parasitologische Schriftreihe 15: 1-170, 1962
50. FAIN A, VANDEPITTE J. Description du nouveau distome vivant dans des kystes ou abcès
rétroauriculaires chez l'homme au Congo Belge. Annales de la Société Belge de Médecine
Tropicale 37: 251-281, 1957
51. FERNANDES BJ, COOPER JD, CULLEN JB,FREEMAN RS, RITCHIE AC, SCOTT AA,
STUART PF. Systemic infection with Alaria americana (Trematoda). Canadian Medical
Association Journal 115: 1111-1114, 1976
52. von FRÖLICH JA. Beyträge zur Naturgeschichte der Eingeweidewürmer. Der Naturforscher,
Halle 29: 5-96, 1802
53. GARRISON PE. A new intestinal trematode of man. Philippine Journal of Science 3:
385-393, 1908
54. HARINASUTA C, VAJRASTHIRA S. Opisthorchiasis in Thailand. Annals of Tropical
55. HIRASAWA I. (On Echinochasmus perfoliatus found parasitic in man and on the final host
of this parasite.) Tokyo Iji Shinshi No. 2577, 1928. In Japanese. Abstracted in Japan Medical
World 8: 275, 1928
56. HOCKLEY AR., Observations on the metacercaria of Spelotrema. Proceedings of the First
International Congress of Parasitology p 525, 1964
57. HSÜ H F. Euparyphium jassyense Leon and Ciurea (= E. melis, Schrank) found at the
autospy of a Chinese. Chinese Medical Journal 58: 552-555, 1940
58. JANSON C. Die Haustiere in Japan. IV. Die Krankheiten der Hausthiere in Japan. (2)
Parasitäre Krankheiten. Archiv für wissenschaftliche und praktisch Thierheilkunde 19, 1893
59. KAGEI N, OSHIMA T, ISHIZAKA K, KIHATA M. (Two cases of human infection with
Stellantchasmus falcatus Onji et Nishio 1915 [Heterophyidae] in Kochi Prefecture.) Japanese
Journal of Parasitology 13: 472-478, 1964. In Japanese, with English summary
60. KATSURADA F. (On the genus Heterophyes in Japan.). Okayama Igakkai Zasshi No. 268,
pp 373-380, 1912. In Japanese
61. KATSURADA F. (On the genus Heterophyes in Japan: suplementary note.). Okayama
Igakkai Zasshi No. 269, 1912. In Japanese
62. KEAN BH, MOTT JE, RUSSELL AJ. Tropical Medicine and Parasitology. Classic
investigations, Cornell University Press, Ithaca, 2 volumes, pp 677, 1978
63. KERR AF. Intestinal parasites in northern Siam. Transactions of the Royal Society of Tropical
64. KHALIL M. A preliminary note on the second intermediate host ofHeterophyes in Egypt.
65. KHALIL M. The life history of the human trematode parasite Heterophyes heterophyes in
Egypt. Lancet ii: 537, 1933
66. KHOLOKOWSKY. Cited in 27
67. KLIKS M, TANTACHAMRUN Y. Heterophyid (Trematoda) parasites of cats in North
Thailand, with notes on a human case found at necropsy. Southeast Asian Journal of Tropical
Medicine and Public Health 5: 547-555, 1974
68. KOBAYASHI H. (On a new genus of the trematodes, Loxotrema ovatum). Saikingaku Zasshi
no. 204, pp 777-786, 1912. In Japanese
69. KOBAYASHI H. A distomid larva infesting the Egyptian mullet. Journal of Helminthology
1: 97-98, 1923
70. KRULL WH, MAPES CR. Studies on the biology of Dicrocoelium dendriticum (Rudolphi
1819) Looss, 1899 (Trematoda: Dicrocoeliidae) including its relation to the intermediate host,
Cionella lubrica (Müller). V. Notes on infections of Dicrocoelium dendriticum in Cionella

lubrica. Cornell Veterinarian 42: 339-351, 1952.
71. KRULL WH, MAPES CR. Studies on the biology of Dicrocoelium dendriticum (Rudolphi
1819) Looss, 1899 (Trematoda: Dicrocoeliidae) including its relation to the intermediate host,
Cionella lubrica (Müller). IX. Notes on the cyst, metacercaria, and infection in the ant,
Formica fusca. Cornell Veterinarian 43: 389-409, 1953
72. LANE C. Artyfechinostomum sufrartyfex. A new parasitic echinostome of man. Indian
Journal of Medical Research 2: 977-983, 1915
73. LANE C. A note on Heterophyes nocens as a distinct species of trematode parasite. Lancet
ii: 505, 1922
74. LEIPER RT. Notes on the occurrence of parasites presumably rare in man. Journal of the
London School of Tropical Medicine 1: 16-19, 1911
75. LEIPER RT. Observations on certain helminths of man. Transactions of the Royal Society of
76. LEON N, CIUREA I. Un nouvel échinostome chez l'homme. Comptes Rendus Hebdomadaires
des Séances et Mémoires de la Société de Biologie 87: 262-264, 1922
77. LEWIS TR, McCONNELL JF. Amphistoma hominis, n. sp. A new parasite affecting man.
Proceedings of the Asiatic Society 8: 182-186, 1876
78. LIE KJ. Further studies on the life history of Echinostoma lindoense Sandground and Bonne,
1940 (Trematoda: Echinostomatidae) with a report of its occurrence in Brazil. Proceedings
of the Helminthological Society of Washington 35: 74-77, 1968
79. LIE KJ, VIRIK HK. Human infection with Echinostoma malayanum Leiper, 1911
(Trematoda: Echinostomatidae). Journal of Tropical Medicine and Hygiene 66: 77-82, 1963
80. von LINSTOW OF. Einige neue Distomen und Bemerkungen über die weiblichen
Sexualorgane der Trematoden. Archiv für Naturgeschichte 1: 95-108, 1873
81. LOOSS A. Ueber den Bau von Distomum heterophyes von Sieb. und Distomum fraternum
n.sp., Kassel, pp 59, 1894
82. LOOSS A. Recherches sur la faune parasitaire de l'Egypte. Première partie. Mémoires
Présentés à l'Institut d'Égypt 3: 1-252, 1896
83. LOOSS A. Weitere Beiträge zur Kenntnis derTrematoden-Fauna Aegyptens zugleich Versuch
einer naturischen Gliederund des Genus Distomum Retzius. Zoologischer Jahrbucher.
Abteilung für Systematik, Oekologie und Geographie der Tiere, Jena 12: 521-784, 1899
84. LOOSS A. On some parasites in the museum of the School of Tropical Medicine, Liverpool.
85. LÜHE MF. Zur Kenntnis einiger Distomen. Zoologische Anzeiger 22: 524-539, 1899
86. LÜHE MF. Parasitische Plattwürmer. I. Trematodes Susswasserfauna Deutschlands
(Brauer), Heft 17, pp 217, 1909
87. McCONNELL JF. On the "Distoma conjunctum" as a human entozoon. Lancet i: 343-344,
1876
88. McCONNELL JF. "Distoma conjunctum". Lancet i: 476, 1878
89. McMULLEN DB. An experimental infection with Plagiorchis muris in man. Journal of
90. MAJIMA M. (On Echinostoma macrorchis found parasitic in human body.) Tokyo Iji
Shinshi No. 2552, 1927. In Japanese. Abstracted in Japan Medical World 8: 70, 1928
91. MARKOVI A. Der erste Fall von Philopthalmose beim Menschen. Archiv für
Ophthalmologie (von Graefe) 140: 515-526, 1939
92. MORISHITA K. Some avian trematodes from Japan especially Formosa, with a reference
list af all known Japanese species. Annotationes Zoologicae Japonenses 12: 143-173, 1929
93. MTSCHEDLIDZÉ J. Sur un cas de dicrocoeliose chez l'homme. Annales de Parasitologie
Humaine et Comparée 9: 68-71, 1931
94. MUANGMANEE L, ASWAPOKEE N, JAROONVESAMA N, VIRANUVATTI V. A
clinical trial of oral dehydroemetine in opisthorchiasis. Southeast Asian Journal of Tropical
95. MUTO M. (Biologische Studien über die Cercarien und die encystierten Cercarien des
Metagonimus yokogawai.) Kyoto Igaku Zasshi 14: 79-100, 1917. In Japanese, with German
summary, pp 54-56
96. MUTO M. (Ueber der ersten Zwischenwirt des Metagonimus yokogawai). Kyoto Igaku
Zasshi 14: 115-134, 1917. In Japanese, with German summary, pp 7-8
97. NÖLLER W. Befunde bei Schnecken von Thüringer Schwafweiden in einem
Lanzettegelgebeite. Tierärtzliche Rundschau 35: 485-489, 1929
98. ODEI MA. A note on dicrocoeliasis andFasciola gigantica infection in livestock in northern
Ghana with a record of spurious and of genuine Dicrocoelium hospes infections in man.
99. ODHNER T. Echinostoma ilocanum (Garr) ein neuer Menschen Parasit aus Ostasien.
Zoologischer Anzeiger 38: 65-68, 1911
100. ODHNER T. Die Verwaudschaftsbeziehungen der TrematodengattungParagonimus Brn.
Zoologiska Bidrag Frân, Uppsala 3: 231-246, 1914
101. ONJI Y, NISHIO K. (General observations on new intestinal flukes.) Igaku Chuo Zasshi 14:
875-883, 1915. In Japanese
102. OZAKI Y, ASADA J. (On a new species of Katsurada's Heterophyes family of parasites
found in a human case.) Tokyo Iji Shinshi No. 2445, 1925. In Japanese. Abstracted in Japan
Medical World 6: 42, 1926. Also: A new human trematode, Heterophyes katsuradai n. sp.
103. OZERETSKOVSKAYA NN, FIRSOVA RA, KARNAUKHOV VK et al. (Effectiveness and
tolerance of the 3-day scheme of chloxyl treatment of opisthorchiasis.) Meditsinskaya
Parazitologiya i Parazitarn e Bolezni 42: 581-585, 1973. In Russian, with English summary.
104. POIRIER MJ. Trematodes nouvelles ou peu connus. Bulletin de la Société Philomathique,
series 10, 7: 27-29, 1886
105. POPOV KK, KALINTINA ZI. (The development of Dicrocoelium dendriticum on high
altitude grounds of central Caucasus.) Zoolohichn Zhurnal Ukrayin 41: 1793-1797,
1962. In Russian
106. PROMMAS C. Report of a case of Opisthorchis felineus in Siam. Annals of Tropical
107. RADOMYOS P, BUNNAG D, HARINASUTA T.Echinostoma ilocanum (Garrison, 1908)
Odhner 1911, infection in man in Thailand. Southeast Asian Journal of Tropical Medicine
and Public Health 13: 265-269, 1982
108. RAGHUNATHAN VS, SRINIVASAN T. Artyfechinostoma mehrai infestation. Journal of
the Indian Medical Association 38: 485-487, 1962
109. RAILLIET A. Les parasites des animaux domestiques au Japan. Le Naturaliste No. 79, 143,
1890
110. RAO MA. A preliminary report on the adult trematode obtained from Cercaria indicae
Sewell, 1922. Indian Journal of Veterinary Science and Animal Husbandry 3: 317-320, 1922
111. von RATZ I. Húsovökben élö trematodák. In, Fleischfressern lebende Trematoden.
Kulonleyamat az Allatani Kozlemenyek 7: 15-20, 1908
112. RIM HJ. Studies on the chemotherapy of trematode infections in Korea. Korean Medical
Journal 12: 425-457, 1975
113. RIVOLTA S. Sopra una specie di Distoma nel gatto e nel cane. Giornale di Anatomia,
Fisiologia e Patologia degli Animali 16: 20-28, 1884
114. RODRIGUEZ JD, GOMEZ LF, MONTALVAN CJ. El Opisthorchis guayaquilensis (una
nueva especie de Opisthorchis encontrada en el Ecuador). Revista Ecuatoriana de Higiene
y Medicina Tropical 6: 11-24, 1949
115. RUDOLPHI CA. Neue Beobachtungen über die Eingeweidewürmer. Archiv für Zoologie
und Zootomie 3: 1-32, 1803
117. SADUN EH. Studies on Opisthorchis viverrini in Thailand. American Journal of Hygiene
62: 81115, 1955
118. SANDGROUND JH. Plagiorchis javensis n. sp. A new trematode parasitic in man. Revista
de Medicina Tropical y Parasitología, Bacteriología, Habana 6: 207-211, 1940
119. SANDGROUND JH, BONNE C. Echinostoma lindoense n. sp., a new trematode parasite
of man in the Celebes, with an accountof its life history and epidemiology. American Journal
120. SANDWITH FM. A case of Distoma heterophyes in a living patient. Lancet ii: 888, 1899
121. SCHEID G, MENDHEIM H, AMENDA R. Die Lanzettegelinfektion (Dicrocoeliasis) beim
Menschen nebst Mitteilung eines neuen Falles. Zeitschrit für Tropenmedizin und
Parasitologie 2: 142150, 1950
122. SCHRANK FP. Zoologische Beobachtungen. Der Naturforscher, Halle 18: 66-85, 1782
123. SCRIABINE KI (=SKRJABIN), PODYAPOLSKAYA WP, SCHOULZ GS. (Human and
animal metagonimiasis in the Far East of USSR.) "Tropical Medicine and Veterinary
Science" 8: 16-25, 1930. In Russian. Abstracted in Tropical Diseases Bulletin 29: 48, 1932
124. SEO BS, HONG ST, CHAI JY. Studies on intestinal trematodes in Korea. III. Natural
human infections of Pygidiopsis summa and Heterophyes heterophyes nocens. Seoul
125. SHEA M, MABERLY AL, WALTERS J, FREEMAN RS, FALLIS AM. Intraretinal larval
trematode. Transactions of the Academy of Ophthalmology and Otolaryngology 770P: 784,
791, 1973
126. SKRJABIN KI. (Echinostoma paraulum - nouveau parasite de l'homme.) Meditsinskaya
Parazitologiya i Parazitarn e Bolezni 7: 129-138, 1938. In Russian, with French summary
127. SKRJABIN KI, PODJAPOLSKAJA WP. Nanophyetus schikhobalowi n. sp. Ein neuer
Trematode aus dem Darm des Menschen. Zentralblatt für Bakteriologie, Parasitologie und
128. SONSINO P. Contributo alla entozoologia d'Egitto. Mémoires Présentés à l'Institut d'Égypte
3: 285-336, 1896
129. STILES CW, GOLDBERGER. Study of the anatomy ofWatsonius (n.g.) watsoni of man
and of nineteen allied species of mammalian trematode worms of the superfamily Paramph-
istomoidea. U.S.A., Treasury Department, Hygienic Laboratory Bulletin No. 60, 1910
130. STILES CW, HASSALL A. Comparison of the type of Distomum longissimum von
Linstow, 1883, with type of D. longissimum corvinum Stiles and Hassal, 1894. Veterinary
Magazine 3: 151155, 1896
131. STILES CW, HASSALL A. The lung fluke (Paragonimus westermani) in swine and its
relation to parasitic haemoptysis in man. Annual Report of the Bureau of Animal Industry,
U.S. Department of Agriculture, pp 560-611, 1900
132. STROM J. (On false distomiasis in the liver of man.) "Revue de Microbiologie et
Epidemiologie" 6: 433-437, 1927. In Russian, with English summary pp 476-477.
133. TANABE H. (Contributions to the knowledge of the developmental cycle of digenetic trem-
atodes. On a new species of trematode, Lepoderma muris n. sp.) Okayama Igakkai Zasshi
No. 385, pp 47-58, 1922. In Japanese
134. TANABE H. (Studies on the trematodes that use the fresh water fishas their intermediate
hosts. II. On the Japanese Echinochasmus perfoliatus, Ratz). Okayama Igakkwai Zasshi No.
387, 1922. In Japanese. Abstracted in Japan Medical World 2: 270, 1922
135. TRAVASSOS L. Sobre um interessante trematodeo parasito dos seios maxilares de gamba
(Didelphis marsupialis). Revista Brasileira Biologia 2: 213-218, 1942
136. TUBANGUI MA, AFRICA CM. The systematic position of some trematodes reported from
the Philippines. Philippine Journal of Science 67: 117-127, 1938
137. TUBANGUI MA, PASCO A. The life history of the human intestinal fluke,Euparyphium
ilocanum (Garrison, 1908). Philippine Journal of Science 51: 581-603, 1933
138. UPATHAM ES, VIYANANT V, KURATHONG S, BROCKELMAN, WY, MENARUCHI
A, SAOWAKONTHA S, INTARAKHAO C, VAJRASTHIRA S, WARREN KS. Morbidity
in relation to intensity of infection in opisthorchiasis viverrini: study of a community in Khon
Kaen, Thailand. American Journal of Tropical Medicine and Hygiene 31: 1156-1163, 1982
139. VOGEL H. Beobachtungen über Cercaria vitrina und deren Beziehung zum
Lanzettegelproblem. Archiv für Schiffs- und Tropen-Hygiene 33: 474-489, 1929
140. VOGEL H. Himasthla muehlensi n. sp., ein neuer menschlicher Trematode der familie
Echinostomatidae. Zentralblatt fürBakteriologie, Parasitenkunde und Infektionskrankheiten,
Abteilung originale 127: 385-391, 1933
141. VOGEL H. Der Entwicklungszyklus von Opisthorchis felineus (Riv.) nebst Bemerkungen
über Systematik und Epidemiologie. Zoologica 33: 1-103, 1934
142. VOGEL H, FALÇÃO J. Ueber den Lebenzyklus des Lanzettegels, Dicrocoelium
dendriticum in Deutschland. Zeitschrift für Tropenmedizin und Parasitologie 5: 275-296,

1954
143. WINOGRADOFF K (=VINOGRADOV). (On a new species of distomum [Distomum
sibiricum] in the human liver.) Izvestia Imperatorskogo Tomskogo Universiteta 4: 116-130,
1892. In Russian. Abstracted in Centralblatt Allgemeine für Pathologie und pathologische
Anatomie 3: 910-911, 1892
144. WITENBERG C. On the anatomy and systematic position of the causative agent of the
so-called salmon poisoning. Journal of Parasitology 13: 258-263, 1932
145. WYKOFF DE, CHITTAKYASOTHORN K, WINN MM. Clinical manifestations of
Opisthorchis viverrini infections in Thailand. American Journal of Tropical Medicine and
Hygiene 15: 915-918, 1966
146. WYKOFF DE, HARINASUTA C, JUTTIJUDATA P, WINN MM. Opisthorchis viverrini
in Thailand - the life cycle and comparison with O. felineus. Journal of Parasitology 51:
207-214, 1965
147. YARWOOD GR, ELMES BG. Paragonimus cyst in a West African native. Transactions
148. YOKOGAWA M, HARINASUTA C, CHAROENLARP P. Hypoderaeum conoideum
(Bloch 1782) Dietz 1909, a common intestinal fluke of man in northeast Thailand. Japanese
149. YOKOGAWA S. (A new parasite involving trout as its intermediate host and its new generic
name.) Okayama Igakkai Zasshi No. 279, 1912. In Japanese
150. YOKOGAWA S. Ueber einen neuen Parasiten Metagonimus yokogawai, der die Forellenart
Plecoglossus altivelis 1(Temminck) zum Zwischenwirt hat. bildung einer neuer Gattung.
Centralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten, Abteilung
originale 72: 158-179, 1913
Chapter 12
Echinococcus granulosus and ECHINOCOCCOSIS or

HYDATID DISEASE
SYNOPSIS
Common name: hydatid

Major synonym: Taenia echinococcus
Distribution: world-wide, particularly in sheep- and cattle-raising countries
Life cycle: The adult tapeworms, 3-6 mm long, live in the small intestinal lumen attach
ed to the mucosa. They produce eggs which are passed in the faeces. When ingested
by an herbivorous or omnivorous animal, each egg hatches a larva (oncosphere)
which migrates through the bowel wall then passes via the portal venous system to
the liver where many are arrested. Some larvae continue their migration to the lungs
where they may either lodge or pass into the systemic circulation and reach other
tissues. In the tissues, the larva grows, encysts and the wall differentiates into an
outer, non-nucleated, laminated layer and an inner, nucleated, germinal layer. During
the ensuing months to years, buds develop from the inner layer and become
vacuolated to form brood capsules; these in turn develop protoscolices on their inner
surface. The whole cyst is surrounded by a fibrous layer of host origin. When a cyst
is ingested by a dog, the protoscolices attach to the small bowel mucosa and develop
into adult worms after several weeks
Definitive host: dogs and other canines
Intermediate hosts: sheep, cattle, pigs, horses, humans
Major clinical features: manifestations of a space-occupying lesion, depending upon the
location of the cyst
Diagnosis: suggested by radiology plus immunological studies; proven at operation
Treatment: surgery, where possible; ? mebendazole or albendazole
AWARENESS OF THE ANIMAL NATURE OF HYDATID CYSTS
Hydatid cysts have been known since ancient times in both animals an d
humans, but the parasitic nature of these "bladders" was long unrecognized .
Mention is made in the Talmud of cystic lesions in the viscera of sacrificia l
animals. Hippocrates (460-37 9 BC) alluded to tumours filled with water in the
lungs of cattle, sheep and pigs. Similarly, in his aphorisms on human medicine,
he wrote: "When the liver is filled with water and bursts into the epiploon, in
this case the belly is filled with water and the patient dies"(VII,55) 57. In his
commentary on the works of Hippocrates, Galen (129-c.200 AD) interpreted
this aphorism as describing an hydatid cyst which had burst into the peritoneal
319
cavity. Galen was also familiar with echinococci and cysticerci (probabl y
Cysticercus tenuicollis, the cystic form of the tapeworm, Taenia hydatigena)
in the abdomen of butchered animals, for he wrote: "The liver is very muc h
inclined to produce hydatids in the surrounding fascia. Sometimes, the liver of
slaughtered animals is full of them" 47. Aretaeus of Cappadocia was also aware
of hydatid cysts in humans. He recorde d a case in which attempted paracentesis
of the abdomen was hindered by blockage of the trocar and cannula wit h
vesicles; this circumstance indicated puncture of an echinococcal cys t
containing daughter vesicles:
Small and numerous bladders, full of fluid, are contained in the place where ascites
is found; but they also float in a copious fluid, of which this is the proof; for if you
perforate the abdomen so as to evacuate the fluid, after a small discharge of the fluid,
a bladder within will block up the passage.8
Hydatid cysts were noted from time to time in medical works of th e
succeeding centuries but their true nature was not generally understood. They
were usually ascribed to being either (1) excrescences or growths in the viscera
produced by collections of serum and mucus, sometimes mixed with pus ,
between laminae of cellular tissue, (2) enlarged and degenerated glands or, (3)
following the discovery of lymphatic glands in the seventeenth century, a s
distended and varicous lymphatics.
It was not until near the end of the seventeenth century that an awarenes s
began to dawn that some of these cysts were animal in nature. Observation s
were made on a variety of cysts in animals and humans. First, came th e
realization that some of these "bladders" wer e really worms. Once this had been
achieved, the various species of cysti c worms, including echinococci, cysticerci
and coenuri, were differentiated. The problem was compounded by th e
common practice of using the term "hydatid" in medicine to refer to any cystic
swelling, with the consequence that echinococcal cysts in humans needed to be
separated from similar non-parasitic tumours.
The clue that some of these cysts were of animal origin was that many o f
them had one of the cardinal att ributes of living animal creatures - spontaneous
movement. The Italian, Francisco Redi, appears to have been the first person
to both observe and record this phenomenon. Working in Florence in 1684, he
found cysts (probably Cysticercus pisiformis ) in the mesentery and also lying
free in the peritoneal cavity of a hare. Within each cyst, he observed a retracted
neck. Moreover, on watching the cysts closely, he noticed that the free cyst s
moved independently. This caused him to comment "quasi animalia foren t
proprio motu arta" 98 meaning that the cysts moved about on their own as if they
were animals.
Redi wondered whether these cysts could possibly be the eggs of the worms,
Fasciola hepatica, that he had found in the biliary system of the same rabbit,
and had noted previously in the livers of sheep. He thought this was unlikely,
however, as the liquid within the cysts did not coagulate when he boiled it, in
contrast to his earlier observations on the behaviour of eggs in mammalia n
Echinococcosis 321
ovaries (in which he had found that the enclosed liquid did congeal). Redi also
discovered a similar cyst in a marten and, realizing the similarity of thes e
various cysts from different animals, grouped them together under the nam e
"Glandette o vesichette verminose" meaning "wormy glands or cyst s
(vesicles)" 98.
In the following year (1685), Philip Hartmann, a professor in the University
of Königsberg, East Prussia (now Kaliningrad, USSR), emphasized the animal
nature of these cysts and clearly related them to intestinal worms. In th e
omentum of a dissected goat, he found cysts that he called "vesicular hydatids"
(probably Cysticercus tenuicollis ), the largest being greater in size than a
chicken's egg. He noticed a small, white, globular appendage at the extremity
of each cyst. When one of these was incised and pressed gently, it was turned
inside out. He wrote that at once "the rounded tail of a protruding intestina l
worm became evident" 52. Furthermore, he thought that he had noticed som e
movement, so he placed the specimen in a container of warm water an d
reported that:
When it was submerged and clinging to the bottom, I saw not only the proboscis but
also the vesicular body begin movement in a marvellous manner; it moved with a
singular form of undulation, exhibiting contraction and expansion with rising and
falling of its parts.52
The sac itself consisted of nothing beyond a very thin membrane which wa s
very smooth on both surfaces and contained a clear liquid lymph within it. On
the following day, another goat, which had just died and was still warm, was
brought to the dissecting room. In this animal, his students, Thormann an d
Litius, found more bladder worms and verified his observations, clearl y
demonstrating movements while the cysts were still within the membran e
formed by the enclosing omentum 52. In 1688, he was again to find a motile cyst,
this time in a pig (Cysticercus cellulosae ; see chapter 13), then in 1694 h e
found Cysticercus fasciolaris in a mouse54.
These early observations were unknown to the Oxford physician, Edwar d
Tyson, when he rediscovered such movements in Cysticercus tenuicollis . In
February 1687, he told a meeting of the Royal Society that "Hydatides i n
Animalls are a sort of Living creatures" 115. He recounted his observations o n
bladders about the size of a pigeon's egg that he had found in the peritonea l
cavity of a gazelle brought from Aleppos (now Halab, Syria). He is recorded
in the Journal Book of the Royal Society as describing the bladders in th e
following terms:
They were found involved in two coats like the corion and the Amnion, the innermost
having a neck of a more Opake and solid substance that the rest of the Bladder, which
neck, (at its first being taken out of the Animall) was observed to move as if alive; the
whole bladder being filled with a Limpid water he supposed might be as the stomach
to the worm.115
Tyson was said to have come to the conclusion that "(they") are worms sui
generis or at least the Embrios of them" 115. This remarkable insight of Tyson's
that the cysts loosely termed "hydatids" were worms or at least the embryos of
them, predated by more than 150 years the experimental demonstration tha t
bladders are the "embryonic form" or intermediate stage in the development of
tapeworms.
Further details of these observatio ns are provided in Tyson's definitive report
published in 1891 (the delay being due to difficulty in publishing th e
Philosophical Transactions of the Royal Society )116. He observed that when-
ever a candle was brought near the cyst , the neck, a small, white protruberance,
moved. Tyson canvassed the possibility that these cysts represented an egg or
embryo of an insect, with the bladder being the amnion and the outer coa t
representing the chorion. He thought this unlikely since he had found man y
such structures that were all in a similar state when dissecting "rotten sheep",
whereas he would have expected that som e of them should have been in a more
mature state if they had been a developing insect. He named these cyst s
Lumbricus hydropicus in the following words:
These Hydatides therefore I cannot but think are a sort of Worms or Insects sui
generis, and because they contain so much water in them, and are usually to be met
with in rotten Sheep which are usually Hydropical; I call them Lumbrici Hydropici 116
Although less definite on this occasion by including "or Insects" in his opinion
on the nature of hydatids, the consensus of his remarks in the text of th e
manuscript, together with the title which he gave it, viz.: " Lumbricus
hydropicus or an Essay to prove that Hydatides often met with in morbi d
Animal bodies, are a Species of Worms, or Imperfect Animals" 116 leaves little
doubt that he considered that hydatid cysts were most likely worms. Never -
theless, he did not think that all such cysts were necessarily verminous i n
nature, for he also wrote: "in some I have not observed this Neck and Structure
of Parts, but only a transparent bl adder fill with a Lymph, and those I take to be
of another kind" 116. Tyson then went on to give his clinical experience wit h
hydropical bodies occurring in humans, some of which were undoubtedl y
echinococci.
Similarly, Marcus Malpighi in 1697, probably unaware of the discoveries of
his contempories, recognized the vitality of cysts he found in pigs ( Cysticercus
cellulosae), and described accurately the small head within each cyst 81.
Despite the major importance of all these observations and the considerable
impetus that they could have given to the elucidation of the nature of the cysts
and the life cycles of these organisms, more than 60 years were to pass before
another significant advance was made. This newly found comprehension of the
animal nature of these cysts was largely ignored or forgotten by naturalists and
the medical profession until 1760. In that year, Morgagni 84 recalled the
researches of Redi, Hartmann and Tyson, and pointed out that th e
bladderworms described by various authors were not all of the same kind.
Just how long it took for the recognition of the animal nature of hydatid and
other verminous cysts to penetrate the general consciousness of the medica l
profession is illustrated by the proceedings of the London Medical Societ y
published in The Lancet as late as the year 1833:
Echinococcosis 323
Mr. Stephens entered the room in some haste, to exhibit to the Society three or four
hydatids which he procured in the course of the afternoon, affording the members an
opportunity to personally witness the existence of life in these 'imperfect animalcules'
as Baillie terms them, though the hydatids shown on this occasion will almost justify
the employment of the less equivocal term 'animal'.
The President immediately drew attention to the exhibition. 'This is very interesting,'
he observed, 'as it settles a point greatly in dispute. Here is a head as clearly as a head
can be. Get a little warm water and see if it will revive the movements.'
Mr. Stephens. 'Most probably it will not, for, unfortunately, they are now expiring, but
they had this afternoon as free and perfect movement as a lively leech, and though
now almost spherical, have assumed an alternately contracted and bulging form.'
The President. 'Gentlemen will please to be very careful in examining them lest they
break and the fact of life shut from our observation.' 2
Thereupon, warm water was procured and motion was demonstrated when the
cysts were placed in it. These cysts, which were not E. granulosus, had been
obtained from the mesentery of a sheep and considerable discussion the n
ensued as to the relationship between these transparent cysts and the semi -
opaque, pulpy cysts which members had encountered previously in sheep and
in humans.
RECOGNITION OF THE MORPHOLOGICAL SIMILARITIE S

BETWEEN CYSTS AND TAPEWORMS, AND THE DIFFER -
ENTIATION OF SPECIES
At almost the same time as Redi, Hartmann and Tyson made the observations
already described, a Swiss physician and pathologist, Johann Wepfer, dis -
covered in 1688 a cyst, later to be known as Cysticercus fasciolaris, in the liver
of a mouse121. It is possible that this parasite may have been seen some 20 years
earlier by Pecquet 90, but he did not at that time appreciate fully the significance
of the observation. Not only did Wepfer r ecognize the animal nature of the cyst,
but he also realized that it resembled the tapeworm then known as "lati s
lumbricus intestinorum". This interpretation was facilitated by the fact that the
caudal vesicle of this cysticercus is relatively small and the head of the worm
is not invaginated into it (hence it has has also been called a strobilocercus) .
Although Wepfer was the first person to establish a link between any species
of tapeworm and its intermediate cystic form, he was completely unaware of the
life cycle of the parasite and merely considered C. fasciolaris as an encysted
tapeworm. Again, news of this observation was not disseminated widely and
it fell into oblivion.
In 1766, Peter Pallas made two major contributions to our knowledge o f
cystic worms. Firstly, by classifying "hydatids" into non-adherent and adherent
forms, he managed to separate cystic worms from serous cysts, respectively .
Secondly, he renewed awareness of the morphological similarities betwee n
cystic worms and the heads of tapeworms 89. He propounded a theory that al l
these cystic worms belonged to a single species which he named Taenia

hydatigena. Furthermore, he proposed that worms in different animal host s
varied in their appearance, especially in the structure of the caudal vesicle. He
was aware, for example, that the cysticercus found in the liver of mic e
(C. fasciolaris) was reminiscent of the head of the cat tapeworm ( Taenia
crassicollis now called T. taeniaeformis). Similarly, he noted the resemblances
between the cysts (C. tenuicollis) found in ruminants and the heads of som e
tapeworms of dogs and cats (now called T. hydatigena), especially in relation
to the circlet of hooks and the sucking pits. Pallas was, however, rathe r
perplexed by the cysts we now know as echinococci. He knew that they were
found most commonly in the liver and lungs of sheep and oxen, but occurred
occasionally in humans as well. He recognized that the cyst walls did no t
encompass a distinct neck and head, but contained instead a large number of
small bodies or corpuscles, but since he was able to observe them only macro-
scopically, he was unable to discern their true nature. Even so, Pallas was still
convinced that these cysts owed their origin to tapeworms:
It seems to me very probable that the incompletely developed water vesicles seen by
many observers in the human body, such as those oftenest found in pathological
cavities in the liver, are caused by and arise from a worm resembling our own
tapeworms.89
Although these cysts appeared to be different in almost every respect from his
T. hydatigena, Pallas still believed that they were derived from the latter .
Similarly, he considered that the Coenurus of sheep had the same origin. I n
fact, he regarded the Coenurus as a many-headed tapeworm, and the Echino-
coccus as being closely related to if not ident ical with it. Moreover, he surmised
that the heads of the coenuri may be but a further development of th e
corpuscles or globules that occurred in echinococci.
Thus, in re-awakening interest in t hese cysts, Pallas made two major contrib-
utions; he differentiated verminous from non-parasitic cysts, and reemphasized
the relationship between them and tapewor ms. In doing this and in adopting the
nomenclature, Taenia hydatigena, though, he did not mean to imply that these
cysts were derived from tapeworms, any more than Tyson would have claimed
that they owed their genesis to roundworms or tapeworms when he used th e
term, Lumbricus hydropicus , to describe these parasites.
Although Pallas regarded echin ococci as being related to tapeworms, he was
unable to provide proof to substantiate this view. The requisite evidence was
first given in 1782 by Johann Goeze when he described the scolices o f
echinococcal cysts and indicate d their similarity to the heads of tapeworms. On
1 November of the previous year, Goeze was given an extremely mutilate d
sheep liver that was so permeated with watery vesicles of various sizes that it
was almost impossible to see the liver parenchyma. When he pricked some of
the vesicles, liquid rushed out like a fountain. Within some of the rather hard
and leather-like vesicles, he found smaller, soft, bluish vesicles. When thes e
were opened in turn, Goeze disce rned a greyish-white, granular material which
Echinococcosis 325
was connected to a very delicate membrane. When part of this membrane was
placed in water, the granules dropped off immediately and appeared to swim
around individually. In one of the vesicles, the size of a pigeon's egg, he found
many thousands of these granules which were so small that they were hardl y
visible to the naked eye. On examining them with a magnifying glass, he saw
plainly that they were true tapeworms:
he bodies were flat and dotted black; in front four suckers and on the rounded
foreshortened proboscis the exceedingly small double-hook crown; however, on each
one, posteriorly, was a small, sloping indentation like an anus. 49
Goeze concluded, therefore, that these cysts were a kind of tapeworm whic h
were distinct from the coenuri that were found in the brain of giddy sheep .
Thus, there was now no doubt that echinococcal cysts were alive, that they were
verminous, and that they were related to tapewo rms. Goeze named them Taenia
visceralis socialis granulosus, meaning the tapeworm which was found in the
viscera and contained a multitude of granules 49. Shortly afterwards (1786) ,
Batsch renamed the parasite Hydatigera granulosa 13.
From this point, unfortunately, progress in the understanding of the nature of
cystic worms ceased for more than half a century. Indeed, a genera l
retrogression occurred. In 1800, Zeder erected a distinct classificatory group
for the cystic worms, thus separating them as a zoological entity from th e
tapeworms 122. At first, he called echinococci, Polycephalus hominis 122 , then
in 1803, he renamed them Polycephalus echinococcus 123. The problem was
then compounded by Laennec (1804) who investigated hydatid cysts i n
humans. He could not find the familiar taeniid heads seen in hydatid cysts from
sheep and oxen, so concluded that they must either belong to another genus, or
else be of a completely different nature. Being less than convinced of thei r
animal nature, he gave them the name "acephalocysts" 71. Because of Laennec's
authority, this view was generally accepted until Livois showed in 1843 tha t
acephalocysts were but ordinary hydatids in which the scolices had not ye t
developed 78.
The views of Zeder were perpetuated by Rudolphi in his major text of 1808-
1810. He placed the tapeworms in the Order Cestoideorum while the cysti c
worms were located in the Order Cysticorum 101. Meanwhile, however,
Rudolphi in 1801 had erected the genus Echinococcus 99, which was later to be
placed in this latter order. The name was derived from a combination of th e
Greek words (ECHINOS) and (KOKKOS/ COCCUS)
meaning "spine" and "berry", respectively. The Index Catalogue of Medica l
and Veterinary Zoology has cited this parasite as Echinococcus granulosu s
([Goeze 1782]) Batsch 1786) Rudolphi 1805, with Rudolphi in his 180 5
paper100 describing Taenia hydatigena granulosa in swine. Later, Rudolph i
divided the genus Echinococcus into three species, E. hominis, E. simiae and
E. veterinorum, which he believed infected humans, sub-human primates, and
sheep or cattle, respectively 101.
In the succeeding decades, there was considerable confusion and disput e
among helminthologists, some admitting the existence of only a single species,

others allowing two, while yet others thought that there was an even greate r
number of species. Thus, Bremser, for example, believed that the same kind of
scolex was recovered from hy datid cysts of man as was seen in hydatid cysts in
animals 19 . This unitarian view was also adopted by Diesing who named th e
worm Echinococcus polymorphus 41.
The most common practice, however, was to divide echinococcal cysts into
two species; E. hominis supposedly occurred in man and had scolices with a
single row of hooklets, while E. veterinorum was thought to occur in animals
and have a double row of hooklets. Küchenmeister in 1855 considered that this
view was untenable for he believed that "E. hominis" had been discovered in
cattle by Haubner and Creplin and that von Ammon had found " E. veter-
inorum" in the human eye. Nevertheless, Küchenmeister believed that tw o
species of these cysts could be distinguished on morphological grounds and he
divided them into E. scolicipariens in which scolices alone were present, and
into E. altricipariens in which daughter cysts were formed as well 69. Rudolf
Leuckart at first followed this cl assification and proposed the names E. simplex
and E. hydatidosa for these two forms, respectively. In 1863, however, Naunyn
showed that adult tapeworms derived from E. altricipariens were identical with
those obtained from E. scolicipariens, and concluded that it was no longe r
proper to separate the two species 87. Furthermore, it was eventually realize d
that, following a single infection, the same animal or human may have cyst s
with or without daughter cysts and that the number of hooklets on each scolex
is extremely variable and is dependent, to some extent, upon the age or stage
of development of the scolices 16.
With the recognition that there was but one species of both the cystic form
and the adult worm, the parasite was finally named E. granulosus since the
genus Echinococcus of Rudolphi remained valid and the specific name reverted
to the Taenia visceralis socialis granulosa of Goeze.
DISCOVERY OF THE ADULT WORM AND ELUCIDATION OF THE

MODE OF TRANSMISSION
THE BACKGROUND
The discovery of the life cycle of E. granulosus becomes comprehensible only

when viewed in the light of earlier studie s investigating the life cycles of related
tapeworms and cystic forms found in a variety of animals. Two ideas wer e
required to pave the way for the necessary experimental studies. Firstly, th e
morphological similarities between parts of certain cysts and the heads o f
various tapeworms had to be recognized and, secondly, the theory of th e
alternation of generations needed to be formulated.
Echinococcosis 327
As has already been discussed , the morphological resemblances between the

heads of cystic worms and tapeworm heads had been first noted in the latte r
part of the seventeenth century by Wepfer, then almost one hundred years later
by Pallas and Goeze. Indeed, Goeze came very close to the truth regarding the
development of C. fasciolaris when he wrote:
On the 13th March, 1780, I found in the liver of the mouse, two clear, crystal
vesicles, in each of which there was a pisiform vesicle, but on this as yet, no body. I
believe that as regards the production and development of this kind of worm, I have
surprised nature in the act.50
Following the same line of thou ght, Goeze's friend, Wagler proposed that tape-
worms of cold-blooded animals should be fed to other cold- and warm-blooded
animals and vice versa, then watched to see if they became degenerate o r
acquired novel properties from their new host.
The second impetus was provided in 1842 by Steenstrup when he formulated
his theory of the alternation of generations 112 (see chapters 2 and 4). H e
conjectured that the cystic worms were early stages in the development o f
helminths that were unknown to him. Steenstrup argued, therefore, that these
worms should no longer be classified a s a separate group, just as he maintained
that certain asexual trematodes such as Cercaria species should also no longer
be categorized separately. It is surprising that Steenstrup did not connect the
cystic worms with tapeworms as not only had Pallas and Goeze recognized the
relationship, but a number o f other authors including Nitzsch, FS Leuckart and
F Müller had already recommended the abandon ment of this unnatural cleavage
of cystic worms from tapeworms. Küchenmeister summed up the reasons for
the general failure of helminthologists to appreciate the connection betwee n
cystic worms and tapeworms when he wrote:
Naturalists either did not correctly comprehend the true direction of progress, or, for
reasons which it is difficult to perceive, they ignored the labours of their
predecessors.69
As a consequence of Steenstrup's promulgation of his doctrine of th e
alternation of generations, however, a number of investigators re-assessed their
ideas. Dujardin in France in 1845 asserted that cystic worms were incompletely
developed tapeworms. He surmised that they were formed by the germs o f
tapeworms which, instead of going into the intestines of their natural hosts ,
somehow arrived in the tissues, and under the influence of this unusua l
dwelling-place, developed abnormally to become cystic worms; he regarde d
them as "une sorte de monstruo sité"42. At around the same time, von Siebold in
Breslau, Germany (now Wroclaw in Poland), expressed similar convictions. As
he later recounted, von Siebold initially had held the simple (and correct) view
that:
In its form, its suckers, and its circlet of hooks, the head of the asexual cystic worms
possesses such a striking similarity to the heads of certain tapeworms, that one is
tempted to believe that the cystic worms are nothing else than undeveloped and
larvae-form tapeworms.104
Von Siebold thought that the adult and larval f orms of the worms must be found
in different animal hosts "since the young brood was so seldom seen near the
cestodes"103. He then changed his mind about the development of these cyst s
and arrived:
at the most decided conviction that the cystic worms are strayed tapeworms which
have remained undeveloped and become degenerated, and of which the body grew
out in foreign soil into a vesicle, without developing sexual organs. 102
Von Siebold voiced this view repe atedly and vociferously. In another paper, he
expounded this theme once more:
I finally became convinced that all cystic Entozoa are nothing else than undeveloped
or larval tapeworms, which, arrested in their wanderings, have become aberrant and
dropsically degenerated.107
This idea was partly engendered by his false belief that, in bladder worms, the
scolex end of the larva was formed first th en this developed a posterior (caudal)
projection which in turn underwent secondary hydropic degeneration. Vo n
Siebold seems to have been unaware that Goeze had already shown in the case
of C. fasciolaris of the mouse, that first the cystic caudal end was formed, then
the scolex appeared. It was not until the Prague zoologist, von Stein ,
demonstrated in 1853 a similar development of a small bladderworm in th e
larva of the mealworm (Tenebrio molitor) that this sequence of events became
generally accepted. Moreover, von Siebold either conveniently forgot, or else,
incredibly, was ignorant of the writings of earlier workers, and claimed, even
as late as 1853, that he was the first person to draw attention to the similarity
between cystic worms and tapeworms 107. This so annoyed Küchenmeister that
he went to great lengths in his textbook to demonstrate that von Siebold was
decidedly in error in this claim 69. Furthermore, von Siebold's championship of
the theory of dropsical or cystic degeneration of tapeworms was to lead to an
acrimonious difference of opin ion with Küchenmeister. Thus, according to von
Siebold, certain eggs of the tape worm of the cat, T. crassicollis (now known as
T. taeniaeformis), frequently strayed into rodents and there degenerate d
dropsically (i.e. filled with fluid) into C. fasciolaris, but when their host was
devoured by a cat and they became transplanted into their "proper soil", they
cast off the degenerated segments, returned to the normal form of T. crassicollis
and arrived at sexual maturity. Von Siebold then went further and claimed that
with the exception of C. fasciolaris of the mouse, and possibly C. crispus, all
of the many other cystercerci have deg enerated so far into a dropsical state, that
by virtue of their gross distension, they were no longer fit to return to the state
of sexual maturity and consequently they perished without descendents 105,109.
In 1850, the Belgian zoologist, PJ van Beneden theorized that the head of a
tapeworm (which he named "scolex") is produced from the egg of a tapeworm
and conjectured that if the egg reached the gut of a suitable animal host, th e
jointed mature tapeworm (which he called "strobila") would develop and grow
without interruption. On the other hand, he hypothesized that if the egg found
its way into the intestine of an unsuitable host, the head would develop but that
the hind part would become inflated and the scolex would sink into it, thu s
Echinococcosis 329
forming a cysticercus 14. Thus, van Beneden deduced that bladderworm s

(Cystici), which had hitherto been regarded as a separate class of helminths ,
were simply larval tapeworms. This correct view was not accepted readil y
because the evidence that he advanced was slight. In any case, van Benede n
was wrong in thinking that eggs developed directly into tapeworms and tha t
bladderworms were an unnecessary stage and appeared only incidentally.
This was the state of affairs when Friedrich Küchenmeister in Zittau, (now
East) Germany began to investigate the effects of administering various cystic
worms to different animals. One cannot but be impressed by the perspicacity
of this remarkable man and wonder about the driving forces which impelle d
him to seek the truth. Not only did he lack the intellectual milieu in which t o
discuss his ideas and concepts, but he found time to pursue his studies in the
midst of running his medical practice, despite the absence of laboratory facil-
ities and technical and financial assistance. In the great tradition of Redi ,
Küchenmeister emphasized the importance of hypothesis and experiment for
helminthology and thus became the major figure in the renaissance of this field
of scientific endeavour. Küchenmeister began with two of the most easil y
accessible cysticerci, C. pisiformis of the rabbit and C. fasciolaris of the
mouse. Between 18 March and 9 April 1851. Küchenmeister fed 40 C.
pisiformis to a fox then recovered young tapeworms which he called initially
Taenia crassiceps 65,66. He then gave C. fasciolaris to a cat and again
succeeded in rearing tapeworms that were rapidly approaching maturity 67.
Furthermore, he showed that when cy sticerci were fed to an inappropriate host,
the cysticerci died and no development took place. He concluded that cysti c
worms were not strayed, dropsical tapeworms as claimed by von Siebold, but
were tapeworm larvae furnished with a vesicle which probably acted as a
reservoir of nutriment. In fact, Küc henmeister indicated that cystic worms were
an essential stage in the development and maturation of taeniae. His firs t
reports in 1851 65,66, did not meet with universal acclamation, partly because he
first identified the tapeworm that he had reared in foxes as T. crassiceps, then
as T. serrata, then finally as T. pisiformis n. sp. (which is its current name) .
Shortly afterwards, however, he successfully reared tapeworms in dogs from
C. tenuicollis of domestic mammals and from Coenurus cerebralis of sheep68.
Von Siebold, annoyed that he, an eminent University professor, had bee n
upstaged by a mere general practitioner and amateur parasitologist, and en -
raged by Küchenmeister's treatment of his theory of dropsical degeneration of
strayed tapeworms, lost little time in repeating the latter's experiments. In 1852
he confirmed the metamorphoses of C. pisiformis and C. fasciolaris and
reported the same phenomenon with Coenurus 106,107. Nevertheless, he clung
to his theory:
Some individuals of the brood of T. crassicollis go astray in rodents and degenerate
into C. fasciolaris; but when their hosts are eaten by cats and the worms are thus
transplanted to their fit soil, they cast off their degenerate joints, and returning to the
normal form of T. crassicollis, become sexually mature.110
At the same time, von Siebold embarked upon a personal attack on Küchen-
meister and tried to claim credit for himself for the discovery of the phenom-
enon in two ways. Firstly, he harked back repeatedly to an earlier comment in
his article "Parasiten" dated 1844 102 (although it actually appeared in 1845) on
the similarity between cystic worms and tapeworms; this, as we have already
seen, was not an original observation. Secondly, he tried to impai r
Küchenmeister's credibility by asserting that if he had not come to the latter's
aid in determining the species of the adult tapeworms, the whole theory of the
process of metamorphosis would have been thrown into such a state of con -
fusion that it could hardly have been corrected 107. To this, Küchenmeister
responded in kind saying: "no-one has so grievously offended in the study o f
cestodes as the professor of zoology" 70.
As we have already seen, Küchenmeister attacked von Siebold's claims t o
priority in drawing attention to the relationship between cystic and tapeworms
and castigated his theory of dropsical degeneration 69. This in turn, drew the
following riposte from von Siebold: "(Küch enmeister) has been led away by his
zeal, to depart from that calmness of tone which becomes scientific contro -
versy."109. When Leuckart came later to review this contre-temps, he sided with
von Siebold: "Küchenmeister in his book underrates von Siebold's share in the
solution of the problem in a way which is, to every unprejudiced critic, utterly
unfair"76. Küchenmeister may have used strong words, but there is no doubt that
his experiments opened the door to the t ruth and his interpretation of the results
thus obtained were correct.
It must also be remarked in passing that not on ly was von Siebold wrong with
his theory that cystic worms were strayed, degenerated, dropsical worms, but
he also came eventually to the view that with the exception of echinococci, all
the cystic worms were derived from one species of tapeworm which he called
T. serrata. Thus, von Siebold claimed that w hen he fed C. pisiformis of rabbits,
C. tenuicollis of cattle, C. cellulosae of pigs and C. cerebralis of sheep to dogs,
he always found T. serrata in the gut. He concluded that the nature of the cyst
is determined by the species of host in which the T. serrata larvae find
themselves. These false observations reinforced his incorrect belief that cystic
worms were a pathological st ate rather than being a physiological necessity for
continuation of the life cycle 109. The only feasible explanation for this amazing
error on von Siebold's part is that his dogs were coincidentally infected with T.
serrata and that the dog was not a favourable host for the development of some
cysticerci such as C. cellulosae.
In passing, it should be noted that the idea that all of these cysts were derived
from T. serrata was one of the points which Pouchet and Verrier used a fe w
years later (1862) to attack the whole concept of cystic migrations o f
tapeworms. They also criticized the experiments of Küchenmeister, van Ben-
eden, von Siebold and others on other grounds, including their belief that the
experiments were "too successful". In th eir own experiments, Pouchet and Ver-
rier recovered more tapeworms than the numb er of scolices that they had given,
Echinococcosis 331
and claimed to obtain two distinct species of tapeworms after feeding a single
coenurus to a dog. This induced van Bene den to return to the fray to refute their
views, but Pouchet and Verrier remained recalcitrant saying:
we cannot believe that a microscopic embryo of a taenia enclosed in the intestines of
a sheep can make for itself a passage up into the brain of the ruminant, and then
undergo transformation into a vesicle, which engenders numerous scolices. 93
Nevertheless, this was the last gasp of the sceptics and the views of Küchen-
meister and others became generally accepted.
EXPERIMENTAL GENERATION OF E. GRANULOSUS ADULT WORMS
By 1852, enough was known to stimulate feeding experiments with echino -

cocci. It was von Siebold who first achieved success. He began his invest -
igations in the summer of 1852 and re ported his results in the following year 108.
He obtained hydatid cysts from sheep, then saturated milk with echinococcal
larvae and poured it down the throat of a number of dogs. In a dog which was
killed 12 days later, no worms were found in the stomach, but the entire small
intestine was lined with innumerable small echinococcal worms, all wit h
extended heads which were placed deep between the villi. They looked littl e
different from the original larvae within the echinococcal cysts except that they
were longer and more slender. When another dog was killed 22 days afte r
infection, the worms were found to have d eveloped further, consisting of a head
and two or three posterior segments. Finally, 27 days after infection, vo n
Siebold discovered mature worms several millimetres long, which had a head
and three posterior segments containing reproductive organs and eggs. These,
von Siebold called Taenia echinococcus, and summarized his findings thus:
Proof that the brood of the E. veterinorum must adapt well in the duodenum of the
dog is the elongated state in which the Echinococcus larvae are seen there after
feedings, the growth of the same which follows soon thereafter, and finally the pro-
duction of eggs and embryos in those body segments having reached sexual matur-
ity....that species of adult tapeworm to which the larval Echinococcus brood belongs
seems to have escaped the eyes of the helminthologists until now. I suspect that this
might be due in part to the small size of this species of tapeworm and in part to the
short time span which is required for its sexual maturation. 108
These adult worms had in fact been noted earlier by a number of observers.
Hartmann may have seen them as early as 1694, but he did not realize wha t
they were53. In 1808, Rudolphi discovered them in the intestine of a young dog
and regarded them as the immature heads of T. cucumerina (= cateniformis =
Dipylidium caninum) formed by spontaneous generation from the intestina l
villi101. They were seen again in 1850 by van Beneden who, thinking that they
were a new species, described them in 1852 as T. nana 15.
Von Siebold's experiments were soon repeated and his results confirmed by
Küchenmeister (1853), Wagner (1854), van Beneden (1857), Leuckart an d
Nettleship (1866). These investigators showed that echinococci from sheep ,

pigs and cattle transformed in the intestines of dogs, but incubation periods of
up to 11 weeks were required. Not only did this discovery clarify much of the
life cycle of this parasite, but it paved the way for resolving the longstanding
battle over the identities of echinococci occurring in various hosts.
Initially, all attempts by Küchen meister, Zenker, Ercolani, Vella and Levison
to rear adult echinococcal tapeworms in the intestines of dogs from cyst s
obtained from humans failed. Success finally attended the efforts of Bernar d
Naunyn working in Berlin, Germany. On 17 February 1863, a large hepati c
cyst was punctured and the fluid drained. Shortly thereafter, the patient die d
from what was said to be typhus and autopsy confirmed the presence of a large
hepatic hydatid cyst with well-preserved daughter cysts; this was thought to be
E. altricipariens. Liquid containing a few hundred scolices was taken from this
cyst and administered to two dogs. One dog, which had received a smalle r
number of worms, was killed 28 days later, but no worms were found. Th e
other dog was killed five weeks after infection; mature, small tapeworm s
identical with the known Taenia echinococcus were found in the small intest-
ine. Thus, Naunyn not only confirmed that echinococcal cysts of human origin
undergo the same process of development as do hydatid cysts of animal origin,
but in demonstrating that the adult worms obtained from the two sources were
similar, also showed that there was but a single species, T. echinococcus 87. As
a result of his experiments, Naunyn reached the following conclusions:
since these taeniae in all known characteristics correspond to the Taenia echinoc-
occus von Siebold, they must be considered identical....this Taenia originates from the
scolices of the human Echinococcus....and....therefore, the Echinococcus of man is
the bladder-worm stage of T. echinococcus living in the intestine of the dog.87
These results were confirmed soon afterwards by Krabbe and Finsen working
in Iceland (1866) 64, then a few years later by JD Thomas in Adelaide, Australia
(1883) 114, all of whom used hydatid cysts obtained from humans.
EXPERIMENTAL GENERATION OF HYDATID CYSTS
To prove beyond all doubt that cystic worms were necessary steps in th e
development of taenia, it was also requisite to show their development fro m
tapeworm eggs. Such an experiment was first undertaken by Küchenmeiste r
with the parasite he knew as Coenurus cerebralis (= T. multiceps). First he
procured coenuri from a sheep then administered them to a dog in order t o
obtain mature proglottids of the tapeworm. These were in turn given to a
healthy sheep on 25 July 1853. Sixteen days later, the sheep became affected
with vertigo (dizziness and loss of balance - coenurosis causes "staggers" i n
sheep). When the animal was killed three days later, 15 small coenuri wer e
Echinococcosis 333
found on the surface and in the substance of the brain. The experiment was then
repeated in collaboration with Prof. Haubner of the Veterinary School i n
Dresden, and at the expense of the government of Saxony. Similar results were
obtained with Coenurus cerebralis, Cysticercus pisiformis , Cysticercus
tenuicollis and Cysticercus cellulosae by these investigators 68. At around the
same time, Leuckart was similarly able to produce Cysticercus fasciolaris in
the livers of mice after feeding these animals with eggs from T. crassicollis
from a cat.
Although a number of investigators in the middle 1850's were able to pro-
duce a variety of cysticerci and coenuri by feeding eggs to appropriate animals,
initial attempts to replicate these results with echinococci were unsatisfactory.
Haubner came close to success when he fed a pig with eggs of T. echinococcus
and found immense numbers of small vesicles resembling cystic worms in the
various organs on dissecting the animal a f ew months later. Unfortunately, none
of them were sufficiently developed for him to be sure that they wer e
echinococcal cysts 55. Success finally crowned the efforts of Leuckart in 1867 75.
He infected four suckling pigs with ova of T. echinococcus and was able to
make careful naked eye examinations of the resulting cysts at intervals afte r
infection. In one pig four weeks after feeding, he noted that the liver wa s
studded with small, tubercular-like nodules 0.35 mm in diameter. Thes e
nodules had a thick, homogenous capsule enclosing semisolid, granula r
contents, and were most frequent in the interlobular spaces and beneath th e
peritoneal coat of the liver. By eight weeks after infection, the parasites were
1 mm in diameter, showed slight lamination of the outer layer, possessed a
well-marked inner germinal layer and contained fluid which escaped from it on
puncture. After 19 weeks, the echinococcal cysts were 10-12 mm in diameter.
Subsequently, Krabbe and Finsen successfully infected sheep wit h
echinocococcal eggs, then Dévé and Dew r outinely infected many experimental
animals.
Two major series of investigations which did much to clarify the details of the
migration of larvae and the deve lopment of cysts were undertaken in Paris then
Rouen in France by Felix Dévé 34,35, and in Melbourne, Australia by Harol d
Dew38 . It was observed that eggs hatched in the stomach then the liberate d
larvae bored through the walls of that viscus or the small intestine and entered
the radicles of the portal vein and were carried to the liver. Indeed, De w
observed larvae in the portal vein within eight hours of feeding ova to pigs 37.
Some larvae penetrated the hepatic filter and passed to the lungs. A few of the
larvae managed to escape through this second net and enter the systemi c
circulation and lodged finally in the peripheral tissues. This sequence of events
fitted with the observed distribution of cysts in the human body. As early a s
1860, Davaine25 analysed reported cases and noted that in 373 cases, nearl y
50% of cysts were found in the liver, 10% in the lungs, and the rest wer e
scattered throughout the rest of the body. Subsequent surveys such as those of
Thomas114, Dévé34 and the "Australasian Hydatid Register "23 largely confirmed
this distribution, except that a larger proportion of cysts were found in the liver,
at the expense of non-pulmonary hydatids. T hese series also showed that a third
or more of patients had multiple cysts.
Goeze had observed a granular coat lining the interior of echinococcal cysts,
but the germinal membrane was first properly described by Goodsir 51. Many
observations were made on the mode of development of scolices and broo d
capsules from this membrane by Huxley (1852), Naunyn (1862), Rasmmussen
(1869) and Leuckart (1885), but considerable differences of opinion existe d
until the position was clarified by Dew who carried out a series of invest -
igations in the 1920's. He studied the microsc opical appearances of echinococci
in the livers of suckling pigs from as early as 12 hours after infection to as late
as 150 days37. Even at the earliest time period, an accumulation of mononuclear
cells was observed around the lar vae, together with lysis of adjacent liver cells;
this was followed by a marked infiltration of eosinophils into the follicle .
Vesiculation commenced in the second week and the follicle wall becam e
marked more clearly into layers by four weeks; the elastic laminated cuticular
membrane was developed and the nuclear material which comprised th e
germinal layers of the cyst was scattered irregularly on its inner surface. These
features were more apparent a t three months and the young cyst was beginning
to be surrounded by a fibrous adventitia derived from the host. Scolices an d
brood capsules did not appear until at least six months after infection. Th e
brood capsules began as small masses on the germinal layer which vacuolated
and formed scolices on their inner surfaces 36. Observations over many years in
both humans and experimental animals showed that the rate of growth of these
cysts was extremely variable, even within the same organ in the same subject.
They undoubtedly grew faster in soft tissues but usually took between two and
many years to grow large enough to produce symptoms.
Occasionally, daughter cysts were found within hydatid cysts, i.e. they were
replicas of the original cyst, bein g composed of an outer laminated layer and an
inner nuclear layer usually containing brood capsules and scolices. It wa s
Naunyn in 1862 who first showed that daughter cysts could arise directly from
the germinal membrane or from brood capsules 86. He also claimed that th e
daughter cysts could develop from sco lices, although this was denied by others.
That he was correct, was proven subsequently by Dévé. Dévé and Dew both
brought forward evidence that suggested that daughter cyst formation may be
stimulated by environmental influences including trauma, entry of chemical s
such as bile or urine into a cyst, and bacterial infection of cysts.
In the late eighteenth century, the great English surgeon and anatomist, John
Echinococcosis 335
Hunter, first formulated the idea that pelvic hydatid cysts were often secondary
to rupture of a visceral cyst and were not the result of multiple infections 59. This
view was criticized by Charcot and Davaine on theoretical grounds, but wa s
revived by Bright in 1861 20 and by Petain and Volkmann (1877), all of whom
warned surgeons about the risk of sowing hydatid elements by puncture of a
fertile cyst. In 1889, Lebedev an d Andreev showed that if young daughter cysts
were released into the peritoneal cavity, they continued to develop int o
fully-fledged hydatid cysts 74. In 1898, Alexinsky in Russia injected hydati d
"sand" (brood capsules and scolices) into the peritoneal cavity of seven rabbits
and eventually recovered echinococcal cysts from four of the animals 1. Dévé
then performed a series of experiments which put the matter beyond all doubt.
On 21 September 1900, he injected brood capsules and scolices from a sheep
hepatic cyst intraperitoneally into two rabbit s, remarking that echinococci never
form daughter cysts in sheep. On dissection 16 weeks later, nine or ten small
secondary echinococcal cysts were found in the peritoneal cavity of one rabbit
and in the injection track in the subcutaneous tissues and in the omentum of the
other rabbit26. Moreover, in the same series of experiments, Dévé demonstrated
that, contrary to previous opinion, hydatid cysts do not die when they ar e
punctured and the fluid drained 27. This still begged the question as to whether
it was brood capsules, scolices, or both that produced secondary cysts. In a later
study, Dévé produced hydatid cysts in many organs by intravenous o r
intra-arterial injection of living scolices alone 29,30. This experience led Dévé to
believe that daughter cysts probably arise most commonly from scolices. Dew
repeated Dévé's experiments and concluded that secondary cysts may b e
formed in all three ways, that is, from daugher cysts, brood capsules an d
individual scolices 38.
One of the most striking features of echinococcosis is the fact that infectio n
with large cysts may be completely asymptomatic. This has been known from
time immemorial. Hydatid cysts (althoug h their true nature was unknown) were
found frequently in slaughtered animals which had seemed perfectly health y
while alive. Similarly, echinococcal cysts were encountered from time to time
at post-mortem examination of humans who had not complained during life of
symptoms that could be ascribed to the parasite. At the same time, it wa s
appreciated gradually that most o f the clinical manifestations of echinococcosis
were due to pressure effects on adjacent tissues, and were thus dependent upon
the size, number and location of such cysts. The Icelandic physician, Joh n
Hjaltelin, summed this up when he wrote in 1869:
(The) symptoms are variable, according to the seat and the size of the parasite, and
consist mainly in the functio laesa of the affected organ. This rule holds good,
whether the hydatid exists in the brain, in the spine, in the organs of the chest, or in
one of the abdominal organs.58
Since these cysts grew slowly, it was noted that the natural history of echino-
coccosis tended to have a slowly progressive, chronic nature.
Perhaps the largest cyst or accumulation of cysts ever recorded was in th e
case of a farmer from near Otago, New Zealand. When he was a child of si x
years, he fell on a large stone and may well have caused a hydatid cyst to burst
into the peritoneal cavity, for he became acutely ill for several weeks, the n
gradually recovered. After two to three years, however, his abdomen gradually
became more prominent and continued to increase in size slowly over the next
30 years. By the age of 39 years, his abdomen measured 57" (145 cm) in girth,
and he weighed 17 stones (108 kg). His health deteriorated to the point where
surgical advice was sought. Peritoneal flu id was aspirated and shreds of hydatid
cyst were found. At operation in 1927, daughter cysts varying in size fro m
cherries to coconuts were evacuated filling bucket after bucket and at least 11
gallons (50 litres) were removed. Ten weeks later, the patient, now weighing
many stones less, returned to work as a shepherd. After three or four years, two
cysts were observed growing in the abdomen, but the patient refused operation
for another 13 years until 1943 when the two cysts, about the size of feta l
heads, were excised 11.
Perhaps the longest duration of infection on record is the case of an English
boy aged 11 years who had an abdominal hydatid cyst removed in St. Barthol-
omew's Hospital, London in 1882. Two years later, he migrated to the United
States of America. He was asymptomatic until 1926 when he developed recur-
rent bouts of abdominal and lumbar back pain. In 1939, at the age of 67, and
56 years after the initial operation, a mass was felt in the right upper quadrant
of his abdomen. At operation, two masses of cysts were found in the liver and
small, isolated lesions were scattered around the peritoneal cavity 72.
The majority of patients have complications arising from echinococcal cysts
of the liver44, while pulmonary echinococcosis has proved to be the secon d
most frequent problem 12. Many patients have been recorded, however, wh o
have suffered with echinococci in sites ranging from the heart (sudden death)
to the bones (fracture).
In addition to pressure effects, certain toxic reactions to echinococci began
to be recognized. Among the more doubtful ones was the claim of Dévé tha t
echinococcosis caused infantilism and that this condition could be improve d
when the cysts were removed. Much more substantial was the appreciatio n
around the turn of this century (at the same time that an understanding o f
allergic reactions began to dawn) that anaphylactic reactions, often fatal, may
occur in echinococcosis, particularly when echinococci ruptured either spont-
aneously or as a result of trauma such as diagnostic aspiration. Finally, major
suppurative complications as a result of secondary bacterial infection wer e
recognized.
Echinococcosis 337
The diagnosis of echinococcosis has always been difficult, since not only does
the parasite itself remain hidden in the tissues, but there are no embryoni c
forms which issue forth into either the bloodstream or the excretions and which
might be searched for. Rarely, a cyst has ruptured into the lungs or into th e
biliary or intestinal tracts and the tell-tale grape-like daughter cysts have been
coughed up or passed in the faeces. Similarly, a mass thought to be an abscess
has been lanced and daughter cysts have extruded through the wound. Suc h
observations have not always been reliable, however, for other lesions hav e
sometimes been mistaken for echinoc occi, such as parts of a hydatidiform mole
discharged from the uterus per vagina.
Following the discovery by Goeze in the late eighteenth century of the path-
ognomonic scolices and hooklets, it became possible to be certain of the diag-
nosis. Nevertheless, this discovery was of only of limited value, particularl y
when diagnostic aspiration of suspected echinococcal cysts fell out of favou r
because of the risk of causing secondary echinococcosis or precipitating a n
anaphylactic reaction. Some writers in the nineteenth century placed grea t
reliance upon the sign of "hyda tid thrill"; this fremitus or vibration is produced
by loosely-packed daughter cys ts shifting within the mother cyst. Nevertheless,
it is so rare as to be of little practical value 10.
For all of these reasons, attention turned during the early years of th e
twentieth century to developing immunological tests to assist in the diagnosis
of echinococcal infection. The first serological test was reported in 1906 b y
Ghedini who described a complement fixation antibody assay using hydati d
fluid from human cysts 48. This was followed in the next year by the demon -
stration by Fleig and Lisbonne of precipitating antibodies in the sera of persons
with hydatid disease46. Weinberg then compared the two procedures, favoured
the former, and did much to standardize the assay 120. The first skin test for
echinococcosis was described in 1911 by Casoni who used carbolized, filtered
antigens from the fluid in a sheep hydatid cyst; he noted the delaye d
inflammatory reaction which developed some hours after immunization 21. Ten
years later, Magath described an immediate reaction occurring within a fe w
minutes of application of antigen 80 then this was confirmed as a more reliable
diagnostic indicator by Dew and his colleagues 40. Much effort was made over
the next few decades to improve these diagnostic tests, but they have remained
only ancillary aids, for they are negative in up to a quarter of patients wit h
proven infection, and are falsely positive in another small proportion o f
patients. Nevertheless, they have proved useful adjuncts to diagnosis in th e
right clinical setting.
An alternative approach has to been to try to define the hydatid cyst b y
radiological techniques, although until recently, these methods have had little
chance of allowing the clinician to be completely confident about the nature of
a space-occupying lesion. Chest radiography revolutionized the ease wit h

which pulmonary echinococcal cysts could be discovered and observed. Con-
trast radiography was of limited value for hydatid cysts in the gastrointestinal
tract and near the biliary tree. Hydatid cysts of the liver were particularl y
difficult to characterize. Selective angiography began to offer possibilities i n
the diagnosis of liver echinococci, but has largely given way to non-invasiv e
techniques, first nuclear scanning of the liver, but now also ultrasound exam-
ination, whole body CT scanning and magnetic resonance imaging. Not only
can these latter two techniques be used in any anatomical region, but in some
cases, morphological delineation of daughter cysts may make the diagnosi s
almost certain, despite the absence of histological confirmation of the presence
of echinococcal tissue.
Despite many attempts to find anthelmintic drugs active against hydatid cysts,
surgery has remained the mainstay of the therapy of echinococcosis. The first
problem which all surgeons have had to face was to decide whether attempts
at surgical intervention were more likely to do harm or good. This wa s
particularly relevant prior to the advent of modern anaesthesia and surgica l
techniques. John Hunter is quoted as saying, concerning hydatids of the liver,
during one of his lectures on the principles of surgery: "When known to be a
bag containing fluid it may be opened, but I would not be in a hurry to d o
this"60. On the other hand, over a century later, another surgeon declared that
although it is well-known that cysts occasionally die and atrophy resulting in
"spontanteous cure", this happy outcome ought never be relied upon in place
of surgery113.
Throughout most of recorded history, surgery has consisted simply of punct-
ure and drainage of a cyst. The experience of Aretaeus at the beginning of the
Christian era8 has already been alluded to, and Bonetus in 1697 recorded the
case of a patient with a liver cyst which discharged more than 200 vesicle s
(daughter cysts) when it was opened 18. Another famous case from the sam e
century is that of the Earl of Shaftesbury who was treated by his persona l
physician, John Locke (cited in 88). Shaftesbury had a palpable abdomina l
tumour for 12 years before it caused him any inconvenience. In May 1668, he
experienced severe abdominal p ain and vomiting then suddenly a soft mass the
size of an ostrich's egg appeared in his abdominal wall. On 12 June it wa s
opened by cautery and a large quantity of purulent matter containing "man y
bags and skins" was discharge d. Some of the most eminent surgeons and phys-
icians in London were consulted and it was decided to keep the abscess open
for drainage by insertion of a silver tube. This operation became commo n
knowledge and Dryden penned the folllowing lines:
The working ferment of his active mind
Echinococcosis 339
in his weak body's cask confined

would burst the rotten vessel where tis bent
but that 'tis trapped to give the treason vent.
Shaftesbury's operation was successful for he survived another 15 years .
Others, however, were not so fortunate. Some patients died from what is now
recognized as an anaphylactic reaction precipitated by release of echinococcal
products into the tissues. Other patients developed recurrent hydatid cysts ,
either in the course of the needle track or in the peritoneal cavity. As has been
noted, there was considerable controversy among surgeons for many years as
to whether this was due to se eding of the hydatid material released at operation
or not. Some surgeons who were concerned about this possibility attempted to
kill parasitic tissue by injection of noxious agents after drainage. One of th e
earliest surgeons to do this was Dr Bobilli er of Dunkirk who in 1851 punctured
a large swelling near the umbilicus of a 36 year old sailor, evacuated a larg e
quantity of clear serum, then enuc leated a hydatid cyst of great size by grasping
a shred which had presented at the aperture site. He then resorted to dail y
injections of iodine for two months, with gradual resolution of the mass an d
recovery of the patient 17. Other substances used for their supposed parasiticidal
properties included alcohol and gall. The opposite viewpoint is exemplified by
Hutchinson (1864) who claimed that injection of these compounds increased
the risk to the patient, and that simple drainage was all that was required 61.
This latter course became unt enable when Dévé and others at the turn of this
century demonstrated experimentally in animals that secondary echinococcal
cysts could be induced. Furthermore, Dévé investigated potentia l
echinococcicides in rabbits and showed that injection of 1:100 solution o f
mercury perchloride or a 1:200 solution of formol for two and half minute s
destroyed the viability of germinal epithelium 28. This approach was taken u p
immediately by Quénu (1903) who injected hydatid cysts with 1% formali n
prior to drainage in three patients. He showed that not only did formalin no t
inhibit prompt and complete recovery, but that the contents of the cyst wer e
killed94.
By 1910, the standard procedure was to isolate the cyst by carefully packing
around it with pads, injection of formalin, aspiration of fluid contents ,
enucleation of the entire cyst wall (germinal epithelium and laminated mem -
brane) and swabbing of the adventitious layer with formalin 79. The subsequent
course was controversial. Possi ble methods of dealing with the evacuated cysts
included marsupialization (sewing of the adventitia to abdominal wall muscle
to allow external drainage), drainage into the peritoneal cavity, filling wit h
saline and sewing it up, or obliterating it with sutures. In his review in 1910,
MacLaurin believed that the first course of action was the safest, but surgeons
came eventually to treat each case on its merits in deciding which method t o
choose. As surgical techniques improved, it became possible sometimes t o
remove the cyst in its entirety, including the adventitial capsule 7. Even if an
apparently solitary hydatid cyst is removed, only time will tell whether ther e
will be a recurrence, either as a secondary cyst resulting from spillage a t

operation, or as the delayed appearance of a more slowly-growing cyst acquired
at the time of the original infection.
Although the success rates of operation have continued to increase over the
years, some cysts have remained inoperable. Cysts are sometimes placed i n
locations that make it too danger ous to intervene, or the cysts are so massive or
widespread as to militate against surgical assault. In these circumstances ,
therapy with drugs is the only potential alternative. No drug showed an y
promise until it was found in 1 975 that the benzimidazole compound, mebend-
azole, retarded the growth of E. granulosus in white mice and killed th e
germinal epithelium 56. This led to enthusiastic trials with this drug in humans
suffering from echinococcal infection. Although initial reports were encour -
aging, hope was dampened by subsequent experience 6, and mebendazole has
not proven to be the answer for the treatment of hydatid infections. Currently,
the related compound, albendazole, is under investigation.
The demonstration by von Siebold that dogs were the definitive host o f
E. granulosus and the experimental generation by Leuckart of echinoccoca l
cysts after feeding eggs to sheep clarified in a dramatic fashion ou r
understanding of the mode of transmission of hydatid infection. The next steps
were to define the incidence of infection in humans, the prevalence of infection
in various intermediate hosts, and the frequency of infection in dogs, and t o
analyse the factors influencing the transmission of the parasite.
It had long been appreciated that hy datid infection was more common among
people with particular occupations such as farmers and butchers and i n
members of their families. The reasons for this were now plain. When suc h
people killed domestic animals such as sheep and cattle, it was their common
practice to feed the offal (which often contained cysts) to farm and house dogs.
These became infected and the resultant adult worms produced multitudes of
eggs which were passed in the faeces. Although infection may be acquired by
children eating dirt or by the consumption of uncooked, contaminated fruit and
vegetables or by drinking polluted water, it was realized that the most potent
source of infection was the caressing of dogs, allowing them to lick the hands
and face, or to feed from common plates and dishes.
Just as the frequencies of hydatid infections in relation to occupation wer e
analysed, so the distribution of echinococcosis in different countries wa s
investigated. It became apparent by the middle of the ninteenth century tha t
echinococcosis in Iceland had reached e pidemic proportions. The Physician-in-
chief of the country, Dr Thorensen, considered that about one in seven of the
inhabitants were so infected, and one o f his successors, John Hjaltelin, believed
from his own experience of numerous autopsies, that echinococcal cysts could
Echinococcosis 341
be found in one or another of the internal organs of nearly every fifth adul t
body58. This remarkable prevalence was attributed to the intimate relationship
between the Icelanders and their sh eep, cattle and dogs. It was estimated at that
time that in Iceland there were 20 dogs per 100 inhabitants 64. For the same
reasons, high frequencies were noted in a number of other sheep-raisin g
countries including Australia, New Zealand, Argentina, Uruguay and nations
of North Africa and the Midd le East. Thus, a writer to the Melbourne Argus in
Australia observed on 10 May 1874 that:
Hydatid disease is endemic in this colony; and though not so constantly met with as
in Iceland, we may probably claim the doubtful honour of holding the second place
in the list of countries so affected....To meet with hydatids as a cause of deranged
health is now a matter of daily expectation with every medical practitioner.
The common occurrence of hydatid infection in humans was found to be co-
existent with a very high frequency of infection in certain stock animals. Thus,
in Iceland in 1863, Krabbe found echinococcal cysts in 12.5% of sheep 64.
Similarly, in a survey in Victoria, Australia in 1929, 16.5% of 11,257 sheep,
23.9% of 4922 cattle and 0.5% of 2497 pigs were found to be infected 45.
Despite the higher frequency of infection in cattle, sheep were of mor e
importance in the maintenance of the life cycle of the parasite since the cysts in
cattle were commonly simple, unilocular and sterile. Similarly, Dévé in 1923
found that in Tunisia, nearly all of the cattle, 20-60% of sheep and 30% o f
camels examined were infected, while infec tions were insignificant in goats and
pigs31.
Occurring pari passu with a high prevalence of infection in cattle and sheep,
was a high frequency of infection in dogs. For example, in Iceland in 1863 ,
28% of dogs were infected 64, while in New Zealand in 1937, about one third of
the estimated 120,000 rural dogs harboured adult E. granulosus 9. It was thus
clear that echinococcosis was a zoonosis with the cycle being maintaine d
between dogs and farm animals, particularly sheep, with human infectio n
occurring incidentally and playing no part in the continued transmission o f
infection.
While the sheep-dog cycle thus described is the most important epidemio -
logical scenario, a number of other life cycles which may be of local importance
have been discovered. These include transmission between kangaroos an d
dingoes in Australia (with the potential for infecting aborigines) and between
deer and wolves in Canada. On the basis of these different intermediate hos t
specificities and/or on morphological characteristics, E. granulosus has been
separated into a number of subspecies including E. granulosus granulosus , E.
g. borealis, E. g. canadensis and E. g. equinus. Although these subdivisions
may be somewhat controversial, all of these data have provided an ample base
on which to evolve effective methods of prevention and control.
Just two years after von Siebold's epochal discovery, Küchenmeister in hi s

textbook laid down one of the cardinal principles on which the control o f
echinococcosis is founded69. He argued that people who slaughtered domest-
icated animals should not be allowed to throw offal containing bladders (cystic
worms) to dogs as food. Further, water should not be drunk unboiled, no r
should raw fruit or vegetables be eaten where there was a chance that the y
could have been contaminated with eggs. These suggestions were not widely
taken up, however, perhaps because:
his sentiments were expressed in a tedious and diffuse style, so characteristic of his
writings, they did not, perhaps, receive the consideration to which they were
undoubtedly otherwise entitled.77
In 1862, an English physician, Arthur Leared, visited Iceland and drew the
attention of the country's doctors to the recent German discoveries on the life
cycle of echinococci. Since dogs were indispensable to the farmers, Leare d
conceived the idea of dealing with the problem by dosing simultaneously all of
the dogs in the country with an efficient a nthelmintic. He concluded that kamala
was the most efficient taeniacide available, and drew up a paper detailing his
proposal for submission to Dr Hjaltelin, the chief physician, who was also a
member of the Legislative Assembly. Leared's paper was translated int o
Icelandic by Hjaltelin and published in two newspapers, then Hjalteli n
undertook to have the plan enacted by parliament. In order to effect this ,
however, it was necessary to communicate with the College of Health i n
Copenhagen, Denmark (Iceland then being a territory of that country). Leared
forwarded his paper to Baron Eschricht, the head of the College. However, as
Leared has recorded:
The result was an amusingly intemperate letter, inveighing against foreign inter-
ference in the affairs of Denmark, and stating that he would himself undertake to send
a competent person to Iceland to investigate the subject. 73
In a footnote to the document, Leared indicated the effectiveness of kamala in
a dog of his own that he brought back to England from Iceland. Hjalteli n
believed that the plan was "both original and practical" 58 but it came to nought.
Eschricht's nominee, Dr. Krabbe was despatched from Denmark "for a very
short time, the greater part of which was spent in making some feeding exper-
iments on dogs" 58. All Krabbe could suggest as a preventive was to kill a great
number of the shepherds' dogs. This proposa l was placed before the Diet where
it was rejected as unsatisfactory. In 1890, however, a law was passe d
controlling dogs by taxation and ensuring their treatment with anthelmintics and
enforcing the burial of material potentially contaminated with echinococci. The
keeping of dogs within the boundaries of Reykjavik, the capital city (with a
quarter of the country's population), was forbidden, and an educational cam -
paign was conducted throughout the country explaining how the disease was
produced and how it might be averted. P erhaps the most important factor of all,
Echinococcosis 343
however, was a fortuitous change in farming practice; male lambs were killed
at a younger age (4-5 months), thus giving cysts insufficient time to reac h
maturity43. The consequences of all these measures were that by 1927, th e
number of dogs had fallen to one for every 15 people from the one per fou r
persons obtaining in 1890, and only 1 in 1500 of the human population ha d
hydatid infection 83.
Campaigns of increasing sophistication were mounted in a number of more
developed countries such as Australia and New Zealand. Educational pro -
grammes alone often had no great effect. Since the infection had no noticeably
detrimental effects on wool and mutton, farmers had no particular incentive to
keep their sheep clean of parasites. They objected especially to the extra labour
involved in boiling offal prior to feeding their dogs. One despairing Ne w
Zealander lamented that "It has been re ported to us that our leaflets are not only
left unread, but are sometimes condemned to ignoble use" 9.
The control of echinococcosis suffered from two major disadvantages com-
pared with campaigns against that other common wormy zoonosis, trichinosis.
In the latter case, epidemics of fatal infection so alarmed the populace that the
legislature was prodded into action. This was reinforced by the sever e
economic consequences of trichinous infe ction. In contrast, echinococcosis was
an infection of low-grade endemicity and did little to penetrate the nationa l
consciousness. Perhaps more importantly, infection of the viscera had n o
deleterious effects on the flesh for food purposes and so did not interfere with
the export of frozen meat which was a staple article of the sheep and cattl e
trade of many countries 3.
Ultimately, however, legislation was enacted in some countries embodying
the control of dogs, the compulsory intermittent administration of anthelmintics
(first arecoline, the active constituent of areca nut, and later of bunamidin e
hydrochloride), prohibition of feeding raw offa l to dogs, educational campaigns,
and the monitoring of the results of these efforts. In many places, thes e
programmes have been eminently successful, but in other countries lackin g
sufficient finanacial and technical resources, echinococcosis continues it s
ravages unchecked. Perhaps immunization of animals may eventually become
a practical proposition, but no-one has yet improved on the unsuccessfu l
attempts of Dévé in 1927 to immunize rabbits challenged with echinococci 32.
OTHER SPECIES OF ECHINOCOCCUS
E. MULTILOCULARIS
During the first half of the nineteenth century, a number of European pathol-
ogists, including Ruysch, Buhr and Luschka, described a peculiar and rar e
tumour of the liver which they called "alveolar colloid" or "colloid carcinoma".
In 1855, Rudolf Virchow recognized the characteristic hooklets of Echino-
coccus in such a tumour and showed that the lesion was not a malignant pro-
liferation but was helminthic in nature. Believing that it was a variation of the
larval form of the common Taenia echinococcus (as E. granulosus was then
known), Virchow termed the lesion "ulcerative multilocular hydatid" 117. He
suggested that growth took place exogenously (instead of endogenously within
a cyst wall) in the lymphatic spaces, the size and shape of which determined the
nature of the growth.
Initially, helminthologists followed Virchow's line that there was only on e
adult echinococcal parasite. It was then realized, however, that this form o f
hydatid infection was restricted in dis tribution to Germany, Switzerland, Russia
and adjacent regions. In 1875, Morin 85 first propounded the view that ther e
were two distinct species, one causing the usual hydatid infection, and the other
producing the lesion described by Virchow. Considerable controversy was to
follow. Klemm in 1883 fed the Virchow- type hydatid to dogs and could discern
no significant differences between the resultant adult worms and th e
well-known T. echinococcus. Thus, he upheld Virchow's statement as to th e
unity of the two forms 63. On the other hand, Mangold in 1892 infected a suck-
ling pig with eggs of an adult echinococcal tapeworm derived previously from
a human alveolar hydatid. Autopsy four months later revealed two small alve-
olar hydatid cysts in the lungs of the pig and Mangold believed that thes e
results supported the dualist conception 82. Posselt in Austria repeated thi s
experiment in 1904 and obtained tapeworms from a dog fed with an alveolar
echinococcal cyst. These worms had minor variations in the size and number
of hooklets and the ova were arranged in a different manner. Posselt regarded
these differences as sufficient to justify the creation of a distinct species which
he named T. alveolaris 91. He also believed (erroneously) that this type o f
hydatid disease was frequent in oxen and its limited geographical distribution
was attributable to close association of humans with these animals. Further -
more, Posselt did not think that the dog was the normal definitive host, although
he did not know the exact means by which man was infected. Other authorities
took up these points to evolve the "double or dualist theory" that postulated the
existence of two species whose larvae had different pathological effects an d
whose adults may be differentiated morphologically. The major point in favour
of this theory was the peculiar geographical distribution of the parasite 92.
Nevertheless, some parasitologists, in particular Dévé, still held to th e
original single form or "unicyst theory" which held that there was one species
of parasite, E. granulosus, which under certain conditions gave rise to th e
alveolar form of hydatid cyst. The main argument in favour of this hypothesis
was that the alveolar hydatids were believed to be confined to humans. Th e
corollary to this was that since dogs do not have access to human livers, th e
variety should have become extinct if they were a separate species. In 1931 ,
Dew reported the first apparent case of alveolar hydatid infection in Australia;
the parasite showed characteristics of both an alveolar hydatid and the multi-
locular form of E. granulosus. He used this observation to support the notion
Echinococcosis 345
that the two lesions were morphological variants of the larval form of the same
adult parasite39. Dévé then obtained, from the Pathological Museum in Vienna,
portions of a tumour which Posselt in 1906 had described as an ordinar y
hydatid and an alveolar hydatid lying side by side in the heart of a human ,
separate and distinct and with no connection or intermediate morphologica l
stages. On re-examination, Dévé fo und all intermediate stages between the two
supposedly distinct forms and decided that the loculative change in the hydatid
must be ascribed to some special environ mental effect 33. A commentator in The
Lancet in 1933 felt that at last the matter had been probably settled and stated
that:
The reasonable conclusion from these facts is that there is one species o f
hydatid which occasionally grows in an abnormal fashion as the result o f
abnormal, presumably extrinsic stimuli; and that the health officer is no t
faced with the attempt to devise special preventive measures in the effort to
combat infection from unknown strobiles inhabiting an unidentified hos t
species.5
But the dualist theory was not yet laid to rest. In 1951, Rausch and Schiller
discovered alveolar hydatid in fections in the tundra vole ( Microtus oeconomus
inuitus) on St. Lawrence Island, Alaska 97. Alveolar echinococcosis was als o
found to be prevalent in the Eskimo population on the island and Rausc h
speculated that this form was probably identical with that causing alveola r
hydatid infections in Europe and in the USSR. Natural infections were the n
found in other mammals, including ground squirrels and shrews. In 1955 ,
Vogel showed by feeding experiments that the Alaskan and European hydatids
were identical118. Moreover, he found that foxes (Vulpes vulpes) in the Serbian
Alps were infected naturally with adult Echinococcus. He took the proglottids
of these worms and fed them to voles and rats, and alveolar echinococcosi s
resulted. Conversely, when a cyst from an infected field vole was fed to a dog,
adult worms were obtained which differed morphologically from E. granulosus
in a number of respects. Ironically, when Vogel re-examined some of Posselt's
material, held in the Innsbruck Pathological Institute, he found simila r
tapeworms in the small intestine of a dog that Posselt had fed with huma n
alveolar material in 1901. Vogel also determined that, unlike E. granulosus,
this parasite also developed in cats and foxes as well as in dogs. Further, h e
could find no major morpholo gical differences between Alaskan and European
collections, and concluded that they were geographical races of the one species.
Finally, Vogel pointed out 119 that on the basis of priority, the valid name for this
species was not E. alveolaris but E. multilocularis Leuckart 1863. This
designation stands today, although it is rather unfortunate as it sometimes lead
to confusion with the multilocular form of echinococcosis commonly seen i n
cattle and which has also been given the name "multilocularis" but is in fact a
form of E. granulosus.
Thus, it became generally agreed that there were two species of Echino-
coccus responsible for human hydatid diseases; E. granulosus matured in dogs

but not in foxes while ungulates were the usual intermediate hosts, whereas E.
multilocularis matured in cats and foxes as well as in dogs while microtin e
rodents were utilized as interme diate hosts. The problems of speciation may be
even more complex, however, with E. granulosus and E. multilocularis per-
haps being at each end of a hypothetical scale encompassing a number o f
"races", strains or subspecies that incorporate a number of features of eithe r
species111.
It was found that these parasites occurred most commonly in the liver ,
although primary lesions were disc overed occasionally in other sites. Patholog-
ical examination of these echinococci revealed that the cysts were often of only
microscopic size. The limits of the parasite were uncertain, there being no true
peripheral encysting layer; when laminated material was laid down, it was often
imperfect, irregular and lacking in rigidity. The cells of the germinal laye r
tended to spread out in long outrunners a long tissue planes into the surrounding
tissues, thus simulating a malignant neoplasm. Scolex formation wa s
uncommon and occurred only in a few tru e, small, spherical cysts. The adjacent
liver cells were necrotic, a chronic inflammatory reaction of lymphocytes ,
epithelioid cells, giant cells, and eosinophils usually developed as did a n
obliterative endarteritis, thus producing central caseation not unlike that seen
in tuberculosis. Again like an infiltrating neoplasm, the parasite tended t o
invade blood vessels and spread by metastasis to other organs, particularly the
lungs, lymph nodes and brain, where the parasites replicated and reproduced
the original lesion.
It was observed that many patients complained of vague abdominal discom-
fort succeeded by jaundice. Clinical examination revealed that the liver wa s
enlarged simulating a hepatoma or secondary malignant deposit. The diagnosis
was made by liver biopsy. Although a few patients have been recorded where
partial hepatectomy with complet e removal of the parasite has been successful,
most patients run a downhill course and die within several years. The quest for
an effective anthelmintic has so far not met with success.
E. VOGELI
The discovery in a Los Angeles zoo of an unusual proglottid in the faeces of a

bush dog (Speothos venaticus) which had been captured recently in Ecuador,
led ultimately to the description of a new species, E. vogeli, by Rausch and
Bernstein in 1972 95. The larval stage of this parasite was first identified in 1979
in two patients in Colombia by D'Alessandro and colleagues; they did this by
feeding parts of the cysts to dogs and recovering adult worms subsequently 24.
Since that time, more cases have been reported from other parts of Central and
South America. Subsequent studies have indicated that the natural cycle o f
infection is between the bush dog and the paca ( Cuniculus paca), but that
Echinococcosis 347
domestic dogs could also be infected and are probably the usual source o f
infection for humans96. In the paca (a rodent), the larva forms a polycysti c
hydatid with endogenous proliferation, but in humans, the parasite is invasive
and spreads by exogenous budding similar to E. multilocularis. Experience of
this infection is limited. Like ot her echinococcal infections, definitive diagnosis
is made by recovery of all or part of the parasite. Treatment is by surgica l
resection where possible, but longterm mebendazole therapy is being evaluated
currently. The prognosis is frequently poor, and prevention is difficult.
REFERENCES
1. ALEXINSKY JP. Ueber ein neues Operationsverfahren zur Entfernung von Echinococcus in
der Leber und anderen parenchymatösen Bauchorganen. Archiv für klinische Chirurgie 56:
819-826, 1898
2. ANONYMOUS. London Medical Society: Living hydatids. Lancet i: 719-720, 1833
3. ANONYMOUS. Hydatid disease and public health. British Medical Journal ii: 970, 1929
4. ANONYMOUS. Some problems of hydatid disease. British Medical Journal i: 146, 1931
5. ANONYMOUS. The alveolar hydatid. Lancet ii: 304, 1933
6. ANONYMOUS. Medical treatment for hydatiddisease? British Medical Journal ii: 563, 1979
7. ARCE J. Hydatid disease (hydatidosis). Pathology and treatment. Archives of Surgery 42:
1-17, 1941
8. ARETAEUS CAPPADOX. De causis et notis etc. In, The extant works of Aretaeus the
Cappadocian, translated by F. Adams, The Sydenham Society, London, pp 510, 1856
9. BARNETT L. Hydatid disease. Prevalence and prevention. New Zealand Medical Journal 36:
105-117, 1937
10. BARNETT L. Hydatid disease: errors in teaching and practice. British Medical Journal ii:
593-599, 1939
11. BARNETT L. Colossal hydatids associated with choloperitoneum. Medical Journal of
Australia ii: 511-514, 1944
12. BARRETT NR, THOMAS D. Pulmonary hydatid disease. British Journal of Tuberculosis
38: 39-95, 1944
13. BATSCH AJ. Naturgeschichte der Bandwurmgattung überhaupt und ihrer Arten insbesondere
nach den neueren Beobachtungen in einem systematischen Auszuge, Halle, pp 298, 1786
14. van BENEDEN PJ. Les vers cestoides ou acolytes, considérés sous le rapport de leur classif-
ication, de leur anatomie et de leur développement. Extracted from Mémoires de l'Académie
Royale de Belgique de Bruxelles, volume 25, pp 190, 1850. Abstracted in British and Foreign
Medico-Chirurgical Review 10: 322-335, 1852
Hebdomadaires des Séances de l'Académie des Sciences, tome 2, Paris, pp 376, 1858 (written
1852, couronné par l'Institut, 1853)
16. BLANCHARD R. Traité de zoologie médicale, J-B Baillière et fils, Paris, two volumes,
pp 1691, 1895-1890
17. BOBILLIER. Extraction of a large hydatid growth from the abdomen; iodine injections;
recovery. Lancet ii: 583, 1851 (Abstract)
18. BONETUS T. Sepulchretum sive anatomica practica ex cadaveribus morbo denatis, L Chonet,
Genevae, four volumes, pp 1706, 1697-1700
Aertze. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. Nebst einem Anhage
über Pseudo-Helminthem, Carl Schaumburg und Comp., Wien, pp 284, 1819
20. BRIGHT R. Clinical memoirs on abdominal tumours and intumescence, London, pp 55, 1861
21. CASONI T. La diagnosa biologica dell'echinococcosi umana mediante l'intradermoreazione.
Folia Clinica Chemica e Microscopica 4: 5-16, 1911
22. COBBOLD TS. Entozoa: an introduction to the study of helminthology with reference more
particularly to the internal parasites of man, Groombridge and Sons, London, pp 480, 1864
23. COLE G. The Australasian hydatidregistry. Health Bulletin No. 83/84, Melbourne, pp 2255-
2261, 1945. Abstracted in Tropical Diseases Bulletin 44: 602, 1947
24. D'ALESSANDRO A, RAUSCH RL, CUELLO C, ARISTIZABAL N. Echinococcus vogeli
in man, with a review on polycystic hydatid disease in Colombia and neighboring countries.
25. DAVAINE C. Traité des entozoaires et des maladies vermineuses de l'homme et des animaux
domestiques, J-B Baillière et fils, Paris, pp 838, 1860
26. DÉVÉ F. Des greffes échinococciques. Comptes Rendus Hebdomadaires des Séances et
27. DÉVÉ F. Du siège sous-séreux des greffes échinococciques péritonéales. Comptes Rendus
28. DÉVÉ F. De la greffe hydatique obtenue par l'inoculation de scolex. Bulletin et Mémoires de
la Société de Chirurgie de Paris 28: 905-910, 1902
29. DÉVÉ F. Echinococcose secondaire emboliquepériphérique. Comptes Rendus Hebdomadaires
30. DÉVÉ F. Secondary echinococcosis. Lancet ii: 835-838, 1919
31. DÉVÉ F. Enquête étiologique sur l'échinococcose en Tunisie. Archives de l'Institut Pasteur de
Tunis 12: 353-356, 1923
32. DÉVÉ F. Essai de vaccination anti-échinococcique par le sable hydatique tyndallisé. Comptes
Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 97: 1130-1131,
1927
33. DÉVÉ F. De l'existence de formes de transition entre l'échinococcosehydatique et l'échino-
coccose alvéolaire chez l'homme. Comptes Rendus Hebdomadaires des Séances et Mémoires
de la Société de Biologie 113: 223-224, 1933
34. DÉVÉ F. L'échinococcose secondaire, Massen et Co., Paris, pp 228, 1946
35. DÉVÉ F. L'échinococcose primitive (Maladie hydatique), Librairie de l'Académie de
36. DEW HR. Observations on the mode of development of brood capsules and scolices in the
encysted stage of Taenia echinococcus. Medical Journal of Australia ii: 381-384, 1922
37. DEW HR. The histogenesis of the hydatid parasite (Taenia echinococcus) in the pig. The
development of the Taenia echinococcus from embryo to hydatid cyst. Medical Journal of
Australia i: 101-110, 1925
38. DEW HR. Hydatid disease. Its pathology, diagnosis and treatment, Australasian Medical Pub-
lishing Company, Sydney, pp 419, 1928
39. DEW HR. Echinococcus alveolaris, with report of an Australian case. Australian and New
Zealand Journal of Surgery 1: 115-141, 1931
40. DEW HR, KELLAWAY CH, WILLIAMS FE. The intradermal reaction in hydatid disease
and its clinical value. Medical Journal of Australia i: 471-478, 1925
41. DIESING CM. Systema helminthum, Wilhelmum Braumüller, Vindobonae, 2 volumes, pp
1267, 1849-1851
43. DUNGAL N. Eradication of hydatid disease in Iceland. New Zealand MedicalJournal 56:
213-222, 1957
44. FAIRLEY KD. Hydatid disease of the liver. Medical Journal of Australia i: 177-186, 1924
45. FAIRLEY NH, WRIGHT-SMITH RJ. Hydatid infestation (Echinococcus granulosus) in
sheep, oxen and pigs, with special reference to daughter cyst formation. Journal of Pathology
and Bacteriology 32: 309-335, 1929
46. FLEIG C, LISBONNE M. Recherches sur un sérodiagnostic du kyste hydatique par al
méthode des precipitins. Comptes Rendus Hebdomadaires des Séances et Mémoires de al
Société de Biologie 62: 1198-1201, 1907
47. GALENUS CC. In, Medicorum graecorum opera quae extant, edited by KG Kühn (Greek text
with Latin translation), 20 volumes, Leipzig, 1821-1833
48. GHEDINI G. Ricerche sul siero di sangue di individuo affetto da cisti da echinococco e sul
Echinococcosis 349
liquido in essa contenuto. Gazzetta degli Ospedali et delle Cliniche 27: 1616-1617, 1906
PA Pape, Blankenburg, pp 471, 1782. Partly translated in 62.
50. GOEZE JAE. Versuch einer Naturgeschichte der Eingeweiderwürmer thierischer Körper,
PA Pape, Blankenberg, pp 471, 1782. Partly translated in 69.
51. GOODSIR. Cited in 16
52. HARTMANNUS PJ. Vermes vesiculares sive hydatoides in caprearum omentis et in pulmon-
ibus arterius furfuracea. Miscellanea Curiosa Sive Ephemeridum Medico-Physicarum
Germanicarum Academiae Naturae Curiosorum. Decuriae II. Annus Quarti Anni
MDCLXXXV (1685). Observatio LXXIII, Johannis Ernesti Adelbulneri, Nuremberg, pp 152-
157, 1705. Translated in 62.
53. HARTMANNUS PJ. De anatome canis hydropici. Miscellanea Curiosa Sive Ephemeridum
Medico-Physicarum Germanicarum Academiae Naturae Curiosorum. Decuriae II, Annus II,
Anni 1694, Leipzig and Frankfurt, p 299, 1695
54. HARTMANNUS PJ. De vesicularibus vermibus in mure. Miscellanea Curiosa Sive Ephemer-
idum Medico-Physicarum Germanicarum Academiae Naturae Curiosorum. Decuriae III,
Annus II, Anni 1694. Observatio CXCIII, Leipzig and Frankfurt, pp 304-305, 1695
55. HAUBNER. Cited in 69
56. HEATH DD, CHRISTIE MJ, CHEVIS RA. The lethal effect of mebendazole on secondary
Echinococcus granulosus, cysticerci of Taenia pisiformis and tetrathyridia of Mesocestoides
corti. Parasitology 70: 273-285, 1975
58. HJALTELIN J. The hydatid disease in Iceland: a few remarks on district-physician John
Finsen's contribution to our knowledge of the disease. Lancet ii: 178-180, 1869
59. HUNTER J. Medical and Surgical Transactions 1: 35, 1793. Cited in 34
60. HUNTER J. Cited in 4
61. HUTCHINSON J. The surgical treatment ofhydatid tumours in the abdomen. British Medical
Journal i: 197-201, 1864
62. KEAN BH, MOTT KE, RUSSELL AJ. Tropical medicine and parasitology. Classic investig-
ations, Cornell University Press, Ithaca, 2 volumes, pp 677, 1978
63. KLEMM H. Zur Kenntnis des alveolären Echinococcus. Münchener Dissertation, pp 1-27,
1883
64. KRABBE. Recherches helminthologiques en Danemark et en Islande, GEC Gad, Copenhagen,
pp 68, 1866
65. KÜCHENMEISTER F. Vorläufige Mittheilung(Über Cysticercus pisiformis der Kaninchen).
Zeitschrift für klinische Medicin 2: 240, 1851
66. KÜCHENMEISTER F. Einiges über den Übergang der Finnen in Taenien und über das
Digitalin. Zeitschrift für klinische Medicin 2: 295-299, 1851
67 KÜCHENMEISTER F. Ueber die Umwandlung der Finnen (Cysticerci) in Bandwuermer
(Taenien). Prager Vierteljahrsschrift für die Praktische Heilkunde 33: 106-158, 1852
68. KÜCHENMEISTER F. Experimente über die Entstehung der Cestoden Zweiter Stufe
zunachst des Coenurus cerebralis. Under Mitwirkung des Herrn Professor Haubner auf
Befehl und Kosten des hohen königliche sachsischen Staatsministerii des Innern. Zeitschrift
für klinische Medicin 4: 448-451, 1853
pflanzischen Parasiten des Menschen, Teubner, Leipzig, 2 volumes, pp 486, 1855. On animal
and vegetable parasites of the human body. A manual of their natural history, diagnosis and
treatment. Volume 1. Animal parasites belonging to the group Entozoa, translated by E
70. KÜCHENMEISTER F. Cited in 76
71. LAENNEC RT. Mémoire sur les vers vésiculaires, principalement ceux qui se trouvent dans
le corps humain, pp 176, 1804
72. LAWSON TC. Echinococcus cysts of the liver of fifty six years' duration. Journal of the
73. LEARED A. The cystic plague of Iceland. Lancet i: 337, 1867

74. LEBEDEV AI, ANDREEV NI. (Transplantation of Echinococcus cysts of man into rabbits).
Vrach, St. Petersburgh 10: 633-635, 1889. In Russian. Translated in Archiv für pathologische
Anatomie und Physiologie und für klinische Medicin (Virchow) 118: 552-556, 1889
75. LEUCKART R. Die menschlichen Parasiten unddie von ihnen herrührenden Krankheiten. Ein
hand- und Lehrbuch für Naturforscher und Aertze, CF Winter'sche Verlagshandlung, Leipzig,
volume 2, pp 882, 1867-1876. (pp 1-256, 1867)
76. LEUCKART R. Die Parasiten des Menschen und die von ihnen herrührenden Krankheiten.
Leipzig, volume 1, pp 1009, 1879-1886. The parasites of man and the diseases which proceed
from them. A textbook for students and practitioners, translated by WE Hoyle, YoungJ
Pentland, Edinburgh, pp 771, 1886
77. LEUCKART R. Cited in 22
78. LIVOIS E. Recherches sur les échinocoques chez l'homme et chez les animaux. Thèse de Paris,
p 123, 1843
79. MacLAURIN C. The clinical manifestations, diagnosis and treatment of hydatid disease of the
liver. British Medical Journal ii: 957-961, 1910
80. MAGATH TB. Echinococcus disease: etiology and laboratory aids to diagnosis. Medical
Clinics of North America 5: 549-571, 1921
82. MANGOLD C. Ueber den multiloculären Echinococcus und seine Taenie. Berliner klinische
Wochenschrift 29: 50-55, 1892
83. MATTHIASON S. Hydatid disease in Iceland. World's Health 8: 408-411, 1927
84. MORGAGNI JB. De sedibus et causus morborum per anatomen indagatis libri quinque etc.,
Remondini-ana, Venetiis, two volumes, 1760-1761
85. MORIN A. Deux cas de tumeur à échinocoques multiloculaires. Thèse de Berne, 1875
86. NAUNYN B. Entwickelung des Echinococcus. Archiv für Anatomie, Physiologie und wissen
schaftliche Medicin, pp 612-638, 1862
87. NAUNYN B. Ueber die zu Echinococcus hominis gehörige tänie. Archiv für Anatomie,
Physiologie und wissenschaftliche Medicin, pp 412-416, 1863. Translated in 62
88. OSLER W. An Alabaman student and other biographical essays, Oxford University Press,
Oxford, pp 334, 1908
89. PALLAS PS. Miscellanea zoologica: quibus novae imprimis atque obscurae animalium
species describuntur et observationibus iconibusque illustrantur, Petrum van Cleff, Hagae
Comitum, pp 219, 1766. Partly translated in 62
90. PECQUET. Extrait d'une lettre de M. P. a M. .... sur le sujet des vers qui se trouvent dans le
foie de quelques animaux. Journal des Sçavants 2: 382-385, 1688
91. POSSELT A. Zur Stellung des Alveolarechinokokkus. Münchener medizinische Wochen-
schrift 53: 537-541, 600-609, 1906
92. POSSELT A. Ueber die Natur des Echinococcus alveolaris und seine Beziehung zum
Echinococcus hidatidosis. Proceedings of the Third International Congress of Comparative
Pathology, Athens, Reports of the Section of Human Medicine, pp 27-55, 1936
93. POUCHET, VERRIER. Expériences sur les migrations des entozoaires. Comptes Rendus
Hebdomadaires des Séances de l'Académie des Sciences 54: 958-963, 1862. Translated ni
94. QUÉNU E. Kystes hydatiques du foie. Technique opératoire contre l'échinococcose second-
aire. Bulletin et Mémoires de la Société de Chirurgie de Paris 29: 719-729, 1903
95. RAUSCH R, BERNSTEIN JJ. Echinococcus vogeli sp. n. (Cestoda: Taeniidae) from the
bush dog, Speothos venaticus (Lund). Zeitschrift für Tropenmedizin und Parasitologie 23:
25-34, 1972
96. RAUSCH R, D'ALESSANDRO A, RAUSCH VR. Characteristics of the larvalEchino-
coccus vogeli Rausch and Bernstein, 1972 in the natural intermediate host, the paca,Cunic-
ulus paca L. (Rodentia: Dasyproctidae). American Journal of Tropical Medicine and
Hygiene 30: 1043-1052, 1981
97. RAUSCH R, SCHILLER EL. Hydatid disease (echinococcosis) in Alaska and the
Echinococcosis 351
importance of rodent intermediate hosts. Science 113: 57-58, 1951

98. REDI F. Osservazioni intorno agli animali viventi che si trovano negli animali viventi, Piero
Matini, Firenze, pp 253, 1684. Partly translated in 62
99. RUDOLPHI CA. Beobachtungen über die Eingeweidewürmer. Archiv für Zoologie und
Zootomie 2: 1-65, 1801
100. RUDOLPHI CA. Bemerkungen aus dem Gebiet der Naturgeschichte, Medicin und Thier-
arzneykunde, auf einer Reise durch einem Theil von Deutschland, Holland und Frankreich,
Realschulbuch, Berolini, two volumes, pp 518, 1804-1805
Wurtz, Paris, 2 volumes, pp 1370, 1808-1810
physiologische Pathologie, R Wagner (Editor), Braun Schweig 2; 650-676, 1844. Partly
translated in 69
103. von SIEBOLD CT. Ibidem. Partly translated in 76
104. von SIEBOLD CT. Lehrbuch der vergleichenden Anatomie, volume 1, Wirbellose Thiere,
Berlin, pp 679, 1848. Partly translated in 69
105. von SIEBOLD CT. Ueber den Generationswechser der Cestoden nebst einer Revision der
Gattung Tetrarhynchus. Zeitschrift für wissenschaftliche Zoologie 2: 198-230, 1850.
Abstracted in British and Foreign Medico-Chirurgical Review 10: 322-335, 1852
106. von SIEBOLD CT. Experiénce sur la transformation des vers vésiculaires ou cysticerques
in taenias. Annales des Sciences Naturelles, series 3, 17: 377-381, 1852
107. von SIEBOLD CT. Ueber die Verwandlung des Cysticercus pisiformis in Taenia serrata.
Zeitschrift für wissenschaftliche Zoologie 4: 400-408, 1853. Translated in Quarterly Journal
of Microscopical Science 2: 255-263, 1854
108. von SIEBOLD CT. Ueber die Verwandlung der Echinococcus-brut in Taenien. Zeitschrift
für wissenschaftliche Zoologie 4: 409-425, 1853. Partly translated in 62
109. von SIEBOLD CT. Über die Band- und Blasenwürmer nebst einer Einleitung über die
Entstehung der Eingeweidewürmer, W Engelmann, Leipzig, pp 115, 1854. On tape and
cystic worms with an introduction on the origin of intestinal worms, translated by T H Hux-
ley, pp 88; bound with volume 2 of F Küchenmeister's Manual of Parasites, The Sydenham
Society, London, 1857.
110. von SIEBOLD CT. Cited in 76
111. SMYTH JD. The biology of the hydatid organism. Advances in Parasitology 2: 169-219,
1964
112. STEENSTRUP JJ. Om Fortplantning og Udvikling gjennem vexlende Generations Raekker,
en saeregen Form for Opfostringen i de lavere Dyreklasser, CA Reitzel, Kjøbenhavn, pp 76,
1842. On the alternation of generations, or, the propogation and development of animals
through alternate generations: a peculiar form of fostering the young in the lower classes of
animals, translated by G Busk from the German translation of CH Lorenzen, Ray Society,
113. STEVENS WM. The spontaneous cure of hydatid cysts. British Medical Journal i: 1139-
1140, 1901
114. THOMAS JD. Hydatid disease with special reference to its prevalence in Australia, E Spiller,
Adelaide, pp 219, 1884
115. TYSON E. Journal Book of the Royal Society, London, volume 7, pp 88 and 90, 1687
116. TYSON E. Lumbricus hydropicus; or An essay to prove that hydatides often met with in
morbid animal bodies, are a species of Worms, or Imperfect Animals. Philosophical Trans-
actions of the Royal Society 17: 506-510, 1691
117. VIRCHOW R. Die multiloculäre ulceriende Echinokokkengeschwulst der Leber Verhand-
lungen. Sitzungsberichte der physikalisch-medicinischen Gesellschaft zu Würzburg 6: 84-95,
1856. (Sitzungen 10 March-12 May 1855)
118. VOGEL H. Über den Entwicklungszyklus die Artzugehörigkeit des europaïschen Alveolar-
echinococcus. Deutsche medizinische Wochenschrift 80: 931-932, 1955
119. VOGEL H. Über den Echinococcus multilocularis Süddeutschlands. I. Das Bandwurme-
stadium von Stämmen menschlischer und tierischer Herkunft. Zeitschrift für Tropenmedizin
und Parasitologie 8: 404-454, 1957
120. WEINBERG M. Valeur comparée de deux procédésde laboratoire (déviation du complement

et précipito-diagnostic) de l'échinococcose. Comptes Rendus Hebdomadaires des Séances et
121. WEPFER JJ. Ventriculi tumor verminosus cum folliculo. Miscellanea Curiosa Sive Ephem-
eridum Medico-Physicarum Academiae Imperator Leopold Naturae Curiosorum. Decuriae
II, Annus VII, Anni 1688, Observatio XVI, pp 26-35, 1689
122. ZEDER JGH. Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer von JAE Goeze
mit Zusätzen und Anmerkungen herausgegeben von Zeder, Siegfried Lebrecht Crusius,
Leipzig, pp 320, 1800
123. ZEDER JGH. Anleitung zur Naturgeschichte der Eingeweidewürmer, Bamberg, pp 432,
1803
Echinococcosis 353
Table 12.1. Landmarks in echinococcosis

___________________________________________________________________
c.400 BC Hippocrates alluded to lesions that were undoubtedly hydatid cysts in the
abdomen of humans
1766 Pallas hypothesized that human hydatid cysts arose from tapeworms
1782 Goeze described the scolices within hydatid cysts and indicated their
similarity with the heads of tapeworms
1851 Bobillier injected iodine into an hydatid cyst
1853 von Siebold discovered the adult tapeworms in the small intestine of dogs
after feeding them with larvae from echinococcal cysts obtained from
sheep
1855 Küchenmeister argued that offal of slaughtered domestic animals should
not be fed to dogs
1855 Virchow discovered characteristic echinococcal hooklets in so-called
"colloid carcinoma", now named E. multilocularis
1863 Naunyn recovered adult tapeworms from the small intestine of a dog fed
with the contents of an hydatid cyst obtained from a human
1867 Leuckart generated hydatid cysts in pigs by feeding them with eggs
obtained from adult tapeworms
1867 Leared reported that kamala eradicated tapeworms from the intestines of
dogs
1889 Lebedev and Andreev showed that daughter cysts released into the
peritoneal cavity of rabbits developed into fully-fledged cysts
1898 Alexinsky demonstrated that cysts developed from "hydatid sand" (brood
capsules + scolices) injected intraperitoneally in rabbits
1906 Ghedini described a complement fixation test for serodiagnosis
1911 Casoni described a skin test for immunodiagnosis
1913 Dévé produced cysts by injection of scolices alone
1922-5 Dew described in detail the development of larvae in the tissues
1975 Heath and colleagues showed that mebendazole had some parasiticidal
activity in experimental echinococcosis
___________________________________________________________________
Chapter 13
Taenia solium AND TAENIASIS SOLIUM AND

CYSTICERCOSIS
SYNOPSIS
Common name: tapeworm

Distribution: cosmopolitan but absent from Australia and some parts of Oceania
Life cycle: the adult tapeworms, usually 2-7 metres in length, live in the small intestine
with the head attached to the mucosa. Eggs and gravid proglottids are passed in the
faeces. When ingested by pigs, eggs hatch in the small intestine and each released
larva (oncosphere) penetrates the mucosa and passes via the bloodstream to the
tissues, especially the muscles, subcutaneous tissues and central nervous system,
where it vesiculates to form a bladder worm (Cysticercus cellulosae); these usually
reach 5-10 mm in size and contain an invaginated head. When ingested by a human,
the head evaginates in the small intestine and develops into an adult tapeworm which
produces eggs after approximately 3 months. Should humans ingest eggs, the larvae
hatch and pass to the tissues in the same manner as they do in pigs
Definitive host: humans
Intermediate host: pigs
Major clinical features:
1. intestinal taeniasis: abdominal discomfort, spontaneous passage of proglottids
2. cysticercosis: epilepsy, visual disturbances may occur
Diagnosis:
1. intestinal taeniasis: finding of eggs (any Taenia) or proglottids (T. solium) in the
faeces
2. cysticercosis: suggested by radiography and other imaging techniques, serology;
proven by excision biopsy
Treatment:
1. intestinal taeniasis: niclosamide, praziquantel
2. cysticercosis: praziquantel, surgery if necessary and possible
AWARENESS OF THE ADULT WORM AND DETERMINATION OF

ITS NATURE
Tapeworms have been known for generations. Individual proglottids o r

segments of worms are so obvious that pr ehistoric man must have noticed them
and wondered about their origin. They were alluded to by a number of writers
at the beginnings of recorded history. Tapeworms were prevalent in ancien t
Egypt and were probably mentioned in the Papyrus Ebers, dating around 1550
355
BC32,85; the parasites may, in fact, have been Taenia saginata since, according
to Herodotus, the ancient Egyptians did not eat pork. Tapeworms wer e
described by the Greeks including Hippocrates (460-375 BC) 51, Aristotle
(384-c.322 BC)8 and Threophrastus (c.372-286 BC) who called them eithe r
µ (HELMINS PLATEIA) meaning "flatworm" or
(TAINIA, TAENIA) meaning "band" or "ribbon" worm. Thus, Threophrastus
remarked:
This worm (flatworm) naturally infects certain races. Speaking generally, the
following are liable to it - the Egyptians, the Arabians, the Armenians....The Thracians
have it not, nor the Phrygians. Among the Hellenes, those Thebans who frequent
wrestling schools and the Boeotians generally are liable to it: but not the Athenians. 105
Romans such as Celsus (c.20 AD) 24, Pliny the Elder (23-79 AD) 20 and Galen
(129-c.200 AD)41 recognized tapeworms and named them "lumbricus latus".
"Lumbricus" was a group term meaning "worm" and "latus" meant "broad" or
"wide". Thus, Galen wrote concerning intestinal worms:
Again, worms also occasionally take possession of the bowel, and these are discharged
at one time from the lower bowels, at another more nastily from the mouth; and we
observe them sometimes to be flattened, which are the worst, at times to be rounded.41
Similarly, these worms were apparent to peoples in many other parts of th e
world, including India and China and mention is made of them in the Asia n
ancient literature 52.
Early writers had various ideas about the nat ure of these worms. Hippocrates,
Aristotle and Galen regarded the tapeworm as an animal, but Aetius 2 (c.550
AD) and Paulus Aegineta 1 (c.640 AD) thought that a tapeworm represented a
transformed strip of intestinal lining. In the latter part of the first milleniu m
after Christ, some Arab authors such as Serapion (c.800 AD) regarded th e
individual tapeworm proglottids as distinct worms 99. These were named
cucurbitini, not only because of their resembl ance to pumpkin seeds ( Cucurbita
species), but also because pumpkin seeds were one of the earliest remedies for
tapeworm infection. Many Arab writers did not consider the whole tapeworm
as a worm at all, but believed that it was a membrane formed by the intestine
to hold these cucurbitini, whereas others, including Ibn Sina (Avicenna ,
981-1037 AD) thought that cucurbitini (pumpkin seed worms) and taeni a
(gigantic worms) were completely different creatures 10.
The name taenia "solium" was apparently first used in relation to tapeworms
in a publication by Arnaldo Villanovani (Arnault de Villeneuve, c.1300 A D)
who wrote:
quidam dicunt quod isti cucurbitini generantur in ventre cujusdam maximi lumbrici
qui aliquando emittitur longior uno vel duobus brachiis, qui solium sive cingulum
dicitur.111
According to Nicholas Andry , this expression was already in verbal use before
Villanovani's time and reflected the erroneous belief that a person could only
be host to a single tapeworm. He wrote that the worm was "called solium from
its being the only one of its species in the body" 4. This view was disputed by
Taeniasis solium and Cysticercosis 357
Leuckart, however, on the grounds that the Latin word for "single" or "alone"
is "solus" whereas "solium" means "seat" or "throne" 66. Leuckart therefore
solicited the views of Dr Krehl, professor of oriental languages at th e
University of Leipzig, who reported: "It is impossible to derive the word solium
from the classic languages" 61. Krehl then went on to say that there were n o
appropriate words in either Arabic or Hebrew, but that: "I should like to offer
as an explanation the certainly somewhat Syriac word for tapeworm, namel y
Schuschl-e (properly 'chains')"61. Krehl postulated that schuschl-e had become
transformed into solium via Arabic then French or Spanish authors of th e
Middle Ages: "Among the Arabians it would be changed into susl or sosl, and
among the romance authors it would lose the second s" 61. This explanation
seems a bit far-fetched. Simpler ones could be invoked equally well; perhaps
the worm has been called "solium" because segments of the worm issue from
the "solium" (meaning "seat" or "ru mp") while sitting on the "solium" (meaning
the "throne", i.e. toilet)!
As will be discussed in the next two chapters, Taenia solium was confused
with Taenia saginata and Diphyllobothrium latum for two thousand years or
more. Although Platter was ab le to discern differences between the strobiles of
Taenia and Diphyllobothrium (see chapter 15), the key to the definitiv e
separation of the various tapeworm species, as well as to a proper under -
standing of the nature of these parasites, was the discovery that tapeworms had
a head. It fell to the Englishman, Edward Tyson, to make this fundamenta l
discovery in 1683107, then, in the following year, the Italian, Francesco Redi ,
independently published small-scale and rather crude illustrations of the heads
of dog and cat tapeworms 90.
Many earlier anatomists had noticed a difference in the size of each end of a
tapeworm segment. Some, including Spigelius104 and Amatus Lusitanius, did
not take the setting of the worm segmen t in relation to the intestine into account
and were misled into describing the more slender end as the tail. Others ,
despite their most diligent enquiries, could not come to any certain conclusion
as to the orientation of the worm within the body. Others again, such as Tulp 106
and Fehr37, even described and illustrated heads that were not heads at all .
Tyson, near the end of the seventeenth century, eloquently summed up th e
current state of knowledge:
The head of the Nile does not seem to be more plerplex't, and obscure to the Ancients,
than that of this Worm, which has created as many controversies among Anatomists
of late, as that has with the Geographers of old. 107
Tyson was fortunate in not only having a number of patients who suffered from
tapeworm infections, but in encountering such worms in a variety of animals.
It was the finding of tapeworms in the intestines of dissected dogs that allowed
him to orientate the worm in the bowel correctly and gave him access to th e
whole worm, thus permitting him to find the head:
And it was in a Dog I opened at our private meeting, at the Anatomical Theater of the
College of Physicians, where I observed this worm alive in the Ilion; not lying streight,
but in many places winding and doubling. Having taken notice how the Joynts were,
I traced it up, by carefully opening the intestine to the smallest Extream; where I
expected the head to be; and which did lye towards the Duodenum; whereas the
broader end was free, and did nothing adhere; whereas that small extream did do
firmly stick, and has fasten'd itself to the inward coat of the Intestine, that it was not
without some trouble, by gently raising it with my Nail, that I freed it from its
adhesion.107
Tyson put the worm in spirit of wine then took it home to examine it at leisure
with a microscope. Thereupon, he found that the head:
very plainly appeared....beset with two orders of Spikes, or Hooks, whereof the larger
did arise from the Center or Middle spreading themselves over the edges of the
circumference; the other which were issuing out about the middle from the Center
and were shorter....I could not upon my strictest Enquiry and with extraordinary
Glasses too, inform myself of any orifice here, which we may suppose to be the
mouth....This end was not perfectly flat, but a little globous and I could perceive....the
neck....For some little space here, I could not observe with the glasses any Joynts at
all, but after, very thick set, and small, and gradually increasing in length, as they
descended towards the Tail.107
Subsequently, Tyson found similar hea ds in other tapeworms and was left in no
doubt as to the correctness of his observations. He was troubled by his failure
to observe a mouth in the head of the worm, and solved this dilemm a
incorrectly by mistaking the genital aperture in each proglottid for a mouth .
Tyson was, however, on the right track in his assessment of the hooks:
Upon the whole, what seems most agreeable to me, and to be the true use of this part
we call the head is this; by means of these hooks, or Spikes it might fasten itself, and
so prevent, its too easy ejection out of the body. For it being so very long, and large
too, and its body in many places winding, and convoluted, the descent of the faeces
upon all occasions would be apt to carry it out with them; had it not this hold, which
is so fast, that rather than loosen itself, parts of the body are sooner broken off, which
we frequently see in the stool....hence it is that this Worm is of so difficult a cure. 107
Tyson also addressed two other questions. Firstly, it had been asserted by a
number of authorities, both ancient and moder n, that tapeworms were not living
creatures. This opinion seemed to Tyson to be wide of the mark, for he, as well
as as many other physicians, had "observed it to move, and therefore to be an
Animal and alive" 107. Secondly, other authors admitted a tapeworm to be alive,
but maintained that it was not a single worm but many worms linked together
and enveloped by a lining derived from the intestine. This sac was deemed not
to be animated itself but received its motion from the proglottids (cucurbitini)
enclosed within it. Thus, Gabucinus in 1547 wrote:
I think the Broad worm to be nothing else, as Hippocrates says, than the white
scourings of the Guts within which living creatures like Gourd-seed are bred....It
comes away very frequently in pieces.39
Tyson disputed this view, for while examining a tapeworm recovered from a
dissected dog, a couple of joints fell off intact, and yet there was no evidence
of any membrane attached to the remainder of the worm. Further, he wa s
unable to find such a structure in any tapeworm he examined, whether o f
human or animal origin.

The discovery of a head, together with the conclusion that a tapeworm was
not a sac containing many cucur bitini, raised more questions as to the nature of
the organism. Tyson himself was perplexed, and did not venture to give an y
definitive answer, observing instead that it had not been his design to raise a
new hypothesis, but to enquire into the truth of those of others, it being much
easier to spy others' faults than to avoid them oneself!
A few years later (1700), Nicholas Andry published his observations on the
anatomy of tapeworms 4. He was the first to illustrate the head of a huma n
tapeworm (which happened to be T. saginata). He did not follow Tyson's view
that the genital pores were mouths, but regarded them as pulmonary openings
through which the tapeworms took air: "the nipples must be looked upon as so
many lungs"4. He was also familiar with the uterus and its ramifications, bu t
mistook them for a tracheal system analogous to the tracheal system i n
silkworms described previously by Malpighi.
These errors were perpetuated by other authors and new ones were made .
Thus, van Doeveren (1764) 30, Rosenstein (1778) 93 and Linnaeus, like Tyson,
mistook the genital openings for mouths. Van Doeveren also considered that
tapeworms had no real head but a sort of mouth at one end, and thought that the
hooks on the scolex were teeth 30. The latter mistake had also been made some
years earlier (1697) by Malpighi 75. Malpighi also considered that the suckers
were eyes, as did Andry, although the latter author quoted Merry (1654-1722)
of the Académie des Sciences as regarding them as nasal openings. Bloc h
(1782), on the other hand, believed that these suckers were mouths; indeed, he
thought that this was a good example of anatomical adaptation to physiological
requirements, there being four mouths to enabl e sufficient food to be swallowed
to sustain the very long body of the tapeworms 17.
In contrast to the many staunch proponents of the theory of the spontaneous
generation of worms, Andry was a firm upholder of the view that worms must
develop from eggs. He believed that he had descried such structures:
We cut up half an Ell (an English ell is 113 cm and a Flemish ell was 68 cm) of it, and
examined it very narrowly....We only perceived all over it heaps of small Globular
Bodies resembling corns of millet, but very round....M. Bellestre....examined these
Globular Bodies, along with me, and is of Opinion, that these are Eggs....These Eggs
are so numerous in the worm, that if you touch them with the Point of a Pin, that
which sticks to the Pin, though no bigger than a grain of Dust, would appear to be an
incredible Pile of small eggs.4
Some later commentators have believed that Andry may have mistaken th e
round, calcareous bodies in proglottids for eggs.
The next significant advance in the understanding of tapeworms was made
by the German, Johann Goeze. He reported in 1782 that he was able t o
demonstrate that the marginal opening at the side of each proglottid which had
been mistaken for a mouth or for an airway was in fact connected with th e
reproductive system:
On the mature lower segments the marginal openings in part project so far that the
protrusion and the indented osculum can be seen with the naked eye. I inserted a
horse hair, and afterwards I pulled off the surface with fine instruments until I saw
with pleasure under the magnifying glass that the hair was in the transverse canal that
led to the ovary.43
Goeze observed eggs in the ovaries and drew rudimentary figures depictin g
them. He was particularly puzzled by the fact that he had never seen an y
tapeworm, whether of human or animal origin, which did not have eggs, and
wondered how fertilization took place. Although Goeze did not know th e
answer, he postulated a number of mechanisms, amongst which was the idea
that these worms may be hermaphroditic:
Are there, therefore, two sexes amongst them? Or is every tapeworm sufficient to
itself and does it fertilize its own eggs? How are the organs for this purpose
constituted and where are they?43
Over the next few decades, many of the details of the anatomy of tapeworms
were elucidated. The absence of a digestive sys tem was confirmed and the pres-
ence of a vascular system was defined. Goeze himself had noticed two smal l
openings on each side of every proglottid, each of which traversed the length
of the proglottid. It was then shown that these vessels were interconnected at
the head and descended throughout the length of the tapeworm, communicating
with each other from proglottid to proglottid at their lateral margins. In 1841,
Eschricht published the first detailed anatomy of a tapeworm ( D. latum) 34. In
1847, Emile Blanchard discovered the nervous system of tapeworms 16. Finally,
the anatomy of the sexual apparatus w as gradually pieced together by a number
of investigators, particularly the Germans, Mehlis, Platner and von Siebold. In
1835, von Siebold had observed that Taenia eggs contained an embryo wit h
small hooks100, then in the following year he had discovered Taenia
spermatozoa101. Leuckart provided a major analysis of the reproductive system
in 1862, then Sommer a few years later provided further details of thi s
system103.
There still remained the problem o f defining the nature of the organization or
individuality of a tapeworm. As mentioned earlier, many of the ancient Greek
and Roman investigators were of the opinion that a tapeworm originate d
through the union of separate proglottids. Some writers believed that th e
cucurbitini were held together by an enclosing membrane derived from intest-
inal mucus, others thought that they were glued together, while yet other s
believed that they held each other by mouth openings. This view that tape -
worms were formed by the union of previously free cucurbitini held sway until
the end of the 17th century when the heads of tapeworms were discovered .
Although this concept was now disposed of, a new question arose. Was a tape-
worm a simple animal with a head and jointed body, or was it a compoun d
animal? Most authors considered the tapeworm as a single animal that main-
tained its hold in the gut by means of the head and fed itself through it; th e
longitudinal canals that had been recognized as running through the entir e
length of the worm were thought to arise in the suckers and were regarde d
erroneously as an intestine. Thus, a tapeworm was viewed as a single animal
with numerous proglottids which were cast off at the posterior end. A n
alternative proposition, championed by P J van Beneden (1850), suggested that
the tapeworm was a compound animal of separate individuals. This concep t
grew out of Steenstrup's theory of the "Alternation of Generations" .
Accordingly, a tapeworm was believed to be a combination of two generations:
the scolex which was single and had arisen by asexual multiplication, and the
proglottids or sexual individuals which were usually present in large numbers.
In essence, the scolex was considered to be the "nurse" to the strobila .
According to van Beneden:
the head (scolex) remains like a true nurse, asexual....By continued budding there
arises from an originally isolated nurse a whole community of individuals - a colony
in which one has to distinguish not only animals at various stages of maturity, but also
one asexual and aberrant member, the so-called 'head'. 12
This view was attractive to Moquin-Tandon who wrote that the Taenia is a
perfect animal which is composed of a scolex and a number of proglottid s
which:
constitute special organisms placed end to end and enjoying a community of life, but
each of which at the same time is provided with all the elements essential to its
individuality.78
Just as there was confusion over t he nature of tapeworms, so have there been
differences of opinion over terminology. Felix Dujardin introduced the ter m
"proglottis" to describe the isolated joint or cucurbitinus. This word wa s
derived from the Greek word (GLOTTIS) meaning "tongue". Strictly
speaking, since the plural of this word is "proglottides", "proglottis" should be
used for a single joint and "proglottides" for more than one. These classica l
niceties have been corrupted in many textbooks, however. I have followed the
practice of the major text on medical parasitology 11 in using the terms
"proglottid" and "proglottids" to describe one or more joints, respectively. The
term "segment" is also vague, but is commonly used to indicate a number o f
proglottids joined together. Similar etymological difficulties confront the user
of the word "scolex". This term was introduced by van Beneden 12 to describe
the head of a tapeworm. It is derived from the Greek word (SKOLEX,
SCOLEX) for a worm. The use of "scolices" as the plural form of this word is
firmly entrenched in the literatu re, presumably by analogy with the Latin words
"index" and "indices". According to the Oxfor d English Dictionary, and as more
recently discussed by Arme 9, such usage is erroneous and the rules of Gree k
declension dictate that it should be "scoleces". Since it is hallowed by custom,
I have continued to use "scolices" in this book. Similar difficulties apply to the
term "strobila", also introduced by van Beneden, to indicate the connecte d
series of proglottids. This word could be derived either from the Greek word
(STROBILOS) meaning "anything twisted" or a "pine-cone" o r
from (STROBILE) meaning "plug of lint twisted into the shape of
a pine-cone" and which became "strobila" in modern Latin. Again, there ar e

problems with the plural form of this word. It should not be "strobilae" (which
would imply falsely a Latin origin). An Anglicized plural form of "strobilas "
could be used; alternatively, Arme has suggested that "strobila" could be used
for both the singular and plural forms of the word9. Perhaps even simpler would
be to Anglicize the word completely and use the terms strobile and strobiles for
the singular and plural forms of the parasite.
Finally, it needs to be said that the worm was given its modern zoologica l
nomen Taenia solium when Linnaeus placed it in the tenth edition of hi s
Systema Naturae 67.
DISCOVERY OF CYSTICERCI
The ancient Greeks were well-acquainted with measly pork although they did
not comprehend its nature. By the time of Aristophanes of Athens (c.448-386
BC), the condition was so well known that he could use it in his play, "Th e
Knights", with the slave Demosthenes suggesting that Cleon (one of the main
characters) should be treated in the same way that pigs were examined:
Let us force a stake into his mouth as do the cooks, and then, by pulling out his
tongue, we will examine boldly and at our ease his wide-opened mouth to see if he is
measled."
Similarly, Aristotle knew the chief localizations of cysts in pigs and compared
them to hailstones 8, while others remarked upon their resemblance to pearls.
Aristotle considered that infected pigs could not remain standing on their hind
legs, and that if the bristles, especially those of the back, were pulled out they
usually had drops of blood on their roots.
J Rumler in 1558 may have been the first person to describe cysticerci i n
humans when he found tumours on the surface of the dura mater in an epileptic
person96. Some authorities also cite Conrad Gesner as having described th e
parasite in 1558, but I have not been able to find a specific reference to such
a passage. Panarolus in 1652 found similar cysts in the corpus callosum of the
brain of an epileptic priest83. In 1656, the Englishman Thomas Wharton found
large numbers of cysts, which he took to be glands, in the adipose tissue and
muscles of a soldier 116. As discussed in chapter 12, none of these observers was
aware of the animal nature of these lesions, and recognition of this fac t
developed pari passu with similar observations made with other cysti c
parasitic worms.
In 1688, three years after he had described the motion of cysticerc i
(Cysticercus tenuicollis) in the omentum of a goat, Philip Hartmann also found
cysts in the heart of a pig. Within each cyst, and attached to its inner surface by
bands which he termed the "frustulum", Hartmann found a worm, although he
did not realize that he was looking at a head with its suckers and circlet o f
hooks:
In the heart of a pig I noticed that there were very many cysts....when the capsules
were cut open a peculiar skin of thin membrane could be removed. This covered both
a clear liquid and a white filament coiled like a white thread - itself a small worm. 48
Marcus Malpighi, at the end of the seventeenth century, discovered independ-
ently the animal nature of these cysticerci, and was the first person to speak of
the head of a worm within each cysticercus. He investigated the structure o f
cysts found in measly pork and saw within each vesicle, a whitish body which
looked like a spiral staircase. At its extremity, he recognized a small head and
wrote: "in apice atollitur capitulum" 75 meaning that at the apex of this body, a
small head was erected. Around this period, Otto Fabricius also recognized the
animal nature of measly pork. Nevertheless, these descriptions were eithe r
vague or remained unnoticed for many years.
In 1784, and apparently ignoran t of these earlier reports, Goeze re-examined
the cysts found in pork, recognized that they were helminthic in nature, an d
described clearly their morphology. In addition, he pointed out the similarities
between the head of the worm with in the cyst and that of an adult Taenia found
in the intestinal tract of humans 44. He included these wormy cysts among hi s
"Taenia viscerales hydatigenae". Nevertheless, Goeze still believed in th e
zoological independence of these parasites from tapeworms.
In 1786, Werner rediscovered these cysticerci in humans. While dissecting
the body of a soldier who had been in good health but who had drowne d
accidentally, he found two small cysts, each of which contained a worm, under
the pectoralis major muscle. These he named "Finna" since they resemble d
measly pork which was called "fi nnen" in Germany 115. Over the next few years,
a number of pathologists including Fischer, Treutler, Brera, Stenbech, Loschge
and Laennec found similar lesions in humans, mostly in the muscles an d
choroid plexus.
When Gmelin came to publish his revision of Linnaeus's Systema Naturae
in 1790, he accepted the verminous nature of these cysts, as well as thei r
resemblances to tapeworms, and called them Taenia cellulosae 42. In 1803,
Zeder created a new genus, Cysticercus, to house these parasites 123. This name
was derived from a combination of the Greek words (KUSTIS,
CYSTIS) and (KERKOS, CERCOS) meaning "bladder" and "tail" ,
respectively. A few years later, Rudolphi adopted this generic classification and
applied the specific name "cellulosae" of Gmelin, the parasite thus becoming
known as Cysticercus cellulosae 95. This name persisted until the genus wa s
abolished when cysticerci were shown to be larval stages of Taenia, but the
term "cysticercus cellulosae" continues to be used to describe the organisms of
this type found in pigs and humans.
ELUCIDATION OF THE MODE OF TRANSMISSION
EXPERIMENTAL GENERATION OF ADULT T. SOLIUM
The origins of intestinal tapeworms were a mystery for most of recorde d

history. Indeed, as late as the early part of the nineteenth century, som e
learned authorities still held that they were the products of spontaneou s
generation (see chapter 2). The origin of tapeworms was uppermost in the
mind of Edward Tyson in 1683 when he wrote the paper in which he des-
cribed the head of a tapeworm, for he began his discourse in the following
manner:
The consideration of Insects, and their manner of generation, as it is a subject of
curious speculation; so of late hath been much illustrated by the laborious researches
of many inquisitive persons: whose travels therin, tho' they have much advanced the
doctrine of univocal generation [i.e. sexual reproduction]; and bid very fair for the
exploding of that, too easily received, and common error, of their production for
putrefaction, yet one great difficulty still remains with me, how to account for several
of those that are bred in Animal bodies not such as we may supposed to be hatched
from eggs of like kind, that are received with the food or other ways, but of whom we
cannot meet with a parallel, or of the same Species, out of the body. 107
Tyson was completely mystified as to h ow tapeworms could have arrived in the
intestines by seeds introduced from the external environment for there were no
free-living worms which resembled these creatures and could have provide d
spawn:
And what I have laid down I think I have made out, how different this sort of Worm,
bred in animal bodys, is from all others hitherto observed out of it; from whence any
Seminal matter of it, it may be supposed to be propogated. 107
This seemed to him to give some credence to the idea of spontaneous gener-
ation and he concluded the title of his manuscript with: "And the whole urged
as a difficulty against the doctrine of univocal generation" 107. Tyson believed
that the genital pores were mouths and considered that the proglottids became
turgid after absorbing "chylous" intestinal contents through these openings .
When he placed proglottids in spirit of wine, they spewed out what he took to
be chylous juice into the receptacle. If he had examined this material under his
rudimentary microscope, he may well have found the eggs and this could have
given him a clue to the origin of the worms.
Following the discovery of tapeworm eggs by Andry at the beginning of the
eighteenth century, some commentators were induced to believe that the ov a
must be involved in the generation of adult worms. A natural experiment was
that reported by Peter Pallas in 1760. He introduced the small red eggs of the
dog tapeworm, T. cucumerina (= Dipylidium caninum), through a small wound
into the abdominal cavity of a pup. One month later, Pallas claimed to fin d
there small tapeworms, less than an inch long and with very short segments 82.
No-one was ever able to repeat this experiment and Küchenmeister in hi s
textbook of 1855 summed up the general view succinctly: "This is ver y

improbable, and, I think a complete mistake" 62. It is very difficult to known how
this error occurred, for Pallas was a very talented and sagacious observer .
Another obvious experiment, suggested by Pallas, Goeze and others, was t o
feed eggs to animals in order to see if adult worms developed in the intestines;
such experiments were entirely ne gative. This inability to produce adult worms
from eggs administered either orally or parenterally, appeared to so confound
the doctrine of "omne vivum ex ova" (all life comes from eggs), that bot h
Rudolphi (1810) and Bremser (1819) actually believed that tapeworm s
constituted the strongest argument known in favour of the doctrine o f
spontaneous generation (see chapter 2).
All this was to change with the demonstration that many cystic worms meta-
morphosed into adult worms in the intestines when ingested by suitable hosts
(see chapter 12). By 1854, the conversion of Cysticercus fasciolaris ,
C. pisiformis, C. tenuicollis, Coenurus cerebralis and Echinococcus
granulosus into their respective mature forms had already been prove n
experimentally. Studies with a number of cysticercus/tapeworm systems ha d
shown that following ingestion of cysticerci, each scolex attached itself to the
intestinal mucosa by hooks and/or suckers, assumed a flattened form, the n
produced, by budding, proglottids which became progressively more distinctly
jointed and sexually mature; these were then cast off at the posterior end. The
morphological similarities between the head of a mature T. solium from
humans and the scolex of C. cellulosae, first pointed out by Goeze in 1784 then
re-emphasized by Dujardin in 1845 31, suggested that a similar connection might
exist between these two forms. In view of the difficulties of experimentatio n
with humans, a number of German investigators including von Siebold i n
Breslau, (now Wroclaw, Poland) , May in Weishenstephen, and Küchenmeister
in Zittau, administered Cysticercus cellulosae to dogs. Both von Siebold and
May claimed to rear mature tapeworms (which the former called Taenia ser-
rata and the latter believed to be Taenia solium) in the intestines of thes e
animals. In his experiment, May had kept his cysticerci preserved in water at
9oC for ten days before feeding. Küchenmeister regarded these results a s
erroneous. He himself never succeeded in obtaining mature tapeworms afte r
feeding C. cellulosae to dogs. Secondly, he demonstrated that the incubation
of C. pisiformis (which metamorphoses easily in dog small bowel) in water for
ten days made them incapable of further development. Finally, Küchenmeister
thought that von Siebold's tapeworm was probably Taenia ex cysticerco
tenuicollo (i.e. Taenia hydatigena) 62.
At the beginning of 1853, however, Küchenmeister determined to examine
the effects of administering C. cellulosae to humans. He obtained permission
to administer bladder worms to a murderess under sentence of death, but was
unable to proceed with the experiment. A year of so later, an opportunit y
presented itself when a convict was scheduled to be executed several mile s
from Küchenmeister's home, although the short time at his disposal gav e
Küchenmeister scant hope for success. The investigation was undertaken i n
collaboration with two medical colleagues, Dr D and Dr Z, whose names h e
was not allowed to publish 63. Since C. cellulosae was not available at the time,
one of these colleagues gave fresh C. pisiformis from a rabbit and C. tenuicollis
from a pig intermingled with noodles in a soup cooled to blood temperature to
the convict, so that he received the bladder worms without knowing it. Three
and a half days before the convict's death, ho wever, Küchenmeister's wife found
some C. cellulosae in their evening meal, which consisted of warm roast pork
obtained from a nearby restaurant. Küchenmeister rushed around to th e
restaurant, and after much pleading, obtained one pound of pork from the pig,
which had been slaughtered 60 hours previously. Next morning, the priso n
doctor gave the convict some blood sausage, from which a few of the fatt y
pieces had been removed and a dozen bladder worms inserted, for breakfast.
Over the next two and a half da ys, the condemned man ingested a further 61 C.
cellulosae in sausage or soup. Forty eight hours after execution, the intestines
were examined by Küchenmeister and his medic al collaborators in the presence
of several professors. Not only did he find young larvae with hooklets, bu t
Küchenmeister found a young tapeworm:
I was successful in finding a small Taenia which was tightly attached with its
projected proboscis to a piece of duodenal mucosa which I had softened in water for
a few minutes.63
This was examined under the microscope and:
we saw a young Taenia with a projected proboscis to which four hooklets pointing
forward were loosely attached; these, when compared with other preparations of T.
solium, T. serrata vera, and Taenia cystic. tenuicolli, proved clearly to be hooklets
of the T. solium.63
Subsequently, they found another nine specimens, one of which had the com-
plete classical crown of T. solium with 22 hooklets in two rows. Küchenmeister
was left in no doubt that all these specimens harboured hooklets of the typ e
seen in T. solium and C. cellulosae and not in the other cysticerci. Most of the
worms were 3-4 mm long, but one was 6-8 mm in length and had an append-
age. No traces of the last feedings were found in the intestines, and Küchen -
meister believed that those cy sticerci were probably already dead at the time of
administration. In reviewing his r esults, he summarized them by saying that the
experiment had established:
(1) that the C. cellulosae is the scolex of the T. solium hominis
(2) that the mode of infection with T. solium is exactly the same as with all others
originating from bladder worms and probably like that of most of the Taeniae
(3) that we, therefore, infect ourselves with T. solium since cysticercus is transmitted
by those foods which we eat raw.63
Küchenmeister recognized, however, that th e experiment needed to be repeated
with a longer time being allowed for comp lete development of adult tapeworms
to occur.
In an attempt to head off any adverse criticis m of the ethics of the experiment,
he concluded his paper by pleading:

that the surely harmless experiment of bladder-worm feeding be allowed to be
repeated on criminals under probable death sentence; so that the whole developmental
cycle of T. solium could be observed....In the case of the subsequent pardon of a
convict, the tapeworms can be easily expelled; this will calm anxious souls and serve
science at the same time.63
Nevertheless, criticism followed inevitably. The Lancet merely abstracted
Küchenmeister's paper including his final point, and made no comment for or
against the investigation, but the anonymous reviewer of his textbook in th e
British and Foreign Medico-Chirurgical Review was scathing in his
comments:
What does our English reader think of the moral side of this experiment? The
reviewer is aware that much may be said of using these and similar opportunities for
the promotion of science. But he protests against a living fellow-creature being
regarded in the light of a mere subject of experiments of this kind, even though he be
a murderer whose hours are numbered. And he ventures to think that few would
controvert the conclusion of one of the most eminent physiologists of the day, who
indignantly alluded to this experiment at being 'debasing to our common nature'. 5
In the same year (1855) that Küchenmeister reported these observations ,
Aloys Humbert produced a patent infection in himself. In the middle o f
December 1854, he swallowed 13 C. cellulosae. During the first few days of
March, he began to pass segments of T. solium; however, notification of this
experience was not published until 1856 when it was mentioned by Bertolus
in his thesis54. In 1856, Rudolf Leuckart confirmed these observations. He gave
four cysticerci to a 30 year old man who, after two and a half months, began to
pass proglottids in his faeces; one month later, he was treated with kousso and
two T. solium were expelled, although one was without a head 65. Leuckart
repeated the experiment twice more that year, but on both occasions failed to
produce a patent infection. In 1859, Hollenbach also infected himself with C.
cellulosae; five months later, he passed a segment of Taenia five feet long, but
lacking in a head 53.
In late 1859, Küchenmeister had the opportunity to repeat his origina l
experiment, but on this occasion, he was able to infect the subject muc h
earlier64. In this instance, Küchenmeister collaborated with Dr. Liebenhaar. The
prisoner was induced to swallow C. cellulosae on 24 November 1859 an d
again on 18 January 1860, totalling 40 bladder worms in all. He was decap -
itated on 31 March 1860 and , at autopsy, half of the swallowed cysticerci were
found to have developed into T. solium, eleven of them possessing sexuall y
mature proglottids and the largest reaching five feet in length. Küchenmeister
believed that the sheer numbe r of tapeworms produced ought to convince even
the most sceptical that they were derived from the cysticerci that had bee n
ingested.
Again, the morality of the experiment was questioned. The British Medical
Journal, after recounting these findings and Küchenmeister's assertion that the
prisoner could have been treated if pardoned, went on to compare this method
of experiment with the ancient way of thinking of the Rationalists, a s

enunciated by Celsus, who thought that criminals might fairly be made use of
for the purpose of extending medica l knowledge. The anonymous commentator
then went on to cloud irrelevantly and emotively the specific issue in question
by referring to:
certain rather go-a-head proceedings in this way done by our Yankee medical brethren
and recorded in Dr. Brown-Séquard's Journal. These gentlemen calmly investigated
the movements of a palpitating human heart rapidly ripped from, the chest of a
criminal, who after execution was cut down with a pulse still beating - we suppose we
may say alive - for the satisfaction, it would appear, of the curiosity of the doctors. 6
and then went on to quote Wordsworth:
Physician art thou, thing of eyes,
Philosopher, a prying knave,
A man who'd peep and botanise
Upon his mother's grave"
These criticisms did not harm Küchenmei ster's ultimate reputation, for he came
to be acclaimed as one of the most eminent parasitologists of his day, and the
person who, above all others, established expe rimental scientific methods in the
study of helminth infections.
Similar results were obtained y et again when Heller gave 22 C. cellulosae to
a patient suffering from phthisis. The person died 18 days later and autops y
revealed twelve heads of T. solium, all small and without any segmentation vis-
ible50. Attempts were then made to infect rabbits, cats, dogs, pigs, sheep and
cynomolgous monkeys with this parasite, but all were in vain, and it becam e
accepted generally that humans were the sole definitive host of T. solium.
EXPERIMENTAL PRODUCTION OF CYSTICERCUS CELLULOSAE
A complete understanding of the life cycle of T. solium required not only that
mature tapeworms be produced in humans after ingestion of C. cellulosae in
measly pork, but that these cy sts should also be generated in pigs following the
consumption of T. solium eggs obtained from proglottids passed by infecte d
humans. This latter course was pursued contemporaneously with the former .
It will be remembered that from the time of Pallas, various experimenters had
fed eggs to animals, but they had sought adult worms in the intestines rather
than cysticerci in the tissues. The first person to demonstrate the generation of
C. cellulosae was the Belgian, P J van Beneden. In 1853, he gave T. solium
eggs to a pig, then when it was slaughtered at the abattoirs four and a hal f
months later, found a large number of C. cellulosae in the muscles. Van
Beneden controlled the investigation by keeping another pig under the sam e
conditions, except that it was not given any eggs; it had no cysticerci a t
autopsy13.
Similar results were then reported by Prof. Haubner in collaboration wit h
Küchenmeister49. In view of the economic importance of the subject, Küchen-
meister and Haubner had been commissioned by the Royal Saxon Ministry of
State to investigate the metamorphosis of cystic worms. Three pigs were given
T. solium proglottids on 7, 24 and 26 J une and on 2 and 13 July 1855. The first
animal was killed on 26 July and small cysticerci with incompletely developed
heads were found. The second pig was slaughtered on 9 August and a thousand
cysticerci were disseminated in the viscera. The third hog, sacrificed on 2 3
August, was massively infected; Haubner and Küchenmeister counted 133 C.
cellulosae in 4.5 drachms of meat which was the equivalent of 80,00 0
cysticerci per stone (approximately 6.4 kg) of pork. In a similar series o f
experiments, they failed to generate C. cellulosae in dogs and sheep fed with
T. solium proglottids.
These observations were confirmed in the following year (1856) by Leuckart
who infected successfully a number of pigs and observed them for up to si x
months after infection 65. Similar experiences were then reported by Mosle r
(1865) and Gerlach (1870).
Occasionally, humans, like the pig, were found to be infected with C. cell-
ulosae although this represented a dead end for the parasite, in civilize d
communities, at least. The obvious conclusion (which, naturally, has neve r
been put to the test), was that such infections in humans were acquired b y
ingestion of T. solium eggs. The ova could either be ingested in contaminated
food or water, or could be transferred directly from the anus to the mouth via
fingers. An alternative possibility, suggested by Leuckart 66, was that reversed
peristalsis might sometimes occur with retrograde movement in the intestines
of mature proglottids which in turn then ruptured to release infective eggs.
Attention then turned to study of the proce sses by which migration and devel-
opment of larvae occurred in animal intermediate hosts. Early workers found
that when eggs were swallowed by a pig, they hatched and the released larvae,
furnished with hooks, bored their way through the intestinal mucosa an d
migrated to the tissues where they lodged and developed into cysticerci ,
producing a scolex by a process which was ter med "asexual gemmation". These
events were then described in great detail by Yoshino 119,120.
TAENIASIS SOLIUM
The sign of tapeworm infection, par excellence, has always been the passage
of proglottids through the anus. Sometimes, huge segments of worm wer e
passed, particularly when anthelmintics were taken, thus engendering consid-
erable terror in the patient. Tyson records the instance of a 20 year old patient
of his, who, upon the use of an emulsion of cold seeds, dragged a tapewor m
from himself "not without some frightful Apprehensions that the Guts and all
were coming out" 107. This parasite measured 24 feet in length and numbere d
507 proglottids. The total length of worm passed could sometimes b e

extraordinary. Borrichius is said to have seen a patient who voided more than
800 feet of tapeworm during the co urse of a year, although whether this was all
from one worm is questionable 18. In more recent times, a healthy woman who
was treated with extract of male fern and castor oil passed four portions o f
tapeworm (species not identified) into a bucket. When laid out and measured,
the total length attained 79'4" (24.2 metres) and in places the proglottids had
a breadth of 1" (2.5 cm). No heads were recovered, but as far as the autho r
could ascertain, all the portions belonged to the same strobile 70.
While many patients are infected wi th only one T. solium, multiple infections
are possible, perhaps the record being the patient who was reported as having
25 mature tapeworms 86.
In order to determine how many proglottids are produced and passed by a
tapeworm, Yoshino (1934) infected hims elf with 3 C. cellulosae then observed
himself for the next two years. Either two or three tapeworms grew and th e
number of gravid proglottids passed were 334 in the first month, 174 in th e
sixth and 126 in the twelfth month of patent infection; this approximates to 1-5
proglottids per worm per day 121,122.
Goeze (1782) quotes the unusual case of a patient of his friend, Dr. Wagler;
he was a young scholar who felt little distress except when he heard music:
Then he had to run away or of fear had to ask that one would stop the music.
Otherwise he was healthy and had great strength. I have seen anxiety and unpleasant
sensation from music in several cases of taeniasis.112
Wagler's observation that the young scholar was otherwise healthy was the
usual finding. The majority of patients were asymptomatic or had vague ,
indefinite abdominal discomfort. Nevertheless, a multitude of symptoms were
ascribed to tapeworm infection, many of them being considered "sympathetic
phenomena" and so-called "proof" of the aetiological relationship bein g
provided by their cessation after removal of the offending parasite. These were
anecdotal accounts, of course, and were not subjected to rigorous, scientifi c
analysis. Thus, according to Davaine (1860), tapeworms might cause general
indisposition, anxiousness, giddiness, noises in the ears, impaired vision, a n
itchy nose or anus, salivation, palpitations, anorexia, indigestion, colic ,
syncope, weariness, emaciation, an insatiable appetite and convulsions 29. To
these might be added chorea 40, insanity117, and diabetes 57. Küchenmeister was
more circumspect than this, noting:
All these symptoms are very deceptive if we should ascribe them to the presence of
the tapeworm. Very often, they do not disappear when the worm is expelled, a proof
that the latter is not their first cause. The stronger an individual is, the less does he
complain of his symptoms when he suffers from tapeworm. 62
Time has supported Küchenmeister's cautions.
The life span of T. solium is uncertain, but these tapeworms probably live for
many years. The fact that humans usually suffer infection with only a singl e
tapeworm was often interpreted as evidence of immunity to reinfection, but is
was realized that this could also indicate non-immunological resistance which
was dependent upon the continuing presen ce of an adult tapeworm 28. Definitive
studies in which the recurrence of infection in a treated subpopulation in a n
endemic area is assessed are still awaited.
CYSTICERCOSIS
Cysticercosis in humans was recognized much less frequently than was taen-
iasis solium. Occasionally the two conditions occurred together in the sam e
patient. Thus, von Graefe (1866) found intestinal tapeworms in five of 8 0
patients with ocular cysticercosis 46. In many cases, patients were asymptomatic,
as instanced by the incidental discoveries by Wharton and Werner of th e
organisms in previously healthy individuals. Some persons had smaller o r
larger numbers of subcutaneous nodules. One of the more dramatic examples
of a patient with disseminated cysticercosis was described thus:
He was pale and the face appeared puffy, but two outstanding features were the chain
of nodules visible on the forehead and the greatly enlarged, apparently well developed
and powerful muscles....The nodules....are found in the subcutaneous tissues of the
forehead, scalp, beneath the left eye, in the neck and in the tissues of the cheek. They
occur singly or in groups of two or three of varying size. When single, they are ovoid,
flattened ovoid, or spherical according to the amount of pressure exerted by the
surrounding tissues. In size, they range downwards from half an inch in longest
diameter. They are found in the aponeuroses of the abdomen, elbow-joints, thighs and
legs. In the muscles, they can be felt singly, in groups and in chains. One cyst is
present in the left eye. . They have never been painful. They are movable and not at
all adherent to the skin. Nearly all the muscles are enlarged, especially those of the
shoulder girdle, and on contraction the muscles present a nodular appearance. He
gives the appearance of being a powerful man....but the muscle power is in fact very
feeble. Enlargement is due to the presence of the cysticerci and to the concomitant
myositis.88
Such infections frequently left no serious musculo-skeletal sequelae, however,
as evidenced by the man with hundreds of calcified cysts in his muscles, who
after three days in hospital following an epileptic fit, attended the Scottis h
Highland Games and took second place in the long jump 35.
By the time Cobbold wrote his textbook on helminthology in 1864, it wa s
well-recognized that cerebral cysticer cosis might cause convulsions and mental
disturbances as well as various cranial nerve and long tract signs 26. In 1934,
interest in this subject was re-awakened when a large number of Britis h
soldiers returning from various outposts of Empire with "idiopathic epilepsy"
were found to be suffering from cerebral cysticercosis 71,72. An unexpected
feature of this study was that parasite s were often present for many years before
the onset of cerebral symptoms; these appeared to be associated with death of
the worms. In explanation of this, MacArthur (1935) hypothesized that th e
biological objective of cysticerci while in the tissues of the intermediate host is
to remain quiescent and he likened them to: "thieves who have entered some
premises where they stay hidden so long as concealment is helpful to thei r
purpose"73 and suggested that death of the parasite may have liberated toxins
which increased the irritation which they caused.

The recognition that humans might develop c ysticercosis by ingestion of eggs
after contamination of their fingers with faeces or by peri-anal scratching lent
urgency to the diagnosis and effective treatment of T. solium infections. At the
same time, it became obvious that the outlook for patients with cysticercosi s
was dependent upon both the number of cysticerc i and their location in the host.
Whereas parasites in most tissues were usually of minor significance and were
generally limited to less than one centimetre in size by the host inflammatory
and fibrotic reaction, those situated in the ventricles of the brain o r
subarachnoid spaces could grow much larger and endanger life. Similarly, a
cysticercus in a strategic organ such as the eye could seriously impair vision.
Whereas little could be done for such patients in the past, advances i n
ophthalmology and neurosurgery and the recent advent of effective anthelm -
intics have improved the outlook considerably for many of these persons.
The diagnosis of tapeworm infection was obvious when a patient passed pro-
glottids, but identification of the species of worm was not possible from these
specimens for many years. After Küchenmeister described in 1852 the appear-
ances of the reproductive organs, parti cularly the number of lateral branches on
the gravid uterus in T. solium and T. saginata (which he called T. medio-
canellata; see chapter 14), identification of the proglottids became possible on
a routine basis. Alternatively, a specific diagnosis could also be made afte r
treatment of a patient and recovery of the tapeworm head, but this was ofte n
less feasible.
At about the same period, it was also found that a diagnosis of tapeworm inf-
ection could be made by demonstration of taeniid eggs in the faeces. The first
person to describe such eggs (which he took to be indicative of a new species
of tapeworm) in faeces was Ransom in 1856 89. He was followed soon
afterwards by Davaine who, in his textbook, emphasized the value of faeca l
examination29. Despite occasional claims to the contrary, subsequent exper -
ience indicated that this technique did not permit differentiation of T. solium
and T. saginata infections. With the introduction of the perianal swab tech -
nique for the diagnosis of enterobiasis (see chapter 17), it was found that this
method also enhanced the ability to diagnose tapeworm infections, particularly
those due to T. saginata 87.
On the other hand, the diagnosis of cysticercosis was an altogether different
proposition. The only certain method of diagnosis was by specific identification
of the parasite following surgical removal of a cyst. This was particularl y
difficult in patients with cerebral cysticercosis, although diagnosis was helped
when eosinophils were found in t he cerebrospinal fluid 113. Despite the manifest
advantages of a reliable immunodiagnostic assay for cysticercosis, repeate d
attempts to develop such tests have not led to significant improvements .

Serodiagnosis of cysticercosis began with the studies in animals of Weinberg 114
and with the demonstration by Fairley that complement fixing antibodies were
present in the serum of only two thi rds of selected patients 36. These assays have
not yet found a routine place in the diagnosis of cysticercosis 38.
Radiology has had more to offer. Calcification of dead cysticerci appears to
have been demonstrated radiologically first by Roth in 1926 94. New radiolog-
ical techniques such as CT scanning and magnetic resonance imaging ma y
facilitate greatly the diagnosis, particularly in patients with cerebra l
cysticercosis.
Remedies effective against tapeworms have been sought and their virtue s
expounded from the earliest time s23. So many agents had been declared to have
anthelmintic properties, that in the middle of the nineteenth century, Küchen-
meister was induced to declare:
if the multitude of remedies recommended for any disease is an evidence of their want
of power against it, we must say that the therapeutics of the tapeworm is extremely
defective.62
Yet this was not entirely fair, for many of these preparations did possess some
antitapeworm activity. Anecdotal clinical experiences over centuries hav e
provided fairly convincing evidence of the efficacies of many of these drugs .
They were often given concurrently with powerful purgatives which increased
peristalsis and assisted in evacuation of the tapeworm. Küchenmeiste r
attempted to produce some order out of the chaos by a series of in vitro
experiments in which he mixed Taenia ova in egg white with various com -
pounds and determined the time that the ova took to die 62. It is only in the last
100 years that various putative anthelmintics have been submitted to carefu l
clinical trial and rigorous scientific analysis.
Perhaps the best known and most commonly used anthelmintic in the treat-
ment of tapeworm infection over the centuries has been oleoresin of Aspidium,
otherwise called filix mas or extract of male fern. This drug, which is prepared
from rhizomes of the plant now known as Dryoptera filix mas, dates from the
time of early Greek medicine. These plants are widespread in the norther n
hemisphere. The rhizomes were collected in the autumn, freed from roots and
dead parts, then dried carefully. An extract was obtained by soaking th e
powdered, dry rhizomes in ether for 48 hours, then the ethereal phase wa s
filtered and concentrated. This elixir, or its principal anthelmintic constituent,
filicic acid or filicin, maintai ned the premier place in the array of antitapeworm
anthelmintics until the middle of the present century 23. Filix mas, in fact, was
the major component of the famous but secret tapeworm remedy of Madame
Nouffer in Morat, Switzerland, which w as purchased for 18,000 francs in 1776
by the French government.

A less toxic drug is kamala which had been known since the late Middl e
Ages. It is found in the glands and hairs covering the fruits of Mallotus
philippinensis, a plant which is widespread in the Orient 23. Another anthelm-
intic which caught the imagination of European doctors during the last century
was kousso, prepared from the blood red flowers of Hagenia abyssinica
(= Brayera anthelmintica), a plant which is common in Ethiopia. The firs t
recorded use of the drug in that country was around 1550 AD and it became an
important article of trade 84. Pumpkins seeds (especially Cucurbita pepo)
ground into a paste is another traditional remedy which has been shown i n
recent years to have considerable antitapeworm activity 77. Betel nut, the seed
of the palm, Areca catechu, cultivated in Asia, has been employed in th e
treatment of tapeworm infections in C hina for 1400 years 69; its active principle,
arecoline, has been used in more recent times. The anthelmintic activity of the
pomegranate, Punica granatum, was recognized during the Middle Empire of
ancient Egypt; this has been shown in recent decades to be due to its alkaloid,
pelleteriene23. Likewise, anthelmintic activity has been claimed for Chrys-
anthemum for many centuries, and pyret hrin powder prepared from the flowers
of C. cinerariifolium has been used recently as an anthelmintic 23. Metallic tin
has been given for tapeworm infections for some centuries, while preparations
based upon the combination of metallic tin with oxide and salts are more recent
origin23.
By the middle of the nineteenth century, male fern and kousso were the most
commonly used drugs, although kamala had its advocates and turpentine was
popular7,19,56,80. Although this last drug was often effective, Jenner (1856 )
believed that:
its horribly nauseous flavour and unpleasant effects on the head and occasionally on
the kidneys (made it) a remedy which should only be used as a last resort. 56
The more enlightened practitioners realized that proof of the effectiveness of
a drug was either recovery of the head of the parasite or failure to pas s
proglottids over the next several months. Nevertheless, finding the head wa s
not a simple task, and some practitioners were not convinced of the necessity,
as evidenced by the following conversation among various learned professors
of Edinburgh University in 1852:
Physiologus (Prof. Bennet). Did you find the heads of the creatures - i.e. taenia?
Medicus (Prof. Christison). No. That is no easy matter; I have been looking for a
tapeworm head all my life but have not yet found one.
Editor (Dr. Robertson). Nor I.
Physiologus (Prof. Bennet). Nor I. Did you ever know any one who has found one?
Chirugus (Prof. Syme). Yes, I knew Rudolphi.
Physiologus (Prof. Bennet). But if you say you did not find the head in your cases,
you can scarcely say the patients were cured.
Medicus (Prof. Christison). So it is pretended, but I doubt the authority. 56
The complexity of the various therapeutic regimens is illustrated by th e
method recommended by Magath and Brown in 1927 in a paper entitled :
"Standardized method of treating tapeworm infections in Man to recover th e

head".74. On the day preceding specific treatment, the patient was prohibite d
from taking either the midday or evening meal, but was permitted black coffee
or water freely. At 6.00 p.m., 15-30 g of magnesium sulphate were admin -
istered then this was repeated next morning at 6.00 a.m. After the bowels had
moved, and without having had any breakfast, the patient was given 30 ml of
an emulsion of oleoresin of aspidium together with powdered acacia in 60 ml
of water. One hour later, a further 30 ml were taken. This was followed after
another two hours by 30 g of magnesium sulphate, then finally, two hours after
this, a large enema of soapsuds was given.
Since the margin between therapeutic and toxic doses of these drugs wa s
slight, many physicians during the last few years of their popularity preferred
to administer them through a d uodenal tube, after Schneider (1924) had shown
that small doses could be used just as effectively but with less sideeffects when
this technique was adopted 98.
A number of synthetic compounds with antitapeworm activity have bee n
introduced in the twentieth century, including thymol 3, carbon tetrachloride 22,
hexylresorcinol 76, quinine102, betanaphthol, mepacrine 79
, chloroquine,
dichlorophen , bithionol , paromomycin and mebendazole 81. Of these,
55 118 97
mepacrine secured the most favoured place for a while, but it was the n
superseded by the introduction of the salicylamide derivative, niclosamide .
Gönnert and Schraufstätter screened a g reat number of salicylamide derivatives
and reported in 1960 that this particular compound was extremely activ e
against Hymenolepis diminuta in rats45. World-wide clinical trials followed and
showed that the drug was highly active against practically all the tapeworm s
infecting man, with cure rates ranging between 80% and 100% 27,60. Niclos-
amide caused lysis of tapeworms in the intestines, so concurrent administration
of a laxative was deemed advisable because of the theoretical risk of causing
cysticercosis in T. solium infections, although this view has been dispute d
recently91.
In 1972, an heterocyclic pyrazino-isoquinoline derivative, praziquantel, was
found to have unusually broad anthelmintic activity. Five years later, it wa s
reported that this drug had cure rates of nearly 100% in patients infected with
T. solium (adult worms), T. saginata and D. latum, and, in addition, was
effective against Hymenolepis species21,33. Furthermore, it was noted to b e
active against C. cellulosae, including cysticerci in the brain, but sinc e
administration of this drug may precipitate severe side-effects, concurrent use
of corticosteroids may be needed to suppress the inflammatory reaction 47,92.
The treatment of cysticercosis has been surgical with removal or parasite s
whenever possible, together with symptomatic treatment of complications such
as epilepsy. It is possible that praziquantel may revolutionize the management
of cysticercosis in many patie nts and obviate the need for surgical intervention.
The elucidation of the life cycle of T. solium by experimental infection o f

humans with C. cellulosae and the production of these cysts in pigs by feeding
them with gravid proglottids obtained from infected humans clarified th e
epidemiology of taeniasis solium. It became obvious that this infection was a
zoonosis and that humans were not only the definitive host of the adul t
tapeworms, but could also be a potential intermediate host with the acquisition
of cysticercosis, although this was, of course, a dead end for the parasite i n
most human societies. Further studies confirmed that humans alone were the
definitive host of the worm and pigs were the only significant vector o f
infection. Thus, the reasons for the previously well-recognized paucity o f
infection in certain religious groups such as Muslims and Jews, who wer e
forbidden to eat pork, were now well-understood.
Attention then turned to defining the prevalence of infection in pigs and i n
humans in various parts of the world110. During the first half of the last century,
approximately 2% of post-mortem examination s of humans conducted in Berlin
revealed cysticercosis. Although the insti tution of control measures has reduced
greatly the prevalence of infection in Europe, similar frequencies are still seen
in many countries of Africa, Asia and Central and South America, wit h
cysticercosis in slaughtered pigs ranging betgween 0.5% and 20% in thes e
regions. This high frequency of infection was explained by the demonstration
that enormous numbers of eggs were released by each proglottid; for example,
Yoshino calculated that each proglottid discharged about 40,000 eggs whil e
creeping about121. Thus, each infected person might release 100,000 eggs or
more into the environment each day.
Comprehension of the life cycle of T. solium provided a rational basis for the
institution of effective control measures. In his paper of 1855 detailing th e
experimental infection of a human with T. solium, Küchenmeister was quick
to point out the implications for a population that was in the habit of eating raw
pork and recommended that the best method of preventing infection with adult
tapeworms would be by "public instruction and warning to be careful wit h
infected pork"63. By public instruction, Küchenmeister meant the necessity for
the thorough cooking of all por k. Further studies on his part revealed that these
cysts could remain viable for up to a week after slaughtering a pig 64. The value
of proper cooking of pork was emphasized several years later when th e
transmission of Trichinella spiralis in this medium was also demonstrated. The
temperatures necessary to kill cysticerci were investigated by Perroncito in a
series of experiments with T. saginata (see chapter 14). Further researche s
indicated that pickled, salted or smoked pork was not necessarily safe 15 but that
freezing at -10 oC for a week110 or at -20oC for at least 12 hours was an effective
control measure 15. Recently, it has also been shown that infected carcasses can
be sterilized by gamma irradiation without affecting the quality of the meat 109.
Similarly, it became apparent that good sanitation, particularly with respect
to disposal of human wastes, was essential for the prevention of both porcine
and human cysticercosis, since Taenia eggs were extremely resistant t o
destruction in the environment (see chapter 14). In this respect, vegetable s
grown in gardens fertilized with human faeces were especially dangerous and
needed to be avoided. By these means, it was hoped that the incidence o f
human cysticercosis would be reduc ed and that the economic wastage resulting
from the condemnation of pork would be curtailed. A mere recitation of th e
facts was often insufficient to attain these ends, however, and intensive health
education was often required to achieve a change of habits. Thus, Viljoe n
(1937) recorded the instance of the South African farmer and his househol d
who preferred to use the rear of a hedge close to the homestead rather than a
stinking, fly-infested privy, to relieve themselves. This area could, moreover,
be cleaned immediately by pigs trained to come at a whistle. Similarly, three
farmers of high repute had the ir faith in the life cycle of T. solium shaken when
their scrupulously-styed pigs developed cysticercosis; subsequent detectio n
revealed that some black members of the staff were in the habit of easin g
themselves in the sty and that one of them had tapeworm infection 110. Finally,
the effectiveness of prompt diagnosis and treatment of T. solium infections in
the reduction of human cysticercosis was appreciated.
In developed countries, taeniasis and cysticercosis are both now kept at bay
by a combination of treatment with effective anthelmintics, personal hygiene,
efficient disposal of human wastes, rigid inspection and disposal of infecte d
meat, and storage of pork in refrigerators.
REFERENCES
1. AEGINETA P. De re medica. The seven books of Paulus Aegineta, translated by F Adams,

The Sydenham Society, London, three volumes, 1844-1847
2. AETIUS ANTIOCHENUS. De lumbrico lato. In, Medica Graeci contractae ex veteribus
medicinae tetrabiblos etc., G et M Beringer, Lugduni, 1549
3. ALLAN W. Thymol for Taenia saginata. Journal of the American Medical Association 59:
197, 1912
4. ANDRY de BOISREGARD N. De la génération des vers dans le corps de l'homme. Avec trois
lettres sur les sujets des vers, les deux premières....par M. Nicolas Hartsoeker et l'autre . . par
M. Georges Baglivi, Laurent d'Houry, Paris, pp 468, 1700. An account of the breeding of
worms in human bodies etc, translated by H Rhodes and A Bell, pp 266, 1701
5. ANONYMOUS. British and Foreign Medico-Chirurgical Review 19: 112-132, 1857
7. ANONYMOUS. The treatment of tapeworm. Lancet i: 442, 1876
8. ARISTOTLE. Opera omnia, graece et latine, cum indice nominum et rerum absolutissimo,
F Dübner, E Heitz and UC Bussemaker (Editors), Didot, Parisiis, five volumes, 1848-1874
9. ARME C. The terminology of parasitology: the need for uniformity. International Journal for
10. AVICENNA (IBN SINA). "Al canon fi Al Tib", c. 1000 AD. In Arabic. Libri in re medica
omnes, qui hactenus ad nos pervenere. Id est, libri canonis quinque, De virisbus cordis, De
removendis nocumentis in regimine sanitas, De sirupo acetosa et cautica, translated by JP
Mongio Hydruntino et J Costaeo Laudens, V Valgrisius, Venetiis, pp 966, 1564. Cited in 59
11. BEAVER PC, JUNG RC, CUPP EW. Clinical parasitology, Lea & Febiger, Philadelphia, pp
825, 1984
12. van BENEDEN PJ. Les vers cestoides ou acolytes, considérés sous le rapport de leur
classification, de leur anatomie et de leur développement. Extracted from Mémoires de
l'Académie Royale de Belgique, Bruxelles, pp 190, 1850. Abstracted in British and Foreign
Medico-Chirurgical Review 10: 322-325, 1852
13. van BENEDEN PJ. Note sur des expériences relatives au développement des cysticerques.
Annales des Sciences Naturelles 1: 104, 1854
14. BERTOLUS G. Dissertation sur les métamorphoses des Cestoides. Thèse de Montpellier,
1856
15. BIAGI F, VELEZ G, GUTIERREZ ML. Destrucción de los cisticercos en la carne de cerdo
parasitada. Boletín de la Oficina Sanitaria Panamericana 58: 303-307, 1965
16. BLANCHARD E. Recherches sur l'organisation des vers. Annales des Sciences Naturelles,
séries 3, Zoologie, 6: 271-341, 1847; 7: 87-127, 1847; 10: 321-364, 1848: 11: 106-202,
1849
17. BLOCH ME. Abhandlung von der Erzeugung-wuermer und den Mitteln wider dieselben,
Sigismund Friedrich Hesse, Berlin, pp 54, 1782
18. BORRICHIUS. Cited in 107
19. BUDD. Report of cases treated by kousso. Lancet i: 773-774, 1850
20. CAIUS PLINIUS SECUNDUS. Historia naturalis, translated by J Bostock and HT Riley,
Bohn's Classical Library, London, six volumes, 1855-1857
21. CANZONIERI CJ, RODR GUEZ RR, CASTILLO HE, IBAÑEZ de BALLELA C,
LUCENA M. Ensayos terapéuticos con praziquantel en infecciones porTaenia saginata e
Hymenolepis nana. Boletín Chileno de Parasitología 32; 41-42, 1977
22. CARMAN JA. A note on the clinical aspect of the treatment of taeniasis withcarbon tetra-
chloride. Transactions of the Royal Society of Tropical Medicine and Hygiene 25: 187-190,
1931
23. de CARNERI I, VITA G. Drugs used in cestode infections. In, International Encyclopedia of
Pharmacology and Therapeutics, Section 64, volume 1, Chemotherapy of Helminthiasis, R
Cavier and F Hawking (editors), Pergamon Press, Oxford, pp 145-213, 1973
24. CELSUS AC. De medicina, translated by WG Spencer, Loeb Classical Library Heinemann,
London, three volumes, 1948-1953
25. CLERICUS (Le CLERC D). Historia naturalis etmedica latorum lumbricorum intra hominem
et alia animalia, nascentium etc., Fratres de Tournes, Genevae, pp 449, 1715. A natural and
medicinal history of worms bred in the bodies of man and other animals etc., translated by J
Brown and J Wilcox at the Green-Dragon, Little Britain, pp 436, 1721
27. da CRUZ FERREIRA FA. Ensaios terapêuticos con o Bayer 2353 (Yomesan) na teniase (T.
saginata). Anais do Instituto Medicina Tropical (Lisboa) 17: 1009-1015, 1960
28. CULBERTSON JT. Immunity against animal parasites, Columbia University Press, New
York, pp 274, 1941
30. van DOEVEREN W. Observations physico-médicales sur les vers, qui se forment dans les
intestins; ou l'on traitement particulièrement du taenia, antrement dit, le ver solitaire, Lyon,
pp 369, 1764
31. DUJARDIN F. Histoire naturelle des helminthes our vers intestinaux, Librarie
32. EBBELL B. Altägyptische Bezeichnungen für Krankheiten und Symptome. Skrifter Utgitt av
Det Norske Videnskaps-Akademi i Oslo. II. Hist.-Filos. Klasse, No. 3, pp 65, 1938
33. ESPEJO H. Tratamiento de infecciones por Hymenolepis nana, Taenia saginata, Taenia
solium y Diphyllobothrium pacificum con praziquantel. Boletín Chileno de Parasitología 32:
39-40, 1977
34. ESCHRICHT DF. Anatomische-physiologische Untersuchungen ueber die Bothryocephalen.
Nova Acta Leopoldino-Carolinae Academiae (Breslau) 19, Suppl. 2: 3-152, 1841
35. EVANS RA. Cysticercosis in an athlete. Transactions of the Royal Society of Tropical
36. FAIRLEY NH. Cited in 72
37. FEHR JM. Hiera picra vel de Absynthio ad normam et formam Academiae Naturae
Curiosorum selecta, 1664; J Tresner, Lipsiae, pp 176, 1667
38. FLISSER A, PEREZ-MONTFORT R, LARRALDE C. The immunology of human and
animal cysticercosis: a review. Bulletin of the World Health Organization 57: 839-856, 1979
39. GABUCINUS H. De lumbricis alvum occupantibus etc., commentarius, H Scotus, Venetiis,
pp 56, 1547. Partly translated in 25
40. GALBRAITH HT. Tapeworm as a cause of chorea. Lancet i: 1348, 1904
41. GALENUS CC. Works of, In, Medicorum graecorum opera quae extant, edited by KG Kühn
(Greek text with Latin translation), Leipzig, 20 volumes, 1821-1833
42. GMELIN JF. Systema naturae per regna tria naturae, secundum classes, ordines, genera,
species cum characteribus differentiis, synonymis, locis, thirteenth edition, GE Beer, Lipsiae,
8 volumes, pp 3021-3909, 1788-1793
43. GOEZE JAE. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper, P A
Pape, Blankenburg, pp 471, 1782. Partly translated in 58
44. GOEZE JAE. Neueste Entdeckung dass di Finnen, im Schweinefleische keine
Drüsenkrankheit sondern wahre Blasenwürmer sind, etc, Halle, pp 40, 1784
45. GÖNNERT R, SCHRAUFSTÄTTER E. Experimentelle Untersuchungen mit
N-(2'-Chlor-4-nitrophenyl)-5-chlorsalicylamid, einem neuen Bandwurmmittel. I. Mitteilung:
Chemotherapeutische Versuche Arzneimittel-Forsch 10: 881-884, 1960
46. von GRAEFE A. Nächtragliche Bemerkungen über die modificirte Linear-extraction. Archiv
für Ophthalmologie 12: 150-223, 1866
47. GROLL E. Cisticercosis humana y praziquantel: una appreciacíon panorámica de las primeras
experiencas clínicas. Boletín Chileno de Parasitología 36: 29-37, 1981
48. HARTMANNUS PJ. Anatomia glandiorum. Miscellanea Curiosa Sive Ephemeridum Medico-
Physicarum Germanicarum Academiae Imperialis Leopoldinae Naturae Curiosorum Decuriae
II. Annus Septimus, Anni MDCLXXXVIII (1688) Observatio XXIV, Literis Joannis Ernesti
Adelbulneri, Nuremberg, pp 58-59, 1716. Partly translated in 58
49. HAUBNER GC, KÜCHENMEISTER F. Weitere Mittheilungen über die Entwickelung der
Band- und Blasenwürmer Nach den Versuchen von Dr. Küchenmeister und Dr. Haubner.
Magazin für die gesellschaft Thierheilkunde 20: 366-368, 1854; 21: 100-118, 1855
50. HELLER A. In, Cyclopaedia of the practice of medicine (H von Ziemssen, editor), volume 3,
Chronic infectious diseases, translated by AH Buck, The Sydenham Society, London, pp
595-613, 1875
51. HIPPOCRATES. Works of, De morbis, Book IV, section 5, translated by WH Jones and ET
Whithington, Loeb Classical Library, four volumes, 1948-1953
Malaya Press, Singapore, pp 526, 1959
53. HOLLENBACH. Wochenschrift der Thierheilkunde und Viehzucht 2: 301, 353, 1859
54. HUMBERT A. Cited in 14
55. JACKSON FC. The treatment of tapeworm infestation with dichlorophen. South African
56. JENNER W. On tapeworm and its treatment by the oil of male fern. Association Medical
Journal 4: 718-721, 1856
57. JUDSON JE. Tapeworms as a possible cause of diabetes. Lancet ii: 1256, 1903
58. KEAN BH, MOTT JE, RUSSELL AJ. Tropical medicine and parasitology. Classic
59. KHALIL M. An early contribution to medical helminthology translated from the writings of
the Arabian physician Ibn Sina (Avicenna) with a short biography. Journal of Tropical
60. KNORR R. Bandwürmbehandlung mit Yomesan abei 36 Patienten. Medizinische Klinik
(München) 55: 1937-1938, 1960
61. KREHL. Cited in 66

Parasiten. Ein Lehr- und Handbuch der Diagnose und Behandlung der thierischen und pflanz-
ischen Parasiten des Menschen, BG Teubner, Leipzig, two volumes, pp 486, 1855. On animal
63. KÜCHENMEISTER F. Offenes Sendschchreiben an die k.k. Gesellschaft der Aertze zu Wien.
Experimenteller Nachweis, dass Cysticercus cellulosae innerhalb des menschlichen
Darmkanales sich in Taenia solium umwandelt. Wiener medizinische Wochenschrift 5: 1-4,
1855. Translated in 58
64. KÜCHENMEISTER F. Erneuter Versuch der Umwandlung des Cysticercus cellulosae in
Taenia solium hominis. Deutsche Klinik 12: 187-189, 1860. Abstracted in Medical Times
and Gazette ii: 414, 1860
65. LEUCKART R. Die Blasenbandwürmer und ihre Entwickelung, Giessen, pp 162, 1856
67. LINNAEUS C. Systema naturae, per regna tria naturae, secundum, classes, ordines, genera,
species, cum characteribus differentiis, synonymis, locis, tenth edition, L Salvii, Holmiae, two
68. von LINNÉ C (LINNAEUS). Vom Bandwurme. Auserlesene Abhandlungen aus der Natur-
geschichte, Physik und Arzneiwissenschaft. Nach den Amoenitates. (Dissertatio de taenia.
Amoenitates Academicae II 1762), übersetzt von E J T H. II., Theil 3, p 101, 1762
69. LIU HL. Betel nut as a useful taeniafuge. Chinese Medical Journal 50: 1273-1278, 1936
70. LUNN WE. Case of tapeworm. Journal of the Royal Army Medical Corps 19: 99, 1912
71. MacARTHUR WP. Cysticercosis as a cause of epilepsy in Man. Transactions of the Royal
72. MacARTHUR WP. Cysticercosis as seen in the British army, with special reference to the
production of epilepsy. Transactions of the Royal Society of Tropical Medicine and Hygiene
27: 343-357, 1934
73. MacARTHUR WP. Cysticercosis of the brain. British Medical Journal ii: 1229, 1935
74. MAGATH TB, BROWN PW. Standardized method of treating tapeworm infestations in man
to recover the head. Journal of the American Medical Association 88: 1548-1549, 1927
76. MAPLESTONE PA, MUKERJI AK. Hexylresorcinol as antihelminthic. Indian Medical
Gazette 67: 610-612, 1932
77. MITTELMAN G. (Treatment of cestode infestation with pumpkin seeds). Meditsinskaya
Parazitologiya i Parazitarn e Bolezni 2: 143-146, 1933. In Russian. Abstracted in Tropical
78. MOQUIN-TANDON A. Elements of medical zoology, translated by RT Hulme, Baillière,
London pp 423, 1861
79. NEGHME A, FAIGENBAUM J. Nueva modalidad de tratamiento en las teniasis. Revista
Médica de Chile 75: 54-57, 1947
80. OGLE JW. Observations of the treatment of taenia, especially by the use of oil of male-fern.
81. OLIVEIRA-GOMES MD. The treatment of taeniasis with mebendazole. Folha Médica 66:
1043-1051, 1975
82. PALLAS PS. Einige Erinnerungen die Bandwürmer bettrefend; in Beziehung auf das zwölfte
und vierzehnte stück des Naturforschers. Neue nordische Beyträge Physikalische und
Geographische Erd- und Völkerbeschriften 2: 113-131, 1781
83. PANAROLUS D. Iatrologismorum, seu medicinalium observationum pentecostae quinque
etc, F Moneta, Romae, pp 445, 1652
84. PANKHURST R. The traditional taenicides of Ethiopia. Journal of the History of Medicine
24: 323-334, 1969

85. PAPYROS EBERS. Das hermetische Buch über die Arzneimittel der alten Aegypter ni
hieratischer Schrift. Herausgegeben mit Inhaltsangabe und Einleitung versehen von Georg
Ebers. Mit hieroglyphische-lateinischen Glossar von Ludwig Stern, two volumes, Leipzig,
1875. The Papyrus Ebers, translated from the German version by CP Bryan, Geoffrey Bles,
86. PINDEA A, BOTERO O, BRAVO C. Taeniasis. Presentación de 74 casos, 2 de ellos con
infección múltiple. Antioquia Médica 22: 417-422, 1972
87. PODYAPOLSKAYA VP. (Diagnosis of helminthic infestations by the examination of
scrapings from the perianal folds.). Meditsinskaya Parazitologiya i Parazitarn e Bolezni 12:
83-85, 1943. In Russian. Abstracted in Tropical Diseases Bulletin 41: 301, 1944
88. PRIEST R. A case of extensive somatic dissemination of cysticercus cellulosae in man.
89. RANSOM WH. On the diagnosis and treatment for roundworm; and on the occurrence of a
new species of Taenia in the human body. Medical Times and Gazette, new series, 12:
598-601, 1856
90. REDI F. Osservazioni intorno agli animal viventi che si trouvano negli animali viventi, Piero
Matini, Firenze, pp 244, 1684
91. RICHARDS F, SCHANTZ PM. Treatment of Taenia solium infections. Lancet i: 1264,
1985
92. RIM HJ, PARK CY, LEE JS, JOO KH, LYU KS. Studies on the human cysticercosis and
its therapeutic trial with praziquantel. Korea University Medical Journal 17: 459-472, 1980
93. ROSEN de ROSENSTEIN N. Traité des maladies des enfants, translated by Febre de
Villebrune, Paris, pp 484, 1793. Original Swedish edition 1788
94. ROTH EJ. Man as the intermediate host of the Taenia solium. British Medical Journal ii:
470-471, 1926
95. RUDOLPHI CA. Entozoorum, sive vermium intestinalium historia naturalis, Treuttel et
Wurtz, Paris, three volumes, pp 1370, 1808-1810
96. RUMLER JU. Secto a me, in capite, pustulae supra duram meningen apparuerunt, erosa ipsa
et cerebro per foramina eminente pluribus in locis. Observationes Medicae, 1558. Cited in
108
97. SALEM HH, al-ALLAF G. Paromomycin and Taenia saginata. Lancet ii: 1360, 1967
98. SCHNEIDER H. Eine Modifikationder üblichen Bandwürmkur mittels der Duodenalsonde.
Wienerüklinische Wochenschrift 37: 338-339, 1924
99. SERAPION (YUHANNA IBN SARA-BIYUN). In, Practica etc, translated from the Arabic,
Venetiis, 1497. Cited in 29
100. von SIEBOLD CT. Helminthologische Beiträge. Archiv für Naturgeschichte 1: 45-83, 1835
101. von SIEBOLD CT. Ueber die Spermatozoen der Crustacean, Insecten, Gasteropoden und
einiger anderer wirbellosen Thiere. Archiv für Anatomie und Physiologie (Mueller) pp
13-53, 1836
102. SOKOLOWSKI W (Transduodenal expulsion of cestodes with quinine.) "Militaer
Medicinische Zeitschrift, Leningrad" 4: 274-276, 1933. In Russian. Abstracted in Tropical
103. SOMMER F. Ueber den Bau und die Entwickelung der Geschlechtesorgane vonTaenia
mediocanellata (Küchenmeister) und Taenia solium (Linné). Zeitschrift für
wissenschaftliche Zoologie 24: 499-555, 1874
104. SPIGELIUS. De lumbrico lato liber (cum ejusdem lumbrici icone et notis), L Pasquati,
Patavii, pp 88, 1618
105. THREOPHRASTUS. Enquiry into plants, translated by AF Hort, Loeb Classical Library,
two volumes, 1948-1949
106. TULPIUS N. Observationes Medicae. Editio nova, L Elzevirium, Amsteloedami, pp 403,
1652
worm, wherein a great many mistakes of former writers concerning it, are remarked; its
natural history from more exact observations is attempted; and the whole urged, as a
difficulty against the doctrine of univocal generation. Philosophical Transactions of the Royal
Society 13: 113-144, 1683
108. VELSCHIUS GH. Sylloge curiatonum et observationum medicinalium, centurias v i

complectens etc, Rumlerus J, pp 63, G Goebelii, Augustae Vindelicorum, pp 448, 1668
109. VERSIER H. The effect of gamma radiation on the cysticerci of Taenia solium.
Onderstepoort Journal of Veterinary Research 43: 23-26, 1976
110. VILJOEN NF. Cysticercosis in swine and bovines, with special reference to South African
conditions. Onderstepoort Journal of Veterinary Science and Animal Industry 9: 337-570,
1937
111. VILLANOVANI A. De lumbricus et ascaridibus. In, Opera omnia, Basileae, 1585. Original
edition c.1300 AD
112. WAGLER. Cited in 43
113. WATERHOUSE R. Cysticercus cellulosae in the central nervous system: with an account
of two cases. Quarterly Journal of Medicine 6: 469-485, 1913
114. WEINBERG. Recherches des anticorps spécifiques dans la distomatose etla cysticercose.
219-221, 1909
115. WERNER PC. Vermium intestinaliorum brevis expositionis continuato secunda. Edita et
animadversionibus atque tabulis a aeneis aucta JL Fischer, Lipsiae, pp 96, 1786
116. WHARTON T. Adenographia: sive glandularum totius corporis descriptio, Londini, pp 287,
1656
117. WOOD W. On a case of insanity caused by tapeworm and cured by kousso. Lancet i: 9,
1851
118. YOKOGAWA M, YOSHIMURA H, OKURA T. The treatment of Taenia saginata with
bithionol. Japanese Journal of Parasitology 11: 39-44, 1962
119. YOSHINO K. (Studies on the postembryonal development of Taenia solium. Part II. On the
youngest form of Cysticercus cellulosae and on the migratory course of the oncosphere of
Taenia solium within the intermediate host.) Taiwan Igakkai Zasshi 32: 1569-1586, 1933.
In Japanese, with English summary.
120. YOSHINO K. (Studies on the postembryonal development of Taenia solium. Part III. On the
development of Cysticercus cellulosae within the definitive intermediate host). Taiwan
Igakkai Zasshi 32: 1717-1736, 1933. In Japanese, with English summary
121. YOSHINO K. (On the evacuation of eggsfrom detached gravid proglottids of Taenia solium
and on the structure of its eggs.) Taiwan Igakkai Zasshi 33: 47-58, 1934. In Japanese, with
English summary
122. YOSHINO K. (On the subjective symptoms caused by the parasitism ofTaenia solium and
its development in Man.) Taiwan Igakkai Zasshi 33: 183-194, 1934. In Japanese
123. ZEDER JG. Anleitung zur Naturgeschichte der Eingeweidewürmer, Bamberg, pp 432, 1803
Table 13.1. Landmarks in taeniasis solium and cysticercosis

___________________________________________________________________
BC Tapeworms in humans and cysticerci in animals were known but their true
nature was not appreciated. Multiple remedies, including extract of male
fern (filix mas), were described for intestinal taeniasis
c.1550 Kamala and kousso were introduced as antitapeworm agents
1558 Rumler probably described cysticerci in a human
1683 Tyson discovered the head of a tapeworm
1688 Hartmann discovered the verminous nature of C. cellulosae in pigs
1784 Goeze pointed out the similarities between the heads of tapeworms found
in the human intestinal tract and the invaginated heads in C. cellulosae in
pigs
1854 van Beneden reported that he had generated C. cellulosae in the muscles
of a pig fed with T. solium ova
1855 Küchenmeister fed C. cellulosae in pork to a condemned murderer and
recovered small tapeworms several days later
1855 Humbert infected himself with C. cellulosae then began passing segments
of T. solium three months later
1856 Ransom described the diagnosis of intestinal taeniasis by finding eggs on
microscopical examination of the faeces
1860 Küchenmeister fed C. cellulosae in pork to a condemned murderer 4 and
2.5 months prior to execution, then recovered a large number of adult T.
solium, one being five feet in length
1926 Roth demonstrated calcified cysticerci by radiography
1934 Fairley showed that antibodies were present in the sera of patients with
cysticercosis
1960 Niclosamide was introduced for the treatment of intestinal taeniasis
1977 Praziquantel was introduced for the treatment of intestinal taeniasis
1980 Praziquantel was shown to be effective in cysticercosis
__________________________________________________________________
Chapter 14
Taenia saginata and TAENIASIS SAGINATA
SYNOPSIS
Common name: tapeworm

Major synonym: T. mediocanellata
Distribution: worldwide
Life cycle: The adult tapeworms, usually about 5 metres in length, live in the small
intestine with the head attached to the mucosa. Eggs and gravid proglottids are passed
in the faeces. When ingested by cattle, the eggs hatch in the small intestine and each
released larva (oncosphere) penetrates the mucosa and passes via the bloodstream to
the tissues, especially the muscles, subcutaneous tissues and central nervous system,
where it vesiculates to form a bladderworm (Cysticercus bovis); these usually reach
10 mm in size and contain an invaginated head. When a cysticercus in insufficiently
cooked beef is ingested by a human, the head evaginates in the small intestine and
develops into an adult tapeworm which produces proglottids after approximately two
months
Intermediate host: cattle
Major clinical features: abdominal discomfort, spontaneous passage of proglottids
Diagnosis: finding of eggs (any Taenia) or proglottids (T. saginata) in the faeces
Treatment: niclosamide, praziquantel
DIFFERENTIATION OF THE SPECIES FROM TAENIA SOLIUM
Tapeworms have been known for generations (see chapter 13), but conceptions
about the three species of large tapeworms that commonly infect man, Taenia
solium, T. saginata and Diphyllobothrium latum , were hopelessly confuse d
and intermingled for many centuries. As discussed in Chapter 15, D. latum
began to be recognized as a separate entity in the seventeenth century, leaving
the other two species lumped together under the name, amongst many others,
of T. solium. Distinction between D. latum and the species of Taenia was
relatively easy, even when a head was not available for examination, because
the shape of the proglottids and the position of the genital pore were quit e
different. It was another matter with the worms we now know as T. solium and
T. saginata, however, for the distinguishing fe atures in the proglottids are much
more subtle and their classification required a knowledge of their interna l
anatomy, particularly the branches of the uterus. It required the discovery o f
tapeworm heads before definite distinction between these two species wa s
385
achieved. Remarkably though, 170 years were to pass after Tyson's discovery
of the head of a tapeworm (see chapter 13), before general agreement on the
two species was obtained.
In 1700, Nicolas Andry de Boisregard described, under the name T. solium
or Taenia sans épine (Taenia without thorns), a cestode which was none other
than T. saginata 2. Andry not only provided illustrations of the proglottids, but
also, for the first time, gave drawings of the head of a tapeworm obtained from
a human. The scolex had no hooks and there is no doubt that this worm was T.
saginata, but he was completely unaware of the existence of two species o f
Taenia. Vallisneri in 1714 again made the same mistake, describing an d
figuring T. saginata under the name of T. solium 39. As discussed in chapter 15,
Charles Bonnet then drew a hybrid tapeworm in 1750, with the head of T.
saginata and the body of D. latum; he did, however, correct this error in 1777.
Again, in his Systema Naturae (1758), Linnaeus, under the designation T.
solium, described what was in fact a T. saginata as the typical form of the
Taenia infecting Man, although he did note that the worm had some variations
in its appearance 27. Peter Pallas was also confused by this variability. He wrote
that T. solium (which he called T. cucurbitina, and to which he ascribed a
crown of thorns) was sometimes delicate, thin and narrow, and at other times,
stout, thick and fat 31. Although he did not realize it, he was in fact describing
T. solium and T. saginata, respectively.
Johannes Goeze, recognizing both the morphological differences and th e
variations in the geographical distribution of the two forms, in 1782, separated
the human taeniid tapeworms into two categories:
I know and possess two species of intestinal tapeworm; the first is well known - long,
with thick, fattened segments which I shall call Taenia cucurbitina, grandis,
saginata. The second seems to be a variety of the first, which under all circumstances
remains the same and is found in my part of the country more frequently than the
former; I call it Taenia cucurbitina, plana, pellucida.12
Like Pallas, Goeze called these worms T. cucurbitina. His name of Taenia
cucurbitina, grandis, saginata indicated that one parasite was large and fat ,
while the Taenia cucurbitina, plana, pellucida reflected the flat and
transparent nature of the other tapeworm. Goeze possessed nine specimens of
T. saginata, seven without heads and two complete examples. He wrote that:
It is truly amazing to compare the pieces of this flattened tapeworm with others. The
most mature lower segments are not as long as in the flat, transparent variety, but are
much thicker. Some have the thickness of half a line [1mm] and are all marked with
little lines lengthwise on the surface. In a section of worm more than one ell [an
English ell is 1.13 metres and a Flemish ell is 68 cm] in length, the marginal openings
are set in each segment, one on each segment, some right, some left....In the next ell
of this specimen, the segments are much narrower and almost pushed one on top of
the other and thereby give a considerable thickness. 12
Goeze was intrigued by variations in position of the marginal openings for he
noted that "The order in the position of the marginal openings, which is hardly
ever the same, still remains very puzzling and yet it cannot be withou t
Taeniasis saginata 387
purpose"12. He did not dwell at length on the appearances of the two heads of
the Taenia cucurbitina, grandis, saginata that he possessed, merely writing:
In the first specimen the head is not flat and ribbonlike but round, ascarislike; in the
latter, however, it is flatter. I am only adding that the head end of both of these
specimens is completely different from the head end of the notched, segmented
tapeworm from the cat, as mere observation shows. In the first, however, one cannot
see, as in the cat's tapeworm, the suckers and the hooks with the naked eye, and the
segments only start after a very narrow neck.12
Goeze then went on to contrast the appearance of the flat, transparent variety,
Taenia cucurbitina, plana, pellucida (i.e. T. solium), after first proving that it
was not simply an immature form of Taenia cucurbitina, grandis, saginata.
Goeze had several specimens of Taenia cucurbitina, plana, pellucida which
were complete with head. He noted that the dendritic ramifications of the uterus
were far more defined and visible in this form of tapeworm than in Taenia
cucurbitina, grandis, saginata, then he described definitively the head of the
tapeworm now called T. solium:
The head of the worm is like a small box and not round. At the four corners of the
head there are four suckers and a superior rostellum which can be seen through the
microscope.12
In addition, the accompanying figures indicate clearly the four suckers and the
crown with two rows of hooks.
Although Goeze's description of the head of T. solium was unequivocal, he
did not stress (and perhaps was not aware of) the value of this feature i n
distinguishing T. solium from T. saginata, the latter species not having a crown
of hooks. Just before Goeze published his findings, M. Bloch, a physician in
Berlin, contributed a discourse which won the gold medal given by th e
Academy of Science at Copenhagen for its prize essay set in 1780. The title of
this essay was "Concerning the seeds of intestinal worms: whether tapeworms
etc. are inborn in animals or enter from outside". Amongst other things, Bloch
proposed in this essay a classif ication of tapeworms in which, for the first time,
the presence or absence of hooks on the head was used as a specific character.
Although he divided the genus Taenia into the "inarmatae" containing 1 6
species and the "armatae" with four species, he did not use this feature t o
differentiate between the human tapeworms, T. saginata and T. solium 7.
Several years later, Batsch expresse d similar views to Goeze. As with Pallas,
he preferred the name T. cucurbitina and distinguished two constant varieties
within this species; these were recognizable by the features mentioned b y
Goeze, as well as upon the ramifications of the uterine branches that he noted.
In addition, Batsch was also aware of regional variations in the relativ e
frequencies of the forms of tapeworms 3.
Nevertheless, these judicious observations largely passed unnoticed or were
ignored. T. saginata continued to be confounded with T. solium, or was simply
considered as a variety of the latter. Thus in Berlin, Rudolphi saw onl y
specimens of Taenia with hooks, while Bremser in Vienna, by contrast ,
encountered only Taenia without hooks. Indeed, Bremser 8 believed, along with
FS Leuckart and Mehlis, that all young taeniae had hooks and lost them with
advancing age, just as an ageing man loses his hair. In 1830, Nicolai agai n
drew attention to the presence of hooks in on e form of tapeworm and named the
parasite T. dentata 29, but his views were still not heeded. Further examples of
regional variations in the type of tapeworm present were described. Thus ,
Wawruch noted that in the parts of Wurtemberg situated in the Danube basin,
only unarmed taeniae were present, while in the region in the Necker basin ,
only armed Taenia occurred40. Similarly in Java, Schmidtmuller examined 148
taeniae in the space of 15 years, and finding them all to be unarmed, name d
them Bothriocephalus tropicus. The situation became so confused that neither
Dujardin (1845) nor Diesing (1849-1851) in their major textbooks admitted
two distinct species of Taenia infecting humans.
In 1852, Friedrich Küchenmeister declared that there were definitely tw o
distinct species of Taenia, clearly distinguishable, not only by their genera l
appearances, but particularly by the structures of their heads and thei r
reproductive systems. He observed that the head of T. solium was armed with
hooks, whereas the other species, which was also larger and fatter, was always
bare of hooks. Again, there were 9-15 lateral uterine branches in the proglottids
of T. solium whereas the other species had 15-20 such branches. To this latter
species, Küchenmeister gave the name T. mediocanellata, the specific epithet
denoting a main transverse channel running through the region between th e
four sucking discs 19,20. When Leuckart reviewed this matter a few years later,
he gave Küchenmeister little credit:
In 1852, Küchenmeister again advanced the opinion that besides T. solium there was
another large-jointed species to be distinguished in man....if Küchenmeister had been
better acquainted with the literature of helminthology, and had consulted it more
carefully, he would have learned that his discovery was not as new as he supposed,
but was rather only a confirmation and extension of observations which would have
long since been fully settled if the observers had a more rich and complete material
to work upon.26
This comment was typical of Leuckart's penchant for unfair criticism o f
Küchenmeister. The fact is that the distinction between T. saginata and
T. solium was not generally recognized until Küchenmeister's publication, but
was accepted thereafter.
Not only was Küchenmeister's designation, T. mediocanellata, founded on
an erroneous anatomical idea, but some of the purists objected to thi s
nomenclature on the suspect ground that t he term "mediocanellata" was derived
from a combination of Greek and Latin roots. Some authors consequentl y
preferred the term T. inerme or T. inermis to describe T. saginata. This created
a dilemma since such usage flew in the face of precedent, but the problem was
solved when Leuckart in 1867 pointed out that Goeze had earlier used th e
designation "saginata" to describ e this species and that the correct name should
therefore be T. saginata 25,26. This name was then adopted generally, although
first Leuckart then Blanchard 6 considered that it would be more in keeping with
the rules of zoological nomenclature to accord the name T. solium to the

unarmed tapeworm and call the tapeworm with hooks, T. pellucida Goeze.
They conceded, however, that such a course was impractical and woul d
augment the already consider able confusion which surrounded the terminology
of tapeworms. Discussion has continued until the present day with som e
taxonomists believing that the unnamed tapeworm of man acquired by th e
consumption of beef should be called Taeniarhynchus saginata whereas other
authorities believe Taenia saginata to be the correct designation. Furthermore,
while most investigators believe there to be only one species of beef tapeworm
infecting humans, some have considered that there are number of suc h
species32.
EXPERIMENTAL PRODUCTION OF C. BOVIS
The successful demonstration in the 1850's of the complete life cycle o f

T. solium naturally suggested that a similar process might occur wit h
T. saginata. The difficulty was to know wh ich animal was the intermediate host
containing cysticerci. A. Judas probably saw cysticerci of T. saginata in the
lungs of cattle in the abattoirs at Orleansville, Algeria in 1854, although he did
not recognise them as such 16. Blanchard6 has canvassed the possibility tha t
Judas had in fact found C. tenuicollis, but thought this unlikely since thi s
species is generally found in the liver and mesentery whereas C. bovis may be
found in the lungs of cattle.
The clue was to come from clinical and epidemiological observations. Phys-
icians had noticed that sickly children, who had been ordered to eat raw beef
in order to strengthen them, particularly those in St. Petersburg (no w
Leningrad, USSR), not infrequently contracted infection with T. saginata 41. It
was also realised that European Jews, who were proscribed from eating pork,
were not afflicted with T. solium, but acquired infections with T. saginata.
Finally, travellers to various parts of the globe reported that T. saginata
infections were more common in cert ain countries. The most notorious of these
was Abyssinia (Ethiopia) where almost everyone was infected and where the
inhabitants ate mostly beef, and that raw, by preference. In 1860, Huber pu t
forward the hypothesis that cysticerci would be found in the tissues of cattle 14.
These pointers, together with the failure o f several previous attempts to infect
pigs and sheep with T. saginata eggs and the observations of Knox, led Rudolf
Leuckart to investigate the effects of feeding such eggs to cattle. Army surgeon
Knox had witnessed a tapeworm epidemic among soldiers who had eate n
"overdriven and unsound" oxen during the first Kaffir War in South Africa 18.
Leuckart knew, moreover, that specimens of Taenia submitted to him from
South Africa were T. saginata. On 13 November 1861, therefore, Leuckart fed
a mature segment of T. saginata about four feet long to a four week old calf,
then reinfected the animal one week later with smaller pieces of the sam e
tapeworm. The animal appeared well but then died suddenly on 8 December.
At post-mortem examination, all the muscles and some of the visceral organs
as well as the lymphatics were permeated with:
cysts which were 1.5-3 mm wide and 2-4 mm in length. They had a whitish
appearance as though filled with a chalky or caseous mass, as I had never observed
in any young cysts of the Cysticercus cellulosae in a similar way. Inside the exudative
layer, which was surrounded by a firm connective tissue membrane, they contained
a light, clear vesicle of 0.4-1.7 mm in diameter. On cutting into this cyst, this
protruded and proved on closer examination to be a young cysticercus....At this stage
of development, no suckers could be found. The inner parts of the head cone showed
little enlargement of the end, and in the region of the smaller cysticerci it was a simple
conical shape.24
Leuckart then repeated the experiment and infected another calf with 25-3 0
proglottids of T. saginata. The animal became quite sick during the third week
after infection, but then recovered completely. Seven weeks after infection, a
biopsy was taken from the sternomastoid muscles and about a dozen cysticerci
were obtained. In contrast to the scolex of C. cellulosae:
this head cone was without a bend and in spite of its small size (hardly 1 mm), also
in spite of the small size of the vesicle (3-4 mm), was already provided with
completely developed suckers. Instead of the protruding hooks, there was on the
bottom of the invagination, between the suckers, a tight circle of small rudiments. 24
Leuckart believed that the larval stage of T. saginata may lag behind that of
T. solium with respect to size, and that this might partly account for it having
escaped the attention of helminthologists up to that time. He concluded that
by these experiments he had established beyond any doubt the specifi c
nature of T. saginata and, furthermore, that he had shown that infection with
this parasite was acquired by humans from cattle and possibly othe r
ruminants22,23.
Leuckart's findings were confirmed twice in 1863 by Mosler 28, by Cobbold
and Simonds in 1864 and again in 1865 38, then by Roll (1865), Gerlach (1870),
Zurn (1872), Saint-Cyr (1873), Jolicoeur ( 1873), Masse and Pourquier (1876),
Perroncito (1877) and others. Various investigators confirmed the earl y
observations that pigs and sheep were insusceptible to this species of tape -
worm, and demonstrated that rabbits were likewise inhospitable hosts. Th e
cysticercus was designated Cysticercus ex Taenia mediocanellatae by Davaine
then as C. bovis by Cobbold 10; the latter name has stuck. One wonders why so
many investigators felt it necessary to confirm these findings. Perhaps the y
wanted a ready demonstration of the almost incredible phenomenon of th e
migration of worms and the alternation of generations, and this provided a
convenient excuse and a workable system. Perhaps they wanted to prove their
mastery over these worms. Perhaps it simply gave them a feeling of achieve-
ment and satisfaction. In any event, it was c lear that cattle were the intermediate
host of T. saginata, and that humans were likely to acquire infection with this
parasite by eating raw or poorly-cooked beef.
EXPERIMENTAL GENERATION OF ADULT T. SAGINATA
Following the experimental production of the cysticercus of T. saginata in

cattle by Leuckart, there seemed little doubt that humans acquired T. saginata
infection in just the same way as they contracted taeniasis solium. Under -
standably enough, no-one went to Küchenmeister's lengths and infected a
criminal destined to be executed. Indeed, it was a number of years befor e
anyone repeated the similar experiment first done with T. solium by Humbert.
John Oliver, a British medical officer stationed with the Royal Artillery a t
Jullundur, India, made some poorly controlled experiments during 1868-1869,
not so much as to demonstrate completion of the life cycle, but in order t o
examine the clinical effects of consumption of measly beef under differen t
conditions. Cysticercosis bovis was endemic in the area and T. saginata
infection was common in the local camel drivers. Oliver's results are recorded
in the annual report for 1870 of the Sa nitary Commissioner for the Government
of India:
1st - After explaining to them the possible consequences of eating it, a buttock of beef
studded with cysticercus was given to three natives of low caste. They all declared that
they were free of taenia. The meat they cook in their own way. These men were under
my observation for some six months. Two of them had no symptoms of taenia, but
the third, who was a low class Mahomedan syce, and had probably eaten the meat in
a very raw state, developed a T. mediocanellata in about three months.
2nd - My own sweeper ate this cyst-infected beef regularly two or three times a week
for some months. He cooked it well, generally as an ordinary stew, and has never
shown a sign of having tape-worm.
3rd - In the case of a Hindoo boy of low caste, two scolices of cysticercus within three
or four months produced a T. mediocanellata.30
This last patient cited is particularly surprising as it would be unheard of for a
Hindu to eat beef - perhaps Oliver administered isolated scolices.
A more precise study was undertaken by Ed uardo Perroncito in Italy in 1877.
In that investigation, which was designed to determine the effects of heating of
cysticerci on their infectivity, a control subject ingested an uncooked C. bovis
on 4 March 1877; 54 days later, he began to pass proglottids. Treatment with
kousso and oil of ricin on the 57th day yielded a T. saginata 4.27 m long and
containing 866 proglottids. It was calculated that this tapeworm produce d
between 13 and 14 proglottids per day 36.
Thus, it was finally proven that T. saginata had a life cycle similar to that of
T. solium, except that infection was acquired by ingestion of contaminated beef
instead of pork.
Although rare claims have been made for findin g C. bovis in humans11, the clin-
ical manifestations of infection with this parasite, for all practical purposes ,
devolve from the presence of intestinal worms. Consequently, the symptom s
and signs are much the same as have been described already for taeniasi s
solium. Proglottids of T. saginata are said to break off more easily than those
of T. solium and Küchenmeister has a particularly graphic description of their
passage which he notes may occur either in the faeces or separately:
The segments pass when the patient is standing quietly and falling into his trousers,
he suddenly has a moist and cool feeling about the legs, and when he seeks to free
himself from this unpleasant sensation, finds a single proglottis attached to or creeping
about the leg. Women especially are afraid lest the proglottides should fall unperceived
upon the ground when they are walking or standing. 21
Presumably they were grateful for the invention of elastic underwear! It ha s
been concluded that 8-9 proglottids are produced per worm per day34. These
tapeworms might also reach remarkable lengths. One patient treated wit h
extract of kamala passed three yards of T. saginata, and then on being treated
again almost immediately with oil of male fern, passed a further 11 yards ,
together with the head, making 14 yards of tapeworm in total 1. Despite their
ability to reach huge sizes, these worms rarely cause intestinal obstruction ,
although several cases of this complication are on record 9. It has even been
claimed that a complete T. saginata, ten feet long, has been removed from the
gall bladder of an old man with acute cholecystitis 4. Infections may also be
multiple. In 1893, Bérenger-Férand 5 reviewed 2686 cases and found that one
worm was present in 87% of persons, two were present in 7.8% and 2.3% had
three tapeworms. Cases with more t han 5 worms was exceptional although one
patient was claimed to have 27 T. saginata and another, 59 tapeworms. More
certain is the patient of Hodson who, when treated in the Khartoum Civi l
Hospital with filix mas, produced 31 specimens of T. saginata 13.
Observations over the centuries have sho wn that the prognosis is good in this
infection since there is no likelihood of people developing cysticercosis.
DIAGNOSIS AND TREATMENT
The diagnosis of taeniasis saginata is made in the same way as is taeniasi s

solium. Although T. saginata was said to be slightly more resistant tha n
T. solium to the older anthelmintics 21, these infections respond well to th e
newer drugs described in chapter 13.
The experimental generation of C. bovis in cattle by feeding them with T. sag-

inata eggs in mature proglottids obtained from infected humans, and the sub-
sequent infections of humans by such cysticerci, clarified the epidemiology of
taeniasis saginata and indicated that, like taeniasis solium, this infection was a
zoonosis. Further researches confirmed that humans were the sole definitiv e
host and cattle were the principal intermediate hosts.
Efforts were made to define the life span of eggs and cysticerci. As wit h
T. solium, enormous numbers of eggs were discharged into the environment,
it being estimated that each proglottid released an average of 80,000 eggs .
Thus, each infected patient might pass about half a million eggs daily 34. These
eggs were remarkably resistant to destruction in the laboratory by a grea t
variety of physical and chemical means 15 and were found to survive for several
months in pastures 35. Studies of experimentally-infected cattle showed tha t
cysticerci lived in the tissues for a variable period but that most were not viable
within four months, and all were dead by nine months after infection 33.
Epidemiological investigations then concentrated on defining the prevalence
of taeniasis in humans and cysticercosis in cattle in various parts of the world.
The organism was found to be spread wide ly but sporadically around the globe.
The discovery that taeniasis saginata was acquired by ingesting contaminated

beef suggested that infection should be preventable by proper cooking of beef.
The observations of Oliver 30 indicated that this was likely then it was confirmed
by the experimental studies of Perroncito 36. The latter investigator expose d
cysticerci to various tempera tures, then administered them to his collaborators.
Dr. Ragni consumed a cysticercus which had been heated to 47 oC; it had no
sign of life and failed to develop. S imilar outcomes awaited the medical student
Gemelli who ingested a cysticercus heated to 45 oC and his colleague Martini
whose cysticercus had been exposed to 44 oC. In contrast, a patent infectio n
developed in a fourth person who ate an unheated C. bovis.
Perroncito further showed that even without heating, cysticerci die between
two and three weeks after slaughter of the cattle. A few years later, Ranso m
found that they could also be killed by refrigeration at -10 oC for six days. 37
In addition to these measures, improved methods for the disposal of human
faeces helped reduce the incidence of infection in many places, as did th e
introduction of compulsory inspection of cattle and condemnation of measl y
beef.
REFERENCES
1. ANONYMOUS. A case in which fourteen yards of Taenia mediocanellata were voided with
the head. (Under the care of Dr. Murchison). British Medical Journal ii: 86, 1867
2. ANDRY de BOISREGARD N. De la génération des vers dans le corps de l'homme. Avec trois
lettres sur les sujets des vers, les deux premières....par M. Nicolas Hartsoeker et l'autre ....par
M. Georges Baglivi, Laurent d'Houry, Paris, pp 468, 1700. An account of the breeding of
worms in human bodies etc., translated by H Rhodes and A Bell, pp 266, 1701
3. BATSCH AJ. Naturgeschichte der Bandwurmgattung überhaupt und ihrer Arten insbesondere,
Halle, pp 298, 1786
4. BENEDICT EB. Taenia saginata in the gall bladder. Journal of the American Medical
Association 87: 1917, 1926
5. BÉRENGER-FÉRAND. Du nombre et de la longueur des taenias que l'on rencontré chez
l'homme. Bulletin de l'Académie de Médecine 29: 12-15, 1893
1689, 1885-1890
7. BLOCH M. Abhandlung von der Erzeugang der Eingeweidewürmer und den Mitteln wider
dieselben. Eine von der königlich dänischen Societät der Wissenschaften zu Copenhagen
gekrönte Preisschrift, Sigismund Friedrich Hesse, Berlin, pp 54, 1782
Aertze. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. Nebst einem Anhange
über Pseudo-helminthen, Carl Schaumburg und Comp., Wien, pp 284, 1819
9. CHRISTOPHERSON JB, IZZEDIN M. Acute intestinal obstruction by tapeworms (T.
saginata): mechanical blocking of the ileo-caecal valves, necessitating laparotomy. British
account of the ectozoa, J&A Churchill, London, pp 500, 1878
11. FONTAN C. Cysticercus bovis chez l'homme localisé à la région mammaire. Taenia inerme
de l'intestin. Parasitism adulte et larvaire chez le meme sujet. Gazette des Hôpitaux 92:
183-185, 1919
Pape, Blankenburg, pp 471, 1782. Partly translated in 17
13. HODSON VS. Tapeworm hospitality. Lancet ii: 728, 1921
14. HUBER. Notizen über das Vorkommen pflanzicher und thierischer Parasiten in unserm
Bezirk. 13 Bericht die Naturhistorische Vereins in Augsburg, pp 121-129, 1860
15. ISOBE M. (On the resistance of the egg of Taenia saginata.) Taiwan Igakkai Zasshi No. 222,
pp 29-75, 1922. In Japanese, with English summary
16. JUDAS A. Nouveau documents sur la fréquence du Taenia en Algérie. Receuil de Mémoires
de Médecine, de Chirugie et de Pharmacie Militaires 13: 230, 1860
18. KNOX R. Observations on the Taenia solium; and on its removal from the human intestinal
canal by spirits of turpentine. Edinburgh Medical and Surgical Journal 17: 384-393, 1821
19. KÜCHENMEISTER F. Ueber eine neue Taenia des Menschen, Taenia mediocanellata
hominis, seu Zittauensis (mihi). Deutsche Klinik 4: 101-103, 1852
20. KÜCHENMEISTER F. Ueber Cestoden im Allgemeinen und die des Menschen insbesondere
etc., Zittau, pp 148, 1853
treatment. 1. Animal parasites belonging to the group Entozoa, translated by E Lankester, The
Sydenham Society, London, pp 452, 1857
22. LEUCKART R. Ueber Taenia solium und T. mediocanellata (Helminthologische
Experimentaluntersuchungen 2). Nachrichten von der königlich Gesellschaft der
Wissenschaften und der GeorgAugusts Universität, Göttingen, pp 15-21, 1862.
23. LEUCKART R. Ueber den Finnenzustand der Taenia mediocanellata. Nachrichten von der
königlich Gesellschaft der Wissenschaften und der Georg-Augusts Universität, Göttingen, pp
195-206, 1862
Hand- und Lehrbuch für Naturforscher und Aertze, C F Winter'sche Verlagshandlung, Leipzig,
volume 1, pp 776, 1863. Partly translated in 17
25. LEUCKART R. Bericht über die wissenschaftlichen Leistungen in der Naturgeschichte der
niederen Thiere während der Jahre 1866 und 1867. Archiv für Naturgeschichte 33J, 2:
163-304, 1867
27. LINNAEUS C. Systema naturae per regna tria naturae, secundum classes,ordines, genera,
species, cum characteribus, differentiis, synonymis locis, tenth edition, L Salvii, Holmiae, two
28. MOSLER KF. Helminthologische Studien und Beobachtungen, A Hirschwald, Berlin, pp 89,
1864
29. NICOLAI KF. Zur Geschichte der Bandwürmer. Neuer Zeitschrift für Natur- und Heilkund
1: 464-471, 1830
30. OLIVER JH. Cited in Seventh Annual Report of the Sanitary Commissioner (1870) of the
Government of India, Calcutta, pp 82-83, 1871
31. PALLAS PS. Bemerkungen über die Bandwürmer in Menschen und Thieren. Neue nordische
Beyträge Physikalische und Geographische Erd- und Völkerbeschriften 1: 39-112, 1781
32. PAWLOWSKI Z, SCHULTZ MG. Taeniasis and cysticercosis (Taenia saginata). Advances
in Parasitology 10: 269-343, 1972
33. PENFOLD HB. The life history of Cysticercus bovis in the tissues of the ox. Medical Journal
of Australia i: 579-583, 1937
34. PENFOLD WJ, PENFOLD HB, PHILLIPSM. Taenia saginata: its growth and propagation.
Journal of Helminthology 15; 41-48, 1937
35. PENFOLD WJ, PENFOLD HB, PHILLIPS M. Ridding pasture ofTaenia saginata ova by
grazing cattle or sheep. Journal of Helminthology 14: 135-140, 1936
36. PERRONCITO E. On the tenacity of life of the cysticercus in the flesh of oxen and on the
rapid development of the corresponding Taenia mediocanellata in the human body. The
37. RANSOM BH. The destruction of the vitality of Cysticercus bovis by freezing. Journal of
38. SIMONDS JB, COBBOLD TS. On the production of the so-called "acute cestode
tuberculosis" by the administration of proglottides of Taenia mediocanellata. Proceedings of
the Royal Society 14: 214-220, 1865
39. VALLISNERI A. Opera fisico-mediche stampate e manoscritte, raccolte da Antonio suo
figliuolo, S Coleti, Venezia, three volumes, pp 469, 1733
40. WAWRUCH AI. Practische Monographie der Bandwürmkrankheit etc., C Gerold, Wien, pp
212, 1844
41. WEISSE JF. Wieder einmal über das rohe Fleisch. Journal für Kinderkrankheiten 16:
384-385, 1851
Table 14.1. Landmarks in taeniasis saginata

__________________________________________________________________
BC Tapeworm infections in humans were known but the various species were
not distinguished. Various anthelmintics were used
1700 Andry drew an illustration of Taenia saginata although he called it
T. solium
1782 Goeze recognized two forms of Taenia but little notice was taken of this
observation
1852 Küchenmeister clearly distinguished T. saginata from T. solium on the
basis of the morphology of the head and the number of lateral branches of
the uterus
1861 Leuckart generated Cysticercus bovis in a calf fed with T. saginata
proglottids
1868-9 Oliver, in a poorly-controlled study, observed T. saginata infection in
persons who ate measly beef
1877 Perroncito infected a person with a single C. bovis and the subject began to
pass T. saginata proglottids 54 days later
1960 Niclosamide was introduced for treatment
1977 Praziquantel was introduced for treatment
___________________________________________________________________
Chapter 15
Diphyllobothrium latum AND DIPHYLLO-

BOTHRIASIS
SYNOPSIS
Common name: broad tapeworm

Major synonyms: Bothriocephalus latus, Dibothriocephalus latus, Dibothrium latum,
Taenia lata
Distribution: foci in Europe (especially Scandinavia and the Baltic countries), northern
USSR, Japan, North America, Chile, Uganda
Life cycle: The adult tapeworm, up to 10 metres in length, lives in the small intestine
with the head attached to the mucosa. Eggs and gravid segments are passed in the
faeces. When deposited in moist environments, each egg hatches and the larva
(coracidium) swims about until it is ingested by certain species of small crustaceans
(copepods). The larva develops over 2-3 weeks into a procercoid in the body cavity
of the copepod. When an infected copepod is ingested by certain species of freshwater
fishes, the procercoid is liberated in the fish's gut and migrates to the muscles where
it develops into a plerocercoid (or sparganum) up to 2 cm in length. When a
plerocercoid in raw or insufficiently cooked fish is ingested by a human, the
plerocoercoid develops into an adult worm and begins to pass eggs 4-6 weeks later
First intermediate host: certain copepods (Cyclops, Diaptomus species)
Second intermediate host: certain freshwater fish, including species of burbot, eel,
lawyer, perch, pike, ruff, salmon and trout
Major clinical features: abdominal discomfort, spontaneous passage of proglottids
Diagnosis: finding of eggs or proglottids in the faeces
Treatment: niclosamide, praziquantel
DIFFERENTIATION OF THE SPECIES FROM TAENIA SOLIUM
Although tapeworms have been known since ancient times (see chapter 13), it
was not until around the beginning of the seventeenth century that it was
realized that more than one species of tapeworm infected humans. According
to Davaine 24, it is now apparent in retrospect that two Swiss observers, first
Thaddeus Dunus in Lucarno in 1592, then Gaspard Wolphius in Zurich, des-
cribed in a recognizable fashion, the worm now known as Diphyllobothrium
latum. Dunus wrote: "De lumbrico lato (mirae longitudinis): squamosus instar
serpentis, nisi rectius geniculatus dicatur, fotus sui simillimus" 26 meaning that
the broadworm of remarkable length had the scaly appearance of a snake
397
except that the leading joints were attached and supported each other.
Nevertheless, these observers did not allude to the differences between this
worm and either of the two species of Taenia now known to infect humans. The
first person to do this, although his description is somewhat vague, was Felix
Platter (Platerus) in Basel (Switzerland) in 1602. Whereas his predecessors and
contemporaries called all tapeworms "Lumbricus latus", Platter discerned two
forms of tapeworms passed by humans. He called the first of these, Taenia
intestinorum, and this became known to later authors as Taenia prima plateri
(the first Taenia of Platter):
One is characterized by a kind of membranous skin, similar to the fabric of the small
intestine, equal to it in length but not at all empty inside as it, and about a finger's
breadth wide. This they call the Latum lumbricorum (the broad intestinal worm), but
more correctly it should be called the Taenia intestinorum (the taenia of the intestines)
since it has no likeness to the lumbricus; it is not alive, as is the lumbricus; nor is it
stirred from its place, but remains fixed for a long time until it is passed....On this
fascia there are generally transverse lines about a finger's breadth apart. They appear
along its whole length and resemble vertebrae, swelling out in the intervals between
them.63
The second form he called Taenia longissima, and this became known as
Taenia secunda plateri (the second Taenia of Platter) to later authors. It
probably refers to T. solium, but may possibly have been T. saginata:
On another occasion, very long taenia of the same type were observed. However, they
were shaped differently and appeared to be composed of many attached segments
which could be separated from one another. These segments, since gourds sometimes
bear square seeds, are called the vermis cucurbitinus. The worm is rarely passed
whole, but generally in many pieces. Previously, each of these individual pieces was
believed to have been an individual worm, called a cucurbitinus; however, they are
only pieces broken off from the fascia.63
Thus, the hallmark upon which Platter based his distinction between the two
species of worms was the shape of the proglottids. His descriptions were
incomplete and to some degree erroneous. He was unaware that tapeworms had
a head and does not appear to have realized that tapeworms were living
organisms.
In 1618, the Dutchman, Adrien van der Spiegel (Spigelius), probably without
being aware of the previous account, again reported the existence of two
distinct species of tapeworms in humans80. Nicholas Andry in 1700 also
recognized two types of tapeworms:
One has....a long Thorn full of knots running along the middle of its body upon the
upper side....The other wants this Thorn, but at every Joint upon the sides, has a sort
of small Nipple open at the Point.3
The first of these he labelled as Taenia à épine (Taenia with a spine) and the
second he called Taenia sans épine (Taenia without a spine). Perusal of his
illustrations of Taenia à épine leaves no doubt that the spine which he
described as running down the middle of the entire length of the worm is in fact
the medially-placed genital openings of the worm now called D. latum.
Diphyllobothriasis 399
Similarly, examination of his figures of Taenia sans épine clearly indicates that
the small nodules that he described at the margin of each proglottid are the
laterally-placed genital pores of T. solium or T. saginata. Thus, the key
distinguishing feature for Andry was the position of the genital apertures
(although he did not recognize them as such, considering them to be pulmonary
openings).
It is not certain who first saw the head of D. latum following the first
description of a tapeworm head by Edward Tyson in 1683. In 1750, in Geneva,
Charles Bonnet published his study of human tapeworms. In this work, he
emphasized the "stigmata umbilicialia" of the broad tapeworm and the
"stigmata lateralia" of Taenia, but he included a figure showing what
Blanchard11 later called "un être fanstastique" (a fantastic being) with the head
of a T. saginata and the body of Diphyllobothrium 12. In 1777, however,
Bonnet corrected his earlier publication and described the head of the broad
tapeworm in detail for the first time, noting its attenuated shape and the two
suctorial grooves, then went on to outline the appearance of the proglottids
("rings", as he called them)13. Shortly thereafter (1779), von Gleichen-
Rusworm likewise described the scolex of the worm31. Bremser in 1819 again
described the worm and created a new genus, renaming the worm Bothrio-
cephalus latus, to indicate that it was the broad worm with the grooved head18.
In 1841, Eschricht published the first detailed description of the anatomy of the
adult worm28. Nine years later, Diesing renamed the parasite Dibothrium
latum 25, then this was changed to Dibothriocephalus latus by Lühe in 189949.
Finally, the parasite was transferred by Lühe50 in 1910 to the genus
Diphyllobothrium erected by Cobbold in 185720. The generic name was
derived from a combination of the Greek words (DIS),
(PHYLLOS) and (BOTHROS) meaning "two", "leaf" and "groove" or
"sucker", respectively.
The origins and mode of transmission of this parasite remained obscure for
many years. Several epidemiological observations, however, pointed towards
the direction in which the solution would be found. As observers became more
confident in their ability to differentiate D. latum from other tapeworms, it
became apparent that this infection had a restricted geographical distribution.
These infections were at first unknown outside Europe and were thought to be
most common in Switzerland and adjacent areas of France, Scandinavia and the
Baltic regions. For example, in the early parts of the nineteenth century, one
quarter of the inhabitants of Geneva were said to be infected21. This indicated
to many commentators that there was something unusual about the mode of
transmission of this infection, but its nature was by no means clear.
Nevertheless, ideas abounded. As early as 1747, the Finn, Herman Spöring,

made the very perspicacious observation that people who lived on the banks of
rivers, rapids, and lakes where there was plenty of fish, suffered from the
tapeworm more commonly than did populaces living in other areas81. This idea
that consumption of fish might be important in the acquisition of tapeworm
infection received a boost with a discovery of Peter Abildgaard in Copenhagen
in 1819. Abildgaard became interested in a cestode worm that lived in the
abdominal cavity of the little fish known as the stickleback. He perceived
certain resemblances between this worm, which had no reproductive organs,
and the tapeworms that he had seen in mergansers and other fish-eating birds.
He wondered whether the worms in the fish could be an immature form of the
bird parasite so he fed some of them to domestic ducks. Abildgaard was
delighted to find later, in the ducks' intestines, tapeworms, filled with mature
eggs, which looked just like those occurring in mergansers 2.
The time was not ripe for a proper appreciation of such revolutionary
discoveries, however, nor did the confirmatory observations of Creplin22 with
Schistocephalus and Ligula receive the acceptance they deserve. More than
fifty years were to pass after Abildgaard's pioneering experiment before
Steenstrup published his theory of the "Alternation of Generations" (see
chapters 2 and 4), and thus opened up new vistas for understanding the manner
of transmission of diphyllobothriasis.
Initially, attention was paid to the ova of D. latum. These had been mentioned
by Andry in 1718 and primitive drawings had been made by Goeze in 178232.
Schubart of Utrecht hatched ova of D. latum in water and observed the
liberated embryo with its mantle of cilia. He died before he could publish the
observations in detail but notice of the finding was given, first by Kölliker in
185176, then by Schubart's friend, Verloren in 185577. Küchenmeister in 1855
described the egg as having a brittle shell with an opercular opening and
containing a limpid vesicle with six hooklets. Probably unaware of Schubart's
findings, Knoch in St. Petersburg (Leningrad), Russia (1862) 43, R Leuckart in
Germany (1863) 48 and Bertolus in France (1863) 8 all observed independently
the hatching of ova. They agreed that hatching took several weeks or months
to occur, depending upon the temperature.
Nevertheless, these observations did little to help answer the fundamental
question of the mode of transmission. Following dissemination of Steenstrup's
ideas on the alternation of generations, concepts about the transmission of
D. latum generally fell into one of two categories. Some scholars, such as
Vogt91 held that transmission was direct with a human to human cycle in which
humans ingested eggs in food contaminated with sewage. Knoch, for example,
believed that he had proved this mode of infection and adduced two pieces of
evidence to support his view. First, he attempted to infect a number of potential
intermediate hosts by introducing embryos to various aquatic animals but met
with no success. Secondly, in 1862, he administered embryonated eggs and
non-embryonated eggs to two dogs. Four months later, he found
diphyllobothria in various stages of development in one dog, then after another

six weeks, found two worms, 45 and 53 cm long, in the other animal43. In
retrospect, it is clear that these dogs had acquired natural infections, for when
similar experiments were repeated by other investigators in non-endemic areas,
particularly Leuckart in Giessen and Grassi in Italy, no worms matured.
The alternate view was that ova developed into larvae in an intermediate host
before ingestion by humans. This hypothesis was strengthened by the discovery
in the 1850's that the taeniid cestodes underwent migration and metamorphosis
in mammalian intermediate hosts. In the case of Diphyllobothrium, however,
the known association of the infection with lakes and rivers, together with the
precedents established with various trematodes (see chapter 4) suggested to
many that the intermediate hosts were likely to be aquatic animals. This notion
was amplified when Stein in 1882 drew attention to the fact that many orthodox
Jews were carriers of D. latum although they never ate raw meat and were not
infected with T. solium 82
Despite earlier suggestions that fish may be related to the acquisition of
infection, Küchenmeister writing in 1855 thought that this was unlikely, for he
was under the misapprehension that infection could only be caught by eating
fish intestines, and this was not the habit of the populace45. This idea flowed
from the Abildgaard's demonstration, referred to earlier, that some cestodes
found in the intestinal tract of fish only matured after ingestion by some
predaceous bird. Küchenmeister thought it more likely that the larvae might
live in snails which could be ingested accidentally with fruit and vegetables.
Others, however, kept returning to fishes as potential intermediate hosts.
Bertolus postulated that Ligula nodosa in salmon was the intermediate form of
D. latum 9, and Leuckart attempted, without success, to infect trout in a stream
near his home by contaminating the water with large quantities of eggs and
hatched D. latum larvae48.
DISCOVERY OF THE PLEROCERCOIDS AND THE FISH SECOND INTERMEDIATE HOST
Since attempts to infect potential hosts with larvae derived from eggs were
unsuccessful, attention turned to the other end of the life cycle. As it was known
that other species of bothriocephali could be found in animals or birds which
either primarily or exclusively ate fish, Max Braun in Dorpat (Tartu), Estonia
(present-day Estonskaya SSR, USSR), decided to look for the intermediate host
of D. latum among the fish eaten ordinarily by the people living in his region.
He therefore examined fish brought to the market in Dorpat from Lake Peipus
and surrounding regions, and soon found young bothriocephali in pike (Esox
lucius) and burbot (Lota vulgaris). More than 90% of the fish in the market
were so infected, with variable numbers of unencapsulated worms being found
in the muscles and viscera. Such worms had been seen previously by Knoch in
St. Petersburg but he had not realized what they were. In fact, plerocercoids of
Diphyllobothrium may have been seen in fish as early as 1688 by PJ Hartmann,

although, of course, he did not relate them to the broad tapeworm infecting
humans36. The worms found by Braun were between 8 and 30 mm in length and
appeared to be analogous to cysticerci and echinococci as they were sexually
immature; he called them plerocercoids 16. At first glance, they did not look
much like Diphyllobothrium for the head was usually withdrawn but Braun
wrote that if the worm: "is placed in warm water or egg white, the head unfolds
and one recognizes the suction grooves on it"16. Subsequent investigations
showed that a number of other species of fish, including perch (Perca
fluviatilis) and ruff (Acerina cernua), were also infected sometimes.
Since diphyllobothriasis was rare in dogs and was never seen in cats in
Dorpat, Braun began, in 1881, a series of feeding experiments to prove that
these plerocercoids could develop into adult D. latum. Initially, he gave
plerocercoids to three dogs then sacrificed them four, eight and eleven days
later. In their intestines, he found worms which resembled the original
plerocercoids but which grew progressively in size. After treatment with a
variety of anthelmintics, Braun infected a number of dogs and cats, sometimes
with positive results, but on other occasions he failed to find any diphyllo-
bothria. In order to be absolutely sure that the infections were not acquired
naturally in some other manner, Braun, at the suggestion of Professor E
Rosenberg, infected a dog which up to that time had only been fed with its
mother's milk:
I was able to give a three-week-old dog 17 pike bothriocephali in one day by forced
feeding....The dog, which ingested only boiled cow's milk, thrived; but because of its
continued howling, had to be killed ten days after infection. In the intestine . . I found
sexually immature bothriocephali 14-15 cm long which matched, although not
completely, corresponding initial parts of B. latus; they can only be attributed to the
infection which took place.16
Finally, Braun investigated the effects of giving plercocercoids to humans.
On 15 October 1882, he gave three or four worms obtained from pike to each
of three medical students who were not carriers of D. latum. After about three
weeks, they began to feel ill and complained of abdominal pain. On examining
the faeces on 18 November, a large number of D. latum eggs were found in the
stools of each student. A few days later, they were treated with ethereal extract
of male fern; one student expelled two specimens of mature D. latum, another
produced three parasites, while the third subject passed only fragments of
tapeworm16,17. These results were confirmed several years later by Grassi and
Ferrara34 then by Zschokke.
DISCOVERY OF THE PROCERCOIDS AND THE CRUSTACEAN FIRST INTERMEDIATE

HOST
The question still remained as to the manner in which the precursors of the
plerocercoids reached these fish. In 1883, Braun found five round holes in the
stomach of a burbot. Two of them still contained a plerocercoid of D. latum

with the head of each worm pointing away from the lumen of the stomach
towards the submucosa. The other three holes were empty but Braun found the
worms not far away in the stomach wall between the glandular and muscular
layers. This observation led him to propose that ciliated embryos of D. latum
develop into cysticerci in an as yet unknown intermediate host, then together
with this intermediate host, they reach the gut of a fish where they are freed
during the process of digestion, then penetrate the intestinal wall of the fish and
migrate into its body wall16. Although this idea was later abandoned by Braun
in favour of a direct infection of fish, the concept was seized upon by the Pole,
Constantin (Konstanty) Janicki who, while working in Lausanne, Switzerland
in the summer of 1916, made a similar observation.
Janicki had first tried to infect fish directly but had failed. Thereupon, he
invited a fellow Pole named Felix Rosen who was working in Neuchatel,
Switzerland to collaborate with him40. Since Janicki had used unstained,
formalin-fixed material, Rosen decided to repeat these experiments in a
modified form. He infected hatchlings of trout (Trutta species), salmon (Salmo
salvelinus), burbot (Lota vulgaris), perch (Perca fluviatilis) and pike (Esox
lucius) with large numbers of ciliated D. latum larvae. Rosen then examined
them carefully each day for up to three months between October 1916 and
April 1917, both directly under the dissecting microsocope and in histological
sections made from paraffin blocks and stained. The results were absolutely
negative70.
When his attempts at direct infection were unsuccessful, Janicki between
April and August 1917 examined the stomach contents of 82 Lota vulgaris,
998 Perca fluviatilis and 3 Esox lucius obtained from the market in Lausanne.
By this means he hoped to determine the nature of their food which might give
him some clue to a possible primary intermediate host then, if possible, to trace
the development of the worm from its appearance in the primary intermediate
host to the plerocercoid stage. In the stomach of Lota vulgaris, he mostly found
enormous quantities of Gammarus; 40% of the Lota were infected, mostly with
plerocercoids in the stomach. Many of the perch were infected and in their
stomachs he found mostly water fleas and copepods (small crustaceans). When
he searched the youngest perch, Janicki found tiny worms, little more than half
a millimetre long but which were clearly very young larvae of D. latum,
encapsulated within the stomach wall. Encouraged by this discovery, he began
to examine small perch systematically for even younger stages of plerocercoids.
On 25 June 1917, he found two of these worms lying free in the stomach mucus
of a tiny perch, the stomach contents of which revealed mainly the copepods,
Cyclops, Diaptomus and Bosmina. A few days later, he found another worm
in a perch which contained only Cyclops and Diaptomus in its stomach. This
led him to the conclusion that a copepod must be the primary intermediate host:
"Thanks to this evidence, I was able to formulate the idea that the primary
intermediary host must be sought among the copepodae" 38. Further

observations revealed to Janicki that, while still free in the stomach lumen,
these young worms carried a caudal appendage furnished with hooks and that
this was cast off before the parasite penetrated the mucosa38.
Meanwhile, Rosen in Neuchâtel arrived at a similar conclusion, having ap-
proached the problem from a different angle. Rosen decided that the first
intermediate host must lie within one of the following four types of food:
plankton, insect larvae; the Gammaridae, and the Oligochaetae. Plankton
seemed to him to be the least likely since Lota vulgaris, being a fish of the
deep, did not eat much plankton, whereas other plankton eating fish such as the
Coregonae were never infected. He therefore examined the latter three groups,
all with negative results. Undismayed, he began experiments with plankton on
17 June 1917. This time his efforts were to be crowned with success. He
collected plankton form Lake Neuchâtel then mixed it with large numbers of
larvae. Again, he had no luck until he turned his attention to the copepods in the
plankton. At first, all seemed hopeless, particularly when Cyclops viridis
ingested then actually digested the larvae. On 24 June, however, he found large
numbers of C. strenuus infected with one to ten oncospheres in the body cavity:
At first I did not observe anything special. The numerous fat droplets which filled the
body of these crustaceans, moreover, prevented a very detailed observation. In rapidly
draining the water from beneath the cover slip, so that the pressure of the latter
removed the little fat droplets, the examination had no more obstacles. My
astonishment was then immense. By examination of some of these fat droplets at a
higher power....I confirmed that several were nothing more than oncospheres which
were already in the body cavity. One after the other, all the specimens examined were
found infected....There was no longer any doubt that we were in the presence of the
primary intermediary host, or in any case of a species very closely related to the true
host.70
Rosen then found that Diaptomus gracilis was also infected, but to a lesser
degree. Subsequent studies revelealed that after the ciliated larvae, 0.024 mm
in diameter, was ingested by a Cyclops, it lost its embryonic envelope,
penetrated the gut wall and reached the body cavity. In that location, it grew
and became more elongated in shape. By the tenth day, it had reached 0.2 mm
in size and the structure had begun to differentiate, particularly at each
extremity. At one end, a spherical appendage containing the hooks evolved; it
became attached by a narrow neck then finally fell off when the larva was
between two and three weeks of age and 0.5-0.6 mm in length. In the mean-
time, a primordial mouth developed at the other end. This stage he called a
procercoid 70. These findings were confirmed two years later by Galli-Valerio
when he infected successfully C. strenuus with D. latum eggs obtained from
the faeces of a dog30, then Redlich showed that D. graciloides was a very
efficient intermediate host67
In order to complete the life cycle experimentally, Rosen infected six small
trout on 6 August 1917 by placing them in an aquarium containing large
numbers of copepods which had been infected for six weeks. One trout was
killed six hours later and free procercoids were found in the stomach contents,
some with and some without caudal appendages. In a fish killed the next day,
Rosen found procercoids in the stomach wall. Four days after infection, he
believed that the larvae could be considered plerocercoids and they migrated
from the gut into the muscles and viscera. Rosen concluded his paper by
writing:
The life cycle of Dibothriocephalus latus is now completed: (1) by the negative result
of the direct infection of fish by ciliated larvae; (2) by the positive result of a mode of
development in cestodes unknown until now; that is, the existence of two
intermediate hosts....The development passes from the oncosphere to the plerocercoid
by an intermediate larva,....the procercoid.70
The following year, Rosen published another paper which provided further
details. In particular, the ciliated body emerging from the D. latum egg was
called a coracidium and the plerocercoid was defined by the development of
two suckers71. Unfortunately, what had begun in friendship and teamwork
between Janicki and Rosen turned sour. In this latter paper71, Rosen, because
he had carried out the last decisive experiment, tried to take the whole credit for
himself and launched a violent diatribe against Janicki. An unpleasant
controversy between the two followed, with Janicki replying to Rosen's attack39.
Von Bonsdorff has portrayed succinctly their subsequent paths: "Janicki, who
was an eminent parasitologist, became professor of zoology at Warszawa;
Rosen made no further scientific career"14.
Felix Platter was remarkably accurate in his summation of the clinical features
of this infection when he wrote in 1609:
While taeniae remain in the body, unless something else happens, few serious
symptoms occur from which it can be perceived that an individual carries this foulness
in his body before they pass unexpectedly, at which time they occasion great fright on
being found. There is a pressing desire to rake food much more often than was
customary and a certain heaviness in the stomach. If anything is in the stomach, it is
felt. The symptoms become worse when an intestinal worm dies or if a segment is
broken off from the others and putrefies.63
With the passage of time, however, all manner of ills were ascribed to this
worm. Thus, Abbotts Smith in 1863 wrote that anal itching, an itchy nose,
swollen abdomen, nausea, vertigo, palpitations during the night, fainting and
epigastric pain could all be caused by D. latum 1.
The clinical manifestations were put on a more certain basis when humans
were infected experimentally. The medical students infected by Braun17
developed malaise and abdominal pain three weeks after ingestion of plero-
cercoids. Le Bas has described in detail the clinical features in three humans
infected experimentally, and concluded that the effects were little more than
discomforting with transient diarrhoea at the onset of patent infection after two
to three weeks, followed by vague dyspeptic symptoms46. The most usual

symptom was of patients complaining of passing segments of worms inter-
mittently. Even more valuable than this study was a comparison of symptoms
between infected and non-infected persons living in an endemic area. Statistical
analysis revealed increased frequencies of a sensation of hunger, diarrhoea,
fatigue, numbness of the extremities and a craving for salt in infected persons74.
In endemic areas, the majority of patients had small numbers of relatively
short tapeworms. Some patients, however, had very large tapeworms or
incredible numbers of them. One Russian woman living in the USA passed a
single worm 8.7 metres in length after treatment78. In Switzerland, a 21 year old
woman passed at least 90 adult worms after therapy. The worms passed out in
a bundle, the patient assisting at the delivery by tearing at the mass with both
hands while at the same time shrieking like a woman in labour; the agonizing
delivery lasted ten minutes and the parasites filled up half a chamber pot72.
Even more heavily infected was a 66 year old man who passed 106 tapeworms
weighing 400 grams33. Perhaps the record in terms of total length, though, was
set by the Russian man who passed 14 worms totalling 83 metres in length62.
The duration of D. latum infections was at one time put at 20 years or more.
This was based largely upon the finding of infected patients in North America
many years after emigration, but before it was realized that diphyllobothriasis
is endemic in parts of that continent. There is no doubt that infection may last
as long as six years. One of three volunteers infected by Le Bas in 1922 was RT
Leiper, professor of helminthology in London. Whereas the other two subjects
were cured completely by carbon tetrachloride administration soon after
infection, Leiper passed less tapeworm heads than the number of plerocercoids
he ingested. Nevertheless, he was well for the next few years and did not notice
any proglottids in his stools. While in Cairo in 1928, however, he had an acute
attack of dysentery and on examination of his stools, was astonished to find vast
numbers of D. latum ova. He continued to observe the passage of these eggs
in his stools for the next ten months until termination of the infection with
anthelmintics. Leiper believed that this was a persistent infection as he had had
no opportunity for acquiring a natural infection during the interval47.
These observations suggest that little immunity to challenge infection
develops, and this concept has been supported by a number of other invest-
igations. In one such study, 125 of the 143 inhabitants of a village in Karelia,
USSR, were found to be infected with D. latum, most of the uninfected persons
being young children. Sixty of the infected people were treated with
anthelmintics - three years later, 20 were reinfected whilst 40 were not; this
was interpreted as evidence for the development of partial immunity86, but
many other factors, such as changes in eating and cooking habits, could have
accounted for this result. Tarassov, who had carried out this study, infected
himself in 1932, treated himself, then challenged himself with six plerocercoids
3.5 months after the original infection; a patent infection developed and
treatment five weeks after challenge produced two heads and 6.3 metres of
worm. Similar challenges one and two years later failed to produce patent
infections. In 1936, four years after the original infection, he again infected
himself with six plerocercoids and patent infection occurred; anthelmintic
therapy seven weeks later resulted in four heads and 26 metres of tapeworm.
Finally, Tarassov infected himself with seven more plerocercoids; he began to
pass eggs in his faeces 14 days later. While harbouring the worms, he had
much abdominal pain, lost 8 kg in weight, and weakness forced him into a
sanatorium. Five weeks after infection, he treated himself and expelled 38
metres of tapeworm with seven heads86. While these results could be inter-
preted as indicating transient immunity one and two years after the initial
infection, it is far more likely that those challenges were made with
non-infective plerocercoids. Certainly, there was no significant immunity
several months and several years after the first exposure to D. latum, and this
is probably the normal state of affairs.
CORRELATION OF PERNICIOUS ANAEMIA WITH D. LATUM INFECTION
In July 1877, Gustav Reyher in Dorpat (Tartu), Estonia (USSR), saw a 66 year
old woman who became steadily weaker and paler during the course of a year.
He diagnosed her as suffering from pernicious anaemia, a disease which had
been defined by Biermer in 1872. She also complained of intermittent
diarrhoea and on one such occasion had passed a segment of D. latum. Reyher
therefore treated her with extract of filix mas and was surprised to find that not
only was the worm expelled, but that within a few weeks, her general health
had returned to normal. Six months later, Reyher encountered a similar
situation in a 30 year old man; treatment resulted in an equally striking cure.
Rehyer then began to collect a series of such cases and by 1884 had seen 12
patients. In late 1883, he began to examine the wet blood films and found that
although the numbers of red cells were reduced markedly, they were often
larger than normal, and he also noted that the white cells were often reduced in
number. The results of this serendipitous bedside observation, which was
skilfully followed up, were finally published in June 188668
Independently of Reyher, JW Runeberg in Helsingfors (Helsinki), Finland
had been following a similar line. In 1883, he had seen a number of cases of
pernicious anaemia, all with a fatal outcome, and had been struck by the fact
that the majority of patients had D. latum in their intestines. Thereafter, the
faeces of patients who were seen in his clinic were examined systematically for
D. latum eggs and, if they were found, an anthelmintic was given. In September
1886, he reported his experiences at a Congress in Berlin; 12 of 19 patients
with pernicious anaemia were also infected with D. latum and all of these
persons were cured by expulsion of the worm73. Nevertheless, the Congress
received his communication with reserve.
It seems probable, however, that in addition to these two investigators, the
idea of a causal relationship between broad tapeworm infection and pernicious

anaemia arose simultaneously in the minds of a number of other investigators,
including Hoffman, professor of medicine in Dorpat, and Albrecht, a path-
ologist in St. Petersburg. According to Wiltschur (1893) (cited in14), Albrecht
used to indicate in his reports, even before 1883, whether D. latum was found
in the intestines of patients dying from pernicious anaemia. However, he never
published his observations. In retrospect, it seems that Reyher ought to be
accorded the greatest credit for the discovery, followed closely by Runeberg.
The contention that some cases of pernicious anaemia were dependent upon
the presence of diphyllobothria in the intestines was supported strongly by
some authorities but disputed hotly by others who claimed that the association
was a mere coincidence. Nevertheless, it gradually became apparent that a
small proportion of infected persons did become anaemic. This anaemia was
not the type recognized in iron deficiency, and in contrast to the anaemia seen
in hookworm infection, the erythrocytes were enlarged and there was a mild
leucopenia with the white cells being hypersegmented. This anaemia could not
be differentiated clinically or haematologically from idiopathic Addisonian
pernicious anaemia, but in many patients, the anaemia resolved after elim-
ination of the tapeworms, thus confirming an aetiological relationship.
The prognosis for the vast majority of patients was good, but in the small
number of persons with severe tapeworm anaemia, the outcome in the early
years of treatment depended upon elimination of the parasites. For example, a
13 year old boy who presented in 1887 with a severe anaemia, the haemoglobin
concentration being only one sixth of normal, made a rapid recovery after
anthelmintic administration produced the passage of a large quantity of D.
latum segments75. In some instances, patients were deemed to be so ill that they
were subjected to blood transfusion (with all its attendant complications in
those days), prior to anthelmintic treatment. The demonstration of the efficacy
of liver (which contains vitamin B12) then the preparation of pure vitamin B12
for injection, and the development of safe blood transfusion procedures has
revolutionized management of such patients. Finally, the discovery of effective
anthelmintics has ensured a favourable outlook for patients with this infection.
INVESTIGATIONS OF THE PATHOGENESIS OF TAPEWORM

PERNICIOUS ANAEMIA
The recognition of anaemia in association with diphyllobothriasis led to

attempts to both delineate the nature of the anaemia and to define the
mechanisms by which it was produced. The anaemia was clearly quite different
to that seen in hookworm disease where the red cells were small (microcytic)
and depleted in haemoglobin (hypochromic) and the body stores of iron were
greatly reduced. In tapeworm anaemia in contrast, the red cells were large
(macrocytic), the white cells were slightly reduced in number and their nuclei
were hypersegmented, and the iron stores were normal. The similarities
between this anaemia and idiopathic pernicious anaemia were striking, but it
must be remembered that, at that time, the genesis of idiopathic pernicious
anaemia itself was unknown. A number of theories were proposed, including
the production of toxins by worms and allergic reactions, but these did not
stand the test of time, even though the allergic theory was held tenaciously for
many years by Tötterman87. Understanding of the nature of tapeworm anaemia
followed, step by step, elucidation of the pathogenesis of idiopathic pernicious
anaemia.
In 1926, Minot and Murphy showed that patients with idiopathic pernicious
anaemia could be restored to health by eating half a pound of raw liver daily.
Thereupon, Isaacs and co-workers tried this treatment in tapeworm anaemia
and found that the anaemia resolved, even though the parasite persisted 37.
Further studies of patients with idiopathic pernicious anaemia indicated that the
anaemia was a consequence of a deficiency of an extrinsic factor, a high
concentration of which occurred in the liver. It was then discovered in 1929 by
Castle and his colleagues that the production of an intrinsic factor in the
stomach was requisite for absorption of the extrinsic factor; the intrinsic factor
was secreted into the gut, combined with the extrinsic factor in the diet, then the
complex was absorbed in the terminal ileum. In 1948, vitamin B12 was
discovered and found to be identical with extrinsic factor. In that same year,
von Bonsdorff suggested that tapeworms interfered with the interaction
between extrinsic factor and intrinsic factor. He then found, using a biological
assay, that tapeworms competed with the host for dietary vitamin B12 and
accumulated large quantities of the vitamin within their substance 15. This
observation was then confirmed using radiolabelled vitamin B12. Indeed, there
was a transient fashion for treating patients with idiopathic pernicious anaemia
by parenteral administration of an extract of dried fish tapeworm, as this
contained a high concentration of vitamin B12 (some fifty times that seen in T.
saginata). Later laboratory studies showed that the parasite was able to take up
both free vitamin B12 as well as that bound to intrinsic factor (reviewed in14).
It was recognized that only a small proportion of infected persons became
anaemic. Thus, in Finland, a mere 0.1-0.5% of infected persons were anaemic.
Furthermore, the intensity of infection did not necessarily correlate with

severity of anaemia. For example, the woman with 90 tapeworms cited earlier
was not anaemic, having a haemoglobin level of 95% on the old Sahli scale,
whereas the man with 106 worms was grossly anaemic with a haemoglobin
concentration of 25%. In 1932, Birkeland reviewed the literature and suggested
that there may be a racial and familial predisposition to the development of
anaemia, for this complication was seen more commonly in Finns than in
persons of other nationalities 10.
In 1956, Nyberg and Östling confirmed that vitamin B12 levels were low in
the serum of persons with tapeworm pernicious anaemia61. This was followed
by the demonstration that absorption of radiolabelled vitamin B12 (Schilling
test) from the bowel was impaired in both patients with tapeworm pernicious
anaemia and in the majority of tapeworm carriers who had normal haemoglobin
levels59,60. Thus, it became apparent that a number of other factors were
necessary to precipitate anaemia in the small proportion of infected persons
who became anaemic. These included a low dietary intake of vitamin B12, the
location of the worms in the gut (von Bonsdorff has proferred some evidence
to suggest that anaemia is more common in people in whom tapeworms are
sited in the jejunum rather than lower down in the bowel), and finally, the
coincidental presence of atrophic gastritis with a consequent reduction in the
production of intrinsic factor5.
The diagnosis of infection with D. latum was obvious if patients passed pro-
glottids and brought them along for identification. With the discovery that
helminth eggs are passed in the faeces, it became possible to diagnose infection
by microscopical examination of the stools. It is uncertain who first applied this
to diphyllobothriasis, but Davaine in his textbook of 1860 provided an
illustration of the appearances of such eggs in the faeces23. When the
association between D. latum infection and pernicious anaemia was
appreciated later that century, physicians in endemic areas realized that it was
necessary to exclude diphyllobothriasis in patients with this form of anaemia.
The anthelmintic therapy of diphyllobothriasis has been similar to that of the

other major tapeworm infections of humans (see chapter 13). Küchenmeister
in his textbook of 1855 regarded diphyllobothriasis as the most easily treated
of the tapeworm infections and considered that filix mas and pomegranate root
were the most satisfactory medicaments45. A large number of anthelmintics with
variable efficacy and toxicity followed, including thymol, carbon tetrachloride,

areca nut, dichlorophen, mepacrine and a preparation of the Finnish broad
buckler fern. In the 1960's, niclosamide was introduced and was shown to cure
about 70-80% of patients66,79. In 1977, praziquantel was used in
diphyllobothriasis 6,19, and subsequent experience has shown that almost all
patients are cured with this drug.
Investigators of diphyllobothriasis realized that the infection was endemic in

areas where people were in the habit of eating improperly cooked fish and
where there were inadequate facilities for the disposal of waste products.
Although many animals have been found infected in nature, or have been
infected experimentally, most workers came to the conclusion that humans
were the most important reservoirs of infection. Considerable efforts were then
expended on locating endemic areas and on identifying the primary and
secondary intermediate hosts in those areas (reviewed in14).
It has now been shown that Diphyllobothrium infections have been present
in Europe for many hundreds of years. In 1944, Szidat reported that the
characteristic eggs were seen in the intestinal contents of a cadaver which had
been recovered from a peat bog in East Prussia; the body was thought to have
been buried about 500 AD84. More recently, D. latum eggs were found in
faeces at a location near Bremerhaven (Feddersen Wiere), where excavations
brought to light remains dated between 100 BC and 500 AD41. At the time
Cobbold wrote his textbook in 1864, diphyllobothriasis had never been found
outside of Europe21. In the latter part of the nineteenth century, however,
sporadic cases of infection were noted in patients in North America, partic-
ularly around the Great Lakes. Since all of these people were immigrants, it
was believed at first that these infections were merely caused by long-lived
tapeworms acquired before emigration. This idea became less tenable when in
1901 a case of native infection was reported in a French Canadian who had
never been outside of Canada and rarely outside the province of Quebec35. Five
years later, Nickerson reported D. latum infection in a three year old boy who
was born in Minnesota of Finnish parents, and who had never left the country57.
Since freshwater fish were not imported into the United States from Finland,
it was concluded that the infection must have been acquired locally. In support
of this view, larvae of D. latum were found in a number of fish caught in the
Great Lakes. As more such cases were reported, it passed beyond doubt that
broad tapeworm infection had been introduced and become endemic in North
America. Stiles predicted in 1907 that this would happen in upper Michigan
since its population contained immigrants who not only brought their tape-
worms with them, but retained their Baltic habit of eating uncooked fish, either
fresh, dried, smoked or cured. In fact, however, the majority of infections
occurred in female Jews who were in the habit of tasting raw fish to test their
skill in flavouring it.
A number of studies were consequently undertaken to determine the primary
and secondary intermediate host of infection in this region. Procercoids were
shown to develop in D. oregonensis 29, D. silicis and D. silicoides53 , while
plerocercoids were found in Stizostedeon canadense-griseum, S. vitreum, Esox
lucius and Lota maculosa 88. Moreover, it was found that heavy infections in
fish occurred in some lakes near which there was a very sparse human
population. Since it was known that carnivores, including dogs, foxes, otters,
bears and cats can harbour adult D. latum, the high frequency of dogs in the
area suggested that these animals may be an important reservoir of infection.
On the other hand, eggs from dog faeces were much less likely to hatch active
coracidia (1.5%) c.f. ova in human faeces (80%)53. The relative contributions
of the various definitive hosts remains obscure, however, as their inputs have
not been subjected to precise mathematical analysis. In any case, investigations
in the USSR subsequently showed that eggs from dogs developed almost as
frequently as eggs from humans, albeit more slowly85.
Continued observations revealed that infection was not only endemic in fish
in Lake Superior and its surrounds, but also in lakes which drained through
Lake Winnipeg into Hudson Bay53. Eventually, endemic foci of infection were
found in Eskimos in northwest Canada and in Alaska. Similarly, the parasite
was introduced into Chile and became established in the Andean Lake District
some 800 kilometres south of Santiago, with Salmo lacustris and S. irideus
proving to be secondary intermediate hosts56.
In 1947, Stoll estimated that there were just over 10 million people infected
with D. latum, about one quarter of them in Europe and most of the rest in the
USSR with small foci in North America, South America and Japan83. Within
the Soviet Union, the broad tapeworm had been first reported by Pallas in St.
Petersburg (Leningrad) in 1781. Subsequent surveys indicated that the
prevalence of infection in Leningrad before the Second World War was
somewhere between 5 and 10% of the population. This region was at first
regarded as the centre of infection, but it became apparent that the worm was
widespread within the USSR, including Siberia62. Very high rates of infection
were found in the Baltic region, for example, around 70% of the population of
the western shore of Lake Peipus in Estonia were infected in 1926. Similarly,
in Finland,which had long been one of the best known zones of endemic
diphyllobothriasis, frequencies varying between 0 and 100% were found in
different parts of the country; parasitism was most frequent in the
Finno-Ungarian linguistic group, probably as a result of their dietary customs10.
In some areas, industrialization altered the ecology and favoured the spread
of infection. Increased intensities of infection sometimes occurred around new
reservoirs in regions where D. latum was infrequent previously, such as on the
Volga River in the USSR69. Similarly, construction of the Moscow Canal
allowed the development of permanent new foci of infection. On the other hand,
construction of water power plants sometimes had a helpful effect. Thus, in

Japan the installation of dams prevented the second intermediate host,
Onchorhynchus species, from migrating and spawning27.
Although D. latum infections have spread in some locations such as in North

America, they have regressed in other regions. At one time, it was said that: "no
good citizen of Geneva was without his tapeworm"4 but by the end of the nine-
teenth century, the infection had become rare in that city. The reasons for this
welcome disappearance of the parasite are by no means clear4.
What is clear is that infection could have been prevented by thorough
cooking of fish. Habit and custom, however, have militated against this
hygienic practice in many places. Apart from health education, a number of
other ways have been mooted to impede the spread of infection. Some of these
were quite impractical, such as a proposal to ban the importation of Canadian
fish into the USA89. More important was the demonstration that freezing fish
for 48 hours at -10oC killed plerocercoids 53. Not only was this of value in the
domestic environment, but it provided a tool which could be exploited
commercially. The two other major weapons which could be used in some
situations were improvements in sewage disposal systems and the mass
administration of anthelmintics. Some doubts surrounded the value of these
measures, though, in places where a significant animal reservoir of infection
was thought to be present, whether it be wild feral animals or domesticated
dogs and pigs85.
Thus, Magath in 1933 included among his recommendations for the control
of infection in North America, treatment of sewage with a killing solution such
as formaldehyde or chlorine before discharge into lakes or streams, education
of people to cook fish properly, freezing of fish in commercial houses, reporting
of all human cases to a central register, examination of the stools of all Baltic
immigrants, undertaking a campaign to discourage feeding of raw fish to dogs,
and further surveys of the extent of infection52. Needless to say, these
recommendations were not put into practice in any organized way.
Nevertheless, diphyllobothriasis does not now seem to be of major importance
in that region.
The same cannot always be said for diphyllobothriasis in more recent times
in parts of Europe and Asia. When Petrushewsky and Tarassow described their
field investigations in Soviet Karelia in 1931-32, they recommended the
following measures: investigation of infection in copepods and fish, studies of
the dietary habits of the population, mass examination of the people for
tapeworm eggs in faeces, organized treatment campaigns, destruction of
expelled parasites, improved sanitation, health education, and periodical review
of the results62. Using these principles, an energetic campaign has been carried
out in the USSR ever since World War II and about 65 million people are
examined annually. The results have been gratifying in some places but
discouraging in others, particularly in the Volga river region64.
In Finland, the attitude was passive for many years, particularly because
people cherished the idea that an absence of the worm was a sign of poor
health. In 1949, however, a pamphlet was published by a hygienist named
Savonen who pointed out that the abundance of D. latum blemished the repute
of Finnish public health. In the next few years, educational campaings were
begun and registration of new cases was made compulsory in 1955. In 1963,
the State Medical Board issued instructions that educational campaigns should
be expanded. The result was that the number of cases registered dropped from
nearly 34,000 in 1959 to just under 3,000 in 197514.
OTHER SPECIES OF DIPHYLLOBOTHRIUM
D. PACIFICUM
The adult tapeworm, which is normally a parasite of fur seals, was first
described by Nybelin in 193158, then renamed D. pacificum by Margolis in
195654. All the cases of human infection with this parasite have been reported
from the western border of South America (Peru and Chile) and from Japan,
the first ones being described by Baer and colleagues in 19677. The infection
was acquired by eating undercooked saltwater fish. The clinical features were
similar to those seen in diphyllobothriasis latum and the condition was found
to respond to treatment with praziquantel 51.
D. URSI
This parasite was described in the brown bear (Ursus arctos) in Alaska by
Rausch in 1954. It has been described in a human recently55.
OTHER SPECIES
D. dendriticum, D. lanceolatum and D. dalliae have been found very rarely in

humans65.
REFERENCES
1. ABBOTTS SMITH M. On human entozoa: comprising the description of the different species
of worms found in the intestines and other parts of the human body and the pathology and
treatment of the various affections produced by their presence, HK Lewis, London, pp 245,
1863
2. ABILDGAARD PC. Almindelige Betragntninger over Indvoldeorme, Bemaerkninger ved
Hundsteilens Baendelorm, og Beskrivelse med Figurer of nogle nue Baendelorme. Skrivter

af Naturhistorie-Gelskabet, Kjøbenhavn 1: 26-64, 1790. German translation in Shriften der
Naturforschen der Gesellschaft, Köpenhagen 1: 24-59, 1793. Partly translated in 42.
3. ANDRY de BOISREGARD N. De la génération des vers dans le corps de l'homme etc.,
Laurent d'Houry, Paris, pp 468, 1700. An account of the breeding of worms in human bodies
etc., translated by H Rhodes and A Bell, London, pp 266, 1701
4. ANONYMOUS. The spread of Bothriocephalus latus. British Medical Journal ii: 809-810,
1891
5. ANONYMOUS. Pathogenesis of tapeworm anaemia. British Medical Journal ii: 1028, 1976
6. APAJALAHTI J. Tratamiento de infecciones por Diphyllobothrium latum con una dosis oral
unica de praziquantel. Boletin Chileno de Parasitologia 32: 43, 1977
7. BAER JG, MIRANDA CH, FERNANDEZ RW, MEDINA TJ. Human diphyllobothriasis in
Peru. Zeitschrift für Parasitenkunde 28: 277-289, 1967
8. BERTOLUS. Sur la développementdu bothriocéphale de l'homme. Comptes Rendus Hebdom-
adaires des Séances de l'Académie des Sciences 57: 569-571, 1863
9. BERTOLUS. Cited in 48
10. BIRKELAND IW. "Bothriocephhalus anaemia". Diphyllobothrium latum and pernicious
anemia. Medicine, Baltimore 11: 1-139, 1932
1691, 1885-1890
12. BONNET C. Sur le ver nommé en Latin Taenia et en français Solitaire. Mémoires de Math-
ématique et de Physique présentés à l'Académie Royale des Sciences, par divers sçavans, &
lus dans les assemblées, Paris, 1: 478-521, 1750. Partly reproduced in 42.
13. BONNET C. Nouvelles recherches sur la structure du taenia. Observations sur la physique
sur l'histoire naturelle et sur les arts, IX, L'Abbé Rozier, Paris, pp 243-267, 1777. Partly
translated in 42
14. von BONSDORFF G. Diphyllobothriasis in man, Academic Press, London, pp 189, 1977
15. von BONSDORFF G, GORDIN R. Antianemic activity of dried fish tapeworm. Acta Medica
Scandinavica, Supplement 266: 283-292, 1952
16. BRAUN M. Zur Frage des Zwischenwirthes von Bothriocephalus latus Brems. Zoologischer
Anzeiger 4: 593-597, 1881; 5: 39-43, 1882; 5: 194-196, 1882; 6: 97-99, 1883. Partly
translated in 42
17. BRAUN M. Bothriocephalus latus und seine Herkunft. Archiv für pathologische Anatomie
und Physiologie und fur klinische Medicin (Virchow) 92: 364-366, 1883
über Pseudo-Helminthen, Carl Schaumburg und Comp., Wien, pp 284, 1819
19. BYLUND G, BANG B, WIKGREN K. Tests with a new compound (praziquantel) against
Diphyllobothrium latum. Journal of Helminthology 51: 115-119, 1977
20. COBBOLD TS. Observations on entozoa, with notices of several new species, including an
account of two experiments in regard to the breeding of Taenia serrata and T. cucumerina.
Transactions of the Linnean Society of London 22: 155-172, 1857
22. CREPLIN FC. Novae observationes de entozois, Berolini, pp 134, 1829
domestiques, second edition, J-B Baillière et fils, Paris, pp 1003, 1877
25. DIESING CM. Systema helminthum, Wilhelmum Braumüller, Vindobonae, two volumes, pp
1267, 1849-1851
26. DUNUS T. De lumbrico lato (mirae longitudinis) Thaddei Duni Locarnensis medici epistolae
medicinales....Miscellaneorum de re medica liber, Tiguri, p 155, 1592
27. EGUCHI S. Diphyllobothrium latum (Linnaeus, 1758). Progress of medical parasitology in
Japan, volume 5, Meguro Parasitological Museum, Tokyo, pp 125-144, 1973
28. ESCHRICHT DF. Anatomische-physiologische Untersuchungen ueber die Bothryocephalen.
Nova Acta Leopoldino-Carolinae Academiae (Breslau) 119, Suppl. 2: 3-152, 1841

29. ESSEX HE. Early development of Diphyllobothrium latum in northern Minnesota. Journal
30. GALLI-VALERIO B. Untersuchungen ueber den Entwicklungszyklus von
Dibothriocephalus latus L. des Hundes. Archiv für Schiffs- und Tropen-Hygiene 23:
602-605, 1919
31. von GLEICHEN-RUSWORM WF. Zergliederung und microscopishe Beobachtungen eines
Bandwurmes, Taenia lata L. und eines Kürbiswurmes, Cucurbitinus. Beschäftigungen der
Berlinischen Gesellschaft naturforschender Freunde 4: 203-224, 1779
33. GRANT F. 106 Bothriocephalusketten bei einem Kranken. Klinische Wochenschrift 9: 502,
1930
34. GRASSI B, FERRARA. Zur Bothriocephalusfrage. Deutsche medicinische Wochenschrift 12:
699, 1886
35. HAMILTON WF. A specimen of Bothriocephalus latus. Montreal Medical Journal 30:
350-351, 1901
36. HARTMANNUSPJ. Anatome glandiorum. Miscellanea Curiosa, sive Ephemeridum Medico-
Physicarum Germanicarum Academiae Imperialis Leopoldinae Naturae Curiosorum.
Decuriae II. Annus VII, Anni 1688, Observatio XXIX, PP 58-59, 1689
37. ISAACS R, STURGIS CC, SMITH M. Tapeworm anemia. Therapeutic observations.
Archives of Internal Medicine 42: 313-321, 1928
38. JANICKI C. Observations sur quelques espèces de poissons afin d'arriver à connaître plus à
fond le contenu de leur estomac et pour trouver des stades encore inconnus de plerocercoide.
Bulletin de la Société Neuchâteloise des Sciences Naturelles 42: 22-29, 1917. Partly translated
in 42
39. JANICKI C. Der Entwicklungscyklus von Dibothriocephalus latus L. offene Antwort an
meinem früheren Mitarbeiter Herrn Dr. F. Rosen. Zugleich ein Beitrag zur Methodologie eines
helminthologischen Problems, Imprimerie Georges Jeanrichard, Sainte-Croix, pp 33, 1919.
40. JANICKI C, ROSEN F. Le cycle évolutif du Bothriocephalus latus L. Bulletin de la Société
Neuchâteloise des Sciences Naturelles 42: 19-21, 1917. Partly translated in 42
41. JANSEN S, OVER HJ. Het voorkomen van parasitien in terpmateriaal uit noordwest
Duitsland. Tijdschrift voor Diergeneeskunde 87: 1377-1378, 1962
43. KNOCH J. Vorläufige Mittheilung über den Bothriocephalus latus, die Entwickelung
desselben, die Wanderung und endliche Uebertragung seines Embryo's in den Menschen.
Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 24:
453-461, 1862
44. KÖLLIKER. Zeitschrift für wissenschaftliche Zoologie 3: 86, 1851
46. LE BAS GZ. Experimental studies on Dibothriocephalus latus in Man. Journal of
47. LEIPER RT. Some experiments and observations on the longevity of Diphyllobothrium
infections. Journal of Helminthology 14: 127-130, 1936
48. LEUCKART R. Die menschlichen Parasiten und die von ihnen herrührenden Krankheiten. Ein
Hand- und Lehrbuch für Naturforscher und Aertze, C F Winter'sche Verlagshandlung, Leipzig,
volume 1, pp 766, 1863
49. LÜHE M. Zur Anatomie und Systematik der Bothriocephaliden. Verhandlungen der
Deutschen Zoologische Gesellschaft 9: 30-55, 1899
50. LÜHE M. Die SüsswasserfaunaDeutschland, Heft 18, II. Parasitische Plattwurmer. Cestodes,
Jena, pp 153, 1910

51. LUMBRERAS H, TERASHIMA A, ALVAREZ H, TELLO R, GUERRA H. Single dose
treatment with praziquantel (Cesol R, Embay 8440) of human cestodiasis caused by
Diphyllobothrium pacificum. Tropenmedizin und Parasitologie 33: 5-7, 1982
52. MAGATH TB. The relation of Diphyllobothrium latum infestation to the public health.
53. MAGATH TB, ESSEX HE. Concerning the distribution of Diphyllobothrium latum in North
America. Journal of Preventive Medicine 5: 227-242, 1931
54. MARGOLIS L. Parasitic helminths and arthropods from Pinnepeda of the Canadian Pacific
coast. Journal of the Fisheries Research Board of Canada 13: 489-505, 1956
55. MARGOLIS L, RAUSCH RL, ROBERTSON E. Diphyllobothrium ursi from man in British
Columbia - first report of this tapeworm in Canada. Canadian Journal of Public Health 64:
588589, 1973
56. NEGHME A, DONCKASTER R, SILVA R. Diphyllobothrium latum en Chile, primer caso
autoctono en el hombre. Revista Médicade Chile 78: 410-411, 1950
57. NICKERSON SD. The broad tapeworm in Minnesota with the report of an infection acquired
in the state. Journal of the American Medical Association 46: 711-713, 1906
58. NYBELIN O. Säugetier- und Vogelcestoden von Juan Fernandez. The natural history of Juan
Fernandez and Easter Islands 3: 493-523, 1931
59. NYBERG W. The influence of Diphyllobothrium latum on the vitamin B12-intrinsic factor
complex. I. In vivo studies with the Schilling test technique. Acta Medica Scandinavica 167:
185187, 1960
60. NYBERG W. The influence of Diphyllobothrium latum on the vitamin B12-intrinsic
factor complex. II. In vitro studies. Acta Medica Scandinavica 167: 189-192, 1960
61. NYBERG W, ÖSTLING G. Low vitamin B12 concentrations in serum in fish tapeworm
anaemia. Nature 178: 934-935, 1956
62. PETRUSCHEWSKY GK, TARASSOW W. Die Bekämpfung des Diphyllobothrium latum
in Karelien. Archiv für Schiffs- und Tropen-Hygiene 37: 307-315, 1933
63. PLATERUS F. Praxeos seu de cognoscendis, praedicendis praecauendis curandiso affectibus
homini incommodantibus tractatus tertius et ultimus. De vitiis, libris duobus agens: quorum.
Primus corpis: secundus. Excretorum via continet, Typis Conradi Waldkirchii, Basel, pp 679,
1602; second edition, three volumes, 609, partly translated in 42. A golden practice of
physick, translated by A Cole and N Culpepper, P Cole, London, 1662
64. PROPOPENKO LI. In, "Diphyllobothriasis symposium", Moscow, pp 3-6, 1968. Cited in 14
65. RAUSCH RL, HILLIARD DK. Studies on the helminth fauna of Alaska. XLIV. The
occurrence of Diphyllobothrium latum (Linnaeus, 1758)(Cestoda: Diphyllobothriidae) in
Alaska, with notes on other species. Canadian Journal of Zoology 48: 1201-1219, 1970
66. RAZUMOVA EP, OCHKUROVA EF, LAPSHINA IG, GUSEVA MK (Effectiveness of
treatment of diphyllobothriasis with dichlosale and phenasale.) Meditsinskaya Parazitologia
i Parazitarn e Bolezni 36: 159-161, 1967. In Russian. Abstracted in Tropical Diseases
Bulletin 64: 993, 1967
67. REDLICH E. Diaptomus graciloides (Lilljeborg), ein neuer erster Zwischenwirt von
Dibothriocephalus latus, nebst Bemerkungen zur experimentellen Entwicklung des
Procercoids dieses Cestoden. Archiv für Wissenschaft und praktische Tierheilkunde 53:
353-361, 1925
68. REYHER G. Beiträge zur Aetiologie und Heilbarkeit der perniciosen Anamie. Deutsches
Archiv für klinische Medicin 39: 31-69, 1886
69. ROMANOV IV. In, "Diphyllobothriasis symposium", Moscow, pp 58-63, 1968. Cited in 14
70. ROSEN F. Recherches expérimentales sur le cycle évolutif du Dibothriocephalus latus.
Bulletin de la Société Neuchâteloise des Sciences Naturelles 42: 29-49, 1917. Partly translated
in 42
71. ROSEN F. Recherches sur le développement des Cestodes. I. Le cycle évolutif des Bothrio-
céphales. Etudes sur l'origine des cestodes et leurs états larvaires. Bulletin de la Société
Neuchâteloise des Sciences Naturelles 43: 1-55, 1918
72. ROUX. Evacuation de quatre-vingt-dix bothriocéphales ou une seule fois.
Correspondenz-Blatt für schweizer Aertze 17: 488-491, 1887. Abstracted in British Medical
Journal ii: 911, 1887

73. RUNEBERG JW. Bothriocephalus latus und perniciöse Anämie. Deutsches Archiv für
klinische Medicin 41: 304-308, 1887
74. SAARNI M, NYBERG W, GRASBECK R, von BONSDORFF B. Symptoms in carriers of
Diphyllobothrium latum and in uninfected controls. Acta Medica Scandinavica 173: 147-154,
1963
75. SCHAPIRO HA. (Cure of pernicious Biermer's anaemia by expulsion of Bothriocephalus
latus.) Vrach 8: 95-96, 1887. In Russian. Abstracted in Lancet ii: 724, 1887
76. SCHUBART. Cited in 44
77. SCHUBART. Cited in 90
78. SINGER JJ. A case of Bothriocephalus latus infection. Journal of the American Medical
Association 66: 1618-1619, 1916
79. SOININEN V. Leveän heisimadon esiintyminen ja joukkohääto Puumalassa. Suomen
Lääkarilehti 18: 2359-2361, 1963
80. SPIGELIUS A. De lumbrico lato liber (cum ejusdem lumbrici icone et notis), L Pasquati,
Patavii, pp 88, 1618
81. SPÖRING HD. Beråttelse om en Qvinna, hos hvilken et stycke af Binnike Masken kommit
utur en bålde i liumskan. Bihand till Kongliga Svenska Vetenscaps-Adakemiens Handlingar,
Stockholm, 8: 103-112, 1747
82. STEIN ST. Die parasitaren Krankheiten des Menschen. Part 1, Lahr, pp 52, 1882
83. STOLL NR. This wormy world. Journal of Parasitology 33: 1-18, 1947
84. SZIDAT L. Zeitschrift für Parasitenkunde 13: 165-174, 1944
85. TARASSOW W. Das Schwein und der Hund als endgültige Träger des Diphyllobothrium
latum. Eine experimentelle Untersuchung. Archiv für Schiffs- und Tropen-Hygiene 38:
156-159, 1934
86. TARASSOV V (TARRASOW W). De l'immunité envers le bothriocéphale Diphyllobothrium
latum (L.). Annales de Parasitologie Humaine et Comparée 15: 524-528, 1937
87. TÖTTERMAN G. On the pathogenesis of pernicious tapeworm anaemia. Annals of Clinical
Research Supplement 18: 1-48, 1976
88. VERGEER T. Diphyllobothrium latum (Linn 1758), the broad tapeworm of man:
experimental studies. Journal of the American Medical Association 90: 673-678, 1928
89. VERGEER T. The broad tapeworm in America with suggestions for its control. Journal of
Infectious Diseases 44: 1-11, 1929
90. VERLOREN M C. Umhüllung von Flimmer-Epithelium bei den Embryonen von
Bothryocephalus (sic) latus. Secretary's abstract. Amtliche Bericht über 33 Versammlung
Deutschen Naturforscher und Aertze (1857), p 147, 1859
91. VOGT C. La provenance des entozoaires de l'homme et leur évolution; Conférence faite au
Congrès international des sciences médicales à Genève, le 15 Septembre 1877, H Georg,
Genève, pp 55, 1878
Table 15.1. Landmarks in diphyllobothriasis

___________________________________________________________________
BC Tapeworm infections in humans were known but the species were not
distinguished. Various anthelmintics were used
1592 Dunus described tapeworms with morphological features now recognized
as those of Diphyllobothrium
1602 Platter differentiated Diphyllobothrium from Taenia on the basis of the
shape of the proglottids
1700 Andry described Diphyllobothrium as "Taenia à épine" to indicate the
central "spine" due to the medially placed genital pores of
Diphyllobothrium c.f. the lateral pores of Taenia
1747 Spöring drew attention to the relationship between broad tapeworm
infection and human habitation near water with an increased consumption
of fish
1777 Bonnet illustrated the head of the adult worm
1860 Davaine described diagnosis by finding eggs in the faeces
1881 Braun found larvae (plerocercoids) resembling Diphyllobothrium in pike,
burbot and other fish, then produced patent infection with adult worms in
dogs fed with plerocercoids
1882 Braun produced patent infections in humans who ingested plerocercoids
1877-86 Reyher found that pernicious anaemia was cured in patients who were also
infected with D. latum and in whom the worm was eradicated with
anthelmintics
1883-86 Runeberg made observations similar to those of Reyher
1901 Hamilton reported a case which had been unequivocally acquired in North
America
1917 Janicki found very young larvae of Diphyllobothrium (procercoids) in the
stomach of fish which also contained many copepods and thought that
copepods may be the primary intermediate host
1917 Rosen independently found procercoids in the body cavity of certain species
of copepods, observed the development of coracidia obtained from D. latum
eggs in these copepods, then obtained plerocercoids in fish by infecting
them with procercoids
1928 Isaacs and colleagues treated successfully tapeworm pernicious anaemia by
the administration of raw liver, even though the parasite persisted
1948 von Bonsdorff showed that tapeworms competed with the human host for
dietary vitamin B12
1963 Soininen showed that niclosamide was effective therapy
1977 Praziquantel was introduced for treatment by various investigators
__________________________________________________________________
Chapter 16
CESTODE INFECTIONS OF LESSER

IMPORTANCE
INFECTION WITH BERTIELLA SPECIES
B. STUDERI
This cyclophyllidean tapeworm was first recovered from an orang-utan (Pongo

pygmaeus pygmaeus), then was described by Raphael Blanchard in 1891 as
Bertia studeri (after Dr Paul Bert)15. Because this generic name was already
occupied, it was renamed Bertiella studeri by Stiles and Hassall in 1902105.
Since that time, it has also been found in other subhuman primates and in dogs
in the Philippines. A number of other species of Bertiella have been described,
including B. mucronata, B. polyordus and B. satyri. Some authorities have
considered that these species are all synonymous with B. studeri 1, but current
opinion separates B. mucronata. The life cycle of B. studeri was described by
Stunkard in 1940; he showed that cysticercoids developed in the mites,
Scheloribates laevigatus and Galumna species107.
Infection in a human was reported for the first time in 1913 by Blanchard,
although he named the parasite B. satyri ; fragments of worm were passed by
an eight year old girl in Mauritius18. Since that time, sporadic cases of human
infection have been reported from a number of regions of the world,
particularly India and Indonesia. Treatment with niclosamide was found to be
successful29.
B. MUCRONATA
The adult tapeworm was first recovered from a howler monkey (Alouatta
nigra) in Paraguay by Meyner in 189578. The first human infection was
described in 1928 by Cram who studied specimens recovered from a young
Spaniard by Dr Alberto Recio in Cuba25. A number of further cases have been
reported from the Americas, some being described as B. studeri, but the
modern view is that they were probably B. mucronata 9.
421
INFECTION WITH DIPLOGONOPORUS SPECIES
D. GRANDIS
This pseudophyllidean tapeworm, which is normally a parasite of whales, was

first described by R Blanchard in 1894 as Krabbea grandis 17, then renamed
Diplogonoporus grandis by Lühe in 189973. The generic name is derived from
a combination of the Greek words (DIPLOOS), (GONOS)
and (POROS), meaning "double", "gonad" and "pore", respectively.
Occasionally, infections with adult worms occur in humans; most patients have
been Japanese, which presumably reflects their penchant for eating raw fish.
The first such patient was described by Ijima and Kurimoto in 1894 on the
basis of a specimen found in a 28 year old man by Nakamura in 189250. By
1971, 55 cases had been reported in Japan. The clinical features are similar to
those seen in taeniasis. Recently, Kamo and his colleagues have shown
experimentally that certain species of copepods act as the first intermediate
host59. The second intermediate host remains uncertain.
D. FUKUOKAENSIS
In 1970, Kamo and Miyakai described this worm as a new species. The
parasite was recovered from a girl in Japan60.
DIPYLIDIASIS
A cyclophyllidean tapeworm of dogs and cats, 10-70 cm long, has been known
for generations. It was named Taenia osculis marginalibus oppositus by
Linnaeus in 1748, Taenia canina by him in 175873, T. cucumerina by Bloch
in 1782 19 Dipylidium cucumerinum by Leuckart in 186370 , then Dipylidium
caninum by Railliet in 189288. The generic name is derived from a combination
of the Greek words (DIS) and (PYLIS) meaning "two" and "gate",
respectively.
The life cycle of the parasite was first investigated by Melnikov who showed
in 1869 that when eggs were ingested by the dog louse, Trichodectes canis, the
hexacanth embryos were liberated in the intestines then migrated to the body
cavity where they tranformed into cysticercoids 77. Although this was later
disputed by Zimmerman122, who could not infect these lice experimentally, the
validity of this vector is generally accepted. Sonsino, in 1888, examined the
possible role of fleas in transmission but convinced himself that the mouthparts
of fleas were too small to allow ingestion of Dipylidium eggs100. In the
following year, however, Grassi and Rovelli showed that eggs hatched in the
intestines of the dog flea, Pulex serraticeps (= Ctenocephalides canis), and the
Miscellaneous Cestode Infections 423
human flea, Pulex irritans, then migrated into the body cavity where they
developed into procercoid then cysticercoid larvae43. They noted that the itch
induced by these arthropods caused the dogs to paw and gnaw at the skin, then
bite and swallow the vectors.
The first human case of dipylidiasis was seen by in 1751 by Godefridus
Dubois, a pupil of Linnaeus. Dubois wrote: "est Taenia species quae....
vulgarites in canibus et saepissime apud homines invenitur"31 meaning that this
tapeworm was commonly found in dogs but rarely in humans. A second spec-
imen recovered from a 13 year old boy in Blasius, then deposited by Mekel in
the Museum of Comparative Anatomy in Halle, was re-examined by Leuckart
who concurred with its identification as D. caninum 70. Salzmann of Esslingen
then found the parasite in a 16 month old child in 186194. Infections have since
been reported sporadically from many parts of the world, most of the affected
individuals being children. The clinical manifestations are similar to those seen
in taeniasis, and niclosamide has been found to be an effective remedy55.
HYMENOLEPIASIS
HYMENOLEPIS DIMINUTA
The cyclophyllidean adult worm, 20-60 cm long, normally lives in the

intestines of rats and mice. It was named Taenia diminuta by Rudolphi in
181992. The worms were recovered from a human for the first time in 1842 by
Dr E Palmer of Boston, USA, when he found them in a 19 month old child; the
parasite was not described until 1858 when Weinland named it T. flavo-
punctata 114. A second case of human infection was reported by E Parona in
1882 as occurring in a two year old girl in Varese, Italy87; this worm was
sometimes referred to as T. varesina. The third case was described by Joseph
Leidy in the USA in 1884. Since then it has been reported sporadically from
many parts of the world. The parasite was transferred to the genus
Hymenolepis of Weinland (see next section) and named H. diminuta by
Blanchard in 189116.
In 1892, Grassi and Rovelli showed that cysticercoids developed in a moth,
Asopia farinalis, as well as in its larval stage, in the othopteran arthropod,
Anislabis annulipes, and in the beetles, Acis spinosa and Scannus striatus 44.
These results were confirmed by Joyeux56 who also demonstrated that the
beetle, Tenebrio molitor, and the larval stages of the fleas, Ceratophyllus (=
Nosopsyllus) fasciatus, Xenopsylla cheopis, Pulex irritans, and
Ctenocephalides canis, were also susceptible. Joyeux then transferred these
infections experimentally to rats that ingested infected arthropods. A number
of other arthropods have since been shown to also act as intermediate hosts;
they are all eaters of faeces or are scavengers during their larval or adult stages.
The clinical features are usually minimal, and the infection has been shown to
respond to treatment with niclosamide 55.
H. NANA
This tapeworm was discovered in 1851 by Theodor Bilharz during the autopsy
of a boy in Egypt who had died from meningitis. He wrote to his mentor, von
Siebold, in Germany, describing his findings:
The first incision into the intestine....disclosed immediately large numbers of a small
tapeworm. The worm was a fully developed Taenia with broad segments; it was the
width of a sewing thread and length of hardly 10 mm.13
Von Siebold duly reported this discovery in his journal, and after noting that
Bilharz had wanted to call it Taenia aegyptiaca in view of the country in which
it was discovered and suggested that "it be named Taenia nana because this
tapeworm differs by its smallness so greatly from the other two species of
man"13.
In 1858, Weinland proposed dismembering the genus Taenia and established
the genus Diplocanthus for T. nana and the genus Hymenolepis for T. murina
and related species114. The name Diplocanthus, however, had already been
used by Agassiz for a genus of fish, so this name was invalid. Meanwhile,
Bilharz had provided some of his worms to museums in Vienna and Halle.
Leuckart then used these specimens to improve the morphological description
of the parasite, and renamed it Taenia (Hymenolepis) nana in 186370.
Eventually, it was designated Hymenolepis nana in 1891 by Blanchard, who
accepted the identity of T. nana and T. murina 16. The generic name,
Hymenolepis, is derived from a combination of the Greek words µ
(HYMEN) and (LEPIS) meaning "membrane" and "shell", respectively.
Although Spooner may have found these worms in the USA in 1873101, they
were not met again with certainty until 1885 when Dr Hoelz in Belgrade recov-
ered 50 small tapeworms from a seven month old girl after treatment with
ethereal extract of male fern; he sent the worms to Leuckart who recognized
them as H. nana 72.
A similar parasite in rodents was described by Dujardin 1845 as Taenia mur-
ina 32 . Since this worm and H. nana were so similar morphologically,
speciation was based upon the susceptibility of rats and humans to the strains
of parasite derived from each species. Grassi (1887) was of the view that
T. nana was merely a variety of T. murina because when he gave mature
proglottids of T. murina to six persons, one individual developed a patent
infection42. This experiment proved little, however, since H. nana infection was
endemic in humans in that district. In 1906, Stiles separated H. nana into a
human variety, H. nana, and a murine variety, H. nana var. fraterna 103. Since
repeated attempts to infect the heterologous host species were unsuccessful,
and as the human and rodent forms appeared to have different geographical
distributions, however, Joyeux (1919) again proposed to separate them into
two distinct species, H. nana and H. fraterna 57. The name, H. fraterna, was
chosen since the prior designation, T. murina of Dujardin, was invalid; this
nomenclature had been used by Gmelin in 1790 to describe the worm related
to Cysticercus fasciolaris of Rudolphi (1808). To confuse the nomenclature
even further, the name Taenia nana had also been used by van Beneden in
185212 for a parasite that was subsequently identified as being the adult form
of Echinococcus granulosus.
In contrast to Joyeux's contention that there were two species, however, Saeki
in 1920 showed that infection could occur across species. He obtained
Hymenolepis eggs from a nine year old girl, then infected successfully mice,
rats and one out of two monkeys93. These results were confirmed by
Uchimara111and Woodland117,118 . Uchimara111 and Kiribayashi then did the
reverse experiment and infected children with Hymenolepis eggs from murine
sources. Thus, these results, together with the morphological similarities,
indicated that H. nana and H. fraterna (or T. murina) were identical.
Studies designed to elucidate the life cycle of both the murine and human
forms of the parasite were pursued concurrently with attempts to define their
host specificity. Grassi in 1887 showed that transmission from rat to rat was
direct without the mediation of a vector42; this was confirmed several decades
later by Joyeux56, Scott (as H. longior)96 and Woodland 117
. In 1920, Saeki
examined the kinetics of infection in mice and also proved that humans could
be infected directly93. On microscopical examination of the intestines of
infected rodents, oncospheres were seen in the villi ten hours after infection,
cysticercoids were noted in the mucosa at four days, then after five days, worms
could be found in the intestinal lumen; proglottid formation began on the eighth
day and eggs were found in the faeces 16-17 days after infection. Saeki then
swallowed 1,000 eggs himself on four occasions, but all his efforts to infect
himself failed. When he tried again and infected a four year old girl, however,
he found eggs in her faeces after 19 days. When she was treated 62 days after
infection, large numbers of adult worms were found. It is possible that heavy
infections are at times the result of autoinfection, for Heynemann47 found that
previously uninfected mice infected with as few as 10-25 larvae developed up
to 1,500 adult worms.
In addition to this direct cycle, Nicholl and Minchin found the cysticercoids
of the parasite in the body cavities of the fleas, Xenopsylla cheopis and Cerato-
phyllus fasciatus 85. This was confirmed by Johnston54, then later Bacigalupo
in Argentina demonstrated that the fleas, Ctenocephalides canis and Pulex
irritans, and the mealworms, Tenebrio molitor and T. obscurus, were also
capable of transmitting the infection5. In all these vectors, however, the
cysticercoids differed morphologically somewhat from those developing
directly in the intestine of the definitive host.
H. nana is now well-recognized as being widespread and common in
children in certain parts of the world. Contrary to initial impressions, the
infection has usually been found to be asymptomatic, even when parasites are
present in large numbers. Treatment at first was difficult. The early
anthelmintics were generally ineffective63. Mepacrine was only moderately
efficacious, but then niclosamide was shown to be partially effective11 and
praziquantel was then found to be even better95.
INFECTION WITH INERMICAPSIFER MADAGASCARIENSIS
This cyclophyllidean tapeworm was first described by Davaine in 1870 as

Taenia madagascariensis 27. The specimen had been recovered from an 18
month old child in the Comoros Islands in the Indian Ocean by Grennert in that
year. In 1891, Blanchard renamed the worm Davainea madagascariensis 15.
This was changed to Raillietina madagascariensis by Joyeux and Baer in
192958, then finally it was classified as Inermicapsifer madagascariensis by
Baer in 19566. The generic name is derived from a combination of the Latin
words "inermis", "capsa" and "fero", meaning "unarmed", "case" and "to carry",
respectively. Infected patients have been reported from Africa and Central and
South America. In Africa, rodents were found to the major definitive host, but
elsewhere is appears to be a parasite of humans only6. The life cycle has not yet
been elucidated. The clinical features resemble those seen in taeniasis, and the
infection has been observed to respond to treatment with niclosamide 48.
INFECTION WITH MESOCESTOIDES SPECIES
M. LINEATUS
The cyclophyllidean adult tapeworm is normally a parasite of dogs, cats, foxes

and other mammals. It was first described as Taenia lineata by Goeze in
1782 41. In 1893, Railliet89 transferred it to the genus Mesocestoides that had
been erected by Vaillant in 1863112. The generic name is derived from a
combination of the Greek words µ (MESOS), (KESTOS,
CESTOS) and (EIDOS) meaning "middle", "tape", and "similar",
respectively. Larvae are found in the body cavity and tissues of reptiles, birds
and small mammals. Adult worms rarely infect humans. Most patients have
been reported from Japan, the first patient being described in 1942 by
Kosaka65.
M. VARIABILIS
The adult worm is normally a parasite of the intestinal tract of foxes, skunks
and similar mammals. It was first described by Mueller in 192881. The larval
stages are found in a wide variety of carnivorous animals. Adult worms are
found rarely in humans. The first case, recorded by Chandler in 1942, was of
a 13 month old child in Texas who passed more than 25 feet of tapeworm
segments when treated with oleoresin of aspidium; these segments were
thought to represent at least four worms22. Subsequently, patients were reported
from Denmark (in a Greenlander), from East Africa (in a European) and from
the USA.
INFECTION WITH RAILLIETINA SPECIES
R. CELEBENSIS
This cyclophyllidean tapeworm was first found in the long-tailed mouse,

Lenomys myeri, and described by Janicki in 1902 as Davainea celebensis (the
genus being named in honour of Casimir Davaine)52. In 1920, Fuhrmann trans-
ferred the worm to the genus Raillietina (named in honour of Professor A
Railliet)37. In 1916, Akashi in Taiwan again recorded infection with the
parasite, this time naming it Davainea formosana 2.
Human infections, mostly in young children, have been reported from Asia
and the Pacific. In these regions, the adult worm is a common parasite of rats.
In 1964, Tang and Tang showed that the intermediate host is ants of the genus
Cardiocondyle; adult ants carry proglottids to the nest and feed them to the
young ants in which the cysticercoids develop109. Rats (or humans) acquire
infection by ingesting infected ants, and worms up to 40 cm long develop in the
intestines. The clinical manifestations are usually minimal and the infection was
found to respond to treatment with niclosamide.
In 1891, Leuckart described a worm recovered from an infant in Bangkok as
Taenia madagascariensis 71; this was probably R. celebensis, as was the
infection found in an adult in Manila and described as Davainea madagascar-
iensis by Garrison in 191138.
R. DEMERARIENSIS
The adult tapeworm, about 60 cm in length, was first found by CW Daniels in

Demerara, British Guiana (now Guyana) in 1895; he named it Taenia
demerariensis 26. A number of other names were then used, but all were
recognized as R. demerariensis by Dollfus in 1939-1940 30. Infections have
since been seen frequently in parts of South America, especially in Ecuador.
INFECTION WITH SPIROMETRA SPECIES
(1) HUMANS AS THE INTERMEDIATE HOST - SPARGANOSIS
In 1881, Patrick Manson in Amoy, China, was in quest of an adult filarial worm
(Wuchereria bancrofti) in order to support his view that elephantiasis was a
consequence of an infection with this worm (see chapter 23). Post-mortem
examinations were extremely difficult to carry out as the populace was opposed
to them and a previous attempt by Manson to perform one had had unfortunate
consequences. When a 34 year old man with elephantiasis, lymph-scrotum and
dysentery died in September of that year, Manson carried out a secret autopsy
with the aid of a trusted servant in the Chinese cemetery at the dead of night by
the light of a flickering candle. Instead of finding adult filariae, he discovered
a dozen ribbon-like worms 30 cm long by 5 mm wide in the retroperitoneal
adipose tissue, similar worms in the pleural cavity, and large numbers of
parasites in the gastrointestinal tract75,76. He sent these specimens to Spencer
Cobbold in London who believed them "to be new to science" and named them
Ligula mansoni ; this name was noted by the editor of The Lancet 3 in an
addendum to Manson's report, the formal description by Cobbold following the
next year23. The worm was renamed Bothriocephalus liguloides by Leuckart
in 1884 then Bothriocephalus mansoni by Blanchard in 1886.
A number of workers, including Manson himself, believed that these worms
were an immature form of cestode, possibly related to Diphyllobothrium. In
1854, Diesing28 had raised the genus Sparganum, the name being derived from
the Greek word (SPARGANOS) meaning "ribbon", to house
worms with similar morphological features. Although this genus could not
stand with the acceptance of the theory of alternation of generations and the
recognition that these worms were immature, Verdun in 1907 suggested that
each immature form of the "Bothriocephaliden" (i.e. diphyllobothriids), whose
adult state was unknown, should be placed provisionally in this genus until the
adult form was ascertained. This had, in fact, already been done by Stiles and
Tayler-Jones106 who in 1902 called the parasite, discovered by Manson,
Sparganum mansoni.
In June 1916, Yoshida and his collaborator, Yamada, fed a Sparganum re-
moved from the abdominal wall of a female patient to a dog that was coincid-
entally infected with Diphyllobothrium cordatum. Thirteen days later, different
eggs began to appear in the faeces. When the dog was killed two months after
infection, the investigators recovered a single, large, pseudophyllidean, adult
tapeworm which they took to be a Dibothriocephalus (= Diphyllobothrium)119.
The complete natural life cycle was then elucidated by Okumura in Japan in
191986. He found adult tapeworms in naturally-infected dogs that were identical
with those raised by Yamada and Yoshida. He took ova from these worms and
infected Cyclops leuckarti, then recovered procercoids as had been shown two
years earlier for Diphyllobothrium latum (see chapter 15). The procercoids
were then fed to experimental frogs and mice and were found to pierce the
intestinal wall, migrate into the body cavity of these hosts, and develop into
plerocercoids or spargana. Furthermore, Okumura showed that similar
parasites were to be found in 30-60% of frogs in that region of Japan, as well
as in the snake, Elaphe climacophora. When plerocercoids from these
naturally infected animals were in turn fed to dogs, similar adult tapeworms
developed in the intestines. In 1922, Yoshida showed that as well as being host
to adult worms, cats and dogs also harboured the larval stages. Further, he
found spargana in chickens and ducks and concluded that humans acquire
infection either by drinking water containing infected Cyclops or from eating
raw, contaminated chicken120.
Sparganosis was prone to afflict the eye, particularly in patients in Indochina.
In May 1927, Casaux presented, to the Indochinese MedicoChirurgical Society,
such a case and recounted that the woman had been in the habit of applying dis-
membered frogs to her eyes; he suggested that there may be direct entry of
spargana into the orbital tissues. Evanno arrived at the same conclusion; he
placed a sparganum in the conjunctival sac of a monkey and recovered it 11
days later from the upper lid. Both of these experiences are recorded by
Motais80 who also reported four similar cases in which ocular sparganosis again
followed application of split frogs to the eyes. Independently, Faust and his
colleagues35 noted that AS Campbell of Foochow, China, had extracted
spargana from the fingers of two patients who had applied split frog poultices
to themselves. The possibility of being infected in such a way was confirmed
by Kobayashi64 who infected himself percutaneously. Penetration of the larvae
caused itching and erythema, then excision of the skin revealed three
plerocercoids in tunnels in the dermis and hypodermis. Two further excisions,
the second 47 days after infection, of hard, rounded, painless, subcutaneous
nodules disclosed more plerocercoids. Mueller and Coulston84 carried this
experiment one stage further. They obtained spargana from a monkey,
inoculated themselves subcutaneously, then excised some of the parasites ten
or more weeks later, and transferred one of them to a cat where it was able to
continue its natural evolution.
By these means, it was determined that infection could be acquired in one of
three ways - by drinking infected water (procercoids), by ingestion of
contaminated flesh (plerocercoids), and by direct penetration of plerocercoids
from poultices through the skin.
In 1929, Faust pointed out that although the term Sparganum mansoni had
been used for all the unbranched spargana recovered from man, there were
several species, all of which had an identical appearance in the sparganum
stage, and which could only be identified after generation of the adult form in
experimental dogs35. Moreover, he declared that the larvae should be referred
to as the larval stage of the appropriate adult worm, thus Sparganum mansoni
indicated the sparganum stage of Diphyllobothrium mansoni. By the early
1930's, six other species were recognized - D. decipiens, D. erinacei, D.

houghtoni, D. okumari, D. ranarum and D. reptans. There were dissenters,
however. Iwata51, for example, believed that all these forms could be found in
different parts of the one strobila, and thus recognized only one species. The
balance of opinion has swung against his view.
In 1935, Mueller showed that those spargana found in North America were
in fact not the larval stage of D. mansoni, but of a new species which had a pro-
cercoid stage in C. leuckarti and other species of Cyclops, a sparganum stage
in mice, and a definitive stage in cats and bobcats, and to a lesser degree in
dogs82. This worm he named D. mansonoides. Several years later, Mueller
partitioned the genus Diphyllobothrium and transferred all of the worms
mentioned into a new genus, Spirometra 83.
Reports of human infection from many parts of the world allowed a picture
of the clinical features to be built up. In Asia, where S. mansoni was the
dominant species, most spargana were found in the subcutaneous tissues,
although they have been recorded from the brain and viscera as well. When
located superficially, they often caused recurrent attacks of inflammation. In the
Americas where S. mansonoides was the most frequent species, patients
usually presented with a subcutaneous nodule which may or may not have
migrated and which may or may not have become inflamed.
The most usual treatment has been by surgical excision which also allows the
diagnosis to be made. In Vietnam, where ocular sparganosis was common, the
injection of 40% ethanol into the worm was recommended by Cornet24. Neither
this therapy nor surgical excision was favoured by the director of the
Ophthalmic Institute in Hanoi, Keller, who had experience of 60 cases, because
the former frequently did not work, and the latter was often complicated by
ophthalmia which necessitated removal of the eye. He claimed excellent result
in 12 patients treated with a course of intravenous injection of
novarsenobenzol 62. The usual treatment today, however, is surgical excision
with antibiotic cover, if necessary. The place of praziquantel has not yet been
established.
A different form of Sparganum was reported by Ijima in 1905. He named the
parasite Plerocercoides prolifer 49, then this was reclassified as Sparganum
proliferum by Stiles in 1908104. The adult form of this sparganum is still
unknown. The sparganum is peculiar in that it proliferates or multiplies by
forming branches which become detached. Most of the few patients reported
have resided in Japan; thousands of spargana have been recovered from their
tissues10.
(2) HUMANS AS THE DEFINITIVE HOST - SPIROMETROSIS
S. houghtoni
The adult form of this pseudophyllidean tapeworm was first recovered from a
patient in Shanghai by Dr HS Houghton and described as D. mansoni by Faust

and Wassell in 192136. Faust and his colleagues renamed this worm as D.
houghtoni in 192935.
S. erinacei
This tapeworm was first recovered from a hedgehog (Erinacea europaea) and
described as Dobium erinacei-europaei by Rudolphi in 181992, then renamed
Sparganum erinacei-europaei by Diesing in 185428, then called Diphyllo-
bothrium erinacei by Faust and colleagues in 192935. Finally, it was transferred
to the genus Spirometra by Mueller in 193783. It has been recorded as a
parasite of man in five cases, all in Japan108.
INFECTION WITH TAENIA SPECIES
(1) HUMANS AS THE INTERMEDIATE HOST - COENUROSIS
Coenurosis is an infection with the larval stages of one of several tapeworms.

Coenuri are characterized as bladder worms with multiple scolices, each in its
own separate and inverted canal. In human infections, it is often impossible to
tell which species is the causative organism, unless the adult worm is generated
by feeding experiments.
The first authentic, recorded, human infection, in a Paris locksmith who
presented with convulsions and aphasia, was described by Brumpt in 1913. At
autopsy, two coenuri (probably T. multiceps) were found in the brain, one
being degenerate and the other containing 75 scolices21. The first proven case
of human coenurosis due to T. serialis was reported in a 59 year old French-
woman by Bonnal and colleagues in 193320; the coenurus was fed to a dog and
seven characteristic scolices were obtained. In the Western hemisphere,
T. multiceps has been absent for many years, so the human cases in that region
are probably caused by the larval form of T. serialis; the first such infection
reported was in 1950 of a two year old Californian boy with cerebral
coenurosis53. T. brauni may cause the African form of coenurosis, the first such
patient being reported by Fain and colleagues in 195633. Turner and Leiper in
1919, however, reported a human infection in Nigeria with a coenurus which
they called Coenurus glomerulatus 110. Similar coenuri had been noted
previously in gerbils by Railliet and Henry90; the adult form and the definitive
host are unknown and the worm is possibly identical with T. brauni or T.
serialis.
Most of the infections reported subsequently have been in the brain, in the
connective tissues of the muscles or subcutaneous tissues, or in the eye. The
clinical features are usually those of a space-occupying lesion. Diagnosis and
treatment both depend upon surgical excision. The effectiveness of praziquantel
in the management of human coenurosis is not yet established.
T. brauni
The adult worm was recovered from the intestines of a dog in northeast Africa
and described by Setti in 189798. It was given its current name of T. brauni by
Fain and colleagues in 195633. Some authorities have considered this species
to be synonymous with T. serialis.
T. multiceps
The adult worm is a parasite of dogs, wolves and foxes. According to Küchen-
meister and Zurn, Scultetten and Rentter in 1634-1645 were the first to refer
to the bladder-worm stage of this parasite97. Wepfer stated that "gid" or vertigo
in sheep and cattle was caused by a bladder in their brain and referred to an
epidemic which occurred in 1658115. In 1780, Leske 69 40
then Goeze
independently discovered the scolices with four suckers and a double row of
hooks in the bladders of this parasite, with the former author naming it Taenia
multiceps (multiceps meaning many-headed) and the latter calling it Taenia
vesicularis, cerebrina, multiceps (meaning the many-headed, cystic worm in
the brain). The cystic form was then renamed Coenurus cerebralis by Rudolphi
in 180891. In 1853, Küchenmeister showed that C. cerebralis, which was
common in herbivores, especially sheep, goats and cattle, was the intermediate
stage of T. multiceps 67, then this was confirmed by Haubner46. In 1910, Hall
erected the genus Multiceps and transferred the parasite to it, the worm's name
thus becoming Multiceps multiceps 45. Finally, in 1967, Versteer transferred the
worm back to the genus Taenia 113.
T. serialis
The adult worm, a parasite of dogs, was described as Coenurus serialis by

Gervais in 184739, then designated T. serialis by Baillet in 1863 7
. It was
transiently known as Multiceps serialis, following Stiles and Stevenson. The
larval stage of the parasite is found in horses. Some authorities have considered
this species to be synonymous with T. multiceps.
(2) HUMAN INFECTIONS WITH INTERMEDIATE FORMS OF OTHER TAENIA SPECIES
T. crassiceps
The adult worm is a parasite of foxes. It was described as Alyselminthus crass-

iceps by Zeder in 1800121, then renamed Taenia crassiceps by Rudolphi in
181091. The larval stage, Cysticercus longicollis, is found in small rodents and
the morel; this form (metacestode) reproduces asexually by budding. Cysti-

cercosis produced by this organism, in which there was proliferation of the
parasite but in which infection was limited to the eye, has been reported in a
young Canadian woman99.
T. taeniaeformis
The adult worm is a common parasite of cats. It was first described by Batsch
in 1786 as Hydatigera taeniaeformis 8, then renamed Taenia crassicollis by
Rudolphi in 181091. It was finally designated T. taeniaeformis by Wolffhügel
in 1911116. The intermediate stage is a strobilocercus, i.e. a larval strobila with
a cyst attached at the posterior end; it was long known as C. fasciolaris and is
a common parasite of rats. Its metamorphosis into an adult Taenia was first
observed by Küchenmeister in 185266. Two infections in humans have been
recorded; in both cases, the strobilocercus was embedded in the liver. The first
case was described by Bacigalupo in 1922 as T. infantis occurring in a five
year old child in Argentina4, and the second patient was a 77 year old
Czechoslovakian man102.
(3). HUMAN INFECTION WITH ADULT FORMS OF OTHER TAENIA SPECIES
T. longihamatus
The adult worm was first described as Multiceps longihamatus by Morishita

and Sawada in 196679. The mature forms were recovered from humans. All the
patients were Japanese, the first being a three year old girl.
REFERENCES
1. ADAMS AR. Two further cases of human infestation with Bertiella studeri (Blanchard,
1891) Stiles and Hassall, 1902, with some observations on the probable synonymy of the
specimens previously recorded from man. Annals of Tropical Medicine and Parasitology 27:
471-475, 1933
2. AKASHI S. Taiwan Igakkai Zasshi No. 167, 1916. In Japanese. Abstracted in China Medical
Journal 31: 166-167, 1917
3. ANONYMOUS. Lancet ii: 617, 1882
4. BACIGALUPO J. Sobre una nueva especie de Taenia, Taenia infantis. Semana Médica 26:
726, 1922
5. BACIGALUPO J. Évolution de l'Hymenolepis fraterna Stiles, chez Pulex irritans L.,
Xenopsylla cheopis Rothschild et Ctenocephalides canis Curtis. Annales de Parasitologie
Humaine et Comparée 9: 339-343, 1931
6. BAER JG. The taxonomic position of Taenia madagascariensis Davaine 1870, a tapeworm
parasite of man and rodents. Annals of Tropical Medicine and Parasitology 50: 152-156, 1956
7. BAILLET C. Recherches sur un cystique polycéphale du lapin et sur le ver qui résulté de sa
transformation dans l'intestin du chien. Mémoires de l'Académie des Sciences, Inscriptions et
Belles-lettres de Toulouse (6) i: 452-482, 1863
8. BATSCH AJ. Naturgeschichte der Bandwürmgattung. Überhaupt und ihrer Arten
insbesondere nach den neueren Beobachtungen in einem systematischen Ausuge, pp 298,

Halle, 1786
9. BEAVER PC, JUNG RC, CUPP EW. Clinical Parasitology, ninth edition, Lea and Febiger,
Philadelphia, pp 825, 1984
10. BEAVER PC., ROLON FA. Proliferating larval cestode in a man in Paraguay. A case report
and review. American Journal of Tropical Medicine and Hygiene 30: 625-637, 1981
11. BELMAR R, FAIGUENBAUM J, SAPUNAR J, CUELLO E. Ensayo terapeutico de la
teniasis por Hymenolepis nana con un derivado de la salicilamida (Yomesan Bayer 2353).
Boletín Chileno de Parasitología 17: 69-71, 1962
Hebdomadaires des Séances de l'Académie des Sciences, tome 2, Paris, pp 376, 1858 (written
1852)
13. BILHARZ T, von SIEBOLD CT. Ein Beitrag zur Helminthographia humana, aus brieflichen
Mittheilungen des Dr. Bilharz in Cairo, nebst Bemerkungen von Prof. C. Th. von Siebold in
Breslau. Zeitschrift für wissenschaftliche Zoologie 4: 53-76, 1852. Partly translated in 61
1691, 1885-1890
15. BLANCHARD R. Sur les helminthes des primates anthropoides. (Première note: Cestodes).
Mémoires de la Société Zoologique de France 4: 186-196, 1891
16. BLANCHARD R. Histoire zoologique et médicale des téniades du genre Hymenolepis
Weinland. Société d'éditions scientifiques, R Antoine Dubois, Paris, pp 112, 1891
17. BLANCHARD R. Notice sur les parasites de l'homme. Comptes Rendus Hebdomadaires des
Séances et Mémoires de la Société de Biologie 46: 699-702, 1894
18. BLANCHARD R. Bertia satyri, de l'orang-outang, est aussi parasite de l'homme. Bulletin de
l'Académie de Médecine, Paris, 69: 286-296, 1913
19. BLOCH M. Abhandlung von der Erzeugang der Eingeweidewürmer und den Mitteln wider
dieselben etc., Sigismund Friedrich Hesse, Berlin, pp 54, 1782
20. BONNAL G, JOYEUX C, BOSCH P. Un cas de cénurose humaine du à Multiceps serialis
(Gervais). Bulletins de la Société de Pathologie Exotique et de ses Filiales 26: 1060-1071,
1933
21. BRUMPT E. Précis de parasitologie, second edition, Masson et Cie, Paris, pp 1011, 1913
22. CHANDLER AC. First record of a case of human infection with tapeworms of the genus
Mesocestoides. American Journal of Tropical Medicine 22: 493-497, 1942
23. COBBOLD TS. Description of Ligula mansoni, a new human cestode. Journal of the Linnean
Society of London, Zoology, 17: 78-83, 1883
24. CORNET E. Essai de traitement de la sparganose rétrobulbaire. Bulletin de la Société Médico-
Chirurgicale de l'Indochine 11: 452-455, 1933
25. CRAM EB. A species of the cestode genus Bertiella in man and the chimpanzee in Cuba.
26. DANIELS CW. Taenia demerariensis. British Guiana Annual Medical and Hospital Reports,
pp 4, 1895
27. DAVAINE CJ. Examen microscopique du Taenia receuilli à Mayotte. Comptes Rendus
28. DIESING C. Ueber eine naturgemässe Vertheilung der Cephaloctyleen. Sitzungsbericht der
Akademie der Wissenschaften in Wien. Mathematische-naturwissenschaftliche Klasse 13:
556-616, 1854
29. DISSANAIKE AS, THOMAS V, NAGAPPAN N. Bertiella studeri (Blanchard 1891) Stiles
and Hassal, 1902 infection in a child - first case from Malaysia. Southeast Asian Journal of
Tropical Medicine and Public Health 8: 421-422, 1977
30. DOLLFUS RP. Cestodes du genre Raillietina trouvés chez l'homme en Amérique
intertropicale. Annales de Parasitologie Humaine et Comparée 17: 415-442, 542-562,
1939-1940
31. DUBOIS G. Dissertatio de Taenia, pp 36, 1748. Also, Taenia, Linnaei Amoenitates
Academicae; seu dissertationes variae physicae, medicae, botanicae, antehae seorsim editae,
nunc collectae et auctae cum tabulis aenaeis, Lugduni Batavorum, Holmiae, etc 2: 59-99.
1751

33. FAIN A, DENISOFF N, HOMANS L, QUESTIAUX G, van LAERE L, VINCENT M.
Cénurose chez l'homme et les animaux du à Taenia brauni setti au Congo Belge et au Ruanda
Urundi. II. Rélation de huit cas humains. Annales de la Société Belge de Médecine Tropicale
37: 679-696, 1956
34. FAUST EC. What is Sparganum mansoni. Journal of Tropical Medicine and Hygiene 32:
76-77, 1929
35. FAUST EC, CAMPBELL HE, KELLOGG CR. Morphological and biological studies on the
species of Diphyllobothrium in China. American Journal of Hygiene 9: 560-584, 1929
36. FAUST EC, WASSELL CR. Intestinal parasites of man in the central Yangtze valley. China
37. FUHRMANN O. Considérations générales sur les Davainea. Festchrift für Zschokke, No. 27,
pp 19, 1920
38. GARRISON P. Davainea madagascariensis Davaine in the Philippine Islands. Philippine
Journal of Science 6: 165-176, 1911
39. GERVAIS P. Sur quelques entozoaires taenioides et hydatides. Mémoires de l'Académie des
Sciences et Lettres de Montpellier 1: 85-103, 1847
40. GOEZE JAE. Von dem Drehen der Schafe. Der Patriot. Gesellschaft in Schlesien neue
öconom. Nachrichten auf das Jahr 1780 1: 21-27, 1780
42. GRASSI B. Entwicklungscyclus der Taenia nana. Dritte Praliminarnote. Centralblatt für
43. GRASSI B, ROVELLI G. Embryolische Forschungen an Cestoden. Centralblatt für
Bakteriologie und Parasitenkunde, Abteilung originale 5: 370-377, 401-410, 1889
44. GRASSI B, ROVELLI G. Ricerche embriologiche sui cestodi. Atti dell'Accademia Gioenia
di Scienze Naturali, Catania, volume 4, memoir 2, 1892
45. HALL MC. The gid parasite and allied species of the genus Multiceps. i. Historical review.
Bulletin 125, Bureau of Animal Industry, United States Department of Agriculture, pp 68,
1910
46. HAUBNER GC. Ueber die Entwicklung der Band- und Blasenwürmer im Allgemeinen, und
die des Coenurus cerebralis insbesondere. Magazin für die Gessamte Thierheilkunde 20:
243-260, 1854
47. HEYNEMANN D. Studies on helminth immunity. III. Experimental verification of
autoinfection from cysticercoids of Hymenolepis nana in the white mouse. Journal of
Infectious Diseases 109: 10-18, 1961
48. HIRA PR. Human and rodent infection with the cestode Inermicapsifer madagascariensis
(Davaine, 1870) Baer, 1956 in Zambia. Annales de la Société Belgique de Médecine
Tropicale 55: 321-325, 1975
49. IJIMA I. On a new cestode larva parasitic in man (Plerocercoides prolifer). Journal of the
College of Science of the Imperial University of Tokyo, 20 (Article 7), pp 21, 1905
50. IJIMA I, KURIMOTO T. On a new human tapeworm Bothriocephalus species. Journal of
the College of Science of the Imperial University of Japan 6: 372-385, 1894
51. IWATA S. Some experimental and morphological studies on the post-embryonal development
of Manson's tapeworm Diphyllobothrium erinacei (Rudolphi). Reprinted from Japanese
Journal of Zoology 5: 209-247, 1933
52. JANICKI C. Über zwei neue Arten der genus Davainea aus celebensischen Säugern. Archives
de Parasitologie 6: 257-292, 1902
53. JOHNSTONE HE, JONES OW. Cerebral coenurosis in an infant. American Journal of
54. JOHNSTON TH. Notes on some entozoa. Proceedings of the Royal Society of Queensland
24: 63-91, 1913
55. JONES WE. Niclosamide as a treatment for Hymenolepis diminuta and Dipylidium caninum
infections in man. American Journal of Tropical Medicine and Hygiene 28: 300-302, 1979
56. JOYEUX C. Sur le cycle évolutif de quelques cestodes. Note préliminaire. Bulletins de la
Société de Pathologie Exotique et de ses Filiales 9: 578-583, 1916
57. JOYEUX C. Hymenolepis nana (v. Siebold 1852) et Hymenolepis nana var. fraterna Stiles,
1906. Bulletins de la Société de Pathologie Exotique et de ses Filiales 12: 228-231, 1919
58. JOYEUX C, BAER JG. Les cestodes rares de l'homme. Bulletins de la Société de Pathologie
Exotique et de ses Filiales 22: 114-136, 1929
59. KAMO H, IWATA S, HATSUSHIKA R, MAEJIMA J. (Experimental studies of the life cycle
of Diplogonoporus grandis. II. Experimental infection of marine copepods with coracidia.)
Japanese Journal of Parasitology 22: 79-89, 1973. In Japanese, with English summary
60. KAMO H, MIYAKAI I. Diplogonoporus fukuokaensis sp. nov. (Cestoda:
Diphyllobothriidae)from a girl in Japan. Japanese Journal of Parasitology 19: 635-644, 1970
61. KEAN BH, MOTT KE, RUSSELL AJ (Editors). Tropical medicine and parasitology: classic
62. KELLER. Note sur une nouvelle méthode de traitement de la sparganose oculaire. Bulletin
de la Société Médico-Chirurgicale de l'Indochine 15: 524-536, 1937
63. KEVORKOV N P. (On some problems of the treatment of Hymenolepis nana.)
Meditsinskaya Parazitologiya i Parazitarn e Bolezni 12: 83-88, 1943. In Russian. Abstracted
64. KOBAYASHI H. (Studies on the development of Diphyllobothrium mansoni [Cobbold 1882]
Joyeux 1927 [Third report]. Experimental studies on the mode of infection by the mature
procercoid.) Taiwan Igakkai Zasshi 30: 3-8, 1931. In Japanese, with English summary
65. KOSAKA S. The first case of Mesocestoides lineatus parasitic on the human body. Japanese
Journal of Parasitology 14: 212, 1942
66. KÜCHENMEISTER F. Ueber die Umwandlung der Finnen (Cysticerci) in Bandwuermer
(Taenien). Prager Vierteljahrschrift für die praktische Heilkunde 33: 106-158, 1852
67. KÜCHENMEISTER F. Experimente über die Entstehung der Cestoden Zweiter Stufe
zunächst des Coenurus cerebralis. Under Mitwirkung des Herrn Professor Haubner auf
Befehl und Kosten des hohen königliche sächsischen Staatsminsiterii des Innern. Zeitschrift
für klinische Medicin 4: 448-451, 1853
68. KÜCHENMEISTER F, ZÜRN FA. Die Parasiten des Menschen, Ambrosius Abel, Leipzig,
two volumes, pp 582, 1878-1881
69. LESKE MG. Von dem Drehen der Schafe und dem Blasenbandwurme im Gehirn derselben
als der Ursache dieser Krankheit, Leipzig, pp 52, 1780
70. LEUCKART R. Die menschlichen Parasiten und die von ihnen herrührenden Krankheiten. Ein
Hand- und Lehrbuch für Naturforscher und Aertze, CF Winter'sche Verlagshandlung, Leipzig,
volume 1, pp 766, 1863
71. LEUCKART R. Über Taenia madagascariensis Davaine. Abhandlungen der deutschen
zoologischen Gesellschaft pp 68-71, 1891
73. LINNAEUS C. Systema naturae per regna tria naturae, secundum classes, ordines, genera,
species cum characteribus differentiis, synonymis, locis, tenth edition, L Salvii, Holmiae, two
74. LÜHE M. Zur Anatomie und Systematik der Bothriocephaliden. Verhandlungen der deutschen
zoologischen Gesellschaft 9: 30-55, 1899
75. MANSON P. Case of lymph scrotum associated with filariae and other parasites. Lancet ii:
616617, 1882
76. MANSON-BAHR P. Patrick Manson as a parasitologist. In, "A critical review". In,
International review of tropical medicine, DR Linicombe (Editor), Academic Press, New
York, pp 77-129, 1961
77. MELNIKOV NM. Ueber der Jugendzustände der Taenia cucumerinum. Archiv für Natur-
geschichte 35: 62-70, 1869
78. MEYNER R. Zwei neue Taenien aus Affen. Ein Beitrag zur Kenntnis der Cestoden.
Zeitschrift für Naturwissenschaft 68:1-106, 1895
79. MORISHITA K, SAWADA I. On tapeworms of the genus Multiceps hitherto unrecorded
from man. Japanese Journal of Parasitology 15: 495-501, 1966
80. MOTAIS F. Considération sur la pathogénie de la sparganose oculaire. Bulletin de la Société
Médico-Chirurgicale de l'Indochine 7: 363-368, 1929
81. MUELLER JF. The genus Mesocestoides in mammals. Zoologische Jahrbücher, Abteilung
für Systematik, Oekologie und Geographie der Tiere, Jena 55: 403-418, 1928
82. MUELLER JF. A Diphyllobothrium from cats and dogs in the Syracuse region. Journal of
83. MUELLER JF. A repartition of the genus Diphyllobothrium. Journal of Parasitology 49:
294-296, 1937
84. MUELLER JF, COULSTON F. Experimental human infection with the sparganum larva of
Spirometra mansonoides (Mueller, 1935). American Journal of Tropical Medicine 21:
399-425, 1941
85. NICHOLL W, MINCHIN EA. Two species of cysticercoids from the rat flea (Ceratophyllos
fasciatus). Proceedings of the Zoological Society of London 1: 9-13, 1911
86. OKUMURA T. An experimental study on the life-history of Sparganum mansoni, Cobbold.
A preliminary report. Kitasato Archives of Experimental Medicine 3: 190-197, 1919
87. PARONA E. Di un caso di Taenia flavopunctata riscontrata in una bambina di Varese.
Giornale dell'Accademia di Medicina di Torino 32: 99, 1882
88. RAILLIET A. Notices parasitologiques. Première series. Bulletin de la Société Zoologique
de France 17: 110-117, 1892
89. RAILLIET A. Traité de zoologie médicale et agricole, second edition, Paris, pp 736, 1893
90. RAILLIET A, HENRY A. Sur un cénure de la gerbille à pieds velus. Bulletins de la Société
de Pathologie Exotique et de ses Filiales 8: 173-177, 1915
91. RUDOLPHI CA. Entozoorum sive vermium intestinalium historia naturalis. Treuttel et
93. SAEKI Y. (Experimental studies on the development of Hymenolepis nana.) Jika Zasshi No.
238, pp 203-244, 1920. In Japanese. Abstracted in Tropical Diseases Bulletin 18: 112, 1921
94. SALZMANN. Ueber das Vorkommen der taenia cucumerina in Menschen. Jahrescheft des
Vereins für Vaterland. Naturkunde in Württemberg 17: 102, 1861
95. SCHENONE H, GALDAMES M, RIVADENEIRA A, MORALES E, HOFFMAN MT,
ASALGADO N, MENESES F, MORA M V, CABRERA G. Tratamiento de las infecciones
par Hymenolepis nana en niña con una dosis oral unica de praziquantel (Embay 8440).
Boletín Chileno de Parasitología 32: 11-13, 1977
96. SCOTT HH. A contribution to the experimental study of the life histories of Hymenolepis
fraterna Stiles, 1906, and Hymenolepis longior Baylis, 1922, in the mouse. Journal of
97. SCULTETTEN, RENNTNER. Cited in 68
98. SETTI. Nuovi elminte dell'Eritrea. Bolletino dei Musea di Zoologia e Anatomia Comparata
della Real Universita di Genova, pp 56, 1897
99. SHEA M, MABERLEY AL, WALTERS J, FREEMAN RS, FALLIS AM. Intraocular
Taenia crassiceps (Cestoda). Transactions of the American Academy of Ophthalmology and
Otorhinolaryngology 77: 778-783, 1973
100. SONSINO P. Ricerche sugli ematozoa del cane e sul ciclo vitate della di tenia cucumerina,
Pisa, pp 47, 1888. Also, Atti della Società Toscana di Scienze Naturali Residente in Pisa 10:
20-64, 1889
101. SPOONER EA. Specimens of Taenia nana. American Journal of Medical Sciences 65: 136,
1873
102. STERBA J, BARUS V. First record of Strobilocercus fasciolaris (Taeniidae-larvae) in man.
Folia Parasitologica 23: 221-226, 1976
103. STILES CW. Illustrated key to the cestode parasites of man. Bulletin 25 of the Hygiene
Laboratories, United States Public Health and Marine Hospital Service, pp 104, 1906
104. STILES CW. The occurrence of a proliferating cestode larva (Sparganum proliferum) in
man in Florida. Bulletin 40 of the Hygiene Laboratories, United States Public Health and
Marine Hospitals Service, pp 7-18, 1908
105. STILES CW, HASSALL A. Bertiella, a new name for the cestode genus Bertia Blanchard,
1891. Science 16: 434, 1902
106. STILES CW, TAYLER-JONES L. A larval cestode (Sparganum mansoni) of man which
may possibly occur in returning American troops. Bulletin 35 of the Bureau of Animal
Industry, United States Department of Agriculture, pp 43-47, 1902
107. STUNKARD HW. The morphology and life history of the cestode, Bertiella studeri.
108. SUZUKI N, KUMAZAWA H, HOSOGI H, NAKAGAWA O. A case of human infection
with the adult of Spirometra erinacei (Rudolphi 1819), Faust, Campbell and Kellogg, 1929.
109. TANG CC, TANG CT. Raillietina (R.) celebensis (Janicki 1902), its development in
intermediate host, epidemiology and taxonomy. Acta Parasitologica Sinica 1: 1-13, 1964
110. TURNER M, LEIPER RT. On the occurrence of Coenurus glomerulatus in man in West
Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene 13: 23-24, 1919
111. UCHIMARA R. (On the development of Hymenolepis nana and Hymenolepis murina.)
Jikwa Zasshi No. 286, 1922. In Japanese. Abstracted in Japan Medical World 3: 53, 1923
112. VAILLANT L. Sur deux helminthes cestoïdes de la genette. Institut, Paris 31: 87-88, 1863
113. VERSTEER A. A taxonomic revision of the genus Taenia Linnaeus, 1758, s. str.
Onderstepoort Journal of Veterinary Research 36: 3-58, 1969
114. WEINLAND DF. Human cestoides. An essay on tapeworms of man etc., Metcalfe and Co.,
Cambridge, Massachussetts, pp 93, 1858
115. WEPFERUS JJ. Observationes anatomicae, ex cadaveribus eorum, quos sustulit apoplexia,
cum excertitatione de ejus loco affecto, JC Suteri, Scaffhusii, pp 304, 1658
116. WOLFFHÜGELK. Los zooparásitos de los animales domésticos en la República Argentina,
Buenos Aires, pp 108, 1911
117. WOODLAND WN. On the life-cycle of the Hymenolepis fraterna (H. nana var. fraterna
Stiles) of the white mouse. Parasitology 16: 69-83, 1924
118. WOODLAND WN. On the development of the human Hymenolepis nana (Siebold 1852)
in the white mouse; with remarks on "H. fraterna", "H. longior" and "H. diminuta".
119. YOSHIDA S. The occurrence of Bothriocephalus liguloides Leuckart, with especial
reference to its development. Journal of Parasitology 3: 171-176, 1917
120. YOSHIDA S. (On the morphology of the adult form of Sparganum mansoni found in the
frog and other animals.) Tokyo Iji-Shinshi Nos. 2271 and 2272, 1922. In Japanese.
Abstracted in Tropical Diseases Bulletin 20: 223, 1923
121. ZEDER JG. Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer von JAE Goeze mit
Zusätzen und Anmerkungen herausgegeben von Zeder, Siegfried Lebrecht Crusius, Leipzig,
pp 320, 1800
122. ZIMMERMAN HR. Life-history studies on cestodes of the genus Dipylidium from the dog.
Chapter 17
Enterobius vermicularis and ENTEROBIASIS
SYNOPSIS
Common names: threadworm, pinworm

Major synonyms: Ascaris vermicularis, Oxyuris vermicularis
Distribution: worldwide
Life cycle: The adult worms live in the region of the caecum. The fertilized female
worms, 2-5 mm in length, crawl out of the rectum at night, and deposit eggs on the
perianal skin. When ova are ingested, each egg in the small intestine hatches a larva
which passes to the caecal region and matures over 2-4 weeks
Major clinical feature: pruritus ani
Diagnosis: finding of eggs on a swab taken with sticky tape from the perianal
skin
Treatment: mebendazole, piperazine, pyrantel, viprynium
AWARENESS OF THE ADULT WORM
The adult form of the helminth now called Enterobius vermicularis was one of
the few worms known to ancient man, for it wa s both big enough to be seen and
had that incontrovertible sign of life - independent motility. Records of it s
existence may be found in the literature of several millenia go. Some authorities
have interpreted the worm described as "Herxetef" in the Egyptian Papyrus
Ebers (c.1550 BC) as indicating this parasite 70. With respect to the Greeks ,
Hippocrates (c.460-375 BC) in his Aphorisms (III, 26) mentions the
occurrence of the worm in children 43, while Aristotle (384-c.320 BC) liste d
among the three kinds of helminths of which he was aware: those which were
large and flat, those which were cylindrical, and those which were thin 2. It is,
the last mentioned worms, the "thin ones", which he called ascaris, tha t
represent the worms now named E. vermicularis, whereas the "cylindrica l
ones" are now designated Ascaris lumbricoides. Similarly, the Roman, Galen
(129-c.200 AD) numbered the pinworm amongst the three species of human
helminths he recognized 31.
Knowledge of these worms continu ed down through the ages; the Arab, Avi-
cenna (Ibn Sina), for example, described them 4. The nature and distinctiveness
of this worm was not always understood clearly, however. Thus, St. Coulet in
1729 failed to distinguish well between E. vermicularis and cucurbitini and
gave the impression that a tapeworm consisted of a large number of E. verm-
439
icularis connected together22. Similarly, Contoli, believing that the structure of

the cuticle of this worm was different from that of other nematodes, regarded
the creature as a minute eel 21.
In 1758 in his Systema Naturae, Linnaeus classified the organism among the
Vermes, naming it Ascaris vermicularis 60. In 1819, Johann Bremser 10
transferred the human pinworm to the genus Oxyuris which had been erected
by Rudolphi in 1803 72 for certain parasites of animals. Earlier, Bremser ha d
found, in the large intestine of rabbits, a number of species of worms which he
placed in this genus. He was then struck by the similarity between these worms
and the worms found in the rectum of humans. After careful study, h e
recognized that whereas ascarids always tapered towards the two extremities
and had three papillae at the anter ior end, oxyurids terminated by a point at one
end (especially in the female) and lacked the three papillae. This led him t o
conclude:
The result of these observations is that the worms known under the name of Ascaris
vermicularis henceforth ought to be classed in the genus oxyuris and not in the genus
ascaris.10
Even more importantly, Bremser distinguished clearly between the male and
female forms. In his observations of oxyurids of animals, he noted that the male
worms were one half to two thirds the size of the females, and that the termin-
ation of the tail in the two sexes were completely different, with the tail in the
male worm being blunter and having a small spiculum. He deduced that male
pinworms from humans ought to have similar characteristics, but initially, he
could not find any such examples in the specimens he had at his disposal .
Eventually, however, Dr. Soemmering sent him a small jar full of oxyurid s
preserved in wine. These worms had been passed by his own son after having
taken an olive oil enema; amo ng them, Bremser found undoubted male worms.
He confirmed this observation when analysing further samples sent b y
Soemmering and by Hermann. Thus, Bremser wrote: "The sexes of thes e
oxyurids can be distinguished by the characteristics that we have reported" 10.
In 1853, Leach56 erected the genus Enterobius, derived from a combination
of the Greek words (ENTERON) and (BIOS) meaning "intest-
ine" and "life", respectively, and transferred this worm to it. This name o f
Enterobius vermicularis was accepted eventually, although Leiper 57 was later
to argue unsuccessfully that it should be called Ascaris vermicularis Linnaeus,
1758 on the grounds of page p reference (and that Ascaris lumbricoides should
be given a different generic name).
The origin of threadworms was shrouded in mystery and for most of recorded
history was generally ascribed to spontaneous generation. By the end of th e
eighteenth century a number of helmint hologists including Goeze and Rudolphi
Enterobiasis 441
had found and described eggs within the female worms. Nevertheless, ther e
was not an instantaneous acceptance of th e idea that the adult worms developed
from the eggs. Thus, Bremser (1819), who readily saw the eggs in femal e
worms, thought it inconceivable that they could be transmitted through th e
media of food, air or water and still clung to the theory of spontaneou s
generation10. Several years earlier (1812), JM Barry in Ireland rejecte d
spontaneous generation and proffered his own explanation, albeit a fallacious
one, as to how transmission might occur. He saw no difficulty with the concept
that minute germs might be imbibed in food or water then grow and develop
within the human body and described an incident which he felt supported his
belief. Twenty years earlier, a patient had come to him seeking removal of the
threadworms which he, his wife, children, servant and visitors had all bee n
afflicted with since moving to a new house four years before. Worms that were
similar in appearance except in col our were found in the water of a nearby well
and he concluded that they may have been the source of the affliction, despite
the objections of a naturalist acquaintance that the creatures were likely to be
of a different species 5.
As late as 1855, Friedrich Küchenmeister was quite astray in his under -
standing of the life cycle of these worms. He had kept ova in water for si x
months, yet after that time, could discern no trace of segmentation, let alone the
formation of a mature embryo. This led him to deduce that development must
take place within the warm milieu of an animal body. Küchenmeister the n
suggested that infection might be transmitted by the adult worms themselves;
he postulated that they crawled out of the anus at night, wandered about th e
bedding, then entered the gut of a bed-fellow (though whether he thought that
this was via the mouth or the anus he did not say), whereupon eggs wer e
released which in turn developed into adult worms:
the emigration of a single pregnant female is sufficient to explain the infection of
whole families with Oxyurides....The sleeping of a married couple, one of whom is
affected with Oxyurides, in the same bed, which is expecially the case amongst the
poor who only possess one bed, the sleeping of these parents and their children, or of
several children together, one of which is troubled with Oxyurides is sufficient to
infect whole families with these worms. For if only a single female which emigrated
at night, has wandered into the intestine of one of these bedfellows who had hitherto
been free from Oxyurides, the perpetual infection is established in consequence of the
abundant reproduction of this parasite.55
Küchenmeister was in fact most unlucky with the Enterobius eggs he chose
to study and the way in which he dealt with them. He saw in the interior of each
egg two large hyaline globules surrounded by finely granular detritus .
Presumably, he was looking at either unfertilized eggs or ova which ha d
degenerated in the water in wh ich he placed them. Several years later, in 1858,
Claparède discovered that the most advanced eggs sometimes containe d
tadpole shaped embryos whilst still within the body of the pregnant femal e
worm17. In 1860, Vix reported that he had seen such eggs in the rectal mucus
and had recovered them from the perianal skin; they were ripe and in th e
process of hatching. This led him to surmise that young Enterobius were
capable of developing directly in the r ectum without having to have a freeliving
phase of existence 85. This view, of course, was very similar to the one already
propagated by Küchenmeister.
Spencer Cobbold writing in 1864 was little more enlightened than either of
the previously mentioned investigators. After noting that it was generall y
supposed that the egg may be reared to an adult in the one and same bearer, he
remarked (perhaps having the precedents of intermediate hosts for trematodes
and cestodes in mind): "I believe this notion to be entirely fallacious" 18.
The only way in which the question as to whether mature eggs could develop
directly when ingested by a human, or whether they first had to pass through an
intermediate hosts, could be resolved was by experiment. In October, 1865 ,
Rudolf Leuckart and three of his students each swallowed a few dozen egg s
which had been kept in a humified incubator. Nearly two weeks later, three of
the investigators found some young adult E. vermicularis 6-7 mm long in their
faeces; Leuckart himself recovered 18-20 worms over four weeks 59. A similar
experiment was repeated by Grassi in 1879. He first assured himself that h e
was free from infection with E. vermicularis, then he ingested six femal e
worms taken from an individual who had died 24 hours previously. After fifteen
days, he became troubled by pruritus ani and he found a number of femal e
worms full of eggs in his faeces; they continued to be passed in each stool for
over a month 36.
Thus, there was no question that an intermediate host was quite unnecessary
or that humans became infected by ingesting mature eggs. The role of mal e
worms in the generation of these eggs had been a matter of controversy fo r
many years, however. As men tioned earlier, Bremser at first could not find any
male threadworms in humans and speculated that reproduction might occur by
parthenogenesis. Despite the eventual discovery of the male sex, the apparent
rarity of this sex encouraged some authors such as Rudolphi and von Siebold
to believe that this hypothesis may well be true. Many years later, however ,
Zenker (1868) proved that it was easy to find many male worms at autopsy by
scraping lightly the mucosal surface of the intestinal canal after removal o f
faecal matter92. There was therefore no longer any reason to doubt that bot h
male and female worms were involved in the reproductive process.
Some uncertainty remained, however, as to whether adult worms coul d
develop directly from eggs laid within the human body. In 1922, Goebe l
claimed that he had succeeded in observing the development of ova that ha d
been deposited in the intestine into mature worms in the lowest parts of th e
small intestine and in the appendix 33. On the other hand, Wundt several years
later collected eggs from the appendix and was unable to stimulate hatching of
eggs with granular contents under any experimental conditions. Moreover, she
found that those ova which contained embryos liberated them in the gastri c
juice but that the larvae were killed by duodenal, jejunal or appendiceal fluid.
Enterobiasis 443
This led her to conclude that it was highly improbable that E. vermicularis
could develop within the gut without the eggs first passing out in the faeces ,
undergoing development in the external environment, then entering again b y
the mouth91. This conclusion was reinforced by the finding of Philpot wh o
showed that the "tadpole" larva was destroyed by digestive juices whereas a
later stage of the parasite, which had developed an oesophagus, becam e
resistant to those juices 68.
Koch in 1925 then investigated the hypothesis put forward that adult worms
might re-enter the anus and produce infection by that means. He injected adult
female worms into the rectum of a child be means of an enema, and took elab-
orate precautions to prevent infect ion by mouth. The child became infected and
Koch concluded that worms multiplied in the intestine without externa l
reinfection involving passage through the stomach. Koch did not, however ,
observe such a phenomenon happening naturally 51. A different means of
retrograde infection was proven experimentally by Schüffner an d
Swellengrebel. They showed that larvae could hatch on the perianal skin, then
migrate back through the anus and develop into adult worms, a process which
they called "retrofection" 80. How important this mode of infection is in nature
remains uncertain.
LOCALIZATION OF THE HABITAT OF THE WORMS
Some of the ancient writers such as Galen 31 were able to differentiate the parts
of the intestinal tract in whic h the three commonly recognized intestinal worms
were located. Enterobius was thought to be localized chiefly in the rectum near
the anus whereas Ascaris lumbricoides was assigned to the upper smal l
intestine and tapeworms were deemed to extend over a considerable length of
the small bowel. The placement of threadworms in the rectum seeme d
eminently reasonable since many practitioners were familar with their habit of
crawling out of the anus at night. This became the accepted dogma until th e
middle of the ninteenth century although there were occasional remarks tha t
worms could be found in the colon and especially in the caecum 46,89.
In the middle of the nineteenth century, however, Dr Gros of Moscow ,
having ascertained on the basis of autopsy studies in Russia, Germany, France
and Italy that these worms resided not in the rectum but in the distal parts of the
small intestine and in the caecum, publicized this finding 37. This observation
was confirmed shortly thereafter by Stricke r in Frankfurt 84, then amplified a few
years later by Zenker.
Zenker examined in detail the mode of development of worms following the
ingestion of eggs. He showed that when eggs were swallowed, the embryo s
hatched in the stomach, then passed into the upper small intestine where they
increased rapidly in size and moulted. Worms i n all stages of development were
found in the small bowel. After copulation, the fecund female worms passe d
into the caecum where they congregated whilst most of the male helminth s
remained in the jejunum and ileum. When the female worms were fully grown
and distended with eggs, they commenced their descent into the large intestine
and finally deposited their eggs in the rectum and on the perianal skin 92.
The behaviour of these worms was studied further by Koch who reported his
observations on ten infected children i n 1925. The external migration of worms
began in the early hours of sleep and lasted about three hours. Koch observed
as many as 65 worms migrating in this fashion from one child. The laying of
eggs began almost immediately and was completed within 15-20 minute s
depending upon the amount of moisture present. Many worms wandered into
the female genitalia, but Koch never observed any returning to the bowel 51. It
had in fact been known for yea rs that female adult worms sometimes wandered
into the female genitalia, on occasion reaching the peritoneal cavity 53.The
observations of Koch were confirmed a few years later by Reardon who also
showed that each female worm deposited about 11,000 eggs 69.
When it was shown in 1916 by Stewart that Ascaris lumbricoides larvae
liberated from eggs in the stomach migrated through the tissues of the hos t
before returning to the bowel, attent ion turned to determining whether a similar
phenomenon occurred with E. vermicularis. No evidence of such larva l
migration was found in mice and other animals infected with E. vermic-
ularis 41,44,68.
The number of worms in the bowel is extremely variable. Perhaps the most
ever recorded is that reported by Bijlmer in 1946; he found at autops y
approximately 10,000 worms in the bow el of a 40 year old emaciated man who
had died in Holland 7.
The cardinal feature of Enterobius infection, perianal itching which is worst at

night, was recognized two and a half thousand years ago by Hippocrate s
(Epidemics, Book 2, Section 1) 43. He understood that worms crawled out onto
the perianal skin at night, and that they sometimes "lost their way" and could be
found in the vulva (Diseases of Women, Book 2, 76) 43. This exacerbation of
symptoms at night has led some commentators to conclude that Avicenna was
referring to E. vermicularis when he wrote: "The symptoms are aggravated in
the evenings and at bedtime" 4. The habits of these worms became well-known
and passed into folk-lore with one writer remarking:
They will crawl out, and old women sometimes amuse themselves by seeing how
many they can catch in a night, in order that they may shew their exploits to the
doctor in the morning.28
The accuracy of Hippocrates' appreciation, moreover, is attested to by it s
Enterobiasis 445
similarity with the description provided by Date in 1872:

Threadworms may exist in considerable numbers without their presence being marked
by any very striking symptoms; but they generally excite a good deal of local
irritation, and, by the intolerable itching which they occasion, they render the patient's
life miserable....In females they sometimes escape into the vagina, and cause
troublesome leucorrhoea....Beyond the local irritation which they occasion, and which
is often annoying enough, threadworms do not cause much harm. 25
This account would be just as acceptable in any textbook published today.
Whether or not enterobiasis caused other clinical manifestations became a
matter of controversy. An unrealistic attempt was made to link Enterobius
infection with trichotillomania (hair-pulling) 81. Debate raged for years as t o
whether E. vermicularis infection caused appendicitis. In 1899, Still dre w
attention to an apparent relationship between appendicitis and the presence of
E. vermicularis 82. In 1902, von Moty reported that he had found threadworms
either in the appendix itself or in the intestine in three out of five cases o f
appendicitis in his own practice. He believed that this frequency could hardly
be accidental and suggested that E. vermicularis, T. trichiura and
A. lumbricoides may play a role in the genesis of appendicitis 64. In this view,
von Moty was supported enthusiastically by Blanchard and Metchnikof f
(reviewed in1). Many articles appeared subsequently, some for and som e
against this hypothesis, but tending towards the belief that enterobiasis was so
frequent that the association was merely coincidental 27,29,34.
In 1939, Brady and Wright reviewed 200 cases of enterobiasis and claimed
that in addition to pruritus ani, the infection may cause enuresis, vaginitis ,
restlessness, insomnia, behavioural disturbances and scholastic difficulties .
Further they believed that: "Many infested children showed gains in weight ,
improved in color, and disappearance of dark circles under the eyes afte r
treatment"8. In contrast, Weller and Sorenson published their observations of
505 children two years later; 1 9% of the children were infected. There were no
significant differences in symptomatology, including the frequency of pruritus
ani, between the infected and uninfected groups 87. The consensus of opinio n
now is that the majority of infectio ns with this worm are asymptomatic, but that
some infections may cause pruritus a ni, particularly if the worm burden is high.
Until relatively recent times, the diagnosis of enterobiasis was dependent upon
the discovery, either by the patient, a clinician, or another observer, of adul t
worms passed spontaneously. Küchenmeister has recounted one such case:
a shoemaker came to me for advice as the Oxyurides disturbed him at night. As soon
as he went to bed and got warm, the Oxyurides began to march out of his anus, with
violent itching, and wander about in the anal folds, and even, in his opinion, attempted
to free themselves by biting. Once when he did not know what to do with himself, he
wakened his wife and begged her to see whether she could not discover what it was
that troubled him so much. By means of a light, the woman found the little white
worms, and picked them off, and since then, whenever he was again troubled, she
always did him the same service.55
The discovery of Enterobius eggs, however, provided an alternative approach
and in his review in 1877, Heller put forward the possibility of diagnosin g
infection by means of finding eggs in rectal mucus 42.
In 1929, Oleinikow showed that E. vermicularis infection could be diagnosed
easily by scraping perianal skin with a spatula and then cleaning the spatula on
the edge of a slide; further, this method was much more reliable than looking
for eggs in faeces 67. In 1937, Maurice Hall described the "NIH swab" for the
diagnosis of enterobiasis. This consisted of a glass rod wrapped in cellophane
at the point and perforating a rubber cork at the other end, the latter being used
to seal the cellophane in a test tube for transport. The cellophane was the n
flattened out on a glass slide, a couple of drops of caustic soda added, then a
cover slide placed in position and the specimen examined microscopically for
eggs39 . A few years later, Graham described a modification of this swab i n
which the cellophane was replaced by transparent Scotch cellulose tape 35; this
has become the most popular and enduring of the diagnostic techniques used
in enterobiasis, particularly after B eaver indicated that the preparation could be
cleared with toluene 6.
The finding of eggs in the faeces has been used recently to demonstrate the
prehistoric existence of infection. The oldest record is of Enterobius ova found
in coproliths, dated approximately 8,000 BC, that were discovered in Utah ,
United States of America 30.
It is generally held that Enterobius infections do not produce an eosinophilia,
although there is an isolated report of doubtful significance by Schmidt wh o
infected himself with the worm and observed his blood eosinophil level ris e
from within normal limits to 28% five weeks later 77.
It had long been recognized that although persons of all ages may be infected
with threadworms, children were infected much more frequently. Thus, D r
Elliotson in his "Lectures on Worms" in 1833 wrote:
"There can be no doubt that children are much more disposed to ascarides [= E. verm-
icularis] and to lumbrici [= A. lumbricoides] than others; and not only so, but as age
advances, the constitution frequently becomes so unfit for the continuance of these
worms that they are absolutely shaken off without any physic at all....Thousands have
ascarides when they are young and never have them afterwards. 28
The clustering of infection, particularly in families became understandabl e
when the direct transmission of infection was demonstrated by Leuckart 59, and
with the recognition that eggs could be fully embryonated soon after discharge
Enterobiasis 447
into the external environment. Not only was the carriage of eggs in bedding ,
food, air and so on feasible, but Zenker and Heller showed how easily auto -
infection could occur, particularly in persons plagued with pruritus ani, for they
found eggs and even whole adult worms under the nails and the skin fold s
around the nails93. It was then an easy matter to transfer these eggs to th e
mouth. Cobbold has recounted what he considered to be a remarkable an d
foolproof method of ensuring such reinfection:
One aristocratic person, who was infected by myriads of these entozoa, confessed to
me that in his extreme distress, and consequent rage, he had freely bitten the live
worms in halves between his teeth. He had thus exposed himself to a terrible revenge
since multitudes of the ova entering his mouth subsequently found their way into the
stomach and intestines.20
Although it had been known since the time of Zenker and Heller that egg s
were transmitted commonly by the fingers, being caught under the finger nails
and in the nail-folds, Lentz was not satisf ied that this was the whole explanation
for infections often recurred despite all appropriate precautions bein g
taken. He then carried out some experiments which showed conclusively that
the ova could become airborne following activities such as restless movements
under bedclothes and changing the bedding 58. His findings were confirme d
several years later when investigators in the United States revealed that house
dust was frequently contaminated with ova 66. Subsequently, it was determined
that most eggs survived for 48 hours when kept in cool, moist air, but that the
majority were dead after this period in dry, cool air, while all were kille d
rapidly by a dry, warm atmosphere 47. Proof that such eggs were viable wa s
provided by Schüffner and Swellengrebel in 1949 when they infected seve n
doctors and students with eggs which had lain in room dust for three days o r
longer80.
The increased ease with which enterob iasis could be diagnosed following the
introduction of the NIH swab resulted in a new appreciation of how common
the infection was. Many surveys showed that a third or more of the population
in a number of countries was infected. Futhermore, it became apparent that in
these countries, E. vermicularis had little respect for sex, age, race o r
socio-economic status23. Infection was found to be less common in tropica l
countries that in nations in temperate zones. Thus, only 1% of schoolchildren
on the island of Guam in the Pacific Ocean were infected in 1947 83 whereas all
of the schoolchildren surveyed in Amsterdam during World War II wer e
infected79.
THE SEARCH FOR EFFECTIVE TREATMENT AND PREVENTIVE

MEASURES
Countless remedies have been used do wn through the ages for the management
of threadworm infection. Bremser recorded in 1819 that Sömmering had used

an olive oil enema on his son with success 10. Elliotson (1833) considered that
oil of turpentine was the most effic acious agent and should be given by the anal
route:
In the case of ascarides (= E. vermicularis)....it is best to give the oil of turpentine by
injection. You thus send it immediately on the parts where the worms reside, you save
the patient the trouble of a filthy dose and you save the stomach from great
disturbance. From a drachm to half an ounce may be given to a child, mixed with
gruel, and it will often bring away thousands. Adults will take a larger dose in an
infection - an ounce of more.28
Küchenmeister (1855) listed a number of drugs including oil, garlic and worm-
wood, and noted the common belief that the best time for administration o f
these agents was when the moon was on the wane 55. The difficulties of treating
enterobiasis were emphasized in 1874 by Cobbold in his usual verbose an d
pompous style:
Gentlemen, - If, in the curative treatment of ascarides, or oxyurides, as they are more
properly termed, you cannot expect an amount of success equal to that which ought
to be obtained in the case of tapeworms, it is at least some satisfaction to know that
the worst of cases may be overcome by perserverance in the application of appropriate
remedies in combination with the employment of hygienic measures ....Patients also
will come to you, especially ladies, requesting both immediate and permanent relief,
some of them, at the same time, taking care to impress upon you the impossibility of
their swallowing active aperients or cathartics.19
He then went on to list drugs which had been recommended including assa -
foetida and aloes, various preparations of steel, santonin, quassia, lime-water,
salt, castor oil, chloric ether, iron sulphate and gentian, usually in the form of
an enema. He emphasized the irrationality of giving enemas alone when it was
known that worms could be found throughout the length of the bowel, partic-
ularly the caecum; oral medicaments were required which would bring th e
parasites within reach of the clysters. Cobbold went on to say, though:
For my own part, I may say that I have ransacked the Pharmacopoeia for permanently
effective remedies, but I have satisfied myself that no single drug, or any combination
of drugs, can be employed with any certainty of success. You cannot find any
remedial agent that exerts what may be called a specially poisonous or specific action
upon the threadworm....I am free to admit that, do what we will, some cases prove
obstinant and apparently incurable.19
He concluded, however, that relapse was alm ost certainly the result of ingesting
more eggs, either from the patient's own person, or from other individuals. It
was clear to him that treatment and hygiene had to go hand in hand:
Obviously, therefore,....it is part and parcel of adequate treatment to recommend such
prophylactic measures as should be likely to reduce the liability of reinfection within
the lowest possible limits. In this view, I am in the habit of enforcing the utmost
attention to cleanliness, not only as regards the person of the patient himself or
herself....but also in respect of household arrangements. Frequent lavaments, purity
of the water used for drinking and other domestic purposes, local washings after
defaecation, frequent changes of linen, especially bed-clothing, the removal and
Enterobiasis 449
beating of the bedroom carpets, washing of the floors....in short, every kind of
procedure which shall operate to prevent the re-introduction of the eggs of these very
common entozoa.19
Over the new few decades, a wide array of drugs was put forward for th e
treatment of enterobiasis, presumably indicating that each of them lef t
something to be desired. These included thymol 9, butolan75, aluminium sub-
acetate76, salvarsan (arsenic) 38 , vermitacet (extract of Tanacetum vulgare)54 ,
chloramin86, cupronat (copper) 50, oxylax (Tubera jalapae plus dihydrooxy-
phthalophenon)12, tetrachlorethylene 90, hexylresorcinol and gentian violet 24. In
1940, following the recognition of its anthelmintic properties by Harwood and
colleages in 193840, Manson-Bahr reported that phenothiazine was ver y
effective in six children and three adults with enterobiasis, all of whom were
cured62. This observation was soon confirmed by a number of investigators but
unacceptable side-effect became apparent and led to abandonment of the drug.
In 1942, Giroud noted that a patient undergoing piperazine treatment fo r
another condition was cured clinically and parasitologically of enterobiasis 32.
The value of the drug was then investigated by Mehrez who wrote a thesis on
the subject in 1947 63. In 1951, Mouriquand and colleagues published, for the
first time in the more accessible literature, the observation that piperazine was
effective in the treatment of enterobiasis 65, then this was confirmed by White
and Standen who demonstrated in a controlled trial that piperazine hydrate was
more effective (83% cures) than gentian violet (70%) and a lactose placeb o
(17%)88. A number of antibiotics including tetracycline 61 and combinations of
bacitracin and succinylsulphathiazole 15, neomycin and phthalysulphathiazole 3,
and spiramycin and diphetarsone 78 were shown to be effective. Tetracycline is
now contra-indicated because of the recognition of its propensity to stai n
permanently the teeth of children. In 1956, the efficacy of a derivative o f
cyanide dye, pyrvinium (viprynium), was reported71,74. In 1965, Davis indicated
that thiabendazole was effecti ve26 while shortly thereafter, the value of pyrantel
was described13 as was the administration of mebendazole 11. Recently, Cho and
colleagues have shown that viprynium and mebendazole remove worms at all
stages or development whereas py rantel and piperazine are inactive against the
larval stages of the parasite 16.
"OXYURIS INCOGNITA" - A SPURIOUS SPECIES OF ENTEROBIUS
In 1919, Koford and White rep orted the discovery of eggs of an unknown type.
They had found these ova in the faeces of 429 of 140,000 soldiers examined in
the laboratory car Metchnikoff during the course of a hookworm survey o f
troops. Since they presumed that the eggs were derived from an unknow n
species of Oxyuris (i.e. Enterobius), Koford and White gave them the name of
Oxyuris incognita 52. Several years later, however, Sandground showed tha t
they were merely eggs of the plant nematode, Heterodera radicicola , which
had been ingested and had passed through the bowel to cause a spuriou s
infection73.
REFERENCES
1. ANONYMOUS. Intestinal worms and appendicitis. British Medical Journal ii: 1595-1596,
1906
F Dübner, E Heitz and U C Bussemaker (Editors), Didot, Parisiis, five volumes, 1848-1874
3. ASKUE E, TUFTS E, DROUGHMAN V. Pthalyl-sulfathiazole (sulfathalidine) in the
treatment of enterobiasis. Journal of Pediatrics 44: 380-385, 1954
4. AVICENNA. Libri in re medica omnes, qui hactenus ad nos pervenere etc., V Valgrisius,
Venetiis, pp 966, 1564. Original Arabic version, "Al Canon fi Al Tib" c. 1,000 AD. Cited in
49
5. BARRY JM. On the origin of intestinal worms particularly the Ascaris vermicularis.
Transactions of the Association of Fellows and Licentiates of the King's and Queen's College
of Physicians in Ireland 2: 392-396, 1812
6. BEAVER PC. Methods of pinworm diagnosis. American Journal of Tropical Medicine 29:
577-587, 1949
7. BIJLMER E. Exceptional cases of oxyuriasis in the intestinal wall. Journal of Parasitology 32:
359366, 1946
8. BRADY FJ, WRIGHT WH. Studies on oxyuriasis. XVIII. The symptomatology of oxyuriasis
as based on physical examinations and case histories. American Journal of Medical Science
198: 367372, 1939
9. BRAU. De l'oxyurose en Indochine. Bulletin de la Société Médico-Chirurgicale de l'Indochine
3: 582-584, 1912
über PseudoHelminthen, Carl Schaumburg und Comp., Wien, pp 284, 1819. Translated from
the 1824 French version of CLF Panoucke in 48
11. BRUGMANS JP, THIENPONT DC, van WIJNGAARDEN I, VANPARIJS OF,
SCHUERMANS VL, LAUWERS HL. Mebendazole in enterobiasis. Radiochemical and pilot
clinical study in 1,278 subjects. Journal of the American Medical Association 217: 313-316,
1971
12. BUCHOLZ CH. Zur Behandlung des Oxuriasis mit Oxylax. Deutsche medizinische
Wochenschrift 51: 1914-1915, 1925
13. BUMBALO TS, FUGAZZOTTO DJ, WYCZALEK JV. Treatment of enterobiasis with
pyrantel pamoate. American Journal of Tropical Medicine and Hygiene 18: 50-52, 1969
14. CAVIER R. Chemotherapy of intestinal nematodes. In, International encyclopaedia of pharm-
acology and therapeutics, section 64, volume 1, Chemotherapy of helminthiasis, R Cavier and
F Hawking (Editors), Pergamon Press, Oxford, pp 215-436, 1973
15. CHAN KF, BROWN HW. The treatment of pinworm (Enterobius vermicularis) infection
with bacitracin and sulfasuxidine. Journal of Pediatrics 43; 290-293, 1953
16. CHO SY, HONG ST, KANG SY, SONG CY. Morphological observations ofEnterobius
vermicularis expelled by various anthelmintics. Korean Journal of Parasitology 19: 18-26,
1981
17. CLAPARÈDE. De la formation et de la fécondation des oeufs chez les vers nématodes,
Genève, pp 101, 1859
19. COBBOLD TS. A lecture on the treatment of threadworm. British MedicalJournal i: 167,
Enterobiasis 451
1874
21. CONTOLI. Cited in 45
22. COULET E St. Disputatio medica inauguralis de ascaridibus et lumbrico lato etc., Lugduni
Batavorum, pp 8, 1728. Also, Tractatus historicus de ascaridibus et lumbrico lato etc.,G
Potuliet, Lugduni Batavorum, pp 228, 1729
23. CRAM EB, REARDON L. Studies on oxyuriasis. XII. Epidemiological findings ni
Washington, D.C. American Journal of Hygiene 29: 17-24, 1939
24. D'ANTONI JS, SAWITZ W. The treatment of oxyuriasis. American Journal of Tropical
Medicine 20: 377-383, 1940
25. DATE W. Intestinal worms. Lancet i: 145-146, 184-185, 1872
26. DAVIS JH. Thiabendazole in pinworm infestations. American Journal of Diseases of Children
109: 567-570, 1965
27. EASTWOOD EH. The relationship between appendicitis, Oxyuris vermicularis and local
eosinophilia in the appendix wall. Journal of Pathology and Bacteriology 26: 69-81, 1923
28. ELLIOTSON J. Lectures on the theory and practice of medicine: worms. London Medical
Gazette 12: 689-695, 1833
29. FISCHER W. Oxyuren und Appendicitis. Deutsche Zeitschrift für Chirurgie 183: 222-245,
1924
30. FRY GF, MOORE GJ. Enterobius vermicularis: 10,000 year old human infection. Science
169: 1620, 1969
31. GALENUS CC. In, Medicorum graecorum opera quae extant, edited by K G Kühn (Greek
text with Latin translation), 20 volumes, Leipzig, 1821-1833
32. GIROUD. Cited in 14
33. GOEBEL F. Die Oxyuriasis. Ergebnisse der Inneren Medizin und Kinderheilkunde 22:
106-138, 1922
34. GORDON H. Appendiceal oxyuriasis and appendicitis based on a study of 26,051 appendixes.
Archives of Pathology 16: 177-194, 1933
35. GRAHAM CF. A device for the diagnosis of Enterobius infection. American Journal of
36. GRASSI GB. I malefazi delle mosche. Nota preliminare. Gazzetta degli Ospedali, Milano 4:
467468, 1883
37. GROS G. Études progressives d'helminthologie. Gazette des Hôpitaux, Paris 27: 538-539,
1854
38. HAJOS K. Die Behandlung der Oxyuriasis mit Salvarsan. Medizinische Klinik 18:
1619-1620, 1922
39. HALL MC. Studies on oxuriasis. I. Types of anal swabs and scrapers, with a description of
an improved type of swab. American Journal of Tropical Medicine 17: 445-453, 1937
40. HARWOOD PD, JERSTAG AC, SWANSON LE. The efficacy of phenothiazine for removal
of ascarids from swine. Journal of Parasitology 24 (Suppl.): 16-17, 1938
41. HASEGAWA T. (On some observations on the development of Oxyuris vermicularis.) Tokyo
Iji Shinshi No. 2367, pp 861-870, 1924. In Japanese. Abstracted in Japan Medical World 4:
203, 1924
42. HELLER A. Oxyuris vermicularis. In, Cyclopaedia of the practice of medicine, volume 7,
Diseases of the chylopoietic system, H von Ziemssen (editor); translated by AH Buck,
Sampson Low, London, pp 752-770, 1877
44. HIRAISHI S. Some experiments on the growth of Oxyuris vermicularis. Japan Medical
World 4: 118-119, 1924
46. HOOPER R. Observations on human intestinal worms being an attempt at their arrangement
into classes, genera and species. Memoirs of the Medical Society of London 5: 224-285, 1799
47. JONES MF, JACOBS L. Studies on oxyuriasis. XXIII. The survival of eggs of Enterobius
vermicularis under known conditions of temperature and humidity. American Journal of
Hygiene 33: 88-102, 1941
48. KEAN BH, MOTT KE, RUSSELL AJ. Tropical medicine and parasitology. Classic investig-
ations, Cornell University Press, Ithaca, pp 677, 1978
50. KNOLLER G. Behandlung der Oxyuriasis mit Cupronat. Deutsche medizinische Wochen-
schrift 51: 1664, 1925
51. KOCH EW. Oxyurenfortpflanzung in Darm ohne Reinfektion und Magenpasse. Zentralblatt
für Bakteriologie, Parasitenkunde und Infektionskrankheiten, Abteilung originale 94:
208-236, 1925
52. KOFOID CA, WHITE AW. A new nematode infection of man. Journal of the American
53. KOLB R. Ueber den Befund van auf dem Peritoneum des Cavum Douglasii angewachsenen
Oxyuriden. Centralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten,
54. KRIMER M. "Vermitacet" gegen Oxyuris vermicularis. Deutsche medizinische
treatment. Volume 1. Animal parasites belonging to the group entozoa, translated by E
56. LEACH. In, Catalogue of the species of entozoa, or intestinal worms, contained in the
collection of the British Museum, W Baird (Editor), pp 132, 1853
57. LEIPER RT. Discussion on the validity of certain generic names at present in use in medical
helminthology. Archiv für Schiffs- und Tropen-Hygiene 30: 484-491, 1926
58. LENTZ FA. Zur Biologie des Oxyuris vermicularis. Zentralblatt für Bakteriologie,
Hand- und Lehrbuch für Naturforscherund Aertze, CF Winter'sche Verlagshandlung, Leipzig,
volume 2, pp 882, 1867-1876
60. LINNAEUS C. Systema naturae per regna tria naturae, secundum classes,ordines, genera,
species cum characteribus differentiis, synonymis, locis, tenth edition, L Salvii, Holmiae, two
61. LOUGHLIN EH, RAPPAPORT I, MULLIN WG, WELLS HG, SHOOKHOFF HB. The
treatment of enterobiasis with terramycine base. Antibiotics and Chemotherapy 1: 588-593,
1951
62. MANSON-BAHR P. Phenothiazine as an anthelmintic in threadworm and roundworm
infections. Lancet ii: 808-809, 1940
63. MEHREZ R. Les nouveaux traitements de l'oxyurose, Thèse, Paris, 1947
64. von MOTY. L'appendicite parasitaire. Écho Médical du Nord 6: 217-221, 1902
65. MOURIQUAND G, ROMAN E, COISNARD J. Essai de traitement de l'oxyurose par al
pipérazine. Journal de Médecine de Lyon 32: 189-195, 1951
66. NOLAND MO, REARDON L. Studies on oxyuriasis. XX. The distribution of the ova of
Enterobius vermicularis in household dust. Journal of Parasitology 25: 173-177, 1939
67. OLEINIKOW SV. (Sur le diagnostic et l'épidémiologie dans l'enterobiase.) "Russian Journal
of Tropical Medicine" 7: 393-401, 1929. In Russian with French summary. Abstracted ni
68. PHILPOT F. Notes on the eggs and early development of some species of Oxyuridae. Journal
69. REARDON L. Studies on oxyuriasis. XVI. the number of eggs produced by the pinworm,
Enterobiasis 453
Enterobius vermicularis, and its bearing on infection. Public Health Reports 53: 978-984,
1938
70. RIAD N. La médecine au temps des Pharaons. La médecine à travers le temps et l'espace,
Librairie Maloine, Paris, pp 319, 1955
71. ROYER A. Preliminary report on a new antioxyuritic, Poquil. Canadian Medical Association
Journal 74: 297, 1956
72. RUDOLPHI CA. Neue Beobachtungen über die Eingeweidewürmer. Archiv für Zoologie und
Zootomie 3: 1-32, 1803
73. SANDGROUND JH. "Oxyuris incognita" or Heterodera radicicola. Journal of Parasitology
10: 92-94, 1923
74. SAWITZ WG, KARPINSKI FE. Treatment of oxyuriasis with pyrrovinyquinium chloride
(Poquil). American Journal of Tropical Medicine and Hygiene 5: 538-543, 1956
75. SCHICKHARDT E. Butolan, ein neues Mittel gegen Oxyuriasis. Münchener medizinische
76. SCHMIDT WT. Zur Therapie der Oxyuriasis. Münchenener medizinische Wochenschrift 69:
400-401, 1922
77. SCHMIDT WT. Neue Beiträge zur Oxyuriasis. Münchener medizinische Wochenschrift 70:
495-496, 1923
78. SCHNEIDER J, BIGUET J, MACHEZ J M. Traitement de l'oxyurose par le diphétarsone -
speramycine et par le diphétarsone. Thérapie 15: 648-654, 1960
79. SCHÜFFNER W. Die Bedeutung der Staubinfektion für die Oxyuriasis. Richtlinien der
Therapie und Prophylaxe. Münchener medizinische Wochenschrift 91: 411-414, 1944
80. SCHÜFFNER W, SWELLENGREBEL NH. Retrofection in oxyuriasis. A newly discovered
mode of infection with Enterobius vermicularis. Journal of Parasitology 35: 138-146, 1949
81. SEMON HC. Trichotillomania due to threadworms. British Medical Journal i: 641, 1922
82. STILL GF. Observations on Oxyuris vermicularis in children. British Medical Journal i:
898-900, 1899
83. STOLL NR, CHENOWETH BM, PECK JL. Low incidence ofEnterobius vermicularis in
natives of Guam, M.I. Puerto Rico Journal of Public Health and Tropical Medicine 22:
235-253, 1947
84. STRICKER W. Physiologisch-pathologische Bemerkungen über Oxyuris vermicularis.
Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 21:
360-361, 1861
85. VIX E. Ueber Entozoen bei Gesiteskranken, ins Besondere Quber die Bedeutung, das
Vorkommen und die Behandlung von Oxyuris vermicularis. Allgemeine Zeitschrift für
Psychiatrie 17: 1-31, 149-198, 225-302, 1860
86. WEINBERGER. Eine Einfache und Zuverlassige Oxyurenbehandlung. Medizinische Klinik
20: 750, 1924
87. WELLER TH, SORENSEN CW. Enterobiasis: its incidence and symptomatology in a group
of 505 children. New England Journal of Medicine 224: 143-146, 1941
88. WHITE RH, STANDEN OD. Piperazine in the treatment of threadworms in children. Report
on a clinical trial. British Medical Journal ii: 755-757, 1953
89. WOLF. De vermibus intestinorum, Giessae, pp 27, 1763
90. WRIGHT WH, BOZICEVICH J, GORDON LS. Studies on oxyuriasis. V. Therapy with
single doses of tetrachlorethylene. Journalof the American Medical Association 109: 570-573,
1937
91. WUNDT N. Ueber Möglichkeit der intraintestinalen Entwicklung von Oxyuren unter
Umgeung der Magenpassage. Münchener medizinische Wochenschrift 71: 546-548, 1924
92. ZENKER F. Ueber die Naturgeschichte des Oxyuris vermicularis. Verhandlungen der
physicalisch-medicinischen Societät zu Erlangen, pp 20-21, 1870 (presented 20 July 1868).
Also, Tageblatt der 42. Versammlung deutscher Naturforscher und Aertze zu Dresden, p 140,
1868
93. ZENKER F, HELLER A. Cited in 42
Table 17.1. Landmarks in enterobiasis

___________________________________________________________________
BC Adult worms have been known from ancient times and various anthelmintics
have been employed
1819 Bremser discovered the male adult worm
1854 Gros showed that adult worms were located primarily in the caecum
1860 Vix recovered eggs from the perianal skin
1865 Leuckart infected himself and three students with ova and recovered adult
worms from their stools two weeks later
1868 Zenker observed the stages of development of larvae in the intestines at
autopsy and found male adult worms in the colonic mucus
1924 Philpot showed that the larva within the eggshell developed further in the
external environment and became resistant to digestive juices
1937 Hall described the "NIH swab" for diagnosis
1941 Graham modified the swab by substituting Scotch tape for cellophane
1956 Viprynium was introduced for treatment
1969 Pyrantel was introduced for treatment
1971 Mebendazole was introduced for treatment
___________________________________________________________________
Chapter 18
Trichuris trichiura and TRICHURIASIS
SYNOPSIS
Common name: whipworm

Major synonyms: Trichocephalus dispar, Trichocephalus trichiurus
Distribution: tropics and subtropics
Life cycle: The adult worms, 30-50 mm in length, live attached by the head to the wall
of the caecum and adjacent parts of the bowel. Eggs are excreted in the faeces and
embryonate over 2 weeks or more, depending upon the temperature. When
embryonated eggs are ingested by a human, each larva hatches in the small intestine,
enters the crypts in the region of the caecum, and matures over 1-3 months
Major clinical features: dysentery, rectal prolapse in very heavily infected persons
(usually children)
Diagnosis: finding eggs in the faeces; rarely, observation of adult worms on procto-
scopy, sigmoidoscopy or colonoscopy
Treatment: mebendazole
Despite the relatively large size of Trichuris trichiura and its not infrequent
occurrence, the ancient writers seem to have been unaware of the existence of
this parasite. The first reference to the worm is found in the works of Joannes
Actuarius, a Byzantine physician who lived during the reign of Andronicus II
(1328-1341 AD). Actuarius mentioned that some worms resembling thi n
strings were sometimes "excreted" from the intestinal wall; he appears to have
believed that they were a stage in the development of the roundworm, Ascaris
lumbricoides, which he considered was generated spontaneously 4. This report
received little recognition and the same fate was to befall the next description
of the parasite.
In 1623, the Portuguese physician and adventurer, Alexei de Abreu, wrote
Tratado de las siete enferme dades (Treatise on the seven diseases ) which has
been described as the earliest book on tropical medicine 34. In this book, de
Abreu discussed certain maladies which he had observed in Angola and Brazil
between 1594 and 1606. One of these conditions appears to be trichuriasi s
which he described in his section on yel low fever, since the worms were almost
invariably found in patients dying from that disease:
455
In those same interior parts wrinkled corrupted and ulcerated in some patients, a little
worm or worms are bred (white like earthworms, the size of a thumb in the length,
the width of sewing thread, not very thick, they have a mild, soft body, the head hard
and black) which eroding that flesh, together with the corruption it keeps rotting, and
eroding, and soon leaves the lower part of the rectum exposed. 3
Only a limited number of copies of this book was printed (perhaps less tha n
20034), and this discovery and descrip tion did not receive the acknowledgement
it deserved.
No further allusion was made to the existence of this worm until Morgagni
in his anatomical letters (published in about 1760) recorded his discovery of
the parasite in 1740:
I dissected 11 cadavers consecutively, and in six of them....I definitely found worms.
The first three or four that I saw were white, very thin, and at most a thumb's breadth
in length. They lay hidden inside feces at the base of the appendix....In another corpse
I found several, all longer than those mentioned, but equal in length to the last two
joints of the little finger; these....were....in the part of the caecum which adjoined the
appendix....They were very pointed at one end and gradually became a little thickened,
turning from white to somewhat dark at the tail which comprised half their length;
otherwise they were totally white and as thin as a hair. 52
This observation of Morgagni was unknown to the Germans who rediscov-
ered the parasite in 1761. During the winter of 1760-1761, an epidemic o f
mucoid diarrhoea (? cholera) raged in Göttingen and killed many of th e
inhabitants as well as French troopers who were stationed there. Whil e
dissecting the body of a five year old girl, one of the medical student s
accidentally opened the caecum and several worms crawled out. One of th e
students, HA Wrisberg, believed that these were worms of a new species but
the prosector, DT Wagler, and some of the other young doctors, after th e
fashion of Actuarius, considere d them to be merely developing E. vermicularis
or A. lumbricoides. The specimens were then taken to Roederer and Buttner to
settle the argument. They pronounced the worm to be previously undescribed
and gave it the name "trichuris" because of the hairlike shape of the tail, th e
name being derived from the Greek words (THRIX) [combining for m
- (TRICH-)] and (OURA) meaning "hair" and "tail", respectively.
Many further examples were found in subsequent autopsies and Roedere r
presented the findings to a meeting of the Academy of Science at Göttingen on
10 October 1761:
The worm is round and cylindrical and at one end has a blunted point; at the other end
it elongates into a thin, threadlike tail. The greatest thickness amounts to about
one-third of a line [1 line = the 12th part of a Rhenish inch; about 2 mm] the length
of the body is seven lines and the tail 15 lines....some (were) rolled together like
spirals; others were less bent. The former are males, the latter females. In all them the
tail is bent. Body and tail are transparent, shiny and white. 61
Not only did Roederer manage to separate the two sexes, but he also saw the
small white eggs which could be expressed together with mucus through th e
genital opening. The marked differences in appearance between the two sexes,
in fact, misled some later investigators into believing that there were tw o
Trichuriasis 457
different species. Roederer, however, made one major error when he mistook
the head for the tail. The true anatomical arrangement was recognized b y
Goeze32 who in 1782 thought it necessary to change the name to Tricho-
cephalos, meaning "hair-like head", but Goeze but did not use binary nomen-
clature and gave it no specific name. Meanwhile, however, Linnaeus (1771 )
had called the worm Ascaris trichiura 48. In 1788, Schrank named it Tricho-
cephalus hominis and Hooper later named it Trichuris vulgaris 38. In 1800,
Zeder renamed the parasite Fusaria, and gave it the specific epithet, dispar,
from the same Latin word meaning "unlik e" or "unequal" 74. In 1810, Rudolphi 65
reverted to the modification by Schrank of Goeze's name for the parasite and
called it Trichocephalus dispar. This remained the popular name for more than
a century until 1941 when the American Society of Parasitologists 59 declared
that the Rules of Zoological Nomenclature concerning priority require d
reversion to the generic name Trichuris of Roederer and Buttner and th e
specific designation trichiura of Linnaeus.
The manner in which the infection was transferred from one person to another
remained a mystery for many years, despite the fact that the eggs of the parasite
were found almost as soon as the adult worms were rediscovered in 1761. In
1855, Küchenmeister put forward an entirely fallacious, albeit ingenious ,
hypothesis to explain the life cycle. T wo recent observations provided him with
stimuli for his idea. First, Leidy had discovered the larvae of Trichinella
spiralis (which Diesing called Trichina affinis) in the muscles of swine (se e
chapter 22). Second, Küchenmeister himself had recently demonstrated tha t
human tapeworm infection was acquired by ingesting Cysticercus cellulosae
in undercooked pork (see chapter 14). He sugg ested, therefore, that T. trichiura
eggs excreted in human faeces were ingested by pigs and the liberated larvae
migrated to the muscles (as T. spiralis). These larvae were in turn ingested by
humans in poorly cooked meat and developed into adult Trichuris in the
intestines45. Küchenmeister attempted to prove this hypothesis by experiments
on dogs but had no success. The untenability of this theory was shown late r
when Virchow and Leuckart discovered adult T. spiralis in the intestines of
experimental animals (see chapter 22).
Küchenmeister did, however, try to observe the fate of eggs and recorded :
"After preserving the eggs of Trichocephalus for six months in water, n o
embryos appeared, but only numerous, clear, but pretty regularly arrange d
globules"45. He was out of luck for he did not observe the ova for long enough,
or at the right season of the year. Several years later, Casimir Davaine in Paris
took up the same problem and reached the following conclusions: eggs were
expelled unembryonated, development only took place outside of the huma n
body, this process took four to six months or more to complete, and the larvae
within each egg may live for over one year 22. Indeed, he later showed that the
larvae could remain alive for five years 23.
Davaine thought it unlikely that an intermediate host was required and that
hatching and development probably took place directly following ingestion of
mature eggs23, but this remained an open question for a number of years .
Eventually, Leuckart undertook some experiments with related species o f
Trichuris in animals. He fed embryonated eggs of Trichocephalus (= Trich-
uris) affinis to a lamb and 16 days later found several hundred youn g
trichocephali about 1 mm in length in the intestine. In a similar experiment ,
Leuckart fed T. crenatus ova to pigs and four weeks later recovered 50-8 0
worms, 10-30 mm long, which were close to sexua l maturity47. Railliet then had
a similar experience. He collected eggs of T. depressiusculus on 19 February
1884, kept them in water until 28 July 1884 and then fed them to a dog. Three
months later, on 27 October 1884, he obtained 150 mature worms 57.
Thus, these experiments proved that related species of Trichuris developed
without an intermediate host but evidence of the same phenomenon happening
with T. trichiura in humans was lacking. In 1886, Salvatore Calandruccio, an
associate of Grassi in Italy, having assured himself that he was not infected with
T. trichiura by examining microscopically his faeces repeatedly over si x
months, swallowed some embryonated T. trichiura eggs on 27 June 1886.
Twenty seven days later, on 24 July, he found whipworm eggs in his faeces for
the first time, thus proving that direct infection occurred in humans an d
showing that the incubation period was nearly four weeks. These results were
published, with minimal acknowledgement to Calandruccio, by Grassi 33 in the
following year, much to the disgust of the former who some years later wrote
a bitter letter to the Journal of Tropical Medicine and Hygiene :
Calandruccio discovers the cycle of evolution of the Ascaris lumbricoides and of the
Trichocephalus dispar, and shows the experiments to Grassi who praises them and
says: 'I shall publish a note under your name in a German paper.' This preliminary note
duly appeared, but not under my name but his, thus expressed 'my pupil
Calandruccio', implying that I had studied under his direction, whereas I had not made
my observations in his laboratory and he was ignorant of them before my
communication.16
For whatever reason, Grassi never replied in the same forum to this attack.
STUDIES OF THE BEHAVIOUR OF WORMS IN THE HOST AN D

PATHOLOGICAL REACTIONS TO THEM
Following the discovery by Stewart that larvae of A. lumbricoides liberated

from eggs in the stomach of the host migrated through the tissues befor e
returning to the gut to mature (see chapter 19), attention turned to the question
of whether a similar phenomenon occurred in T. trichiura infections. Fülleborn
Trichuriasis 459
examined the route of migration a nd in 1923 reported the result of experiments

with species of Trichuris from man, monkeys and rabbits. He showed tha t
when fed to normal hosts, the larvae developed directly within th e
gastro-intestinal tract. He also found that T. trichiura ova hatched in the gut,
principally in the caecum, of guinea pigs, but that the larvae only survived for
about four days, giving rise to worms s ome 200 um in length 30. In the following
year, Hasegawa reported the results of similar experiments; he fed white rats
with T. trichiura ova then found that larvae hatched within 20 hours an d
penetrated the villi of the intestine, especially in the caecum, but failed t o
develop. When Hasegawa gave T. depressiusculus to puppies, similar hatching
and penetration took place, with the larvae remaining in the mucosa fo r
approximately two days. By three days after ingestion, they returned to th e
lumen of the bowel. Thereafter, they remained coiled in the neighbourhood of
the crypts of Lieberkühn, the cells of whic h were destroyed; the worms matured
and mated, with eggs appearing in the faeces after five weeks 36.
The interaction between the worms and the intestinal mucosa was the n
investigated by a number of pathologists. Some suggested that the head of a T.
trichiura bored its way into the intestinal mucosa to form tunnels in the bowel
wall. Similarly, Sagredo found that adult worms were not always free in th e
intestinal canal, nor merely buried in the mucus, but that the head, sometimes
the tail, and occasionally the whole worm were buried in a sort of tunnel in the
intestinal mucosa 66. Oudendal (1924) could not accept these views, however.
He studied material obtained from the bodies of Indians and Chinese infected
with the helminth, and concluded that the worm did not bore or tunnel its way
into the mucosa. Rather, he believed that the parasite inserted its way into the
lumen of a gland, became fixed, then rolled its anterior end around it s
longitudinal axis. Oudendal considered that in so doing, the epithelial cell s
which gathered around the worm lost their individuality and became a
syncitium, and together with polymorphonuclear leucocytes, formed a closed
groove simulating a tunnel 54,55. A number of years later, Hartz examine d
histological sections of the colonic mucosa of children with massive Trichuris
infections and could find no l esions which could be attributable to the infection
except for mechanical compression of the mucosal cells 35.
The coincidence of finding many examples of Trichuris infection at the same

time as an epidemic of diarrhoea was occurring led Roederer and Wagler t o
speculate on the possibility that these worms may have been the cause of the
latter affliction. They found, however, that many persons who died from cholera
were not infected with Trichuris whereas the worms were often found i n
persons who had died from other causes, so they were forced to abandon this
hypothesis62.
In 1838, Bellingham in Ireland set himself the task of determining:

whether the mere presence of these animals in the intestines must of necessity be
injurious or whether they may not exist in considerable numbers even in the human
subjects without causing the slightest inconvenience. 11
He examined 29 successive individuals at autopsy and found the worms in 26
of them. Yet in none of these cases could be found evidence of any symptoms
which could have been ascribed to Trichuris infection11. Thus, by the time
Abbotts Smith came in 1863 to publish his book (which was largely a trans-
lation of much of the first edition of Davaine's textbook), he concluded that the
clinical manifestations, if any, were "almost unknown" 2. Furthermore, Date, in
his review of intestinal worms in 18 72, apparently thought Trichuris of so little
importance that he did not even mentio n it20. Attempts were made subsequently
to link T. trichiura infection with beriberi 28, appendicitis (see chapter 17) and
a predisposition to typhoid fever 14, but none of these postulates stood up t o
critical analysis.
In 1895, Moosbrugger, after referring to the prevailing view that this parasite
was of no clinical significance, detailed three cases of Trichuris infection in
whom he observed severe complications. Moosbrugger concluded that infect-
ions of light or medium intensity were asymptomatic, but that heavy infection
(he instanced one with 900 worms) may produce a fairly well-defined clinical
picture consisting of anaemia, prolonged and obstinate diarrhoea with mucus
plus or minus blood in the stools, colicky abdominal pains and debilitation 51.
This view was supported by Kahane (1907) who reported the case of a fou r
year old girl with intransigent anaemia in whom innumerable whipworms were
found in the appendix, caecum and co lon, some being embedded in the mucous
membrane while others were swimming freely in the intestinal contents 41.
Similarly, Musgrave and colleagues described a "diathesis" of anaemia ,
diarrhoea, cramps, dizziness, oedema and indigestion as a consequence o f
heavy Trichuris infection53.
Some writers went to extreme lengths in ascribing pathogenic roles to whip-
worms. For example, Fernán-Nuñez (1927) considered that trichuriasis might
cause dysentery, purpura, acrocyanosis dystrophica, pernicious anaemia ,
urticaria and goitre29. Swartzwelder in 1939 analysed 81 patients who wer e
infected with Trichuris but no other intestinal parasites. He concluded tha t
abdominal pain, usually right-sided, and vomiting were the commones t
symptoms, that constipation was more frequent than diarrhoea, and that most
cases showed a mild anaemia 68; this study was uncontrolled, however, as he had
no uninfected subjects with whom he could compare the frequency o f
symptoms.
Nevertheless, it gradually became apparent that massive infections (mor e
than 1,000 worms) in children may cause dysentery, anaemia, malnutrition and
rectal prolapse31,44,72. The importance of the relationship between intensity of
infection and severity of disease was underlined by the investigations of Jung
and Beaver that were reported in 1951. Those authors divided their cases into
Trichuriasis 461
three grades; patients with light infections (< 7,500 eggs/g faeces) usually had
no symptoms, those with moderate worm burdens (7,500-30,000 eggs/ g
faeces) sometimes had vague abdominal pains, usually in the right lowe r
quadrant, and urticaria, while those with heavy infection (> 30,000 eggs/ g
faeces) had dysentery, abdominal pain, tene smus and sometimes rectal prolapse
with the worms being visible easily to the naked eye on the mucosa of th e
prolapsed bowel 39.
For almost a century after the re-discovery of T. trichiura by Roederer and his
colleagues, a diagnosis of trichuriasis was made only occasionally in livin g
patients, and that was when worms were passe d spontaneously, usually with the
faeces, as recorded by Roederer: "sometimes they were passed by the patient" 61.
A most unusual way of diagnosing Trichuris infection was recounted by Wedl
in 1854. H Ulrich removed a concretion about the size of cherry stone from an
inguinal abscess which had resulted from an intestinal perforation .
Microscopical examination of this material disclosed ova of T. trichiura in the
midst of other material derived from faeces 71.
Diagnosis was put on a simple and sound basis, however, when Ransom in
1856 and then Davaine in 1857 reported that int estinal helminthiasis, especially
trichuriasis, could be diagnosed by microscopical examination of faeces fo r
ova. In the summer of 1852, while examining the faeces of cats and dogs for
ova of nematodes, it occurred to WH Ransom that intestinal helminthiasis i n
humans might be diagnosed by a similar means. In July 1854, he found eggs of
Trichuris and of an unknown tapeworm in the stools of a nine year old girl 58.
In 1853, while examining the stools of dogs with cholera, Davaine foun d
Trichuris eggs in the excrement. He had the opportunity to confirm thi s
observation in humans several years later when he found large number o f
Trichuris eggs in the faeces of an individual with meningitis; the patient died
and large numbers of adult Trichuris were found in the caecum at autopsy 21.
Davaine noted that the characteristic eggs were recognized easily by thei r
brown colour, ovoid shape, the small bulges at each end, the absence of a n
operculum, and length of 0.05 mm. This description by Davaine has bee n
hailed incorrectly as the foundation of the diagnosis of intestinal helminthiasis
by microscopical examination of the stools 5,69.
The finding of eggs in faeces has been used to demonstrate the prehistori c
existence of infection. Thus, Aspöck and colleagues found ova in faeces (dated
between 800 and 350 BC) obtained from saltmines in Austria 6.
Trichuriasis can sometimes be diagnosed and an assessment made of th e
damage produced by proctoscopic or sigmoidoscopic examinations. Perhaps
the first person to record the use of this technique was Ross who in 194 2
described the sigmoidoscopic appearances in a 2 8 year old woman with chronic
diarrhoea:
This confirmed the diagnosis in a remarkable manner, showing a little reddening and
thickening of the mucosa of the lowest 9 in. of the bowel, most conspicuous about 7
in. from the anus where the mucous membrane was seen to be covered by a layer of
sticky mucus, underlying which were several haemorrhagic spots 1-2 mm. in
diameter; attached to some of these spots moving whipworms could be seen, and
several were removed with forceps.64
When compared with A. lumbricoides and E. vermicularis, relatively little

attention was paid during the nineteenth century to the treatment of Trichuris
infection. Elliotson (1833) remarked vague ly, after discussing various intestinal
worms including T. trichiura, that oil of turpentine given orally was one of the
best anthelmintics 27. In the early part of this century, benzine enemas9 , garlic
enemas41, thymol41 and "latex of Higueron" (fig-tree sap or juice prepared from
Ficus glabrata)12 were employed. In 1922, Duque Lince reported his trials of
various drugs including kousso, male fern, eucalyptus, betanaphthol, thymol,
oil of chenopodium and latex of higueron as remedies for trichuriasis an d
concluded that only the last had any specific effect on T. trichiura 26. Spruit67
supported the view that latex of higueron was active, then the effectiveness of
the elixir was investigated further by Caldwell and Caldwell in 1929. In a
preliminary survey of nine cases, one patient passed 1956 worms afte r
treatment. Accordingly, a series of 234 patients were treated with eithe r
higueron latex or oil of chenopodium; the two drugs produced cure rates o f
54% and 2%, respectively, and the reductions in egg counts were 85% an d
17%, respectively17. The active agent in the latex was held by Robbins to be a
proteolytic enzyme, ficin 60. Unfortunately, the crude latex needed to b e
prepared freshly in order to prevent fermentation, and its restricte d
geographical distribution inhibited wide usage.
In the following few decades, a number of drugs including hexylresorcinol 46,
emetine15, papain50 and pentavalent arsenicals 7 were recommended, but these
frequently did not live up to expectations. In 1957, Hoekenga reported that he
had tried 13 drugs or combinations of drugs and that none was ver y
successful37. Dithiazanine was introduced in the early 1960's and wa s
moderately successful but two children treated with the drug died 1,63 and the
drug was withdrawn from the market. With the exception of this agent an d
diphetarsone 40, none of the various anthelmintics introduced after World War
II was found to be effective agains t T. trichiura until mebendazole appeared on
the scene. This benzimidazole compound was synthesized by Jansse n
Pharmaceutica in Belgium and shown in 1971 to be active against Enterobius
vermicularis (see chapter 17). A number of investigators then proved that i t
was effective in trichuriasis as well 56,73.
Trichuriasis 463
UNDERSTANDING THE EPIDEMIOLOGY; PREVENTION AN D

CONTROL
It was recognized early that Trichuris infection was more common in children
than in adults. As helminthiasis su rveys were undertaken in various parts of the
world, it became obvious that the infection was more frequent in tropical than
temperate countries. The discovery by Calandruccio that infection wa s
transmitted directly without the mediation of an intermediate host paved th e
way for investigations of the factors controlling the epidemiology of infection.
These included the demonstration that the time taken for development of eggs
was dependent upon temperature. Dinnik and Dinnik showed that larva e
developed within 11 days at 35 oC, but that 180 days were required when they
were kept at 15oC24. The other major factor determining the spread an d
intensity of infection was the usage of infected human excreta to fertiliz e
vegetable gardens, for it had been known since the times of Davaine that eggs
were able to survive for many months under moist conditions. Similar factors
determined the epidemiology of ascariasis, and it was realized that the tw o
infections tended to go hand in hand. Little attention has been paid specifically
to the prevention and control of trichuriasis, but where it has, it has depended
largely upon general environmental sanitary measures.
OTHER SPECIES OF TRICHURIS
T. SUIS
Although some authorities have failed to differentiate between Trichuris

species from humans and pigs, it is accepted generally that whipworms from
these two different hosts are distinct species. Dinnik, for example ,
demonstrated minor morphological variations, including the sizes of the eggs
and the infective larvae, and differences in chromosome numbers 25. In 1940,
Tukalevski swallowed 87 infective eggs of T. suis but isolated only two larvae
from his stools 51 days later 70. In 1971, Beer reported that a 23 year old male
(presumably himself) had been infected expe rimentally with 1,000 T. suis eggs.
This resulted 60 days afterwards in a light patent infection (20 eggs/gram o f
faeces) which lasted for at least ten weeks; no clinical manifestation s
occurred10. Interactions between human and porcine trichuriasis in nature ,
however, remain unclear.
T. VULPIS
From time to time, human infections with T. vulpis have been reported, with the
diagnosis being based upon t he increased size of T. vulpis eggs compared with
those of T. trichiura. For example, de Carneri and colleagues in 1971 reported

two such infections, separated by an interval of over one year, in the same five
year old girl; she was living on a farm in Italy 18. Similarly, Kenney and
Termakov have reported the i nfection of a human with the dog whipworm 43. T.
trichiura, however, sometimes produces eggs which are larger and resemble
those of T. vulpis. Little in 1968 recovered such eggs from human faeces then
fed 22 of them to a human volunteer who fifteen weeks later developed a patent
infection which produced eggs of both normal and large sizes 49. This
observation was confirmed subsequently by Correa and his colleagues 19, so it
remains uncertain whether any of the infections reported as due to T. vulpis
were really caused by this species.
REFERENCES
1. ABADIE SH, SAMUELS M. A fatality associated with dithiazanine iodide therapy .
2. ABBOTTS SMITH W. On human entozoa: comprising the description of the differen t
species of worms found in the intestines and other parts of the human body, and th e
pathology and treatment of the various affections produced by their presence, HK Lewis,
3. de ABREU A. Tratado de las siete e nfermedades, Pedro Craesbeeck, Lisboa, 1623. Partly
translated in 34
4. ACTUARIUS J. Methodi medendi libri sex, quibus omnia, quae ad medicina m
factitandam pertinent, fere complectitur, CH Malthisius interprete, Venetiis, pp 399, 1554
5. ANONYMOUS. The week. British Medical Journal ii: 65, 1863
6. ASPÖCK H, FLAMM H, PICHER O. Darmparasiten in menslichen Exkrementen au s
prähistorischen Salzbergwerken der Hallstatt-Kultur (800-350 v. Chr.). Zentralblatt fü r
Bakteriologie, Abteilung originale 223: 549-558, 1973
7. BASNUEVO JG. Tricocefaliasis y arsenicos organicos pentavalentes. Revista Kub a
Medicina Tropical y Parasitologia 4: 185-188, 1948
8. BEAVER PC, JUNG RC, CUPP EW. Clinical parasitology, ninth edition, Lea an d
Febiger, Philadelphia, pp 825, 1984
9. BECKER E. Ueber die durch Trichocephalus dispar verusachten krankheitszustande .
Deutsche medizinische Wochenschrift 28: 468-470, 1902. Abstracted in British Medical
Journal, epitome of the current medical literature p 13, 1903
10. BEER RJ. Experimental infection of man with pig whipworm. British Medical Journal i:
44, 1971
11. BELLINGHAM O'B. On the frequency of the presence of the Trichocephalus dispar in
the human intestines. Dublin Journal 12: 341-347, 1838
12. BERRIO LP. Contribution à l'étude de la trichocéphalose et de son traitement par le latex
d'higueron. Revue de Médecine et d'Hygiene Tropicale 9: 178-184, 1912
13. BLANCHARD R. Traité de zoologie médicale. J-B Baillière et fils, Paris, two volumes,
pp 1691, 1885-1890
14. BLANCHARD R. Sur un travail de M. le Dr. J. Guiart intitulé: Rôle du trichocéphal e
dans l'étiologie de la fièvre typhoïde. Archives de Parasitologie 9: 122-128, 1904
15. BURROWS RB. MOREHOUSE WG, FREED JE. Treatment of trichuriasis wit h
"enseals" of emetine hydrochloride. American Journal of Tropical Medicine 27: 327-328,
1947
16. CALANDRUCCIO S. Unicuiq ue suum, Prof. J.B. Grassi! (Every man his own Professor
Trichuriasis 465
Grassi). Translated by P. Falcke. Journal of Tropical Medicine and Hygiene 4: 218-221,

1901
17. CALDWELL FC, CALDWELL EL. A study of the anthelmintic efficiency o f
higuerolatex in the treatment of trichuriasis, with comment as to its effectiveness against
Ascaris infestation. American Journal of Tropical Medicine 9: 471-484, 1929
18. de CARNERI I, GAZZOLA E, BIAGI F. Ripetute infestazioni presumibilmenta d a
Trichuris vulpis in una bambina residente in una zona endemica de tricocefalosi. Rivista
di Parassitologia 32: 135-136, 1971
19. CORREA LL, YAMANAKA MT, CORREA M, SILVA M, SILVA R. Ocorrência de
ovos grandes de Trichuris trichiura em fezes humanas. Revista do Instituto Adolfo Lutz
40: 59-64, 1980. Abstracted in Tropical Diseases Bulletin 76: 1418, 1980
21. DAVAINE C. Sur le diagnostic de la présence des vers dans l'intestin par l'inspectio n
microscopique des matières expulsées. Comptes Rendus Hebdomadaires des Séances et
Mémoires de la Société de Biologie, second series, 4: 188-189, 1857
22. DAVAINE C. Recherches sur le développement et la propogation du trichocéphale d e
l'homme et de l'ascaride lombricoïde. Journal de la Physiologie 2: 295-300, 1859 .
Translated in 42
23. DAVAINE C. Nouvelles recherches sur le développement et la propogation de l'ascaride
lombricoïde et du trichocéphale de l'homme. C omptes Rendus Hebdomadaires des Séances
de l'Académie des Sciences, third series, 4: 261-265, 1862
24. DINNIK JA, DINNIK NN. (Influence de la temperature, de l'absence d'oxygène et d u
desséchement sur les oeufs de Trichocephalus trichiurus (L).) Meditsinskaya
Parasitologiya i Parazitarn e Bolezni 6: 603-617, 1937. In Russian, with French summary
25. DINNIK NN. (Indépendence des espèces Trichocephalus trichiurus (L 1771) et
Trichocephalus suis (Schrank 1788).) Meditsinskaya Parastilogiya i Parazitarn e Bolezni
7: 907-917, 1938. In Russian, with French summary
26. DUQUE LINCE E. Colitis trichocefaliana. Repertorio de Medicina y Cirugía 13 :
246-274, 1922
27. ELLIOTSON J. Lectures on the theory and pract ice of medicine. Worms. London Medical
Gazette 12: 689-695, 1833
28. ERNI H. Trichocephalus dispar , ein Beitrag zur Beri-Beri-Frage. Berliner klinisch e
Wochenschrift 23: 614-616, 1886. Abstracted in Lancet i: 545, 1886
29. FERNÀN-NUÑEZ M. The pathogenic role of Trichocephalus dispar (Trichuris
trichiura). Archives of Internal Medicine 40: 46-57, 1927
30. FÜLLEBORN F. Ueber die Entwicklung von Trichozephalus im Wirte. Archiv fü r
31. GETZ L. Massive infection with Trichuris trichiura in children. Report of four cases, with
autopsy. American Journal of Diseases of Children 70: 19-24, 1945
PA Pape, Blankenburg, pp 471, 1782
33. GRASSI B. Trichocephalus und Ascarisentwicklung. Preliminarnote. Centralblatt fü r
34. GUERRA F. Alexio de Abreu (1568-1630), author of the earliest book on tropica l
medicine describing amoebiasis, malari a, typhoid fever, scurvy, yellow fever, dracontiasis,
trichuriasis and tungiasis in 1623. Journal of Tropical Medicine and Hygiene 71: 55-69,
1968
35. HARTZ PH. Histopathology of the colon in massive trichocephaliasis of children .
Documenta de Medicina Geographica et Tropica 5: 303-313, 1953
36. HASEGAWA T. Beitrag zur Entwicklung von Trichozephalus in Wirte. Archiv fü r
37. HOEKENGA MT. Experiments in the therapy of human trichuriasis and hookwor m
disease. American Journal of Tropical Medicine and Hygiene 5: 529-533, 1956
38. HOOPER R. Observations on human intestinal worms, being an attempt at thei r

arrangement into classes, genera and species. Memoirs of the Medical Society of London
5: 224-285, 1799
39. JUNG RC, BEAVER PC. Clinical observation s on Trichocephalus trichiurus (whipworm)
infection in children. Pediatrics 8: 548-557, 1951
40. JUNOD C. Essai de traitement de la trichocéphalose par la diphétarsone. Bulletin de la
Société de Pathologie Exotique 58: 653-660, 1965
41. KAHANE R. Beitrag zur Trichozeph aliasis. Correspondez-Blatt für Schweizer Aertze 37:
235-241, 1907. Abstracted in British Medical Journal, an epitome of the current medical
literature p 45, 1907
43. KENNEY M, YERMAKOV V. Infec tion of man with Trichuris vulpis, the whipworm of
dogs. American Journal of Tropical Medicine and Hygiene 29: 1206-1208, 1980
44. KOUR P, VALDÉS-DIAS R. Concepto actual sobre el papel patógeno del Tricocéfalo
dispar (Trichuris trichiura). Revista Kuba de Medicina Tropical y Parasitologia 8: 37-41,
1952
45. KÜCHENMEISTER F. Die in und an dem Körper des lebenden Mensche n
vorkommenden Parasiten. Ein Lehr- und Handbuch der Diagnose und Behandlung de r
thierischen und pflanzischen Pa rasiten des Menschen, BG Teubner, Leipzig, two volumes,
pp 486, 1985. On animal and vegetable parasites of the human body. A manual of their
natural history, diagnosis and treatment. Volume 1. Animal parasites belonging to th e
group entozoa, translated by E Lankester, The Sydenham Society, London, pp 452, 1857
46. LAMSON PD, BROWN HW, ROBBINS, BH, WARD CB. Field treatments o f
ascariasis, ancylostomiasis and trichuriasis with hexylresorcinol. American Journal o f
Hygiene 13: 803-822, 1931
47. LEUCKART R. Die menschlichen Paras iten und die von ihnen herrührenden Krankheiten.
48. LINNAEUS C. Mantissa plantarum altera generum, editiones VI et specierum editionis
II, Holmiae, pp 143-588, 1771
49. LITTLE MD. A strain of Trichuris trichiura having large eggs. Presented at the 43r d
Annual meeting of the American Society of Parasitologists, Madison, Wisconsin, 1968.
Cited in 8
50. McCARTHY E. Infestation with Trichocephalus dispar. Ten cases in an Irish orthopaedic
hospital. Lancet i: 436, 1954
51. MOOSBRUGGER. Ueber Trichoceph aliasis. Münchener medizinische Wochenschrift 42:
10971099, 1895. Abstracted in British Medical Journal, epitome of the current medical
literature p 17, 1896
52. MORGAGNI GB. Epistolarum anatomicarum duodeviginti ad scripta pertinentiu m
celeberrime viri Antonii Marie Valsalvae pars altera. Epistola Anatomica XIV, Apu d
Franciscerum Pitteri, Venice, p 45, 1740. Partly translated in 42
53. MUSGRAVE WE, CLEGG MT, POLK M. Tr ichocephaliasis (with a report of four cases
including one fatal case). Philippine Journal of Science B 3: 545-566, 1908
54. OUDENDAL AJ. Over slijmvlies-veranderingen door den Trichocephalus dispa r
veroorzaakt. Herinneringsbundel Instituut voor Tropische Geneeskund te Leiden, p p
110-124, 1924
55. OUDENDAL AJ. About changes of the mucous membrane caused by Trichocephalus
dispar. Mededeelingen van den Dienst der Volksgezondheid in Nederlandsch-Indië, p p
333-344, 1926
56. PEÑA CHAVARRIA A, SWARTZWELDER JC, VILLAREJOS VM, ZELED N R.
Mebendazole, an effective broad-spectrum anthelmintic. American Journal of Tropica l
Trichuriasis 467
57. RAILLIET A. Cited in 13

58. RANSOM WH. On the diagnosis of, and treatment for, roundworm; and on the occurrence
of a new species of taenia in th e human body. Medical Times and Gazette, new series, 12:
598-600, 1856
59. REPORT OF THE COMMITTEE ON NOMENCLATURE, 16th annual meeting of the
American Society of Parasitologists. Trichuris Roederer 1761 vs. Trichocephalus Schrank
1788. Journal of Parasitology 27: 279-282, 1941
60. ROBBINS BH. A proteolytic enzyme in ficin, the anthelmintic principle of leche d e
higueron. Journal of Biological Chemistry 87: 251-257, 1930
61. ROEDERER JG. Nachrichten von der Trichuriden der Societät der Wissenschaften i n
Goettingen. Göttingische Anzeigen von Gelehrten Sachen: Unter der Aufsaicht de r
königliche Gesellschaft der Wissenschaften, part 25, pp 243-245, 1761. Translated in 42
62. ROEDERER JG, WAGLER JC. De morb o mucoso liber singulis, quem nuper speciminis
inauguralis loco ediderunt, V Bossigelium, Goettingae, pp 211, 1762
63. RODRIGUEZ de CURET H, del PILAR ALIAGA M. Dithiazanine intoxication, a case
report. Boletin de la Asociacion Médica de Puerto Rico 55: 469-473, 1963
64. ROSS DF. Chronic diarrhoea due to Trichocephalus trichiurus . Lancet ii: 97-98, 1942
65. RUDOLPHI CA. Entozoorum sive vermium intestinalium historia naturalis, Treuttel e t
66. SAGREDO N. Trichocephalus dispar in der Darmwand. Archiv für pathologisch e
Anatomie und Physiologie und für klinische Medizin (Virchow) 256: 268-274, 1925
67. SPRUIT CB. The treatment of trichuriasis with Leche de Higueron. American Journal of
68. SWARTZWELDER JC. Clinical Trichocephalus trichiurus infection. An analysis of 81
cases. American Journal of Tropical Medicine 19: 473-481, 1939
69. THEORIDES J. Un centenaire en parasitolo gie. Davaine et le diagnostic des helminthiases
par l'examen microscopiques des selles (1857). La Presse Médicale 65: 2124, 1957
70. TUKALEVSKI IM. Meditsinskaya Parasitologiya i Parasitarn e Bolezni 9: 444, 1940
71. WEDL C. Grundzuge der patho logischen Histologie, Carl Gerold & Sohn, Wien, pp 825,
1854. Rudiments of pathological histology, translated by G Busk, The Sydenham Society,
72. WHITTIER L, EINBORN NH, MI LKLER JF. Trichuriasis in children. A clinical survey
of fifty cases and reports of three cases with heavy infection and striking clinica l
symptoms. American Journal of Diseases of Children 70: 289-292, 1945
73. WOLFE MS, WERSHING JM. Mebendazole: treatment of trichuriasis and ascariasis in
Bahamian children. Journal of the American Medical Association 230: 1408-1411, 1974
74 ZEDER JG. Erster Nachtrag zur Naturgeschicht e der Eingeweidewürmer von J A E Goeze
mit Zusätzen und Anmerkungen herausgegeben von Zeder, Siegfried Lebrecht Crusius ,
Table 18.1. Landmarks in trichuriasis

___________________________________________________________________
c.1330 Actuarius described worms that were probably Trichuris

1623 de Abreu described the adult worms that he had found 20 years earlier in the
bowel of patients dying from yellow fever
1760 Morgagni reported his finding 20 years earlier of the adult worms in the large
bowel
1761 Wagler, Roederer and others independently rediscovered the adult worms in
the large intestine of patients dying from what was probably cholera
1856 Ransom described microscopical diagnosis by finding eggs in the faeces
1886 Calandruccio swallowed embryonated eggs and found T. trichiura ova in his
stools 27 days later
1923 Fülleborn showed in experimental animals that development of larvae took
place solely within the gastrointestinal tract
1973 Mebendazole was shown to be an effective treatment by a number of
investigators
__________________________________________________________________
Chapter 19
Ascaris lumbricoides and ASCARIASIS
SYNOPSIS
Common name: roundworm

Distribution: widespread, especially in tropics and subtropics
Life cycle: the adult worms, 15-30 cm long, live in the lumen of the upper small
intestine. Eggs are passed in the faeces and embryonate over several months, the
duration depending upon the temperature. When an egg is ingested, the larva hatches
in the small bowel, penetrates the intestinal mucosa, and passes via the portal system
to the liver, then to the lungs where it enters the alveolar spaces, ascends the airways
to the pharynx, is swallowed, and returns to the small intestine where it matures over
8-12 weeks
Major clinical features: occasionally - abdominal pain, intestinal obstruction; rarely -
jaundice, pancreatitis
Diagnosis: finding eggs in the faeces
Treatment: levamisole, mebendazole, piperazine, pyrantel
Ancient man must have been w ell aware of, if not terrified by, the large, motile
creatures resembling earthworms that he pass ed in the faeces from time to time,
or, more rarely, escaped through other orifices. These large roundworms were
mentioned in the Egyptian Papyrus Ebers (c.155 BC) 95, and were discussed by
a number of Greek and Roman writers including Hippocrates (c.460-375 BC)
in his Aphorisms (III,26)57, Aristotle (384-c.320 BC) 6, and Pliny (23-79 AD) 21.
The Greeks called these roundworms µ (HELMINS
STRONGYLE) meaning "worm" and "rou nd", respectively. Roman authors re-
ferred to them as "lumbricus teres", in view of their fancied resemblance to the
common earthworm, and to disti nguish them from "lumbricus latus" (the broad
worm, i.e. tapeworm), and "ascaris" of the Greeks (which, confusingly ,
indicated the worm now known as Enterobius vermicularis ). At the beginning
of the Christian era, Celsus (c.20 AD) wrote:
Again, worms also occasionally take possession of the bowel, and these are discharged
at one time from the lower bowels, or more nastily from the mouth; and we observe
them sometimes to be flattened, which are the worse, at times to be rounded. 23
Galen (129-c.200 AD)42 and Alexander Trallianus (c.525-605 AD) knew that
A. lumbricoides normally inhabited the upper part of the small intestin e
469
whereas tapeworms extended over a considerable length of the bowel, an d

E. vermicularis was thought to be seated chiefly in the rectum. This parasit e
was also the first human helminth recorded in the Chinese literature, bein g
mentioned in the work, Nei Chung, which was probably written about 300 -
200 BC59.
It was not until the late seventeenth century, however, that investigator s
began to pay much attention to the details of the anatomical structure of these
parasites. The first person to publish such an account (1683) was the English
don, Edward Tyson; he clearly distinguished A. lumbricoides (which he called
"lumbricus teres") from the earthworm. Having observed that they were about
a foot in length, he wrote:
They are about the bigness of a wheat straw, or a goose quill, their colour white....I
did not observe those feet, or asperities on the annuli, as in the earthworm. At both
extremes they grow narrow. Their mouth is composed of three lips....The anus is a
transverse slit a little below the extreme point of the tail. 133
On dissecting the parasite, Tyson found a large, spiral muscle layer under the
skin, a copious body fluid, a straight intestine, and genital parts which largely
filled the body cavity. He recognized that the sexes were separate, an d
described the appearance of the male and female reproductive organs .
Moreover, he discovered the eggs of Ascaris:
I opened the cornua uteri and found them turgid with a milky juice, having placed a
little of it upon a microscope. I plainly perceived 'twas nothing else but an infinite
number of small eggs, tho' to the naked eye it appeared onely as a fluid body. These
eggs when fresh, appeared....covered with an abundance of small asperities, but as
they grew dry, their surface appeared smooth.133
In the following year, the Italian, Francisco Redi, also described the anatomy
of this worm104, as did Vallisnieri in 1713. Although the latter commentato r
illustrated both the male and female sexual organs, he misinterpreted hi s
observation and thought that the female Ascaris was hermaphroditic and that
the male worm belonged to a different species of helminth altogether 134.
In the tenth edition of his Systema Naturae in 1758, Linnaeus designated this
worm Ascaris lumbricoides 77. The generic name was taken from the Gree k
word (ASKARIS, ASCARIS) meaning "worm". Leiper in 1926 73
claimed that the correct name was Stomachida lumbricoides (Linnaeus 1758)
Perebroom 1780, on the ground that since Linnaeus had described Ascaris
vermicularis first in his tenth edition of Systema Naturae in 1758, Enterobius
vermicularis should have retained this designation. The first person t o
subsequently use another name for A. lumbricoides was Perebroom who, in
1780, called it Stomachida. However, Stiles and Hassall had earlier argued that
Bremser's removal in 1819 of Ascaris vermicularis to the genus Oxyuris of
Rudolphi eliminated it and left the name open for Ascaris lumbricoides. In
1915, the International Commission on Zoological Nomenclature by Opinion
66 confirmed this view by ruling that lumbricoides was the type species of
Ascaris 61. Perhaps fortunately, Leiper's assertions did not receive genera l
Ascariasis 471
acceptance and the name Ascaris lumbricoides retains official recognition.
It was generally held for many centuries that A. lumbricoides, like other
intestinal worms, arose by a proces s of spontaneous generation (see chapter 2).
During the sixteenth and seventeenth centuries, however, a number o f
observers came around to the view that these worms were viviparous, i.e. they
brought forth smaller versions of themselves. Thus, Amatus Lusitanius told of
a girl who voided a large worm and, when her father trod on it, other worm s
escaped from its interior 3. Similarly, Felix Platter recounted the story of a boy
who died and when his abdomen was opened, his intestines were stuffed with
a great number of living worms which were in turn filled with other smalle r
worms98. Dominicus Panarolus claimed that from two persons:
flesh-coloured worms about 16 inches long were expelled. These worms bore many
little worms in them and the little worms looked like so many little sticks of wood.
These small worms were innumerable; they were slender and white, being about six
inches long, and on being born they slithered like so many tiny serpents. 94
Tyson, however, being certain of his discovery of the eggs, was convinced that
all this was nonsense: "Whatever is related of this nature, I cannot but think is
a mistake....For they are not viviparous but oviparous as I have shewn" 133. It is
possible, though, that Tyson may have thought erroneously that the whole cycle
of reproduction and growth could occur within the same host, for he went on
to say:
their containing so vast a number of eggs in the cornua uteri, as I have expressed, does
not sufficiently account for the prodigious quantity, that are sometimes observed to
be bred in animal bodies.133
Alternatively, he may simply have meant that a vast number of eggs wer e
available to contaminate the environment. In any event, the concept tha t
Ascaris was viviparous died hard. More than a century after Tyson clearl y
described the eggs, Church wrote:
Everyone who has examined this worm attentively when newly discharged from the
body must have observed an appearance like white threads, folded, as it were together
about the middle of the worm. This substance has in general been supposed to the
intestines of the worm filled with chyle....but the fact I am going to relate seems to
prove beyond doubt that this white appearance is in reality the young worms nearly
fit for exclusion from the parent.26
The "evidence" Church advanced was that when he put a roundworm passed
by a child in a cup of water and spirit, it produced three worms about one inch
long which were exactly like the parent worm. He then went on to speculat e
that infection might be acquired by worms creeping into the mouth while a
person lay asleep on the ground 26.
By the middle of the nineteenth century, however, there could no longer be
any doubt that transmission depended upon eggs being excreted in the faeces,
and that worms developed from them. At tention turned, therefore, to discerning
the way in which this occurred. In particular, the question arose as to whether
or not an intermediate host was involved in this process. Initially, development
within the egg was examined. The first person to study this aspect was Gros in
Moscow in 1849. He put moistened eggs into an incubator at a temperature of
15-16 oC and found that they began to develop within 24 hours, but require d
four months to reach a perfect state o f larval development 53. Richter in Dresden
made similar observations and showed that eggs remained alive for up t o
eleven months. He placed unsegmented A. lumbricoides eggs in water on 15
November 1854 but did not examine them again until 15 October 1855, a t
which time he found living larvae within the egg shells although none of them
had hatched108. Similarly, Leuckart found that larvae remained motile within the
egg shells for six months and showed them to the Congress of Germa n
naturalists in 1857 74. Furthermore, Leuckart found that the period necessary for
the development of the larvae was variable and was dependent upon th e
temperature.
These processes were reinvestigated by Davaine in 1859. He found tha t
development of larvae took four to six months or even more to be completed,
and reported at that time that they remained alive for more than one year 31. Sub-
sequently, he discovered that larvae were still viable five years afte r
collection32. Davaine also ascertained that incubation of eggs in gastric juice in
vitro did not dissolve the egg shell and permit escape of the enclosed larva. He
therefore performed an experiment in which he introduced two small fabri c
containers, one containing embryonated A. lumbricoides eggs, and the other
holding unembryonated ova, into the stomach of a dog. The flasks wer e
recovered from the faeces two days later and the contents examined. In th e
latter flask, unembryonated eggs were found, while in the former container ,
only a few free larvae could be detected. Davaine interpreted these results as
indicating that:
the egg shell is not dissolved by the intestinal juices because undivided eggs were
found intact in the flasks but the eggs are sufficiently softened so that the embryos
within, activated by the heat of the intestines, could pierce it and escape. 32
In October 1861, Davaine gave 300-400 A. lumbricoides eggs to a cow but
could find no worms in the intestines four months later; he concluded that the
cow was not a susceptible host to this parasite. In October 1862, he fed large
numbers of eggs which had been kept viable for five months to a rat. Whe n
Davaine killed the animal twelve hours later, he found large numbers of intact
eggs in the stomach and the upper small bowel, but in the more distal parts of
the small intestine, he discovered liberated larvae and larvae that were in the
process of hatching through a small pore in the shell. In a subsequen t
experiment upon another rat, he found that these freed larvae were expelled in
the faeces. Davaine summarized his findings:
eggs of....A. lumbricoides develop outside the body of man, but the embryo only
hatches when it is brought into the intestine by food or drink. Two conditions are
Ascariasis 473
doubtless necessary for this hatching: the softening of the shell by intestinal juices and
the activity of the embryo under the influence of heat of about 40 oC. In whichever
animal supplies these conditions, the egg hatches if it remains in the intestine long
enough; however, the embryo does not linger if the animal is not of the kind where
the worm can (sic) acquire its final form.32
Although Davaine thought that transmission was direct, a number of authors
after him believed that an intermediate host was probably necessary. Negative
results with direct feeding experiments were obtained by Mosler in 1860 .
Mosler first swallowed A. lumbricoides eggs himself, but a patent infection, as
assessed by the subsequent administration of anthelmintics, failed to develop.
He then fed mature eggs to a number of c hildren, initially in small numbers, but
later gave several dozen ova to each child. No worms were ever evacuated after
anthelmintic therapy, but in one or two children, fever with dyspnoea occurred
a few days after administration of the eggs 85. Similarly, Leuckart in 1867 failed
to achieve patent infections in dogs, rabbits, pigs and mice fed wit h
embryonated eggs. Likewise, he failed to infect a horse directly with eggs of A.
megalocephala (= Parascaris equorum), a dog with those of A. marginata (=
Toxocara canis), and a cat with eggs of A. mystax (= Toxocara mystax = T.
cati), all of these ascarids being natural parasites of these hosts. These findings
convinced Leuckart that there must be intermediate hosts for this group o f
parasites. In support of such an hypothesis, he noted that A. acus, which was
found as an encysted larva in Leuciscus alburnus, occurred in the adult form
in the pike, and that a larval Ascaris encysted in the muscles of a mole ,
continued to develop when administered to a buzzard. Finally, Leuckar t
considered that Davaine's experiment with rats indicated that the rat was th e
intermediate host, and the free larvae excreted in the rat's faeces would mature
after subsequent ingestion by humans 75. Others took up similar ideas. Fo r
example, von Linstow (1886), believed that a garden myriapod, Iulus
guttulatus, was the vector. He suggested that these creatures ingested Ascaris
eggs in human excrement deposited in the garden, the eggs then hatched and
the larvae encysted in their organs. The myriapods then parasitized variou s
fruits and were eaten accidentally by humans 78.
On the other hand, experiments with other ascarids suggested that no inter-
mediate host was necessary. In 1868, Unterberger showed that A. maculosa (=
Heterakis maculosa = Ascaridia columbae) of the pigeon developed directly,
and Henry (1873) found that A. mystax of the cat and dog were transmitted in
a similar fashion. In 1879, Battista Grassi in Italy undertook an experiment in
an attempt to settle the matter. On 20 July 1879, he ingested about 10 0
embryonated eggs of A. lumbricoides that had been obtained the precedin g
October from the large intestine o f a cadaver and that had been cultivated since
that time. On 21 August 1879 (22 days later ), he claimed to have found Ascaris
eggs in his faeces, thus indicating that direct infection had occurred 51. This
report must be viewed with some circumspection, however, in view of th e
unusually short incubation period that he indicated. A few years later ,
Calandruccio repeated this experiment. He swallowed a large number o f

embryonated eggs but was not able to infect himself. He had more success ,
however, with a seven year ol d boy who had been infected naturally previously
but had then been cured. At the end of September 1886, he gave 150 eggs in
a pill to the lad. He found no eggs in the faeces over the next 20 days, s o
abandoned the search until the end of November when he found the faeces to
be full of Ascaris ova. At the beginning of January, without having had an y
overt symptoms or signs of helminthiasis, the boy expelled 143 ascarids about
20cm in length. As discussed in chapter 18 concerning a similar study with the
transmission of Trichuris trichiura, Grassi published the results of thi s
experiment under his own name 52, without giving due acknowledgement t o
Calandruccio.
Similar experiments by a number of subsequent investigators confirmed the
result obtained by Calandruccio. Lutz in Brazil in 1887 infected a 32 year old
woman with 96 embryonated eggs over a period of one month. A few day s
later, she developed a severe bronchitis accompanied by a remittent fever .
When she was later given an anthelmintic, she passed 35 adult Ascaris 80.
Epstein in Germany then infected three children experimentally by feedin g
them with A. lumbricoides ova on 28 January 1891. Two of the three children
remained in hospital and systemati c examination of their faeces for nearly three
months failed to reveal any Ascaris eggs. On 24 April (86 days after infection),
however, microscopical examination showed great numbers of ova in the stools
of both children. The subsequent administration of santonin expelled 2 2
Ascaris from one child and 72 worms from the other. Moreover, Epstei n
became infected accidentally during the course of his experiments 37. Finally,
Koino infected himself successfully with A. lumbricoides in 1922 (see next
section).
DISCOVERY OF MIGRATION OF LARVAE WITHIN THE HOST
When the development of the larva within the egg had been discovered, attent-
ion turned eventually to studyi ng the anatomy of the newly-liberated larvae, the
most important studies in this regard being done by Hallez 54,55. However,
uncertainty still surrounded the nature of the events occurring betwee n
ingestion of the eggs and maturation of the worms. A number of observer s
including, Heller, Leuckart, Grassi, Laennec, Küchenmeister and Vix had seen
immature worms. For example, Heller in Erlangen in present-day Wes t
Germany, had found 18 small worms between 2.75 and 13 mm in length in the
small intestine of a madman; each head had the three characteristic lips but the
sexes were indeterminate 56. It seemed clear, therefore, that growth an d
maturation took place within the small intestine, but the details were unclear.
In order to examine an analogous system, Leuckart studied the development of
A. mystax in the cat. According to Blanchard, Leuckart found larvae 0.4 mm
Ascariasis 475
long in the stomach soon after ingestion. They stayed there until they wer e
1.5-2 mm in length, then passed into the intestine. When the worms ha d
reached 2.8 mm in size, they moulted, losing their perforating tooth an d
acquiring the three lips that were prominent in adult parasites. Blanchar d
(1890) commented that it was likely that A. lumbricoides developed in the
same manner in humans 12. On the other hand, Martin found that the larvae of
the ascarids of the calf, pig, horse and dog only hatched when eggs reached the
small intestine, as indeed Davaine had found in rats that had been given A.
lumbricoides.
No further significant advances were made until Francis Stewart, an English-
man working in Hong Kong, began to exp eriment with Ascaris in pigs in 1915.
First, he fed large numbers of embryonated A. suum eggs to a pig on 13
occasions between 20 September and 6 December 1915. When the animal was
killed on 15 December, only one small Ascaris was found. A second pig was
given large numbers of mature A. lumbricoides ova between 27 September and
2 December 1915; its faeces were examined repeatedly until 17 April 1916 ,
but no eggs were found. Stewart interpreted these findings as indicating tha t
direct infection did not occur, so he reverted to the modes of investigation used
50 years earlier by Davaine. On 6 April 1916, he fed mature A. lumbricoides
ova to four rats. Faeces passed between six and 22 hours later contained free
larvae of A. lumbricoides. Thereupon, Stewart gave A. suum ova three times
to three of the rats and twice to the fourth rat which then received a second dose
of A. lumbricoides ova. Two days after its final infection, the last rat died. At
autopsy of this animal, the lungs appeared congested and microscopica l
examination revealed numerous active larvae. A few larvae were also found in
the liver. The other three rats seemed to have pneumonia, so one of them was
killed and abundant larvae were again found in the lungs. Histologica l
examination of the lungs of these rats r evealed larvae in the alveolar spaces and
in the bronchi. The third rat was killed 12 days after the last infection, but no
larvae were found. In order to determine whether larvae in the lungs of a ra t
were capable of further development in another host, Stewart gave portions of
infected lung to a pig. He killed the animal two weeks later but failed to fin d
any ascarids. Nevertheless, he advanced some possible reasons to explain this
negative finding and concluded:
The life history of A. lumbricoides presents an alternation of hosts....When ripe eggs
reach the alimentary canal of the rat....or mouse....they hatch. The larvae liberated
enter the bodies of their host, a few only escaping in the faeces. Between four and six
days after infection they are found in the blood vessels of the lungs and liver . . On the
sixth day, they have passed from the blood vessels into the air vesicles of the lung
causing haemorrhage into them....they are (then) found....in the bronchi....On the
sixteenth day the host is free from parasites....It is obvious that the transfer of the
parasite from the bronchi of the rat and mouse to the intestine of man and of the pig
could be readily effected. The intermediate host might readily contaminate the food
of the definitive host and the dust and earth of his surroundings. 115
Stewart's paper was published in the British Medical Journal of 1 July 1916 115.
In the issue of the following week, a laudatory letter written by Ronald Ross,
the discoverer of the life cycle of malaria, appeared:
Will you allow me space to offer my warmest congratulations to Captain F.H. Stewart
I.M.S., upon his work on the above subject [the life history of Ascaris lumbricoides],
the most important medical work which has been done for a long time past. The mode
of entry of Ascaris has perplexed everyone from the beginning of parasitology,
because no intermediate host could be found, or even suggested, while direct infection
seemed unlikely for many reasons, in spite of the alleged result of various
experiments. That rats and mice are apparently the intermediate hosts will come as a
great surprise to many, and will constitute a valuable addition to medical zoology. 109
No doubt with his own experie nce in mind of when he was ordered to abandon
his malaria research at a critical stage in favour of studies on kala azar, Ross
added:
His paper is also another proof of the common observation that important discoveries
must wait until the proper kind of worker comes along to tackle them. I hope sincerely
that, in spite of the war, every facility will be given to Captain Stewart to complete his
invaluable work.109
In fact, this was the first of a series of fragmented, confusing and contradictory
reports which were spread over the next five years. Stewart at first placed an
emphasis on his observation exactly the opposite to the correct state of affairs.
However, an editorial in the British Medical Journal discussing Stewart's first
paper made no reference to his theory that rats and mice were intermediat e
hosts in the life cycle of A. lumbricoides and, no doubt with the experiments of
Calandruccio and others in mind, suggested instead that the complete cycle of
migration through the lungs and d evelopment within the one host might occur 5.
There was, of course, precedent for this idea, for Looss had demonstrated ten
years earlier a similar sequence of events in ancylostomiasis (see chapter 20).
Nevertheless, Stewart was so upset that he wrote complaining that insufficient
weight had been given to his experiments on pigs in which he failed to induce
direct infection and he rejected as untenable the idea that Ascaris passes
through the lungs of the same host as that in which it attains full maturity 116. It
must be said in Stewart's defence, however, t hat these experiments were carried
out under extremely difficult conditions during wartime. He himself was well
aware of the deficiencies for he wrote in a footnote to one paper:
The author regrets that he is obliged to publish incomplete work and pleads in excuse
that he has been obliged to discontinue the research, not knowing when he will have
an opportunity of resuming it.121
Although Stewart made a major contribution in discovering the systemi c
migration of Ascaris larvae, subsequent events were to show that he was quite
wrong in ascribing transmission to an intermediate host. In fact, he did not give
up the idea of an intermediary role for rod ents for some time. He postulated that
larvae might escape from the rodents in their saliva, and showed that larva e
obtained from the lungs could survive for up to 24 hours on damp bread 117. He
then repeated his attempts to transfer A. lumbricoides larvae to pigs; he fed
infected rat and mouse lung to four pigs and recovered small numbers (1-15)
Ascariasis 477
of ascarids in three of them and no worms in the fourth pig. Although Stewart
wrote that these experiments could hardly be considered very satisfactory, the
fact that two control pigs had no worms, enabled him to cling to the belief:
The experiments which have been conducted so far tend to prove that the larvae from
the lungs of rodents can infect the pig, and it is probable that in nature infection in
man and the pig takes place by food contaminated by rats and mice. 117
More enduring, however, were his studies of the migration of worms in mice.
Stewart believed that A. lumbricoides larvae hatched when the eggs wer e
ingested then either bored their way into the venules of the portal system o r
ascended the bile duct. He found larvae in dilated hepatic capillaries between
two and five days after infection following which they escaped through th e
hepatic veins to the lungs where they were filtered out in the pulmonar y
capillaries. They then passed together with effused blood into the alveola r
spaces on the sixth day and the worms ascended the bronchial tree and reached
the mouth by the eighth day117,119. Stewart found later, however, that the larvae
in the mouth were swallowed subsequently and passed through the intestines
to be excreted in the faeces 118,120.
In 1917, Ransom and Foster in the United States repeated many of Stewart's
experiments. They confirmed the systemic migration of A. suum larvae in rats
and mice. They also attempted to infect pigs, and although they failed t o
achieve patent infections, suggested, on very tenuous grounds, that this ma y
have been due to the age of the animals rather than indicating that an inter -
mediate host was required 101. Nevertheless, Sadao Yoshida reported in 1918
that it was possible for infection to be acquired from larvae obtained from an
intermediate host. He swallowed A. lumbricoides larvae taken from the lungs
of a guinea pig, but at first had a negative result. He then ingested 50 large r
larvae (1.65 mm long) recovered from the trachea of a guinea pig and foun d
eggs in his faeces 75 days later 141.
Meanwhile, because of repeated suggestions that no intermediate host was
necessary and that migration and maturation occurred within the same host ,
Stewart undertook further experiments with A. suum infections in pigs. He
showed that, in this host too, larvae migrated through the lungs with the pigs
suffering from Ascaris pneumonia. However, he failed to find convincin g
evidence of adult worms in the gut three to four weeks later and considered (in
1918) that while the matter was not yet fully resolved: "the evidence of these
six experiments is opposed to the hypothesis of direct development without an
intermediate host"121. Even so, he continued to be plagued with uncertainty. In
1919, Stewart reported the results of infecting two four-day-old pigs wit h
22,000 A. suum eggs. Large numbers of ascarids were seen in the intestines of
one pig two weeks later, but none at all could be found in the other pig killed
after another five days. A third pig, two months old, was given 50,000 eggs ,
and when killed 31 days later; no worms could be found. Stewart wrote with
masterly understatement: "these experiments are very puzzling" 122.
Later in that same year (1919), Ransom and Fos ter announced that A. lumbri-
coides larvae migrated systemically in g uinea pigs and rabbits as they do in rats
and mice. They also infected a goat twice with A. suum eggs. It died ten days
later and numerous larvae, 1-2 mm long, were found in the lungs, trachea ,
oesophagus and stomach, and thousands of young ascarids, 10 mm in length,
were seen in the small intestine. A lamb had also been fed with ova and killed
103 days later; 50 immature ascarids, 6-13 cm long, were recovered from the
bowel. These results reinforced Ra nsom and Foster in their belief that infection
was direct 102.
Stewart later (1920) came round to this view when he found young worms
in the small intestine of three pigs fed with A. suum eggs124, for he wrote in
1920: "It is extremely probable that the worm can undergo full development in
one host alone - that is, man or the pig" 123.
Final proof that this was indeed the case was provided by Shimesu Koin o
(pen name Sui) in 1922. On 28 August, he ing ested 2,000 A. lumbricoides ova.
A single larva was found in his sputum three days after infection, five on th e
next day, and 178 on the fifth day. He was unable to collect any sputum on the
succeeding two days because he was seriously ill but larvae were then found
again for the next four days. Fifty days after ingestion of eggs, he took a n
anthelmintic and recovered 667 immature A. lumbricoides. Thus, Koino proved
that A. lumbricoides larvae both migrate through the lungs and develop within
the intestine of the same human host 68.
While it was now clear that systemic migrati on occurred and that worms mat-
ured in the one host, uncertainty remained about the precise route by whic h
larvae reached the lungs after hatching in the gut. Yoshida (1918) claimed on
the basis of his experiments that Ascaris larvae bored their way through th e
intestinal wall into the peritoneal cavity, pierced the diaphragm, entered th e
pleural space, then finally penetrated into the lungs from the surface, as ha d
been shown with Paragonimus 142. This view was refuted by a number o f
investigators who showed that larvae passed via the portal vein to the liver ,
then by the hepatic veins and inferior vena cava through the right heart to the
pulmonary vasculature, or via the mesenteric lymphatics and the thoracic duct
to the venous system, and that larvae in the viscera reached those location s
through the systemic circulation 7,40,86,87,100, although one of the authors 7
considered that some larvae might also reach the liver via the peritoneal cavity.
In addition, Ohba in 1925 showed that larvae could be excreted in the urin e
during the migratory stage, with t he maximum output occurring five to six days
after infection 88.
In 1927, Fülleborn41 put all the known facts together and postulated that the
reason why A. lumbricoides larvae could not settle in the gut initially wa s
because this species may have originally re quired an intermediate host, as is the
case with certain fish ascarids, and that later, the definitive host became th e
intermediate host as well. Since Kondo 69 had shown under experimenta l
conditions that artificially-liberated Ascaris larvae smeared on the ski n
Ascariasis 479
penetrated the integument then underwent migration, Fülleborn believed that

in order for maturation to occur, larvae must first penetrate either the skin or
gut wall, then pass to the lungs where they would be returned by the ciliate d
epithelium to the oesophagus. Thus, it seemed that the definitive host could be
infected not only by larvae which had penetrated its own intestine (the usua l
case), but also (unusually) by eating an animal which contained larvae which
had passed through that animal's lungs (as shown by the experiment o f
Yoshida), or when such larvae penetrated the skin (as shown by Kondo' s
experiment).
Controversy has also surrounded the nature and timing of the moulting o f
Ascaris larvae. In 1924, Asada reporte d that, shortly after hatching, the Ascaris
larva moulted in the small intestine. He though t that a second ecdysis took place
while the worms were in the airways, then two further moults occurred o n
return of the worms to the intestine 8. In 1918, however, Yoshida ha d
recognized that the first moult took place while the larvae was still within the
egg shell141. For many years, it was accepted that the infective stage whic h
emerged from the egg was a second stage larva. In 1968, Thust reported that
the larva moulted twice while within the egg shell 131, although Maung believed
that the second ecdysis might be completed during early migration 82. Recent
studies in experimental animals have shown that the third moult occurs when
the larva lies within the intestinal mucosa and is about 2 mm long. The worms
then live free in the intestinal lumen and have a final moult three to four weeks
after infection with egg production beginning eight to twelve weeks afte r
infection.
The adult worms live for between one and two years. Keller in 1931 showed
that in a group of patients living in an are a unsuitable for transmission, and who
did not receive treatment, the infections were eliminated spontaneously over a
period of fifteen months 66. Similar observations on Japanese prisoner s
suggested that the worms survived for an average of seventeen months (range
10-24) 58.
Whether or not resistance to reinfection occurs is controversial though th e
weight of evidence suggests that i t does not. Jung 64 believed that superinfection
does not occur when eggs are newly ingested during the tenure of a curren t
infection, but there have been litte data since to support or refute this view .
Certainly, reinfection seems to occur easily following eradication of a prio r
infection with anthelmintics. Otto and Cort in 1934 showed that reinfection was
rapid, widespread and intensive after treatment of nearly 300 children wit h
hexylresorcinol; eight months after treatment, 85% of the children wer e
reinfected, and the mean number of Ascaris eggs per gram of faeces wa s
33,000 c.f. 23,000 before therapy 91. Similarly, a Japanese study showe d
showed that reinfection appeared approximately two months after treatment 93,
while another investigation in the Philippines indicated that 69% of childre n
were reinfected after four months and 90% were infected eight and a hal f
months after treatment 44.
The number of complaints that have been ascribed to Ascaris infection over the
centuries is legion. Spontaneous passage of the worms was well-known an d
Hippocrates wrote that this may be preceded by abdominal pain 57. Caelius
Aurelianus (c.450 AD) believed that these worms may cause the gnashing of
teeth by sleeping children, and that when large numbers were present, th e
abdomen became hardened 10. Paulus Aegineta of Alexandria (c.640 AD) des-
cribed in detail what he considered to be the clinical manifestations o f
ascariasis:
Those who have roundworms experience pain of the intestines and stomach, small
dry tickling cough, and in some cases hiccough, sleep with palpitations and irregular
startings; and some start from their sleep with a scream, and again fall over asleep.
The pulse is unequal and the fever has irregular exacerbations, making its attacks with
coldness of the joints, and coming on three and sometimes four times in the day or
night. Children have mastication and projection of the tongue....and grinding of the
teeth; they shut their eyes and wish to remain silent and are offended when disturbed.
Their eyes appear bloody, their cheeks red, and again change to pale. But these things
occur at intervals in a short time. Sometimes the worms crawling up to the stomach
occasion nausea, gnawing pain, and anorexia....When forced to take food, they can
scarcely swallow for nausea, or they vomit what they have taken, or their bowels are
loose with corruption of the food, or are inflated like a bladder, but the rest of the body
is wasted....But one must not expect to find all these symptoms in all cases, but certain
ones, according to prevailing circumstances.1
According to Hoeppli, the Chinese physicians of around the third century AD
considered that ascariasis altered the character of the pulse in various ways:
A pulse felt at the upper Kuan portion to be under light tension and sliding in quality
indicates that ascaris becomes active....A pulse felt....to be floating in quality indicates
that the patient has stagnant heat in his stomach and will vomit ascaris. 59
Again, Hoeppli cites the following exchange:
"What is the distinguishing feature of the pulse in a case of abdominal pain caused by
worms?" somebody asked. The physician replied: "During the ordinary abdominal
pain the pulse becomes feeble and thready. If, on the contrary, it is full and bounding,
it indicates the sure presence of ascaris in the abdomen." 59
Such views changed little over the centuries. As late as 1829, the Englis h
surgeon, William Rhind, gave a comprehensive and remarkable account of the
symptoms and signs that were then believed to attend the presence of intestinal
worms (both roundworms and tapeworms):
The most general symptoms observable in those affected with worms are the
following: - The appearance of the countenance is changed, it is generally very pale
or of a leaden colour, with a red, circumscribed spot in one or both cheeks. The eyes
lose their brilliance, the pupil is enlarged, and a blue rim is perceivable round the
under eyelid. The nose is swelled and very generally the upper lip is somewhat
Ascariasis 481
tumified, and there is continual itching and irritation of both these. Sometimes, too,
there is a bleeding from the nose. There is also headache, throbbing in the ears, a foul
tongue, more saliva than natural in the mouth and the breath is very fetid especially
early in the morning. The appetite is variable; sometimes it is quite gone and at other
times it is voracious with a continual gnawing sensation in the stomach. There is also
nausea and a desire to vomit; when this takes place, the fluid ejected is limpid like
water. There are often violent gripings, and these are principally felt around the
umbilical region. The urine is turbid and after it has deposited a sediment, it has the
appearance of milk and water. The belly too is hard, and feels like a drum. There is
a general emaciation of the body; the sleep is troubled and accompanied by grinding
of teeth. The patient is generally lazy and indolent, sometimes in good and sometimes
in irritable temper. Blindness, deafness, delirium, and even apopleptic and epileptic
fits have been known to have their origin from these worms. The last and most
decisive symptom observed is that in the matter vomited, but more generally in the
alvine secretions, entire worms or portions of them are perceived. 107
Rhind did, however, add some caveats:
It must be remarked that all the above symptoms are not always found in the same
individual; nor do any of them, except the last, exclusively indicate the presence of
worms. When these symptoms occur and cannot be attributed to any other cause, the
strong presumption is that the cause is worms....At the same time, it may be
mentioned that worms sometimes exist, and that in considerable quantities, without
causing any inconvenience or bad symptom whatsoever. 107
The observation that worms may cause no i ll-effects had even led some observ-
ers such as Avicenna, Roeder er and Abildgaard to suggest that worms may not
only be harmless, but may be very useful in the alimentary canal by consuming
excessive nutrients and stimulating bowel movements. Rhind thought that this
was fanciful and deprecated such ideas, saying:
like all other diseases and all other evils which are incident to man, they are to be
combated and warded off by the wisdom and foresight with which he is endowed for
that purpose.107
In contrast to all-encompassing views of the symptomatology of Ascaris
infection, such as espoused by Rhind, Küchenmeister was closer to the trut h
when he wrote baldly in 1855: "as a general rule, the host and his guests agree
very well together and give one another very little mutual trouble" 70. Küchen-
meister did recognize, however, that these parasites could occasionally cause
intestinal obstruction or rarely produce jaundice, pancreatitis or layryngea l
spasm, and had been known to wander through intestinal fistulae.
Even so, a wide range of clinic al manifestations of Ascaris infection was still
accepted by many practitioners, and w as explained on the basis of two different
mechanisms33. Firstly, gastrointestinal symptoms and signs were clearly local
reactions consequent upon the presence of worms in the alimentary system. It
was recognized that roundworms were u sually located in the small intestine but
occasionally they were met with in the biliary system, mouth and pharynx, or
respiratory system. Secondly, "ref lex irritation" or "sympathetic excitation" was
held to account for the diverse non-gastrointestinal symptoms commonl y
blamed upon intestinal helminthiasis. This vague concept seemed to man y
observers to be the only reasonable explanation for the coincidence betwee n

expulsion of intestinal helminths and resolution of the symptoms. Date in 1872
summed up the attitudes prevailing at the time:
It has been the fashion of recent writers....to assert that worms, of themselves, never
give rise to symptoms of any kind. This view, no doubt, is a reaction from the old
notion which attributed to intestinal worms all sorts of extraordinary phenomena. The
truth....seems to lie between the two extremes. I have repeatedly seen cases in which
the expulsion of the worm has been followed by a relief of urgent symptoms so
immediate and marked as to convince me that the worm itself was the cause of the
mischief. . On the other hand, it cannot be denied that worms may and often do exist
in the intestinal canal, even of delicate children, without giving rise to any special
symptoms. It may be that reflex irritation is induced only in children of very excitable
temperament, or in certain peculiar states either of the general nervous system or of
the intestinal mucous membrane. Certainly the gravity of the symptoms does not
appear to depend upon the number of worms, except in those rare cases where they
have multiplied to such a degree as to cause obstruction of the bowel. 29
Debate continued until the turn of that century over the validity of the refle x
irritation theory, but it gradually fell by the wayside. For example, it becam e
accepted slowly that the passage of rou ndworms during an epileptic fit or in the
course of a febrile episode was the consequence of an inhospitable milie u
rather than the cause of those disturbances.
The discovery by Stewart in the early twentieth century of the pulmonar y
migration of Ascaris larvae caused a number of observers to look back in the
literature and see evidence of pulmonary ascariasis in the patients of Mosler 85
and Lutz80 who developed respiratory symptoms shortly after the experimental
ingestion of A. lumbricoides ova. This was confirmed in a dramatic fashion in
1922 by Koino, who recovered larvae from his sputum and described hi s
symptoms and signs after ingestion of 2,000 such eggs:
On the sixth day....there was fever followed by chills, headache was severe and
respiration and pulse were increased. The face was flushed and I was thirsty. There
was a heavy feeling over the chest....The temperature on the second day after the
onset rose up to 39.8 and remained between 38.7 and 40.2. It began to come down
by crisis on the seventh day and on the ninth day was normal. Respiration increased
and became shallow. On the fifth and sixth days there was severe respiratory difficulty
and the face was cyanotic. The number of respirations was from 56 to 58 per minute.
From the seventh day on the number of respirations decreased....The cough increased
with the rise of temperature....It came in paroxysms with intervals of two to five
minutes at the height of the attacks....The amount of sputum increased with the
increase of coughs. There was 35 cc. of sputum on the first day. On the fifth day up
to 7 p.m. it was 155 cc. There was a large amount of output for the following few
days. A noticeable thing was that sputum of the fifth and sixth day contained
well-mixed blood. The eighth day on it decreased.... Appetite....was lost....There was
severe lumbago on the third and fourth day and pains in the gastrocnemius
muscles....As to the objective symptoms....the rales [moist sounds heard on
auscultation of the lungs] and dullness increased day after day until breathing became
difficult and weak. But when the crisis had begun, the rales and dullness gradually
decreased....The liver....was enlarged to two finger's breadth below the costal margin
Ascariasis 483
on the right mammary line....On the twelfth day it was scarcely palpable. . The spleen
was not palpable.68
This clinical picture was re-described in 1932 by Löffler who, in addition to
recounting the clinical features noted by Koino, showed that transien t
pulmonary opacities were present in chest radiographs and that there was an
associated eosinophilia in the peripheral blood 79. Although Löffler's syndrome
was caused commonly by migrating Ascaris larvae, it was recognized tha t
migrating hookworm and Strongyloides larvae, as well as other agents, could
also cause the syndrome. Similar effects were noted ten years later by Voge l
and Minning in Germany who gave Ascaris ova to six volunteers 136, and then
by Brudastov and colleagues in Russia who undertook experimental self -
infections16.
In 1967, Gelpi and Mustafa found that outbreaks of acute respirator y
infection recurring each spring among young local employees of an oi l
company in Saudi Arabia were due to infection with A. lumbricoides; larvae
were found in the sputum then eggs were recovered from the faeces two t o
three months later 46. It was then realized that this presentation was mos t
common in areas where transmission was seasonal, for Spillman 113 showed that
pulmonary ascariasis was rare in areas where transmission was continuou s
throughout the year.
Because populations rarely have solitary A. lumbricoides infections, there
have been few studies of the clinical manif estations of pure intestinal ascariasis,
and it is probable that Küchenmeister's summation of the situation may years
ago was fairly accurate. Nevertheless, small numbers of worms in ectopi c
locations can cause significant and sometimes fatal disease. There have been
hundreds of such reports in the literature of the twentieth century alone, bu t
they represent a very small fraction of the total number of infected persons .
Ascarides have on occasion caused obstructive jaundice, liver abscess ,
pancreatitis, appendicitis and respiratory obstruction, and have migrate d
through intestinal perforations and fistulae, and out through the mouth and the
nose. Of all the various complications, however, intestinal obstruction is th e
most frequent. In a series of 202 cases who had either solitary ascariasis or light
infections with Trichuris trichiura as well, Swartzwelder in New Orleans ,
USA, found in an uncontrolled and selected study that abdominal discomfort
was the chief symptom, fever was quite often present, and that intestina l
obstruction occurred in 18 patients 125.
Although most individuals have only one or two worms, rare patients have
vast numbers. An adult patient in Peiping, China presented with a perforated
intestine; even though 1533 worms were removed from the peritoneal cavity
at operation, he died subsequently and a further 445 worms were recovered at
autopsy, bringing the total number to 1978 ascarids 60. Similarly, 1488 worms
were removed from a patient in Malaysia110, 990 were recovered from a nine
year old European girl and 899 from an eleven year old Hottentot in Sout h
Africa76, and 693 worms were obtained from a two year old child with intestinal
obstruction in East Africa 47.

Argument over the contribution of ascariasis to malnutrition has raged fo r
decades 112, but perhaps the first person to pay any serious attention to thi s
subject was an English ship's surgeon, Percy Rendall, in 1892. He was i n
charge of 557 Indian coolie emigrants on a voyage from Calcutta to Demerara.
He weighed every person then administered santo nin to everyone and recovered
989 roundworms, but thought that many more had gone over the side of th e
ship. He weighed his patients again two months later and found that there was
a net increase of 2240 pounds in their weight and considered that:
this result, though doubtless due to the generous dietary provided by the Colonial
Governments in some part, may I think, be not unfairly attributed to the fact that this
large number of roundworms had been expelled which would otherwise have caused
grave interference with the digestive functions and prevented the due assimilation of
food products.106
A diagnosis of Ascaris infection has been made from time to time when adult
worms are expelled spontaneously, usually in the faeces. The diagnosis i s
normally made, however, by finding Ascaris eggs in the stools. Such ova i n
faeces were first illustrated clea rly by Swayne in 1849, although he had no idea
of their true nature, believing them possibly to be involved in the causation of
cholera 126. Indeed, the Rev Mr Berkeley, in discussing the nature of thes e
bodies, went so far as to remark that: "w e still remain to discover what they are,
as it should seem that no ova of entozoa are known which can be reconcile d
with them"11. In 1854, Wedl described the histological examination of a n
intestinal concretion removed from an ingu inal abscess by H Ulrich. In addition
to T. trichiura eggs which Wedl illustrated clearly, other bodies were present
which he noted: "most nearly rese mbled those of Ascaris lumbricoides"137. The
eye of faith is required, however, to recognize such an egg in the figure h e
provided. The diagnosis of ascariasis by microscopical examination of th e
faeces was first put on a sound basis in 1856 by the English physician, W H
Ransom. Ransom described the case of a 12 year old girl who presented at the
Nottingham General Hospital complaining of abdominal pain and giving a
history of having passed two round worms after the administration of a n
aperient. Examination of her stools revealed "very numerous ova of ascari s
lumbricoides, the characters of which are well known and easil y
recognisable"103. and Ransom provided clearcut illustrations of Ascaris ova. It
is perhaps most remarkable that only seven years after an argument had raged
in the columns of The Lancet and the London Medical Gazette, and the College
of Physicians had been disposed to produce a report on the nature of thes e
so-called "cholera bodies", that Ransom was able to write so facilely that the
morphological characteristics of these eggs were well-known and were easily
Ascariasis 485
recognizable. In the following year, Davaine in France likewise demonstrated

Ascaris eggs in the faeces of a child who ex pelled subsequently five or six adult
worms30.
The diagnosis of ascariasis turned out to be extremely easy, for it was found
that female worms produced vast numbers of eggs. Brown and Cort calculated
that approximately 200,000 ova were excreted in the faeces by each femal e
worm every day15. This technique had been put to use to make retrospectiv e
diagnoses of ancient Ascaris infections. For example, eggs have been found in
human coproliths, dated 800-300 BC, recovered from a prehistoric salt mine
in Austria9, and from the intestinal contents of a girl's body (600 BC) recovered
from a peat bog in East Prussia 127.
While most eggs are characteristic, variations occur and mistakes have been
made in diagnosis. In 1922, Miura and Nishiuchi drew attention to the appear-
ance of the not uncommon unfertilized eggs 83. Vegetable matter has bee n
mistaken for Ascaris ova, perhaps the most famous example being the erron-
eous report by Tullis that 90% of asthmatics who lived in a non-endemic area
in Canada had ascariasis 67,132.
These roundworms are so large that they may be seen radiologically, partic-
ularly with contrast radiography. In 1922, Fr itz reported that X-ray examination
had revealed ascarids wandering from the duodenum into the stomach 39. In the
following year, Reiter described one patient in whom numerous roundworms
were seen in the jejunum and ileum, and another in whom an Ascaris was seen
lying coiled in the stomach 105. In 1924, Schinz reported that X-ray examination
of a 40 year old woman after a bismuth meal revealed a "worm-like absence of
shadow"111 and that roundworms were passed after anthelmintic therapy 111.
Pulmonary ascariasis may be diagnosed by finding larvae in the sputum a s
was shown by Koino 68. Many years later, Proffit and Walton indicated tha t
ascariasis may also be diagnosed during the migratory phase by finding larvae
in gastric aspirates 99.
The immunological diagnosis of ascariasis has not proved to be particularly
useful. Ghedini in 1907 described complement fixing antibodies in the serum
of patients with Ascaris infection48, while skin reactivity in such patients was
described by Brunner 18, and by Coventry and Taliaferro 27,
Over the centuries, a large number of agents has been used for the treatment of
ascariasis. These comprised two major grou ps of compounds: purgatives which
expelled worms by increasing peristalsis and stimulating intestinal secretion,
and vermifuges, including substances of vegetable, animal or mineral origin,
which poisoned the worms themse lves. Concerning purgatives, Elliotson in his
lecture on worms in 1833 wrote that:
As to getting rid of worms, in the first place, any brisk purgative may answer the
purpose. A good dose of calomel and jalap is an old remedy and a very excellent
one....(or) twelve grains of calomel and half a drachm of rhubarb. 36
With respect to destruction of roundworms, Elliotson advised that oil o f
turpentine was one of the best remedies available:
(it) should be given by the mouth and the dose then is from half an ounce to three
ounces. It is best not to give it fast lest it should create sickness and be lost....The
effect it generally produces is that of making the patient sick, purging him
violently....and causing extreme vertigo.36
As the century progressed, this drug was replaced gradually in popularity by
santonin, the active principle of semen-contra-vermes, so-called because of its
vermifugal properties and its fanci ed resemblance to semen. The drug was pre-
pared from the dried, unexpanded flower heads of the genus Artemisia,
especially A. cina which is common in the Midd le East. Thus, Anderson (1864)
wrote:
The introduction of 'santoninum' into the British Pharmacopoeia was no more than
was expected by those practitioners who have for several years been convinced of its
efficiency, and especially of its superiority to all known anthelmintics in the treatment
of roundworm.4
Because of its toxicity and non-uniformity in its therapeutic effectiveness ,
however, santonin fell into disuse as better drugs became available. Thes e
agents included oil of chenopodium and its active principle, ascaridole ,
prepared from Chenopodium ambrosioides var. anthelminthicum, common in
the United States of America, and thymol found in a large number of plants of
the genera Thymus (thyme), Origanum and Carum (ajowa). Thus, Vervoort in
1913 compared oil of chenopodium, thymol, Eucalyptus oil and sundry other
anthelmintics, and concluded that wormseed oil (oil of chenopodium) was a
good anthelmintic in ascariasis, rather more expensive than thymol, bu t
possessing the advantage of being able to be given in capsules 135.
Another product active agains t Ascaris was helminal, a dried extract of a red
alga, Digenea simplex 35, which had long been used as a popular vermifuge in
Japan, the active principle of which was kainic acid. The anti- Ascaris
properties of the alkylated phenol, hexylresorcinol, were first studied b y
Lamson and colleagues in 1931 71 and this drug became popular for the treat-
ment of ascariasis in the United States. Betanaphthol and carbon tetrachloride
also enjoyed transient popularity with some practitioners. Following the use of
piperazine in enterobiasis (see chapter 17), F ayard in a thesis presented in Paris
in 1949 gave an account of its efficacy in some 2,000 patients with ascariasis;
70-95% of people passed roundworms on the second and third day afte r
treatment, but stool examinations in order to assess the percentage of cures and
the reductions in egg excretion were apparently not performed 38. The efficacy
of the drug in its various forms was confirmed in many published studies ,
beginning in 1954 with those of Brown 14 and Brumpt and Ho-Thi-Sang17 .
Meanwhile, the piperazine derivative, diethylcarbamazine, was shown b y
Ascariasis 487
Oliver-Gonzalez and colleagues in 1949 also to be effective 89.

Bephenium hydroxynaphthoate, one of a new series of drugs first described
in 1958, was shown in the same year by G oodwin and his colleagues during the
course of a pilot study of its effectiveness against hookworm, to be active i n
ascariasis50. In a follow-up study using varying doses of the drug, Jayewardene
and her colleagues found that approximately 90% of patients had at least a n
80% reduction in eggs counts in the faeces 63. In 1962, Bui-Quoc-Hong an d
co-workers reported that the benzimidazole compound, thiabendazole (se e
chapter 21), cured 80% of patients with ascariasis 19. Nine years later, it was
shown by several groups of investigators that the related compound ,
mebendazole (see chapter 3), was highly active against Ascaris
lumbricoides 24.
In 1966, Do Nascimento and colleagues indicated that a new compound ,
tetramisole, eliminated Ascaris infection in 80-90% of patients 34. Several years
later, it was shown that the laevo-isomer of tetramisole, levamisole, was even
more active than the racemate 130.
Another new series of anthelmintics, the pyrante l compounds, was discovered
in 1966. In 1970, pyrantel pamoate was found to be useful in the treatment of
ascariasis by Amato Neto and colleagues 2.
While the administration of anthelmintics is the almost universal method of
treating ascariasis, one physical measure which enjoyed some transien t
popularity in the Soviet Union must be mentioned. One to two litres of oxygen
were given intermittently over ten minutes through a duodenal tube, then a
magnesium sulphate aperient was given two hours later. Dead ascarids were
then usually passed two to three days afterwards, and Talyzin (1954) wrote :
"The above method is so simple and safe that it has often been used fo r
outpatients, and large groups of people can be disinfested quickly" 129.
Finally, surgery has been used for most of this century to treat certai n
complications of ascariasis, such as intestinal and biliary obstruction b y
roundworms.
Comprehension of the factors controlling the distribution and prevalence o f

ascariasis dawned only slowly over t he seventy years between the studies in the
middle of the nineteenth century by Gros, Davaine and others on the develop-
ment of the egg, and the general acceptance at the end of World War I tha t
transmission was direct. Considerable uncertainty surrounded the roles of pigs
and the pig ascarid in the epidemiology of human ascariasis for some time (see
Ascaris suum). It transpired eventually that although pigs may be susceptible
to infection with A. lumbricoides, and despite the experimental infection o f
various subhuman primates with A. lumbricoides 90, humans are the most
important host of A. lumbricoides and the major determinant of th e

epidemiology of this infection.
A number of investigators demonstrated that larval development within the
egg occurred at a faster rate in warmer temperatures, and that moist, shad y
locations facilitated such development 13,101. It was shown that maximu m
transmission took place when the soil was composed of clay or fine silt, fo r
these materials provided a light covering to Ascaris eggs after rains, thus
protecting them from dessication but leaving them near the surface where they
were more likely to be ingested. Furthermore, the ova were found to b e
relatively resistant to low temperatures, dessication, various chemicals an d
putrefaction28,141. Under certain conditions, they may remain dormant for years,
thus permitting reactivation of infection upon the return of favourabl e
environmental circumstances.
Consequently, it was apparent that transmission was dependent upon frequent
contamination of the soil with faeces, favourable climatic and soil factors, and
ingestion of contaminated eggs in various vehicles 92,138,139. The precise nature
and importance of these various determinants was found to vary from region to
region. In some areas, promiscuous defaecation by small children was the main
source of contamination138, while in other areas, the use of human night soil as
a fertilizer in vegetable gardens was a major factor 140. In his review of the
modes of infection, Lane (1934) indicated that the most common means o f
transmission were consumption of eggs adhering to vegetables or other food,
the drinking of contaminated water, and ingestion of infected soil by children.
Of possible but unproven significance were inhalation of airborne eggs an d
percutaneous infection by liberated larvae 72. Under adverse conditions ,
breakdown of sanitary measures may result in an increased incidence o f
ascariasis, such as occurred in Germany after World War II, probably as a
result of eating vegetables and ground-fruit on land irrigated with untreate d
waste water 45.
Many years ago, Chandler wrote that A. lumbricoides has been one of Man's
most faithful and constant companions from time immemorial, and has clung
to mankind through the stone, copper and iron ages up to the present day. He
went on to predict that modern plumbing would eventually dissolve th e
partnership25. The financial, technical, and educational difficulties in providing
effective waste disposal systems in most endemic areas, however, ar e
enormous, and the words Lane wrote fifty years ago are just as apposite today:
Sewered privies cleanly kept are sure safeguards for the user. But to devise privies of
demonstrable effectiveness and inoffensiveness, to provide them for millions of
people of poor means, and to alter the habits of these so that they religiously use and
clean them, is a task which will not be completed within the lifetime of any of us. 72
Ascariasis 489
The problem is compounded in communities were human nightsoil is used

as a fertilizer. The difficulties in such a situation are almost insuperable fo r
composting and the fashioning of faecal "bricks" 62 are ineffective in destroying
the parasites. Under such circumstances, reliance must be placed upon thor -
ough cooking of the vegetables, but this is of little relevance in the case o f
vegetables such as lettuces and ground-fruits such as strawberries which ar e
eaten raw.
Mass treatment has been tried on a limited scale in selected localities, bu t
administration of anthelmintics has to be repeated frequently because of th e
persistence of viable ova in the environment. Such measures reduced th e
prevalence of ascariasis from 60% to 1.9% in one area of Japan over a period
20 years84, and similar results were obtained in another study in the Philip -
pines20. Unfortunately, such measures remain beyond the financial resources of
many countries that host endemic ascariasis.
OTHER SPECIES OF ASCARIS
A. SUUM
This parasite was so named by Goeze in 1782 49, but has also been referred to
frequently in the older literature as A. suilla, a designation given by Dujardin
in 1845. Confusion has reigned for many years as to the relationship between
A. lumbricoides and A. suum. Various investigators could not discern an y
morphological differences between the two form s until Sprent (1952) described
alterations in the labial denticles 114. While many workers have confirmed and
extended Sprent's observations, others have found them to be inconsistent, and
sometimes individual worms could not be differentiated reliably from on e
another. Similarly, differences of opinion have occurred over chromosoma l
numbers and biochemical and immunological characteristics. The sam e
problem has bedevilled using physiological differences in the infectivity o f
roundworms derived from humans or pigs for the opposite host as a
distinguishing feature.
In 1925, Payne and her colleagues infected five young pigs with embryonated
Ascaris eggs of human origin; all anima ls suffered respiratory disturbances, but
no adult worms were recovered from the gut 96. On the other hand, Galvi n
(1968) infected successfully pigs with A. lumbricoides ova, but the percentage
of ova which matured and the duration of infection were reduced when com-
pared with pigs infected with A. suum 43.
Koino in 1922 gave 500 A. suum ova to his brother and produced a severe
respiratory disease. He failed to find Ascaris larvae in the sputum or evidence
of intestinal infection, and contrasted t his with the results of infection of himself
with A. lumbricoides:
The pig Ascaris can not parasitise till adult worms in human. Therefore although
morphologically they are the same, they are entirely different. If there is a strain of pig
Ascaris which can parasitise in human, it must be a deviated strain. Human body is
not a good host for pig Ascaris.68
Similarly, Payne and her colleagues gav e A. suum ova to two human volunteers
but failed to produce patent infections 96. On the other hand, Takata claimed to
infect successfully 7 of 17 human volunteers who swallowed 2-25 A. suum
eggs, but the prepatent period in many of th em was extraordinarily short (25-29
days)128. Lýsek recovered mature worms from the gastrointestinal tract afte r
administering A. suum eggs to himself 81. Finally, four students in Montreal ,
Canada, swallowed unknowingly large numbers of eggs in food which had been
contaminated maliciously. They all developed severe respiratory infections. In
two of them, immature worms were passed in the stools four months afte r
ingestion of eggs, but no worms were recovered following anthelmintic therapy
seven months after ingestion 97.
Epidemiological evidence suggests that ther e is not much cross-over between
porcine and human ascarids. For example, Caldwell and Caldwell reported in
1926 that 45% of pigs in one region were infected with Ascaris c.f. only 1% of
humans, despite apparently fa vourable conditions for infection of humans from
that source22. Similar observations have been made since in other parts of the
world.
Thus, although the contribution of A. suum to human ascariasis cannot b e
determined precisely, it would seem that A. suum is a possible, though not a
major cause of this condition.
REFERENCES
1. AEGINETA P. De re medica. The seven books of Paulus Aegineta, translated by F
Adams, The Sydenham Society, London, three volumes, 1844-1847
2. AMATO NETO V, LEVI GC, CAMPOS LL. Observaçoes sobre a atividad e
anti-helmintica do pamoato de pirantel. I. Tratamento da ascaridiase. Revista do Instituto
de Medicina Tropical de São Paulo 12: 207-210, 1970
3. AMATUS LUSITANIUS. Medici physici praestantissimi. Curationum medicinaliu m
centuria quatuor etc, B Constantinus, Venetiis, pp 645, 1557
4. ANDERSON W. On santonine: with especial reference to its use in the round an d
thread-worm. British Medical Journal i: 443-445, 1864
5. ANONYMOUS. The life history of Ascaris lumbricoides . British Medical Journal ii: 23,
1916
F Dübner, E Heitz et UC Bussemaker (Editors), Didot, Parisiis, five volumes, 1848-1874
7. ASADA J. (Experimentelle Unt ersuchung ueber die Entwicklung und Infektionswege von
Ascaris lumbricoides.) Tokyo Iji Shinshi pp 161-168, 218-223, 1921. In Japanese .
Abstracted in Tropical Diseases Bulletin 21: 568-569, 1924
8. ASADA J. (On the development of ascarid larvae in the body of the host. Especially on
the desquamation of the ascarid larvae and the nourishing substances for the ascari d
larvae.) Tokyo Iji Shinshi No 2366, pp 812-815, 1924. In Japanese. Astracted in Japan
Ascariasis 491
9. ASPÖCK H, FLAMM H, PICHER O. Darmparasiten in menschlichen Exkrementen aus

prähistorischen Salzbergwerken der Hallstatt-Kultur. Zentralblatt für Bakteriologie ,
Abteilung Originale 223: 549-558, 1973
10. AURELIANUS C. On acute and on chron ic diseases, translated by IE Drabkin, University
of Chicago Press, Chicago, pp 1019, 1950
11. BERKELEY MJ. On the larger cell s observed in cholera evacuations by JG Swayne Esq.,
M.D., Dr. Budd, and others. London Medical Gazette 44: 1035-1037, 1849
12. BLANCHARD R. Traité de zoologie médicale, J-B Baillière et fils, Paris, two volumes
pp 1691, 1885-1890
13. BROWN HW. A quantitative study of the influence of oxygen and temperature on th e
embryonic development of the eggs of the pig ascarid ( Ascaris suum Goeze). Journal of
14. BROWN HW. The treatment of Ascaris lumbricoides infections with piperazine. Journal
of Pediatrics 45: 419-424, 1954
15. BROWN HW, CORT WW. The egg production of Ascaris lumbricoides . Journal of
16. BRUDADASTOV AN, LEMELEV VR, KHOLMUKHAMEDOV SK, KRASNONOS
LN. (Clinical picture of the migration phase of ascariasis in self-infection.) Meditsinskaya
Parazitologiya i Parazitarn e Bolenzni 40: 165-168, 1971. In Russian
17. BRUMPT L, HO THI SANG. Traitement de l'ascaridose et de l'oxyurose par les dérivés
de la pipérazine. Bulletin de la Société de Pathologie Exotique 47: 817-822, 1954
18. BRUNNER M. Immunological studies in human parasitic infestation. Journal o f
Immunology 15: 83-101, 1928
19. BUI QUOC HONG, BUI HOI, TRAN LU Y, TANG NHIEP, NGUYEN VAN DICH,
VY DINH MINH. Activité anthelminthique du 2(4' thiazolyl) benzimidazole che z
l'homme. Chemotherapia 5: 326-331, 1962
20. CABRERA BD, ARAMBULO PR, PORTILLO GP. As cariasis control and/or eradication
in a rural community in the Phili ppines. Southeast Asian Journal of Tropical Medicine and
Public Health 6: 510-518, 1975
21. CAIUS PLINIUS SECUNDUS. Hist oria naturalis, translated by J Bostock and HT Riley,
Bohn's Classical Library, London, six volumes, 1855-1857
22. CALDWELL FC, CALDWELL EL. Are Ascaris lumbricoides and Ascaris suilla
identical? Journal of Parasitology 13: 141-145, 1926
23. CELSUS AC. De medicina, translated by WG Spencer, Loeb Classical Library ,
Heinemann, London, three volumes, 1948-1953
24. CHAIA G, CUNHA A S. Therapeutic action of mebendazole (R-17.635) against human
helminthiasis. Folha Médica 63: 843-852, 1971
25. CHANDLER AC. Animal parasites and human disease, third edition, John Wiley an d
Sons, New York, pp 573, 1926
26. CHURCH J. Remarks on the Ascaris lumbricoides . Memoirs of the Medical Society of
London 2: 63-67, 1788
27. COVENTRY FA, TALIAFERRO WH. Hypersensitivity to helminth proteins. I .
Cutaneous tests with proteins of ascaris, hookworm and trichuris in Honduras. Journal of
Preventive Medicine 2: 273-288, 1928
28 CRAM EB. The influence of low temperatures and disinfectants on the eggs of Ascaris
lumbricoides. Journal of Agricultural Research 27: 167-175, 1924
30. DAVAINE C. Sur le diagnostic de la présence des vers dans l'intestin par l'inspectio n
microscopiques des matierès expulsées. Comptes Rendus des Séances et Mémoires de la
Société de Biologie, second series, 4: 188-189, 1857
31. DAVAINE C. Recherches sur le développement et la propagation du trichocéphale d e
l'homme et de l'ascaride lombricoïde. Journal de Physiologie 2: 195-200, 1859
32. DAVAINE C. Nouvelles recherches sur le développement de la propagation de l'ascaride
lombricoïde et du trichocéphale de l'homme. Comptes Rendus Hebdomadaires de s

Séances de l'Académie des Sciences, third series, 4: 261-265, 1862. Translated in 65
33. DAVAINE C. Traité des entozoaires et des maladies vermineuses de l'homme et de s
animaux domestiques, J-B Baillière et fils, Paris, pp 1003, 1877
34. DO NASCIMENTO OB, HALSMAN M , ORIA H, CAMPOS JV. Ensaio terapeutico na
ascariase com doses unica de novo antihelmintico de sintese (tetramisole). Revista d o
35. EICKELBERG T. Zur Diagnose und Behandlung von Askaris-Erkankungen. Deutsch e
medizinische Wochenschrift 49: 1020-1021, 1923
36. ELLIOTSON J. Lectures on the theory an d practice of medicine: worms. London Medical
Gazette 12: 689-695, 1833
37. EPSTEIN A. Ueber die Uebertragung des menschlichen Spulwurme ( Ascaris
lumbricoides). Eine klinisch-experimentalle Untersuchung. Jahrbuch für Kinderheilkunde
und physische Erziehung 33: 287-301, 1892
38. FAYARD C. Ascaridiose et pipérazine, Thèse, Paris, 1949
39. FRITZ O. Ascariden des Magendarmtraktes in Röntgenbild. Fortschritte auf dem Gebiete
der Roentgenstrahlen 29: 591-593, 1922
40. FÜLLEBORN F. Ueber die Wanderung von Askaris- und anderen Nematoden-larven im
Körper und intrauterine Askarisinfektion. Archiv für Schiffs- und Tropen-Hygiene 25 :
146-149, 1921
41. FÜLLEBORN F. Ueber das Verhalten der Larven von Strongyloides stercoralis ,
Hakenwürmer und Ascaris lumbricoides im Körper des Wirtes und ein Versuch, e s
biologisch zu deuten. Archiv für Schiffs- und Tropen-Hygiene, 31, No. 2: pp 56, 1927
42. GALENUS CC. Works of, In: Medicorum graecorum opera quae extant, edited by KG
Kühn (Greek text with Latin translation), Leipzig, 20 volumes, 1821-1833
43. GALVIN TJ. Development of human and pig Ascaris in the pig and rabbit. Journal o f
Parasitology 54: 1085-1091, 1968
44. GARCIA EG, CABRERA BD, CRUZ TA , JUECO NL. Reinfection rates of successfully
treated cases of ascariasis. Journal of the Philippines Medical Association 37: 239-243,
1961
45. GÄRTNER H, MUTING L. Beitrag zur Verbreitung der Wurmkrankheiten. Deutsch e
46. GELPI AP, MUSTAFA A. Seasonal pneumonitis with eosinophilia. A study of larva l
ascariasis in Saudi Arabs. American Journal of Tropical Medicine and Hygiene 16 :
646-657, 1967
47. GHANDI BP. Intestinal obstruction due to roundworm. East African Medical Journal 42:
124, 1965
48. GHEDINI G. Anticorpi elmintiaci nel siero di sangue di individui affetti da elmintiasi ,
anticorpi anchilostomiaci e ascaride. Cronac a della Clinica Medica di Genova 13: 58, 1907
50. GOODWIN LG, JAYEWARDENE G, STANDEN OD. Clinical trials with bephenium
hydroxynapththoate (Alcopar) against hookworm in Ceylon. British Medical Journal ii :
1572, 1958
51. GRASSI B. Note intorno ad alcuni parassiti dell'uomo. III. Intorno all' Ascaris
lumbricoides. Gazzetta degli Ospitali, Milano 2: 432, 1881 Also: Weiteres zur Frage der
Ascarisentwickelung. Centralblatt für Bakteriologie und Parasitenkunde, Abteilun g
originale 3: 748-749, 1888
52. GRASSI B. Trichocephalus und Ascarisentwicklung. Preliminarnote. Centralblatt fü r
53. GROS G. Fragments d'helmin thologie et de physiologie microscopiques. Sur les lombrics
cholériques. Bulletin de la Société Impériale des Naturalistes de Moscou 22: 549, 1849
54. HALLEZ P. Sur le développement des nématodes. Comptes Rendus Hebdomadaires des
Ascariasis 493
Séances de l'Académie des Sciences 101: 831, 1885

55. HALLEZ P. Nouvelles études sur l'embryogénie des nématodes. Comptes Rendu s
Hebdomadaires des Séances de l'Académie des Sciences 104: 517, 1887
56. HELLER C. Ueber Ascaris lumbricoides. Sitzungsbericht der physiche-medische Societät
in Erlangen 4: 71, 1872
57. HIPPOCRATES. Works of, transla ted by WH Jones and ET Whithington, Loeb Classical
58. HOBO B. (Epidemiological studies on Ascaris infection among prisoners and the length
of life of Ascaris lumbricoides in human host.) "Japanese Journal of the Nation's Health"
25: 1-14, 1956. In Japanese, with English summary. Abstracted in Tropical Disease s
Bulletin 53: 1255, 1956
59. HOEPPLI R. Parasites and parasitic infection in early medicine and science, University
60. HSU HF, FAN YC, TAN CC, CHIN KY. Two cases of heavy infection by Ascaris
lumbricoides. Chinese Medical Journal 57: 168-175, 1940
61. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE .
Nematode and Gordiacea names placed in the official list of generic names (Opinion 66),
Smithsonian Institution Publication 2359, Washington D C, pp 171-176, 1915
62. ISHIKAWA S. On the fate of the ova of Ascaris in heaped manure mixed with huma n
faeces, and the investigation of eggs adheri ng to vegetables. "Journal of Oriental Medicine"
11: 127-131, 1929. In Japanese. Abstracted in Tropical Diseases Bulletin 28: 225, 1931
63. JAYEWARDENE G, ISMAIL MM, WIJAYARATNAM Y. Bepheniu m
hydroxynaphthoate in treatment of ascariasis. British Medical Journal ii: 268-271, 1960
64. JUNG RC. The predominance of single-brood infections in human ascariasis. Journal of
66. KELLER AE. Ascaris lumbricoides : loss of infestation without treatment. Journal of the
67. KNIGHT R. Discussion of reference 132. Tropical Diseases Bulletin 67: 5355, 1970
68. KOINO S. Experimental infections on the human body with ascarides. Japan Medica l
World 15: 317-320, 1922
69. KONDO K. (Experiments on the infection of Ascaris lumbricoides . I. Percutaneous
infection.) Tokyo Iji Shinshi No 2181, pp 1123-1125, 1920. In Japanese. Abstracted in
group Entozoa, translated by E Lankester, The Sydenham Society, London, pp 452, 1857
71. LAMSON PD, CLADWELL EL, BROWN HW, WARD CB. Hexylresorcinol in th e
treatment of human ascariasis. American Journal of Hygiene 13: 568-575, 1931
72. LANE C. The prevention of Ascaris infection: a critical review. Tropical Diseases Bulletin
31: 605-615, 1934
73. LEIPER RT. Discussion on the validity of certain generic names at present in use i n
medical helminthology. Archiv für Schiffs- und Tropen-Hygiene 30: 484-491, 1926
74. LEUCKART R. Amtlicher Bericht uber die 33. Versammlung deutscher Naturforsche r
und Aertze zu Bonn, 1857
Ein Hand- und Lehrbuch für Nat urforscher und Aertze, C F Winter'sche Verlagshandlung,
Leipzig, volume two, pp 882, 1867-1876
76. LEVIN JJ, PORTER A. Surgical and parasitological notes on four cases of intestina l
obstruction due to accumulation of very large numbers of round worms. British Journal of
Surgery 11: 432-438, 1924
77. LINNAEUS C. Systema naturae sive per regna triae naturae, secundum classes, ordines,
genera , species, cum characteri bus, differentiis, synonymis, locis, tenth edition, L Salvii,
Holmiae, two volumes, pp 823, 1758
78. von LINSTOW O. Ueber den Zwischenwirth von Ascaris lumbricoides L. Zoologischer
Anzeiger 9: 525-528, 1886
79. LÖFFLER W. Zur Differential-Diagnose der Lungenfiltrierungen: uber fluchtig e
SuccedanInfiltraten (mit Eosino philie). Beiträge zur Klinik Tuberkulose und specifischen
TuberkuloseForschung 79: 368-382, 1932
80. LUTZ A. Zur Frage der Uebertragung des mensichlichen Spulworms. Weiter e
Mittheilungen. Centralblatt für Bakteriologie und Parasitenkunde, Abteilung originale 3:
425-428, 1888
81. LÝSEK H. P ispevek k otázce patogenity škrkavky prase i pro lov ka. eskoslovenska
Epidemiologie, Mikrobiologie, Imunologie 10: 134-136, 1961
82. MAUNG M. The occurrence of the second moult of Ascaris lumbricoides and Ascaris
suum. International Journal for Parasitology 8: 371-378, 1978
83. MIURA K, NISHIUCHI K. Ueber befruchte und unbefruchtete Ascarideier i m
menschlichen Kote. Centralblatt für Bakteriologie, Parasitenkunde un d
84. MORISHITA K. Studies on the epidemiological aspects of ascariasis in Japan and basic
knowledge concerning its control. In, Progress of medical parasitology in Japan, K
Morishita, Y Komiya and H Matsubayashi (Editors), Meguro Parasitological Museum,
Tokyo, volume 4, pp 3-153, 1972
85. MOSLER F. Ueber einen Fall von Helminthia sis. Archiv für pathologische Anatomie und
Physiologie und für klinische Medizin (Virchow) 18: 242-250, 1860
86. NETTESHEIM W. Das Wandern der Spulwurmlarven in inneren Organen. Münchener
87. NISHIGORI M, OHBA T. (On the route of migration in the host's body taken by th e
Ascaris.) Nissin Igaku 13: 13-16, 1924. In Japanese. Abstracted in Japan Medical World
4: 263, 1924
88. OHBA T. (Investigation on the presence of Ascaris-larvae in the urine during the initial
stage of infection with Ascaris.) Taiwan Igakka Zasshi No 242, pp 465-469, 1925. I n
Japanese, with English summary
89. OLIVER-GONZALEZ J, SANTIAGO-STEVENSON D , HEWITT RI. Treatment of six
cases of ascariasis in man with 1-diethylcarbamyl 4-methylpiperazine hydrochloride .
Southern Medical Journal 42: 65-66, 1949
90. ORIHEL TC. Primates as models for parasitological research. In, Medical Primatology,
S Karger, Basel, pp 772-782, 1971
91. OTTO GF, CORT WW. Further studies on post-treatment reinfection with Ascaris in the
United States. Journal of Parasitology 20: 245-247, 1934
92. OTTO GF, CORT WW, KELLER AE. Environmental studies of families in Tennessee
infested with Ascaris, Trichuris and hookworm. American Journal of Hygiene 14 :
156-193, 1931
93. PAN C, RITCHIE LS, HUN TER GW. Reinfection and seasonal fluctuations of Ascaris
lumbricoides among a group of children in an area where night soil is used. Journal of
94. PANAROLUS D. Iatrologismorum seu medicinalium observationum pentecosta e
quinque etc., F Moneta, Romae, pp 445, 1652. Partly translated in 133
95. PAPYROS EBERS. Das hermetische Buch über die Arzneimittel alten Aegypter i n
hieratischer Schrift. Herausgegeben, mit Inhaltsangabe und Einleitung versehen vo n
Georg Ebers, Mit hieroglyphisch-lateinischem Glossar von Ludwig Stern, Leipzig, two
volumes, 1875. The Papyrus Ebers, translated from the German version by CP Bryan,
Ascariasis 495
Geoffrey Bles, London, pp 167, 1930

96. PAYNE FK, ACKERT JE, HA RTMAN E. The question of the human and pig Ascaris.
American Journal of Hygiene 5: 90-101, 1925
97. PHILLS JA, HARROLD AJ, WHITEMAN GV, PERELMUTTER L. Pulmonar y
infiltrates, asthma and eosinophil ia due to Ascaris suum infestation in man. New England
Journal of Medicine 286: 965-970, 1972
98. PLATTER F. (PLATERUS). Cited in 133
99. PROFFIT RD, WALTON BC. Ascaris pneumonia in a two-year-old girl. Diagnosis by
gastric aspirate. New England Journal of Medicine 266: 931-934, 1962
100. RANSOM BH, CRAM EB. The course of migrat ion of Ascaris larvae. American Journal
101. RANSOM BH, FOSTER WD. Life history of Ascaris lumbricoides and related forms.
Preliminary note. Journal of Agricultural Research 11: 395-398, 1917
102. RANSOM BH, FOSTER WD. R ecent discoveries concerning the life history of Ascaris
lumbricoides. Journal of Parasitology 5: 93-99, 1919
103. RANSOM WH. On the diagnosis of, and treatment for, roundworm; and on th e
occurrence of a new species of taenia in the human body. Medical Times and Gazette,
new series, 12: 598-600, 1856
104. REDI F. Osservazione intorno agli animali viventi che si trovano negli animali viventi,
Piero Matini, Firenze, pp 224, 1684
105. REITER J. Zum Röntgenologischen Nachweis von Askariden in Magendarmtrakt .
Wiener klinische Wochenschrift 36: 592, 1923
106. RENDALL P. "Death from irritation of ascarides." Lancet ii: 1303, 1892
107. RHIND W. A treatise on the nature and cure of intestinal worms of the human body ,
Samuel Nighley, London, pp 153, 1829
108. RICHTER HE. Beobachtungen über die Eier der Eingeweidewürmer. Allgemein e
Deutsche naturhistorische Zeitung (Sachse) 1: 1-5, 1856
109. ROSS R. The life-history of Ascaris lumbricoides . British Medical Journal ii: 5-7, 1916
110. RYRIE GA. Intestinal obstruction due to Ascaris infection. Malayan Medical Journal 3:
166-167, 1928
111. SCHINZ HR. Askariden in Röntgenbild. Deutschen Zeitschrift für Chirurgie 184 :
105-109, 1924
112. SCHULTZ MG. Ascariasis: nutritional implications. Reviews of Infectious Diseases 4:
815-819, 1982
113. SPILLMAN R. Pulmonary ascariasis in tropical communities. American Journal o f
114. SPRENT JF. The dentigerous ridges of the human and pig Ascaris. Transactions of the
Royal Society of Tropical Medicine and Hygiene 46: 378, 1952
115. STEWART FH. On the life-history of Ascaris lumbricoides . British Medical Journal ii:
5-7, 1916
116. STEWART FH. The life history of Ascaris lumbricoides. British Medical Journal ii: 474,
1916
117. STEWART FH. Further experiments on Ascaris infection. British Medical Journal ii :
486-488, 1916
118. STEWART FH. On the life history of Ascaris lumbricoides . British Medical Journal ii:
753-754, 1916
119. STEWART FH. On the development of Ascaris lumbricoides Lin. and Ascaris suilla
Duj. in the rat and mouse. Parasitology 9: 213-227, 1917
120. STEWART FH. On the development of Ascaris lumbricoides and Ascaris mystax in the
mouse. Part II. Parasitology 10: 189-196, 1918
121. STEWART FH. On the life history of Ascaris lumbricoides L. Part III. Parasitology 10:
197-205, 1918
122. STEWART FH. Recent experiments on the life history of Ascaris lumbricoides . British
Medical Journal i: 102, 1919

123. STEWART FH. Life-history of Ascaris lumbricoides . British Medical Journal ii :
818-819, 1920
124. STEWART FH. On the life history of Ascaris lumbricoides . Part V. Parasitology 13 :
37-47, 1921
125. SWARTZWELDER JC. Clinical ascariasis. An analysis of two hundred and two cases.
American Journal of Diseases of Children 72: 172-180, 1946
126. SWAYNE JG. Observations on the report of the College of Physicians relative to th e
organic bodies discovered in the evacuati ons of cholera patients. Lancet ii: 530-532, 1849
127. SZIDAT L. Über die Erhaltungsfähgkeit von Helmintheneiern in Vor- un d
Frühgeschichtlichen Moorleichen. Zeitschrift für Parasitenkunde 13: 265, 1944
128. TAKATA I. Experimental infection of man with Ascaris of man and pig. Kitasat o
Archives of Experimental Medicine 23: 49-59, 1951
129. TALYZIN FF. The oxygen treatment of ascariasis. Lancet ii: 314-315, 1954
130. THIENPONT D, BRUGMANS J, ABADI K, TANAMAL S. Tetramisole in th e
treatment of nematode infestations in man. American Journal of Tropical Medicine and
Hygiene 18: 520-525, 1969
131. THUST R. Submikroskopische Untersuch ungen über die Morphogenese des Integuments
von Ascaris lumbricoides L. Zeitschrift für wissenschaftliche Zoologie 178: 1-39, 1968
132. TULLIS DC. Bronchial asthma associated with intestinal parasites. New England Journal
of Medicine 282: 370-372, 1970
133. TYSON E. Lumbricus teres, or some anatomical observations on the round worm bred
in human bodies. Philosophical Transactions of the Royal Society 13: 153-161, 1683
134. VALLISNIERI A. Nuovo osserva zioni ed esperienze intorno all'ovaja scoperta ne' vermi
tondi dell'uomo, nomo e de' vitelli con varie lettre spettanti all storia medica e naturale,
G Manfrè, Padova, pp 184, 1713
135. VERVOORT H. Oleum chenopodii anthelmintici, een Wormmiddel tegen Ankylostomum
en Ascaris. Geneeskundig Tijdschrift voor Nederlandsch-Indië 53: 435-445, 1913
136. VOGEL H, MINNING W. Beiträge zur Klinik der Lungen-Ascariasis und zur Frage der
flüchtigen eosinophilen Lungeninfiltrate. Beiträge zur Klinik der Tuberkulose un d
spezifischen Tuberkulose-Forschung 98: 620-654, 1942
137. WEDL C. Grundzuge der pathologischen Histol ogie, Carl Gerold & Sohn, Wien, pp 825,
1854. Rudiments of pathological histology, translated by G Busk, The Sydenha m
Society, London, pp 637, 1855
138. WINFIELD GF. Studies on the control o f fecal-borne disease in North China. III. Family
environmental factors affecting the spread of Ascaris lumbricoides in a rural population.
139. WINFIELD GF, CHIN TH. Studies on the control of fecal-borne diseases in Nort h
China. VI. The epidemiology of Ascaris lumbricoides in an urban population. Chinese
140. YOSESATA M, SUMI I. (Helminth eggs on vegetables in Mukden.) "Journal of Oriental
Medicine" 16: 493-506, 1932. In Japanese. Abstracted in Tropical Diseases Bulletin 29:
739, 1932
141. YOSHIDA S (T). On the development of Ascaris lumbricoides L. Verhandlungen der
japanischen pathologischen Gesellschaft zu Tokyo 8: 160-162, 1918. Also (same title),
142. YOSHIDA S (T). On the migrating course of ascarid larvae in the body of the host .
Journal of Parasitology 6: 9-17, 1919. Original reports in Japanese in Tokyo Iji Shinshi
No. 2066, pp 555-561; No. 2072, pp 867-872, 1918
Ascariasis 497
Table 19.1. Landmarks in ascariasis

___________________________________________________________________
BC Adult worms have been known since ancient times and various
anthelmintics have been employed
c.170 AD Galen knew that adult worms normally inhabited the upper small intestine
1683 Tyson described the anatomy of the worm and clearly distinguished it from
the earthworm. He discovered the eggs
1849 Gros found that eggs took several months to embryonate
1856 Ransom showed that ascariasis could be diagnosed by finding eggs in the
faeces
1862 Davaine showed that eggs remained viable for up to five years
1862 Davaine discovered that when embryonated eggs were fed to rats, larvae
were liberated in the small intestine then were passed in the faeces
1879 Grassi swallowed embryonated eggs and claimed to find evidence of a
patent infection 22 days later
1886 Calandruccio gave 150 eggs to a boy and recovered 143 worms after
anthelmintic administration three months later
1916 Stewart found that larvae liberated from eggs in the intestines of rats
underwent systemic migration through the lungs then returned to the gut
1922 Koino infected himself with 2,000 eggs, recovered larvae from his sputum
several days after infection, then recovered 667 immature worms from his
intestines after anthelmintic administration 50 days after infection
1949 Fayard reported that piperazine was a useful treatment
1958 Bephenium was shown by Goodwin and colleagues to be useful for
treatment
1962 Bui Quoc Hong and co-workers showed that thiabendazole was an effective
treatment
1966 Tetramisole was demonstrated by Do Nascimento and colleagues to be
efficacious
1969 Thienpont and colleagues showed that levamisole was even more effective
than tetramisole
1970 Amato Neto and co-workers indicated that pyrantel was active
1973 Mebendazole was shown by a number of investigators to be useful in
ascariasis
__________________________________________________________________
Chapter 20
Ancylostoma duodenale, Necator americanus and

HOOKWORM DISEASE
SYNOPSIS
Common name: hookworm, causing hookworm disease

Major synonyms:
1. Ancylostoma duodenale: Agchylostoma duodenale, Anchylostomum duodenale,
Ankylostoma duodenale, Dochmius ankylostomum, Sclerostoma duodenale,
Uncinaria duodenale
2. Ancylostoma ceylanicum: A. braziliense
3. Necator americanus: Uncinaria americana
Distribution: widespread, especially in the tropics and subtropics
Life cycle: The adult worms, about 1 cm long, live attached by the mouth to the small
intestinal mucosa. Eggs are passed in the faeces then hatch and moult twice in the soil
over two weeks or so to become infective (filariform) larvae. These penetrate the
intact skin and pass via the bloodstream to the lungs where they enter the alveolar
spaces, ascend the airways to the pharynx, and are swallowed and pass to the small
intestine where they mature over 1-2 months
Definitive host: A. duodenale, N. americanus - humans
A. ceylanicum - dogs, cats, humans
Major clinical features: dermatitis, pulmonary infiltrates with eosinophilia, indigestion,
iron deficiency anaemia
Diagnosis: finding eggs in faeces
Treatment: bephenium, mebendazole, pyrantel, thiabendazole; blood transfusion if
necessary
In May 1838, while dissecting the body of a peasant woman who had died of
pulmonary infarction in the Maggiore Hospital in Milan, the Italian doctor,
Angelo Dubini, encountered "a little worm in the small intestine, in the midst
of much gray mucus....this worm impressed me as having really distinct generic
characteristics" 70. Dubini did not publish news of this discovery, however, until
he came across the parasite again four and a half years later. In November
1842, Dubini found another example of this peculiar worm in the jejunum of
an old lady who had suffered with dropsy (oedema). Both of these parasites,
and the specimen he found in a third patient in the following month, were all
499
female worms. On 15 December 1842, Dubini found a dozen worms in the first
part of the jejunum of a woman who had died from a chest abscess, and this
time, male helminths were present. The parasites were so frequent, that in the
course of 100 autopsies, he encountered them in more than twenty cadavers.
Dubini described the worms as being:
somewhat curved in on themselves....about four and one half lines [= 1 cm] in length,
transparent in the anterior, and marked by wavy yellow brown or red stripes in the
posterior three quarters. A black spherical dot marks the boundary between the
transparent and colored parts. Posteriorly, the female has a blunt tail which is slightly
curved.70
Dubini recognized that the worms were nematodes, for they were cylindrical
in shape, elastic, possessed a complete intestinal tract with a mouth at one end
and an anus at the other, and were unisexual. There were a number of char-
acteristics, however, which he felt justified the erection of a new genus in which
to place this worm. He described the salient features:
Head not distinct from body; round mouth furnished with four hooks folded back
towards the center and situated above conical eminences which project from the
interior of the pharynx; esophagus enlarged at the bottom like a club and distinct from
the spherical, blackish stomach; blunt tail in the female, spread out like a fan in the
male; a single central penis in which are inserted two small vas deferens.70
Dubini named the genus Agchylostoma, being a mistransliteration of the Greek
words (AGCHYLOS i.e. ANCHYLOS because before [CH]
should be transliterated as "N" and not "G") and µ (STOMA), meaning
"curved" and "mouth", respectively. Dubini thought that was the
Greek word for "hook" and intended the name to reflect the hooked shape of the
body of the parasite and its prominent mouth. In addition, he gave it the specific
epithet, duodenale, to indicate its common location in the intestine.
Dubini considered the reasons why the worm, despite its moderate size, had
not been discovered earlier. Until a short period before his own era, it had not
been the general practice to open the bowel at autopsy, and the worm was so
small that there would have been no chance of feeling it through the intestinal
wall when squeezing the gut. When it became common to open the intestines
and examine the mucosa (particularly in patients with typhoid fever and
tuberculosis), the usual procedure was to wash out the intestinal lumen with
large volumes of water which would probably have carried away many worms.
Finally, the worms were ordinarily embedded in somewhat opaque mucus
which made it extremely difficult to visualize them.
Dubini's discovery was confirmed several years later in Egypt by the German
physician, Pruner (1846) 171, then by the latter's compatriots, Bilharz 31
and
Griesinger , also in Egypt. In 1865, Wucherer found the parasite in Brazil204,
92
then the worm was found subsequently in many countries. A number of studies
were then made of the anatomy of the worm, the most complete and extensive
being those of Looss in Cairo141.
Confusion and controversy reigned over the proper name of the worm. In
addition to Dubini's name of Agchylostoma duodenale, it was called Ancylo-
Hookworm Disease 501
stoma duodenale by Creplin (1845) 60, Anchylostomum duodenale by Diesing

(1849-1851), Ancylostomum duodenale by Küchenmeister (1855), and
Ankylostoma duodenale by Blanchard (1885-1890), and renamed Strongylus
quadridentatus by von Siebold (1851), Dochmius ankylostomum by Molin
(1860), Sclerostoma duodenale by Cobbold (1864), and Uncinaria duodenale
by Railliet (1885), amongst other names. With the acceptance of the Inter-
national Rules of Zoological Nomenclature (see chapter 1), it was clear that by
the law of priority, Dubini's name should stand. Considerable argument took
place, however, over the relative merits of Agchylostoma, Anchylostoma,
Ankylostoma and Ancylostoma. By Opinion 66 in February 1915, the Inter-
national Commission on Zoological Nomenclature settled the matter by
declaring that the valid name of the genus was Ancylostoma, with duodenale
being the type species105.
DIFFERENTIATION OF NECATOR AMERICANUS FROM

ANCYLOSTOMA DUODENALE
In 1868, Camuset appreciated that the hookworm found in South America was
distinct from A. duodenale seen in Europe and Africa and indicated clearly the
differential characteristics. This information was buried in a thesis52, however,
and was not generally known until Leger drew attention to it in 1921125.
Likewise, Adolfo Lutz in 1888 noted some differences between the Brazilian
hookworm and the European form, but did not classify the former as a new
species143. In 1901, Dr AJ Smith in Galveston, Texas, USA, recognized that the
worms expelled by a patient from a plantation in southern Mexico were not the
same as Dubini's A. duodenale but thought that they might be identical with
Uncinaria stenocephala of dogs189. Smith sent specimens to CW Stiles in
Washingtom as did Drs CA Claytor in Washington, DC, and BK Ashford in
Puerto Rico. Stiles described a number of morphological differences between
this parasite and classical A. duodenale (which, following Railliet, he called
Uncinaria duodenalis), including replacement of the hook-like teeth in the
mouth by semilunar plates, the location of the vulva, and appearance of the
caudal bursa of male worms. In addition, he thought that the eggs of the
American worm were slightly larger. Stiles concluded that:
These parasites differ from all of the members of the genus Uncinaria which I can
find recorded, and on that account, I propose to base a new species, Uncinaria
americana, upon them.192
In 1903, Stiles suggested splitting up the genus Uncinaria (i.e. Ancylostoma)
and placed the American hookworm in the subgenus, Necator 193. He elevated
this subgenus to generic status in 1906194. The name meant "the killer" and was
derived from the Latin word "neco", meaning "to kill". In 1915, the Inter-
national Commission on Zoological Nomenclature in Opinion 66 declared that
the official name for the parasite was Necator americanus 105.
DIFFERENTIATION OF ANCYLOSTOMA CEYLANICUM FROM

A. DUODENALE
In 1910, Dr Gomes de Faria recorded the occurrence of a new species of

hookworm, which he named Ancylostomum braziliense, in the intestines of cats
and dogs at Manguinhos, Brazil73. In the following year, Looss described
another hookworm which he named Agchylostoma ceylanicum; this parasite
had been recovered from a civet cat and sent to him by Willey in Ceylon142.
Shortly thereafter (1913), Major Clayton Lane of the Indian Medical Service
examined stools of prisoners in a gaol in India and in three cases found
hookworms which did not conform to the ordinary type of parasite (A. duo-
denale). Closer examination revealed that they were A. ceylanicum 116. Later
in the same year, Leiper expressed an opinion that A. ceylanicum was identical
with A. braziliense 133, with which view Lane later concurred 118. Since de Faria
had described the parasite first, this name held general sway. In 1951, however,
Biocca reviewed the relationship between A. braziliense and A. ceylanicum and
differentiated the two species on morphological grounds32. This distinction was
then confirmed by Rep and his colleagues in cross-breeding experiments in
1968173.
STUDIES OF THE DEVELOPMENT OF LARVAE IN THE EXTERNAL

ENVIRONMENT
Dubini made little mention of hookworm ova other than to say that the elliptical
eggs could be seen in the oviduct of female worms, and to provide a
rudimentary drawing of them in situ 70. Not much attention was paid to the eggs
over the next twenty years, and Wucherer in 1866 wrote "Nothing is known
about the way in which the eggs or embryos of Ancylostoma are introduced into
the human body and under what conditions they exist outside it"204.
In view of the unavailability of A. duodenale in Germany at the time, Rudolf
Leuckart, in the same year that Wucherer wrote those words, made some
observations on the related hookworm of dogs, Dochmius trigonocephalus
(now called Uncinaria stenocephala) in order to study any developments
which may occur within the egg. He found that when the eggs were placed in
damp earth or mud, the segmented embryo formed a larva which hatched after
three or four days. The larvae moulted after a further three days, then a second
moult at the end of another week coincided with a marked change in the
internal organization of the worms, and they were no longer able to feed.
Leuckart supposed that these forms, which resembled Rhabditis (a free-living
worm), must enter some intermediate host, but preliminary experiments were
negative. He therefore introduced some of these third-stage larvae in muddy

water directly into the gastrointestinal tract of some dogs. Leuckart found that
they grew for eight days then moulted. Another moult took place and he
recovered mature worms three weeks after infection. This convincing
experiment led Leuckart to surmise that A. duodenale of humans would have
a similar development and infection must be acquired by drinking free-living
larvae in dirty water134.
This finding stimulated Wucherer to make similar observations on human
hookworms. He placed eggs in a damp place and found that larvae developed
within 24 hours, then escaped from the egg shell in the same fashion as the dog
hookworm. The larvae increased in size and cast off their cuticles once or
twice, but then died. Unfortunately, Wucherer was unable to pursue these
investigations any further as he had insufficient laboratory resources at his
disposal.
The next significant studies were not made until 1878 when the Italians,
Giovanni Battista Grassi, Corrado Parona and Ernesto Parona studied the
development of hookworm eggs of human origin. They observed the repeated
segmentation of the embryo within the egg shell, and found that when the larva
had reached a length approximately three times that of the egg, it pierced the
shell. They then observed moulting of the parasite:
This larva will gradually increase in size, becoming quite long and undergoing at least
two moults; that is, it will shed its skin at least twice....However, as of today, we are
unable to say what happens afterward.90
Grassi and his colleagues found that the best medium for the development of
the larvae was the faeces itself, and that all stages of development were
hastened by increased temperatures.
Shortly thereafter, their compatriot, Eduardo Perroncito in Turin, used eggs
obtained from the faeces of miners infected while building the St. Gothard's
tunnel to study further the extracorporeal development of hookworms. Perron-
cito found that the larvae hatched from the egg shells asynchronously, begin-
ning a day or so after incubation. He described the anatomy of the larva in
detail, then recorded the progessive changes which occurred in the internal
organization of the growing worm. He failed to recognize the first moult and
misinterpreted the second moult as cyst formation or encapsulation:
Whilst the pharynx is greatly modified, the skin separates a substance chitinoid (?)
glassy, transparent, which in a very short time is condensed, and forms a capsule
which encloses the living larva. This is seen to move freely in its capsule or cyst,
which completely repeats its shape.166
Perroncito considered that the capsule provided some resistance to dessication
and postulated that the "cysts" might be transported by the wind as well as in
water then produce infection when ingested in contaminated food or water.
Further, he believed that the cyst became calcified and that the larva was
liberated by the hydrochloric acid of the gastric juice:
After from one to two days, [the larva's] skin separates from the salts of chalk
(particularly from the carbonate of chalk)....and becomes one with the capsule. Thus,
this always becomes more rigid and friable.166

Perroncito's conclusions were repudiated a few years later (1886) by
Schulthess in Germany who correctly interpreted the "cyst formation" as rep-
resenting merely a phase in ecdysis and dismissed the calcification as being a
process of degeneration 184. These phenomena were also investigated by
Leichtenstern who misguidedly tried to support Perroncito's views with regard
to cyst formation, although he did not agree with the concept of calcification.
Like Perroncito, Leichtenstern denied that moulting of larvae occurred128.
Ten years later, Arthur Looss in Egypt re-examined the development of
larvae and confirmed, although he does not appear to have been aware of it at
the time, the observations and interpretations of Schulthess. Looss watched the
development and hatching of the larva, then found that at the prevailing
temperature (27oC), a moult occurred after two to three days. After five days,
changes in the internal morphology of the larva began to take place, particularly
in the mouth, buccal cavity and oesophagus. A second moult then occurred, but
the old cuticle was usually retained:
the body membrane is seen to consist of two layers, the outer one of which begins to
detach itself more and more from the body until it finally loses connection with it
completely and covers it all around with an exceptionally thin and delicate chitinous
coat....the body....seems to contract a little in length so that the old skin extends to a
degree over head and tail....In the great majority of cases they do not cast off the outer
chitinous skin.136
These larvae were non-feeding, infective forms and ripe for transfer. Looss, like
Schulthess, realized that it was this process that Perroncito and others had
called "encystment" and was nothing more than an ordinary shedding process
except that the old coat was not cast off completely. Looss was able to keep
such larvae alive for 10-20 days in water and confirmed that they could not
withstand dessication.
Looss began the paper alluded to above by saying that very little was known
about the life history of A. duodenale. This statement was made despite the
numerous investigations of Perroncito, Parona, Grassi, Lutz, Leichtenstern and
others, but he did acknowledge that all the pertinent literature was not available
to him. This did not save him, however, from a savage attack by Leichtenstern
who charged that Looss's paper was nothing more than a re-hash of the known
facts, combined with a curious ignorance of, if not intentional disregard for, the
literature129,130. To this, Looss replied vigorously, saying that for one such as
him incarcerated in Egypt and denied the scientific aids and libraries to which
those in Europe were accustomed, he had one of two choices; either he worked
for his own pleasure and kept all his discoveries to himself, or he published
them, whether the form was perfect, as could rightfully be expected in the
centres of scientific life, or not. He chose the latter course and wrote:
It is my intention to contribute to the improvement of our knowledge as far as I am
able, and it is my conviction that the merits of prior authors will prevail in any
scientific question, regardless of whether they are or are not cited in every later
work.138
In any case, Looss was not convinced that everything had indeed been clarified
about the life cycle. He then claimed that in eight months he had advanced
knowledge further than Leichtenstern had done over many years, and went on
to justify this assertion by describing the percutaneous penetration of infective
larvae138 (see later).
Another blind alley also bedevilled a proper understanding of the in vitro
development of hookworms for over thirty years. In 1886, Leichtenstern first
put forward the proposition that hookworms underwent heterogony, i.e. larvae
developed outside the human body into a generation of sexual animals which
in their turn produced offspring. Such a phenomenon had been described with
Strongyloides stercoralis (see chapter 21). Leichtenstern wrote:
By observing suitable culture methods....a freeliving, sexually mature rhabditis form,
reproducing itself through unlimited generations, was successfully cultivated from the
egg and larva of ankylostoma; a form which is essentially distinct form the parasitic
ankylostoma....I foresee that my observations, being that of an 'outsider' will not at
once be accepted by zoologists, but rather be received with careful reserve and
incredulity.126
Nevertheless, Leichtenstern wrote categorically: "I am in a position entirely to
dispose of all such doubts and objections" 126. He then went on to canvass the
possibilities that these freeliving worms might be identical with either
freeliving nematodes which frequently occur in decaying matter, or may be
S. stercoralis which was sometimes found in association with hookworms in
the intestines. Later that year, however, Leichtenstern retracted these statements
when further experiments convinced him of his error127. Many years later,
Looss remarked somewhat pontifically:
Supreme personal confidence in his method of research, and neglect inspired by this
confidence of the biological probabilities pointed out by specialists on the subject,
were the reasons which made it possible that Leichtenstern was deceived. It is
fortunate in the interests of science that he was soon convinced himself that he was
in the wrong; for where personal convictions play the most prominent part it is not
always easy for impersonal reason brought forward by others, to gain a hearing.142
Ironically, the same trap was to befall Looss with his insistence that the
transmission of schistosomiasis was direct, yet, unlike Leichtenstern, Looss in
that instance remained obdurate.
Although the question of the existence or non-existence of heterogony in
A. duodenale was settled rapidly as far as the German literature was concerned
by the recantation of Leichtenstern, the same did not apply to English
investigators. In 1889-1890 and quite independently of Leichtenstern, Captain
GM Giles of the Indian Medical Service in Assam made observations during
the course of an investigation into the aetiology of kala azar and beri beri which
caused him to claim that heterogony occurred with hookworm83. Giles's views
were soon opposed by Macdonald who repeated the experiments but failed to
verify the findings; he believed that Giles had inadvertently cultured S.
stercoralis 145. This view was echoed by Kynsey112 then Sonsino suggested that
Giles may have cultured freeliving nematodes. On the other hand, Giles was
supported by Sandwith in Egypt who claimed to have raised heterogonic

hookworms. The subject was raised again when Giles re-asserted his views at
the annual meetings of the British Medical Association in 189984 and 190085.
A few years later, he was supported by Ozzard who wrote in 1902:
During the last two years I have been able to completely confirm the experiments of
Giles. That this is an example of dimorphism or heterogenesis I have not the slightest
doubt.160
Ozzard reiterated these views in 1909 and wrote that it was absurd to describe
the freeliving adult worms as S. stercoralis 161. This immediately brought forth
a response from Leiper criticizing Ozzard's assertions 132. Finally, and at great
length, Looss in 1911 examined the pitfalls into which previous workers had
fallen. He noted that the proponents of heterogony had looked at the first and
last stages of development only, and had failed to follow carefully the evolution
of individual worms. Nor had sufficient attention been paid to differentiating
between first-stage larvae of Strongyloides and hookworms. Furthermore,
Looss was convinced that the facts had been made to fit the theory rather than
vice versa. He was in no doubt that the various workers had been dealing with
S. stercoralis or a nonparasitic, freeliving nematode and pleaded: "It is much
to be desired that the legend of heterogony of the ankylostomes should at last
definitively disappear from scientific literature" 142. It did.
PROOF OF THE ORAL ROUTE OF INFECTION
The first persons to attempt to transmit human hookworm infection experi-

mentally were Grassi and an unnamed colleague. Grassi swallowed a large pill
laden with segmenting hookworm eggs; after 45 days of observation, no
symptoms attributable to hookworm infection had appeared and no eggs were
found in the faeces. Likewise, his colleague, who wished to remain anonymous,
consumed some faeces loaded with A. duodenale rhabditiform larvae, again
without effect. They also fed a large quantity of faeces full of eggs to a dog, but
it eliminated many of them unchanged or nearly unchanged on the following
day90. Why these investigators should have swallowed eggs or first-stage larvae
when they knew that larvae underwent further development in vitro is unclear.
Perhaps, as Looss has surmised142, they wished to counteract the suggestion of
Sangalli that eggs developed directly into adults without passing out of the
body179. It was in this paper too, that Grassi and his colleagues postulated that
Filaria sanguinis hominis (i.e. the microfilaria of Wuchereria bancrofti) might
be an ancylostome larva circulating in the bloodstream. The suggestion was
based upon the geographical coexistence of filariasis and hookworm infection,
the fact that the adult filaria was not known to them, and the statement by
Bilharz that he sometimes found female worms in the intestinal submucosa.
The idea was negated rapidly, however, when the adult filarial worm was found
by Bancroft (see chapter 23).

It was not until twenty years after Leuckart's demonstration of the oral trans-
mission of Dochmius trigonocephalus of the dog that it was shown that a
similar mode of infection could occur with A. duodenale. In 1886, Leichten-
stern undertook feeding experiments with human volunteers and found ova in
the faeces four to five weeks after ingestion of larvae that had undergone the
morphological changes, which have just been described, during in vitro
cultivation 127.
In 1897, Looss attempted to repeat Leichtenstern's experiment by infecting
experimental animals orally with A. duodenale. At first, all the animals vomited
the infected worms. He then overcame this problem by cleaning his
preparations and exposed a number of species of animals, including monkeys,
dogs and cats, to this parasite. He had the best results with newly-weaned
animals, but even then, most of the larvae passed directly through the
gastrointestinal tract without settling. In older animals, this was the inevitable
result. In those cases where helminths did persist in the gut, however, the
worms did not complete their development and failed to produce fertilized ova.
Looss did not deny that oral transmission of hookworm infection could take
place, but concluded that these hosts were insusceptible to infection with
hookworm recovered from humans137.
Confirmation of this mode of infection was provided, however, when Joyeux
in 1912 reported that he had infected monkeys (Cercopithecus patas) by caus-
ing them to swallow N. americanus infective larvae. The first monkey died 37
days after infection, and many worms were found attached to the small bowel
mucosa which was congested and contained numerous haemorrhages. The
second animal died several days later and harboured small numbers of male and
female adult worms106.
DISCOVERY OF THE PERCUTANEOUS ROUTE OF INFECTION
In 1898, Arthur Looss reported that infective hookworm larvae penetrated the
intact skin. This was a momentous discovery, for it was the first time that the
percutaneous penetration of any worm was shown. The discovery itself was
serendipitous. Looss had attempted to infect himself experimentally with
Strongyloides stercoralis, and on examining his faeces, was surprised to find
numerous Ancylostoma eggs. He reflected, therefore, on how this might have
occurred. He had never had any misgivings about allowing water containing
hookworms to settle on his hands, although he had ensured that they had been
kept away from his mouth. The matter remained inexplicable to him until he
had another experience:
A drop of water with a high larva content fell on my hand one day and rolled off. I
paid no attention to this moist spot which dried itself after a few minutes. But at the
same time I felt there an intense burning....and the spot became extremely red. What
was the meaning of this? The cause could only be the Ancylostoma larva.138
Looss then repeated the process with water alone, but had no repetition of the
reaction. Thereupon, he applied some more larvae to the skin:
The reddening of the skin and the burning sensation started exactly as before. I then
scraped off the last moisture residue from the epidermis....The Ancylostoma larvae
previously present in such abundance had disappeared except for a few very indolent
ones; in their place among the scraped-off epidermal cells were found numerous
empty worm skins! The larvae themselves could only have penetrated the skin.138
In fact, his hand was so swollen the next day that he thought it best to ask for
medical help. Two or three months later, he noted a considerable increase in
the number of hookworm eggs in his stools138.
This assertion by Looss that hookworm larvae penetrated the skin was met
with hostile criticism from a number of quarters, so much so that he determined
to say nothing more on the subject till he could prove his point. The most
telling argument against his hypothesis was that he could have acquired the
infection naturally as he lived in an endemic area. This necessitated morph-
ological confirmation by Looss of penetration of the skin by larvae. First, he
tried to infect skin removed from a cadaver and heated to 37oC; this was
unsuccessful. Next, with the cooperation of his colleague Maddern, who was
professor of surgery at Kasr-el-Aini Hospital in Cairo, he extended his
observations by infecting a 13 year old boy who was about to have his leg
amputated. One hour before operation, a drop of fluid containing many larvae
was spread out on the skin. Immediately following removal of the leg at
operation, a section of skin was excised and histological sections were
prepared. Looss found that the larvae entered the skin and that they did this via
the hair follicles:
Inside the hair follicles the larvae crowded toward the hair papilla. When particularly
numerous in the same follicle, they completely destroyed the outer root sheath.
Having reached the hair papilla they left the follicles to penetrate the adjacent tissue
of the cutis vera.139
and concluded "That actual penetration of the Ancylostoma larvae into the skin
does occur can now be looked upon as unassailable" 139.
Looss's colleague, FM Sandwith, professor of medicine at the same hospital,
later in the year (1901), presented Looss's observations to the annual meeting
of the British Medical Association 177. (This caused some confusion and Sand-
with later had to specifically emphasize that it was Looss's and not his own
research to which he was alluding178.) In the ensuing discussion, GM Giles,
despite being opposed to Looss in the matter of heterogonic development of
hookworm, supported ardently the latter in this respect, and remarked that he
had examined Looss's histological sections when in Cairo a short while
before86. Patrick Manson, on the other hand, was somewhat more cynical:
I would deprecate premature interpretation of the fact as indicating a phase in the
normal life-history of the parasite or as a method of infection....Before the fact can be
accepted as more than a curiosity, further experiments....should be carried out.147
In view of the continued scepticism, Looss persuaded an hospital attendant
to volunteer for an experimental infection. The subject's faeces were examined

daily for six weeks and were found to be free of hookworm ova. A drop of
culture containing infective larvae of A. duodenale was then placed on his
forearm. The first egg was found in his faeces 71 days later, and every stool for
the next month was positive142.
Looss's hypothesis soon received independent confirmation from another
source. In 1901, Charles Bentley, a medical officer to the Empire of India and
Ceylon Tea Company in Assam, India, began to investigate the cause of a
condition variously called "ground-itch", "pani-ghao", "water-itch" and
"coolie-itch", which was prevalent in the tea gardens of the Indian subcontinent
and in sugar plantations in the West Indies. This illness was characterized by
a vesicular dermatitis of the feet which occurred epidemically in workers during
the rainy season. In 1901, Dalgetty had suggested that the affliction might be
caused by an acarus (mite)62. In order to verify this suggestion, Bentley took
some soil from a known infective area, moistened it, and applied it to the arm
for six hours; the typical eruption resulted. Microscopical examination of the
used soil and an unused aliquot of the same material failed to reveal any acari,
but disclosed the presence of A. duodenale larvae, minutes leeches, small
earthworms, rotifers, various protozoa, fungi and bacteria. In order to exclude
sensitization to a chemical, a portion of the soil was sterilized by heating and
the experiment repeated; no eruption resulted. Bentley then examined soil from
a non-infective area and found only earthworms, leeches and protozoa, so he
concluded that either the hookworm, a fungus, or a bacterium was responsible.
He then scraped the skin of patients with early cases of ground itch and found
empty hookworm sheaths on the surface. His next procedure was to culture soil
with or without faeces containing hookworm ova for a week, take two samples
from each culture, then kill the hookworm larvae in one sample from each
culture by gentle drying. On application of these four specimens to the skin,
only the one containing living hookworm larvae caused ground itch.
Microscopical examination of that specimen failed to reveal any larvae and
Bentley concluded:
Apparently, therefore, the living larvae had entered the skin, and their entry had been
followed by lesions similar in every particular to those found associated with the
condition known as water-sore.28
Bentley then went on to consider the rarity of ground itch among the general
rural population and suggested that this reflected a different method of disposal
of human excreta, and postulated that the severe inflammation in ground itch
might be due to bacteria associated with passage of the hookworm larvae28.
In the years following these observations, patent infections were produced
percutaneously with a variety of species of hookworms. Austregesilo reported
that he had infected two students (presumably with N. americanus); eggs
appeared in the faeces 67 or more days later21. Caldwell recorded the accidental
infection of a laboratory worker with N. americanus. Fluid containing larvae
was spilt upon the hand and produced immediate itching. The following day,
the area was grossly inflamed. After two days, axillary lymphadenitis was
present, then marked bronchitis succeeded on the third day. The stools became
positive 38 days after infection51. In 1933, Maplestone reported the successful
experimental infection of humans with A. ceylanicum 148.
Thus, there was no doubt that infection could be acquired percutaneously.
The next question concerned the relative importance of the oral and per-
cutaneous routes in human hookworm infection. Peiper in German East Africa
(1912) conducted a careful series of studies and concluded that although a
small proportion of infections may be acquired orally, either by drinking
contaminated water or by consumption of contaminated, raw vegetables, the
usual mode of infection was undoubtedly by way of the skin, with larvae being
either brushed off damp grass or taken up from infected soil by the feet165.
Finally, two other routes of infection have been suggested. In 1917, Howard
reported the discovery of ova in the stool of an infant only 14 days old102, then
de Langen found them in the faeces of a six day old infant122. The only possible
explanation other than that unclean habits on the part of an infected mother may
have introduced ova into the mouth, and that these passed through the gastro-
intestinal tract unchanged, was that prenatal, transplacental infection had
occurred. More recently, it has been suggested that hookworm larvae may be
transmitted in breast milk.
DETERMINATION OF THE ROUTE OF MIGRATION OF LARVAE
Having proven to his own satisfaction, if not to everyone else's, that larvae
penetrated the skin, Looss then turned his attention to examining the course of
migrating larvae within the body, and in the process of defining this remarkable
pathway, proved the truth of his theory beyond any doubt. For these
experiments, Looss used dogs and infected them with the hookworm,
A. caninum, which was able to complete its development in that host. First, he
infected some puppies percutaneously, and when they died nine days later,
found immature ancylostomes in the small intestine. He then infected a group
of puppies and killed them at various times after infection. Looss showed that
larvae entered the lymphatics in the subcutaneous tissues and passed via the
draining lymph nodes to the bloodstream, or else entered the veins and were
carried through the right heart to the lungs. He found larvae both in the
pulmonary capillaries and in the alveolar air spaces, although he did not see a
worm precisely in the act of escaping from a capillary to an alveolus. The
larvae then migrated quickly upwards along the surface of the bronchiolar,
bronchial and tracheal epithelium, then passed through the larynx to the
oesophagus. During their migration through the respiratory tree, Looss noted
that the larvae began to grow and became prepared for the third ecdysis,
although that event did not take place until the worms had reached the intest-
ines. He then repeated this experiment with A. duodenale in dogs, and found
that the larvae penetrated the skin and passed to the lungs, but that in their
ascent of the airways, they grew less rapidly and that no trace of the provisional
mouth-capsule, which normally appeared prior to moulting, was present.
Furthermore, most of the larvae made their way into the tracheal mucosa and
very few reached the gut; those that did were passed in the faeces. Looss pre-
sented his findings to the International Congress of Zoology in Berne in 1904
and published his results in detail in the following year141.
Looss's observations were soon confirmed by other workers. Fritz Schaudinn
of the German Imperial Board of Health infected monkeys with hookworm
larvae percutaneously. The first animal died 13 days later and 36 worms were
found in the small bowel. A second monkey was infected on 11, 29 and 30 June
1904, then killed six hours after the last infection; worms were found in the
skin, heart, lungs and intestine181. In the following year, Lambinet produced
patent infections in dogs given A. caninum orally, percutaneously and
subcutaneously; he found that most of those given orally or subcutaneously
matured but that a proportion of those given percutaneously perished in the
process113.
In 1914, Friedrich Fülleborn reported an extensive series of investigations
on the migration of S. stercoralis and Ancylostoma in dogs. Fülleborn inter-
rupted the tracheo-oesophageal route by tracheotomy or oesophagotomy in
order to see whether this route was essential for the maturation of worms in the
gut. When the former operation was performed and a dog was then infected
percutaneously, larvae were found in the tracheal mucus 2-6 days later, but a
few eggs were seen in the faeces. When another dog underwent the latter
operation and was then infected subcutaneously, no hookworms developed in
the gut. Consequently, Fülleborn concluded that the vast majority of larvae
followed the pulmonary circuit78.
Soon afterwards, Miyagawa (1916) investigated the migratory route of
A. caninum larvae in dogs and confirmed the pulmonary-oesophageal route
after percutaneous infection. In addition, he showed that some of the larvae
given orally also followed this pathway after boring through the oesophageal
or gastric mucosa151. On the other hand, Yokogawa and Oiso repeated this
experiment with tracheotomized dogs some ten years later, and concluded that
the pulmonary route was not necessary for maturation 207. Nevertheless, both
Fülleborn 79 and Okada158 introduced A. caninum larvae into isolated loops of
small intestine and found mature worms in the normal bowel, thus indicating
that systemic migration must have occurred. The question remains incompletely
resolved, and the behaviour of A. duodenale and N. americanus in humans
after oral infection is unknown.
What is clear is that worms mature in the gut two to three months after
infection. A number of studies have been carried out on the persistence of
hookworms under conditions in which reinfection is not possible. These

investigations have shown that the life span of hookworms is generally one to
two years, with 50-70% of worms being lost in one year, although a few para-
sites seem to persist for many years55,149. Stoll, in a small series of patients,
calculated that each female N. americanus produced some 9,000 eggs per
day197, while Hill in a much larger series, concluded that the figure was closer
to 2,500 ova per female worm per day99.
In the first four patients found by Dubini, all the worms were located in the
intestinal mucus. In the next positive cadaver that he dissected (on 1 January
1845), however, he saw that "Two of them (the worms) were firmly attached
by their heads to the mucosa, and the mucosa was specked with small red
dots"70. Subsequently, Dubini found hookworms in many patients, either in a
free state, or sucking onto the intestinal mucosa. As a result of his accumulated
observations during many post-mortem examinations, he reached the following
conclusions about the worms:
- their exclusive habitat is the duodenum and the beginnings of the jejunum.
- the mucosa, to which the worms sometimes adhere by their oral cavity, may appear
to be normal or else slaty, greatly specked with black or red, or also simply
hypervascular.
- the variety of illnesses from which these people died does not permit us to establish
a relationship between the affliction and the presence of these worms70
Although he did not realize their significance, Dubini made two observations
necessary for a proper understanding of the pathogenesis of hookworm disease
- the attachment of worms to the small intestinal mucosa by their mouth and the
small haemorrhages around worms.
The person who was able to herald the pathological importance of hookworm
infection was Wilhelm Griesinger while working in Cairo. Many patients in
Griesinger's clinic suffered from severe anaemia, the syndrome being labelled
by Griesinger and his colleagues as Egyptian chlorosis. He sought the aetiology
of this condition without success for several months. During one of his last
autopsies (17 April 1852) before his return to Germany, much light was shed
on the matter. A twenty year old soldier died, apparently from diarrhoea. At
autopsy, all the organs were extremely anaemic, the heart was dilated and the
lungs were markedly oedematous. When Griesinger examined the intestines,
however, he found that:
the duodenum, the whole jejunum and even the upper half of the ileum were
completely filled with fresh, red, partly coagulated blood. Thousands of ancylostomes
were hanging in the mucosa of the small intestine, each with its own small petechia
resembling the bite of a leech.92
He concluded, therefore:
It was clear that in every respect the deceased belonged to the 'chlorotics', and had bled
to death. Since then I have become convinced that the 'Egyptian chlorosis' is an
entozoal disease, above all an ancylostomiasis.92
Griesinger postulated that the daily loss of blood in the gastrointestinal tract
must result in anaemia. He asserted that such haemorrhage need not be visible
macroscopically, since not only did bleeding come from the upper small bowel,
but the faeces of Egyptians were copious and mushy as they consumed large
quantities of bread. Rather, he believed that the continuous extraction of blood
for their own sustenance by hundreds or thousands of hookworms over the
years would be sufficient to account for the development of anaemia. Griesinger
left Egypt shortly thereafter and was unable to prove his views statistically, but
had no doubt that subsequent investigators would confirm his hypothesis92. In
fact, his colleague, Theodor Bilharz, who carried on this work, came to the
same conclusions and published his observations 31 two years before
Griesinger's paper appeared.
Despite these tantalizing suggestions, little further attention was paid to the
subject until Otto Wucherer in Brazil recognized the same phenomenon. In
December 1865, he was called to see a slave in a sugar mill who was grossly
oedematous and markedly anaemic. The patient died within 24 hours and at
autopsy, Wucherer found many hookworms and the same features that Gries-
inger had described. In order to ensure that the association was not
coincidental, Wucherer made post-mortem examinations on twelve persons
with other diseases and failed to find any hookworms. Furthermore, since he
found subsequently the parasites in the bodies of five more patients who had
this syndrome (which he called hypoaemia or tropical chlorosis), he was
convinced of a causal relationship between the two events204,206. The publication
of Wucherer's findings led J R de Moura in Rio de Janeiro to examine the
bodies of patients with tropical chlorosis and he also found hookworms in
them153 . Subsequently, Grenet in the French colony of Comoros (1867) 91
,
Camuset in French Guiana (1868) 52, and Kérangel in the French colony of
Cayenne (1868) 108 confirmed Wucherer's observations.
The findings of Wucherer and de Moura were discussed at the Academy in
Rio de Janeiro and the general opinion was reached that hookworms were not
a primary and necessary cause of tropical anaemia, but rather a cooperating
agent in its production (cited in206). In his turn, Wucherer protested against this
view205. Thus was born a controversy which was to persist for decades. There
were two great questions: (1) did hookworm infection cause disease at all?; and
(2) how many worms were necessary to cause illness?
In 1878, Sangalli179 in Italy, like Dubini, cast doubt on the idea that
hookworms caused any significant disease when he showed that autopsy
examinations in the University of Pavia revealed that half of the cadavers were
infected with hookworm, but that the symptoms and signs of disease did not by
any means appear to be as serious as might have been inferred from previous
descriptions, particularly those of Griesinger and Bilharz.
The potential importance of hookworm infection was brought home to many

European doctors, however, by the outbreak of hookworm disease which
occurred during the building of the St. Gothard tunnel, a railway tunnel in the
Swiss Alps which was opened in 188347,48,164. At the beginning of 1880, a large
number of workmen, mainly from Piedmont, returned home ill. Despite their
evacuation from the tunnel, the condition of many patients worsened and
several died. In February 1880, one of these persons died in hospital in Turin
from what had been labelled "pernicious anaemia". A post-mortem examination
by Francisco-Vittoria Colomiatti, professor of pathology at the University,
disclosed some 1500 ancylostomes in the small bowel. Considerable argument
at both medical and political levels then ensued as to whether the St. Gothard
anaemia was due to ancylostomiasis or to poor hygienic conditions, particularly
bad air, poor light and unsuitable food. Some investigators, such as Bozzolo
and Pagliani, supported the latter view, at least initially41. The former view
eventually prevailed, however, particularly as a result of the work of Eduardo
Perroncito who found large numbers of hookworm eggs in the faeces of many
patients, and showed that they responded to treatment with anthelmintics 57,167,168
The confusion over the role of hookworms in the genesis of disease is further
illustrated by the following sample of views expressed over the next few years.
In 1882, JF McConnell reported for the first time that hookworms were present
in India, and noted that anaemia was present in only 40% of these patients. He
made no reference to the worm burden, but wrote: "My opinion is that their
presence is to be regarded in the majority of cases as purely accidental, and
their relation to any special disease a coincidence" 144. Similarly, Attygale in
Ceylon in 1888, could not find ancylostomes in half of his patients with
anaemia. Furthermore, he realized that hookworms could not reproduce in the
bowel and presumed that the worm burden depended upon the number of eggs
ingested, so asked the question:
Might it not also be considered with greater reason that whatever induced the disease
[i.e. anaemia]....in cases in which the anchylostoma was absent, was also the cause
[when they were present], and that the presence of anchylostoma in these cases was
of no more import in its causation that that of the lumbrici found in common with it
in a large number of cases?17
Sonsino (1890) forthrightly denied any connection between hookworm infect-
ion and severe illness of the type described by Griesinger when he wrote:
I think the so-called African cachexia and Griesinger's Egyptian chlorosis cannot
rightly be identified with ankylostomiasis, inasmuch as they are the combined result
of different morbid conditions into which frequently, but not constantly,
ankylostomiasis enters as an element.190
In like manner, Dobson in India (1893) examined the stools of 1,249 persons,
most of them healthy coolies en route to work from various parts of India on the
Assam tea plantations. He found hookworms in 76% of these individuals, with
numbers varying from very few to hundreds. Moreover, it sometimes happened
that a person with very few worms was in very bad health whereas some
persons in whom there was a great abundance of parasites were robust and
healthy. Furthermore, in 15 cases of kala azar (which some persons had
postulated was caused by hookworm infection), there were only 0-36 hook-
worms, so Dobson concluded that hookworms had no great influence as a
factor in the genesis of disease, whether it be the "beri-beri of Assam" or
anything else69. Such views were echoed by Williams203 and by Zinn and
Jacoby208.
On the other hand, Kynsey in Ceylon (1887) 112 and Giles in Assam (1890) 83
were both convinced that the so-called "beriberi" of Ceylon and Assam or "kala
azar" of Assam were due to ancylostomiasis. This occasioned some confusion,
for "beriberi" was a rather elastic term including a number of entities such as
wet beriberi (cardiac failure) and dry beriberi (peripheral neuropathy) that are
now recognized as being due to thiamine deficiency, and kala azar is the name
now given to the disease caused by infection with Leishmania donovani.
Nevertheless, the disease then called beriberi in Assam and Ceylon was of the
wet variety in both cases and may well have been related to ancylostomiasis in
the form of marked hookworm-induced anaemia and consequent congestive
cardiac failure. An anonymous commentator in the British Medical Journal
came very close to the truth when he remarked in 1893:
In the healthy and robust native, with a liberal physiological margin to draw on, a few
hundreds of minute nematodes in the alimentary canal may be a circumstance of little
importance; but when the native has been half starved all his life, and is further
reduced by actual famine, by malaria, dyspepsia, enteritis, overwork, and other
conditions tending to diminish the amount of aliment absorbed, while at the same time
they tend to increase waste and destruction - in these conditions a daily steady drain
of blood by a swarm of anchylostomata, though it may after all be but a small one,
may prove to be the last straw which breaks the camel's back, the final factor which
determines the starting of the vicious pathological circle.7
Two events in particular which occurred around the turn of the century did
much to convince the sceptics that hookworm infection sometimes culminated
in serious disease. The first of these was the spread of ancylostomiasis from the
St. Gothard's tunnel and elsewhere to the rest of Europe. Miners and expatriates
returning from the tropics carried hookworms with them to the congenial sur-
roundings of the brickfields of Austria, Hungary and Germany, and to the coal-
mines of France, Belgium and England, where the parasites flourished in the
warm, damp, insanitary conditions underground8,77,159. This epidemic confirmed
the pathogenicity of the parasite, for many people developed severe anaemia,
and it stimulated many investigations into the habits of the larvae, the genesis
of anaemia, and means of prevention.
The second series of observations emanated from the Western Hemisphere.
In August 1899, a hurricane wreaked havoc in Puerto Rico. Bailey K Ashford
of the United States Army was put in charge of a temporary hospital to deal
with the thousands of sick, homeless, starving peasants who were mountain
dwellers of Spanish descent. When they were fed on the nourishing diet of the
American soldier, they developed diarrhoea. When they left camp and returned
to their normal, bulky diet, the diarrhoea resolved but the anaemia with which
they were also afflicted did not. A search for malarial parasites as a cause of the
anaemia revealed the presence of a blood eosinophilia which in turn stimulated
inspection of the faeces for hookworm eggs. These were found in abundance
and on 24 November 1899, Ashford in Ponce sent a telegram to the chief
surgeon in San Juan: "Have this day proven the cause of many pernicious,
progressive anemias of this island to be due to Ankylostoma duodenale.
Ashford"14. He published his findings in the following year 15
. Several years
later, Ashford headed a commission for the study and treatment of anaemia; his
earlier belief that hookworm infection was a major cause of disease was
confirmed fully16.
As a result of these and other observations, the tide of opinion began to turn,
with Baker (1903) writing:
I firmly believe that ankylostomiasis is productive, both directly and indirectly, of far
greater mortality than the vast majority of medical men have any conception of. The
large number of deaths ascribed to unknown causes, the heavy mortality attributed to
general dropsy and debility, and the great loss of life occurring among paupers found
dying the streets of tropical towns, I am convinced, were in the past and are today in
no small measure due to ankylostomiasis. There are few things more remarkable in
the whole history of tropical medicine than the failure to realize and the reluctance to
admit, on the part of many medical men, the injurious tendency of an invasion of the
body by the parasite which gives rise to ankylostomiasis.25
Similarly, Boycott (1911) said in his Milroy lectures:
Taking the world as a whole, with the possible exception of the malarial organisms,
ankylostoma is, I suppose, responsible for more unhappiness and inefficiency than any
other parasite, and for the most part indirectly for no inconsiderable number of deaths.
Practically all tropical countries are permeated with the worm, and in places where the
conditions for its propogation are favourable it may reduce four-fifths of the
population to a continual state of chronic ill-health which is only terminated by the
premature decease, commonly with some secondary infection.37
Around this time, however, the pendulum began to swing even further away
from the point at which it had at one time stood. Far from saying that
hookworms were never pathogenic, some authors began to claim that hook-
worms always caused disease, even when the worm burden was small. This
was brought about by observations flowing from the campaign to control hook-
worm in the southern USA just before World War I. It seemed that hookworm
carriers, i.e. those with hookworm infection but with no apparent ill-effects
from the infection, improved in health and energy after treatment. This was
interpreted as an indication that they were not simply carriers, but that their
general ineptitude, which had been put down to laziness, carelessness, or race,
was in fact due to hookworm infection. Thus, Stiles in 1914 was induced to
write:
There still exist a number of persons who believe that light infections are of no clinical
importance....The view that infection with less than 100 or 50 worms is clinically
unimportant is negatived by the fact that treatment of such cases has resulted in the
children in question having made greater improvement in certain respects, in a given
time, than has a control group of children who did not show hookworm infection and
a control group of children who did have the infection but were not treated.195
This view was echoed by Lane (1918). He quoted passages from the Reports
of the Rockefeller Sanitary Commission which, he believed, demonstrated that
the officials of the Commission began with the premise that light infections
were of little moment to the host, yet finished thoroughly convinced that even
very mild infections constituted a grave handicap. Similarly, he quoted letters
from managers of tea estates in Darjeeling, India, where there was widespread
but moderate hookworm infection, who were pleased with the effects of
anthelmintic treatment on the health of their labourers. This stimulated Lane to
write: "We seem then to have no option but to conclude that light infections are
of clinical moment to the individuals concerned"117. Lane later indicated that the
practical import of this view was that the only safe course was to regard no
infection as clinically unimportant until such time as the dividing line between
hookworm infection and hookworm disease had been defined scientifically 120.
As late as 1935, he proclaimed: "the host's interests demands complete
deworming"121. Stiles in the USA and Lane in the United Kingdom were the
most ardent, prolific and persuasive writers on this subject, expounding the
view either that light infections were important, or that, at the very least, it was
not proven that they were unimportant.
Not everyone accepted this belief, however, Boycott in 1911 drew a dis-
tinction between Ancylostoma infection and ancylostomiasis, defining any
individual who harboured parasites in his intestines but without having any
symptoms or signs of the infection as a "worm-carrier" and as the subject of
hookworm infection, whereas those infected persons who had dyspepsia or
anaemia as a consequence of that infection were deemed to suffer from ancylo-
stomiasis37. Similarly, Gordon in 1925 reported that his studies of West African
males revealed no effect by hookworm infection on haemoglobin level,
physique or mental alertness, and recommended that the effects of hookworm
infection on a particular population should be assessed by correlating
pathogenic effects with intensity of infection before embarking upon mass
treatment89. This information caused Harold Scott in his review of the paper to
write:
This article is of great interest and serves as a refreshing counterblast to exaggerated
records of the dire evils of hookworm infection....(which have been recorded as
ranging from) rheumatism to nyctolopia [night blindness].185
This idea was taken further by Smillie and Augustine (1926) in the USA who
divided children up into groups on the basis of hookworm numbers. They found
that no adverse effects upon clinical status or haemoglobin level were seen
when less than 100 worms were present, and more than 500 worms were
required for the full clinical disorder to be produced187. When they analysed
changes three months after treatment, they discerned no effects of this
intervention in children who had less than 25 worms, an improvement in

haemoglobin concentration only in those with 25-100 worms, and enhanced
gains in height, weight and haemoglobin level in those who had more than 100
worms188. In the same vein and as a result of his own investigations in
Argentina, Fülleborn declared:
One becomes more and more convinced I think, that in the past the damage caused
by a slight hookworm infection has often been overestimated, at least as far as
Necator is concerned.80
Also in 1929, Chandler reviewed the evidence. He noted that the difficulty with
the early Rockefeller reports was that they grouped all grades of infection
together, so that improved health and efficiency in a small number of heavily
infected individuals might be sufficient to provide the observed improvement
in the group as a whole. He remarked, however, that more recently, incidence
data had been supplemented with information on the intensity of infection,
which brought him to hold the opposite conclusion to Stiles and write:
Recent investigations have, fortunately, made the opinion that any hookworm
infestation, however light, is harmful, practically untenable. No doubt even a single
hookworm does some injury to its host, but this injury, in a normal individual, is so
easily compensated that it is of little or no consequence.56
It was only with the elucidation of the pathogenesis of hookworm anaemia, as
described in the next section, that the controversy was resolved, with the view
being generally upheld that heavy worm burdens were usually required for the
production of anaemia.
DETERMINATION OF THE PATHOGENESIS OF HOOKWORM

ANAEMIA
Amongst those who accepted that hookworms might cause anaemia, the quest-
ion arose as to how the anaemia was produced. The first and most obvious way,
as reported by Griesinger, was as a consequence of massive bleeding into the
gut. At one time, it was thought that only a few worms were necessary, for it
had been shown that when hookworms moved, they left wounds behind them
which continued to bleed, and this led one anonymous reviewer to write in
1889: "Hence it is easy to understand how a very few may cause fatal
anaemia"6. An alternative possibility was canvassed by Rake in 1894:
Is the anaemia the result of a simple drain of blood from the gut by worms, or is it, as
William Hunter contends, the result of excess blood destruction in the portal
circulation effected by the action of certain poisonous agents absorbed from the gut
through breaches made by the worms?172
The likely importance of this latter mechanism seemed to be heightened when
the authoritative and prestigious Looss declared that the epithelial cells of the
small bowel rather than blood provided the food supply of hookworms 140.
Before any proper understanding of hookworm anaemia could be gained,
however, the condition had to be differentiated from idiopathic pernicious
anaemia. One of the first persons to investigate hookworm anaemia in detail

was Arthur Boycott who studied miners in Cornwall infected with hookworm.
He recognized (1907) that the degree of anaemia was in general proportional
to the number of worms present, although he qualified this statement by saying
that exceptions occurred, and suggested that the frequency with which further
infections were acquired may be a more important factor. This latter comment
was based largely upon the improvement often seen when patients were
removed from an endemic location, thus allowing worms to be expelled
gradually and haemoglobin concentrations restored. The importance of this
observation was that the natural history of hookworm anaemia was clearly
different from the progressive downhill course of pernicious anaemia. So was
the appearance of the blood film. Boycott emphasized that in hookworm
anaemia the red cells were microcytic and that the colour index fell (i.e. they
were hypochromic), whereas in pernicious anaemia the erythrocytes were
macrocytic and the colour index was normal36. Nevertheless, Boycott was
puzzled by the mechanism by which the anaemia was produced, for he did not
believe it was due to gastrointestinal haemorrhage, and considered that the
haemolysin and anticoagulant factor which had been found in hookworms a
short while before by Loeb and Smith135 were of no great import.
Experimental studies by Huart in Leiden, Holland104 and by Fülleborn and
Kikuth in Hamburg, Germany81 in 1919 using dogs infected with A. caninum
and A. braziliense, however, re-emphasized the role of gastrointestinal
haemorrhage in the genesis of hookworm anaemia, and failed to identify a place
for haemolysis in the production of the anaemia. The processes by which
haemorrhage occurred were observed in vivo by Wells, who watched the
behaviour of A. caninum in the opened intestine of anaesthetized dogs. Worms
moved around on the mucosa for hours, but eventually attached themselves to
the bases of some villi. The vessels of the villi became distended, blood
appeared in the mouth of the worm, and the oesophageal muscles pumped
blood through the gut at the rate of 2-4 pulsations per second. Wells calculated
that each A. caninum wasted nearly 0.84 ml of blood a day201.
The importance of gastrointestinal blood loss was then underlined by three
studies reported in 1934. Biggam and Ghalioungui in Egypt found that oral iron
corrected hookworm anaemia, even when the patient was still harbouring
worms, but that removal of the worms alone produced little or no change in the
blood picture30. Rhoads and Castle showed in a study of 150 patients with
hookworm anaemia in Puerto Rico, that either the intramuscular injection of
erythrocytes or the oral administration of iron, but not liver extract (rich in
vitamin B12), stimulated red cell production and a rise in haemoglobin con-
centration. They concluded that since deficient diets were the rule, and as
gastric hypochlorhydria was present frequently, it seemed likely that dietary
deficiency and gastrointestinal disturbances were of major aetiological
significance 174. The role of iron deficiency in the genesis of this anaemia was
also supported by Cruz in Argentina; he observed that a rich meat diet or the
administration of large doses of iron prevented the appearance of anaemia61.

Similarly, Napier and his colleagues in India a few years later considered that
even a heavy load of worms did not produce anaemia unless the diet was defic-
ient in iron. Further, they showed that a return of haemoglobin level to
normal could be achieved with iron alone, but that this was not maintained
unless the worms were removed by anthelmintic therapy156. In the same
manner, Andrews in the southern USA concluded that hookworm disease was
more likely and more severe when worm burdens were high and protein con-
sumption was low3.
Thus, the pendulum began to swing once more, and it became generally ac-
cepted that the likelihood of anaemia was directly proportional to the worm
burden and inversely proportional to the iron and protein intake in the diet. By
the same token, growing children and menstruating or pregnant women were
more likely to develop disease with a lower worm burden by virtue of increased
demands upon, or losses of, these nutrients. In 1957, Roche and his colleagues
quantified gastrointestinal blood loss in human hookworm infection by labelling
erythrocytes with radioactive chromium then measuring the radioactivity sub-
sequently lost in the faeces. They calculated that approximately 0.03 ml blood
was lost per day for each N. americanus, but that 0.2 ml was lost for every A.
duodenale 175.
In most people with a normal or highly nutritious diet, therefore, there was
little probability of a significant fall in haemoglobin concentration. More than
2,000 eggs per gram of faeces were necessary before anaemia was seen in
Venezuela123, anaemia was not seen unless egg counts were greater than 1,000
per gram in the Gambia199, and considerably higher counts were required in
Nigerians who had a much higher daily intake of iron87. This realization led to
an increased emphasis on hookworm disease and less on hookworm infection,
and the arguments which had been raised over the efficiencies of various
concentration techniques for the diagnosis of hookworm infection (see later)
became less relevant. As a parenthetical postscript, it may be remarked that
blood-letting activities of hookworms have even been made use of thera-
peutically in the treatment of polycythaemia rubra vera45,71.
Classical descriptions of illnesses that were possibly or probably a consequence

of hookworm infection were described long before the worms themselves were
recognized. Attempts have been made to find evidence of hookworm disease
in the Egyptian Papyrus Ebers (c.1550 BC)162, particularly in the - - disease
which was said to be a chronic disorder of the gastrointestinal tract followed by
a disturbance of the circulatory system182, although more modern opinion
favours its association with schistosomiasis101,169. Nevertheless, Ebell expressed
the opinion in his translation of the Papyrus Ebers that the anaemia mentioned
in association with the worm was probably hookworm anaemia72. Hippocrates

(c.460-375 BC) may have been dealing with hookworm infection when he
spoke of pallor in people who ate dirt100. In 50 BC, Lucretius wrote of the pallor
of those who worked in mines. Khalil109 has claimed that Avicenna (981-1037
AD) referred to hookworms, although this view is not now generally
accepted101.
Various accounts emanating from Central and South America are consistent
with a diagnosis of hookworm disease, as in the following extract from a book
by an anonymous author who was apparently a doctor and a planter:
When a negro is languid and listless, and so much indisposed to motion as to require
to be impelled to it by threats, when he is short-breathed and unable to ascend a hill
without stopping, his efforts for that purpose being accompanied with a throbbing of
the temples and a violent palpitation of the heart; when he complains of giddiness, his
lips being pale and his tongue white, you may know him to labour under that disorder
which the French call mal d'estomac and the English after them by the same name or
'dirt-eating' from the propensity which there is in that case to eat chalk or clay or some
other kind of dirty substance....This disorder which as I observed is very common in
West Indies estates is also one of the most obstinate and troublesome that negroes are
afflicted with. It disables them from effective labour for a considerable time,
sometimes for years, and often terminates in dropsy.5
As mentioned earlier, Griesinger in Egypt was familiar with the syndrome of
Egyptian chlorosis before he discovered its relation to hookworm infection. He
wrote that the symptoms and signs of this affliction were simply those of
anaemia:
The milder stages are characterized by pallor of the skin and the mucosa....a tendency
to palpitations, a prolonged tachycardia, and slight fatigue on exertion....(In) the
chronic form....the patients....develop edema in the lower extremities, the eyelids and
other parts; their skin....becomes a dirty pale yellow, yellow or green-white....At the
same time it becomes very withered, flabby, cool, dry and scaly; the conjunctiva is
blue-white, and the lips and all visible mucous membranes are a deathly pale. Marked
generalized weakness and fatigue....makes the patient very indolent and
apathetic....Palpitations corresponding to the heart beat, the intensity of which we
have never seen before, persist in many patients....The pulse is very rapid and weak.
In all the larger arteries one hears a blowing sound....Patients often suffer from
vertigo....Dyspnea occurs after a few steps ....The overall condition of the patient must
be viewed as a state of advanced anemia or fluid retention.92
Clearly, in these patients, the anaemia had become so intense that marked
features of congestive cardiac failure had supervened.
The same clinical manifestations were then described by Wucherer204,206, de
Moura153 and others in South and Central America. In 1878, Grassi and his col-
leagues in Italy published clinical notes on patients with hookworm infection,
a number of whom were anaemic90. Similarly, the clinical features of anaemia
in association with ancylostomiasis were highlighted in miners working in the
St. Gothard Tunnel in 188047,57, and islanders living on Puerto Rico15. Thus, it
was recognized that the clinical features of severe hookworm disease were
those of marked anaemia produced by the mechanisms discussed earlier.
While the clinical features of gross hookworm anaemia were clear, the other
manifestations of infection were rather more obscure. Dermatitis (ground itch
- see section on the proof of the percutaneous route of infection) was only
observed sometimes. Migration through the lungs was thought to produce
cough, wheezes and hoarseness in some patients10. Conflicting accounts were
published on growth retardation and mental sluggishness 89,187,188,200. The
gastrointestinal symptoms were also difficult to define because concurrent
infections with other gastrointestinal pathogens was so common. Experimental
infection with sole hookworm infections, however, provided some useful
information. Brumpt infected patients with hypertension or polycythaemia with
about 400 hookworm larvae and noted an initial dermatitis, subsequent upper
respiratory symptoms (but no indication of Löffler's syndrome), then
indigestion and diarrhoea. The abdominal discomfort soon cleared up but the
diarrhoea sometimes persisted for a month45. Similarly, experimental infection
with A. ceylanicum indicated temporary, but severe, indigestion, flatulence and
abdominal distension 202.
The diagnosis of ancylostomiasis was first made only post-mortem. Wucherer

in 1866 posed the question as to whether it might not be possible to determine
the presence of hookworms during life in order to distinguish hookworm
anaemia from the anaemia of "malarial cachexia". He found, however, that thus
far he had not been able to locate adult worms in the faeces, even after the use
of anthelmintics, and remarked further: "this diagnostic tool, even if it were
reliable, would not be used very frequently by our colleagues" 204.
It is surprising that neither Wucherer nor any of his contemporaries paid any
attention to looking for hookworm eggs in the faeces, since Ransom (1856) and
Davaine (1857) had shown the value of this diagnostic technique in ascariasis,
trichuriasis and taeniasis, and Davaine had publicized it widely in his textbook
of 186066. It was not until 1878 that the Italian parasitologists, GB Grassi,
Corrado Parona and Ernesto Parona reported that:
the diagnosis of Ancylostoma is very easy. To do this rapidly, it suffices to examine
a little feces or vomit, diluted with any medium, at the microscopic magnification of
at least 90 diameters. If the material is fresh, only Ancylostoma ova undergoing
segmentation will be found; if it is stale, embryos and larvae will also be found.90
Grassi and his colleagues proved the diagnosis in several of their cases by the
administration of anthelmintics and the recovery of adult worms; in one patient,
an estimated 440 worms were found in the faeces90. This method of diagnosis
was likewise taken up with success two years later by Perroncito when he
diagnosed Ancylostoma infection in St. Gothard tunnel miners presenting to
Concato's clinic57.
As the technique became more widely used, it was realized that simple faecal
smears did not always detect light infections. The forceful opinions expressed
by some that light infections were of clinical significance generated intensive
efforts, particularly in the first third of this century, to develop concentration
techniques in order to permit detection of such infections. The various tests
designed up to about 1930 have been reviewed by Lane120, who himself
devoted many years to the problem. Later concentration techniques have been
described in chapter 9. In addition, Harada and Mori in 1955 described a
completely new method of cultivating hookworm larvae on moistened filter
paper which they believed was considerably more efficient than flotation
methods for detecting infection96. Quantitative techniques have permitted
counting of the number of eggs in the faeces and this has been widely accepted
as providing an index of the worm burden, although there have been a few
vocal opponents of this view121.
The identification of hookworm eggs in the faeces has been used in recent
times to confirm the antiquity of hookworm infection, although this test is not
able to differentiate between the species of hookworms. Hookworm eggs have
been seen in human faeces in Brazil dating from 430-3490 BP74.
A number of efforts have been made to develop immunological tests for the
diagnosis of hookworm infection. Ghedini (1907) found complement fixing
antibodies in the serum of patients with hookworm infection82. Pirie and
colleagues in 1929 reported a skin test for the diagnosis of hookworm
infection170. Such efforts, however, have been largely unrewarding as the
diagnosis is made relatively easily by parasitological methods except in
prepatent infections, and immunodiagnosis gives no indication of the worm
burden. Similarly, the blood eosinophilia in hookworm infection, first described
by Müller and Rieder in 1891154, is nonspecific and is merely a pointer to the
possible presence of infection.
The diagnosis is sometimes suggested by radiography. Krause and Crilly re-
ported that barium meal examination revealed alterations in the small bowel
mucosal outline which they called a "deficiency pattern"111. Finally, as
sophisticated gastrointestinal endoscopic facilities become more widely avail-
able, someone in the near future will undoubtedly report the diagnosis of
hookworm infection by the observation of adult worms during duodenoscopy.
As early as 1866, Wucherer in Brazil reported that latex d'higueron, an extract

of the figs, Ficus laurifolia and F. glabrata, was effective in the treatment of
hookworm infection204. Indeed, because of its effectiveness and local avail-
ability, this drug at one time became the basis of a hookworm control campaign
in Venezuela 152. The preparation was not generally obtainable in Europe,
however, and Grassi and his colleagues in Italy treated their patients with a
combination of santonin, calomel, jalap and sugar with a modicum of success90.

Interest in the treatment of hookworm infection was stimulated by the out-
break of ancylostomiasis in miners working in the St. Gothard tunnel around
1880. Perroncito in Turin26,167, then Ernesto Parona at Varese43,163 , Italy,
claimed that the well-known remedy for tapeworm infection, filix mas (oleo-
resin of Aspidium, male fern) prepared from the powdered rhizomes of the fern,
Dryopteris filix mas and related species) had antihookworm properties.
Perroncito showed that an extract of filix mas killed larvae in vitro within five
to ten minutes, then reported that he had reduced hookworm numbers in two
patients by repeated administration of the drug167. Meanwhile, Camillo Bozzolo
investigated the properties of thymol which is prepared from a large number of
plants of the genera Thyme, Origanum and Carum. He had used it in 1879 in
one patient with ancylostomiasis without effect38. The St. Gothard epidemic
provided him with an opportunity to re-evaluate the drug more intensively. He
increased the dosage and in 1881 claimed to have cured six patients39,40 with the
consequence that the drug became very popular for the next several decades.
Although there were claims from time to time that the drug was toxic and could
be fatal, these were not accepted by Lane in his review of antihookworm agents
in 1935121.
Eucalyptus oil was a popular remedy for a time, but a number of investigators
found it to be ineffective. Chloroform had been shown in 1885 to be active
against tapeworms when used in combination with a purgative which caused
passage of the anaesthetized worms27. Consequently, Herman in 1905
introduced a mixture of eucalyptus oil and chloroform for hookworm infection97
and this enjoyed transient fashionableness. Betanaphthol, a synthetic organic
compound, was used by Bentley in 190429. Unfortunately, it sometimes caused
haemolysis or nephritis, and occasionally death, and eventually fell into
disrepute.
Oil of chenopodium (American wormseed oil), prepared from Chenopodium
ambrosioides var. anthelminthicum, an indigenous plant in the USA, had been
a common household remedy for ascariasis in that country for many years.
Baumler (1881) and Breton (1905) had tried it without success for
ancylostomiasis, but then Bruning began to use it successfully in 190946.
Subsequently, Schüffner in the Dutch East Indies (Indonesia) reported that it
was more effective than thymol, betanaphthol or eucalyptus oil. He found that
following a single treatment, oil of chenopodium eliminated 92% of hook-
worms, thymol dislodged 83%, betanaphthol expelled 64%, and eucalyptus-
chloroform-castor oil mixture removed 38% of worms, while male fern came
a poor last183. Some 300,000 patients were treated with various remedies by the
Puerto Rico Commission on hookworm, and an analysis of the results revealed
that male fern was ineffective, eucalyptus was nauseating, and that thymol and
betanaphthol were about equally efficacious16. All of these drugs, and many
more, were investigated by Caius and Mhaskar in a major series of studies
carried out in India50. Mhaskar in 1922 reviewed the results and concluded that
of 54 substances investigated, oil of chenopodium, thymol and betanaphthol
were the most effective drugs150.
It was at this juncture that a new drug, carbon tetrachloride, was introduced.
In 1921, MC Hall of the US Bureau of Animal Industry published a paper
indicating that this agent was a useful anthelmintic in animals93. He then
swallowed some of the chemical himself without ill-effect, and suggested its
use in human hookworm infection94. A number of reports soon followed show-
ing that it was effective in human ancylostomiasis 24,124,157. Considerable
differences of opinion then ensued over the safety of the drug. Being aware that
prolonged use of fat solvents such as carbon tetrachloride, chloroform and
tetrachloroethane could cause severe liver disease, Nicholls and Hampton gave
carbon tetrachloride twice to a condemned murderer then examined the organs
after execution one to three weeks later. No signs of degeneration were found
and they concluded that when given in a single dose, carbon tetrachloride was
safe157. The drug became used widely and was employed with apparently few
side-effects by some workers. For example, Bishop administered the drug to
25,000 cases in Trinidad and Tobago with little report of illness33, while Khalil
claimed only one fatal result in 150,000 treatments 110. Nevertheless, these
reports must be viewed with some circumspection, since there may have been
a considerable latent period between the ingestion of carbon tetrachloride and
the appearance of liver failure which may have obscured the relationship
between the two events. On the other hand, some workers had sad experiences.
For example, Straub and Kouwenaar had 16 deaths and gave up using the
drug198, while Nag reported three deaths in 289 children 155
. With great
indignation, Lane (1930) condemned its use, particularly in mass treatment
campaigns where it had often not been shown that a particular individual was
infected:
For carbon tetrachloride....the fatal dose is [he should have said 'may be'] 1.5 c.cm.;
while the dose advised as effective is 3 c.c., or twice the fatal dose. This advised dose
has naturally killed a varying proportion of those who have taken it. Further, it has
been freely administered without troubling to discover whether any particular recipient
was infected, in which case it remains unknown whether the individuals so sacrificed
should have been treated at all.119
Carbon tetrachloride was soon followed by its relative, tetrachlorethylene.
This drug was introduced by Hall and Shillinger in 192595, and its effectiveness
was confirmed by Schapiro and Stoll two years later180. The advantage of tetra-
chlorethylene over carbon tetrachloride was highlighted when Lamson and his
colleagues in 1929 showed in experimental dogs that the hepatic necrosis
evident after the latter drug was administered was absent when tetrachlor-
ethylene was used115. In 1931, the same group of workers reported that hexyl-
resorcinol, an alkylated derivative of phenol and related to thymol, was
effective in ancylostomiasis 114, but this drug did not find a major place in
treatment.
The merits and demerits of the various anthelmintics known at this time led
to contrasting views on the drug of choice in the treatment of hookworm
infection. Lane (1935) damned carbon tetrachloride and extolled the virtues of
thymol121, while Andrews (1942) espoused carbon tetrachloride and relegated
tetrachlorethylene as being less effective3.
The next major advance did not take place until 1958. In that year, it was
shown that a new series of quaternary ammonium compounds was active
against a broad range of nematodes parasitic in laboratory and domestic
animals58. Goodwin and his colleagues then showed in a trial in Ceylon that one
of these agents, bephenium hydroxynaphthoate, was active in human hookworm
infection. The drug was shown to have an effectiveness comparable with that
of tetrachlorethylene. Furthermore, it had the added advantages of less toxicity
and some activity against Ascaris lumbricoides 88.
In 1961, Brown and his colleagues described a new benzimidazole
derivative, thiabendazole44, then a number of authors showed that it eliminated
most nematodes from the intestines of sheep, pigs and horses. In the following
year, Bui Quoc Huong and colleagues reported that thiabendazole cured 85%
of humans infected with hookworm49, then many subsequent workers confirmed
the effectiveness of the drug.
In 1966, Austin and his colleagues discovered a new series of broad
spectrum anthelmintics. One of these, pyrantel pamoate was active against
mature and immature nematodes in animals20. Several years later, pyrantel
embonate was shown to be effective in human ancylostomiasis, with 84% of
patients being cured68. These findings were then confirmed by many other
workers. Finally, Chaia and Cunha in 1971 showed that mebendazole, another
benzimidazole derivative, was also very effective in hookworm infection54.
The discovery and use of agents directed specifically against hookworms has
not been the only way in which the problem of hookworm anaemia has been
approached. As long ago as 1866, and before the mechanism of hookworm
anaemia was defined and the biochemistry of anaemia due to blood loss was
understood, Wucherer remarked that patients seemed to do better with the
combined use of iron preparations and anthelmintics than when anthelmintics
alone were given. In 1914, Day reviewed his experience in treating over 300
patients with gross hookworm anaemia (the average haemoglobin concen-
tration was only 22% of normal), and showed that the addition of iron prep-
arations hastened the recovery from anaemia after anthelmintic administration 67.
As has already been indicated in the review of the pathogenesis of hookworm
anaemia, many subsequent studies confirmed the value of treating hookworm
anaemia with iron as well as giving anthelmintic therapy30,61,156,174.
More recently, Topley concluded that although all hookworms should ideally
be eliminated, this was most desirable in the most anaemic patients, and that for
less severely affected persons, particularly men, iron therapy alone was often
adequate. An anonymous writer in The Lancet concurred with this view:
Ferrous sulphate is cheap, and now that iron-deficiency has been shown to be the
commonest cause of anaemia among these people, whether from hookworm disease
in men, or other causes in women, there seems every reason for training auxiliaries
to test for it, keep records, and distribute tablets. Patients with severe anaemia, and
those who did not respond to treatment, could be referred for more definitive
treatment. The final answer to the problem of hookworm disease probably lies in
environmental measures, but the use of oral iron could increase the economic
potential of many populations.13
Such comments as this would have sent shudders up the spine of Stiles and of
Lane, even if they did not cause them to turn in their graves, but they serve to
exemplify how far conceptions concerning the management of hookworm
infection and disease have swung.
Both A. duodenale and N. americanus are disseminated widely throughout the

tropical world, but their origins are uncertain. It was at first thought that
A. duodenale emanated from the Old World and that N. americanus was indig-
enous to the Western Hemisphere. In 1905, Looss examined some hookworms
obtained from six Central African pygmies and found that they were N.
americanus. This observation led him to suggest that N. americanus may have
been carried to the Americas from Africa by negro slaves140. Leiper (1907)
confirmed Looss's observations, finding N. americanus not only over wide
areas of Africa apart from Egypt, but also in specimens emanating from the
Indian subcontinent131 and from Australia. Furthermore, Soper (1927) believed
that A. duodenale had a much longer history in Central and South America than
had been thought and suggested that, in addition to being brought over by the
early Spaniards, the parasite may have been indigenous to the Indian race191.
The longstanding presence of A. duodenale in South America was supported
when an apparent A. duodenale was found in the small intestine of a
mummified body discovered in Peru and dating from about 900 AD2.
An understanding of the epidemiology of hookworm infection was largely
incomprehensible until the percutaneous mode of infection was discovered by
Looss around the turn of the present century. Thus, all sorts of inexplicable
difficulties arose when attempts were made to explain the presence of ancylo-
stomiasis in the St. Gothard tunnel. For example, Bozzolo and Pagliani
postulated that impurities in the water used for drinking in the galleries
contributed to the spread of hookworm ova, but Lombard, a staunch opponent
of the parasitic theory of miner's anaemia, was able to counter with the reply
that a perfectly safe supply of water was piped in164. Nevertheless, the
recurrence of anaemia in miners stimulated interest in observing the habits of
hookworm larvae and determining the factors which inhibited or enhanced their
development. This interest was heightened enormously when the percutaneous
route of infection was proven, as this would assist in the development of

effective control measures. The optimal conditions of temperature, humidity
and oxygen tension necessary for development of larvae were defined, and the
actions of various larvicides such as salt, carbolic acid, and izal were
investigated 22,23,35,77.
Similarly, this new understanding of the mode of transmission improved
ideas about the spread of infection in endemic areas. Stiles (1915) realized that
ancylostomiasis was entirely due to bad sanitation and considered its
prevalence as an index of the sanitation in the district where it occurred. In an
investigation of hookworm infection in schoolchildren in the USA, he found
that those children who came from sewered homes were relatively protected,
but that those who lived in houses where there was a privy were more subject
to infection. Further, Stiles believed that privies were not only inefficient, but
may have positively evil effects because they concentrated contaminated faeces
in focal areas rather than allowing them to be dispersed widely, thus reducing
the chances of infection: "a privy has a radius of influence in every direction of
the compass"196.
This concept was confirmed by Baermann working in Indonesia (1917). He
developed a novel method (the Baermann technique) for recovering larvae from
soil samples, and found that hookworm larvae were not diffused over wide
areas, but were concentrated in the neighbourhood of latrines and in constantly
damp soil around water storage vessels. Baermann observed that hookworm
larvae wandered from earth into water, moving in loose earth at the rate of 1 cm
per minute. He found that larvae in shaded, moist areas under plants or grass
survived for at least a month22,23. These observations were then confirmed and
extended by Cort and Payne in Trinidad using Baermann's apparatus. They also
found heavy soil infection around "natural latrines" but little evidence of
contamination in houses59. Augustine then showed that larvae could migrate
laterally for only several centimetres 18, and tended to remain in the upper
regions of the soil, creeping up vegetation, decaying wood and other objects as
far as the film of moisture allowed19. Progressive understanding of all these
facts led to the evolution of better preventive and control measures.
The first major attempts to control ancylostomiasis were undertaken in infected

mines in Europe. A combination of approaches was tried. In 1904, laws were
passed in Belgium compelling the installation of surface waste disposal systems
in mines near Liège, sanitary buckets below ground, periodic examination and
treatment of infected men, and instruction in the principles of personal
prophylaxis. Ten years later, the percentage of infected miners had fallen from
23% to less than 2%, and hookworm disease was abolished146. Similar
principles were adopted in mines in other parts of Europe.

Salt was one of the first chemicals suggested for the control of transmission.
In 1880, Perroncito showed that salt was toxic to Ancylostoma larvae. This
idea was reinforced when it was discovered that miners working in salty mines
in Poland, France and Cornwall were protected from infection. Scattering of
salt around mines was recommended 9, but perhaps because of its simplicity, it
was not received with much enthusiasm. The value of the measure was
forgotten and was rediscovered by WO Fischer working in gold mines in the
Rand, South Africa76. Weekly disinfection with salt around underground
latrines was adopted and infected miners were given anthelmintics with
excellent results12.
While methods such as these were successful in localized areas such as
mines, completely different approaches were needed in the massive endemic
areas of the tropics. The first region in which major attempts at control were
initiated was the island of Puerto Rico into which the large resources of the
United States government were thrown. A commission headed by BK Ashford
was set up in 1904; it embarked upon the study and treatment of hookworm
disease with considerable reward.
Encouraged by Ashford's success, and stimulated by increasing reports of
hookworm infection in the southern United States itself, Charles Stiles
persuaded John D Rockefeller to finance the organization of a Sanitary
Commission to eradicate hookworm disease in that area. In 1909, Rockefeller
gave a million dollars to a Commission of thirteen leading educators, physicians
and business men to be used during the next five years to work towards the
eradication of hookworm. The twin planks upon which the campaign was to be
based were the installation of sanitary privies for all people in infected areas
and by the treatment of every infected person. During the first five years, 1.25
million people were examined and over 690,000 were found to be infected.
These people were treated, either by local practitioners working in cooperation
with the Commission, or by temporary dispensaries set up especially for that
purpose. The Commission believed that hookworm produced vast suffering,
partial inhibition of physical and mental growth, great loss of life, and
decreased economic efficiency. The "lazy niggers" and "poor white trash" of the
South were found in reality to be the unsuspecting victims of this insidious
infection which sapped their strength and vitality. The results of the campaign
were eulogized:
The witnessing by the people of the transformation from invalidism, blighted
ambition, misery and poverty to health, happiness and productive activity does the
teaching which excites them to action.75
Because of these efforts, there was a noticeable improvement in living
conditions, together with the awakening of an intelligent public interest in
hygiene and sanitation34,53.
These results encouraged Rockefeller to consider an extension of the work
and scope of the Commission to outside of the USA. In 1913, The Rockefeller
Foundation was formed and its International Health Commission, later Inter-
national Health Board, undertook to become involved in hookworm control
campaigns in other countries. This extension was first begun in 1914 in certain
countries of the British Empire where the stability of government and the
official use of English facilitated work. The first countries to be tackled were
some of the West Indian islands, British Guiana, Egypt, Ceylon and Malaya.
The Commission then moved into Central American countries, Brazil and
China, until by the middle of the 1920's, campaigns were being carried out on
a more or less extensive scale in the majority of infected countries in the world.
The Foundation worked through, and cooperated with, governmental bodies
in the countries concerned, and began on a small scale in order to develop the
most appropriate strategy for that country. Two basic approaches were adopted.
The "Dispensary Method" consisted of the examination and treatment of people
who presented themselves, together with surveys of infection and sanitation.
This was replaced progressively, however, by the "Intensive Method" whereby
a defined area was examined systematically, the whole population was tested,
all those found infected were treated, and attempts were made to improve
general sanitation103. This was in turn modified at times, with some members
of the Board, such as Darling, urging mass treatment of heavily infected
populations without first verifying the diagnosis in individual persons. Further,
Darling asserted that it was sufficient to remove most of the worms from a
patient, without wasting time, funds, or generating toxicity by attempting to
achieve total eradication 64,65.
Unfortunately, and as many anticipated, evidence began to accumulate that
hookworm infection reappeared in populations which had undergone mass
treatment, albeit at lower intensities of infection, at least initially98,186. The
logical inference was that mass treatment had to be accompanied by effective
sanitary measures:
Mass treatment without coincidental soil sanitation is likened to bailing a
sieve-bottomed boat, universal use of a sanitary latrine constituting the only hope of
eradicating the infection.11
The validity of proper sanitary measures had been well shown in several
studies. Perhaps the most impressive of these was that of Baermann who built
well-constructed, ventilated, clean latrines in the Dutch East Indies, and whose
use was supervised. The overall mortality (to which hookworm was thought to
be a major contributor) fell over ten years from 40 per thousand to 4 per
thousand of population 23.
The use of footwear and other agents to protect the skin as a prophylactic
against hookworm infection has given conflicting results. Manson in 1904
recalled how a West Indian sugar planter had his coolies dip their feet in a
mineral oil tar coated with sand, but Dalgetty pointed out the difficulties of such
arrangements 63. Investigations in later years showed that hookworm larvae
easily penetrated wet canvas footwear, and most observers were not impressed
with the results of wearing the shoes that were commonly available in most
endemic areas. Abdallah, however, did claim that the prevalence of infection
was diminished in a village where a cheap kind of footwear made from old
rubber tyres was used when compared with a neighbouring village in which
this was not the practice1.
Despite the vast efforts put into the control of hookworm infection in the
early parts of this century, it still remains a major problem. Universal, effective
sanitary systems which are actually used would eliminate the scourge, but this
seems unlikely in the foreseeable future. The only other prospect, as yet dim,
is the development and deployment of a powerful and durable vaccine.
REFERENCES
1. ABDALLAH A. Epidemiology of ankylostomiasis in Egypt. Journal of the Ministry of

Health, Cairo 1: 4-12, 1959
2. ALLISON MJ, PEZZIA A, HASEGAWA I, GERSZTEN E. A case of hookworm
infestation in Precolumbian America. American Journal of Physical Anthropology 41:
103-106, 1974
3. ANDREWS J. Modern views on the treatment and prevention of hookworm disease.
Annals of Internal Medicine 17: 891-901, 1942
4. ANDREWS J. New methods of hookworm disease investigation and control. American
Journal of Public Health 32: 282-288, 1942
5. ANONYMOUS. On the management of Negro slaves. Cited in 42
6. ANONYMOUS. Death from Ankylostomum duodenale in Australia. British Medical
Journal 1: 792, 1889
7. ANONYMOUS. Indian helminthology. British Medical Journal ii: 807-808, 1893
8. ANONYMOUS. Ankylostomiasis among miners. Lancet i: 1883, 1903
9. ANONYMOUS. The prophylaxis of ankylostomiasis. British Medical Journal ii: 1418,
1905
10. ANONYMOUS. (Hookworm as a cause of respiratory disturbances.) Nippon
Biseibutsugakkai Zasshi No. 1, 1918. Abstracted in Tropical Diseases Bulletin 15: 224,
1920
11. ANONYMOUS. Hookworm infection in the Straits settlements. Lancet ii: 1301, 1928
12. ANONYMOUS. Hookworms in gold-mines. Lancet i: 1400-1401, 1934
13. ANONYMOUS. Iron and hookworms. Lancet i: 766, 1969
14. ASHFORD BK. Cited in 120.
15. ASHFORD BK. Ankylostomiasis in Puerto Rico. New York Medical Journal 71:
552-556, 1900
16. ASHFORD BK, GUTIERREZ-IGARAVÍDEZ P. Uncinariasis (hookworm disease) in
Porto Rico; a medical and economic problem. United States 61st Congress, third session,
Senate Document 808, Government Printing Office, Washington, pp 335, 1911
17. ATTYGALE. Anchylostomiasis. British medical Journal i: 1387-1388, 1888
18. AUGUSTINE DL. Experiments on the migration of hookworm larvae in soils. American
Journal of Hygiene 2: 162-171, 1922
19. AUGUSTINE DL. On the position of infective larvae in the soil. American Journal of
Hygiene 2: 172-176, 1922
20. AUSTIN WC, COURTNEY W, DANILEWICZ JC, MORGAN DH. Pyrantel tartrate,
a new anthelmintic effective against infections of domestic animals. Nature 212:
1272-1274, 1966
21. AUSTREGESILO A. Infestation de l'ankylostomiase par la peau. Archivos Brasileiros de
Medicina 4: 27-33, 1914

22. BAERMANN G. Ueber ankylostomiasis, deren Ausbreitungsbedingungen durch die
Bodeninfektion und deren Bakaempfung. Geneeskundig Tijdschrift voor Nederlandsch-Indië
57: 579-669, 1917
23. BAERMANN G. Eine einfache Methode zur Auffindung von Ankylostomum (Nematoden)
Larven in Erdproben. Mededeelingen uit het Geneeskundig Laboratorium te Weltevreden,
Feestbundel, Batavia, pp 41-47, 1917. Abstracted in Tropical Diseases Bulletin 12: 181, 1918
24. BAIS WJ. Tetrachloorkoolstof als mijnwormmiddel. Geneesundig Tijdschrift voor Neder-
landsch-Indië 62: 381-391, 1922
25. BAKER O. On ankylostomiasis. British Medical Journal i: 718-720, 1903
26. BELLONI L. Dalla scoperta dell'Ankylostoma duodenale all vittoria dull'anemia dei
minatori. Minerva Medica 57: 3215-3223, 1966
27. BENNETT WH. The treatment of Taenia by chloroform. Medical Record, New York, 28:
319-320, 1885
28. BENTLEY CA. On the causal relationship between "ground-itch" or "pani-ghao" and the
presence of the larvae of Ankylostoma duodenale in the soil. British Medical Journal i:
190-193, 1902
29. BENTLEY CA. Some notes on ankylostomiasis in Assam. Indian Medical Gazette 39:
135-136, 1904
30. BIGGAM AG, GHALIOUNGUI P. Ancylostoma anaemia and its treatment by iron. Lancet
ii: 299-304, 1924
31. BILHARZ T, von SIEBOLD C. Ein Beitrag zur Helminthographia humana, aus brieflichen
Mittheilungen des Dr. Bilharz in Cairo, nebst Bemerkungen von Prof. C. Th. v. Siebold in
Breslau, Zeitschrift für wissenschaftliche Zoologie 4: 53-76, 1852. Partly translated in 107
32. BIOCCA E. On Ancylostoma braziliense (de Faria, 1910) and its morphological
differentiation from A. ceylanicum (Looss, 1911). Journal of Helminthology 25: 1-10, 1951
33. BISHOP H. Notes on the use of carbon tetrachloride (CCl4) in Trinidad and Tobago. Journal
of the Port-of-Spain Medical Society, pp 21-24, 1924
34. BOCCACCIO M. Ground itch and dew poison. The Rockefeller Sanitary Commission
1909-1914. Journal of the History of Medicine and Allied Sciences 27:30-53, 1972
35. BOYCOTT AE. Ankylostomiasis. Transactions of the Epidemiological Society of London,
new series, 24: 113-142, 1905
36. BOYCOTT AE. Anaemia in ankylostomiasis. British Medical Journal ii: 1318-1320, 1907
37. BOYCOTT AE. The Milroy lectures on Ankylostoma infection. Lancet i: 717-721, 783-790,
859864, 1911
38. BOZZOLO C. L'anchilostomiasi e l'anemia che ne conseguita (anchilostoanemia). Giornale
Internazionale delle Scienze Mediche, new series, 1: 1054-1069, 1245-1253, 1879
39. BOZZOLO C. Di un'altra sostanza attiva contra l'anchilostoma Dubini. Giornale della Reale
Accademia di Medicina di Torino, third series, 26: 66-67, 1881
40. BOZZOLO C. Ampia casistica terapeutica a favore des timolo fu prodotta da Grazieda B. II.
Timolo nella cura dell'anchilostomanemia. Giornale della Reale Accademia di Medicina di
Torino, third series, 30: 821-855, 1882
41. BOZZOLO C, PAGLIANI L. Lettera da Airolo. La Perseveranza, 9 March 1880. Cited in
168
42. BRANCH CW. Notes on Uncinaria and other intestinal parasites in the West Indies. Journal
of Tropical Medicine and Hygiene 8: 261, 1905
43. BRONDA F. Ernesto Parona e la scoperta dell'anchilostoma duodenale. Minerva Medica 57:
3245-3249, 1966
44. BROWN HD, MATZUK AT, ILVES IR, PETERSON CH, HARRIS SA, SARETT LH,
EGERTON JR, YAKSTIS JS, CAMPBELL WC, CUCKLER AC. Antiparasitic drugs. IV.
2-(4'-thiazolyl)-benzimidazole,a new anthelmintic. Journal of the American Chemical Society
83: 1764-1765, 1961
45. BRUMPT LC. Déductions cliniquées tirées de cinquante cas d'ankylostomiase provoquée.
Annales de Parasitologie Humaine et Comparée 27: 237-249, 1952
46. BRUNING H. Zur Frage der Helminthiasis-Therapie in den Tropen. Archiv für Schiffs und
47. BUGNION E. On the epidemic caused by Ankylostomum among the workmen in the St.
Gothard tunnel. British Medical Journal i: 382, 1881
48. BUGNION E. L'ankylostome duodénal et l'anémie du Saint-Gothard. Revue Médicale de la
Suisse Romande 1:269-289, 405-440, 1881
49. BUI QUOC HONG, BUU HOI, TRAN LU Y, TANG NHIEP, NGUYEN VAN DICH, VU
DINH MINH. Activité anthelminthique du 2(4' thiazolyl) benzimidazole chez l'homme.
Chemotherapia 5: 326-331, 1962
50. CAIUS JF, MHASKAR KS. The correlation between the chemical composition of
anthelmintics and their therapeutic values in connection with the hookworm enquiry in the
Madras Presidency. Indian Journal of Medical Research 7: 429-463, 1919; 7: 570-609, 1920;
8: 125-130, 372-394, 1920; 9: 35-55, 191-209, 1921; 10: 343-360, 1922
51. CALDWELL FC. An accidental infection with Uncinaria. Parasitology 14: 51-52, 1922
52. CAMUSET L. De l'anémie tropicale observée à la Guyane française, Thèse de Montpellier,
pp 50, 1868
53. CASSEDY JH. The "germ of laziness" in the South, 1900-1915: Charles Wardell Stiles and
Progressive Paradox. Bulletin of the History of Medicine 45: 159-169, 1971
54. CHAIA G, CUNHA CA. Therapeutic action of mebendazole (R-17.635) against human
helminthiasis. Folha Médica 63: 843-852, 1971
55. CHANDLER AC. The rate of loss of hookworms in the absence of reinfections. Indian Journal
of Medical Research 13: 625-634, 1926
56. CHANDLER AC. Hookworm disease. Its distribution, biology, epidemiology, pathology,
diagnosis, treatment and control, MacMillan and Co., London, pp 494, 1929
57. CONCATO L, PERRONCITO E. Sull'anchilostomiasi. Osservatore, Torino 16: 144, 1880.
Also, Sur l'anchylostomiase. Comptes Rendus Hebdomadaires des Séances de l'Académie des
Sciences 90: 619-620, 1880
58. COPP FC, STANDEN OD, SCARNELL J, RAWES DA, BURROWS RB. A new series of
anthelmintics. Nature 181: 183, 1958
59. CORT WW, PAYNE GC. An epidemiologic study of hookworm disease in a cacao estate.
American Journal of Hygiene 2: 149-161, 1922
60. CREPLIN FC. Nachträge zu Gurlt's Verzeichniss der Thiere, bei welchen Entozoen gefunden
worden sind. Archiv für Naturgeschichte 11J, 1: 325-330, 1845
61. CRUZ WO. Pathogenesis of anaemia in hookworm disease. Parasite carriers. Relationship
between the activity of the helminth and iron deficiency in the genesis of disease. Memorias
do Instituto Oswaldo Cruz 28: 391-486, 1934
62. DALGETTY AB. Water-itch; or, sore feet of coolies. Journal of Tropical Medicine and
Hygiene 4: 73-77, 1901
63. DALGETTY AB. The prevention of ankylostomiasis. British Medical Journal i: 17, 1905
64. DARLING ST. Suggestions for the mass treatment of hookworm infection. Lancet ii: 69-72,
1920
65. DARLING ST. The hookworm index and mass treatment. American Journal of Medicine 2:
397-447, 1922
67. DAY HB, FERGUSON AR. The treatment of Ankylostoma anaemia. Lancet i: 82-87, 1914
68. DESOWITZ RS, BELL T, WILLIAMS J, CARDINES R, TAMARUA M. Anthelmintic
activity of pyrantel pamoate. American Journal of Tropical Medicine and Hygiene 19:
775-778, 1970
69. DOBSON EF. Notes regarding the prevalence of Dochmius duodenalis. Indian Medical
Gazette 27: 354-357, 1892; 28: 1-4, 40-43, 68-72, 1893
70. DUBINI A. Nuovo verme intestinal umano (Agchylostoma duodenale) costituente un sesto
genere dei nematoidea proprii dell'uomo. Annali Universali di Medicina 106: 5-13, 1843.
Translated in 107
71. DUVOIR M, BRUMPT LC. Le traitement des polyglobulies par l'ankylostomose provoquée
(apropos de cinq cas). Annales de Parasitologie Humaine et Comparée 20: 1-2, 35-42,
1944-1945
72. EBBELL B. The Papyrus Ebers, the greatest Egyptian medical document, translated by B
Ebbell, Levin and Munksgaard, Copenhagen, pp 135, 1937

73. de FARIA G. Contribução para a sistematica helmintolojica brazileira. III. Ancylostomum
braziliense n. sp. parazito dos gatos e câia. Memorias do Instituto Oswaldo Cruz 2: 286-293,
1910
74. FERREIRA LF, de ARAÚJO AJ, CONFALONÍERI UE. The finding of eggs and larvae of
parasitic helminths in archaeological material from Unai, Minas Gerais, Brazil. Transactions
75. FERRELL JA. Methods for the eradication of hookworm disease. American Journal of Public
Health 3: 492-493, 1913
76. FISCHER WO. Über eine Methode zum Abtöten von Hakenwurmlarven in Boden. Archiv fur
77. FRANÇOIS E. Anémie des Mineurs: Étiologie, séméiologie, prophylaxie, organisation
médicale, A. Maloine, Paris, pp 110, 1906
Ankylostomum und die Biologie dieser Parasiten. Archiv für Schiffs- und Tropen-Hygiene 18:
26-80, 1914
79. FÜLLEBORN F. Ueber das Verhalten der Hakenwurmlarven bei der Infektion per os. Archiv
für Schiffs- und Tropen-Hygiene 30: 638-653, 1926
80. FÜLLEBORN F. Epidemiological observations on hookworm infection. Discussion of the
question of immunity and specific reactions of the host in helminthic infections. British
81. FÜLLEBORN F, KIKUTH W. Wie entseht die Anämie bei Hakenwurminfektion. Archiv für
82. GHEDINI G. Anticorpi elmintiaci nel siero de sangue di individui affetti da elmintiasis,
anticorpi anchilostomiaci e ascaride. III. nota. Gazetta degl'Ospedali e della Cliniche 28: 476,
1907
83. GILES GM. A report of an investigation into the causes of the diseases known in Assam as
kala-azar and beri beri, Assam Secretariat Press, Shillong, pp 156, 1890
84. GILES GM. The life-history of the free stage of Ankylostoma duodenale. British Medical
85. GILES GM. A discussion on ankylostomiasis. British Medical Journal ii: 539-541, 1900
86. GILES GM. Discussion of 177. British Medical Journal ii: 691, 1901
87. GILLES HM, WATSON-WILLIAMS EJ, BALL PA. Hookworm infection and anaemia.
An epidemiological, clinical and laboratory study. Quarterly Journal of Medicine 33: 1-24,
1964
88. GOODWIN LG, JAYEWARDENE LG, STANDEN OD. Clinical trials with bephenium
hydroxynaphthoate against hookworm in Ceylon. British Medical Journal ii: 1572-1576,
1958
89. GORDON RM. The effect of ancylostome, ascaris and trichuris infections on the health of
the West African native. Annals of Tropical Medicine and Parasitology 19: 429-460, 1925
90. GRASSI GB, PARONA C, PARONA E. Intorno all'Anchilostoma duodenale (Dubini).
Gazzetta Medica Italiana Lombardia 38: 193-196, 1878. Translated in 107
91. GRENET AL. Présence de l'ankylostome duodénal sur un sujet mort à Mayotte de cachexie
aqueuse ou malcouer. Archives de Médecine Navale 8: 70-72, 1867
92. GRIESINGER W. Klinische und anatomische Beobachtungen über die Krankheiten von
93. HALL MC. Carbon tetrachloride for the removal of parasitic worms, especially hookworms.
Journal of Agricultural Research 21: 157-175, 1921
94. HALL MC. The use of carbon tetrachloride for the removal of hookworms. Journal of the
95. HALL MC, SHILLINGER J. Tetrachlorethylene, a new anthelmintic. American Journal of
96. HARADA Y, MORI O. A new method for culturing hookworm. Yonago Acta Medica 1:
177-179, 1955
97. HERMAN M. Le traitement de l'anchylostomasie par l'essence d'eucalyptus associée au
chloroforme et à l'huile de ricin. Bulletin de l'Académie Royale de Médecine de Belgique,
fourth series, 19: 144-155, 1905.

98. HILL RB. Hookworm reinfestation in sanitated and unsanitated areas. Southern Medical
Journal 18: 665-668, 1925
99. HILL RB. The estimation of the number of hookworms harbored, by the use of the dilution
egg count method. American Journal of Hygiene 6: Supplement, pp 19-41, 1926
100. HIPPOCRATES Works of, translated by WH Jones & ET Whithington, Loeb Classical
Library, Heinemann, London, four volumes, 1948-1953.
102. HOWARD HH. Prenatal hookworm infection. Southern Medical Journal 10: 793-795, 1917
103. HOWARD HH. The control of hookworm disease by the intensive method. The Rockefeller
Foundation, Publication No. 8, International Health Board, New York City, pp 189, 1919
104. HUART AJ. On the causes of anaemia in ankylostomiasis. Acta Leidensia (Scholae Medicae
Tropicae) 4: 48-109, 1929
105. INTERNATIONALCOMMISSION ON ZOOLOGICAL NOMENCLATURE. Nematode
and Gordiacea names placed in the official list of generic names (Opinion 66), Smithsonian
Institution Publication 2359, Washington, DC, pp 171-176, 1915
106. JOYEUX C. Le Necator americanus en Haute-Guinée. Notes d'epidémiologie. Bulletins de
la Société de Pathologie Exotique et de ses Filiales 10: 843-846, 1912
107. KEAN BH, MOTT KE, RUSSELL AJ. Tropical medicine and parasitology. Classic invest-
igations, Cornell University Press, Ithaca, two volumes, pp 677, 1978
108. KÉRANGEL R. L'ankylostome duodénal observé à Cayenne. Archives de Médecine Navale
10: 311-322, 1868
110. KHALIL M. Note on the toxicity of carbon tetrachloride in the treatment of ankylostomiasis.
Lancet i: 547-548, 1926
111. KRAUSE GR, CRILLY JA. Roentgenologic changes in the small intestine in the presence
of hookworm. American Journal of Roentgenology and Radium Therapy 49: 719-730, 1943
112. KYNSEY WR. Report on anaemia or beri-beri of Ceylon, Colombo, pp 56, 1887. Cited in
British Medical Journal ii: 1205, 1892
113. LAMBINET J. Recherches sur le mode d'infection de l'organisme animal par les larves de
l'anchylostomes.Bulletin de l'Académie Royale de Médecine de Belgique, fourth series, 19:
56-75, 1905
114. LAMSON PD, BROWN HW, ROBBINS BH, WARD CB. Field treatment of ascariasis,
ancylostomiasis and trichuriasis with hexylresorcinol. American Journal of Hygiene 13:
803-822, 1931
115. LAMSON PD, ROBBINS BH, WARD CB. The pharmacology and toxicology of tetrachlor-
ethylene. American Journal of Hygiene 9: 430-444, 1929
116. LANE C. Agchylostoma ceylanicum, a new human parasite. Indian Medical Gazette 48:
217-218, 1913
117. LANE C. Final report on the ankylostome enquiry in the Darjeeling District of India. Indian
118. LANE C. Ancylostoma braziliense. Annals of Tropical Medicine and Parasitology 16:
347-352, 1922
119. LANE C. Fatal and medicinal doses. Lancet i: 1317, 1930
120. LANE C. Hookworm infection, Oxford University Press, London, pp 319, 1932
121. LANE C. The appraisement of hookworm-killing drugs. Lancet i: 1459-1464, 1935
122. de LANGEN CD. Prenatal infection by ankylostoma. Mededeelingen van den Burgerlijken
Geneeskundigen Dienst in Nederlandsch-Indië pp 275-277, 1923
123. LAYRISSE M, ROCHE M. The relationship between anemia and hookworm infection.
Results of surveys of a rural Venezuelan population. American Journal of Hygiene 79:
279-301, 1964
124. LEACH CN. Carbon tetrachloride in the treatment of hookworm disease. Journal of the
125. LEGER M. À propos de Necator americanus, Stiles 1902. Bulletins de la Société de

Pathologie Exotique et des ses Filiales 14: 159-161, 1921
126. LEICHTENSTERN O. Zur Entwickelungsgeschichte von Ankylostoma duodenale.
Vorläufige Mittheilung. Centralblatt für klinische Medicin 7: 132-133, 1886. Partly
translated in 142
127. LEICHTENSTERNO. Fütterungsversuche mit Ankylostomalarven. Eine neue Rhabditisart
in den Fäces von Ziegelarbeitern: Berichtigung. Centralblatt für klinische Medicin 7:
673-675, 1886
128. LEICHTENSTERN O. Einiges über Ankylostoma duodenale. Deutsche medicinische
Wochenschfrift 13: 565-568, 594-596, 620-623, 645-647, 669-672, 691-694, 712-715,
1887
129. LEICHTENSTERN O. Ueber Ankylostoma duodenale. Wiener klinische Rundschau 12:
361-363, 377-378, 393-395, 412-414, 428-429, 1898
130. LEICHTENSTERNO M. Die Lebensgeschichte des Ankylostoma duodenale. Centralblatt
für Bakteriologie und Parasitenkunde, Abteilung originale 24: 974-980, 1898
131. LEIPER RT. The distribution of the "American" hookworm. British Medical Journal i: 683,
1907
132. LEIPER RT. The alleged heterogenesis of Ankylostoma duodenale. British Medical Journal
ii: 1332, 1909
133. LEIPER RT. The apparent identity of Agchylostoma ceylanicum (Looss, 1911) and
Agchylostoma braziliense (Faria, 1910). Journal of Tropical Medicine and Hygiene 16:
334-335, 1913
134. LEUCKART R. Zur Entwicklungsgeschicht der Nematoden. Archiv für wissenschaftliche
Heilkunde, Leipzig, new series, 2: 235-250, 1866
135. LOEB L, SMITH AJ. The presence of a substance inhibiting the coagulation of the blood in
Ankylostoma (with discussion). Proceedings of the Pathological Society of Philadelphia, new
series, 7: 173-178, 1904
136. LOOSS A. Notizen zur Helminthologie Egyptens. I. Die Lebensgeschichte des
Anchylostomum duodenale (Dub.). Centralblatt für Bakteriologie und Parasitenkunde,
Abteilung originale 20: 865-870, 1896. Translated in 107
137. LOOSS A. Notizen zur Helminthologie Egyptens. II. Die Uebertragung der Larven
(Anchylostomum duodenale). Centralblatt für Bakteriologie und Parasitenkunde, Abteilung
originale 21: 913-917, 1897. Translated in 107
138. LOOSS A. Zur Lebensgeschichte des Ankylostoma duodenale. Centralblatt für
Bakteriologie und Parasitenkunde, Abteilung originale 24: 441-449, 483-488, 1898. Partly
translated in 107
139. LOOSS A. Ueber das Eindrigen der Ankylostomalarven in die menschliche Haut.
Centralblatt für Bakteriologie und Parasitenkunde, Abteilung originale 29: 733-739, 1901.
140. LOOSS A. Note on intestinal worms found in African pygmies. Lancet ii: 430-431, 1905
141. LOOSS A. The anatomy and life-history of Agchylostoma duodenale (Dub.). A monograph.
Part I. The anatomy of the adult worm. Translated from the German by M Bernhard, Records
of the School of Medicine, Egyptian Ministry of Education, National Printing Department,
Cairo, 3: 1-159, 1905
142. LOOSS A. The anatomy and life history of Agchylostoma duodenale Dub. A monograph.
Part II. The development in the free state. Translated from the German by M Bernhard,
Records of the School of Medicine, Egyptian Ministry of Education 4: 163-613, 1911. Pp
252-277 reprinted in the Journal of Tropical Medicine and Hygiene 15: 155-157, 171-174,
182-185, 199-201, 235-238, 1912; Abstracted in Journal of the Royal Army Medical Corps
19: 42-55, 1912
143. LUTZ A. Ueber Ankylostoma duodenale und ankylostomiasis. Sammlung klinischer
Vorträge in Verbindung mit Deutschen Klinikern 9: 2295-2350, 2467-2506, 1885.
Translated in Gazeta Medica da Bahia, third series, 5: 487-496, 541-544; 6: 60-65, 113-124,
157-166, 254-264, 1888
144. McCONNELL JF. On Dochmius duodenalis (Sclerostoma vel Anchylostoma duodenale)
as a human parasite in India. Lancet ii: 96-97, 1882
145. MacDONALD JD. First Indian Medical Congress, 1890. Cited in 176
146. MALVOZ E. Dix années de lutte contre l'ankylostomasie des mineurs. Bulletin de
l'Académie Royale de Médecine de Belgique, series 4, 27: 264-278, 1913
147. MANSON P. Discussion of 177, British Medical Journal ii: 691, 1901
148. MAPLESTONE PA. Creeping eruption produced by hookworm larvae. Indian Medical
Gazette 68: 251-256, 1933
149. MHASKAR KS. Hookworm infection and sanitation. Indian Journal of Medical Research
8: 398-406, 1920
150. MHASKAR KS. Mass treatment of hookworm infection. Indian Medical Gazette 57:
208-210, 1922
151. MIYAGAWA Y. Ueber den Wanderungsweg der Ankylostoma duodenale innerhalb des
Wirtes bein Oralinfektion und ueber ihren Hauptinfektionsmodus. Mittheilungen aus der
medicinischen Facultät der kaiserlich-japanischen Universität zu Tokyo 15: 411-452, 1916
152. MOUAT-BIGGS CE. The treatment of ankylostomiasis in Venezuela. Transactions of the
Royal Society of Tropical Medicine and Hygiene 8: 216, 1915
153. de MOURA JR. Note sobre um caso de hypoemia intertropical terminado pela morte;
autopsia e verificação da existencia de entozoarios da especie - Anchylostomum duodenale.
Gazeta Medica da Bahia 1: 122-125, 136-138, 1866
154. MÜLLER H F, RIEDER H. Ueber Vorkommen und klinische Bedeutung der eosinophilen
Zellen, Erlich im circulirenden Blute des Menschen. Deutsches Archiv für klinische Medizin
48: 96-121, 1891
155. NAG SC. Notes on the use of carbon tetrachloride. Indian Medical Gazette 64: 683, 1929
156. NAPIER LE, DAS GUPTA CR, MAJUMDAR DN. The treatment of hookworm anaemia.
Indian Medical Gazette 76: 1-11, 1941
157. NICHOLLS L, HAMPTON GG. Treatment of human hookworm infection with carbon
tetrachloride. British Medical Journal ii: 8-11, 1922
158. OKADA R. Experimental studies on the oral and percutaneous infection of Anchylostoma
caninum. Fourth report. Japanese Journal of Experimental Medicine 9: 269-280, 1931
159. OLIVER T. Ankylostomiasis in Westphalia, Hungary and Cornwall. Lancet ii: 1635-1637,
1904
160. OZZARD AT. Life history of the Ankylostoma duodenale. Journal of Tropical Medicine and
Hygiene 5: 273-274, 1902
161. OZZARD AT. Life-history of Ankylostoma duodenale. British Medical Journal ii: 779-780,
1909
162. PAPYROS EBERS. Das hermetische Buch über die Arzeneimittel der alten Aegypter in
hieratischer Schrift. Herausgegeben, mit Inhaltsangabe und Einleitung versehen von Georg
Ebers. Mit hieroglyphisch-lateinischem Glossar von Ludwig Stern, W Engelmann, Leipzig,
two volumes, 1875. The Papyrus Ebers, translated from the German version by CP Bryan,
Geoffrey Bles, London, pp 167, 1930
163. PARONA E. L'estratto etereo di felce maschio e l'anchilostomiasi die minatori del Gottardo.
Osservatore, Torino, 17: 19-49, 1881
164. PEDUZZI R, PIFFARETTI JC. Ancylostoma duodenale and the Saint Gothard anaemia.
165. PEIPER O. Über den Infektionmodus der Ankylostomiasis in Deutsch-Ostafrika. Archiv für
166. PERRONCITO E. Helminthological observations upon the endemic disease developed
among the labourers in the Tunnel of Mount St. Gothard. Journal of the Quekett
Microscopical Club 6: 141-148, 1880. Also, Observations helminthologiques et recherches
experimentelles sur la maladie des ouvriers du Saint-Gothard. Comptes Rendus
Hebdomadaires des Séances de la Académie des Sciences 90: 1373-1375, 1880
167. PERRONCITO E. On the action of chemical agents and medicinal substances on the larvae
of Dochmius duodenalis and Anguillulae; including therapeutical considerations relative to
the cure of patients from Mount St. Gothard. Veterinarian 53: 824-828, 1880
168. PERRONCITO E. La malattia dei minatori dal S. Gottardo al Sempione: una questione
risolta, Carlo Pasta, Torino, pp 335, 1910
169. PFISTER F. Über die - - -Krankheit der Papyri Ebers und Brugsch. Archiv für Geschichte
der Medizin 6: 12-20, 1912

170. PIRIE JH, RETIEF F, FERGUSON AL. Skin reactions in ankylostomiasis. Proceedings of
the Transvaal Mine Medical Officers' Association 9: 19-20, 1929
171. PRUNER. Die Krankheiten des Orient's vom Standpunkte der vergleichendin Nosologie
betrachtet, Palme und Enke, Erlangen, pp 472, 1847
172. RAKE B. Extracts from an inaugural address on the opportunities for research in Trinidad.
British Medical Journal i: 289, 1894
173. REP BH, VETTER JC, EIJSKER M. Cross-breeding experiments in Ancylostoma
braziliense de Faria, 1910 and A. ceylanicum Looss, 1911. Tropical and Geographical
Medicine 20: 367-378, 1968
174. RHOADS CP, CASTLE WB. Observations on the etiology and treatment of the anemia of
hookworm disease in Porto Rico. Journal of Clinical Investigation 11: 809, 1932 (Abstract)
175. ROCHE M, ENRIQUETA PEREZ-GIMENEZ M, LAYRISSE M, di PRISCO E. Study of
urinary and fecal excretion of radioactive chromium Cr51 in Man. Its use in the measurement
of intestinal blood loss associated with hookworm infection. Journal of Clinical Investigation
36: 1183-1192, 1957
176. ROGERS L. The debate on ankylostomiasis: a correction. British Medical Journal ii:
1348-1349, 1900
177. SANDWITH FM. Note on the entrance of Ankylostoma embryos into the human body by
means of the skin. British Medical Journal ii: 690-691, 1901
178. SANDWITH FM. Hookworm. Lancet i: 255, 1905
179. SANGALLI G. Annotazioni critiche sull'anchilostoma duodenale. Rendiconti del Reale
Istituto Lombardo di Scienze e Lettere, Milan, series 2, 2: 460-467, 1879
180. SCHAPIRO L, STOLL NR. Preliminary note on the anthelmintic value of tetrachlorethylene
based on egg counts before and after one treatment. American Journal of Tropical Medicine
7: 193-198, 1927
181. SCHAUDINN F. Ueber die Einwanderung der Ankylostomum-larven von der Haut aus.
Vorläufige Mitteilung. Deutsche medizinische Wochenschrift 30: 1338-1339, 1904
182. SCHEUTHAUER G. Beiträge zur Erklärung des Papyrus Ebers, des hermetischen Buches
über die Arzneimittel der alten Aegypter. Archiv für pathologische Anatomie und Physiologie
und für klinische Medicin (R Virchow) 85:343-354, 1881
183. SCHÜFFNER W. Der Wert einiger Vermifuga gegenüber dem Ankylostomum mit
Bemerkungen über die Wurmkrankheit in Niederländisch-Indien. Archiv für Schiffs- und
184. SCHULTHESS W. Noch ein Wort über Ankylostoma duodenale. Berliner klinische
185. SCOTT HH. Review of 89. Tropical Diseases Bulletin 23: 262-263, 1926
186. SISCO DL. Incidence of hookworm disease among persons who were cured five years ago.
187. SMILLIE WG, AUGUSTINE DL. Hookworm infestation. The effect of varying intensities
on the physical condition of school children. American Journal of Diseases of Children 31:
151-168, 1926
188. SMILLIE WG, AUGUSTINE DL. The effect of varying intensities of hookworm infestation
upon the development of school children. Southern Medical Journal 19: 19-28, 1926
189. SMITH AJ. Cited in 56
190. SONSINO P. Ankylostomiasis and beri-beri. Lancet i: 435-436, 1890
191. SOPER FL. The report of a nearly pure Ancylostoma duodenale infestation in native South
American Indians and a discussion of its ethnological significance. American Journal of
Hygiene 7: 174-184, 1927
192. STILES CW. A new species of hookworm (Uncinaria americana) parasitic in man.
American Medicine 3: 777-778, 1902
193. STILES CW. Report upon the prevalence and geographic distribution of hookworm disease
in the United States. Hygienic Laboratory Bulletin No. 10, United States Public Health and
Marine Hospital Service, Washington, DC, pp 121, 1903
194. STILES CW. The American hookworm (Necator americanus) in Guam and China. Johns
Hopkins Hospital Bulletin 17: 313, 1906
195. STILES CW. Report of the scientific secretary, The Rockefeller Sanitary Commission for the
Eradication of Hookworm Disease, Publication No. 2, New York, 1914
196. STILES CW. Recent studies on school children, with special reference to hookworm disease
and sanitation. New York Medical Journal 102: 906-907, 1915
197. STOLL NR. On the relation between the number of eggs found in human feces and the
number of hookworms in the host. American Journal of Hygiene 3: 156-179, 1923
198. STRAUB M. Tetrachloorkoulstofvergiftiging in twaalf gevallen. Geneeskundig Tijdschrift
voor Nederlandsch-Indië 65: 624-645, 1925
199. TOPLEY E. Common anaemias in rural Gambia. Hookworm anaemia among men.
200. WAITE JH, NEILSON IL. A study of the effects of hookworm infection upon the mental
development of north Queensland school children. Medical Journal of Australia i: 1-7, 1919
201. WELLS HS. Observations on the blood sucking activities of the hookworm Ancylostoma
caninum. Journal of Parasitology 17: 167-182, 1931
202. WIJERS DJ, SMIT AM. Early symptoms after experimental infection of man with
Ancylostoma braziliense var. ceylanicum. Tropical and Geographical Medicine 18: 48-52,
1966
203. WILLIAMS CH. On the prevalence of Ankylostomum duodenale in Madras. Lancet i: 192,
1895
204. WUCHERER OE. Sobre a molestia vulgarmente denominada oppilação ou cançaço. Gazeta
Medica da Bahia 1: 27-29, 39-41, 52-54, 63-64, 1866. Partly translated in 107
205. WUCHERER OE. Anchylostomos duodenaes. Gazeta Medica da Bahia ii: 150-151, 1868
206. WUCHERER OE. Ueber die Anchylostomenkrankheit, tropische Chlorose oder tropische
Hypoämie. Deutsches Archiv für klinische Medicin 10: 379-400, 1872
207. YOKOGAWA S. On the oral infection by hookworm. Archiv für Schiffs- und
Tropen-Hygiene30: 663-679, 1926. Also, YOKOGAWA S, OISO T. (Investigations on the
life history of Ankylostoma and Strongyloides stercoralis. On oral infection with
Ankylostoma.) Taiwan Igakkai Zasshi Nos. 241 and 243, 1925. In Japanese, with English
summary
208. ZINN W, JACOBY MJ. Ueber das regelmäsige Vorkommen von Anchylostomum
duodenale ohne secundäre Anämie bei Negern, nebst weiteren Beiträgen zur Fauna des
Negerdarmes. Berliner klinische Wochenschrift 33: 797-801, 1896
Table 20.1. Landmarks in hookworm disease

__________________________________________________________________
1838 Dubini discovered the adult worm

1852-54 Bilharz/Griesinger proposed that hookworm was the cause of "Egyptian
chlorosis" (gross anaemia)
1866 Wucherer indicated that latex d'higueron (fig extract in South America) was
an effective treatment
1868 Camuset appreciated that hookworm in the Americas differed
morphologically from A. duodenale but did not publicize the observation
1878 Grassi, Parona and Parona described the in vitro development of hookworm
ova and larvae and showed that infection could be diagnosed by finding
eggs in faeces
1880 Outbreak of hookworm anaemia in miners building the St. Gothard tunnel
in the Italian Alps
1880 Parona showed that filix mas (male fern) was effective in treatment
1881 Bozzolo showed that thymol was effective in treatment
1886 Leichtenstern observed patent infections in humans 4-5 weeks after
ingestion of infective larvae
1898 Looss first suggested that infection may be acquired by percutaneous
penetration by larvae
1901 Looss demonstrated histologically the penetration of intact human skin by
infective larvae
1901 Bentley described hookworm infective larvae as the cause of "ground-itch"
1902 Stiles described the morphological distinctiveness of N. americanus
1905 Looss described the migratory course throught the lungs of infective larvae
in dogs
1907 Boycott differentiated microcytic hookworm anaemia from the macrocytic
anaemia produced by Diphyllobothrium latum
1909 Bruning reported that oil of chenopodium was effective in treatment
1909 John D Rockefeller established a Sanitary Commission to control
hookworm infection in the United States of America
1910 Looss described A. ceylanicum recovered from a civet cat by Willey in Sri
Lanka (Ceylon)
1911 Looss reported the development of a patent infection in a person 71 days
after percutaneous exposure
1913 Lane found humans infected with A. ceylanicum
1913 The Rockefeller International Health Commission (later Board) began
hookworm control campaigns in countries outside the USA
1921 Hall introduced treatment with carbon tetrachloride
1925 Hall and Shillinger introduced treatment with tetrachlorethylene
1929 Experimental studies emphasized the role of gastrointestinal bleeding in the
genesis of hookworm anaemia
1935 Anumber of investigations showed clearly the role of iron deficiency in the
causation of hookworm anaemia
1958 Bephenium hydroxynaphthoate was shown to be an effective treatment by
Goodwin and his colleagues
1962 Bui Quoc Hong and his colleagues reported that thiabendazole was an
effective treatment
1970 Pyrantel was found by Desowitz and co-workers to be an effective
antihookworm agent
1971 Chaia and Cunha observed that mebendazole was highly active against
hookworm
__________________________________________________________________
Chapter 21 RETURN TO
Strongyloides stercoralis and STRONGYLOIDIASIS
SYNOPSIS
Major synonyms: Anguillula stercoralis, A. intestinalis, Rhabditis stercoralis,

Rhabdonema strongyloides, Strongyloides intestinalis
Distribution: widespread, especially in the tropics and subtropics
Life cycle: The parthenogenetic female adult worms, 2.5 mm in length, live in the
epithelial layer of the small intestine. First-stage (rhabditiform) larvae are passed in the
faeces then, in the external environment, either moult twice to form third-stage
(infective or filariform) larvae (the direct cycle) or moult four times to become
free-living male and female adult worms which in turn produce eggs which hatch to
form rhabditiform larvae which moult twice to form filariform larvae (the indirect
cycle). Infective larvae penetrate the intact skin and pass via the bloodstream to the
lungs where they enter the alveolar spaces, ascend the airways to the pharynx, and are
swallowed and pass to the small bowel where they mature over one month or so. In
addition, rhabditiform larvae released in the bowel lumen may moult to form
filariform larvae and penetrate the colonic mucosa to continue the cycle (internal
autoinfection) or penetrate the perianal skin to continue the cycle (external
autoinfection). Finally, massive infection with widespread dissemination of larvae may
supervene in immunosuppressed persons
Definitive hosts: humans, dogs, cats
Major clinical features: urticaria, abdominal pain, diarrhoea, weight loss, pruritus ani
Diagnosis: finding larvae in faeces or duodenal fluid; serology
Treatment: thiabendazole (mebendazole, cambendazole, albendazole)
DISCOVERY OF LARVAL AND ADULT WORMS AND DETERM-

INATION OF THEIR RELATIONSHIP
In the latter part of the ninteenth century, many French troops who had bee n
posted to Cochin China (Vietnam) were afflicted with severe diarrhoea which
was sometimes fatal. In July 1876, a number of patients were repatriated t o
France where they came under the care of Louis Normand, physician to th e
Naval Hospital of St Mandrier in Toulon. Normand examined the faeces o f
these patients and in some of them he found specimens of a worm which had
never been described before. The parasite was just visible to the naked eye ,
being about one quarter of a millimetre in length. Although they were ofte n
sparse, on other occasions worms were present in prodigious numbers with a
million or so being excreted during the course of 24 hours. When he examined
543
faecal samples with a microscope, Normand occasionally saw a large number

of worms squirming about in an almost transparent mass as if they were trying
to escape from an enclosing membrane. At other times, he observed individual
worms which were sometimes caught in a clump of epithelial cells. Normand
reported his discovery to Vice-Admiral Jurien de la Gravière:
Today in regard to the disease called diarrhea of Cochin China, I can prove that from
time to time and most often in serious cases, a parasite is found which has never been
found before under similar circumstances. I searched in vain for this parasite in other
patients afflicted with analogous symptoms but their afflictions apparently came from
other sources.81
The Admiral in turn transmitted extracts of Normand's report together with a
resumé of Normand's findings to the President of the Academy of Science s
where it was presented and published on 31 July 1876 81.
Meanwhile, Normand entrusted the worms to the care of his colleague, ARJB
Bavay, professor of pharmacy in the Navy . Jurien de la Gravière, in the original
presentation of Normand's discovery, had noted that Bavay had already called
the parasite Anguillula stercoralis. This name reflected the eel-like shape of the
worm as well as the discovery of the parasite in the faeces, both names being
derived from the latin words "anguilla" meaning "eel", and "stercus" denoting
"dung". Bavay made a number of observations on this parasite and in October
1876, P Gervais presented Bavay's more detailed description of the worm to the
Academy6. In this publication, however, Bavay remarked that the wor m
resembled the free-living worm, Rhabditis terricola of Dujardin or the genus
Leptodera of Schneider, and indicated that he believed that the differences did
not justify the creation of a new genus. Nevertheless, in his first paper, Bavay
called the parasite both Anguillula stercorale and Rhabditis stercoralis 6, while
in two subsequent papers he referred to it as Anguillula stercoralis "Du
sous-genre [of the subgenus] Rhabditis, ou [or] Leptodera Schneider" 7,8.
Bavay noted that the forms usually met by clinicians were the larvae, 0.3 3
mm in length by 0.022 mm in width, that were found in the faeces. If thes e
larvae were left under favourable conditions in vitro, however, Bavay
discovered that they developed into male and female adult worms after fiv e
days or so. He wrote that the free-living femal e worms were 1 mm in length and
cylindrical in shape, then described the morphology of the mouth, oesophagus,
intestine, uterus and vulva. He noted that the eggs on deposition containe d
well-formed, motile embryos and that the young forms had sometimes actually
broken out of the egg-shell while still within the uterus. The male worms, on
the other hand, were smaller than the female helminths. Bavay described th e
anatomy of the male reproductive organs and stated that he had sometimes seen
male and female worms in copula. He summarized the important differential
characteristics which justified its description as a separate species:
In summary, this nematode, which is very similar to the Rhabditis terricola of
Dujardin....differs in its invariably smaller size, but specially in the shape of the penile
apparatus.6
Strongyloidiasis 545
In an addendum to this paper, Bavay reported that Normand had now found the
larvae of A. stercoralis at autopsy in the stomach and the whole length of the
intestine, as well as in the bile, pancreatic and hepatic ducts and in the gal l
bladder6.
Shortly thereafter, Normand also described the development of free-livin g
adult worms from larvae in faeces then observed the course of events whic h
occurred after eggs were liberated b y free-living female worms. Like Bavay, he
observed that when eggs were expelled, each one contained a distinct, motile
embryo within a membrane. After each egg had hatched, the released larva was
about 0.1 mm in length. These grew gradually to about 0.3 mm long, the n
developed a jagged border which gave them the appearance of a chain-saw ,
then moulted. Normand was unable, however, to obtain a second generation of
free-living worms 82, nor did Bavay have any such success 6.
Verification of Normand's discovery did not take long in coming, eve n
though there was scepticism on the part of some and incredulity on the part of
others. In early 1977, Alphonse Laveran (the discoverer of malarial parasites)
reported that, at an autopsy he performed on 28 January 1877, he had foun d
larvae which matched those d escribed by Bavay 66 in the intestines, then shortly
afterwards he reported finding four more such cases 67. Laveran was followed
by Libermann72, Roux95 , Chastang17 and Chauvin18 who found the worms in
patients that had been infected in China or in Martinique. With the exception
of Chauvin, however, these authors did not observe the maturation of larvae to
adult worms in the stools.
In the meantime, the situation had become somewhat more confused. In late
1876, Normand, at the autopsy of a man who had died from Cochin-Chin a
diarrhoea, found another worm, which appeared to be different from A.
stercoralis, in the intestines. He sent these worms to Bavay. The latter studied
them and those that were obtained from a further four post-morte m
examinations and concluded that they were a distinct species of worm. Again
through the agency of M Gervais, B avay published a description of the parasite
in February 1877, naming it A. intestinalis in order to reflect its discovery in
the intestinal tract 7. These worms were about 2.2 mm in length and all of the
200 specimens or so that he examine d were female. Bavay noted that Normand
had found that they were most abundant in the duodenum, less common in the
jejunum, and did not reach the ileum, but that in any case, they were much less
frequent than A. stercoralis.
In addition to describing this parasitic female adult worm, Bavay recorde d
that he and Normand had found a new type of larva which they believed was
the larval form of A. intestinalis:
In the stools of three diarrhoeic patients that we have kept in order to follow the devel-
opment of Anguillula stercoralis, we have found that after several days, they
contained certain larvae that were different from the first. They were longer, with a
cylindrical oesophagus which passed almost to the middle of the body, and a tail,
which instead of terminating in a fine point, was, on the contrary, apparently
truncated. Although culture of these larvae could not be persisted with long enough
to establish in an irrefutable fashion their identity with Anguillula intestinalis, we
have hardly any doubt in this regard.7
Bavay went on to say that two of the patients who had had this form in thei r
stools had since died, and that post mortem examination had revealed adult A.
intestinalis. Moreover, he and Normand had looked in vain for these worms in
the body of a man who had returned from Cochin-China three years before and
in whom A. stercoralis was extremely abundant. Both the adult and larva l
forms of the parasite were illustrate d by Bavay in a publication which appeared
in July 18778. Although he did not realize it, Bavay had described the direc t
development of larvae excreted in the faeces into infective (filariform) larvae.
Similar worms were noted in the following year by Chauvin 18.
Thus, at this point, it was believe d that there were two distinct species. In the
case of A. stercoralis, larvae were found in the faeces and adult worm s
developed in the external environment. In the instance of A. intestinalis,
parasitic female adult worms were found in the gut, and they were thought to
produce larvae with the truncated tail.
In 1878, Grassi and Parona discovered A. intestinalis at a number of
autopsies in Pavla, Italy 49. Like Normand and Bavay, they observed that th e
parasitic worms were located principally in the lower duodenum and uppe r
jejunum. They found that these worms deposited eggs in the intestinal lumen
which hatched almost immediately after being laid. Further, they observed that
these larvae in the small intestinal lumen were identical with those excreted in
the faeces and these in turn appeared to be the same as the larvae described as
A. stercoralis by Normand and Bavay. When m oistened faeces containing these
larvae were cultured, the worms grew into forms about 0.75 mm long with an
oesophagus occupying half the length of the worm. Grassi and Parona realized
that these worms (now known as infective or filariform larvae) wer e
undoubtedly the same forms that Bavay, and after him, Chauvin, had believed
were the larvae of A. intestinalis. At no time did Grassi and Parona grow any
of the free-living adult worms which other workers had obtained when A.
stercoralis larvae had been cultured. Thus, the sequence of events seemed to
be that parasitic female worms ( A. intestinalis) produced larvae (now known
as rhabditiform larvae because of the similarity of the oesophagus with tha t
seen in the genus Rhadbitis) in the intestine, which in turn developed int o
filariform larvae in the free-living state. In 1879, Grassi erected a new genus
which he called Strongyloides, ( [STRONGYLOS] = "round" ;
[EIDOS] = "similar") because of its closeness to the genus Strongylus,
in which to place the worm 43, then later in that year in a review of his ow n
article, he indicated that the worm should be called Strongyloides
intestinalis 44.
Shortly afterwards, Eduardo Perroncito drew attention to the presence o f
these parasites, as well as Ancylostoma duodenale , in the intestinal tract o f
miners working in the St. Gothard tunnel (see chapter 20) 88. Initially, he
believed that both A. intestinalis and A. stercoralis were present, with the
former appearing in the faeces as eggs, and the latter as larvae. He described
the development and hatching of the so-called A. intestinalis eggs, then
recounted their subsequent development. He found that after 24 hours the y
doubled their length and underwent internal reorganization, particularly with
respect to the anatomy of the alimentary canal. As with A. duodenale,
Perroncito misinterpreted the moulting process as cyst formation, and described
subsequent calcification of the capsule. Similarly, he described the larvae of A.
stercoralis, indicated some differences from the larvae of A. intestinalis and A.
duodenale, and stated that after one day of life they too became encysted. Thus,
Perroncito persisted in the erroneous differentiation of two species o f
Strongyloides, believed incorrectly that A. intestinalis eggs were excreted in
the faeces, described some non-exi stent morphological differences between the
larvae, and became completely misled in ident ifying "encystment" of both forms
of larvae89.
Subsequently (1881), however, Perroncito succeeded in cultivatin g
free-living adult worms (which h e renamed Pseudorhabditis stercoralis ) from
rhabditiform larvae in the faece s, and described accurately their copulation, the
laying of new eggs, the hatching of these and the transformation of the second
generation of worms into filariform larvae 91. These filariform larvae were very
similar to those that Grassi and Parona had described as developing directl y
from A. intestinalis larvae. The situation was now very confused for filariform
larvae had been described as developing in two ways. According to Bavay and
to Grassi and Parona, filariform larvae developed from A. intestinalis whereas
Perroncito had demonstrated that they were produced by free-living adul t
A. stercoralis.
Perroncito's assertion that A. intestinalis eggs were excreted in the faeces led
to a spirited controversy with Grassi who eventually proved beyond doubt that
Perroncito had been dealing with hookworm eggs 45-48,92. Grassi insisted that the
rhabditiform larvae found in the faeces were direct descendants of the wor m
known as A. intestinalis. Furthermore, he postulated in 1882 that as thes e
larvae often developed in culture into freeliving adults called A. stercoralis,
then A. intestinalis, like Ascaris nigrovenosa was dimorphobiotic 45. By this, he
meant that the parasitic worm in the intestines was parthenogenetic o r
hermaphroditic and produced eggs which hatched rhabditiform larvae. H e
believed that when these escaped in the faeces, they developed into sexuall y
differentiated free-living male and female adult worms which in turn produced
descendants that were capable of develop ing again into parasitic mother worms
after ingestion by the host.
Rudolf Leuckart supported this view in the following year when he reported
his own observations on the development of A. stercoralis. A case of strong-
yloidiasis, which was studied by Seifert 102,103, occurred in Gerhardt's clinic at
Würzburg. The faeces contained large numbers of rhabditiform larvae typical
of those described by Normand and Bavay and by Perroncito as A. stercoralis

on the one hand, and as A. intestinalis by Grassi and Parona on the other .
Seifert sent samples of the faeces to Leuckart in Leipzig who reported tha t
when these were cultured, they developed into free-living male and femal e
A. stercoralis, and that the new embryos developing from the eggs produced
by these worms metamorphosed into filariform larvae. Leuckart was convinced
that these filariform larve must pas s into another host in order to complete their
development, for their structure was su ch that he did not believe that they could
possibly change again into the rhabditiform form. He considered that th e
mature stage of these larvae wa s undoubtedly the parasitic adult A. intestinalis,
for the shape of its body and oesophagus resembled strongly that of filariform
larvae. He considered that all these worms were but different phases of the life
cycle of a single heterogonic parasite i.e. that there was an alternation between
parasitic and free-living generations of adult worms. Leuckart renamed th e
parasite Rhabdonema strongyloides 70 and concluded that:
The Rhabditis stercoralis itself is to be erased from the list of essential parasites; it
represents, like the Rhabditis ascaridis nigrovenosa, despite its sexual differentiation,
an intermediate generation, developing externally, which forms a link in the chain of
development of the Anguillula intestinalis.70
Evidence supporting this view was provided when Seifert, at the suggestion of
Grassi, treated the patient who had provi ded the faeces with male fern, santonin
and thymol and recovered two parasitic females in the faeces and a degenerated
specimen from the vomitus, whereas no sexually diffferentiated adult A.
stercoralis was ever observed in the stools 102,103.
Two important questions remained unanswered, however. The firs t
concerned the development of filariform larvae and the second related t o
whether the parasitic worms were hermaphroditic or parthenogenetic. A s
already mentioned, some observers 7,8,18,49 had noted direct development o f
filariform larvae in faeces, whereas others 70,91 had described their production
from larvae liberated by free- living adult worms. Leuckart, in fact, should have
been in a position to resolve this prob lem, for both modes of development were
observed in his laboratory in the same faecal specimens, although he wa s
unaware of the event. In an illuminating insight into Leuckart's research an d
teaching methods, Arthur Looss, who at the time had been a student o f
Leuckart, recounted nearly 30 years later the circumstances:
I....took part in these investigations in the sense that Leuckart entrusted me with the
starting and controlling of the cultures, the making of the preparations etc. . and so far
as I can remember personally examined only the finished preparations, not the
cultures themselves. In the latter, a good many unmistakable filariform larvae were
found even at a time when sexual animals were not yet mature. Since Leuckart,
however, as it then appeared to me, seemed interested only in the fate of the sexual
animals and I myself as yet understood but little of the purport of the investigations,
I did not specially report the direct transformation of the larvae to my teacher and the
fact of its existence remained unknown to him. 75
Nevertheless, Grassi (1883) once more drew attention to this capacity o f
rhabditiform larvae to develop directly into filariform larvae 46. In 1884, Golgi
and Monti in Pavia studied further cases and followed both the direc t
transformation of some rhabditiform larvae obtained from parasitic femal e
worms into filariform larvae, as well as indirect development of others through
the free-living sexually differentiated generation: they believed the forme r
course to be the commoner 40,41. This view was echoed later by Leichtenster n
who studied over many years cases of strongyloidiasis occurring in brick -
workers along the Rhine, as well as cases imported from the tropics. He tried
to vary the proportion of worms developing in each direction by altering th e
environmental conditions but failed to do so 68. He then suggested that strains
of temperate origin developed directly whereas those acquired in the tropic s
tended to develop indirectly69. That these different courses were not due to two
different strains of the worm was shown by Wilm s in Leichtenstern's laboratory,
for he infected a human with filariform larvae which had developed directl y
then showed that some of the rhabditiform larvae subsequently excreted in the
stools developed indirectly 119. Leichtenstern's suggestion of geographica l
variations in the form of free-living development was also not sustained when
Darling working in Panama 22 and later Sandground in Honduras 97 found both
modes of development with the indirect cycle predominating in the experience
of the former observer and direct transformation being most common in th e
hands of the latter investigator.
Uncertainty also surrounded the status of the parasitic adult worms found in
the intestinal tract. Bavay questioned whether the absence of male worms was
due to their rapid disappearance following fertilization, or whether the worms
were hermaphroditic with a female habitus 8. Shortly afterwards, Grass i
suggested that they may be hermaphroditic or parthenogenetic 45. Leuckart
concurred with these two last possibilities, and while expressing no fir m
opinion, inclined to the view that they were hermaphroditic 70,71. In 1888,
however, Rovelli concluded that the worms were parthenogenetic 96. On the
other hand, Sandground (1926) believed that the parasitic adult worm wa s
really hermaphroditic 98 but this view has not been sustained. The proble m
became even more controversial when in 1932 Kreis in Faust's laboratory in
New Orleans claimed to have found parasitic male adult worms in the faeces
of infected humans and dogs 61. Faust endorsed the view remarking:
occasionally parasitic females and males are passed in diarrheic stools....The rare
parasitic males are practically indistinguishable from the free-living males of the
indirect cycle.29
Faust then proceeded to compound the problem. He traced the development of
twelve strains of S. stercoralis (from humans, primates and a dog) in forty dogs
and declared that filariform larvae developed into "pre-adolescent" and adul t
male and female worms in the respiratory tract. Fertilization was then believed
to take place either there or in the lumen of the upper alimentary canal before
the fertilized females became embedded in the intestinal mucosa. He furthe r
proposed that fertilized eggs proceeded to direct development and unfertilized
ova underwent indirect development 30. Although Faust continued to describe

the parasitic male in his textbook as late as 1970 32, no other investigators were
able to find such worms and the concept fell into disrepute. In fact, in 1936 ,
Graham succeeded in producing patent infections in rats exposed to a single S.
ratti filariform larva each 42. The only possible conclusions from thi s
observation were that the worm was either parthenogenetic or hermaphroditic,
and detailed anatomical studies of the parasite since that time have confirmed
the former proposition.
When the identity of A. stercoralis and A. intestinalis was realized, it became
necessary to use the same name for both species. Since the generic nam e
Anguillula was already occupied for species of eel, however, the designation
Strongyloides intestinalis suggested by Grassi in 1879 was generally accepted.
As S. stercoralis had been described before A. intestinalis, however, Stiles and
Hassall considered that the correct name should be Strongyloides
stercoralis 110. This view was confirmed by the International Commission on
Zoological Nomenclature in Opinion 66 delivered in 1915 57.
When Normand reported the presence of A. stercoralis larvae in the stools of

patients with Cochin-China diarrhoea, he was in no doubt that the parasite s
were the cause of this syndrome, although he w as careful to add the proviso that
there were other causes of a similar condition 81. He expanded this view i n
subsequent papers, but also noted that worms could be present withou t
producing ill-effects82,83. When Bavay published the discovery of a secon d
worm (A. intestinalis) in the gut, he asked in a rhetorical question whethe r
these worms were pathogenic and concluded that it was premature to say that
they were, for these worms were present in such small numbers when com -
pared with the frequency of A. stercoralis larvae7,8.
A number of early observers including Laveran 66,67, Roux95 and Dounon 25
concurred with Normand's view that A. stercoralis was a potent cause of
diarrhoea. Others, however, including Libermann 72, Chastang 17 Breton14 and
Grassi43,44 were less certain. Indeed, Grassi found the parasite in the stools of
so many apparently healthy individuals that he eventually asserted that thes e
worms were innocent commensals of man 47. Perroncito believed that the y
played a part with hookworms in the genesis of anaemia in workers in the St.
Gothard tunnel 88, but this was disproven when eradication with anthelmintics
of hookworms but not S. stercoralis larvae cured the anaemia.
Subsequent studies, however, did confirm that the parasites could hav e
profound pathological consequenc es. Golgi and Monti at autopsy (1884) found
intestinal changes with worms in the crypts of Lieberkühn 40,41, then Sonsino
(1891) discovered eggs and larvae, not only in the depths of the lumen of the
crypts, but also in the mucosa 107. This was confirmed by Askanazy in 1900 who
demonstrated the presence of female worms in the epithelium of the uppe r
small bowel and rhabditiform larvae in the mucosa associated with a chronic
inflammatory infiltrate. He also noted that eggs were often deposited in tunnels
in the mucosa. He summarized his findings:
The A. intestinalis bores into the intestinal wall, primarily into the mucosa and often
into the epithelium of its glands, in order to absorb food....But in this connection the
mother animals perform still another function, in that they deposit their eggs in the
tissue of the mucous membrane. These eggs change into embryos which then emerge
toward the intestinal lumen.3
Askanazy was in no doubt that the worm was pathogenic, for he conclude d
from studies using special stains that the adult worms fed on the juices of the
intestinal wall, and deposited their offspring in the midst of living tissue.
In 1905, Thayer reviewed the question of the pathogenicity of the parasit e
and summarized the position in the following way:
The weight of evidence appears to be in favour of the view that, while the parasites
may exist in the intestine for long periods of time without ill effects, they are by no
means, as Grassi says, 'innocent commensals of man'. It would seem probably that this
parasite alone may be the primary agent in many cases of chronic diarrhea. 113
The precise location of parasitic adult worms, however, continued to be a
matter of argument. Whereas Ask anazy3 and others 38,63 were of the opinion that
the parasites frequently entered the stroma of the mucous membrane, other s
disagreed. Thus, Ophüls (1929) wrote:
I have been unable to convince myself that either the mother worms or the
rhabditiform embryos ever enter the stroma of the mucous membrane. They cause,
however, much epithelial destruction.85
Recent observations using transmission electron microscopy in infecte d
animals suggest that Ophüls was correct.
With the discovery of autoinfection and overwh elming infection with S. sterc-
oralis, as will be described shortly, it became absolutely clear that infectio n
with this parasite could have devastating consequences. The means by which
these effects are brought about, however, remain uncertain. Many earl y
observers assumed that the effects were purely mechanical 40, while Askanazy
suspected that the worm may produce a toxin 3. A few years later, Thira
suggested that bacteria may enter the tissues through the portals in the mucosa
left behind by the invading worms and thus exacerbate the illness 114.
When Blanchard in 1890 reviewed the probable means by which infection oc-
curred, he remarked that the possibilities were not too difficult to conceive .
Water had been incriminated, but samples taken from the Mekong river in a
heavily endemic area had been examined without finding any Strongyloides
larvae. He presumed, therefor e, that the most likely method of infection was by
consumption of vegetables which had been contaminated with worms, thu s

allowing the ingested larvae to develop into parasitic adult worms in th e
bowel11. That this could indeed occur was shown experimentally when Wilms
(1897) infected a human volunteer experimentally by the oral route; seventeen
days after swallowing infective larvae, rhabditiform larvae began to appear in
the stools119.
Shortly afterwards, however, Looss demonstrated that the similar hookworm
larvae could produce infections by penetrating the intact skin. This stimulated
Paul van Durme, a Belgian working at the Liverpool School of Tropica l
Medicine in England, to investigate whether a similar route of entry might not
occur with Strongyloides. Although he entitled his paper of 1901-1902 "Some
observations on the larvae of Strongyloides intestinalis and their penetration
through the skin", van Durme was in fact almost certainly dealing wit h
S. fuelleborni, for he not only stated that the larvae were cultivated from a
chimpanzee imported four months previously from Africa, but remarked that
he always found eggs in the faeces (which is a characteristic of that species).
Filariform larvae were applied to t he abdominal skin of guinea pigs. They were
found to disappear from the cutaneous surface within half an hour, the n
biopsies were taken at intervals. He wrote:
After half an hour, the larvae are found already deeply engaged in the dermis. One
encounters them most often in the areas surrounding the hair follicle, at the level of
the sebaceous glands. The fixed skin sections, after an hour, present fragments of
larvae down to the subcutaneous areolar tissue. Twenty hours after inoculation, all the
larvae have not disappeared; although less numerous they can be seen at different
levels in the dermis.26
Van Durme lamented that he was u nable to continue his investigations in order
to determine whether worms introduced in this way passed to the intestine and
produced patent infections. In 1904, Looss succeeded in infecting himself by
placing several hundred S. stercoralis larvae on the skin of his forearm; 64 days
later, he first found larvae in his stools and they were present in subsequen t
examinations74. More than twenty years after van Durme's studies, Kosug e
examined the mechanism of skin penetration in experimental animals in more
detail, and concluded that larvae penetrated thin skin directly, but effecte d
entrance of thick skin via the hair follicles 60. Fülleborn then investigated th e
penetration of human skin by these larvae and found that only a proportion of
worms succeeded in penetrating the integument, and that this was more likely
when the skin was thin and the person was younger. When he tried to infec t
himself (then aged 59), Fülleborn concluded that a larva only penetrated th e
forearm skin when the epidermis was broken 35.
DETERMINATION OF THE ROUTE OF MIGRATION AND TH E

DISCOVERY OF AUTOINFECTION AND OVERWHELMIN G
INFECTION
Normand may have unwittingly app reciated the possibility of autoinfection, i.e.
the multiplication of worms within the body of the host without passing to the
external environment, for he noted that although worms may persist in the gut
for years without causing undue inconvenience, anything which tended t o
diminish the patient's resistance often resulted in an exacerbation of symptoms
to produce the clinical picture of Cochin-China diarrhoea 82,83. This idea was
reinforced by Grassi in 1883 when he pointed out that immature specimens of
S. intestinalis were not infrequently found in the cadavers of patients who had
remained in hospital for several months and in whom oral infections were most
unlikely. When this observation was taken in conjunction with th e
demonstration by Parona and himself that rhabditiform larvae could develo p
directly into filariform larvae, and that the free-living adult forms were absent
from the bowel, Grassi deduced that direct transformation of rhabditifor m
larvae into parasitic adult worms must be taking place within the host without
the interpolation of a sexually differentiated generation 46. Grassi undoubtedly
envisaged that moulting and maturation of worms from the rhabditiform larval
stage through to adult worms took place in the gut, but such concepts remained
shadowy and vague until the routes of infection and migration of worms were
established. A clue was provided in 1895 when Teissier claimed that he ha d
found larvae in the peripheral blood of a patient with strongyloidiasis. From his
description, however, the worms must have been rhabditiform larvae (which
is most unusual); possibly he was dealing with a different parasite 112. In any
event, the significance of the observation was not appreciated.
As already indicated, Wilms had shown that infection could be acquired by
ingestion of infective larvae, and van Durme had demonstrated that larvae had
the capacity to penetrate the skin. Furthermore, Looss had shown that afte r
hookworm larvae had penetrated the skin, they passed to the lungs where they
escaped into the airways, ascended the respiratory tree and passed to th e
intestine where they completed their development (see chapter 20). In the light
of all these observations, Friedrich Fülleborn in Hamburg, Germany began to
investigate the migratory route of S. stercoralis larvae in 1911. In his initia l
experiment, Fülleborn performed a tracheotomy on a dog then infected i t
percutaneously. Three days later, large numbers of larvae, some of whic h
appeared to be moulting, appeared in the viscid tracheotomy mucus; the y
continued to be passed until six days after infection. In this artificial situation
which restricted worms to the trachea, some of the larvae moulted and became
female adult worms. Furthermore, despite interruption of the pulmonary -
oesophageal circuit, a few rhabditiform larvae were found in the faece s
beginning eight days after infection. In a second experiment, another dog had
its oesophagus excised and was also infected percutaneously. Two days later,
numerous larvae were recovered from the dog's saliva (the mouth was washed
out with water), then on the following day, larvae were discharged from th e
upper oesophageal fistula and continued to do so for the next three days .
Between eight and twelve days after infection, rhabditiform larvae originating
from female worms were found in the tracheal mucus. Fülleborn conclude d
from these experiments that "the majority of Strongyloides....larvae are
eliminated after interruption of the tracheo-oesophageal tract but even so, a
slight infection occurs" 34. In order to determine whether the slight infection that
he had noted might result from larvae which passed through the lungs the n
embolized to the small bowel in the systemic circulation, Füllebor n
tracheotomized a dog then injected larvae which had been obtained from th e
tracheal mucus of another dog directly into the duodenal artery. Six days later,
the animal was killed and female adult worms were found in the duodenum ,
while the lung was free from infection. In another experiment in which free -
living filariform larvae were injected directly into the stomach of th e
tracheotomized dogs, the resul ting infection was minimal, whereas if filariform
larvae obtained from tracheal mucus was injected, a severe intestinal infection
developed. He concluded that in spite of only minimal morphological alter -
ations, the filariform larvae were altered biologically during their systemi c
migration and became resistant to destruction by the gastric juices. Fülleborn
summarized all these experiments thus:
Chief results of the series of experiments on percutaneous infection: These proved
that the normal route of infection of percutaneous penetrating....Strongyloides was
from the lung to the intestine via trachea and esophagus. A small number of
parasites....may pass from the lung veins and the left heart and reach the intestine by
embolism via the intestinal arteries.34
In this series of infections, Fülleborn so metimes found filariform larvae in the
kidneys and liver, and supposed that they reached this site via the systemi c
circulation. In 1920, however, Yos hida reported that after oral infection, larvae
were found in the abdominal and p leural cavities within 24 hours, and that they
appeared within the abdominal cavity and viscera within a similar period when
placed on the abdominal skin. These findings led him to suggest that the larvae
migrated directly through the connective tissues 121.
Concurrently with studies on the migration of larvae, further evidence began
to accumulate gradually that was suggestive of the phenomenon of repeate d
infection or autoinfection. As already mentioned, Askanazy 3 then von Kurlow 63
found larvae in the deeper layers of the intestinal wall. In 1911, John Gage in
the United States reported his observations on a 48 year old alcoholic patient
who presented with an acute pneumonia. On examination of the sputum, Gage
was surprised to find S. stercoralis filariform larvae. The pneumonia resolved
but the patient's course continued downhill and he died two months later; larvae
were found throughout the wall of the intestine and in the lungs 38. Gage
canvassed the ways in which autoinfection could occur. He rejected Grassi's
hypothesis that direct transformation of rhabditiform larvae into filarifor m

larvae then into adult worms may occur within the bowel as he failed to fin d
evidence of intermediate stages of the parasite at autopsy. With remarkabl e
accuracy, he postulated both mode s of autoinfection (external and internal) that
are generally accepted today:
The finding of larvae in the sputum....after the patient had been in bed for two
months, indicates that he was reinfecting himself. Because of his personal filthiness
and the irritation of the skin over his buttocks and back, I thought that the larvae were
gaining entrance through the skin at this place, and some probably did. However, the
presence of larvae in the lymph-spaces and lymph vessels of the intestinal wall
suggests another plausible explanation - that the larvae pierce the intestinal walls,
enter the lymph stream, pass up the thoracic duct into the subclavian vein, thence
through the right heart to the lungs, appear in the sputum and, when swallowed,
develop into adult parasites. . In this way a vicious circle is set up and the infection
grows steadily worse....This must be a slow process and extend over many years. 38
Similarly, Yokogawa in 1913 reported that at autopsy he had found larva e
(whether he was referring to r habditiform or filariform larvae is not made clear
in the abstract of the Japanese paper) not only in the mucosa, muscularis and
serosa of the large intestine around an ulcer, but also in the wall of the ileum,
liver, lymphatic system and bloodstream of a patient 120. In 1919, Thira, also in
Japan, examined the intestines of two humans and carried out experiments in
cats and dogs. He found that rhabditiform larvae may transform into filariform
larvae within the body, for he saw the latter forms in the muscularis and i n
lymphatics and veins of the submucosa of the bowel. He concluded tha t
autoinfection was possible, and in order to support this concept, infecte d
successfully a dog by the rectal administration of filariform larvae obtaine d
from a fresh stool 114. This view was supported by Shimura and Ogawa in 1920
who, like Gage, found filariform larvae in the sputum of a man who wa s
suffering from cancer of the kidney, chronic enteritis and chronic "bronchia l
catarrh", and who also had large numbers of rhabditiform larvae in his stools
and vomitus 105.
The factors which determine whether a rhabditif orm larva was excreted in the
faeces or developed into a filariform larva within the gut were (and remain )
uncertain. Stekhoven described a case in whi ch the administration of purgatives
resulted in the passage of hard faecal pellets which contained filariform larvae
and suggested that this stage of the parasite could cause autoinfection 108.
Similarly, in order to assess the role of constipation, Nishigori (1928) reduced
intestinal motility in infected dogs by the injection of opiates or th e
administration of bismuth, and found that a small proportion of rhabditifor m
larvae in the constipated stools had moulted. He then described the sam e
phenomenon in an infected soldier who became constipated. Further, Nishigori
believed that whereas filariform larvae could penetrate the bowel mucos a
easily, rhabditiform or second-stage larvae could only do so if the mucosa was
already ulcerated. Nevertheless, all the larvae that he found in the variou s
organs (lungs, spleen, kidney etc) and bloodstream were filariform. Nishigori
therefore injected rhabditiform larvae intravenously or into the abdomina l

cavity of dogs and found that they had transformed into filariform larvae a s
early as 24 hours later. He postulated that in the process of autoinfection, larvae
followed one of three routes:
(1) They enter the lymphatic....vessels in the mucosa of the large intestine; they leave
the intestinal wall in the flow of lymph; they then enter the lymph nodes....then,
through the thoracic duct, by way of the heart, they reach the lungs.
(2) Actively piercing the intestinal wall, they reach the abdominal cavity. Some of
them immediately penetrate through the diaphragm into the thoracic cavity;
afterwards, from the surface of the pulmonary pleura, they invade the parenchyma
(lung); others penetrate through the capsule of the liver, entering the parenchyma;
afterwards, they reach the lungs by way of the heart.
(3) From the surface of the mucosa of the large intestine the invading larvae enter the
blood capillaries; they pass through the portal system to the liver and the heart and so
reach the lungs.79
Nishigori also believed filariform larvae produced by direct and indirec t
means could be distinguished morphologically, with the former worms being
smaller and having more cells in the genital primordium 79. This could not be
confirmed by most investigators but Faust c laimed to be able to identify a dwarf
filariform larva of direct type which he proposed to call "hyperinfective strain"
as he considered that there was considerable evidence that this was the for m
which was responsible for autoinfection 27.
In confirmation of some of these speculations, Ophüls in the following year
described a 36 year old man who died of gastroenteritis and in whom post -
mortem examination revealed large numbers of filariform larvae in the mucosa
and submucosa of the colon and in the mesenteric lymph nodes 85 then similar
effects were described in patients with a dual infection with strongyloidiasis and
leprosy in the Philippines 80 and in two patients in Brazil 116.
In addition to reinfection within the intestinal tract (internal autoinfection),
Fülleborn in 1926, like Gage before him but probably unaware of that person's
postulate, suggested that autoinfection might also occur in another wa y
(external autoinfection). As will be detailed later, a number of persisten t
carriers of infection complained of urticaria on the buttocks which Fülleborn
thought was due to migrating filariform larvae:
It is entirely possible that, after defecation, rhabditiform phases can develop into
filariform larvae in the anal folds in residual fecal matter, particularly as I ascertained
that at....the 'natural hatching oven' of the anal folds, the filariform stage of
Strongyloides larvae can be found after less than 24 hours....The penetration into the
surrounding skin of filariform Strongyloides larvae....not only causes urticaria but also
must be a cause for permanent new infection of the Strongyloides carrier.35
By these means of internal and external autoin fection, Strongyloides infection
may persist for many years. Normand understood that the natural history o f
strongyloidiasis was very variable, with many people being cure d
spontaneously with elimination of all the paras ites, whereas some patients at the
other extreme went downhill progressively, became severely dysenteric an d
died. In the early part of the present centu ry, it was realized gradually that there
was a group of individuals who acquired a chronic illness with minimal o r
moderate symptoms. Fülleborn in 1926 mentioned the instance of one of hi s
patients who had been followed by him for 24 years and remarked that thi s
probably represented the "welt-rekord" 35. Since that time, many patients have
been reported with even longer durations of infection. Thus, infection was still
present in a group of Australian former prisoners-of-war between 34 and 3 7
years after removal from an endemic area 50. Why some patients shoul d
eradicate the worms while others tolerate their presence has not yet bee n
discovered. Sandground showed many years ago that dogs infected exper -
imentally acquired some resistance to reinfection but this finding does no t
necessarily extrapolate to all humans 100. There may well be genetic variations
in susceptibility to infection and the capacity to mount a completely effective
immune reaction but these have not yet been defined. Certainly, some patients
appear to be unable to eliminate all the worms yet are able to contain the m
within bounds and prevent their excessive multiplication.
It has been recognized increasingly over the last 25 years, however, that this
relatively happy state of affairs is not always sustained. It has become apparent
that overwhelming infection, otherwise known as hyperinfection, massiv e
infection, or disseminated strongyloidiasis, in which there is a greatl y
heightened multiplication of worms, could supervene if patients becam e
immunosuppressed for one reason or another (see next section), with con -
sequent breakdown of resistance to the parasites. That these effects were not
simply due to massive exposure to infective larvae in the environment wa s
confirmed when dogs were infected experimentally with a defined number of
worms, immunosuppressed, then a vast number of worms recovered 52. Con-
sequently, the prognosis of strongyloidiasis is uncertain, with all patients being
at risk from severe disease, even though the probability of such an outcom e
may be small.
Normand in 1876 reported that the symptoms associated with infection wit h
this parasite were variable, but he was in no doubt that this infection coul d
cause a severe and at times fatal disease. He described four clinical categories:
Some patients who are afflicted with diarrhea of Cochin China suffer a less intense
infection; the causal agent disappears quickly;....recovery comes quickly....Other
patients, more heavily infected, relapse easily, even after the diarrhea has been
arrested....After some time, more than a year after infection, the patient may recover.
The diarrhea sometimes ceases suddenly and, little by little, he recovers a degree of
vigor and weight. At other times, the disease evolves progressively into a terminal
condition. This third group of patients develops enterocolitis, either after an intense
infection or after a long period of alternating recovery and relapse....inflammation
develops analogous to that which accompanies a serious dysenteric infection, and in

a few hours, the patient is dead.- At other times the process is less rapid and may
become entirely chronic. The patient, having fought for a long time against the effects
of diarrhea, develop an extreme marasmus and succumbs, due to anemia. 81
Thus, the most important symptom was diarrhoea, which was at times mil d
with three or four soft, pale motions a day, while on other occasions wa s
associated with blood and mucus in the stools or was more choleraic (watery)
in character.
On the other hand, Darling (1911), like Grassi and others before him ,
concluded after a study of Strongyloides infection in humans and animals in the
Canal Zone of Panama, that the parasite was not a causative factor in th e
production of diarrhoea 22. Nevertheless, experimental animal studies b y
Thira114 and Sandground 99, and continuing clinical observations confirmed that
diarrhoea was a prominent feature of the infect ion. Thus, Gage (1911) observed
that a chronic but intermittent diarrhoea was present in 13 of his 15 patient s
with strongyloidiasis 38. Barlow in 1915 studied 23 infected persons i n
Honduras and divided the clinical picture into four stages - "invasion "
characterized by erythema and irritation of the skin at the site of entry of th e
larvae, "latent" in which laxatives had an unduly excessive effect, "diarrhoea"
which was intermittent, painless and unaccompanied by blood or mucus, and
"neurasthenia" with anorexia, vertigo, malaise and emaciation 5.
The other major symptom was a skin rash. Looss reported in 1905 that, i n
older persons, some larvae:
are kept back in the tissues where they wander around under the skin producing the
skin disease known as creeping eruption etc. They are able to live in the of form
wandering larvae....about five years.74
Although this report has been cited as indicating Strongyloides infection38, the
eruption may well have been due to hookworms. In 1926, Fülleborn notice d
that when S. stercoralis infective larvae were applied to the skin of previously
uninfected individuals, there was a transient itch, but when a person who had
been a carrier for many years was infected likewise, a severe urticarial ras h
developed which extended gradually along the skin over the next few hours and
appeared to be due to larvae migratin g through the integument or subcutaneous
tissues. Enquiry revealed that eight out of ten of his patients who were chronic
carriers experienced itching of the buttocks:
an irritating pruritus accompanying the urticaria occurs, intermittently, at any time
during the day but especially during the night in bed. With rubbing and scratching of
the skin the urticarial patches become so large that....areas the size of a hand, at the
buttocks, are indurated 'hard as a board' with urticaria; at other times the urticaria
extends to the waistline in bands one or two fingers wide. 35
In 1958, Arthur and Shelley introduced the term "larva currens" to reflect the
rapid rate of migration compared with cutaneous larva migrans 2.
Primary involvement of organs other than the gastrointestinal tract or ski n
were described from time to time. These included affection of the urogenita l
tract presenting with haematuria 37 and of the lungs causing cough and wheeze 84;
larvae were found in the urine and sputum, respectively.

One of the major difficulties which has confronted attempts to define th e
symptomatology of strongyloidiasis is frequent concurrent infection with other
gastrointestinal pathogens. Hinman in 1939 in an uncontrolled analysis of 85
patients reported that abdominal pain was the most frequent presenting com-
plaint, then this was followed by diarrhoea, nausea, vomiting, headache ,
anorexia, weight loss and weakness 56. Grove solved this problem by analysing
the symptomatology of 44 men with chronic strongyloidiasis (35 years) wh o
had long since left the endemic area and were no longer infected with othe r
parasites, then controlled the study by a comparison with uninfected men who
had been prisoners in the same camps in Southeast Asia or in non-endemi c
areas of Europe. He found that two thir ds of patients complained of intermittent
urticaria, with 30% having the pathognomonic larva currens, and tha t
gastrointestinal symptoms including diarrhoea, indigestion, lower abdomina l
pain, pruritus ani and weight loss were significantly more common in infected
individuals 50.
In 1951, Galliard reviewed reported cases of fatal strongyloidiasis and
suggested that the patient had been debilitated in all cases of autoinfection so
far recorded39, then this was echoed by Hartz55 . If it had been said that all the
patients reported with overwhelming infection had been debilitated, then this
would have been closer to the truth. Massive infections were recognized i n
patients who were irradiated 94, given corticosteroids 20,118, or who were suffering
from leprosy80, lymphoma1,94 or protein-calorie malnutrition 55,93
. In 1978,
Scowden and his colleagues reviewed this syndrome, described the frequen t
concomitant bacterial infections, particularly septicaemia and meningitis ,
emphasized that immunosuppression is usually present, and concluded tha t
S. stercoralis is a powerful opportunistic pathogen 101.
Normand described a potent means of diag nosing strongyloidiasis when he first

discovered the worms, for he found them during a microscopical examination
of the faeces. He also indicated that this technique was useful for assessment
of the parasitological responses to treatment in patients in whom diarrhoe a
persisted after therapy: "The microscope revealed immediately whether it was
a matter of persistent infection or the effect of parasitism" 81.
Nevertheless, many observers over the years have recognized that examin-
ation of simple faecal smears often fails to provide the diagnosis and a number
of attempts have been made to improve diagnostic sensitivity by th e
development of concentration techniques. Those which have been usefull y
employed in strongyloidiasis include the zinc sulphate concentratio n
technique31, coproculture 53, and a modification of the Baermann technique 33.
In 1925, Deschiens and Taillandier showed that the diagnosis could also be
made by finding parasites in duodenal fluid r emoved via a duodenal tube 24. This
was claimed to be a much more effective tool for diagnosis by some authors 87,
but not by others19. In 1970, Beal and his colleagues described a simplifie d
method for obtaining duodenal fluid by means of a string coiled in a gelatin e
capsule9. In many modern centres, duodenal fluid may now also be obtained at
upper gastrointestinal endoscopy and may reveal parasites 50.
The diagnosis has also been made from time to time by recovering larva e
from other body fluids and secretions. These include urine 37, sputum38,84 ,
vomitus105, cerebrospinal fluid 78 and ascitic fluid 4.
Radiological studies may suggest the diagnosis and provide an indication of
the severity of intestinal damage. Deschiens and Taillandier describe d
thickening of the duodenal wall on barium meal examination of the uppe r
gastrointestinal tract 24.
Gage in 1911 recounted a case of Dr AC Eustis who in 1907 had shown that
the patient had strongyloidiasis and an eos inophilia of 56% 38. The first recorded
case of eosinophilia in strongyloidiasis, however, was probably that of Daland
who in 1908 reported a patient who had a blood eosinophil level of 38% 21. The
incidental finding of an eosinophilia on routine examination of blood smear s
has not infrequently stimulated a search for S. stercoralis 13. Indeed, de Langen
in 1928 realized that the condition which he had previously reported a s
"idiopathic hypereosinophilia" was in fact due to S. stercoralis infection64,65.
Nevertheless, it is now realized t hat most patients with chronic strongyloidiasis
either have no eosinophilia or, at most, a mild increase in blood eosinophi l
levels50.
Attempts have been made to develop immunoassays of strongyloidiasis a s
experience has shown that infection is often hard to diagnose parasitologically
in chronic cases. These immunodiagnost ic techniques, include skin testing with
Strongyloides antigen36 and the demonstration of antibodies in the serum 12.
The first therapeutic regimen which Normand tried was to put his patients on
a "rational diet" of milk. He believed this often suppressed mucus production
and caused disappearance of parasites (this was undoubtedly coincidental) .
Nevertheless, many patients failed to respond to such therapy and he wrote that
he was currently experimenting with santonin, mercury and arsenic, and then
proposed to try essential oils, sulphurs, quinine and mineral waters i n
"rebellious" cases81. In the following year, he reported that large quantitites of
olive oil were useful because o f its mechanical action 82. Perroncito 90 and others
after him considered that ethe real extract of male fern was valuable, but Seifert
did not agree and believed that thymol was better 102. Grassi, however, asserted
that no known anthelmintic was of any value 46; this view turned out to be quite
correct. Similarly, new agents introduced for the treatment of hookworm such
as oil of chenopodium, betanaphthol, carbon tetrachloride an d
tetrachlorethylene were found to be ineffective in strongyloidiasis.
In 1925, Kudiche showed that some dye-stuffs such as crystal violet an d

fuchsin killed filariform larvae in vitro 62. Three years later, de Langen reported
that gentian violet given orally in conjunction with intravenous injection o f
tartar emetic relieved the sympto ms, reduced the eosinophilia and expelled the
worms64. In the following year, however, he advised that patients whom he had
thought were cured had relapsed 65. Subsequently, Faust also showed that crystal
violet and gentian violet were active in vitro, then experimented in monkey s
and claimed striking results. He declared that oral administration of gentia n
violet caused all infections to undergo the direct mode of larval development,
and stated that examination of autopsied animals revealed that parasitic female
worms were killed in situ although the viability of already hatched larvae was
unaffected28. Two hundred human cases were then treated with oral gentia n
violet and 45 of the 47 patients followed up we re said to be cured 29. Subsequent
observations, however, have supported de Langen's view and failed to confirm
the efficacy of the drug 104. Similarly, there was no support for the belief tha t
"compound solution of iodine" was effec tive as had been held by some 106, or for
the claims that bismuth and tin were efficacious 23.
In 1957, MacCowen and his colleagues demonstrated the anthelminti c
properties of a dye in the dicarbocyanine series called diathiazanine iodide 76.
Unlike previous anthelmintics, this drug was shown to be active agains t
S. stercoralis by Swartzwelder and co-workers who claimed cure to 89% of 18
patients111. Several fatal reactions to the drug occurred109 , however, and the
drug was withdrawn from the market.
In 1961, Brown and his collaborators described a new benzimidazole drug,
thiabendazole, which had a broad spectrum of anthelmintic activity 16. In the
following year, Vilela and colleagues re ported that this agent cured 100% of 38
patients117 but subsequent investigators did not find such uniformly high rates.
Because a few resistant worms may multiply, thus permitting a relapse of the
illness, attention has turned to finding a drug which will eradicate all th e
worms. Martirani and Rodrigues (1976) used cambendazole, another benz -
imidazole compound, with ap parent success 77 and this may turn out to be more
effective than thiabendazole. Finally, recent studies of mice infected with S.
ratti and S. stercoralis have indicated that ivermectin, a member of the recently
discovered avermectin family of anthelmintics, may be active i n
strongyloidiasis 51.
UNDERSTANDING THE EPIDEMIOLOGY AND THE EVOLUTION

OF EFFECTIVE PREVENTIVE AND CONTROL MEASURES
Perroncito (1880) was perhaps the first person to point out an associatio n
between infection with S. stercoralis and with hookworm 88,89. Similar
observations have been made by many investigators since that time. Con -
sequently, the factors determining the prevalence of strongyloidiasis are very
similar to those already described for hookworm infection. Strongyloidiasis is
but one of a number of soil-transmitted helminth infections, and no attempt s
have been made to control it in isolation. The toxicity and ineffectiveness o f
most anthelmintics has militated against mass treatment programmes. The most
effective control measures have been the installation and usage of safe waste
disposal systems, but these are unavailable in many endemic areas.
OTHER SPECIES OF STRONGYLOIDES
S. FUELLEBORNI
This organism is a common parasite of old world monkeys and apes. It wa s

described by von Linstow in 1905 73. Infections in humans were first reported
by Blackie in Southern Rhodesia (Zimbabwe ) in 1932 10. In contrast to infection
with S. stercoralis, the diagnosis is made by finding the characteristic egg s
instead of larvae in the faeces. Tomita reported in 1941 that he found eggs in
the stools between 16 days and 11 months after experimental percutaneou s
infection of a human 115, then Pampiglione and Ricciardi demonstrated ova 28
days after experimental human infection 86. In this instance, a rash appeared at
the site of infection and was followed by lymphangitis. A cough was noted on
the fifth day, then anorexia, malaise, abdominal pain and bouts of diarrhoe a
appeared after three weeks. Infections may also be acquired by transmammary
transmission. Brown and Girardeau in Zaire reported in 1977 that they ha d
found that 34% of 76 children under the age of six months were infected, and
they recovered three larvae from the breast milk of a nursing mother 15.
In parts of Papua New Guinea, infection has been described with a S. fuell-
eborni-like worm which affects infants causing abdominal distension ,
respiratory distress and generalized oedema 59.
REFERENCES
1. ADAM M, MORGAN O, PERSAUD C, GIBBS WN. Hyperinfection syndrome with
Strongyloides stercoralis in malignant lymphoma. British Medical Journal i: 264-266, 1973
2. ARTHUR P, SHELLEY W. Larva currens. A distinctive variant of cutaneous larva migrans
due to Strongyloides stercoralis. Archives of Dermatology 78: 186-190, 1958
3. ASKANAZY M. Ueber Art und Zweck der Invasion der Anguillula intestinalis in die
Darmwand. Centralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten,
Abteilung originale 27: 569-578, 1900. Translated in 58
4. AVAGNINA MA, ELSNER B, IOTTI RM, RE R. Strongyloides stercoralis in
Papanicolaoustained smears of ascitic fluid. Acta Cytologica 24: 36-39, 1980
5. BARLOW N. Clinical notes on infection with Strongyloides stercoralis intestinalis, based
upon a series of twenty three cases. Interstate Medical Journal 22: 1202-1208, 1915
6. BAVAY A. Sur l'Anguillule stercorale. (Presentée par M. P Gervais) Comptes Rendus Hebdo-
madaires des Séances de l'Académie des Sciences 83: 694-696, 1876. Partly translated by DI
Grove
7. BAVAY A. Sur l'Anguillule intestinale (Anguillula intestinalis), nouveau ver nématoïde,
trouvé par le Dr. Normand chez les malades atteints de diarrhée de Cochinchine. (Presentée
par M. P Gervais) Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences
84: 266-268, 1877
8. BAVAY A. Note sur l'anguillule intestinale (Anguillula intestinalis) nouveau ver nématoïde
trouvé par le Dr. Normand chez les malades atteints de diarrhée de Cochinchine. Archives de
Médecine Navale 28: 64-67, 1877
9. BEAL CB, VIENS P, GRANT RG. A new technique for sampling duodenal contents: demon-
stration of upper small bowel pathogens. American Journal of Tropical Medicine and Hygiene
19: 349-352, 1970
10. BLACKIE WK. A helminthological survey of Southern Rhodesia. London School of Hygiene
and Tropical Medicine, Memoir Series, pp 91, 1932
1691, 1885-1890
12. BRANNON MJ, FAUST EC. Preparation and testing of a specific antigen fordiagnosis of
human strongyloidiasis. American Journal of Tropical Medicine 29: 229-239, 1949
13. BRAU P. De l'Anguillula intestinalis en Cochinchine et de son diagnostic hématologique.
14. BRETON. Note sur les parasites de la dysenterie et de la diarrhée dite de Cochinchine.
Archives de Médecine Navale 31: 441, 1879
15. BROWN RC, GIRARDEAU MH. Transmammary passage of Strongyloides sp. larvae in the
human host. American Journal of Tropical Medicine and Hygiene 26: 215-219, 1977
16. BROWN HD, MATZUK AR, ILVES IR, PETERSON LH,HARRIS SA. Antiparasitic drugs.
N-2-(4'thiazolyl)-benzimidazole, a new anthelmintic. Journal of the American Chemical
Society 83: 1764-1765, 1961
17. CHASTANG E. Diarrhée dite de Cochinchine. Quelques notes sur son origine parasitaire et
son traitement par la chlorodyne. Archives de Médecine Navale 30: 29-39, 1878
18. CHAUVIN. L'anguillule stercorale dans la dysenterie des Antilles. Archives de Médecine
Navale 29: 154-155, 1878
19. COUTINHO JO, CROCE J, CAMPOS R, AMATO NETO V. Estudo comparativo entre a
pesquisa de larvas de Strongyloides stercoralis no suco duodenal e nas fezes. Folia Clinica
et Biologica, São Paulo 18: 125-131, 1952
20. CRUZ T, REBOUÇAS G, ROHA H. Fatal strongyloidiasis in patients receiving
corticosteroids. New England Journal of Medicine 275: 1093-1096, 1966
21. DALAND J. Strongyloides intestinalis in Philadelphia. New York Medical Journal 87: 761,
1908
22. DARLING ST. Strongyloides infections in man and animals in the Isthmian Canal Zone.
23. DESCHIENS R, BENEZ J. Essais expérimentaux et cliniques de traitement de l'anguillulose
intestinale par le sous-nitrate et par le carbonate de bismuth. Bulletin de la Société de
24. DESCHIENS R, TAILLANDIER O. Présence de larves rhabditoides de Strongyloides

stercoralis (Bavay, 1877) dans le liquide duodénal receuilli par tubage. Considérations
cliniques sur l'anguillulose. Bulletins de la Société de Pathologie Exotique et de ses Filiales
18: 525-527, 1925
25. DOUNON PL. Étude sur l'anatomie pathologique de la dysenterie chronique de Cochinchine.
Archives de Physiologie Normale et Pathologique, second series, 4: 774, 1877
26. van DURME P. Quelques notes sur les embryons de "Strongyloides intestinalis" et leur
pénétration par la peau. Thompson Yates Laboratories Report 4: 471-474, 1901-1902
27. FAUST EC. The Panama strains of human Strongyloides. Proceedings of the Society for
Experimental Biology and Medicine 28: 253-255, 1930
28. FAUST EC. Human strongyloidiasis in Panama. American Journal of Hygiene 14: 203-211,
1931
29. FAUST EC. The symptomatology, diagnosis andtreatment of Strongyloides infection. Journal
of the American Medical Association 98: 2276-2277, 1932
30. FAUST EC. Experimental studies on human and primate species of Strongyloides in the
experimental host. American Journal of Hygiene 18: 114-132, 1933
31. FAUST EC, D'ANTONI JS, ODOM V, MILLER MJ, PERES C, SAWITZ W, THOMEN
LF, TOBIE J, WALKER JH. A critical study of clinical laboratory technics for the diagnosis
of protozoan cysts and helminth eggs in feces. American Journal of Tropical Medicine 18:
169-183, 1938
32. FAUST EC, RUSSELL PF, JUNG RC. Craig and Faust's Clinical Parasitology, eighth edition,
Lea and Febiger, Philadelphia, pp 890, 1970
33. FERRIOLLI F. Diagnóstico da estrongiloidíase. Modificações do métode de
Baermann-Moraes. Revista do Instituto de Medicina Tropical de São Paulo 1: 138-140, 1959
Ankylostomum und die Biologie dieser Parasiten. Archiv für Schiffs- und Tropen-Hygiene 18:
35. FÜLLEBORN F. Hautquaddeln und "Autoinfektion" bei Strongyloides-strägern. Archiv für
Schiffs- und Tropen-Hygiene 30: 721-732, 1926. Partly translated in 58
36. FÜLLEBORN F. Spezifische Kutanreaktionen bei Infektion mitStrongyloides und anderen
Helminthen. Archiv für Schiffs- und Tropen-Hygiene 30: 732-749, 1926
37. FURÑARA P. Un caso di ematuria da strongyloide intestinale. Policlinico 30: 75-80, 1923
38. GAGE JG. A case of Strongyloides intestinalis with larvae in the sputum. Archives of
Internal Medicine 7: 55-59, 1911
39. GALLIARD H. Recherches sur l'infestation expérimentale à Strongyloides stercoralis au
Tonkin. Annales de Parasitologie Humaine et Comparée 25: 441-473, 1950; 26: 67-84, 1951
40. GOLGI C, MONTI A. Intorno ad una questione elmintologica. Rendiconti del Reale Istituto
Lombardo di Scienze e Lettere, Milano, second series, 17: 285-288, 1884
41. GOLGI C, MONTI A. Sulla storia naturale e sul significato clinico-patologico delle cosi-dette
anguillule stercorali e intestinali. Atti della Reale Accademia delle Scienze di Torino 21:
55-59, 1885. Also, Archivio per le Scienze Mediche, Torino 10: 93-107, 1886
42. GRAHAM GL. Studies on Strongyloides. I. S. ratti in parasitic series, each generation in the
rat established with a single homogonic larva. American Journal of Hygiene 24: 71-87, 1936
43. GRASSI GB. Sovra l'Anguillula intestinale. Rendiconti del Reale Istituto Lombardo di
Scienze e Lettere, Milano, second series, 12: 228-233, 1879
44. GRASSI GB. Parassitologia umana Rivista. Sovra l'Anguillula intestinale. La Medicina
Contemporanea, Milano 3: 495-497, 1879
45. GRASSI GB. Anchylostomi e anguillule. Gazzetta degli Ospedali e delle Cliniche, Milano 3:
325, 1882
46. GRASSI GB. Un ultra nota sulle anguillule e sugli anchilostomi. Giornale della Reale
Accademia di Medicina di Torino, third series, 31: 119-121, 1883
47. GRASSI GB. Intorno ad una questione parassitologica. Un ultima parola al Prof. Perroncito.
Gazzetta Medica Italiana Lombardia, Milano, eighth series, 5: 260-262, 1883
48. GRASSI GB. Intorno ad una questione parassitologica. Un ultissima parola al Prof.
Perroncito. Gazzetta Medica Italiana Lombardia, Milano, eighth series, 5: 391-392, 1883
49. GRASSI GB, PARONA. Sovra l'anguillula intestinale (dell'uomo) e sovra embrion i
probabilmente d'anguillula intestinale. Archiv per le Scienze Mediche, Torino 3: 1-15 ,
1879
50. GROVE DI. Strongyloidiasis in Allied ex-prisoners of war in southeast Asia. Britis h
51. GROVE DI. Effects of 22,23 dihydroavermectin B 1 on Strongyloides ratti and S.
stercoralis infections in mice. Annals of Tropical Medicine and Parasitology 77: 405-410,
1983
52. GROVE DI, HEENAN PJ, NORTHERN C. Persistent and disseminated infections with
Strongyloides stercoralis in immunosuppressed dogs. International Journal fo r
53. HARADA Y, MORI O. A new method for culturing hookworm. Yonago Acta Medica
1: 177-179, 1955
54. HARTZ PH. Human strongyloidasis with internal autoinfection. Archives of Pathology
41: 601-611, 1946
55. HARTZ PH. Strongyloidasis wit h internal autoinfection in children. Documenta Medicina
Geographica et Tropica 6: 61-68, 1954
56. HINMAN EH. A study of eighty five cases of Strongyloides stercoralis infection, with
special reference to abdominal pain. Transactions of the Royal Society of Tropica l
Smithsonian Institution Publication 2359, Washington DC, pp 171-176, 1915
58. KEAN BH, MOTT KE, RUSSELL AJ. Tropical Medicine and Parasitology. Classi c
Investigations, Cornell University Press, Ithaca, pp 677, 1978
59. KELLY A, LITTLE MD, VOGE M. Strongyloides fülleborni -like infections in man in
Papua New Guinea. American Journal of Tropical Medicine and Hygiene 25: 694-699,
1976
60. KOSUGE I. Histologische Untersuchungen ueber das Eindringen von Strongyloides
stercoralis in die Haut von Versuchstieren. Archiv für Schiffs- und Tropen-Hygiene 28:
15-20, 1924
61. KREIS HA. Studies on the genus Strongyloides (Nematoda). American Journal o f
Hygiene 16: 450-491, 1932
62. KUDICHE R. Neue Verfahren zur Untersuchu ng und Prüfung von Wurmmiteln. Versuche
an Finnen und Strongyloidesl arven. Archiv für Schiffs- und Tropen-Hygiene 29: 189-197,
1925
63. von KURLOW MG. Anguillula intestinalis als Ursache akuter blutiger Durchfalle beim
Menschen. Centralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten ,
Abteilung originale 31: 614, 1902
64. de LANGEN CD. Anguillosis en het ziektebe eld van de "idiopathische hypereosinophilie".
65. de LANGEN CD. Postscript about anguillosis and eosinophilia. Mededeelingen van den
66. LAVERAN A. Note relative du nématoïde de la dysenterie de Cochin-Chine. Gazett e
Hebdomadaire de Médecine et de Chirurgie 14: 42-43, 1877
67. LAVERAN A. Deuxième note relative aux auguillules de la diarrhée chronique d e
Cochinchine. Gazette Hebdomadaire de Médecine et de Chirurgie 14: 116-117, 1877
68. LEICHTENSTERN O. Ueber Anguillula intestinalis . Deutsche medicinisch e
69. LEICHTENSTERN O. Zur Lebensgeschichte der Anguillula intestinalis . Centralblatt für
Bakteriologie, Parasitenkunde und Infek tionskrankheiten, Abteilung originale 25: 226-231,
1899
70. LEUCKART R. Ueber die Lebensgeschichte der sogenannten Anguillula stercoralis und
deren Beziehungen zu der sogenannten Anguillula intestinalis . Bericht über die
Verhandlungen der königlich sachsischen Gesellschaft der Wissenschaften zu Leipzig .
Mathematische-Physische Classe (1882) 34: 85-107, 1883. Partly translated in 113
Leipzig, volume 1, pp 1009, 1879-1886. The parasites of man and the diseases whic h
proceed from them. A textbook for students and practitioners. Natural history of parasites
in general. Systematic account of the parasites infesting man, translated by WE Hoyle ,
Edinburgh, pp 771, 1886
72. LIBERMANN. Diarrhée de Cochinchine. Gazette des Hôpitaux, Paris i: 237-238, 1877
73. von LINSTOW OF. Strongyloides fülleborni n. sp. Centralblatt für Bakteriologie ,
74. LOOSS A. Die Wanderung der Ancylostoma- und Strongyloides Larven von der Haut
nach dem Darm. Comptes Rendus du Sixième Congrès Internationale de Zoologie, Berne,
pp 255-233, 1905. Partly translated in 38
75. LOOSS A. The anatomy and life h istory of Agchylostoma duodenale Dub. A monograph.
Part II. The development in the free state. Translated from the German by M Berhard .
Records of the School of Medicine, Egyptian Ministry of Education, National Printin g
Press, Cairo 4: 163-613, 1911
76. MacCOWN MC, CALLENDER ME, BRANDT MC. The anthelmintic effect o f
dithiazinine in experimental ani mals. American Journal of Tropical Medicine and Hygiene
6: 894-897, 1957
77. MARTIRANI I, RODRIGUES LD. Ensaio clinico com o cambendazole, uma nova droga
na terapeutica anti-helmintica (nota praevia). Revista do Instituto de Medicina Tropical de
Sao Paulo 18: 71-75, 1976
78. MELTZER RS, SINGER C, ARMSTRONG D, MAYER K, KNAPPER WH .
Antemortem diagnosis of central nervous system strongyloidiasis. American Journal o f
Medical Science 227: 91-98, 1979
79. NISHIGORI M. (The factors which influence the external development of Strongyloides
stercoralis and on autoinfection with this parasite.) Taiwan Igakkai Zasshi No. 277, p p
1-56, 1928. In Japanese. Partly translated in 58.
80. NOLASCA JO, AFRICA CM. A fatal case of paralytic ileus associated with sever e
Strongyloides infestation suggesting internal autoinfection. Journal of the Philippin e
Islands Medical Association 16: 275-283, 1936
81. NORMAND L. Sur la maladie dite diarrhée de Cochinchine. (Extrait d'une lettre adressée
à M. le President par M. le vice-amiral Jurien de la Gravière). Comptes Rendu s
Hebdomadaires des Séances de l'Académie des Sciences 83: 316-318, 1876
82. NORMAND L. Mémoire sur la diarrhée dite de Cochinchine. Archives de Médecin e
Navale 27: 35-55, 102-133, 1877
83. NORMAND L. Du rôle étiologique de l'anguillule dans la diarrhée de Cochinchine .
Archives de Médecine Navale 30: 214-224, 1878
84. NWOKOLO C, IMOHIOSEN EA. Strongyloidiasis of respiratory tract presenting a s
"asthma". British Medical Journal i: 153-154, 1973
85. OPHÜLS W. A fatal case of strongyloidiasis in man, with autopsy. The life cycle o f
Strongyloides intestinalis in man. Archives of Pathology 8: 1-8, 1929
86. PAMPIGLIONE S, RICCIARDI ML. Experimental infestation with human strai n
Strongyloides fuelleborni in man. Lancet i: 663-665, 1972
87. de PAULA e SILVA GS. Estrongyloidiase duodenal. Brasil-Medico 52: 835-839, 1939
88. PERRONCITO E. Observations helminthologiques et recherches expérimentales sur l a
maladie des ouvriers du Saint-Gothard. Comptes Rendus Hebdomadaires des Séances de
l'Académie des Sciences 90: 1373-1375, 1880
89. PERRONCITO E. Helminthological observations upon the endemic disease developed
among the labourers in the tunnel of Mount St. Gothard. Journal of the Queket t
Microscopical Club 6: 141-148, 1880
90. PERRONCITO E. On the action of chemical agents and medicinal substances on th e
larvae of Dochmius duodenalis and Anguillulae: including therapeutical considerations
relative to the cure of patients from Mont St. Gothard. The Veterinarian 53: 824-828 ,
1880
91. PERRONCITO E. Observations sur le développ ement de l'Anguillula stercoralis (Bavay)
Pseudorhabditis sterc oralis (Mihi) hors de l'organisme humain. Journal de l'Anatomie et

de la Physiologie 17: 499-519, 1881
92. PERRONCITO E. Osservazioni alla nota del Dott. Grassi fatte nella seduta in cui essa
venne letta. Giornale della Reale Accademia di Medicina di Torino, third series, 31 :
121-133, 1883
93. PURTILO DT, MEYERS WM, CONNOR DH. Fatal strongyloidiasis i n
immunosuppressed patients. American Journal of Medicine 46: 488-493, 1974
94. ROGERS WA, NELSON B. Strongyloidiasis and malignant lymphoma. "Opportunistic
infection" by a nematode. Journal of the American Medical Association 195: 685-687,
1966
95. ROUX PA. De l'anguillule stercorale et de son rôle dans l'étiologie de la diarrhée d e
Cochinchine, Thèse, Paris, pp 42, 1877
96. ROVELLI G. Ricerche sugli organi genitali degli Strongyloides (Anguillula,
Rhabdonema), Como, 1888. Abstracted in Centralblatt für Bakteriologie un d
Parasitenkunde, Abteilung originale 4: 660-661, 1888
97. SANDGROUND JH. Some biological studies on the life cycle in the genu s
Strongyloides. Archiv für Schiffs- und Tropen-Hygiene 13: 528-533, 1926
98. SANDGROUND JH. Biological studies on the life cycle in the genus Strongyloides
Grassi, 1879. American Journal of Hygiene 6: 337-388, 1926
99. SANDGROUND JH. The role of Strongyloides stercoralis in the causation of diarrhea.
Some observations on the condition of dogs and cats experimentally infected with th e
parasite. American Journal of Tropical Medicine 6: 421-433, 1926
100. SANDGROUND JH. Some studies on susceptibility, resistance and acquired immunity
to infection with Strongyloides stercoralis (Nematoda) in dogs and cats. America n
Journal of Hygiene 8: 507-538, 1928
101. SCOWDEN EB, SCHAFFNER W, STONE WJ. Overwhelming strongyloidiasis: a n
unappreciated opportunistic infection. Medicine (Baltimore) 57: 527-544, 1978
102. SEIFERT O. Ueber Anguillula stercoralis und Cochinchinadiarrhoe. Sitzungsberichte der
physikalische-medicinischen Gesellschaft zu Würzburg pp 22-32, 1883
103. SEIFERT O. Ueber ein Entozoon. Verhandlungen der Congress für innere Medicin ii:
337, 1883
104. SHIKOBALOVA NP, SEMENOVA NE. (On the problem of the clinical study an d
treatment of strongyloidiasis.) Meditsinskaya Parazitologiya i Parazitarn e Bolezni 11:
76-83, 1942
105. SHIMURA S, OGAWA T. (O n the filariform larvae found in vomit of a patient infested
with Strongyloides.) Tokyo Iji Shinshi No. 2197, pp 1829-1836, 1920. In Japanese .
Abstracted in Tropical Diseases Bulletin 19: 223, 1922
106. SIMPSON VE. Strongyloidiasis. Journal of the American Medical Association 112 :
828-832, 1939
107. SONSINO P. Tre casi malattia da Rhabdonema intestinale e rhabdonemiasis. Rivist a
Generale Italiana di Clinica Medica, Pisa 3: 47-56, 1891
108. STEKHOVEN JH. Researches on nemas and their larvae. III. Strongyloides stercoralis
Bavay. Zeitschrift für Parasitenkunde 1: 231-261, 1928
109. STEMMERMAN GN, NAKASONE N. Strongyloides stercoralis infestation.
Malabsorption defect with reaction to dithiazanine iodide. Journal of the America n
110. STILES CW, HASSALL A. Strongyloides stercoralis , the correct name of the parasite
of Cochin China diarrhea. American Medicine 4: 343, 1902
111. SWARTZWELDER JC, FRYE WW, MÜHLEISEN JP, MILLER JH, LAMPERT R,
PEÑACHAVARRIA AA, ABADIE SH, ANTHONY SO, SAPPANFIELD RW .
Dithiazanine, an effective broad spectrum anthelmintic. Journal of the American Medical
Association 165: 2063-2067, 1957
112. TEISSIER P. De la pénétration dans le sang de l'homme des embryons de l'anguillule
stercorale: rapports de la présence de ces embryons dans le sang avec certain fièvres des
pays chauds. Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences
120: 171-172, 1895. (Presentée par M Potain)

113. THAYER WS. On the occurrence of Strongyloides intestinalis in the United States.
Journal of Experimental Medicine 6: 75-105, 1901-1905
114. THIRA T. (Studien über Strongyloides stercoralis .) Mittheilung der medicinische n
Gesellschaft zu Tokio 33: (11) 2-3, 1919. In Japanese, with German summary
115. TOMITA S. (On local reaction of infected skin, clinical symptoms and changes in blood
picture in experimental infection with Strongyloides papillosus amd S. fülleborni.)
Taiwan Igakkai Zassi 40: 427-442, 1941. In Japanese. Abstracted in Tropical Diseases
Bulletin 39: 100, 1942
116. TORRES CM, de AZAVEDO AP. Lesoes produzidas no honem por Strongyloides.
Sobre a 'hyperinfection'. Livro Jub ilar do Prof. L. Travassos, Rio de Janeiro, pp 475-488,
1938. Abstracted in Tropical Diseases Bulletin 36: 844, 1939
117. VILELA M de P, RODRIGUES LD, CAPELL JI, BRANDÃO JA, MARTIRANI I ,
ZACATO M. O emprego do tiabendazol no tratamento da estrongiloidiase de outra s
parasitosis humanas. Hospital, Rio de Janeiro 62: 691-710, 1962
118. WILLIS AJ, NWOKOLO C. St eroid therapy and strongyloidiasis. Lancet i: 1396-1398,
1966
119. WILMS. Anchylostoma duodenale und Anguillula intestinalis . Schmidt's Jahrbucher der
In- und ausländischen gesammten Medicin 256: 272, 1897
120. YOKOGAWA S. On the pathogenesis of Strongyloides stercoralis . Far Eastern
Association of Tropical Medicine: Comptes Rendus Troisième Congrès Biennal, Saigon
(1913), pp 329, 1914. Abstracted in Tropical Diseases Bulletin 6: 304, 1915
121. YOSHIDA S. A new course for migrating Ancylostoma and Strongyloides larvae after
oral infection. Journal of Parasitology 7: 46-48, 1920
Table 21.1. Landmarks in strongyloidiasis

___________________________________________________________________
1876 Normand discovered larvae (in retrospect, rhabditiform), which were then
named Anguillula stercoralis by Bavay, in faeces of French troops returned
from Indochina, and proposed the parasite as a cause of Cochin-China
diarrhoea
1876 Bavay described the development of free-living adult worms from faecal
larvae and the subsequent appearance of larvae (rhabditiform) [He observed
the indirect cycle of development]
1876 Normand, at autopsy, discovered parasitic adult worms in the intestine; this
was at first considered to be a distinct species and was named A. intestinalis
1877 Normand and Bavay found larvae (in retrospect, filariform) in faeces which
had been kept for several days. They believed that the larvae were the
offspring of the worm found by Normand in the intestines of a patient
[Although they did not realize it, they had observed the direct development of
rhabditiform into filariform larvae]
1878 Grassi and Parona showed that the larvae produced by A. intestinalis in the
gut were identical with A. stercoralis larvae, and observed their further
development in vitro into filariform larvae but not into free-living adults (the
direct cycle)
1880 The parasite was found to infect miners working in the St. Gothard tunnel
1881 Perroncito cultivated free-living adults from rhabditiform larvae, then
observed the laying of eggs and the hatching of rhabditiform larvae which
developed into filariform larvae (the indirect cycle)
1882 Grassi postulated that the parasitic adult worms were parthenogenetic
1883 Looss observed both direct and indirect development in vitro simultaneously
in the same preparations but did not report the fact
1883 Leuckart concluded that A. intestinalis and A. stercoralis were the same
parasite and that there was an alternation between the parasitic and free-living
generations
1883 Grassi suggested that autoinfection with direct transformation of rhabditiform
to filariform larvae may take place in the gut
1884 Golgi and Monti reported that rhabditiform larvae could undergo either direct
or indirect development
1891 Sonsino described the presence of parasites in the mucosa of the small
intestine
1897 Wilms produced a patent infection in a human volunteer 17 days after
ingestion of filariform larvae
1901-2 van Durme described the penetration of Strongyloides (probably S.
fuelleborni) filariform larvae through the skin of guinea pigs
1904 Looss produced a patent infection in himself after placing larvae on the skin
of his forearm
1905 S. fuelleborni was described as a parasite of monkeys and apes
1911 Fülleborn showed using dogs with a tracheotomy or oesophagostomy that the
majority of migrating filariform larvae followed the tracheo-oesophageal route
described for hookworm by Looss
1911 Gage found filariform larvae in the sputum of a human
1919 Thira produced patent infections by rectal administration of filariform larvae,
thus supporting the possibility of internal autoinfection

1925 Larvae were found in duodenal fluid obtained with a duodenal tube
1926 Fülleborn suggested that external autoinfection may occur when rhabditiform
larvae develop into filariform larvae in the perianal folds, described the
frequent occurrence of urticaria in infected patients, and described a skin test
for the diagnosis of strongyloidiasis
1932 Kreis and Faust claimed (erroneously) to have found male adult parasitic
worms
1932 S. fuelleborni was described by Blackie as a parasite of humans
1945+ Disseminated infections in immunosuppressed persons became increasingly
recognized
1957 Dithiazinine iodide was reported to be an effective treatment by MacCowen
and colleagues but was subsequently withdrawn following fatal reactions
1962 Thiabendazole was reported to cure patients with strongyloidiasis by Vitela
and coworkers
1976 Martirani and Rodrigues reported that cambendazole cured patients with
strongyloidiasis but the drug was subsequently withdrawn
___________________________________________________________________
Chapter 22
Trichinella spiralis and TRICHINOSIS
SYNOPSIS
Common name: fleshworm

Major synonym: Trichina spiralis
Distribution: worldwide except Oceania
Life Cycle: When infective larvae in cysts in meat are ingested by a
carnivore, they excyst in the upper small intestine, invade the gut epithelium and
moult four times. The adult worms, 1-2 mm long, produce newborn larvae which
enter the bloodstream and seed the muscles.They penetrate intracellularly, become
surrounded by a cyst wall, and become infective within three weeks
Hosts: most mammals
Major clinical features: fever, diarrhoea, myositis in persons with heavy
infections
Diagnosis: demonstration of larvae in muscle biopsy; serology
Treatment: supportive
DISCOVERY OF THE LARVA
IN HUMANS
In December 1834, Paolo Bianchi, a middle-aged Italian barometer-maker, was

admitted to St. Bartholomew's Hospital in London, England under the care of
Dr George Roupell, lecturer in materia medica. Bianchi complained of loss of
appetite, cough and back pain and was found on examination to be emaciated
and weak and to have an enlarged liver and lower limbs swollen with fluid. His
urine tasted sweet suggesting the presence of sugar and contained large
quantities of protein. Despite supportive treatment with various tonics and
sedatives, a nutritious diet, and the application of leeches, his condition
deteriorated. His abdomen became distended and painful and he died on 29
January 1835 following the passage of bloody, diarrhoeic stools. At
post-mortem examination, tuberculous cavities were found in the upper lobe
of each lung, the liver was enlarged and fatty, the kidneys showed features of
chronic nephritis, and the small intestine was ulcerated92.
When the body was dissected three days after death, an immense number of
minute, whitish specks were observed scattered throughout the muscles. Such
a condition had come to the attention of the demonstrator of anatomy, Thomas
Wormald, on a number of occasions previously, sometimes as a result of the
571
gritty nature of the specks leading to rapid blunting of the scalpels. These
specks had been regarded as bone spicules in the muscles, or else were thought
to be caused by deposition of earthy matter.
In the dissecting room at the time was James Paget, a 21 year old first year
medical student. It is uncertain whether Paget himself was the first to observe
the specks in this patient. Certainly, Owen thought so, for he wrote in his paper
printed later that year: "it was observed by Mr. Paget, an intelligent student,
that the muscles presented an uncommon appearance" 76 and also: "Mr.
Paget....first observed the worms in the Italian"74. On the other hand, Paget
himself recalling the events 31 years later wrote: "The report soon ran through
the dissecting room that there was another body with spiculae of bone in the
muscles"80, thus suggesting that another dissector may have first noticed the
abnormality. What is clear, however, is that Paget did not rest content with the
explanation of bony spiculae, or else wished to see them in more detail for
himself, for he examined the specks with a lens and found that they were cysts.
Moreover, almost immediately afterwards, he found that a small worm was
coiled up within nearly every cyst. Being desirous of investigating these
creatures further, he sought a microscope with which to them examine them
more closely. Unfortunately, no such instrument was to be found in the hospital
at that time, so he repaired to the only scientist he knew in London, one Mr.
Children, principal keeper of the natural history collection at the British
Museum. Children had no microscope either, so he took Paget to the celebrated
botanist, Robert Brown. Paget himself has recounted what then happened:
I remember that when Mr. Children entered his room, he said 'Brown, do you know
anything about intestinal worms?' and answer was, 'No, thank heaven - nothing
whatever.' Mr. Brown at once lent me his simple dissecting microscope, with which
I soon observed structures within the worm which were before invisible. He
dexterously pulled a worm from a cyst, and I believe I still possess my sketch of it.80
Thus began a saga which has remained a subject of interest, controversy, and
at times, acrimonious debate, even to the present day.
A number of factors must have contributed to the successful outcome of
Paget's tenacious search. He was clearly of an energetic nature and enquiring
mind. There is no doubt as to his intellectual ability for he won the prizes in
medicine, surgery, chemistry and botany in 1835. Finally, he was well-
acquainted with the biological world, for despite his youth, he had already
published together with his brother Charles a book on the natural history of
Yarmouth. Paget himself attributed his success to the fact that he "looked-at"
and "observed" the specks rather than merely "saw" them as others, both
teachers and fellow-students, had done83.
As the discoverer of the entozoon, Paget was invited to communicate his
findings to the Abernethian Society which was the medical students' society at
St. Bartholomew's Hospital. This he did on 6 February 1835 with Dr. Arthur
Farre in the chair, the salient features being recorded in the Minute Book of the
Society101. Paget's presentation met with sufficient approbation that he was
Trichinosis 573
encouraged by Edward Stanley, lecturer in anatomy and physiology at St.

Bartholomew's Hospital, to submit a manuscript describing the discovery to the
London Medical Gazette. Such a report headed "Description of a peculiar
animalcule observed in human muscle"81,82 was duly written, together with an
introductory note, dated 10 February 1835, to the Gazette's editor. Paget
described the appearances of elliptical cysts with pointed ends 1/40 of an inch
in length and the entrapped, spirally-coiled worms 1/25 of an inch long. He
noted that the parasites were rounded bluntly at both ends but tapered towards
the end that appeared to be the head, and believed that they possessed an
intestinal canal. Paget considered that the genus to which the entozoon most
closely approached was that of the roundworm, Capsularia, described by
Zeder110 . But the paper was never sent and it was to remain unpublished for
nearly 150 years until it was printed in 197882 and again in 197981. It was at that
point in 1835 that the story began to go awry.
Instead, it was left to Richard Owen, 30 years of age and lecturer in compar-
ative anatomy at St. Bartholomew's Hospital, to publicize the discovery, name
the worm, and become immortalized in print. On the evening of 24 February
1835, Owen presented a paper entitled "Description of a microscopic entozoon
infesting the muscles of the human body"75 to the Zoological Society of London
and demonstrated the parasite with the aid of a microscope belonging to Mr
Prichard. This presentation was published with minor variations not fewer than
four times in the ensuing year; it was written twice in the first person76,77 and
twice ostensibly as third person reports but undoubtedly written by Owen74,75
Owen had some trouble classifying the parasite, but finally admitted it to the
Class Entozoa of Rudolphi, created a new genus, Trichina, from the Greek
(THRIX) [combining form - (TRICH-)] meaning "hair", and gave
it the specific designation "spiralis" to indicate its spiral form. The terms
"trichinosis" or, occasionally, "trichiniasis" were therefore used to denote the
disease caused by the organism. In 1896, Railliet86 altered the generic name to
Trichinella since the name Trichina had been employed for a genus of the
Diptera (flies) in 1830. Although the disease might therefore more correctly be
called "trichinellosis", "trichinosis" is entrenched in the literature and is
hallowed by tradition.
Since Paget had not only discovered the worm but had prepared an account
for publication, it is almost incredible to find that it was Owen who provided
the definitive report. Given that this happened, however, one then turns to
Owen's text for due and explicit acknowledgement of Paget's role. The best that
can be said for Owen is that he obscured the truth by a masterpiece of
dissembling. In one version published in April 183574,75, Paget's name was
sandwiched between those of Wormald and Farr, with the comment being made
that Wormald had previously seen them a number of times (thus implying that
Paget's finding was not out of the ordinary) and Farr being praised as one "who
has paid much attention to the subject"75. Concerning Paget, it was merely said
that:
(the specks) having been again remarked....by Mr. Paget, a student of the hospital,
who suspected it to be produced by minute Entozoa. The suspicion was found to be
correct, and Mr. Owen was furnished with portions of the muscle and made the
following observations.75
In the account printed in the following December, Paget is patronized as an
"intelligent student"76 and this time a footnote, the antithesis of clarity, is added:
The existence of the entozoon was at the same time satisfactorily determined by Mr.
Paget with the assistance of Mr. Brown and Mr. John Bennett at the British
Museum.76
The clear implication of this, of course, is that Owen claimed for himself the
priority of independent discovery of the parasite.
Why should Paget have given way to Owen like this? Many years later
(1866), Paget wrote: "The admirable memoir of Professor Owen (was) much
more complete and exact in zoological detail than anything I could have
written"80. This suggestion that Paget was incapable of writing an expert
zoological description does not stand up to critical analysis. When Paget's and
Owen's texts are both examined, the former compares quite favourably with the
latter. Indeed, Paget did not make the two blunders that Owen did when he
called the tail of the worm its head and denied the existence of an alimentary
tract in the parasite. This question has recently been discussed intensively by
Campbell26 who has also published two letters written by Paget soon after the
discovery. In writing on 11 February 1835 to his brother Charles, Paget said:
You will be interested in learning that I have lately discovered a perfectly new
animalcule, infesting in myriads the human muscle, during life....and the account is
to be published either in the Transactions of the Zoological or the Medico-Chirurgical
Society. I do not yet know whether I shall write the description myself, or whether Mr.
Owen, our lecturer on comparative anatomy will do it - I should rather think the latter,
as he having used far more powerful microscopes than I had, has been able to make
out their organization more clearly. Whichever be the case, I have taken care that I
should receive at least some credit for the discovery, though this was not to be had
without some trouble.81,82
In a subsequent letter two weeks later, he added:
I think I have done rightly in not publishing this account for the folln. among many
reasons. It is a subject with which I was PREVIOUSLY entirely unacquainted, and
I might very easily have fallen into error as to the affinity of species - as well as to their
peculiar structures....I should probably have been obliged to send it to some (minor?)
periodical, or the Society at which the description might have been read, would not
have printed it in their earliest transactions, giving preference to papers by members.
Besides the subject....comes so near the marvellous that it required some good name
to authenticate it to prevent its being....utterly disbelieved. You may add perhaps, self
interest, (wh.?) said that it would in the end be best not to stand too far forward, but
I fear not modesty....I am very well contented that in the papers which will probably
be published....I shall be mentioned as the first observer of their existence.81,82
From all of this, Campbell26 has distilled four likely reasons for Paget's actions.
First, despite his explicit denial, modesty seems a strong factor for he was but
Trichinosis 575
a first year medical student embarking on a career in an intensely hierarchical

profession. To this may be added political expediency, for he was a student of
Wormald who, as Paget later indicated "disliked me . . and became the chief
opponent of my progress" 83. Thirdly, it is possible that Paget may have been
embarrassed and frustrated by having no suitable illustrations of the parasite
whereas he could have expected Owen and his illustators to produce masterful
and detailed drawings. Finally, his lack of access to a powerful microscope
made him diffident about describing the structure of the worm in detail. Thus,
Paget was in a position of ethical superiority but political and technical
weakness. Not only did he have his own reasons for yielding to Owen, but the
two of them struck a deal. Owen agreed to give Paget credit in his presentation,
but this accord was gained only with "some trouble" on Paget's part, and as has
been seen, was carried out in the most niggardly and obscurantist fashion by
Owen.
It is little wonder then, that for the next three decades, most writers on this
subject generally referred to Owen as the discover or Trichina spiralis. During
this period, however, the waters were muddied even further. The definitive
discovery of the parasite caused various commentators to attempt to diagnose
in retrospect some of the reports in the earlier literature. Owen and Paget had
done this themselves, for they both referred to the patient recorded in 1833 by
John Hilton, demonstrator in anatomy at Guy's Hospital, London55. Hilton had
described cysts in the muscles of a cadaver but had thought that they were
probably cysticerci. It now seemed probable that they were in fact T. spiralis.
Furthermore, it became apparent that a specimen of sternomastoid muscles
deposited in Guy's Hospital museum in 1828 by its then curator, Mr H
Peacock, also contained cysts of this worm; this finding had never been
published 107.
In a similar vein, a number of German writers led by Henle52 in turn insisted
that these bodies were first seen by F Tiedemann and published in Froriep's
Notizen in 1822. This passage has been translated by Cobbold:
At the post-mortem examination of a man who had been a great brandy drinker and
who died from thoracic dropsy after several severe attacks of gout, Tiedemann found
white stony concretions in most muscles, especially at the extremities. They lay in the
cellular tissues between the fibre-bundles; frequently also attached to (or near) the
walls of the arteries, being from two to four lines long, and roundish. the chemical
examination conducted by Gmelin yielded 73 parts phosphate of lime, 7 parts
carbonate of lime, and 20 parts of animal matter, resembling albumen or fibrin.98
Claims that Tiedemann's concretions were trichinellae were dismissed by
Leuckart on the grounds that they were too big and the work was mostly
concerned with chemical analysis of their nature67. In any event, it is now clear
that whether or not they were trichinellae is irrelevant since they were certainly
not recognized as such by Tiedemann.
It was not until the epidemics of trichinosis in Germany in the 1860's brought
the worm and the affliction that it caused to general attention that interest in the
question of its discovery was rekindled. When a writer in the Pall Mall Gazette
in England indicated that the history of Trichinella "was not yet clearly made
out". Spencer Cobbold thought it his duty to write to The Times to put forth the
facts. This led to a spirited exchange in the columns of both that paper and The
Lancet. This included a letter from Paget himself making plain his view of the
facts80 and a communication from "Two former presidents of the Abernethian
Society"101 who quoted an extract from the Society's minute book of 6 February
1835 which described Paget's talk. Cobbold summed it up by writing in The
Lancet:
In the interests of truth, I rejoice that our knowledge of the circumstances connected
with the discovery of the fleshworm is now complete. The letters....unequivocally
establish Mr Paget's priority in this relation.32
Perhaps not surprisingly, Owen remained uncharacteristically silent publicly
during this period, although he was to comment sixteen years later. It may be
that senility impaired his judgement or his memory when he took up the cudgels
again in the correspondence columns of The Lancet in November 1882, and
once more claimed to be the discoverer of the T. spiralis 78. Indeed, his own
communication did little to advance his cause, for he quoted the note from
Wormald which accompanied the specimen of muscle:
Dear Owen, - I send you some sort of organised being, as I believe, which occupies
the muscle of a subject under dissection at St. B. H., and, as I know you are a keen
hand for parasitical things, from 'crabs' downwards, I send the enclosed for your
inspection.109
Not only does this note imply that it was already known that the specks were
of an animal nature, but the apparent spontaneity of the missive does not square
with Owen's own account in 1835 when Owen declared that he had sought the
material from Wormald. This last letter of Owen's stimulated another exchange
between Cobbold34,35 and Owen79, with the latter's incomprehensible circum-
locution doing nothing to change Cobbold's conviction that Paget had
discovered the parasite.
Paget's discovery and Owen's promulgation of awareness of the parasite
raised many important questions. These included the nature of the organism and
its cyst and its significance for the host. But first it was critical that the initial
observations be validated by finding the same parasite in other people. This
was not long in coming from a number of quarters. In St. Bartholomew's
Hospital itself, a second patient was found to be infected just two weeks after
the initial discovery74 and yet a third patient from that hospital was described
later that year by Farre41. Cases were then reported by Harrison in Ireland,
Knox in Edinburgh and by various observers in continental Europe and in
North America.
Uncertainty surrounded the nature of the cyst enclosing the spiral worm.
Owen thought it was a single layer of host origin, saying: the cyst is
adventitious, foreign to the entozoon and composed of the cellular substances
of the body infested, morbidly altered by the irritation of the worm"76. On the
Trichinosis 577
other hand, a number of investigators including Vogel, Bristowe and Rainey

considered that the cyst was a product of the worm itself, while Hubert
Luschka, professor of anatomy at Tübingen, (in present-day West) Germany,
was of the view that it had two components, an outer coat of fine fibres laid
down by the host, and an inner homogeneous layer derived from the parasite70.
It is only in recent times that it has been shown with the aid of the electron
microscope that the cyst is formed by multiple infoldings of the sarcolemmal
sheath of the muscle fibre38.
Although Owen had described the parasite correctly as a worm, its precise
nature was obscure to the early observers for they had little concept of helminth
life cycles. In particular, it was not at first realized that the parasite living in
muscles was a larva and not an adult worm. Even though Owen was inaccurate
in many aspects of his description of the worm, he was correct in denying the
presence of mature reproductive organs; he thought it possible that the worms
reproduced by a process of gemmation or budding74. Farre in the same year
described a complete digestive tract which convinced him that the worm was
not one of the "simple parenchymatous forms" but approximated the "more
highly organised species of entozoa"41, in particular, the roundworms.
However, Farre identified certain structures as gonads and mistakenly thought
that the encysted worms were sexually mature animals, an error which was
perpetuated by Theodor Bischoff, a prominent anatomist in Heidelberg, (West)
Germany22. Some of these erroneous observations were corrected by Luschka
who demonstrated that what Owen had called the head was in reality the tail,
but the most telling points had been made several years earlier by the German,
Carl von Siebold95, and the Frenchman, Felix Dujardin 40
, who both stated
unequivocally that the encysted trichinella was a juvenile form. Moreover,
those workers were of the view that trichinellae were probably the offspring of
a roundworm that was already known in its adult state by another name.
The stage was about to be set for elucidation of the life cycle of the parasite,
but first it was necessary to have a system in which these events could be
investigated experimentally.
IN ANIMALS
In 1846, Joseph Leidy, a 23 year old American doctor was at home eating a
slice of pork when he noticed some minute specks in the meat which reminded
him of the trichinous spots that he had seen in the muscles of a human cadaver
only a few days previously. When he examined a portion of the flesh under the
microscope, he found that it was teeming with chalky cysts, each containing a
coiled worm; fortunately for him, they had all been killed by cooking62. Leidy
could detect no difference between this parasite and the T. spiralis observed in
human muscle and duly communicated his findings to a meeting of the
Academy of Natural Sciences in Philadelphia. A brief abstract was prepared by
the secretary of the society and was published in its minutes61. Despite its
annotation in a British journal and in a German publication, the implications of
this observation for an understanding of the epidemiology of trichinosis were
not realized. In fact, Diesing in his Systema Helminthum in 1851 classified the
worm found by Leidy as T. affinis 39 on the assumption that T. spiralis was
peculiar to humans.
Trichinellae had in fact been observed in a non-human host a year earlier
than Leidy had seen it. In August 1845, Ernst Herbst had found large numbers
of trichinellae, which corresponded exactly with those described by Owen, in
the voluntary muscles of an old cat. Herbst then extended these observations in
1848 by finding similar worms in the muscles of a dog. Neither of these
discoveries were reported until 185153 by which time, Guret (1849) had
recorded his discovery of trichinellae in a cat48. Subsequently, a wide range of
mammals was found to be infected in nature, and others were shown in the
laboratory to be susceptible to infection with this organism33,37,45.

OF THE ADULT WORMS
EXPERIMENTAL TRANSMISSION OF INFECTION
When von Siebold declared in 1844 that trichinellae in human muscle were
larvae, he suggested that they were an intermediate stage awaiting transfer to
another host95. This idea followed naturally from the recent publication by
Steenstrup of his theory of the alternation of generations (see chapter 2).
Nevertheless, von Siebold could see difficulties with this postulate; in the
current state of civilisation, the eating of human flesh was not a common
occurrence, and transmission of the parasite this way must have been rare
indeed. The discovery of trichinellae in pigs, cats and dogs opened the way for
exploration of these ideas and it was Herbst who had the initiative and
perseverance to follow it through.
When Herbst found trichinellae in a cat in 1845, he first attempted to transmit
the infection directly by inserting 30 cysts containing live larvae between the
skin and muscles of another cat. On examination four weeks later, the cysts had
attached to the connective tissues and the muscles, but the encapsulated worms
were dead. The second experiment followed his discovery of trichinellae in a
badger. Herbst had kept this badger in captivity for one and a half years and had
fed it partly on vegetables and partly on the remains of animals that he used in
his work. When the badger died in November 1850, Herbst found a
considerable number of trichinellae in its muscles. This time, he fed the flesh
to three dogs that were six weeks old. One animal was sent to the country and
left free to roam while the other two were retained. Three and a half months
Trichinosis 579
later, abundant worms were found in the muscles of both dogs. The third dog
was examined one year after eating infected badger meat and multiple
trichinellae were found in a biopsy of one of its muscles. Herbst was convinced
of the source of infection in these dogs and speculated that, in some as yet
undetermined fashion, eggs were liberated in the gut and passed via the
bloodstream to the muscles: "there can be no doubt that their growth in the
aforementioned three dogs had resulted from the intake of badger meat"53.
These findings were greeted with considerable scepticism, principally
because the trichinellae of animals were regarded as being distinct from those
found in humans, but also because Herbst's descriptions of the worm were
inaccurate and it was believed that he may have confounded some other species
of roundworm with trichinellae. A number of years were to pass before similar
experiments were repeated and Herbst's observations were confirmed and
extended.
Three figures - Leuckart, Virchow and Zenker - were to play leading roles in
the next phase of discovery. They each undertook investigations independently
and almost contemporaneously in the mid 1860's. Heller has remarked that it
is not easy to determine the merits of each one from his publications,
particularly as Virchow106 and Zenker112 felt compelled to defend their positions
against Leuckart who was constantly appearing in print with incomplete
notices. The account which follows generally approximates the conclusions that
Heller made after a careful examination of the literature51. To Virchow must go
the credit for first finding the adult worms in the intestines, while Zenker
hammered into place the final link in the chain of events by explaining how
human infections were acquired. But these achievements only came after a false
start induced by a theory of Friedrich Küchenmeister.
Küchenmeister, who had recently shown that cystic worms, previously
thought to be distinct species, were in reality immature stages of tapeworms,
carefully examined the anatomy of T. spiralis and other nematodes found
commonly in humans. He came to the conclusion that T. spiralis was an
immature form of the intestinal whipworm, Trichocephalus dispar (now
known as Trichuris trichiura). By the same token, Küchenmeister believed it
likely that the trichinellae found in the pig were identical with T. spiralis and,
with a modicum of misguided foresight, thought that humans might possibly
become infected with T. dispar by consumption of pork beset with trichinellae.
Alternatively, he suggested that ingestion of Trichuris eggs by humans might
result in liberation of larvae which then bored through the intestinal wall and
migrated to the muscles where they encysted as T. spiralis 58.
Rudolf Leuckart took up the question and fed T. spiralis cysts to rabbits, cats
and dogs; he searched without success for Trichuris adults that might have
developed from ingested trichinellae. In 1857, however, he reported that when
he had examined the intestinal mucus of mice shortly after ingestion of such
cysts, he had found that the larvae had escaped from their capsules and doubled
in size63 . In 1859, Leuckart fed trichinous flesh to pigs, but on this occasion
waited five weeks before examination of the intestines. He found a dozen
mature Trichuris in the bowel and, in accordance with Küchenmeister's
hypothesis, Leuckart took these to be the sexual form of T. spiralis. He
despatched word of this observation to PJ van Beneden in Louvain, asking him
to communicate these results to the Academy of Sciences in Paris. This van
Beneden undertook to do, but, in translating Leuckart's letter from the German,
inadvertently mistook "duizend" (dozen) for dutzend (thousands), and thus it
was printed on 26 September 185964.
In the meantime, Rudolf Virchow had not been idle. In July 1859, he fed
trichinous meat to a dog; three and a half days later it died. When the intestines
were examined macroscopically at autopsy, the only parasites apparent were
tapeworms. On microscopical examination of the mucus, however, Virchow
found swarms of lively nematodes 1-2 mm long within which he could see eggs
or sperms. These parasites did not resemble Trichuris at all, but in view of
Kuchenmeister's assertions, Virchow merely concluded cautiously that muscle
trichinellae are able to continue their development in the intestinal tract of a
carnivorous animal. Since he was about to leave for Norway, Virchow made
known his results at a meeting of the Berlin Medical Society on 1 August
1859 102 then sent a written account to the Academy of Sciences in Paris.
According to Reinhard88, however, there was difficulty in deciphering his
handwriting and a French version was not published until 7 November 1859103.
His detailed paper followed the next year104
On receipt of this information, and in a true spirit of scientific enquiry,
Leuckart repeated his studies and infected a number of dogs and cats. He found
the fullgrown worms described by Virchow in the intestines of these animals
and, in an exemplary and forthright fashion, Leuckart declared that Virchow
was absolutely right65.
At the same time as Leuckart confirmed Virchow's observations in
experimental animals, Zenker independently found adult worms in the small
intestine of a human111, as will be described later. Zenker sent portions of
trichinous muscles from this person to Leuckart, Luschka and Virchow, and all
four of them began experimental studies using this material.
STUDIES ON THE MIGRATION AND DEVELOPMENT OF LARVAE
When Herbst transmitted experimentally infection from a badger to dogs, he

remarked that:
the greatest difficulty lies in explaining the process by which the very small and very
Trichinosis 581
elastic, but solidly formed particles representing worm eggs have been able to enter
the blood vessels from the intestinal cavity, since the ample, simultaneous, and equal
distribution of the trichinae through all voluntary muscles justifies the assumption that
their eggs have been carried to the respective places of settlement by means of the
blood circulation.53
The discoveries of Virchow, Leuckart and Zenker provided the clue to the
solving of this question. In his series of experiments, Leuckart made two further
important observations. Firstly, he found that in contrast to muscle larvae, adult
worms were mere transients in the bowel. For example, by the twelfth day after
infection, adult worms had moved from the small intestine to the colon prior to
expulsion. Secondly, Leuckart discovered that female adult worms were
viviparous and released minute filariform embryos that immediately penetrated
the intestinal mucosa then passed to the muscles. There, he found that the
worms penetrated the fasciculi and within the space of 14 days acquired the
size and structure of the well-known T. spiralis 66. Unfortunately, Leuckart
blotted his copybook by declaring that it could scarcely be doubted that Man
acquired his trichinellae, like echinococci, from the dog.
Meanwhile, Virchow was independently pursuing his own studies. Initially,
he fed trichinous flesh to rabbits and found that they died five to six weeks later
as a consequence of muscular degeneration. He passaged the worms through
five successive generations and found that the severity of illness and the
likelihood of death was dependent upon the size of the inoculum of infective
larvae. Like Leuckart, Virchow observed that trichinellae were larviparous and
found larvae within seven days of ingestion in the mesenteric glands and the
serous cavities, but he could not find them in the bloodstream. He then studied
the development of larvae and showed for the first time that they were located
not between the muscle fibres, as had been previously thought, but within them.
In addition, he noted that the cyst was first seen four to five weeks after
infection and that the muscle fibres then atrophied105.
Although the development of adult worms in the gut and of infective larvae
in the muscles was fairly well understood, there was considerable doubt as to
the manner in which larvae passed from the gut to the muscles. Leuckart66 held
that the larvae reached the muscles via the connective tissues and, because of
his great authority, this view held sway for many years. Nevertheless, there
were voices of dissent. Virchow105 had found larvae in the mesenteric lymph
nodes, thus suggesting that the worms might find their way into the
bloodstream, although he was not able to prove this point. This view was
supported by Zenker111 and sustained by Fiedler43 who found larvae in the right
heart of experimentally infected rabbits. Final proof that larvae may travel via
the bloodstream was provided by Herrick and Janeway who in 1909 found
newborn larvae in the blood of a woman suffering from trichinosis 54.
Uncertainty has surrounded the relationship between intestinal adult worm
numbers and muscle worm burdens. It has never been defined clearly in
humans how many muscle larvae are produced for each adult worm in the gut
during the course of an infection, but it was eventually shown in

experimentally-infected guinea pigs that approximately 1,300 muscle larvae are
produced per female adult worm91.
Whether or not immunity to reinfection develops in humans has never been
clearly shown, but extrapolation from animal experiments suggests that some
resistance probably develops. It has been shown in such animals that consid-
erable resistance is induced by natural infection71 and after immunization with
Trichinella antigens72. Furthermore, this resistance can be partially transferred
with immune serum36 and with immune lymphoid cells60 and is directed against
both the larval stages in the muscles as well as against the worms in the
intestines29.
In his discussion of the two patients who were found to be infected in the St.
Bartholomew's Hospital dissecting room in 1835, Owen remarked that al-
though there were vast numbers of parasites in the voluntary muscles, neither
person had any symptoms referable to the muscular system. He concluded that
"it is not improbable that in all cases the patient himself will be unconscious of
the microscopic parasites which are enjoying their vitality at his expense"76.
Paget, on the other hand, was more cautious, noting in his private letter to his
brother Charles on 11 February 1835 that "their immense numbers may prove
important when more cases have been found and compared, so as to see
whether they accompany any particular illness"81.
Publication of Owen's paper induced Henry Wood, a practitioner in Bristol,
England to challenge Owen's view and describe a patient who in retrospect may
well have had symptomatic trichinosis. A 22 year old man had been admitted
to the local infirmary in October of the previous year with "acute rheumatism"
of the trunk and extremities. He died a few days later and post-mortem
examination disclosed pneumonia, pericarditis and multiple punctate lesions
in the muscles. Despite observing the latter with a microscope, Wood was
unable to make out their nature. When he read Owen's paper, however, Wood
wondered whether the patient had had trichinosis. He therefore suggested that
it may "be well to ascertain....(if) there was any symptom or inflammation of
any kind in the muscular system"108 in retrospect in patients in whom
trichinellae were found at autopsy.
Nevertheless, Wood's was a voice crying in the wilderness and Farre in 1850
expressed the consensus of opinion when he wrote that trichinellae:
have been found equally in the diseased and in the healthy; in those who have died
from chronic diseases attended by atrophy; and in those who have been cut off in
robust health by some violent accident. No symptoms have been in any case
manifested during life which could lead to the supposition of their existence; and in
all cases, the individuals themselves appear to have been unaware of their presence.42
Trichinosis 583
All this changed dramatically at the beginning of 1860. On 12 January of that

year, a 20 year old servant girl was admitted to hospital in Dresden, (East)
Germany under the care of Dr Walther. She had become ill two weeks
previously when she complained of great fatigue, thirst and painful abdominal
distension. Despite the absence of splenomegaly, a provisional diagnosis of
typhoid fever was made whereupon she suddenly developed severe pains in,
and marked swelling of, the muscles which prevented her from flexing her
knees or elbows. This was followed by the appearance of pulmonary symptoms,
thought to be consistent with a diagnosis of typhoid fever, and she died on 27
January. Prior to formal autopsy, samples of her muscles were examined by
Friedrich Zenker who was particularly interested at that time in the pathological
changes occurring in muscles during typhoid fever. He was astounded to find
in his first glance at the first microscopical preparation, dozens of unencysted
trichinellae lying free in the muscle parenchyma. Further examination showed
that all the muscles were permeated in this way by massive numbers of worms.
Moreover, the muscle fibres were extensively degenerated. On complete
post-mortem examination, nothing could be found to substantiate a diagnosis
of typhoid fever, the only other discernible abnormalities being
bronchopneumonia and intestinal inflammation. Zenker was in no doubt that
the patient had died from a trichinous invasion of the musculature 111.
Not only did Zenker demonstrate the potential clinical importance of
trichinosis, but this patient also enabled him to make some important con-
tributions to the understanding of the zoology, pathogenesis and epidemiology
of this infection. Firstly, on careful examination of the musculature, he found
some larvae that were smaller in size but similar in form to the usual trich-
inellae; this observation led him to conclude rightly that they were embryos
infiltrating the muscles, probably reaching that site via the bloodstream.
Secondly, he had put aside a portion of intestinal mucus obtained at autopsy;
when he examined a sample of this material two weeks later, he found, again
in the first drop, abundant sexually mature worms that were identical with those
described shortly before by Virchow. This was the first time that adult worms
were found in a human. Thirdly, as will be described later, Zenker ascertained
the source of infection in this patient.
Zenker's discovery was followed by reports of a number of epidemics of
trichinosis, as will be recounted later. It was rapidly accepted that the severity
of the clinical manifestions was dependent upon the intensity of the dose of
infective larvae30. One study later calculated that patients with <100 larvae per
gram of muscle were likely to be asymptomatic whereas severe clinical mani-
festations was probable if there were >1,000 larvae per gram49. Only the most
heavily infected persons died and these often developed features of pneumonia,
myocarditis, encephalitis and renal damage in addition to the usual
gastrointestinal and muscle disturbances23. Recovery in the survivors was rarely
followed by any permanent sequelae, most patients feeling well within several
months21. This was despite the continuing presence of infective larvae in the
muscles which may remain viable for many years. For example, calcified,
encysted trichinellae were found at autopsy in the muscles of a man who had
died in the Vienna Krankenhaus (Hospital). Enquiry revealed that 26 years
previously he had suffered from a severe attack of "rheumatism" that had kept
him confined to bed for several months. When these cysts were fed to rabbits,
trichinellae developed in the gut and muscles100.
It was soon realized that a diagnosis of trichinosis could be suspected on

clinical grounds in a patient who had features resembling those of typhoid fever
except that a rash and splenomegaly were replaced by severe muscle pain and
swelling. Nevertheless, confirmation of the diagnosis depended upon
demonstration of the parasite. There were a number of ways in which this could
be done. Firstly, trichinellae could be sought in the faeces. This had been
successfully achieved by Zenker and Waldeck by 1862113, but subsequent
experience showed that it was an unsatisfactory method because such worms
were few in number and were present only early in the illness. An alternative
approach was to demonstrate larvae in muscle biopsies. This was suggested by
Küchenmeister in 186159, then the value of the technique was proven in the
following year by Friedreich of Heidelberg, (West) Germany, who found
parasites in a fragment of muscle taken from a butcher44. This has remained the
method of choice for the diagnosis of trichinosis to the present day, although it
suffers from the twin disadvantages of necessitating the subjection of a patient
to a biopsy and the probability of finding a worm being dependent upon the size
of the specimen removed and the intensity of infection. Using this technique,
it has been claimed that a T. spiralis cyst was found in an intercostal muscle of
a 3,200 year old Egyptian mummy buried in the Valley of the Kings across the
river Nile from Luxor24.
The third method depends upon observing larvae in the peripheral blood.
This was first achieved in 1909 by Herrick and Janeway54 who investigated a
small family outbreak of trichinosis. A mother and seven of her children ate
contaminated pork chops on 24 February of that year; larvae were found in the
blood of the mother 23 and 25 days later but not in the children's blood. This
diagnostic method became popular and successful in the early part of this
century. For example, Salzer94 claimed that he had found T. spiralis larvae in
the blood of 9 out of 14 patients. Nevertheless, this method of diagnosis has
fallen out of favour and is rarely mentioned in modern textbooks. Finally, larvae
have been found in the cerebrospinal fluid16,68, but this is not a standard
diagnostic technique.
Another laboratory investigation which may point towards the diagnosis of
Trichinosis 585
trichinosis is the appearance of an increased number of eosinophils in the

blood. This was first observed in 1896 by Thomas R Brown, a medical student
at Johns Hopkins University, Baltimore, USA, who found a marked eosino-
philia in a 23 year old man six or seven weeks after the onset of the symptoms
of trichinosis25. Although much has been made of this observation by a number
of American writers, it is of limited diagnostic value since eosinophilia is
common in other tissue helminth infections as well as a in variety of unrelated
conditions.
Greater diagnostic specificity was sought by employment of immuno-
diagnostic techniques. Ströbel in 1911 was the first to investigate these
possibilities. He prepared an extract of Trichinella antigen from trichinous
meat after digestion of the muscle fibres with pepsin and hydrochloric acid.
Although alcoholic extracts of this material were not promising, caustic soda
and antiformin extracts yielded antigens which gave positive complement
fixation reactions with sera from infected humans and experimental animals97.
Bachman introduced an improved antigen with which he was able to demon-
strate the presence of precipitating antibodies in the serum of experi-
mentally-infected rabbits and guinea pigs, as well as the induction of delayed
hypersensitivity reactions after intradermal injection of antigen into these
animals19,20. This was followed by the demonstration that such antibodies could
be found in the serum and that similar skin reactions occurred in humans with
trichinosis18. Despite refining of techniques, immunological tests have remained
of limited value as they are not able to differentiate between recent and
long-standing infections17, nor are they able to quantify the intensity of
infection.
The initial attempts to treat trichinosis were directed towards accelerating

expulsion of the adult worms from the intestines. Logically enough, the effects
of various purgatives such as calomel, turpentine and Glauber's salts were
tried 30,37. Professor Mosler of Giessen, (West) Germany in 1864 convinced
himself that:
benzine is of all the remedies the best anthelmintic and that it may be taken by man
in large doses....it destroys the trichinae in the intestines and thereby prevents the
spread of their embryos; that it is therefore the only rational remedy which can be
employed in trichina disease in man.73
The concept was rational enough, but the approach was scarcely feasible in the
vast majority of instances since the diagnosis was rarely made before the adult
worms in the gut had done their damage seeding the muscles and then been
largely expelled. Indeed, this is a problem which has bedevilled the
anthelmintic therapy of trichinosis to the present day. A multitude of
anthelmintic drugs were tried in trichinosis but were found to be uniformly
unsuccessful until Campbell and Cuckler in the early 1960's showed that the
new benzimidazole, thiabendazole, eliminated intestinal worms and killed many
muscle larvae in infected pigs27,28. This drug was then used on an infected
woman who, whether coincidentally or not, improved96. Nevertheless, a
controlled trial of thiabendazole in human trichinosis does not appear to have
been done. In any case, it is doubtful whether any agent effective against muscle
larvae will be of much benefit as much of the damage will already have been
done before the diagnosis is made and treatment instituted85.
An alternative approach was tried by Salzer in 1916 who gave serum from
previously infected persons to two patients; he claimed that this procedure
produced a fall in temperature and in the level of eosinophilia 94. This was
followed by experimental studies in trichinous animals50, but immunological
treatment has not found a place in the management of trichinosis. The
realization that the inflammatory reaction around muscle larvae was responsible
for producing many of the ill effects of trichinosis led to trial of ACTH69 and
corticosteroids 90 in the alleviation of symptoms. Although some success was
claimed at first, the value of such therapy is probably small, particularly as it
may inhibit immunological expulsion of worms from the gut and thus lead to
even greater numbers of muscle larvae. This could probably be overcome by
the simultaneous administration of thiabendazole, but the value of such a
regimen remains to be proven.
When Zenker found mature worms in the intestines of his patient, he realized
that trichinellae go through their whole cycle of development in one and the
same host. He reasoned, therefore, that infection was likely to have been
acquired by consumption of trichinous meat. Consequently, he went to the
nearby village of Plauen, (East) Germany where the dead woman had come
from and interviewed the owner of the estate. The farmer indicated that he had
ordered a pig to be slaughtered on 21 December but could not say whether the
servant girl had eaten any raw meat, although he was aware that she was fond
of picking at food. Further enquiry revealed that the owner of the estate and the
housekeeper had both been ill with an abdominal complaint in early January
and the the butcher had been extremely ill, being confined to his bed for three
weeks with fever and a paralysing weakness. Fortunately, some of the original
ham was still available and on microscopical examination of it, Zenker found
numerous encysted T. spiralis larvae111. Thus, it became clear that humans
were infected by eating trichinous pork and that infection presumably passed
from pig to pig by consumption of trichinous scraps.
Sporadic cases of illness or death attributed to trichinosis were reported
following Zenker's detailed description and a mild epidemic was recognized in
Trichinosis 587
Plauen in 1862, but it was not until 1863 that the full import of trichinosis
impressed itself upon the minds of both the medical profession and the public
at large. In October of that year, an outbreak of trichinosis occurred in
Hettstadt, a small town of about 6,000 inhabitants near the Hartz mountains in
(East) Germany. Just over 100 people attended a dinner in a hotel in the town
in order to celebrate the fiftieth anniversary of the battle of Leipzig. Included
on the menu were Röstwurst und Gemüse (roast sausages and vegetables). The
Röstwurst had been ordered from the butcher a number of days previously in
order that it could be properly smoked. The butcher went to a neighbour and
bought a pig from his steward. Unfortunately, the steward sold a sickly pig
contrary to his employer's instructions. The pig was duly killed and the pork
worked into sausages which were then smoked and delivered to the hotel where
they were in turn fried and served to the guests at the dinner table. On the
following day, several persons who had been at the dinner were attacked with
diarrhoea, abdominal discomfort, prostration and fever. The number of persons
so afflicted rapidly increased and there was great alarm and apprehension that
an epidemic of typhoid fever was impending. When some of the patients
developed pneumonia and evidence of muscle inflammation, Zenker's report
was remembered. The remnants of the sausages were examined
microscopically and found to be swarming with encapsulated trichinellae.
Muscle biopsies were taken from several of the victims and larvae of T. spiralis
were found in all stages of development. Most of the diners became ill and over
20% of them died. A number of others in the town were also infected with this
pork; eventually nearly 150 became ill and 28 persons died, the diagnosis of
trichinosis being confirmed at autopsy1,3.
Awful though this was, even worse was to befall the town of Hedersleben in
Germany two years later in 1865. In this small village of 2,100 people, 398
persons, most of them young, fell ill and 102 of them died4,8,57. A visitor to the
town soon afterwards has described the scene, saying that:
the place was almost deserted, the manufactory closed, and that 90 orphans were
weeping over the graves of their parents. Upwards of 200 convalescents were
wandering about without work, and bearing in their features traces of the fearful
malady.8
The background to this outbreak has been recorded most graphically:
All this havoc has been caused by one trichinous pig! The butcher, having recognised
the abnormal appearance of the meat of this pig, had carefully disguised it by mixing
it with the meat of two healthy pigs, or added it in small pieces to larger joints of pork
to make up weight. He made this confession shortly before his death, which was
caused by trichinosis contracted from his own meat. His wife also died of the disease.8
Following the outbreak of trichinosis in Hedersleben, a review was made of
the epidemic which had occurred in 1849 in Wegeleben, a community located
about half a mile away, in which 160 persons had been affected and 30 had
died. Biopsies of muscles from some of these people who were still alive
showed that that epidemic had also been caused by T. spiralis 93. A number of
other epidemics in various parts of Europe were also diagnosed in retrospect,

although with much less certainty.
In the wake of the outbreak of trichinosis at Hedersleben, Professors Delpech
and Reynal of France were charged with studying trichinosis in Germany. In the
following year, they presented their pioneering report in which it was
concluded that every clinical case had been caused by eating imperfectly
cooked pork7. The prevalence of infection in humans was investigated in
Leipzig, (East) Germany where 6 in every 100 persons coming to autopsy were
found to be infected. In places where infection was common, such as Dresden,
(East) Germany and Vienna, Austria, rats inhabiting the slaughterhouses were
often infected with T. spiralis. Similar studies in France by the same observers
found little evidence of trichinosis, and the Englishman, Cobbold,
self-righteously observed that trichinosis was most prevalent in Germany
because "the otherwise abstemious inhabitants of the Fatherland display a
remarkable fondness for chopped pork"30. Indeed, the use of raw meat had
become very common in Prussia and Saxony because workmen, having no
means of cooking or else not taking the trouble to do so, found it more
convenient to eat raw, minced pork6.
Despite the institution of control measures, there were 13 major epidemics
of trichinosis in Saxony alone between 1860 and 1876 with 1,266 people being
afflicted12. Similar epidemics have since been noted in many other parts of the
world, but with improving public health control measures and agricultural
methods, they have declined in both frequency and severity.
The recognition that humans became infected with T. spiralis by consumption

of contaminated meat, especially pork, caused some to look backwards and
seen the Mosaic interdiction (Leviticus 11: 7, Authorised Version), "and the
swine, though he divide the hoof and be clovenfooted, yet he cheweth not the
cud, he is unclean to you", as evidence that the Israelites recognized the
relationship between trichinosis and swine. It seems more likely, however, that
if they were able to connect pigs and human illness at all, then the tapeworm,
Taenia solium, was responsible as this parasite is at least visible macro-
scopically. The Mosaic prohibition was perpetuated in Islamic law and has
undoubtedly serendipitously prevented many Muslims from being infected with
T. spiralis.
Understanding of the mode of transmission opened up means for the pre-
vention of infection. The prevalence of infection in both animals and humans
needed to be ascertained, methods had to be found for the destruction of muscle
larvae, then appropriate measures had to be encouraged and, if necessary,
policed. In many places, public health policy and political considerations
Trichinosis 589
became inextricably linked.

However, not everyone believed that trichinosis was a serious problem. A
Prussian ministerial journal asserted that "trichina-disease" was nothing but a
revolutionary proceeding propagated by the enemies of the government 6. In
another incident, Virchow addressed a meeting of town councillors, butchers,
doctors and a sprinkling of the general public shortly before Christmas 1865
on the prevention of trichinosis. At the conclusion of his speech, he handed to
the president of the meeting a piece of smoked sausage and a piece of meat
from a pig which had been recognized as trichinous. What happened next has
been recorded in The Lancet:
Thereupon a veterinary practitioner, of the name of Urban, rose and combated all that
science had acquired during the last five years as an unfounded illusion. 'Trichinae',
he said, 'are the most harmless animals in the world. It is only the doctors without
practice who make a noise about them in order to create some occupation for
themselves.' &c. (Great interruption; the president is obliged to stop the veterinarian).
Drs. Virchow and Mason demand an apology from M. Urban. Dr. Mason challenges
Urban to eat some of the sausage on the President's table (Great applause). Urban
wishes to explain. The meeting calls upon him to eat. 'He had not spoken of Berlin
doctors (Eat! Eat!); but of those at Hedersleben (Eat!). He would first see if the
sausage contained trichinae.' (Great laughter and continued shouts of Eat! eat! eat!).
Whereupon M. Urban suddenly seizes the sausage on the president's table, bites off
a piece and eats it, and leaves the hall forthwith, amidst the applause and laughter of
the assembly. About five days later (on 23 December), the Oelkszeitung reported that
the veterinarian, Urban, was ill. He was confined to his bed and his arms and legs
were paralysed. A hope was expressed that the illness was not caused by trichinae in
the sausage of which he had been badgered to swallow a piece. Vain hope!"8
It appeared at that time that the prevention of trichinosis was founded upon
two practical propositions - recognition of infected meat and the cooking of
pork sufficiently well to kill the worms. Prof. Kuhne of Halle in (East) Germany
had shown in his report to the Prussian government that it was frequently not
possible to recognize a trichinous pig9. The (undoubtedly apochryphal) story
has been told about how a Holstein peasant solved this problem. When he
killed a pig, he was careful to send a portion of it - ham or sausage - to his
pastor then await the consequences for 14 days. If the pastor remained healthy,
then he felt perfectly easy in his mind and, assured that the pork was fit to eat,
thereupon disposed of it amongst his own family13. This technique not being
generally applicable, the butchers of Berlin, finding that the trade was almost
extinguished, voted 200 to 9 in December 1865 to make arrangements for
microscopical examination of all pork and petitioned the municipality to make
such examinations obligatory upon them all8.
This was done in many parts of Germany and between 1864 and 1874, 623
infected pigs were found and withdrawn before human infection could occur11.
Eventually, thorough microscopical examination by government inspectors of
pork products for sale was commonplace throughout Germany, with any such
products found to be infected being confiscated. This was done by compressing
fragments of meat between two plates of glass and searching for parasites with
the aid of a magnifying glass or the low power lens of a microscope. In one
instance, the Supreme Court of Prussia found a butcher guilty of manslaughter
because he sold trichinous meat which caused the death of a person, the meat
not having been examined microscopically 11.
There were some, however, who remained sceptical. Reinhard88, for example,
believed that not only was microscopical examination inaccurate, but that the
frequency of trichinosis in swine was so small as to not justify the effort made
at its detection. A vivid demonstration that microscopical examination could
not be relied upon occurred at Emersleben in Germany in 1883. In September
of that year, a butcher bought a pig, killed it on the 12th and sold its flesh from
the 13-19th of that month. Out of a population of 700 persons, 250 were
attacked and 42 died. Although incompetent, there is little doubt that the
inspector, a barber, acted in good faith for both he and the butcher partook of
the infected meat and suffered in consequence 15.
In the 1870's, it became apparent, following several epidemics of trichinosis
in humans and the demonstration that 3-16% of the pigs in Indiana were
infected, that trichinosis was not uncommon in the United States of America10.
Much of this pork was exported to Europe in the form of hams and sides of
bacon. Despite being strongly salted and dried, some worms remained viable
as was indicated by the outbreak of trichinosis which occurred in Bremen,
(West) Germany, after consumption of sides of imported American pork. In
1879, ordinances were passed in Austria, Hungary and Italy prohibiting the
importation of porcine products from the United States, then a similar decree
was proclaimed in the following year in Germany, Norway, Portugal and Spain.
By the end of the decade, the majority of European countries forbade the
importation of American pork. The economic consequences of these actions
were such that the United States Congress in 1890 passed an act requiring
microscopical examination of all pork destined for export. Between 1896 and
1906, more than 8 million carcasses were examined and 1.4% were eliminated
as being trichinous 46. On subsequent examination of the remaining certified
pork, German inspectors found that another 1% were still infected.
Consequently, Germany reinstated the prohibition which had been repealed in
1890 on the initiation of testing.
Extensive post-mortem surveys were undertaken in the USA to define the
prevalence of infection in humans and in swine. Sixteen per cent of 11,000
human cadavers examined between 1931 and 1942 were infected. Studies of
swine showed that the frequency of pigs infected with this parasite depended
upon the method of feeding them; those fed on cooked garbage or allowed to
forage in the open fields and woods, 0.5%; those fed principally on grain,
1-1.5%; those given uncooked garbage, 4-6%; and those permitted to feed on
slaughter-house offal, 10-20% 46. In 1952, a severe epidemic of vesicular
exanthema, a viral infection of swine, broke out which led to legislation
requiring that pigs grown for commercial use be fed cooked garbage or grain.
Trichinosis 591
This resulted parenthetically in the prevalence of trichinosis in the pigs falling

from 0.95% in the 1930's to 0.12% in 1961-5 114, and in humans from 16% to
4% in 1966-8 115.
The other feasible prophylactic measure was proper preparation of meat to
ensure destruction of larvae. Salting was found to often render meat innocuous,
but this was unreliable since the time necessary to achieve killing of larvae was
uncertain and variable14. Similarly, smoking could not be trusted to
decontaminate meat. Cooking by boiling was the most effective method if
continued for long enough but quick roasting leaving the central parts of the
meat red was of little avail. Eventually, it was shown that refrigeration at -15o
C for 20 days was also an effective means of killing larvae87. Finally, irradiation
has been shown to be effective47, but this technique has not found widespread
commercial application.
Despite the marked association between human trichinosis and the con-
sumption of infected pork, other sources of infection have sometimes occurred.
T. spiralis has been found in nearly 60 different species of mammals.
Occasional localized outbreaks of human trichinosis have followed the
consumption of a variety of contaminated meats ranging from polar bear to
white whale, emphasizing that the only sure prophylactic measure is thorough
cooking of all meat before ingestion46.
REFERENCES
1. ANONYMOUS. Recent outbreaks of fleshworm disease, or trichiniasis, in Germany. British

2. ANONYMOUS. Benzine and trichinosis. British Medical Journal ii: 395, 1864
3. ANONYMOUS. The new disease. Lancet i: 100-101, 1864
7. ANONYMOUS. Trichinosis. British Medical Journal i: 375-376, 1866
8. ANONYMOUS. The last new disease. Lancet i: 16, 1866
9. ANONYMOUS. Scientific report on the trichina. Lancet i: 163, 1866
10. ANONYMOUS. Trichinosis. Lancet ii: 843, 1875
11. ANONYMOUS. Trichiniasis. Lancet i: 76, 1876
12. ANONYMOUS. Trichina epidemics. British Medical Journal ii: 492-493, 1877
13. ANONYMOUS. New test for trichinae. British Medical Journal ii: 714, 1880
14. ANONYMOUS. Trichinae. Lancet i: 385, 1881
15. ANONYMOUS. Trichinosis. British Medical Journal i: 118-119, 1884
16. ANONYMOUS. Trichinae in the cerebrospinal fluid. Lancet ii: 240, 1916
17. ANONYMOUS. Laboratory tests for trichiniasis. Lancet ii: 295, 1943
18. AUGUSTINE DL, THEILER H. Precipitin and skin tests as aids in diagnosing trichinosis.
19. BACHMAN GW. A precipitin test in experimental trichiniasis. Journal of Preventive
Medicine 2: 35-48, 1928
20. BACHMAN GW. An intradermal reaction in experimental trichiniasis. Final report. Journal
of Preventive Medicine 2: 513-523, 1928
21. BERCOWITZ Z. Residual symptoms in patients following recovery from acute infestation
with trichinosis. American Journal of Tropical Medicine 20: 849-857, 1940

22. BISCHOFF TL. Ein Fall von Trichina spiralis. Medicinishe Ann., Heidelberg 6: 232-250,
1840
23. BLUMER G. Trichinosis with special reference to changed conceptions of pathology and their
bearing on symptomatology. New England Journal of Medicine 214: 1229-1235, 1936
24. de BONI U, LENCZNER MM, SCOTT JW. Autopsy of an Egyptian mummy - ROM I:
trichinosis. Canadian Medical Association Journal 117: 461-473, 1977
25. BROWN TR. Studies on trichinosis. Johns Hopkins Hospital Bulletin 8: 79-81, 1897
26. CAMPBELL WC. History of trichinosis: Paget, Owen and the discovery of Trichinella
spiralis. Bulletin of the History of Medicine 53: 520-552, 1979
27. CAMPBELL WC, CUCKLER AC. Effect of thiabendazole upon experimental trichinosis in
swine. Proceedings of the Society of Experimental Biology and Medicine 110: 124-128, 1962
28. CAMPBELL WC, CUCKLER AC. Thiabendazole treatment of the invasive phase of
experimental trichinosis in swine. Annals of Tropical Medicine and Parasitology 56: 500-505,
1962
29. CHUTE RM. The dual antibody response to experimental trichinosis. Proceedings of the
Helminthological Society of Washington 23: 49-58, 1956
particularly to internal parasites of man, Groombridge and Sons, London, pp 480, 1864
31. COBBOLD TS. On the discovery of Trichina. Lancet i: 224-225, 1866
32. COBBOLD TS. On the discovery of Trichina. Lancet i: 291, 1866
33. COBBOLD TS. Experiments with Trichina spiralis. Journal of the Linnean Society 9:
205-212, 1867
34. COBBOLD TS. The discovery of Trichina spiralis. Lancet ii: 911, 1882
35. COBBOLD TS. The discovery of Trichina spiralis. Lancet ii: 1056, 1882
36. CULBERTSON JT, KAPLAN SS. A study upon passive immunity in experimental
trichiniasis. Parasitology 30: 156-166, 1938
37. DAVAINE C. Faits et considérations sur la trichine (Pseudalius trichina). Gazette Médicale
de Paris, third series, 18: 58-59, 75-78, 130-131, 174-177, 1863. Abstracted in Lancet i:
424-426, 1863
38. DESPOMMIER DD. Adaptive changes in muscle fibres infected with Trichinella spiralis.
American Journal of Pathology 78: 477-496, 1975
39. DIESING CM. Systema Helminthum, Wilhelmum Braumüller, Vindobonae, two volumes,
pp 1267, 1849-1851
41. FARRE A. Observations on the Trichina spiralis. London Medical Gazette 17: 382-387,
1835
42. FARRE A. Cited in 99
43. FIEDLER CL. Beiträge zur Entwicklungsgeschichte der Trichinen nebst einigen
Mittheilungen über die Einwirkung einzelner Medicamente und anderer Agentien auf
dieselben. Archiv der Heilkunde 5: 1-29, 1864
44. FRIEDREICH N. Ein Beitrag zur Pathologie der Trichinenkrankheit beim Menschen. Archiv
für Anatomie und Physiologie und für klinische Medicin (Virchow) 25: 399-413, 1862
45. FUCHS CJ, PAGENSTECHERHA. Die Trichinen. Nach Versuchen im Auftrage des Gross-
herzoglich Badischen Handelsministeriums ausgeführt am zoologischen Institute in
Heidelberg, W Engelmann, Leipzig, pp 116, 1865
46. GOULD SE. The story of trichinosis. American Journal of Clinical Pathology 55: 2-11, 1971
47. GOULD S E, GOMBERG HJ, BETHELL FH. Control of trichinosis by gamma irradiation
of pork. Journal of the American Medical Association 154: 653-658, 1954
48. GURET. Lehrbuch der pathologische Anatomie der Hausthieren, Berlin, pp 144, 1849
49. HALL MC, COLLINS BJ. Studies in trichinosis. III. The complex clinical picture of
trichinosis and the diagnosis of disease. Public Health Reports 52: 539-551, 1937
50. HALL MC, WIGDOR M. An experimental study of serum therapy in trichinosis. Archives
of Internal Medicine 22: 601-609, 1918
51. HELLER A. In, Cyclopaedia of the Practice of Medicine, H von Ziemssen (editor), volume
Trichinosis 593
3, Chronic infectious diseases, translated by AH Buck, The Sydenham Society, London, pp

615-660, 1875
52. HENLE. Annotation to a German translation of reference 74. Archiv für Anatomie,
Physiologie und wissenschaftliche Medicin, p 228, 1835
53. HERBST M. Beobachtungen über Trichina spiralis. Nachrichten von der Georg-August
Universität, Göttingen. Königliche Gesellschaft der Wissenschaften, pp 260-264, 1851.
Abstracted in Quarterly Journal of Microscopical Science 1: 209-211, 1853. Translated in 56
54. HERRICK WW, JANEWAY TC. Demonstration of the Trichinella spiralis in the circulating
blood in man. Archives of Internal Medicine 3: 263-266, 1909
55. HILTON J. Notes of a peculiar appearance observed in human muscle, probably depending
upon the formation of very small cysticerci. London Medical Gazette 11: 605, 1833
57. KRATZ F. Die Trichinenepidiemie zu Hedersleben, Wilhelm Engelmann, Leipzig, pp 125,
1866
58. KüCHENMEISTER F. Die in und an dem Korper des lebenden Menschen vorkommenden
59. KüCHENMEISTER F. Ueber Trichinen. Deutsche Klinik 13: 367-368, 1861. Abstracted in
60. LARSH JE, GOULSON HT, WEATHERLY NF. Studies on delayed (cellular)
hypersensitivity in mice infected with Trichinella spiralis. I. Transfer of lymph node cells.
Journal of the Elisha Mitchell Society 80: 133-135, 1964
61. LEIDY J. Entozoon in the superficial part of the extensor muscles of the thigh of the hog.
Secretary's abstract. Proceedings of the Academy of Natural Sciences, Philadelphia 3:
107-108, 1846
62. LEIDY J. Remarks on Trichina. Secretary's abstract. Proceedings of the Academy of Natural
Sciences, Philadelphia 10: 9, 1866
63. LEUCKART R. Bericht über die Leistungen in der Naturgeschichte der niedern Thiere
wahrend des Jahres 1856. Archiv für Naturgeschichte 23: 165-272, 1857
64. LEUCKART R. Expériences sur la trichina spiralis (ce ver devient un trichocéphale dans
l'intestin du porc). Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences
49: 453-457, 1859
65. LEUCKART R. Der geschlechtrsreife Zustand der Trichina spiralis. Eine vorlaüfige
Mittheilung. Zeitschrift für rationeile Medicin 8: 259-262, 334-335, 1860. Translated in
66. LEUCKART R. Untersuchungen über Trichina spiralis. Nachrichten von der Georg-August
Universität, Göttingen. Königliche Gesellschaft der Wissenschaften, pp 135-138, 1860.
Translated in Quarterly Journal of Microscopical Science 8: 168-171, 1860
68. LINTZ W. Trichinosis and the cerebrospinal fluid. Journal of the American Medical
Association 66: 1856, 1916
69. LUONGO MA, REID DH, WEISS WW. The effect of ACTH in trichinosis: a clinical and
experimental study. New England Journal of Medicine 245: 757-760, 1951
70. LUSCHKA H. Zur Naturgeschichte der Trichina spiralis. Zeitschrift für wissenschaftliche
Zoologie 3: 69-79, 1851
71. McCOY OR. Immunity of rats to reinfection with Trichinella spiralis. American Journal of
Hygiene 14: 484-494, 1931
72. McCOY OR. Artificial immunization of rats against Trichinella spiralis. American Journal
of Hygiene 21: 200-213, 1935
73. MOSLER. Cited and partly translated in 2
74. OWEN R. Description of a microscopic entozoon infesting the muscles of the human body.
London Medical Gazette 16: 125-127, 1835
Proceedings of the Zoological Society of London, part 3, pp 23-37, 1835. Identical with 74;
very similar to 76, 77
London Medical Gazette 17: 472-478, 1835. Identical with 77; very similar to 74, 75
Transactions of the Zoological Society 1: 315-324, 1835. Identical with 76; very similar to
74, 75
78. OWEN R. The discovery of Trichina spiralis. Lancet ii: 869, 1882
79. OWEN R. The discovery of Trichina spiralis. Lancet ii: 989, 1882
80. PAGET J. On the discovery of Trichina. Lancet i: 269, 1866
81. PAGET J. Cited in 26
84. PAGET S. Memoirs and letters of Sir James Paget, Longmans, Green and Co., London, pp
438, 1901
85. PHILLIPSON RF, KERSHAW WE. The production, deposition and growth of the larvae of
Trichinella spiralis and their significance in the chemotherapy of the infection. Annals of
86. RAILLET A. Quelques rectification à la nomenclature des parasites. Receuil de Médicine
Véterinaire 3: 157-161, 1896
87. RANSOM B H. Effect of refrigeration upon larvae of Trichinella spiralis. Journal of
Agricultural Research 5: 819-854, 1916
88. REINHARD. Statistiche Rückblicke auf die Trichinen-Epidemien im Königreich Sachsen.
Archiv für Heilkunde 18: 241-250, 1877. Abstracted in British Medical Journal ii: 492-493,
1877
89. REINHARD EG. Landmarks of Parasitology. II. Demonstration of the life cycle and
pathogenicity of the spiral threadworm. Experimental Parasitology 7: 108-123, 1958
90. ROSEN E. Cortisone treatment of trichinosis. American Journal of Medical Science 223:
16-19, 1952
91. ROTH H. Experimental studies on the course of trichina infection in guinea pigs. I. The
minimum dose of trichina larvae required to produce infestation of the muscles; with an
account of the productiveness of the female trichina. American Journal of Hygiene 28:
85-103, 1938
92. ROUPELL G. Cited in 76
93. RUPRECHT B. Eine Besuch in Hedersleben. Berliner klinische Wochenschrift 2: 503-507,
1865
94. SALZER BF. A study of an epidemic of 14 cases of trichinosis with cures by serum therapy.
physiologische Pathologie, R Wagner (Editor), Braun Schweig, 2: 641-692, 1844
96. STONE OJ, STONE CT, MULLINS JF. Thiabendazole - probable cure for trichinosis.
Report of a case. Journal of the American Medical Association 187: 536-538, 1964
97. STRöBEL H. Die Serodiagnostik der Trichinosis. Münchener medizinische Wochenschrift
58: 672-674, 1911
98. TIEDEMANN F. In, Froriep's Notizen aus dem Gebiete der Natur und Heilkunde, p 64,
99. TOPHAM J. Notes of interesting cases occurring in medical practice. Lancet i: 45-46, 1850
100. TURNER DF. Trichinosis. Lancet i: 934, 1889
101. TWO FORMER PRESIDENTS OF THE ABERNETHIAN SOCIETY. On the discovery
of Trichina. Lancet i: 270, 1866
102. VIRCHOW R. Futterungverswuch mit Trichina spiralis. Deutsch Klinik 11: 430, 1859
103. VIRCHOW R. Recherches sur le développement de la trichina spiralis (Ce ver devient adulte
dans l'intestin du chien). Comptes Rendus Hebdomadaire des Séances de l'Académie des
Sciences 49: 660-662, 1859
104. VIRCHOW R. Helminthologische Notizen. 3. Ueber Trichina spiralis. Archiv für
Trichinosis 595
pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 18: 330-345,
1860. Abstracted in British and Foreign Medico-Chirurgical Review 26: 515-516, 1860
105. VIRCHOW R. Note sur le Trichina spiralis. Résultat de ses nouvelles expériences. Comptes
Rendus Hebdomadaires des Séances de l'Académie des Sciences 51: 13-16, 1860. Abstracted
in British Medical Journal ii: 563-564, 1860
106. VIRCHOW R. Trichinosis. Archiv für pathologische Anatomie und Physiologie und für
klinische Medicin (Virchow) 32: 332-371, 1865
107. WILKES S. The discovery of trichinae. British Medical Journal i: 190; Lancet i: 269-270,
1866
108. WOOD H. Observations on the Trichina spiralis. London Medical Gazette 16: 190-191,
1835
109. WORMALD T. Cited in 78
110. ZEDER JG. Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer von JAE Goeze mit
Zusätzen und Anmerkungen herausgegeben von J G H Zeder, Siegfried Lebrecht Crusius,
111. ZENKER FA. Ueber die Trichinen-krankheit des Menschen. Archiv für pathologische
Anatomie und Physiologie und für klinische Medicin (Virchow) 18: 561-572, 1860.
Translated in 56
112. ZENKER FA. Beiträge zur Lehre von der Trichinenkrankheit. Deutsche Archiv für klinische
Medizin 1: 90-124, 1866
113. ZENKER, WALDECK. Cited in 59. Abstracted in British Medical Journal ii: 402-403, 1862
114. ZIMMERMANN WJ, BRANDLEY PJ. The current status of trichiniasis in U.S. swine.
Public Health Reports 80: 1061-1066, 1965
115. ZIMMERMANN WJ, STEELE JH, KAGAN IG. The changing status of trichinosis in the
United States. Public Health Reports 83: 957-966, 1968
Table 22.1. Landmarks in trichinosis

___________________________________________________________________
1835 Paget discovered larvae in the muscles of a human and Owen reported the fact
1845 Herbst found larvae in the muscles of a cat but did not report the observation
1846 Leidy observed larvae in pork
1851 Herbst infected dogs by feeding them infected badger flesh
1857 Leuckart observed that cysts hatched larvae in the small intestine of mice
1859 Virchow found adult worms in the small intestine of a dog fed with trichinous
meat
1860 Leuckart confirmed Virchow's discovery and found newborn larvae
1860 Zenker proved that T. spiralis may cause a severe illness in humans, found
adult worms in the small intestine of a human, demonstrated that muscle
larvae were located intracellularly, and connected acquisition of infection with
consumption of uncooked trichinous pork
1863 First major epidemic, with high mortality, of trichinosis recognized in
Hettstadt, Germany
1865 Another major outbreak of trichinosis in Hedersleben, Germany in which 102
persons died
1909 Herrick and Janeway found larvae in the blood
1911 Ströbel described a complement fixation test
1963 Treatment with thiabendazole suggested
___________________________________________________________________
Chapter 23
Wuchereria bancrofti, Brugia species and

FILARIASIS
SYNOPSIS
Common name: filaria causing elephantiasis

Major synonyms:
i. Wuchereria bancrofti: Filaria Bancrofti, Filaria sanguinis hominis, Filaria
nocturna, Wuchereria pacifica
ii. Brugia malayi: Filaria malayi, Wuchereria malayi, microfilaria malayi
iii. B. timori: Timor microfilaria
Distribution:
i. Wuchereria: tropics and subtropics
ii. Brugia: southeast Asia
Life cycle: The thread-like, adult worms, 4-10 cm long, dwell in lymph nodes and
adjacent lymphatic vessels. Microfilariae are produced and released into the
bloodstream; they usually appear in the bloodstream only at a defined time in each
24 hours, a phenomenon which is known as periodicity. When microfilariae are
ingested by appropriate mosquitoes of the genera Aedes, Anopheles, Culex and
Mansonia, they develop over two weeks into infective larvae which pass to the
proboscis and infect the host at the next blood meal. Infective larvae migrate to the
lymphatic system and mature over the next 12 months or so
Definitive host:
i. Wuchereria, periodic B. malayi, and B. timori: humans
ii. subperiodic B. malayi: humans, monkeys
Major clinical features:
i. acute inflammatory filariasis: lymphangitis, epididymitis
ii. chronic obstructive filariasis: lymphoedema, hydrocele, elephantiasis
Diagnosis: demonstration of microfilariae in the peripheral blood
Treatment: diethylcarbamazine
DISCOVERY OF THE MICROFILARIA
In July 1862, an 18 year old man, originally from Havana, Cuba, presented to
a hospital in Paris with a left-sid ed scrotal tumour. A trocar was inserted by the
surgeon, Jean-Nicolas Demarquay and whitish-yellow fluid similar to milk was
aspirated. In August of the following year, the patient returned with a similar
problem on the other side of the scrotum. Demarquay again inserted a trocar,
aspirated some 100 ml of thick, bluish-white fluid, ascertained that the testi s
was normal and demonstrated that the fluid had been located in the tunic a
597
vaginalis. The hydrocele fluid was examined microscopically by one of th e

house surgeons, Dr Lemoine. In addition to the fat globules, pus cells an d
filaments of fibrin, he found many specimens of a parasite:
Attention was drawn above all to a little elongated and cylindrical creature. The
anterior four fifths of the body had almost a uniform diameter: the posterior fifth
became thinner and thinner and terminated in a fine point. This worm had extremely
rapid movement of coiling and uncoiling in its different parts, especially its terminal
extremity. The worm was completely transparent and did not show anything which
resembled the digestive system or the genital system. 73
Samples of the fluid were sent to CJ Davaine for an expert opinion. H e
devoted half an hour to searching vainly for the parasites. Nevertheless, h e
remarked that from a consideration of the drawings that had been made of the
worms and from the description of a ctive movements, it seemed likely that they
were nematodes, or more probably in view of the absence of visible organ s
within the parasite, larvae of a nematode. He added that the only larva l
nematodes which had been observed th us far in humans were those of Trichina
(= Trichinella) spiralis and Filaria (= Dracunculus) medinensis.
Demarquay was disappointed by Davaine's failure to confirm their observ-
ations, but remarked sagely:
If we were mistaken, this fact would thus remain useless; but if, as we think, it
relates a new fact, subsequent observations will not fail to provide all its scientific
value.73
He was also perplexed about the means by which the worms had entered the
body, but with a flash of insight suggested that the whole phenomenon may be
related to the patient having lived in Cuba.
The discovery of these worms by Demarquay and his team heralded little
interest and three years were to pass before they were seen again. In 1866 in
Bahia, Brazil, they were found, this time in the urine, by Otto Wucherer who
was completely unaware of the French discovery. Two years earlier, Wucherer
had been stimulated by a letter from Griesinger in Germany to examine th e
urine of patients with haematuria in order to see if he could find any evidence
of Schistosoma haematobium infection in South America. He looked at speci-
mens from a number of such patients but without success. On 4 August 1866,
Wucherer inspected a clot from some milky urine obtained from a femal e
patient who was under the care of Dr Silva Lima in the Misericordia Hospital.
Using the microscope he saw:
some threadlike worms which were very thin at one end and blunt at the other. In
the blunt end a small point was visible which could not be identified as an opening.
The body was transparent and seemed to contain a granular mass; however, it was
not possible to distinguish its internal structure. 239
Suspecting that these may have been a contaminant, he asked the woman t o
void again into a clean container and onc e more found the helminths. Neverthe-
less, since he had examined the urine of haematuric patients many times an d
never found anything similar on previous occasions, Wucherer attached n o
great importance to this discovery. On 9 October 1866, however, he agai n
Filariasis 599
found similar worms in the urine of another lady with haematuria. Wuchere r
wondered whether they came from the vagina, but this idea was negated when
some time later he found the same parasites in the chylous urine of a man:
They were alive and were making very brisk, wavy motions. They had the diameter
of a white blood corpuscle and their length exceeded that of the latter, 60 or 70
times.239
Wucherer could find no reference to similar parasites in the works of Küchen-
meister, Cobbold or Davaine, but he did not report them as a new species .
According to Manson-Bahr 173, Wucherer sent specimens of the worm preserved
in glycerine to the renowned parasitologist, Leuckart in Leipzig, Germany, but
the latter dismissed them as being of no importance, considering the parasites
to be members of the family Strongylidae.
Wucherer's observations were confirmed several years later by Timoth y
Lewis in India and by Jules Crevaux of the French Navy 65, the worms found by
the latter also being described by Corre 63. In March 1870, Lewis, apparentl y
unaware of Wucherer's discovery, fo und the worms in the chylous urine of a 25
year old East Indian. When he examined the urine, Lewis found delicat e
filaments which he at first thought were fungi. On continued observatio n
though, he saw that they coiled and uncoiled and realized that they wer e
worms131. Subsequently, Lewis found the same worms in somewhere between
15 and 20 patients 132.
As with many other important discoveries in medical helminthology, there
was the odd pretender to the throne. Spencer Co bbold claimed that in July 1870
he had found similar worms in the urine of a South African girl wit h
schistosomiasis. Cobbold did not publish news of this observation until 1872,
when he also asserted that the worms found in the urine of a patient in 1868 by
Salisbury in the United States 207, and which that observer had called Trichina
cystica, were in reality filariae 54. Lewis's co-investigator, Cunningham ,
disposed of this latter instance by showing that the patient was a 55 year ol d
rheumatic woman suffering from cystinuria, not chyluria, and that the parasites
were almost certainly those of Enterobius vermicularis , then expressed the
same view about the worms found in Cobbold's patient 67. Despite these cogent
arguments, they were not accepted by Cobbold 60. Even more remarkable was
the letter by WO Priestly written to the British Medical Journal :
As long ago as 1857, I described a case of chylous urine, in which the milk-like fluid
passed from the bladder was found on microscopical examination to contain
innumerable linear vibrios, or filariae which moved in every direction across the
microscopic field.195
This was demolished summarily and in caustic fashion by a correspondent:
The 'active linear vibrios' common in decomposing fluids....have, of course, nothing
to do with these nematoid filariae; unless, indeed, we adopt very advanced views on
transmutation not of species, but of classes.197
Meanwhile, the original discovery by Demarquay and his colleague s
remained unappreciated. Two authorities, Cobbold and da Silva Lima, in their
historical reviews in 1878 of the discovery of this parasite were ignorant o f
Demarquay's contribution, with the former writing "the larval forms firs t
described by Wucherer" 60 and the latter remarking "Dr Wucherer....the firs t
investigator who proclaimed the existence of a new human entozoan, demon-
strating its embryos in chylous urine" 220. It was not until 1888 that Demarquay's
contribution became widely known when his countryman, Lanceraux i n
Guadeloupe, pointed out with som e acerbity that not Wucherer but Demarquay
had first found the parasite 125.
Two years after Lewis found organisms in chylous urine, he made a much
more important further observation. In July 1872, while examining the blood
of a patient with diarrhoea who was under the care of Dr Chuckerbutty in the
Medical College Hospital in Calcutta, Lewis "observed nine minute Nematoid
worms in a state of great activity, on a single slide" 132. He showed them to his
colleague, Douglas Cunningham, who co ncurred with Lewis's opinion that they
were the same as those that had been seen earlier in chylous urine. On th e
following morning, Lewis went back to the Hospital to review the patient' s
clinical history, but found to his intense disappointment that the patient ha d
discharged himself one hour earlier. All attempts to find him, even invoking the
aid of the police, proved fruitless. Several days later, however, Lewis agai n
found worms in the urine of a woman with haematochyluria. Perhaps burned
by his previous experience, L ewis visited her that same evening. In view of the
subsequent discovery of the nocturnal periodicity, i.e. the transient surge o f
microfilariae into the bloodstream at night after a complete or almost complete
absence during the day, this was undoubtedly a fortuitous event, for "O n
pricking her finger with a needle, and distributing a drop of blood over several
slides, I found that Filariae were present in it also" 132. Lewis kept her under
observation for about two months, and found that although there was littl e
change in her clinical condition and there was only a slight reduction in worms
in the urine, the numbers of worms in the blood diminished markedly (blood
samples were presumably taken during the day):
the numbers obtainable by pricking the fingers or toes certainly decreased and
eventually, out of half a dozen or more slides, not more than one or two
Haematozoa could be detected; on a few occasions several slides were examined
without any being found.132
Shortly afterwards, Lewis encountered a third patient, a 22 year old Eas t
Indian who spent most of his time employed as a cook on a lighter lying in the
mouth of the River Hooghly. Lewis was amazed to find:
that no matter at what portion of his body the circulation is tapped with the point of
a needle, numerous active, well-developed Haematozoa are invariably obtained; on
one occasion I observed as many as 12 of these creatures on a single slide....the
number infesting his whole body may be imagined. 132
Indeed, Lewis calculated that one patient was host to some 140,000 of th e
parasites. Nevertheless, he noted that this was not a common occurrence and
that it was often necessary to examine several of the slides before the parasite
could be found, each slide taking about 15 minutes to complete.
When Lewis went to the Government Printing Es tablishment to examine the
Filariasis 601
galley proof of his report on the discovery of microfilaria in the blood, he was
astounded to find that the man setting up the type was none other than the first
patient in whom he had found microfilaria in the urine. Enquiry revealed that
he was healthy and examination of his blood disclosed the presence of sparse
numbers of worms 132.
Lewis described the morphology of the parasite and discerned the sheath,
indicating that it was an extremely delicate tube closed at both ends, withi n
which the worm was capable of elongating and shortening itself. This feature
led him to surmise that the pa rasite had no means of perforating the tissues and
that its normal habitat was the blood. In addition, he noted a bright spot at the
blunt end of the worm which was suggestive of a mouth.
Lewis's long paper was published as an appendix to the Annual Report for
1871 of the Sanitary Commissioner 132 and was abstracted later in The Lancet 7,
but news of his discovery was first revealed in an annotation in The Lancet of
31 August 1972 5. The same commentator noted that the nature of the worm had
been determined by George Busk , who stated that the helminth belonged to the
genus Filaria of Müller179 and that Busk had also suggested a name for th e
parasite:
A specimen of the embryo of the chylous-urine worm has been submitted to Mr.
Busk, who considers it to be some kind of Filaria; and it may not be inappropriate
to christen the new entozoon 'Filaria sanguinis hominis'.5
The name, of course, meant that the filar ia had been found in human blood. The
name "filaria" was a modern Latin derivative, "filarium" indicating "ball o f
thread", of the Latin word "filum", meaning "thread".
Nematodes and flukes had been found in the blood of molluscs, fish, frogs,
birds, rats and dogs, but this was the first occasion on which multitudes o f
worms had been found in the general circulation of humans, although schisto-
somes had been found in the portal vein and its tributaries by Bilharz in 1851
and it was suspected that Trichinella spiralis larvae might migrate to th e
muscles through the bloodstream. The discovery by Lewis of worms in th e
blood, which he termed haematozoa, caught the imagination of the Englis h
medical world in particular, and became the subject of a multitude of paper s
and letters. An editorial writer in the British Medical Journal remarked:
That organisms so high in the scale as nematoids should be found to swarm as
parasites in this situation is not a little surprising, though it is perhaps still more
astonishing that they should produce such a comparatively trivial amount of
inconvenience.6
Lewis's discovery was confirmed by Sonsino in Egypt on 1 February 1874
while searching for schistosomes in peripheral blood:
I put a drop of blood (from the finger of the boy) under the microscope, placing it
directly under the objective glass, when with astonishment I discovered a living
organism in the midst of haematic globules. The nematoid had the shape of an
Anguillula. It glided amongst the blood globules, which were tossed to and fro by
lively movements.221
Also in 1874, Rowland 206 and then Bancroft22 , both in Australia, foun d
microfilariae in blood, the latter's observation being announced by Cobbold 56

who observed microfilariae in blood sent to him in capillary tubes vi a
Bancroft's old teacher, Dr W Roberts of Manchester, a specialist in urinar y
diseases.
WUCHERERIA BANCROFTI
After Cobbold received a specimen of blood from Joseph Bancroft in Australia,

he wrote to Bancroft suggesting that he look for the adult worms whic h
Cobbold felt must be present in the human body. Cobbold was strengthened in
this belief when he saw an empty egg shell which he interpreted as being the
remnant of the egg from which the filarial larva had come (it is impossible in
retrospect to say what in fact this was). Bancroft took up Cobbold's suggestion
and on 21 December 1876 found an adult worm. Subsequently, he found four
more specimens and wrote to Cobbold on 20 April 1877 of his discovery:
I have laboured very hard to find the parental form of the parasite, and am glad to
tell you that I have now obtained five specimens of the worm. The worm is about
the thickness of a human hair, and is from three to four inches long. By two loops
from the centre of its body it emits the filariae described by Carter in immense
numbers. My first specimen I got on December 21st 1876 in a lymphatic abscess
of the arm. Four others I obtained alive from a hydrocele. 23
Cobbold sent Bancroft's letter together with some explanatory notes to The
Lancet wherein it was published on 14 July 1877. In his letter, Cobbold named
the worm Filaria Bancrofti in honour of Bancroft: "Such Sir, is Dr Bancroft's
account of his 'finds', and from the brief description furnished I propose to call
the adult nematode Filaria Bancrofti.57
Bancroft later described the circumstances surrounding his discovery i n
somewhat more detail:
I opened an abscess in the arm of a youth employed as a butcher. I collected the
matter as usual in a small vessel. As a preliminary enquiry, the blood had to be
inspected for embryonic filariae. This was the second case in which the blood
contained the parasite in question. On examining the matter....a threadlike body
came into view, under the microscope it was without doubt a worm, and embryos
were seen coming out of its body. On March 21, the following year, I tapped a
hydrocele, in an elderly patient with a trochar and cannula. On withdrawing, a lash
of hairlike bodies was caught in the eyes of the instrument. At once suspecting their
real nature, I put them in the hydrocele fluid when they began to move around with
great activity. Embryos in abundance were found in the hydrocele fluid and in the
patient's blood.21
Meanwhile, Bancroft sent the adult filariae to Cobbold who received them
on 28 August 1877. Cobbold found four female worms and multitudes of ova
and larvae which he described in some detail in a paper published on 6 October
Filariasis 603
187758. In this paper, he persisted in an error which he had made previously in

believing that the microfilarial sheath was a commencing ecdysis.
In the previous issue (29 September 1877) of the same journal, Timoth y
Lewis also described his find ing of two adult worms after spending eight hours
searching through scrotal tissue removed at operation from a young man i n
Calcutta by Dr Gayer:
At last, however, whilst teasing a blood clot under a dissecting microscope, my eye
was arrested by white thread-like objects in a state of great activity. These on being
transferred for examination under a higher power, were found to be specimens of
two mature filariae. One of these contained ova, with embryoes identical in
appearance with the free embryoes in the blood. 134
One parasite was clearly a female worm. The other helminth was damaged
and Lewis thought it may have been a fragment of a male worm, but th e
important caudal part was unfortuna tely missing. In contrast to Cobbold, Lewis
recognized that the egg "shell" became the sheath of the microfilaria:
It is....difficult to state whether they are to be considered as freed embryoes or not,
as the egg-'shell' has become so extremely attenuated and translucent as can only
with difficulty be distinguished....It would, however, appear probable that, even
when the embryo acquires worm-like appearances, the envelope is usually not lost
in this species as long as it continues in the blood. 134
Moreover, Lewis emphasized the diagnostic impo rtance of this feature in differ-
entiating these microfilariae from those found in the blood of dogs.
Despite being aware of Cobbold's designation of a similar worm as Filaria
Bancrofti, Lewis retained the name originally applied to the embryo - Filaria
sanguinis hominis - on the grounds that a new name would only lead t o
confusion. Cobbold therefore attached an appendix to his second paper on the
subject of the adult worm:
Since the above was written, Dr Lewis has himself furnished additional means of
identification. His mature Filaria sanguinis hominis and my F. Bancrofti are clearly
the same species....If Lewis's trinomial name for the adult worm be adopted in place
of Filaria Bancrofti, I have personally no objection.58
Subsequently, female adult worms we re found in patients in South America
by da Silva Araujo on 16 October 1877 218 and by dos Santos on 12 November
1877210, then by Manson in Amoy, China in 1881 161.
It was not until 1888 that a complete specimen of a male worm was found.
Brigade-Surgeon Sibthorpe at the Madras General Hospital, India, foun d
worms in an amputated lymph scrotum and sent them off to Alfred Bourne ,
professor of biology in the Presidency College. Bourne found that one of th e
parasites was a male filaria. He published a brief record of the discovery in the
British Medical Journal in 1888 37, then a more detailed descriptio n
incorporating Bourne's written comments was published by Sibthorpe in th e
same journal in the following year 217. Meanwhile, Bourne himself als o
published an extended, illustrated version in an Indian journal 38. Although
Bourne and Sibthorpe claimed that this was the first time the complete mal e
worm was described, Saboia in Bahia, Brazil in 1886 had found two filaria l
parasites in the right side of the heart of a boy who had died from a n
undisclosed illness. It is possible they were immature Dirofilaria immitis,
although de Magalhães 150 sent a copy of this account, including figures, t o
Joseph Bancroft in Brisbane who accepted them as a female and male Filaria
bancrofti, noting that this was the first time in which the male parasite had been
described 21. On the other hand, Daniels considered the parasites distinct ,
giving them quite different dimensions 71.
Several other names apart from Filaria sanguinis hominis and Filaria
bancrofti have been used to describe these parasites. Manson called it Filaria
nocturna in order to distinguish it from the microfilaria which had a diurna l
periodicity (which turned out to be Loa loa)165, and Manson-Bahr proposed the
name Wucheria pacifica for the aperiodic form of the parasite 172. In 1877, da
Silva Araujo called the worm which he found in a lymph scrotum "Wuchereria
Filaria"218, but whether he meant to use "Wuchereria" as a true generic name is
doubtful; more likely he was refer ring to "Wucherer's filaria". In any event, two
years later, da Silva Araujo called the same worm Filaria wuchereri 219. In
1921, Seurat formally separated this pa rasite from the other filarial parasites on
zoological grounds and adopted da Silva Araujo's Wuchereria as the generic
name, the worm henceforth being known as Wuchereria bancrofti 216.
DIFFERENTIATION OF BRUGIA SPECIES
In 1927, Lichtenstein in Bireu ën in the Dutch East Indies (Indonesia) indicated

that filariasis was common in the area but that the microfilariae, although of a
periodic type, were not infective to a variety of culicine mosquitoes 137. In the
following paper in the same journal, SL Brug reported that the microfilaria e
which were present in the blood sa mples, that had been sent to him by Lichten-
stein, were different morphologically from those of W. bancrofti. In contrast to
the latter worm, there were t wo or three nuclei in the tail and the anal pore was
further forward. It was not possible to obtain adult worms because o f
opposition to autopsy examination by the local Muslim population, but Brug
proposed the name Filaria malayi for the parasite 41.
Although it is generally accepted that Brug first proposed the name Filaria
malayi, Sasa211 believes that the credit should be given to Lichtenstein who not
only found the microfilariae, described the essential morphological differences
and reported the unexpected insusceptibility of Culex fatigans (= quinque-
fasciatus), but also wrote that the filaria discovered in Bireuën is hencefort h
named Filaria malayi 137. Parenthetically, it must also be said that in 190 5
Ashburn and Craig described a ca se of filariasis in the Philippines in which the
microfilariae were not only different morphologically from those of W. ban-
crofti, but were also non-periodic; they named this parasite Filaria philip-
pinensis 16. It is quite possible that these worms were B. malayi, a belief which
is supported by Manson-Bahr's statement that he had examined the photo -
Filariasis 605
micrographs in Ashburn and Craig's paper and concluded that it was possible
that they had described microfilaria malayi 172. If this is true, then the correct
name for B. malayi would be Brugia philippinensis.
Be that as it may, microfilariae morphologically indistinguishable fro m
Brug's worm were recognized increasingly in parts of Southeast Asia an d
southern India, beginning with Korke in India 123. The resemblance betwee n
these microfilariae and those of Loa loa led to some speculation that the parent
worm of these microfilariae may resemble the latter worm. In 1939, Poynton
and Hodgkin indicated that they had found similar microfilariae in a Kr a
monkey (Macacus irus)194. In the following year, Rao and Maplestone reported
the recovery of the parent worms of microfilaria malayi from a patient with a
lymphatic cyst on the forearm. The female specimens were quit e
indistinguishable from those of W. bancrofti, but those authors detected some
slightly more substantial differences in the male worms, so they included them
in the genus Wuchereria. Nevertheless, they believed that the morphological
appearance of the microfilariae and their development in different species o f
mosquitoes justified specific status, so they designated the worms Wuchereria
malayi 198. Their views were confirmed soon afterwards by Bonne and hi s
colleagues35, then a more complete description of what was presumed to be W.
malayi was provided by Buckley and Edeson with material recovered from a
monkey47. On the basis of a study of these specimens, Buckley erected a new
genus, Brugia, in honour of Brug, to house B. malayi and two closely related
worms, B. pahangi of cats, dogs and monkeys in Malaysia, and B. patei of dogs
and cats in East Africa 45,46.
In 1955, Buckley and Edeson described Wuchereria pahangi, a parasite of
cats47. As already mentioned, this worm was subsequently renamed Brugia
pahangi by Buckley46. That the parasite was capable of infecting humans was
proven by Edeson and his colleagues in 1960: two volunteers were infected ;
both experienced episodes of lymphangitis and lymphadenitis, then on e
developed microfilaraemia 84 days after inoculation 80.
In the early 1960's, HL David observed that two kinds of microfilariae were
present in the blood of military recruits in what was then Portuguese Timor .
One was microfilaria bancrofti and the other resembled microfilaria malayi. In
1965, David and Edeson published their finding that this latter worm was a
distinct microfilaria which they named Timor microfilaria 72. Eventually,
Partono and his colleagues fed Aedes togoi on people with this microfilaraemia
in a village on Flores, Indonesia, infected Mongolian gerbils with the infective
larvae, then recovered and described the adult worms which they designate d
Brugia timori 190.
In 1971, Ash and Little described Brugia beaveri, a parasite of the
raccoon15. Six human cases of infection in the United States with this or a
closely related parasite have been published, the first being reported b y
Rosenblatt and colleagues 203.
ELUCIDATION OF THE LIFE CYCLE: DISCOVERY OF TH E

MOSQUITO INTERMEDIATE HOST
In 1873, some microfilariae that had been discovered in the blood by Lewi s
were exhibited at a meeting of the Pat hological Society of London. This excited
considerable interest and in the ensuing discussion consideration was given to
the possible life cycle of this parasite. Cobbold, basing his argument upon the
recent demonstration of the role of crustaceans in the transmission o f
Dracunculus medinensis, extrapolated this to conclude that an intermediat e
host was always required for nematodes. While this would prove to be false as
a general rule, it turned out to be true in this particular case. Cobbol d
postulated that either adult worms which produced these forms were normally
present but unnoticed in humans or that they we re the progeny of an adult worm
which had strayed into humans from some carnivorous animal 55. Bastian and
Harley objected to any idea that man could be an intermediate host; they could
not believe that tens of thousands of these worms could get in from the external
environment, so inferred that adult worms must live within the human body 31.
All of these ideas remained mere speculation, however, until Patric k
Manson entered the fray. Manson had practised for eight or nine years in the
Orient and had seen many cases of elephantiasis and lymph scrotum. When he
returned to Britain on furlough in 1875, he acquired both a microscope an d
knowledge of Lewis's discovery. 1876 saw him back in Amoy, China, and he
soon found microfilariae in the blood of a number of patients. He was puzzled
about the fate of these larvae and determined to try to ascertain their destiny.
Since a person might harbour hundreds of thousands of larvae, Manson thought
it most unlikely that they matured withi n the human body, otherwise they would
kill the host and thus prevent transmission to another host. This was clearl y
untenable as it would lead to extermination of the parasite. He postulated that
the larvae must escape from the host, then develop further, either in a
free-living state, or in some intermediate host where they matured befor e
ingestion by another person. Manson dedu ced that the most likely means of exit
was via a blood-sucking insect, so he considered the possible roles of fleas ,
bedbugs, lice, mosquitoes and sandflies. In blissful ignorance of the almos t
world-wide dissemination of mosquitoes, he selected these insects as th e
probable candidates because he thought their geographical distributio n
coincided most closely with t hat of the parasite. In order to test this hypothesis,
he procured some mosquitoes and fed them on 10 August 1877 on the blood
of his gardener, Hin-Lo, who had a marked microfilaraemia, then examine d
their abdominal contents at daily intervals. In an almost banal fashion, Manson
wrote:
I found that my idea was correct, and that the haematozoon which entered the
mosquito a simple, structureless animal, left it, after passing through a series of
hightly interesting metamorphoses, much increased in size, possessing an alimentary
canal, and being otherwise suited for an independent existence. 156
Filariasis 607
Manson's true feelings on that day in 1877 may be guessed better from a
speech which he later gave and which was reported in the Daily Telegraph:
I shall not easily forget the first mosquito I dissected. I tore off its abdomen and
succeeded in expressing the blood the stomach contained. Placing this under the
microscope, I was gratified to find that, so far from killing the filaria, the digestive
juices of the mosquito seemed to have stimulated fresh activity. And now I saw a
curious thing. The little sac or bag enclosing filaria, which hitherto had muzzled
it....was broken through and discarded.169
The bare bones of his find have been recorded in his diary:
Hin-lo brought me four mosquitoes which he had caught this morning in his
mosquito net and which were distended with his blood. I examined them this
morning.
No. 1. Blood corpuscles not distinct....Several cylindrical bodies of a pale grey
colour and distinct outline. These were about the size and might have been embryo
filariae dead.
No. 2. Blood corpuscles also digested and two bodies one of which had a distinct to
and fro movement of the head half of the body and the appearance of ciliary current
at the mouth.
No. 3. and 4. Blood corpuscles distinct - in both live active filariae and in one of
them ten specimens. Different from those in man's blood in being perhaps more
active. Tail not well seen; anterior head loop often very distinct, oral movements
very apparent. Perhaps an oesophagus developing. Double outline and transverse
striation on the integument most distinct.168
In his original paper, Manson noted that the mosquitoes took only a minute
or two to become engorged with blood and seemed to have the capacity t o
concentrate microfilariae fro m the bloodstream. He then described the changes
in the appearance of the microfilariae. Thirty six hours after ingestion by th e
mosquito, the larvae ceased their movements and entered a "sort of chrysalis
condition" and became shorter and fatter s o that by the third day they resembled
a sausage. A mouth and intestinal tract then appeared and the worms grew in
length. Manson had great difficulty in observing these later stages, whic h
occurred around the fourth to the sixth day because most of his mosquitoe s
died. Out of hundreds of mosquitoes that he watched, only four lived beyond
this stage, and in one of these he saw a gradation of forms from the passiv e
chrysalis to an active larvae between 0.5 and 1 mm in length. Because of the
paucity of specimens, he was uncertain of the details of this stage o f
metamorphosis but found that the alimentary tract became distinguished more
clearly and thought that the worm may have a boring apparatus on its head.
Manson remarked that these processes always took place within femal e
mosquitoes, for he had never seen a male mosquito engorged with blood .
Further, he stated that his studies were always performed with the mor e
common of the two mosquitoes prevalent in his region, a dingy brown insect
about 8 mm in size (C. quinquefasciatus, while the other species was probably
Aedes aegypti). He observed the replete mosquitoes fly off to near stagnan t
water, remain there for several days, then deposit eggs, following which, h e
assumed, they died. Manson surmised that the life cycle of the worm wa s
completed in the following manner:

There can be little doubt as to the subsequent history of the Filaria, or that, escaping
onto the water in which the mosquito died, it is through the medium of this fluid
brought into contact with the tissues of man, and then either piercing the
integuments, or, what is more probable, being swallowed, it works through the
alimentary canal to its final resting place. Arrived there, its development is perfected,
fecundation is effected, and finally the embryo filariae we meet within the blood are
discharged.156
Manson knew little about the natural history of mosquitoes. He was wrong
about their geographical distribution and their life span and was not aware that
they could bite more than once. But he was not alone - there had been littl e
incentive to interest anyone in mosquitoes prior to his epochal discovery .
Desperately searching for inf ormation, he wrote to the British Museum and the
relevant authority replied regretfully that no such work existed, and forwarded
him a treatise on cockroaches in the hope that that would do instead. Indeed,
Manson was positively misled about these aspects by the one book that h e
eventually found on the subject.
Manson's paper was first published in the Medical Reports of the Chin a
Imperial Maritime Customs 156. He sent copies to Lewis in India, Cobbold in
England and Leuckart in Germany. Manson eloquently expressed his reasons
for this in his letter to Cobbold of 27 November 1877:
I live in an out-of-the-world place, away from libraries, and out of the run of what
is going on, so I do not know very well the value of my work, or if it has been done
before, or better.167
Lewis replied to him from Calcutta on 14 January 1878:
Allow me to congratulate you on your extremely interesting observation regarding
the embryonic nematode in the mosquito. I had frequently examined these insects,
but in a cursory way, but had not observed any parasites in them at all resembling
the embryo, Filaria sanguinis hominis, until I received your note. On receipt of this,
I repeated such examinations and found that several of the mosquitoes which were
examined contained little nematodes resembling most perfectly those found in
human blood. Whether they are actually identical or not it would, perhaps, hardly
be safe to assert positively without further experience. 136
Cobbold received Manson's communication on 4 January 1878. He wrot e
immediately to The Lancet (12 January 1878) conveying news of the observ-
ation and also remarking that Joseph Bancroft in a letter to Cobbold in April
the previous year had written:
I have wondered if mosquitoes could suck the haemotozoa and convey them to
water. They appear to die in water. I will examine some mosquitoes that have bitten
a patient to see if they suck up filariae.24
Nevertheless, Cobbold was fulsome in his praise of Manson:
Whether or not this conception of the possible host-relationship, as between man
and mosquito, primarily originated with Bancroft or some other observer, I cannot
stop to inquire, but certain it is that what Bancroft surmised Dr Manson has
demonstrated to be a fact....I consider Manson's discovery almost of a par with the
separate announcements of Lewis and Bancroft. 59
Filariasis 609
Adequate recognition has not been given t o Bancroft in this regard. Manson
was lucky while Bancroft was unlucky. Manson chanced upon an efficien t
vector of the parasite (C. quinquefasciatus) for use in his studies. According
to Cilento53, Bancroft in April 1877, before Manson had begun his studies, fed
some Aedes vigilax, a poor vector as it turned out, on an infected person bu t
was discouraged by the negative results.
In March 1878, Cobbold communicated formally Manson's account i n
which the latter characterized the mosquito as a "nurse" of the worm, to th e
Linnean Society in London. In the discussion that followed, Manson's opinions
were accepted by a number of eminent authorities. The publication 157 which
followed Cobbold's verbal report was the same as the parasitological com -
ponent of Manson's Custom's Report 156 except that the illustrations of th e
various forms of developing larvae were omitted. It was not until June of that
year, however, that the British Medical Journal was constrained to publish an
editorial entitled "Is the mosquito the intermediary host of the Filaria sanguinis
hominis?"8. This article was stimulated by the publication by Lewis in Calcutta
of the results of his attempts to repeat Manson's experiments. At first Lewi s
was in considerable doubt, for in contrast to Manson who had squashed th e
whole of the posterior portion of the mosquito and assumed that the variou s
events took place within the gut, Lewis removed the alimentary canal an d
examined it separately, and saw fe w parasites after the third day. Subsequently,
however, he found that the same worms "actually perforate the walls of th e
insect's stomach, pass out, and then undergo developmental stages in it s
thoracic and abdominal tissues" 135. Lewis's conclusion was very cautious ,
although it left open the possibility of mosquitoes being the intermediate host
of filariae:
With regard, however, to the inference that the mosquito is the particular
intermediary host of nematoid haematozoa, it cannot be said that even these later
observations are sufficiently conclusive to warrant a positive statement being made
at present; for though, assuming that of the various parasitic forms which have been
seen several are actually transitional stages in the development of one and the same
entozoon, it is to be noted that even the most advanced stage hitherto observed is
still a very immature one . . and every attempt hitherto made by myself to obtain a
more advance condition has been unsuccessful. Further observation, however, may
overcome or explain this want of success.135
In the middle of 1878, da Silva Araujo in Brazil also confirmed Manson' s
observations when he found W. bancrofti larvae in mosquitoes fed on the blood
of a French priest who had a microfilaraemia 219.
While Cobbold accepted Manson's views unreservedly, and Lewis did not
altogether dismiss them, Leuckart appeared to pay no attention at all to them.
Manson's biographers, Manson-Bahr and Alcock, have remarked that Leuckart
was initially an unbeliever and seems never to have given Manson's discovery
anything but a grudging and disparaging a cknowledgement 175. This seems a fair
comment, for in the 1886 edition of his Parasites of Man, Leuckart discourses
at some length on the discovery of microfilariae in the urine (mostly quotin g

Lewis) as a means of escape for microfilariae and although he alluded t o
Manson's discovery of the periodicity of microfilariae, made no mentio n
whatever of his studies with mosquitoes:
The haematozoa, then, after a longer or shorter sojourn in the blood-vessels, would
appear to leave the body of their host in some way or other, and continue their
life-history under other conditions.130
Stung by such indifference to his discovery, or the reservation with which
it was accepted, Manson repeated and amplified his observations in 1883 and
communicated the results through Cobbold to the Linnean Society in London
in 1884. He dissected over 1,000 mosquitoes. The most advanced larvae were
recovered from two mosquitoes 6.5 days after they had fed on Hin-lo, th e
gardener; these were infective larvae 1.5 mm long. Manson illustrated th e
metamorphoses in great detail and anticipated the fact that the larval filaria e
underwent at least two ecdyses in the mosquito. Finally, he pointed out that of
the four species which he now recognized in Amoy, only the form now known
as C. quinquefasciatus permitted complete development and one of the other
three allowed development only up to a certain point 164. In the same year,
Sonsino in Egypt also confirmed Manson's observations when he found a n
infective larva in a C. pipiens captured in the house of a filarious woman 222.
Although Manson suggested the possibility of skin penetration by infective
larvae through the use of the "boring apparatus", he preferred the alternativ e
option of ingestion of larvae liberated f rom dead mosquitoes in water. In March
1888, an anonymous reviewer (?Cobbold) in the Veterinarian suggested the
true mechanism when he wrote that the infective larva (which he called th e
"parent") is "deposited by the mosquito in the act of biting" 10. This suggestion
was not taken up with any enthusiasm. Indeed, another anonymous reviewe r
five years later stated that the larvae probably penetrated the skin of bathers 11.
It was not until 1899 that Thomas Bancroft, Joseph's son, put the piece s
into place so that the puzzle cou ld be solved. Thomas Bancroft, in Queensland,
discovered that mosquitoes could be bred and kept alive in confinement for up
to two months when fed upon ripe bananas 26. Carlos Finlay in Cuba had in fact
shown in 1881 that mosquitoes could be kept alive for weeks on blood o r
sugar86 but this information was lost sight of and never acted upon. Ronal d
Ross also re-discovered this phenomenon in his experiments on the malaria l
parasites of birds, when he kept them alive by re-feeding them on blood 205, but
Bancroft was apparently unaware of these contributions. In the event, Bancroft
used these laboratory-reared and maintained mosquitoes ( C. ciliaris = C.
quinquefasciatus) and fed them upon a 15 year old girl. As so frequentl y
happens in science, the course of events did not run smoothly, for whe n
Bancroft was ready to embark upon the scheduled experiments, he found that
his patient had left town, having secured a position elsewhere as a domesti c
servant. Fortunately, he was able to induce her with the aid of a seven pound
grant from the Queensland B ranch of the British Medical Association to return
Filariasis 611
and live with her parents for three months. In contrast to Manson who ha d
found filariae in various stages of development within the one mosquito ,
Bancroft observed that all of his larvae were at the same stage of development.
Moreover, 16 days were required in warm temperatures for development to be
completed, then no further changes occurred for the next six weeks. In view of
these findings, Bancroft suggested that the rare, fully-developed larvae which
Manson had seen seven days or so after feeding must have been derived from
an earlier blood meal, for Manson had caught wild mosquitoes. Bancroft first
published notification of his findings in the Australasian Medical Gazette in
189925. In that letter he noted that infective larvae were not killed by bein g
placed in water, and suggested that infection for the human host via thi s
medium should be confirmed experimentally on life-sentenced prisoners and
offering them a free pardon as a reward. In his more detailed report published
later that year, however, Bancroft modified his earlier statement and reported
that the larvae died three to four hours after immersion in water. This led him
to cast doubts of the water-transmission theory, and he wrote in an addendum
dated 1 June 1899:
It has occurred to me that young filariae may gain entrance to the human host whilst
mosquitoes bearing them are in the act of biting. The entrance of warm blood into
the mosquito may excite the young filariae in consequence of which they pierce the
oesophagus and pass down the proboscis into the human skin. In this way, injury
from human digestive agents would be avoided.26
Bancroft then sent some filariated mosquitoes that he had prepared t o
Manson in London who in turn passed them on to George Low who was work-
ing under his direction at the London School of Tropical Medicine. Thes e
mosquitoes were fixed in celloidin and histological sections were cut. In June
1900, Low published some magnificent figures of larval filariae in the abdomen
and thorax then illustrated their passage past the salivary glands into th e
proboscis, pushing forward between the labium and hypopharynx: "Here I have
frequently found them stretching along almost the entire length of th e
proboscis, the head being invariably in advance" 140. With masterly
understatement Low then wrote:
It is difficult to avoid the deduction that the parasites so situated are there normally,
awaiting an opportunity to enter the human tissues when the mosquito next feeds
on man.140
Many commentators have given Low the credit for discovering the tru e
manner of transmission of filariasis from mosquito to man. Nevertheless, h e
was but the technician who made the final but inevitable observation. Thomas
Bancroft determined the underlying conditions necessary for carrying out the
experiment, prophesied the outcome, and actually prepared the mosquitoe s
from which the sections were made. If he had had the appropriate technica l
resources at hand, he would undoubtedly have followed the whole proces s
through to its logical conclusion.
Much credit must also be given to Captain SP James of the Indian Medical
Service in Travancore, India. Stimulated by Thomas Bancroft's report tha t

mosquitoes could be kept alive by feeding them on bananas, he adopted th e
same technique and independently of Low, showed that infective larva e
migrated into the proboscis of certain anopheline mosquitoes 116. Shortly
afterwards, the members of the second malaria expedition to West Africa of the
Liverpool School of Tropical Medic ine, stimulated by Low's report, announced
that they had confirmed the observations by finding filariae in the proboscis of
Anopheles 12.
Soon after publication of Low's paper, Kennard in British Guiana, afte r
noting that Low had stated that the larvae were located between the labium and
hypopharynx, objected that the la bium is not inserted when the mosquito feeds,
but is applied against the skin and encircles those parts of the proboscis which
do penetrate the integument - the hypopharynx, mandibles and maxillae .
Kennard did not believe it possible for the hypopharynx to admit so large a n
organism as the infective larva, so cast do ubt upon this mode of transmission 118.
Similar comments were made by Grassi and Noè who wrote that when dogs
were bitten by Anopheles mosquitoes infected with Dirofilaria immitis, the
larvae escaped through a rupture in the bent labium 99. These authors, then Noè
alone183,184 claimed that the mosquito propagation of filariasis was an "Italian
discovery", a claim that was roundly cond emned by Sambon 208 and Ross204. The
latter (who had suffered previously at the hands of Grassi with respect t o
malaria research) wrote trenchantly:
the work is not a serious effort of science, but only an attempt to peg out a fresh
claim for priority by, or on behalf of, Professor Grassi. One notes at once that he
adopts in his new enterprise precisely the same devices as he used previously in
connexion with the mosquito theory of malaria. The moment Dr. Low's work was
published, he hastily issued with Dr. Noè a 'preliminary note' in which he began by
implying (but without giving details) that he himself had independently made the
same discovery - a thing for which I have reasons for disbelieving; and then
proceeded to deprecate Dr. Low's work by inventing imaginary faults in it - an
artifice which he consistently adopts in regard to my own work. Having thus shifted
the merit of the inoculation hypothesis of filariasis to his own credit, he permits his
pupil, Dr. Noè to draft the entire subject into his account by saying that the 'Italian
discovery now at last enables us to place the prophylaxis of filariasis upon a solid
basis'. Needless to say, neither he nor his pupil has ever made a single new
observation on filariasis.204
Ross then recounted a number of other i nstances of similar chicanery by certain
(but by no means all) Italian writers, and concluded:
It is a question how to deal with such efforts. In my humble opinion, science is too
great a thing to be made a field for tricks like those of a pettifogging village attorney
and we have every right to resent their introduction. Moreover, absolute honesty is
the first qualification in all scientific work and the man who attempts to deceive his
readers on the question of priority can hardly complain if we refuse to believe in his
researches....Others may do as they please, but for my own part....I fear I cannot do
myself the honour of including the labours of Professor Grassi in any future writings
Filariasis 613
of my own and think that science will not lose much if the papers by him and Dr.
Noè on filariasis are similarly excluded from monographs on that subject. 204
Meanwhile, Thomas Bancroft in 1901 used D. immitis as a model to show
clearly that larvae escaped through the labe lla at the tip of the labium 27. Further,
in a well-controlled experiment on 30 December 1902, he exposed a thre e
week old uninfected pup to 183 filariat ed mosquitoes, two of which bit the dog.
Nine months later, microfilar iae appeared in the peripheral blood, then the dog
was killed and 16 male and 16 female adult D. immitis were recovered from the
right ventricle and the pulmonary artery 28. Thus, there seemed little doubt that
a similar mechanism was involved in human filariasis.
Basic knowledge of mosquito biology was poor in those early years. No t
only were the behaviour and natural history of mosquitoes dimly understood,
but many species were undiscovered or unnamed. Neverthless, mosquitoe s
were observed, categorized, and their ability to permit development o f
microfilariae determined experimentally. In 1900, 110 species of mosquitoes
were known. By 1922, more than ten times that number had been described 81.
The original mosquitoes which Manson had used in his experiments wer e
proven more than 50 years later to be Culex quinquefasciatus (= fatigans)
when some mosquitoes that he had filariated and sent to Cobbold wer e
discovered in bottles at the Royal College of Surgeons in England 174. In 1900,
James in India reported that Anopheles rossi was a vector of W. bancrofti 116,
then he was followed by Annett, Dutton and Elliott in Nigeria in 1901 wh o
showed that Anopheles costalis was a vector 3 and then by Bahr in Fiji wh o
worked with Aedes variegatus (= pseudoscutellaris = polynesiensis)19. By
1922, Edwards was able to list seven species in which complete development
of W. bancrofti microfilariae had been shown. In addition, 23 species were said
to allow partial development 81. In 1930, Brug and de Rook reported that th e
newlydiscovered B. malayi completed its development in Taeniarhynchus
annulipes (= Mansonia annulipes = M. dives) and T. annulatus (= Mansonia
annulata)43, then several years later, Feng showed that the major vector of this
parasite in Huchow, China was Anopheles hyrcanus var. sinensis 85. When
Sasa came to write his review of filariasis in 1976, hundreds of species o f
mosquitoes were known to be transmitters of this infection, although wit h
varying degrees of efficiency 211.
DISCOVERY OF THE NOCTURNAL PERIODICITY OF

MICROFILARAEMIA
During 1876 and 1877, Manson noticed that microfilariae could not always be
found in patients whom he knew from previous observations to be infected .
Eventually, he trained two Chinese a ssistants to make blood examinations. One
of these persons worked during the day and the other laboured at night. Manson
was struck by the fact that the night worker found more parasites than did the
daytime attendant but he did not arrive at the correct explanation. In 1879 ,
however, he gave directions for a particular patient's blood to be examine d
daily and found that on some days there were abundant microfilariae whereas
on others there were none or ve ry few. Closer analysis of these results revealed
that more microfilariae were found on busy days when the blood examination
had to be left to the evening. This reminded him of the earlier discrepancie s
with his two assistants, so he made a series of systematic examinations every
few hours on this patient and in a number of others. He wrote to Cobbold in a
letter dated 27 February 1880:
The young escape into the circulation at regular intervals of twenty four hours, the
discharge commencing soon after sunset and continuing till near midnight, from
which time till the following noon their numbers gradually decrease. By 2 or 4
o'clock till 6 they are nearly completely absent....It is marvellous how nature has
adapted the habits of the filariae to those of the mosquito. The embryos are in the
blood just at the time the mosquito selects for feeding. 168
Manson confirmed his observations on further patients and published th e
results in the Customs Report 159. In addition, Cobbold presented Manson' s
communication to the Quekett Microscopical Club on 27 February 1880 160.
Manson was very thankful for the efforts, for he later wrote to Cobbold:
I am very grateful to you for the trouble you have taken in bringing these forward
and cannot but feel that unless for your kind assistance, my work would lie
entombed in the 'Customs Gazette' of little use to anyone. 160
Cobbold's presentation of Manson's finding was greeted with astonishment
by some and with downright disbelief by others, with one wag enquirin g
"whether the filariae carried watches" 9. In 1881, however, WW Myers o n
Formosa (Taiwan) confirmed Manson's observations 180, then the scoffers were
silenced when Stephen MacKenzie in London in the same year not onl y
demonstrated microfilarial periodicity in a 26 year old patient who had acquired
the infection in India but, at the suggestion of Vandyke Carter, succeeded i n
reversing the periodicity by persuading the patient to sleep by day and stay up
at night146.
On hearing about MacKenzie's experiment , Manson repeated the procedure
in three patients and found partial or compl ete reversal four days later 162. Mean-
while, Manson had wondered whether th e microfilariae died each day and were
replaced by a new brood, or whether they hid themselves during the day. H e
tried to investigate this with a dog inf ected with D. immitis, which he found had
partial periodicity. The animal was killed with prussic acid and Manson found
that most of the microfilariae were in the lungs 163. Many years later, he had an
opportunity to prove that the same phenomenon occurred in humans. On 1 9
February 1897, a man who had been known to have a microfilaraemi a
committed suicide with prussic acid and died almost instantly at 8.30 in th e
morning. Following a post-mortem examination, Manson concluded:
Filaria nocturna during its temporary absence from the cutaneous circulation is
present in the larger blood vessels, particularly the arteries, that a few are found in
Filariasis 615
the capillaries of the muscles and brain, a few in the vessels of the kidneys, a
considerable number in the muscle of the heart; but the majority are lodged in the
blood vessels of the lungs.166
The mechanism by which this phenomenon occurs has attracted a great deal of
attention since those early days but still remains a mystery. The central thesis
proposed by Lane 126 was that there was a cyclical release of embryos from adult
worms, but most other authors fro m Manson on 14,108,171 have thought it far more
likely that periodicity depends upon an interaction between the microfilaria e
and the host, with microfilariae retiring to the viscera during the daytime.
In 1896, Thorpe reported that the microfilariae seen in Tonga in the south
Pacific exhibited no nocturnal perio dicity, being found in the blood both by day
and by night228, then this observation was confirmed by Lynch in Fiji145 . In
1912, Fülleborn showed that this aperiodic form of W. bancrofti was present
only eastwards of approximately 140oE longitude. Whereas he found aperiodic
W. bancrofti in Samoan troops stationed in Hamburg, Germany, when h e
visited northeastern New Guinea and parts of eastern Indonesia, onl y
nocturnally periodic W. bancrofti was seen93.
Lichtenstein in 1927 showed that the new microfilaria in his area, late r
named B. malayi, was nocturnally periodic, like that of W. bancrofti 137. In
1957, Turner and Edeson 230, then Wilson and his colleagues 236 , reported that
there were two distinct patterns of microfilarial periodicity in B. malayi
infections in Malaya. In addition to the previously recognized periodic for m
which was transmitted by Anopheles mosquitoes and was endemic in open rice
fields and swamp areas, a subperiodic form (i.e. microfilaraemia occurre d
throughout the 24 hours with a mild peak at night) was seen among inhabitants
of forested areas. This strain was shown to be transmitted by Mansonia
mosquitoes, and was found to be a zoonosis, occurring in wild and domesti c
animals, especially cats and monkeys 79,124.
Swollen legs have been recognized since an tiquity. While the commonest cause
of subacute cases of this condition is conges tive cardiac failure and even though
relatively frequent problems such as deep vein thrombosis and rare conditions
such as Milroy's disease (congenital absence of the lymphatics) and Dercum's
disease (lipomatosis) may have accounted for a proportion of patients wit h
chronic enlargement of the limbs, the most common cause in endemic areas has
undoubtedly been filarial parasites. In gross cases with thickening of the skin,
the resemblance of the limb to that of an elephant's leg led to the description of
the condition as "elephantiasis". Similarly, there are many causes of hydrocele,
but again, the majority of such cases in endemic areas, especially whe n
associated with lymphatic thickening of the scrotal tissues have probably been
due to filariasis. A statue of Mentuhotep I II, a pharaoh of the XI Dynasty (about

2,000 BC) shows pronounced enlargement of both legs which may be due to
filariasis112,127,215. T Lucretius Carus, a Roman living in the century befor e
Christ, regarded elephantiasis as a characteristic disease of Egyptians, stating
that elephantiasis arose along the Nile and was facilitated by the climate o f
Egypt: "est elephas morbus qui propter flumina Nili signitur Aegypto in media
nequen praetera usquam" 144.
Elephantiasis was also known in West Africa and has been reproduced in
ancient works of art. For exampl e, in the museum of Jos in Nigeria, there is the
torso of a terracotta statuette of the Nok period (c.500 BC-200 AD) whic h
reveals elephantiasis of the scrotum 112. Similarly, a figurine recovered from a
Mayan temple in Yucatan, Central America, dating from around 500 AD dis-
plays gross scrotal swelling 2.
Descriptions of hideous deformity have been provided in more recent times.
The Portuguese, Tomé Pires, who had been apoth ecary to Prince Alphonso, son
of King John II of Portugal, and was later to become ambassador to China, was
sent to the Malabar coast of India (Kerala) as factor of drugs from 1512-1515.
In the record of his experiences, he wrote:
Many people in Malabar, Nayars as well as Brahmans and their wives - in fact about
a quarter or a fifth of the total population, including the people of the lowest castes
- have very large legs, swollen to a great size; and they die of this, and it is an ugly
thing to see....the swelling is the same from the knees downward, and they have no
pain, nor do they take notice of this infirmity.193.
Later that century, Ralph Fitch, an Englishman living in India described th e
same condition at Cochin:
This bad water causeth many of the people to be like lepers, and many of them have
legs swollen as big as a man in the waste, and many of them are scant able to go. 88
Indeed, the tradition arose that Thomas, the disciple of Christ, had lived an d
preached in that part of the world and was there slain with a lance whil e
praying in the church. This in turn led to the legend that this illness was th e
result of the curse of St. Thomas 128. The Dutchman, John Hughen van Lin -
schoten, who had lived in Goa between 1588 and 1592, gave the followin g
account:
they say that the progeny of those that slew him, are accursed by God, which is that
they are all borne with one of their legges and one foote from the knee downwards
as thick as an Elephantes legge....whereof I have seen many, both men and women
for that thereabouts there are whole villages and kyndreds of them that are borne in
the said land of St. Thomas . . They have no let nor trouble in their going, but only
the unsightliness and evil favoured fashion.138
While legs appeared to be affected most in this region (and was possibl y
due to B. malayi), involvement of the genitals appears to have been mor e
common in West Africa, as described by John Barbot in 1732:
Here is another unknown and foul distemper, the Blacks are subject to, throughout
all the country about Sierra Leone, and in Quoya; i.e. a wonderful swelling of, or in
the Scrotum....which causes violent pains, and hinders their co-habiting with
women.29
Filariasis 617
A particularly gross case was recorded in t he India Journal of Medical Science

and abstracted in The Lancet in 1844:
Moodoosudun Dos, aged 23, an emaciated, sickly-looking native Christian, admitted
into the surgical ward of the College Hospital, Calcutta on the 20th November
1843, with an enlarged scrotum, indurated in appearance, and extending down
nearly to his knees. the prepuce presented a knotty appearance in the centre of the
tumour; the integument over the pubes was not much implicated in the disease, and
the spermatic cords could be felt easily on either side. 4
After having reviewed the operative treatment, the armchair reviewer back in
the comfort of England facilely remarked that with such opportunities, ou r
knowledge of the nature and cause of this formidable disease should have been
advanced even more that it had been by the communication unde r
consideration. An even worse case in a 30 year old Indian living in Madras was
described by Godfrey in 1851:
The tumour is of immense size, hanging down nearly to the level of the ankles, and
causing him by its bulk and weight great difficulty in moving about. The following
are the dimensions taken in the erect position; length from superior to inferior part
26 inches [65 cm]; circumference, one yard and a half [135 cm]; general shape
ovoid; feels dense, brawny, oedematous.95
The tip of the penis was buried at the end of a tunnel 10 inches [25 cm] deep.
Not surprisingly, the patient had not the least sexual desire. The diseased mass
removed at operation weighed 70 lb [32 kg] and would have weighed eve n
more had not the fluid that it contained esc aped. The record size for an enlarged
scrotum was probably that reported by Pelletier who operated on one whic h
weighed 100 kg 192.
There was considerable confusion in the minds of many concerning thi s
complex of diseases. Two forms of elephantiasis were described. Clinician s
gradually separated Elephantiasis Graecorum fro m Elephantiasis Arabum. With
the discovery of the organisms causing each condition, it became apparent that
Elephantiasis Graecorum was leprosy and that Elephantiasis Arabum wa s
filariasis.
A third clinical syndrome, chyluria, was also recognized, although it s
relationship with the other presentations of filariasis was not appreciate d
immediately. One such patient was recorded by G eorge Bonyun in Georgetown,
British Guiana (Guyana) in 1846:
H.K.-, aged thirty-one, creole of Demerara, good constitution, bilious temperament,
has enjoyed good health for several years; on the 8th May observed that his urine
was turbid of a brownish colour; this turbidity increased from day to day, until the
urine acquired a milky appearance....June 8th.- Urine decreased in quantity, quite
white, and coagulating immediately after being passed, so as to resemble
blancmange ....Tenth month....urine, three pints daily....white, firmly coagulating,
and separating after remaining some hours into a substance resembling curds and
whey.36
The relationship between these chronic conditions, as well as acute inflam-
mation of the lymphatics, with filarial parasites unfolded only slowly, and was
for a number of years the subject of much controversy, as will be described in
the next section. To this constellat ion of disorders, some authors gave the name
"filariasis", a term which Cobbold damned, bellowing that "this vague and too
comprehensive sort of nomenclature cannot be allowed to stand" 62. His
opposition, however, was doomed.
During the second world war, an opportunity arose to study the clinica l
manifestations of early filariasis in detail. Several hundred American service-
men stationed in the south Pac ific, particularly in Samoa, became infected with
W. bancrofti. Acute inflammatory lesions were seen in persons who had been
in the endemic area for three months or more. Lesions in a limb usually began
as a lymphadenitis which then spread in a retrograde or centrifugal fashion ,
while genital involvement was indicated by a highly characteristic scrotal lesion
with funiculitis and epididymitis. There w as a tendency to multiple involvement
and recurrence, the attacks generally lastin g for a few days and being associated
with fever in about 20% of cases 76,119. The minds of not a few United State s
servicemen were distressed by the possibility that these symptoms were a
harbinger of hideous deformity yet to come. Babione in 1945 wrote a
reassuring article entitled: "A few facts about filariasis for folks who fear that
filaria-infected fellows will fetch f ilariae from the front" 18 in which he predicted
that few individuals would suffer serious consequences and divined tha t
development of microfilaraemia and secondary transmission was unlikely. He
was eventually proven correct, for when Trent reviewed these patients 15-16
years later, he found that only less than 1% had a swollen leg or genita l
complaint, and none of them had either elephantiasis or microfilaraemia 229.
When infection with Brugia malayi was differentiated, the symptomatology
in malayan filariasis was found to be broadly similar to that seen in bancroftian
filariasis, although there were differences in emphasis. Lichtenstein in 192 7
observed that acute filarial disease was infrequent and that even thoug h
elephantiasis was common, this was generally restricted to the lower lim b
without involvement of the genitals 137. His views were echoed by Brug 41 and
many subsequent workers, although acute inflammation was recognized from
time to time and genital disease was seen occasionally.
CORRELATION OF INFECTION WITH PATHOLOGY AN D

CLINICAL FEATURES
Although the pathogenesis of elephantiasis was a matter of much dispute, an

English surgeon, E Bascome, who h ad spent many years of residence in British
Guiana was remarkably accurate in his perception of the problem. After sep-
arating the condition from leprosy, he wrote in 1845:
I am induced to think the hypertrophy is caused in two ways - viz., from erysipelas,
and from a want of tone in the lymphatics....When the sequelae of erysipelas, it is
not until after repeated attacks of the disease, and the persistence longer of each
attack, that enlargement of the part ensues, the inflammatory action at each
accession seemingly penetrating deeper, involving the whole of the subcutaneous
Filariasis 619
cellular substances producing infiltration of that tissue and ultimately, extensive

partial disorganization, which degenerating into a variety of shapes, becomes
studded with stone-like excrescences....intersected....with weeping fissures. When
it commences in the lymphatics, a weariness is felt along their course in the limb,
and a benumbed sensation....It is unattended by fever or discoloration....Should the
scrotum become fastened on, a puffiness and intolerable itchiness are present, and
if the surface be abraded....lymph exudes profusely forming crusts....The parts
by-and-by become thickened into lumps, and run into one confused mass, attaining
in some cases to an enormous size, with so little sensation as to admit of its being
kicked like a football; in one case, when amputated, the scrotum weighed ninety two
pounds avoirdupois, filling a pork-barrel! The testes are usually sound....hydrocele
is, however, a pretty frequent concomitant.30
Nevertheless, Bascome had no idea what was the underlying cause of thes e
changes and put them down to climatic conditions. The involvement of th e
lymphatics was confirmed a few years later by surgeons working in India 83.
When Demarquay discovered worms in hydrocele fluid in 1863, he wa s
admirably cautious about drawing any connection between the two events, but
invited others to report any similar observations 73. In like manner, when
Wucherer published a report of his finding parasites in chylous urine in 1868,
he also refrained from conjecturin g about any aetiological relationship between
the worms and haematuria and chyluria until he had the chance of examining
a cadaver of an afflicted patient at autopsy. Unfortunately, he had no suc h
opportunity before his death five years later 239.
Lewis, on the other hand, had no such compunction when he indicated his
discovery of microfilariae in the bloodstream of patients, some of whom ha d
chyluria:
The blood of persons who have lived in tropical countries is occasionally invaded
by living microscopic Filariae....which may continue in the system for months or
years without any marked evil consequences being observed; but which may, on the
contrary, give rise to serious disease, and ultimately be the cause of death. The
phenomena which may be induced by the blood being thus afflicted are probably
due to the mechanical interruption offered (by the accidental aggregation, perhaps,
of the Haematozoa), to the flow of the nutritive fluids of the body in various
channels, giving rise to obstruction.132
At first, Lewis connected microfilaraemia only with chyluria. As he continued
his observations, however, he fou nd microfilariae in the blood of 11 patients or
in one or other of the tissues or secretions in 30 individuals. Since all of these
persons suffered from either chyluria or elephantiasis, this convinced him that
his previous proposal of a causal relationship was correct. Further, Lewi s
suggested that these problems were due to lymphatic obstruction which was in
turn possibly a consequence of either encysted mature worms or migratin g
immature worms in the lymphatics, or the result of the activity of liberate d
microfilariae 133.
The views of Lewis were soon supported by Manson. During his first tour
of duty in Amoy, Manson had encountered a number of examples of elephant-
iasis and had concluded from his surgical observations that the scrotal disease
was "a sort of dropsy" 154. On his return to China after furlough in Britain ,
Manson examined 190 local people who were selected randomly, the onl y
requirement being that they were willing to have a finger pricked; he foun d
microfilariae in the blood of 15 of them. Manson noted that some of thes e
infected persons were in perfect health but that others had evidence o f
lymphatic obstruction with lymph scrotum, elephantiasis, or recurrent attacks
of fever accompanied by oedema which was not due to heart disease or renal
failure155. During 1877, he confirmed his investigations and found parasites in
62 of 670 persons. Among these individu als were patients with lymph scrotum,
elephantiasis of the leg or genitalia, chyluria and inguinal lymphadenopathy ;
some 60% of these patients had microfilaraemia compared with less than 10%
of the normal population. Although the tests of experimental infection an d
post-mortem examination were wanting, Manson was convinced that he ha d
proven that these diseases were due to the worm, and like Lewis, conclude d
that the essential feature was obstruction of the lymphatics by these parasites.
Nevertheless, he appreciated that ther e were two unresolved problems - the not
infrequent presence of microfilaraemia without disease, and the somewhat less
common reverse situation. Manson thought that the former merely indicate d
that the disease was merely an accidental side-effect, and explained the latter
on the basis that the worms h ad either died, the infection was unisexual, or that
the adult parasites had become encysted so that the larvae could not escape .
These clinical findings were published, together with his observations on the
development of larvae within mosquitoes, in the Customs Reports 156, then
reprinted in the Medical Times and Gazette 158.
In the meantime, confirmation of the existence of lymphatic pathology was
provided by Bancroft's discovery of an adult worm in a lymphatic abscess, and
was consistent with his subsequent recovery of them from hydrocele fluid 20.
Nevertheless, there were still opponents of these ideas. Dr Tilbury Fox, a
London dermatologist, published a pa per in 1878 denigrating the work of these
"recent writers"90. Following a presentation of two cases of elephantiasis b y
Joseph Fayrer at a meeting of the Pathological Society of London 84, Fox again
asserted that evidence linking filarial infections with elephantiasis was ver y
weak, claimed to have seen cases of elephan tiasis in patients who had never left
England, and emphasized the abs ence of microfilaraemia in some patients with
elephantiasis or chyluria, and cont rasted that with the extremely high frequency
of microfilaraemia that Manson had observed in China. Furthermore, Fo x
claimed that it was not proven that elephantiasis and lymph scrotum were the
same disease, and argued that the escape of chyle in the urine and effusion of
lymph into the tissues were two quite different matters. To this, Fayrer replied
that while he did not stand up as the champion for the filarial theory of th e
disease, the association was of great interest and he considered, moreover, that
the observations of men working in the tropics should not be disparage d
because it was a very different thing researching in China and India compared
with similar undertakings in London 91.
Filariasis 621
Stimulated by Fox's criticisms, Manson over a period of nine month s

collected a series of six patients who were in a transitional state or who had a
combination of elephantiasis of the limb and lymph scrotum. He noted tha t
inguinal lymphadenopathy was prominent in all these patients, and succeeded
in aspirating microfilariae from the glands, even in patients with elephantiasis
of the legs and normal genitals who had no microfilariae detectable in th e
blood159. On two occasions, he recov ered ova rather than microfilariae from the
lymph nodes. This observation caused him to evolve the theory that adul t
worms live in the lymphatic vessels distal to the draining nodes and that they
sometimes expelled ova prematurely. He postula ted that the ova are then caught
in the nodes where they cause stasis, regurgitation of lymph, anastomosis o f
lymph vessels, and hypertrophy of the tissues, sometimes going on to produce
lymphorrhoea or chyluria, depending upon the si te of the obstructed lymphatics.
Moreover, Manson believed that the parent worms may sometimes die, giving
rise to an abscess, usually in the scrotum or thigh 162. The flaw in his argument,
of course, was the idea that fe male worms "miscarried" with release of ova, but
in many other respects he was right in his interpretation of the sequence o f
events.
Many of the sceptics were silenced (Fox having died in the interim) when
in 1882 MacKenzie presented the post-mortem findings in the patient in whom
he had succeeded in reversing filarial periodicity once before. The young man
had died from an abscess near the clavicle, pneumonia and pyelonephritis .
Autopsy revealed that the thoracic duct was obliterated and embedded i n
inflammatory tissue, and that the ly mphatics below the obstruction were dilated
enormously, thus confirming t hat the habitat of mature filariae in humans is the
lymphatic system, and suggesting that chyluria was due to rupture of distended
lymphatics146. There is little doubt that Manson himself would have advanced
the understanding of the pathology of filariasis much more rapidly if he had had
the opportunity. He was hampered, however, by the bitter antipathy which the
Chinese had to examination of the body after death. An illustration of th e
difficulties he went through in this cause is recounted in chapter 11 where his
accidental discovery of Sparganum mansoni while looking for adult filariae is
described. On an earlier occasion, Manson and his brother David had paid a
widow 200 dollars in return for permission to make a limited examination of
a man with elephantiasis and microfilaraemia. While they were engaged in the
autopsy, a mob gathered outside shouting death to the foreign devils, and they
had to flee for their lives 174.
Despite all these evidences, Prout in 190 8 forcefully advanced the view that
filariae were not the cause of either the inflammatory disorders (lymphangitis
and abscess) or obstructive lesions (lymph varices, lymph scrotum, hydrocele
and elephantiasis) that had been associated with filariasis 196. He based his
arguments upon epidemiological observations that filariae were not alway s
found even though the vector was present, the fact that these lesions had no t
been produced experimentally, and the record by Maxwell in 1901 177 that he
had found remains of adult filariae in only one of 23 abscesses, despit e
microfilaraemia being present in almost al l of the patients. Prout postulated that
bacteria produced the acute inflammatory lesions and that recurrent attack s
caused the obstruction of lymphatics. Despite formidable opposition fro m
Manson170 and others including Low and Manson-Bahr 143, this concept slowly
gained ground. Indeed, in 1915, Dutcher and Whitmarsh announced th e
"discovery" of a bacterium similar to Bacillus subtilis which they called
B. lymphangiticus and which they believed was "the cause of those disease s
grouped under the designation of 'filariasis'" 77.
Meanwhile, Wise and Minett in British Guiana (Guyana) had studied care-
fully 28 abscesses and had found evidence in favour of both helminthic an d
bacterial causation. Complete worms or pieces of adult filariae were found in
the advanced pus in 22 patients, and 21 abscesses grew streptococci in pur e
culture, four grew Staphylococcus aureus, and three were sterile 238. In contrast,
Anderson and his colleagues working in the same country a few years late r
found adult worms in only one of 48 abscesses, streptococci in 41 patients, and
staphylococci in 22 cases 1.
Consequently, the Royal Society and the London School of Tropica l
Medicine in 1926 launched an investigation into the bacterial complications of
filariasis in British Guiana. The report published a few years later concluded
that a "filarial attack" was really lymphangitis, the usual cause of which was a
beta haemolytic streptococcus. It was opined, however, that neithe r
lymphangitis nor elephantiasis occurred to any great extent in the absence of W.
bancrofti 98. The role of the worm was thus relegated to that of a foreign body
which acted as a focus for the opera tion of bacteria. In the 1930's, however, the
pendulum began to swing back in favour of the parasitic cause of the problem.
In 1931 McKinley reported the results of a study designed to answer th e
question: "Can we have acute filarial lymphangitis without bacteria l
infection?"148. He investigated 39 cases of acute filarial inflammation and found
that blood cultures and microbiological studies of aspirates from inflame d
tissue were uniformly negative whereas bacteria were always isolated from a
control group of non-filarial abscesses 148. FW O'Connor then re-emphasized the
correlation between the presence of insect vectors of W. bancrofti and these
complaints, the lack of correlation between chronic filariasis and bacteria l
infections, the failure of McKinley to aspirate streptococci in filaria l
lymphangitis, and his own pathological studies in which serial sections o f
involved tissues revealed large numbers of parasites but no evidence o f
bacteria. He concluded that adult worms and their larvae were entirel y
responsible for the acute inflammation and chronic obstructive changes see n
in filariasis. More importantly, he believed that living worms produced n o
serious pathology but that the tissue reactions were usually in response to death
of the worms and were probably allergic in nature 185. This belief in an
Filariasis 623
immunological reaction was supported when large numbers of early ,

inflammatory filarial lesions in Ame rican troops were biopsied and histological
examination revealed a typical picture of granulomatous lymphangitis 107,232.
The prepatent period of filarial infections in humans has not been defined
well. As mentioned earlier, microfilaraemia developed 84 days after infection
of a human volunteer with B. pahangi 80. An attempt to infect a human similarly
with B. malayi was unsuccessful, but a prepatent period of between 67 and 98
days has been found in experimental monk eys188. Such an experiment has never
been undertaken with W. bancrofti in humans, but recently Cross and hi s
colleagues have infected Taiwan monkey s (Macaca cyclopis) with this parasite
and obtained prepatent periods ranging between eight and eighteen months 66.
The life span of the adult worms is also unclear. Jachowski and hi s
colleagues studied filariasis in Samoans in Samoa (the endemic area) and i n
Samoans in Hawaii (a non-endemic area), and calculated that W. bancrofti
microfilariae disappeared from the blood in a little over five years 114. This is
presumed, but has not been proven, to be when the adult worms had died .
Similar deductions have been made by other investigators, although there has
been a report of microfilaraemia in the blood of a Frenchwoman who had not
lived in an endemic area (Tahiti) for 40 years 49.
Ways of diagnosing filariasis became evident with the discovery of parasites in

various tissue fluids or excretions as has been recounted in the preceding pages.
Thus, Demarquay found microfilariae in hydrocele fluid 73 then Bancroft
recovered adult worms from the same source 20. Wucherer demonstrate d
embryos in the urine 239, Lewis discovered microfilariae in the periphera l
blood131 and Manson found them in lymph node aspirates 159 . Nevertheless, it
rapidly became evident that not only were adult worms hard to find, but als o
that microfilariae could often not be demonstrated in the bloodstream o f
infected persons, especially in patients with gross obstructive disease. A
number of approaches were therefo re used to enhance diagnostic ability. These
included the assessment of immunodiagnostic tests, biopsy of affecte d
lymphatics, and the development of techniques for the concentration o f
microfilariae from the blood.
A clue may be given to the diagnosis by finding an eosinophilia, a n
observation that was first made by Gulland in 1902 102. It was soon realized,
however, that this was a very nonspecific finding, being seen not only in other
tissue helminthiases, but also in a variety of unrelated conditions. Rarely ,
calcified worms have been noted to produce opacities on X-ray examination,
particularly in the thigh and groin 186, but this does not provide an aetiological
diagnosis.
Somewhat more specific were the immunologic al tests that were developed,
beginning with skin testing using Dirofilaria immitis antigen, as described by
Taliaferro and Hoffman in 1930 225, and the independent development of th e
same test as well as an assay for c omplement fixing antibodies by Fairley in the
following year82. Much effort was made to improve the sensitivity an d
specificity of these assays by fractionating Dirofilaria antigens213,214 and by
using W. bancrofti 113 and B. malayi 101 antigens. More promising, since they
differentiate between past and present infection and may provide an index of
intensity of infection, have been recent attempts to measure filarial antigens in
tissue fluids or circulating in the peripheral blood 105,199.
Morphological demonstration of the worms, however, is the most definitive
means of proving a diagnosis. Experience of early, inflammatory filariasis i n
American troops during World War II indicated that the diagnosis could b e
made in many patients by biopsy of inflamed lymphatics 76,107,119,232. The
commonest practice over the years, however, has been to examine for th e
presence of microfilariae in one or more drops (20 µl) of blood smeared on a
glass slide. The development of concentration techniques has assisted greatly
in the demonstration of microfi lariae in the peripheral blood. One of the first of
these techniques used in filariasis was that of de Beaurepaire Aragão who i n
1919 described mixing 0.5 ml of blood with 5 m l of a solution containing acetic
acid (which haemolysed the erythr ocytes) then inspecting the centrifuged pellet
for parasites32. This technique had, in fact, been used five years earlier in both
loiasis and filariasis by Smith and Rivas as is described in chapter 24. Possibly
independently, Suganumu in Japan described essentially the same method i n
1921224. The same principle was employed by Haga in Indonesia 103; he used a
preparation of the locally available soap fruit ( Sapindus rarak, which contains
saponine) to haemolyse red blood cells. This was also the basis for the much
publicized "Knott's technique" which did not require (in his origina l
description) centrifugation: 1 ml of blood was added to 10 ml of 2% standard
aqueous formalin in a measuring flask and was allowed to stand for 12-2 4
hours - a compact pellet containing microfilariae formed under the action o f
gravity121. More recently, filtration of venous blood through variou s
microscopic filters has become popular in view of its simplicity an d
effectiveness 33,74.
The treatment of the obstructive complications of filariasis has long exercised

the mind of surgeons. Operative removal of diseased scrotal tissue has bee n
practised for at least 150 years. The surgical treatment in 1853 of Moodoo -
sudun Das (referred to earlier) who was "anaesthetized" with laudanum an d
brandy was recorded as follows:
Filariasis 625
Professor Raleigh.....made two parallel incisions over each spermatic cord,

commencing over the pubes, and extending down the tumour about 14 inches in
length; after dissecting up each testicle, a semilunar-shaped incision was made
transversely across the pubes, uniting the two former incisions. The penis was next
dissected up, and the whole tumour removed by making two small lateral flaps, with
a long catlin; the haemorrhage was mostly venous, and not great; two small arteries
only required ligature.4
Remarkably, the patient recovered, as did 13 of the next such 15 patients .
Similar operations were described by a number of surgeons 95,96,154.
Dreadful as are the problems with enlargement of the genitalia ,
elephantiasis of the limb has proven almost unassailable. Compression of the
limb was tried but found to be of only temporary benefit 87, although Knott 70
years later was more impressed with its usefulness 120. Carnochan in 1851
introduced the operation of deligation, or tying of the main artery to the limb 50.
This procedure sometimes had disastrous consequences and was roundl y
condemned 87,151. Surgical removal of the adult worms was investigated b y
Maitland152, but since the procedure involved excision of the involved tissues,
it had the manifest disadvantage of exacerbating lymphatic obstruction .
Maitland's operation was criticized by a number of surgeons, and despite his
plea that it was safe and effective 153, failed to find a solid place in the surgical
armamentarium.
Near the turn of the present century, Handley proposed an operation o f
lymphangioplasty for the cure of elephantiasis, but he himself was doubtful as
to its value106 and others were distinctly unimpressed 149. Kondoléon in Athens
believed that lymph stasis occurred chiefly in the fascia in the non-tropica l
cases that he studied, so he devised an operation in which a strip of fascia was
removed in order to make a broad communication between the disease d
subcutaneous tissues and the lymphatics in the muscles 122. In 1930,
Auchincloss described another operation which was intended to lighte n
elephantoid legs and remove focal tender spots by excision of large slabs o f
skin, subcutaneous tissues and fascia 17, then a similar operation was described
by Gorter97. These operations, however, were major procedures in gross cases
(when they were most necessary), and at best gave only partially satisfactor y
results.
From time to time, various unorthodox therapeutic modes, including radio-
therapy115,231 and protein shock therapy 142 have been tried to cure filariasis, but
they have been valueless or even dangerous.
The medical treatment of filariasis has proved almost as depressing as the
surgical management. As early as 1846, Bonyun claimed to cure chyluria with
the bark of the mangrove tree, but his account hardly makes convincin g
reading36. Myers experimented with the effects of quinine, salicylic acid ,
arsenic and santonin on microfilariae in vitro, but concluded that the amount
of drug required to kill the wo rms would be sufficient to kill the host as well 180.
Lawrie in India in 1891 considered that chyluria could be removed wit h
thymol129, but subsequent investigators were unable to confirm his observ -

ations. Similar evanescent claims were made for methylene blue 89, salvarsan
(arsenic) 39, pepper201, antimony 202, hectine226, anthiomaline 40and arsphen-
amine227. A vast number of other drugs were also tried and found wanting. For
example, Chopra and Rao reported in 1919 that they had assessed 72 different
drugs without finding any worthwhile filaricidal activity 52. Sulphonamides,
however, were shown to be of some value in acute inflammatory filariasis ,
presumably because of their action on secondary bacterial infections 78.
In 1947, Hewitt and his colleagues reported that a new piperazin e
derivative, diethylcarbamazine, produced a rapi d disappearance of microfilariae
from the blood of cotton rats infected with Litomosoides carinii and in dogs
with Dirofilaria immitis infections, although there was little effect on the adult
worms themselves 111. Clinical trials were then carried out in the West Indies by
Santiago-Stevenson and colleagues : 26 patients with filariasis were treated and
a striking reduction in the level of microfilaraemia was observed and toxi c
effects were tolerable 209. Subsequent studies showed that the drug and it s
metabolites did not have a direct effect on microfilariae in vitro or on
microfilariae in hydrocele fluid. Hawking and his colleagues concluded that the
drug modified the microfilariae in some way so that they were removed by the
reticulo-endothelial system109,110. Despite the high hopes held initially for this
drug, it has not revolutionized the treatment of filariasis, often having only a
transient effect on microfilaraemia and sometimes precipitating acut e
inflammatory reactions, especially in malayan filariasis, which may merel y
accelerate the natural history of the disease.
The distribution and prevalence of filariasis was quite inexplicable unti l

Manson discovered that microfilariae developed in mosquitoes. Even then ,
another 20 years were to pass before the method of transference back t o
humans was understood. In 1908, George Low wrote a paper entitled "Th e
unequal distribution of filariasis in the tropics" 141 as a result of his experiences
of that condition in the West Indies. He emphasized that the dicta "N o
Anopheles, no malaria" or "No Stegomyia fasciata [= Aedes aegypti], no
yellow fever" could be extended to "No Culex fatigans or suitable mosquito,
no Filaria nocturna"141. Low remarked, however, that what was more difficult
to explain was why the disease should remain localized in certain parts of the
world although the intermediate hosts were much more widely distributed. He
noted that filariasis was perhaps the most tedious of all the tropical diseases of
which to study the epidemiology, for:
the only way to arrive at a conclusion of how many individuals in a given district are
infected is to make exhaustive night blood examinations of the population
generally.141
Filariasis 627
Nevertheless, countless inve stigators have burnt the midnight oil and hundreds
of papers describing the distributio n and intensity of filarial infection in various
communities have appeared since Low's time. These have all given rise to the
same general conclusions, namely that human s are the only significant reservoir
of W. bancrofti but that subperiodic B. malayi is a zoonosis, the prevalence of
microfilaraemia in endemic areas increases with age or plateaus in adult life,
the prevalence of disease with chronic lymphatic obstruction increases wit h
age, and that vectors of filariae in clude species of Aedes, Anopheles, Culex and
Mansonia. There are a number of physiological forms within the W. bancrofti
complex, however, which differ in their capacity for development in variou s
mosquito vectors211. Furthermore, it became clear that the transmission o f
infection is remarkably inefficient. Hairston and de Meillon 104 first drew
attention to this in 1968 when they showed that bites by an average of 15,500
mosquitoes carrying infective larvae were necessary for the production of each
new case of microfilaraemia i n Rangoon, Burma. Furthermore, less than 1% of
mosquitoes carried infective larvae. Infection only occurred because th e
average person was bitten by around 100,000 mosquitoes per year.
The distribution of filariasis is not static. The infection was probabl y
brought to the Western Hemisphere by the transportation of infected slave s
from Africa 212 and was introduced into the sugar canefields of Queensland by
infected labourers from the south Pacific islands. With improving standards of
living, the worm has disappeared from some developed countries such as in the
southeastern USA212 and northeastern Australia147 . On the other hand, rapi d
urbanization and industrialization without concurrent provision of wast e
disposal systems has lead to an increased breeding of culicine moquitoe s
(especially Culex quinquefasciatus) which, when coupled with immigration of
infected persons from endemic areas, has resulted in the inception of, or a n
increase in, transmission of the infection 200.
Means of preventing the exit of microfilariae from the host became obviou s
when the uptake of microfilariae by mosquitoes was shown by Manson. These
ways were either the eradication of the mosquitoes or the prevention of inter-
action between the insect and the human. The first was frequently impossible
but there was hope for the latter with the us e of mosquito nets and the screening
of houses. It was not obvious, however, that the same measures would prevent
infection until it was discovered that infective larvae entered the host directly
from the biting mosquito rather than by being ingested in water. Fortunately,
these same measures were effective in the prevention of malaria and yello w
fever, and it was fear of the latter devastating infections that usually stimulated
the installation of antimosquito measures. Nevertheless, filariasis in its ow n
right has also been the subject of control efforts. As early as 1900, an attempt
was made to institute a campaign against filariasis in Barbados, but although

considerable attention was given to educational measures, little was achieved.
This resulted in 1912 in a particularly ill-informed and racist editorial which
compared the prospects for control in white Australia versus the black Wes t
Indies:
of course, the difficulty, even for Brisbane, would be finding the carriers....and this
difficulty for native populations, such as the negroes in the West Indies would be
almost insurmountable. In the same way, having found that a negro was a carrier,
it would be practically impossible to make him sleep under a mosquito net, or to
explain to him the danger he was to other people. This will always be the difference
in dealing prophylactically with white and native populations. 13
and concluded that the destruction of the int ermediate host was the only feasible
proposition. Nevertheless, attempts to control breeding of mosquitoe s
(particularly those that were specifically transmitters of infection, a procedure
known as "species sanitation") and obstructions to contact between man an d
mosquito remained the mainstays of filariasis control until the introduction of
the powerful chlorinated hydroca rbon insecticides (e.g. DDT) after World War
II and the discovery of diethylcarbamazine in 1947.
Modifications to the physical environment, in cluding elimination of polluted
water in urban areas (C. quinquefasciatus) 68, water containers in Tahit i
(An. polynesiensis) 176, and drainage of swamps (Mansonia) 187, have been tried
with variable success. Insecticides, including chlorinated hydrocarbons an d
organophosphate compounds, have been used to control larvae and adul t
worms, but their expense and the evolution of resistance to these agents i s
creating increasing problems 68. In areas where Anopheles species are the major
vectors, house spraying with residual insecticides has resulted in the welcome
byproduct of filariasis control 234. Major efforts to control filariasis with either
mass or selective administration of diethylcarbamazine have met with littl e
effect except in circumscribed island communities 100. Limitations of
human-mosquito contact with flyscreens and the humble mosquito net offe r
perhaps the most promising prospects for control.
Despite pockets of success, more people are infected now than whe n
Manson discovered the vector over 100 years ago, but the prevalence an d
severity of filariasis would be even worse were it not for:
the efforts of a devoted but largely anonymous band of health officers,
entomologists and their assistants which have been responsible for mosquito control
in all the major cities, towns and even many small townships of the tropics. These
measures were rarely aimed specifically against the vectors of filariasis but more
against the vectors of malaria and arboviruses. In many cities, the original purpose
is forgotten and mosquito control remains an exercise in aesthetics which makes life
more tolerable by removing 'nuisance' mosquitoes.182
Filariasis 629
TROPICAL EOSINOPHILIA
In 1939, Meyers and Kouwenaar described a series of seven Javanese men who
had lymphadenopathy and a marked eosinophilia. When the lymph nodes were
biopsied, eosinophilic granulomas surrounding microfilariae were found .
Nevertheless, observation for as long as three years failed to reveal an y
microfilariae in the peripheral blood, n or were any adult filariae seen in excised
glands. The patients had no evidence of lymphatic obstruction but two ha d
asthma and two had haemorrhag ic nephritis so the authors suggested that these
syndromes were possibly allergic reactions to filariae 178. In the paper
immediately following this report, Bonne, in the same journal, describe d
finding extraordinary eosinophilic granulomas with giant cells around micro-
filariae in the spleen of a Javanese man killed in a motor vehicle accident .
Bonne thought that this condition was similar to that described by Meyers and
Kouwenaar and suggested that the finding represented either an undescribe d
phase in the life cycle of one of the common filarial species or a manifestation
of an unusual filarial parasite 34. In 1942, Dhayagude and Amin in Bomba y
reported a further 11 cases of microfilarial granuloma 75.
Meanwhile, in 1940, Frimodt-Möller and Barton had described a series of
175 patients with what they termed a "pseudo-tuberculous condition" charact-
erized by dyspnoea, eosinophilia a nd extensive, persistent mottling of the lungs
on chest X-ray92. In 1943, Weingarten reported a condition which he had seen
in 81 cases, and which he believed to be a new disease entity, that he calle d
tropical eosinophilia. The illness was characterized by fever, paroxysma l
cough, dyspnoea, wheezing, splenomegaly and eosinophilia while chest X-ray
examination of the lungs disclosed a distinctive, disseminated mottling. I n
contrast to Löffler's syndrome, the illness persisted for weeks or months an d
responded to treatment with arsenicals 235. Weingarten could find no cause for
the condition but noted that it was common in coastal regions. The relationship
with the conditions described by Meyers and Kouwenaar and by Bonne was not
immediately apparent and there was considerable speculation to its cause ,
although a parasitic aetiology seeme d likely. In 1944, Carter and his colleagues
postulated that the cause was the cheese mite 51. In 1955, Winter suggested that
tropical eosinophilia may be regarded as an accentuated state of sensitivity in
persons infected with filariae 237.
In 1957, Gault and Webb reported that liver biopsies in four children with
tropical eosinophilia (including the typical pulmonary symptoms) showed a
striking eosinophilic infiltration in the portal triads, then found similar changes
together with granulomatous foci around nematode larvae in a surgical biopsy
from a further patient with hepatomegaly 94. In the following year, Danaraj and
his colleagues in Singapore noted that W. bancrofti microfilariae occurred in
Chinese, Indians and Malays, but that eosinophilic lung was virtually confined
to Indians. Furthermore, these latter patients had high titres of antibodies to D.
immitis antigen and responded well to tr eatment with diethylcarbamazine. They
postulated, therefore, that the illne ss was due to infection with a filarial parasite
of animal origin which could n ot complete its development in humans 69,70. This
view seemed to be supported when Buckley reported that the condition wa s
evoked in a human volunteer infected with Brugia malayi then B. pahangi 44.
In 1960, Webb and his colleagues demonstrated the presence of microfilarial
granulomas in lung biopsies of patients wi th tropical pulmonary eosinophilia 233.
In 1979, Ottesen and his colleagues reported that patients with this condition
had evidence of immediate hypersensitity reactions to filarial antigens 189.
Although it remains unproven, the consensus of opinion now is that W.
bancrofti and B. malayi are the most probable causes of the affliction, th e
differences from the usual manifestations of filariasis resulting from a failure
of microfilariae to evade the host's immune responses so that the parasites are
screened out in the lungs, spleen and liver.
REFERENCES
1. ANDERSON J et al. Filariasis in British Guiana (A report of the Filariasis Commission,

1921). London School of Tropical Medicine Research Memoir Series, Number 7, pp 122,
1921
2. ANDREWS EW. Dzibilchaltun; lost city of the Maya. National Geographic Magazine 115:
90-119, 1959
3. ANNETT HE, DUTTON JE, ELLIOTT JH. Report of the malaria expedition to Nigeria of
the Liverpool School of Tropical Medicine and Medical Parasitology. Part II. Filariasis.
Thompson Yates Laboratory Reports, volume 4, 1901
4. ANONYMOUS. Elephantiasis scroti. Lancet ii: 43-44, 1844
5. ANONYMOUS. Worms in urine and blood. Lancet ii: 310, 1872
6. ANONYMOUS. Haematozoa and chyluria. British Medical Journal i: 147-148, 1873
7. ANONYMOUS. The newly-discovered haematozoon inhabiting human blood. Lancet ii:
889-890, 1872; i:56-57, 1873
8. ANONYMOUS. Is the mosquito the intermediate host of the Filaria sanguinis hominis?
British Medical Journal i: 904, 1878
9. ANONYMOUS. Discussion of 160
10. ANONYMOUS. The Veterinarian, 1883
11. ANONYMOUS. The life-history of Filaria sanguinis hominis. British Medical Journal i:
1073, 1888
12. ANONYMOUS. British Medical Journal ii: 443, 682, 1900
13. ANONYMOUS. The prevention of filariasis. Journal of Tropical Medicine and Hygiene 15:
91-92, 1912
14. ANONYMOUS. Filarial periodicity. Lancet ii: 270-271, 1937
15. ASH LR, LITTLE MD. Brugia beaveri sp. n. (Nematoidea: Filarioidea) from the raccoon
(Procyon lotor) in Louisiana. Journal of Parasitology 57: 1043-1051, 1971
16. ASHBURN PM, CRAIG CF. A new blood filaria of man: Filaria philippinensis. American
Journal of Medical Science 132: 435-443, 1905
17. AUCHINCLOSS H. A new operation for elephantiasis. Porto Rico Journal of Public Health
and Tropical Medicine 6: 149-150, 1930
18. BABIONE RN. Mumu. A few facts about filariasis for folks who fear that filaria-infected
fellows will fetch filariae from the front. Hawaii Medical Journal 5: 69-71, 1945
19. BAHR PH. Filariasis and elephantiasis in Fiji. Report to the London School of Tropical
Medicine, Witherby and Co., London, pp 192, 1912
20. BANCROFT J. Cases of filarious disease. Transactions of the Pathological Society o f
Filariasis 631
London 29: 407-417, 1878

21. BANCROFT J. On filaria. Transactions of the Intercolonial Medical Congress of Australasia,
pp 49-54, 1889
22. BANCROFT J. Cited in 56
25. BANCROFT TL. Filarial metamorphosis in the mosquito. Australasian Medical Gazette 18:
20, 1899
26. BANCROFT TL. On the metamorphosis of the young form of Filaria bancrofti, Cobb
(Filaria sanguinis hominis, Lewis; Filaria nocturna, Manson) in the body of Culex ciliaris,
Linn., the "house mosquito" of Australia. Journal and Proceedings of the Royal Society of
New South Wales 33: 48-62, 1899. Reprinted in the Journal of Tropical Medicine and
Hygiene 2: 90-94, 1899; 2: 149-153, 1900
27. BANCROFT TL. Preliminary notes on the intermediary host of Filaria immitis, Leidy.
Journal and Proceedings of the Royal Society of New South Wales 35: 44-46, 1901
28. BANCROFT TL. On some further observations on the life-history ofFilaria immitis, Leidy.
Journal and Proceedings of the Royal Society of New South Wales 37: 254-257, 1903.
Reprinted in British Medical Journal i: 822-823, 1904
29. BARBOT J. A description of the coasts of North- and South Guinea and of Ethiopia inferior
etc, London, six volumes, 1732
30. BASCOME E. On elephantiasis. Lancet i: 435-436, 1846
31. BASTIAN H, HARLEY J. Cited in 191
32. de BEAUREPAIRE ARAGÃO H. Novo methodo para facilitar o diagnostico e a coservação
dos embryos de filarias no sangue e de parasitas nas fézes. Brazil Medico 33: 1-2, 1919
33. BELL D. Membrane filters and microfilariae: a new diagnostic technique. Annals of Tropical
34. BONNE C. Over hypereosinophilie in de milt gecombineerd met een filaria-infectie.
35. BONNE C, LIE KJ, MOLENKAMP WJ, MYEREN FW. Wuchereria malayi, de
Macrofilaria behoorende bij de Microfilaria malayi. Geneeskundig Tijdschrift voor
Nederlandsch-Indië 81: 1487-1501, 1941
36. BONYUN GR. Report of a case of chylous urine successfully treated with the bark of
Rhizopus racemosa, or mangrove, a tree indigenous to British Guiana. Lancet i: 95-96, 1846
37. BOURNE AG. A note on Filaria sanguinis hominis: with a description of the male specimen.
38. BOURNE AG. Transactions of the South Indian Branch of the British Medical Association
2: 396-398, 1888
39. BRANCH ER. Salvarsan in filariasis. Journal of Tropical Medicine and Hygiene 16: 364-365,
1913
40. BROWN HW. The treatment of filariasis (Wuchereria bancrofti) with lithium antimony
thiomalate. Journal of the American Medical Association 125: 952-958, 1944
41. BRUG SL. Een nieuwe Filaria-soort (Filaria malayi) parasiteerendi bij den mensch
(voorloopige mededeeling). Geneeskundig Tijdschrift voor Nederlandsch-Indië 67: 750-754,
1927
42. BRUG SL. Filariasis in Nederlandsch-Indië. Geneeskundig Tijdschrift voor
43. BRUG SL, de ROOK H. Filariasis in Nederlandsch-Indië. II. Deoverbrenging van Filaria
malayi. Geneeskundig Tijdschrift voor Nederlandsch-Indië 70: 451-472, 1930
44. BUCKLEY JJ. Tropical pulmonary eosinophilia in relation to filarial infections (Wuchereria
spp.) of animals. Preliminary note. Transactions of the Royal Society of Tropical Medicine and
Hygiene 52: 335-336, 1958
45. BUCKLEY JJ. A new genus, Brugia, for Wuchereria spp. of the malayi group. Abstract of
Papers, Sixth International Congress of Tropical Medicine and Malaria, Lisbon, p 35, 1958
46. BUCKLEY JJ. On Brugia gen. nov. for Wuchereria spp. of the "malayi" group i.e. W. malayi
Brug, 1927, W. pahangi Buckley and Edeson, 1956, and W. patei Buckley, Nelson and
Heisch, 1958. Annals of Tropical Medicine and Parasitology 54: 75-77, 1960
47. BUCKLEY JJ, EDESON JF. On the adult morphology ofWuchereria sp. (malayi?) from a
monkey (Macaca irus) and from cats in Malaya, and on Wuchereria pahangi n. sp. from a
dog and a cat. Journal of Helminthology 30: 1-20, 1956
48. BURNELL AC. The voyage of John Hughen van Linschoten to the East Indies, Hakluyt
Society, London, volume 1, pp 307, 1885
49. CARME B, LAIGRET J. Longevity of Wuchereria bancrofti var. pacifica in mosquito
infection acquired from a patient with low level parasitemia. AmericanJournal of Tropical
50. CARNOCHAN. Cited in 151
51. CARTER HF, WEDD G, D'ABRERA V. The occurrence of mites (Acarina) in human
sputum and their possible significance. Indian Medical Gazette 79: 163-168, 1944
52. CHOPRA RN, RAO SS. Chemotherapy of filarial infection. Indian Journal of Medical
Research 27: 549-592, 1939
53. CILENTO R. Tropical diseases in Australia, second edition, W R Smith and Paterson,
Brisbane, pp 461, 1942
54. COBBOLD TS. On the development of Bilharzia haematobia; together with remarks on the
ova of another urinary parasite (the so-called Trichina cystica of Dr. Salisbury) occurring in
a case of haematuria from Natal. British Medical Journal ii: 89-92, 1872
55. COBBOLD TS. Cited in 191
56. COBBOLD TS. Verification of recent haematozoal discoveries in Australia and Egypt. British
57. COBBOLD TS. Discovery of the adult representative of microscopic filariae. Lancet ii: 70-71,
1877
58. COBBOLD TS. On Filaria Bancrofti. Lancet ii: 495-496, 1877
59. COBBOLD TS. Discovery of the intermediary host of Filaria sanguinis hominis (F.
Bancrofti). Lancet i: 69, 1878
60. COBBOLD TS. The life-history of Filaria bancrofti, as explained by the discoveries of
Wucherer, Lewis, Bancroft, Manson, Sonsino, myself and others. Journal of the Linnean
Society (Zoology) 14: 356-370, 1878
62. COBBOLD TS. Introduction to observations on filariae by Drs. Patrick Manson, John R.
Somerville, Joseph Bancroft, J.F. da Silva Lima, J.L. Paterson, Pedro S. de Magalhaes and J.
Mortimer-Granville, communicated, with an introduction by the President. Journal of the
Quekett Microscopical Club 6: 58-60, 1880
63. CORRE A. Note sur l'helminthe rencontré dans les urines hématochyleuses. Revue des
Sciences Naturelles, 1872
64. CORTESÃO A. The Suma Oriental of Tomé Pires, Hakluyt Society, London, pp 578, 1944
65. CREVAUX J. De l'hématurie chyleuse ou graisseuse des pays chauds, Thèse de Paris, pp 64,
1872
66. CROSS JH, PARTONO F, HSU MK, ASH LR, OEMIJATI S. Experimental transmission of
Wuchereria bancrofti to monkeys. American Journal of Tropical Medicine and Hygiene 28:
56-66, 1979
67. CUNNINGHAM DD. The haematozoon; notes on its discovery and its relation to the canine
filaria. Lancet i: 835-837, 1873
68. CURTIS CF, FEACHEM RG. Sanitation and Culex pipiens mosquitoes: a brief review.
69. DANARAJ T. The treatment of eosinophilic lung (tropical eosinophilia) with
diethylcarbamazine. Quarterly Journal of Medicine 27: 243-263, 1958
70. DANARAJ TJ, da SILVA LS, SCHACHER JF. The serological diagnosis of eosinophilic
lung (tropical eosinophilia) and its etiological implications. American Journal of Tropical
71. DANIELS CW. Discovery of the parental form of a British Guiana blood worm. British
72. DAVID HL, EDESON JF. Filariasis in Portuguese Timor, with observations on a new
microfilaria found in man. Annals of Tropical Medicine and Parasitology 59: 193-204, 1965
Filariasis 633
73. DEMARQUAY JN. Note sur une tumeur des bourses contenant un liquide laiteux
(galactocèle de Vidal) et renferment des petits êtres vermiformes que l'on peut considérer
comme des helminthes hematoides à l'état d'embryon. Gazette Médicale de Paris 18: 665-667,
1863. Translated in 117
74. DENNIS DT, KEAN BH. Isolation of microfilariae: report of a new method. Journal of
Parasitology 57: 1146-1147, 1971
75. DHAYAGUDE RG, AMIN BR. Microfilarial granuloma of the spleen. American Journal of
Pathology 18: 351-361, 1942
76. DICKSON JG, HUNTINGDON RW, EICHOLD S. Filariasis in Defense Force, Samoan
Group. Preliminary report. United States Naval Medical Bulletin 41: 1240-1251, 1943
77. DUTCHER BH, WHITMARSH PL. The results of blood cultures from thirty six individuals
with their possible bearing on the etiology of the so-called filarial diseases; and description of
a new parasitic bacillus, believed to be the causative agent of filariasis. American Journal of
Tropical Diseases and Preventive Medicine 3: 69-74, 1915
78. EARLE KV. The use of sulphonamide compounds in filarial complications. Medical Journal
of Australia ii: 200-202, 1941
79. EDESON JF, WHARTON RH. The experimental transmission ofWuchereria malayi from
man to various animals in Malaya. Transactions of the Royal Society of Tropical Medicine
and Hygiene 52: 25-38, 1958
80. EDESON JF, WILSON T, WHARTON RH, LAING AB. Experimental transmission of
Brugia malayi and B. pahangi to man. Transactions of the Royal Society of Tropical
81. EDWARDS FW. The carriers of Filaria bancrofti. Journal of Tropical Medicine and Hygiene
25: 168-170, 1922
82. FAIRLEY NH. Serological and intradermal tests in filariasis. A preliminary report.
83. FAYRER J. Naevoid elephantiasis. Indian Annals of Medical Science 19: 76-80, 1865
84. FAYRER J. Elephantiasis arabum. Transactions of the Pathological Society of London 30:
488-503, 1879. Abstracted in Lancet ii: 267-268, 1879
85. FENG LC. Some experiments with mosquitoes and Microfilaria malayi in Huchow
(Chekiang) China. Transactions of the Ninth Congress of the Far Eastern Association of
Tropical Medicine, Nanking 1: 491-494, 1934. Abstracted in Tropical Diseases Bulletin 32:
647, 1935
86. FINLAY CJ. Anales de la Reale Academia de Ciencias Médicas Físicas y Naturales de al
Habana 18: 147-169, 1881
87. FISHER G. Die Behandlung der Elephantiasis arabum mittelst Ligatur oder Compression der
Hauptarterie. Archiv für pathologische Anatomie, Physiologie und für klinische Medicin
(Virchow) 46: 328-350, 1869
88. FITCH R. Cited in 139
89. FLINT A. A case of Filaria sanguinis hominis, with chyluria, successfully treated with
methylene blue. New York Medical Journal 61: 737-739, 1895
90. FOX WT. Clinical lecture on a case of elephantiasis arabum. Medical Times and Gazette ii:
427-429, 1878
91. FOX RT. Discussion of 84
92. FRIMODT-MÖLLER C, BARTON RM. A pseudotuberculous condition associated with
eosinophilia. Indian Medical Gazette 75: 607-613, 1940
93. FÜLLEBORN F. Über Mikrofilarien des Menschen im deutschen Südsee-Gebiet und deren
"Turnus" nebst Bemerkungen über die klinischen Manifestationen der dortigen Filariasis.
Archiv für Schiffs- und Tropen-Hygiene 16: 533-547, 1912
94. GAULT EW, WEBB JK. Tropical eosinophilia. Hepatic lesions related to presence of
nematode larvae. Lancet ii: 471-472, 1957
95. GODFREY F. On a case of elephantiasis scroti. Lancet i: 352-353, 1851
96. GOODMAN G. Report of a case of elephantiasis scroti with successful operation. Lancet i:
889-890, 1876.
97. GORTER AJ. De operatieve behandeling van elephantiasis der onderste extremiteiten.
98. GRACE AW, GRACE FB. Researches in British Guiana 1926-1928 on the bacterial
complications of filariasis and endemic nephritis, with a chapter on epidemic abscess and
cellulitis in St. Kitts, British West Indies. Memoir Series of the London School of Hygiene
and Tropical Medicine, No. 3, pp 75, 1931
99. GRASSI B, NOÈ G. The propogation of the filariae of the blood exclusively by means of the
puncture of peculiar mosquitoes. British Medical Journal ii: 1306-1307, 1900
100. GROVE DI. Selective primary health care: strategies for the control of disease in the
developing world. VII. Filariasis. Reviews of Infectious Diseases 5: 933-944, 1983
101. GROVE DI, CABRERA BD, VALEZA FS, GUINTO RS, ASH LR, WARREN KS.
Sensitivity and specificity of skin reactivity to Brugia malayi and Dirofilaria immitis
antigens in bancroftian and malayan filariasis in the Philippines. American Journal of
102. GULLAND GL. The condition of the blood in filariasis. British Medical Journal i: 831-832,
1902
103. HAGA J. Filariasis-onderzoek over dag. Geneeskundig Tijdschrift voor Nederlandsch-Indië
63: 864-884, 1923
104. HAIRSTON NG, de MEILLON B. On the inefficiency of transmission of Wuchereria
bancrofti from mosquito to the human host. Bulletin of the World Health Organization 38:
935-941, 1968
105. HAMILTON RG, HUSSAIN R, OTTESEN EA. Immunoradiometric assay for detection of
filarial antigens in human serum. Journal of Immunology 133: 2237-2242, 1984
106. HANDLEY WS. A prospective cure for elephantiasis. Lancet i: 31-33, 1909
107. HARTZ PH. Contribution to the histopathology of filariasis. American Journal of Clinical
Pathology 14: 34-43, 1944
108. HAWKING F. The 24-hour periodicity of microfilariae: biological mechanisms responsible
for its production and control. Proceedings of the Royal Society, Series B 169: 59-76, 1967
109. HAWKING F, LAURIE W. Action of hetrazan on filariasis and onchocerciasis. Lancet ii:
146-147, 1949
110. HAWKING F, SEWELL P, THURSTON JP. Mode ofaction of hetrazan in filariasis. Lancet
ii: 730-731, 1948
111. HEWITT RI, KUSHNER S, STEWART HW, WHITE E, WALLACE WS, SUBBAROW
Y. Experimental chemotherapy of filariasis. Journal of Laboratory and Clinical Medicine 32:
1293-1329, 1947
112. HOEPPLI R. Parasitic diseases in Africa and the Western Hemisphere. Acta Tropical
Supplementum 10, pp 240, 1969
113. HUNTER GW. Skin testing for filariasis with homologous antigen. Proceedings of the Sixth
International Congress of Tropical Medicine and Parasitology 2: 479-483, 1948
114. JACHOWSKI LA, OTTO GF, WHARTON JD. Filariasis in American Samoa. I. Loss of
microfilaria in the absence of continued reinfection. Proceedings of the Helminthological
Society of Washington 18: 25-28, 1951
115. JAFFE HL. Evaluation of roentgen therapy in filariasis. American Journal of Roentgenology
and Radium Therapy 53: 483-490, 1945
116. JAMES SP. On the metamorphosis of theFilaria sanguinis hominis in mosquitos. Especially
with reference to its metamorphosis inAnopheles rossi and other mosquitos of the Anopheles
genus. British Medical Journal ii: 533-536, 1900
investigations, Cornell University Press, pp 677, 1978
118. KENNARD CS. Filaria and mosquitoes. British Medical Journal ii: 754, 1900
119. KING BG. Early filariasis diagnosis and clinical findings: a report of cases in American
troops. American Journal of Tropical Medicine 24: 285-298, 1944
120. KNOTT J. The periodicity of the microfilaria of Wuchereria bancrofti. Preliminary report
of some injection experiments. Transactions of the Royal Society of Tropical Medicine and
Hygiene 29: 59-64, 1935
121. KNOTT J. The treatment of filarial elephantiasis of the leg by bandaging. Transactions of
122. KONDOLÉON E. Die operative Behandlung der elephantiasischen Ödeme. Zentralblatt für
Filariasis 635
Chirurgie 39: 1022-1025, 1912

123. KORKE. Observations on filariasis in some areas in British India. Part III. Observations on
the atypical variety of W. bancrofti and its significance. Indian Journal of Medical Research
16: 1023-1032, 1929
124. LAING AB, EDESON JF, WHARTON RH. Studies on filariasis in Malaya: the vertebrate
hosts of Brugia malayi and B. pahangi. Annals of Tropical Medicine and Parasitology 54:
92-99, 1960
125. LANCERAUX. De la filariose. Semaine Médicale 8: 332-333, 1888
126. LANE C. The mechanism of filarial périodicity. Lancet i: 1291-1293, 1929
127. LAURENCE BR. Elephantiasis in Greece and Rome and the Queen of Punt. Transactions
128. LAURENCE BR. The curse of Saint Thomas. Medical History 14: 352-363, 1970
129. LAWRIE E. The cure of chyluria depending on filariae in the blood by thymol. Lancet :i
364-365, 1891
Leipzig, volume 1, Abtheilung 1, pp 1009, 1879-1886. The parasites of man and the diseases
which proceed from them. A textbook for students and practitioners, translated by WE
Hoyle, Young J Pentland, Edinburgh, pp 771, 1886
131. LEWIS TR. A report on the microscopic objects found in cholera evacuations, etc. Sixth
Annual Report of the Sanitary Commissioner with the Government of India (1869),
Appendix A, pp 125-178, 1870
132. LEWIS TR. On a haematozoon inhabiting human blood, its relationto chyluria and other
diseases. Eighth Annual Report of the Sanitary Commissioner with the Government of India
(1871), Appendix E, pp 241-266, 1872. Abstracted in Lancet ii: 889-890, 1872; i: 56-57,
1873
133. LEWIS TR. In, Tenth Annual Report of the Sanitary Commissioner with the Government
of India (1873), Appendix B, pp 111-133, 1874. Abstracted in Lancet i: 209-210, 1875
134. LEWIS TR. Filaria sanguinis hominis (mature form), found in a blood clot in naevoid
elephantiasis of the scrotum. Lancet ii: 453-455, 1877
135. LEWIS TR. Remarks regarding the haematozoa found in the stomach of Culex mosquito.
Proceedings of the Asiatic Society of Bengal, pp 89-93, 1878
136. LEWIS TR. Cited in 175
137. LICHTENSTEIN A. Filaria-onderzoek te Bireuën. Geneeskundig Tijdschrift voor
138. van LINSCHOTEN JH. Cited in 48
139. LOCKE JC. The first Englishmen in India, Routledge, London, pp 229, 1930
140. LOW GC. A recent observation on Filaria nocturna in Culex: probable mode of infection
in man. British Medical Journal i: 1456-1457, 1900
141. LOW GC. The unequal distribution of filariasis in the tropics. Lancet i: 279-281, 1908
142. LOW GC, DIXON DS. Elephantiasis treated by protein shock. Lancet i: 72-73, 1930
143. LOW GC, MANSON-BAHR P. Filaria bancrofti in the production of elephantiasis and
kindred diseases. British Medical Journal ii: 233-234, 1920
144. LUCRETIUS CARUS T. Cited in 112
145. LYNCH GW. A note on the occurrence of Filaria in Fijians. Lancet i: 21, 1905
146. MACKENZIE S. A case of filarial haematochyluria. Transactions of the Pathological Society
of London 33: 394-410, 1882. Abstracted in Lancet ii: 722-723, 1881 and British Medical
Journal i: 740-741, 1882
147. MACKERRAS MJ. The decline of filariasis in Queensland. Medical Journal of Australia i:
702-704, 1958
148. McKINLEY EB. The role of bacteria in acute filarial lymphangitis. Porto Rico Journal of
Public Health and Tropical Medicine 6: 419-427, 1931
149. MADDEN FC, IBRAHIM A, FERGUSON AR. Onthe treatment of elephantiasis of the legs
by lymphangioplasty. British Medical Journal ii: 1212-1214, 1912
150. de MAGALHÃES PS. Filaria bancrofti. Gazeta Medica da Bahia, third series, 4: 97-100,
1886
151. MAITLAND J. Elephantiasis and allied disorders, Government Press, Madras, 1891
152. MAITLAND J. A case of "filarial disease" of the lymphatics in which a number of adult
filariae were removed from the arm. British Medical Journal i: 844-846, 1894
153. MAITLAND J. The operative treatment of lymphangiectasis of filarial origin. British
154. MANSON P. Description of operation for elephantiasis of the scrotum. Customs Gazette,
Medical Reports, Shanghai, 13: 26-33, 1872
155. MANSON P. Filaria sanguinis hominis. China Imperial Maritime Customs. Medical
Reports for the half year ended 31st March 1877, 13th issue, pp 30-38, 1877
156. MANSON P. Further observations of Filaria sanguinis hominis. China Imperial Maritime
Customs. Medical Reports for the half year ended 30th September 1877, 14th issue, pp 1-26,
1878
157. MANSON P. On the development of Filaria sanguinis hominis and on the mosquito
considered as a nurse. Journal of the Linnean Society (Zoology) 14: 304-311, 1878
158. MANSON P. On Chinese haematozoa. Medical Times and Gazette i: 220-223, 249-250,
304-305, 1878
159. MANSON P. Additional notes on Filaria sanguinis hominis and filaria disease. China
Imperial Maritime Customs. Medical Reports for the half year ended 30th September 1879,
18th issue, pp 31-51, 1880. Abstracted in British Medical Journal ii: 891, 1880
160. MANSON P. Further observations on microfilariae, with descriptions of new species,
communicated (with a prefatory note) by the President. Journal of The Quekett
Microscopical Club 6: 130-140, 1880
161. MANSON P. Additional notes on Filaria sanguinis hominis and filaria disease. Discovery
of adult F. bancrofti. China Imperial Maritime Customs. Medical Reports for the half year
ended 30th September 1880, 20th issue, pp 13-15, 1881. Reprinted as: Lymph scrotum
showing filaria in situ. Transactions of the Pathological Society of London 32: 285-302,
1881
162. MANSON P. Notes on filaria disease. China Imperial Maritime Customs. Medical Reports
for the half year ended 31st March 1882, 23rd issue, pp 1-16, 1882. Abstracted in British
163. MANSON P. The Filaria sanguinis hominis and certain new forms of parasitic diseases in
India, China and certain warm countries, London, pp 186, 1883
164. MANSON P. The metamorphosis of Filaria sanguinis hominis in the mosquito.
Transactions of the Linnean Society of London, series 2, 2: 367-388, 1884
165. MANSON P. The geographical distribution, pathological relations and life history of Filaria
sanguinis hominis diurna and Filaria sanguinis hominis perstans in connexion with
preventive medicine. Transactions of the Seventh International Congress of Hygiene and
Demography, London, August 10-17, 1891 i: 79-97, 1892. Abstracted in Medical Press and
Circular 103, new series, 52: 202-205, 1891 and Semaine Médecine 11: 342, 1891
166. MANSON P. On filarial periodicity. British Medical Journal ii: 644-646, 1899
170. MANSON P. Discussion of 196
171. MANSON-BAHR P. The mechanism of filarial periodicity. Lancet ii: 45-47, 1929
172. MANSON-BAHR P. The nomenclature of the filaria of the Pacific region producing
non-periodic embryos (Wuchereria pacifica). Tropical Diseases Bulletin 38: 361-367, 1941
173. MANSON-BAHR P. The story of Filaria Bancrofti. A critical review. Journal of Tropical
Medicine and Hygiene 62: 53-61, 85-94, 106-117, 138-145, 160-173, 1959
174. MANSON-BAHR P. Patrick Manson as a parasitologist. A critical review. International
Review of Tropical Medicine, DR Linicombe (Editor), Academic Press, New York, pp
77-129, 1961
175. MANSON-BAHR PH, ALCOCKA. The life and works of Sir Patrick Manson, Cassell and
176. MARCH HN, LAIGRET J, KESSEL JF, BAMBRIDGE B. Reduction in the prevalence of
clinical filariasis in Tahiti following adoption of a control program. American Journal of
Filariasis 637

177. MAXWELL JP. Filarial abscess. British Medical Journal ii: 609-612, 1901
178. MEYERS FM, KOUWENAAR W. Over hypereosinophilie en over een merkwaardigen
vorm van filariasis. Geneeskundig Tijdschrift voor Nederlandsch-Indië 79: 853-873, 1939
179. MÜLLER OF. Verzeichniss der bisher entdeckten Eingeweidewürmer der Thiere, in welchen
sie gefunden Worden, und besten Schriften, die derselben erwähnen. Naturforscher, Halle 22:
33-86, 1787
180. MYERS WW. Observations on Filaria sanguinis hominis in South Formosa. China Imperial
Maritime Customs. Medical Reports for the half year ended 31st March, 21st issue, pp 1-21,
1881
181. MYERS WW. Further observations on the Filaria sanguinis hominis in South Formosa.
Transactions of the Epidemiological Society, new series, 6: 58-103, 1888
182. NELSON GS. Issues in filariasis - a centuryof enquiry and a century of failure. Acta Tropica
38: 197-204, 1981
183. NOÈ G. Propagazione delle filarie del sangue esclusivamente per mezzo della puntura delle
zanzare. 2. Nota preliminare. Atti della Reale Accademia der Lincei. Rendiconti della Classe
di Scienze Fisiche, Matematiche e Naturali, Roma, fifth series, 9: 357-362, 1900
184. NOÈ G. Sul ciclo evolutivo della Filaria Bancrofti (Cobbold) e della Filaria immitis
(Leidy). Ricerche dello Laboratorio Anatomica Comparativa e Normale della Reale
Universita, Roma, 8: 275-353, 1901
185. O'CONNOR FW. The aetiology of the disease syndrome in Wuchereria bancrofti infections.
186. O'CONNOR FW, GOLDEN R, AUCHINCLOSS H. The roentgen demonstration of
calcified Filaria bancrofti in human tissues. American Journal of Roentgenology and
Radium Therapy 23: 494-502, 1930
187. OEMIJATI S, PARTONO F, HUJODO, HADI TR, CLARK MD, GUNNING JJ, CROSS
JH. Brugia malayi in Kresek, West Java, Indonesia: the effect of environmental changes on
filarial endemicity. Tropical and Geographical Medicine 30: 301-304, 1978
188. ORIHEL TC, PACHECHO G. Brugia malayi in the Philippine macaque. Journal of
Parasitology 54: 1234-1235, 1968
189. OTTESEN EA, NEVA FA, PARANAJAPE RS, TRIPATHY SP, THIRUVENGADAM
KV, BEAVEN A. Specific allergic sensitization to filarial antigens in tropical eosinophilia
syndrome. Lancet i: 1158-1161, 1979
190. PARTONO F, PURNOMO A, DENNIS DT, ATMOSOEDJONO S, OEMIJATI S, CROSS
JH. Brugia timori sp. n. (Nematoda: Filarioidea) from Flores island, Indonesia. Journal of
191. PATHOLOGICAL SOCIETY OF LONDON. Meeting on 4 March 1873. Lancet i: 446,
1873
192. PELLETIER J. Cas d'éléphantiasis du scrotum observés au Sénégal. Bulletins de la Société
193. PIRES T. Cited in 64
194. POYNTON JO, HODGKIN E P. Two microfilariae of the Kra monkey (Macaca irus).
195. PRIESTLEY WO. Haematozoa and chyluria. British Medical Journal i: 185, 1873
196. PROUT WT. On the role of filaria in the production of disease. Transactions of the Society
197. PYE-SMITH PH. Haematozoa and chyluria. British Medical Journal ii: 271, 1873
198. RAO SS, MAPLESTONE PA. The adult ofMicrofilaria malayi Brug, 1927. Indian Medical
Gazette 75: 159-160, 1940
199. REDDY MV, MALHOTRA A, HARINATH BC. Detection of circulating antigen ni
bancroftian filariasis by sandwich ELISA using filarial serum IgG. Journal of Helminthology
58: 259-262, 1984
200. REPORT OF EXPERT COMMITTEE ON FILARIASIS. Wuchereria and Brugia
infections. World Health Organization Technical Report Series, Number 233, 1962
201. ROBERTSON JA. Pepper in the prophylaxis and treatment of filariasis. British Medical
202. ROGERS L. Preliminary report on the intravenous injection of antimony in filariasis. Lancet
ii: 604-608, 1919
203. ROSENBLATT P, BEAVER PC, ORIHEL TC. A filarial infection apparently acquired in
New York City. American Journal of Tropical Medicine and Hygiene 11: 641-645, 1962
204 ROSS R. Some recent chicanery in science. Lancet ii: 775, 1902
205. ROSS R. Cited in 223
206. ROWLAND. Cited in 21
207. SALISBURY JH. On the parasitic forms developed in parent epithelial cells of the urinary
and genital organs, and in their secretions. American Journal of Medical Science 110:
371-380, 1868
208. SAMBON LW. Remarks on the life-history of Filaria bancrofti and Filaria immitis. Lancet
ii: 422-426, 1902
209. SANTIAGO-STEVENSON D, OLIVER-GONZALEZ J, HEWITT RI. Treatment of
filariasis bancrofti with 1-diethylcarbamyl-4-methylpiperazine hydrochloride ("Hetrazan").
210. dos SANTOS F. Filaria bancroft, verificação no Brazil da descoberto de Bancroft, no
Australia. Progresso Medico, Rio de Janeiro 2: 95-100, 1877
211. SASA M. Human filariasis: a global survey of epidemiology and control, University Park
Press, Baltimore, pp 819, 1976
212. SAVITT TL. Filariasis in the United States. Journal of the History of Medicine and Allied
Sciences 32: 142-150, 1977
213. SAWADA T, SATO K. Studies on skin test antigen FST for immunodiagnosis of filariasis.
III. Separation and characterization of FST3-1 by isoelectric focusing technique. Japanese
214. SAWADA T, SATO S, MATSUYAMA S, MIYAGI H,SHINZATO J. Intradermal skin test
with antigen FST (FSCD1) on individuals inendemic area. Japanese Journal of Experimental
Medicine 38: 405-414, 1968
215. SCHACHER JF, SAHYOUN PF. A chronological study of the histopathology of filarial
disease in cats and dogs caused by Brugia pahangi (Buckley and Edeson, 1956).
216. SEURAT LG. Orthogénèse des filaires. Bulletin de la Société d'Histoire Naturelle de
l'Afrique du Nord 12: 28-37, 1921
217. SIBTHORPE. On the adult male Filaria sanguinis hominis. British Medical Journal i:
1334-1335, 1889
218. da SILVA ARAUJO AJ. Caso de chyluria, elephancia do escroto, escroto lymphatico,
craw-craw e erysipela em um mesmo individuo, descobrimento da Wuchereria Filaria na
lympha do escroto. Tratamento pela electricidade com excellentes resultados. Gazeta Medica
da Bahia, second series, 2: 492-504, 1877
219. da SILVA ARAUJO AJ. Caso de chyluria, elephancia do escroto, escroto lymphatico,
craw-craw e erysipela em um mesmo individuo, descobrimento da Filaria wuchereri na
lympha do escroto. Tratamento pela electricidade com excellentes resultados. Gazeta
Medica da Bahia, second series, 4: 455-465, 1879
220. da SILVA LIMA JF. The late Dr. Wucherer and the filaria bancrofti. Lancet i: 440-441,
1878
221. SONSINO P. Ricerche intorno alla bilharzia haematobia in relazione colla Ematuria
endemica dell'Egitto, e nota intorno ad un nematoideo trovato nel sangue umano. Rendiconti
dell'Accademia delle Scienze Fisiche e Matematiche, Napoli, 1874. Partly translated in 60
222. SONSINO P. La Filaria sanguinis hominis osservato in Egitto, e gli esperimenti intorno al
suo passagio nelle zanzare e in altri insetti ematofagi. Giornale della Reale Accademia di
Medicina de Torino, third series, 32: 365-380, 1884
223. SONSINO P. The life history of Filaria bancrofti in the body of the mosquito. British
224. SUGANUMU S. (On the count of microfilaria.) Chugai Iji Shimpo No. 994, 1921. In
Japanese. Abstracted in Japan Medical World 1 (8): 24, 1921
225. TALIAFERRO WH, HOFFMAN WA. Skin reactions to Dirofilaria immitis in persons
infected with Wuchereria bancrofti. Journal of Preventive Medicine 4: 261-280, 1930
Filariasis 639
226. TANON L, GIRAUD G. Traitement des filarioses sanguines par les injections sous-cutanées
d'hectine. Revue de Médecine et Hygiene Tropicale 12: 82-86, 1920
227. THETFORD ND, OTTO GF, BROWN HW, MAREN TH. The use of phenyl arsenoxide
in the treatment of Wuchereria bancrofti infection. American Journal of Tropical Medicine
28: 577-583, 1948
228. THORPE VG. Filaria sanguinis hominis in the South Sea Islands, with photomicrographs
from Tonga and the Friendly Islands. British Medical Journal ii: 922-924, 1896
229. TRENT SC. Re-evaluation of World War II veterans with filariasis acquired in the Pacific.
230. TURNER LH, EDESON JF. Studies on filariasis in Malaya; the periodicity of the
microfilariae of Wuchereria malayi. Annals of Tropical Medicine and Parasitology 51:
271-277, 1957
231. WARDEN AA. Note on the treatment by radium of lymphatic obstruction (cervical,
submaxillary and axillary) in a patient suffering from Filaria nocturna. Lancet ii: 224-225,
1909
232. WARTMAN WB. Lesions of the lymphatic system in early filariasis. American Journal of
233. WEBB JK, JOB CK, GAULT EW. Tropical eosinophilia; demonstration of microfilariae in
lung, liver and lymph nodes. Lancet i: 835-842, 1960
234. WEBBER RH. Eradication of Wuchereria bancrofti infection through vector control.
235. WEINGARTEN RJ. Tropical eosinophilia. Lancet i: 103-105, 1943
236. WILSON T, EDESON JF, WHARTON RH, REID JA, TURNER LH, LAINGAB. The
occurrence of two forms of Wuchereria malayi in man. Transactions of the Royal Society
237. WINTER H. "Tropische Eosinophilie" als symptomarme Filariasis. Zeitschrift für
Tropenmedizin und Parasitologie 6: 99-105, 1955
238. WISE KS, MINETT EP. Report of tropical diseases research in the Government
Bacteriological Laboratory, British Guiana, for the six months October 1911 to March 1912.
Report of the Advisory Committee of the Tropical Diseases Research Fund for the Year
1912. H.M. Stationery Office, London, pp 108-114, 1913. Abstracted in Tropical Diseases
Bulletin 2: 93-94, 1913
239. WUCHERER OE. Noticia preliminar sobre vermes de una especie ainda não descripta,
encontrados na urina de doentes de hematuria intertropical no Brazil. Gazeta Medica da
Bahia 3: 97-99, 1868. Translated in 117
Table 23.1. Landmarks in filariasis

___________________________________________________________________
BC Elephantiasis recognized from antiquity

1863 Demarquay and colleagues discovered microfilariae in hydrocele fluid
1866 Wucherer found microfilariae in chylous urine
1872 Lewis observed microfilariae in blood
1876 Joseph Bancroft discovered a female adult worm
1877 Manson found microfilariae in the stomach of a mosquito and observed their
subsequent development
1879 Manson discovered the nocturnal periodicity of W. bancrofti microfilaraemia
in China
1880 Manson reported finding microfilariae in aspirates of lymph nodes
1888 Sibthorpe isolated and Bourne described a male adult worm
1896 Thorpe reported the diurnal subperiodicity of the Pacific form of W. bancrofti
1899 Thomas Bancroft suggested that infection may be acquired via the proboscis
of a biting mosquito
1900 Low demonstrated infective larvae in the proboscis of filariated mosquitoes
prepared by Thomas Bancroft
1927 Lichtenstein and Brug described a different microfilaria which was named
microfilaria malayi
1939 Meyers and Kouwenaar described a syndrome of marked eosinophilia and
lymphadenopathy with eosinophilic granulomas around microfilariae in the
lymph nodes
1940 Rao and Maplestone described the parental form of B. malayi
1947 Hewitt and colleagues showed that diethylcarbamazine caused a rapid
disappearance of Litomosoides carinii microfilariae from the blood of cotton
rats
1948 Santiago-Stevenson and co-workers demonstrated a similar effect in humans
with bancroftian microfilaraemia
1958 Danaraj showed that tropical pulmonary eosinophilia responded to treatment
with diethylcarbamazine
1960 Webb and colleagues demonstrated the presence of microfilarial granulomas
in lung biopsies from patients with tropical pulmonary eosinophilia
1965 David and Edeson described the Timor microfilaria
1977 Partono and colleagues described Brugia timori, the parental form of the
Timor microfilaria
___________________________________________________________________
Chapter 24
Loa loa and LOIASIS
SYNOPSIS
Common name: eyeworm causing Calabar swellings

Major synonyms: Dracunculus loa, Filaria lacrymalis, F. loa, F. oculi humani, F. sub-
conjunctivalis, microfilaria diurna
Distribution: West and Central Africa
Life cycle: The adult worms, 30-70 mm long by 0.35-0.5 mm wide, migrate throughout
the connective tissues. Microfilariae are produced and released into the bloodstream;
they appear only during the day, a phenomenon known as diurnal periodicity. When
microfilariae are ingested by tabanid flies of the genus Chrysops, they develop over
10-14 days into infective larvae which pass to the proboscis and infect the host at
the next blood meal
Definitive host: humans, (subhuman primates)
Major clinical features: recurrent, transient, urticarial, subcutaneous swellings (Calabar
swellings). Occasionally adult worms are seen migrating through the subconjunctiva
Diagnosis: clinical (obervation of Calabar swellings); observation of the adult worm in
the eye; demonstration of microfilariae in the blood
Treatment: diethylcarbamazine, suramin
Since the adult Loa loa is several centimetres in length and moves from time
to time through the subconjunctival tissues of the eye, this worm must hav e
been recognized by people living in endemic areas for many centuries past. The
name of the first European to see and describe this worm, however, has been
a matter of some dispute. When the Frenchman, Guyon, described a case i n
1864, he reviewed the literature and believed that the first recorded evidence
of this parasite was a certain copper engr aving which he interpreted as showing
the extraction of Loa loa from the eye48. This engraving, which had been drawn
by the engraver and publisher, JT de Bry, appeared in 1598 in the secon d
volume of a two volume work called Collectiones peregrinationum in Indiam
orientalem et occidentalem (known as India Orientalis for short) 14. The text
was concerned in part with the travels to Asia of the Dutchman, Huighen van
Linschoten, and included, amongst other things, his description o f
dracunculiasis on Hormuz island in the Persian Gulf (see chapter 26), an d
recounted how the king blinded his relatives to prevent assassination an d
rebellion. The first volume, which had appeared in 1597 in German and was
641
then issued in 1598 in Latin, contained an account about Africa by th e

Portuguese, E Lopez; the reco rd of Lopez had been translated from Portuguese
into Italian by Phillip Pigafetta in 1593 then into German by A Cassiodo r
Reinus. Its Latin title began: " Vera descriptio regni Africani quod tamabincolis
quam Lusitanis Congus appellatur per Phillipum Pigafettam ....MDXCVIII".
Guyon connected the words Congo and 1598 in the title of volume 1 with the
engraving in volume 2 and concluded that the engraving was indicatin g
pictorially the removal of Loa from the eye. This view was accepted b y
Blanchard9, who believed that Pigafetta was the author of this publication, and
by many other writers. In fact, there is no loiasis in the Persian Gulf, an d
Ward91 and Grüntzig and Jennes46 have shown that there was no reference to
this parasite in these accounts. Indeed, the latter authors have argue d
convincingly that these engravings were not scientific reproductions, but were
fashioned with the aid of de Bry's fertile imagination, for his primary purpose
was not to serve science but to offer entertaining literature to the educate d
general public.
The first definitive account of the worm was published in 1770 by Mongin,
a French surgeon who saw the para site at Santo Domingo in the Caribbean. He
was called by the Count of Cockburn to see one of his black female servant s
who had been complaining of a severe stabbing pain in the eye of 24 hours '
duration. Mongin wrote that there was no inflammation, but he:
saw a worm which seemed to crawl superficially on the eye, but when I tried to
catch it with forceps, I realized that it was between the conjunctiva and the cornea.
When it approached the transparent cornea, the pains became more severe....it was
one and a half inches long, the width of a violin string, and dark colored. One end
was bigger than the other, although both ends were very pointed. 75
Although Mongin was the first t o publish an account of the worm, his com-
patriot, Bajon in Cayenne, saw and removed one earlier in July 1768. A ship's
captain from Guadeloupe brought him a young African girl six to seven years
old in whose eye he saw:
a motile small worm the size of a small thread; I examined it and observed a small
animal almost two thumbs in length; it moved around the eyeball in the cellular
tissue which unites the conjunctiva with the sclera. On stimulating it to move, I saw
that its movements were not straight but tortuous and oblique; the colour of the eye
never changed and the small negress complained of no pain even though the worm
moved in the way it did; she did, however, have an almost continuous small
watering of the eyes.8
Bajon saw another case, again in a negress, in 1771. In this patient, however,
the conjunctiva was inflamed. He reported his experiences with this condition
in 1777 8 . Further cases were seen by Guyot in Angola (1778) 49 , Clot Bey in
Egypt (1838)18, Blot10 then Guyon47 in Martinique, and Loney in West Africa 62.
This last-named author, who was a surgeon on Her Majesty's brigantin e
Dolphin, gave the first account in English. He saw two patients in 1848:
They applied to me....with itching, and a sensation as if something was moving
around in the eye. On examination, I observed a worm moving round and round the
Loiasis 643
cornea, beneath the conjunctiva, causing very little if any, irritation....neither of the
dracunculi when extracted were found to exceed two inches in length. 62
Worms were encountered by many surgeons subsequently, but it was not until
1895 that the British ophthalmologist, Argyll-Robertson, in collaboration with
Manson, provided the first detailed descriptions of the male and femal e
parasites5. Further detailed descriptions were then provided by Looss 63 and by
Huffman and Wherry 51.
Many of the early French writers referred to the worm as a "dragonneau "
(i.e. dracunculus or guinea worm), but it soon became clear this parasite was
a different creature from Dracunculus medinensis . In 1845, Dujardin placed
the worm in the genus Filaria of Müller78 and named it Filaria oculi humani 26,
then Dubini called it Filaria lacrymalis 25, Gervais and van Beneden designated
it Filaria oculi 40, and Guyon labelled it Filaria subconjunctivalis48 . The
French naval surgeon, Guyot, who had seen several cases while cruising off the
coast of Angola in 1778 mentioned, in his description of the parasite man y
years later, that the local native name for the parasite was "loa" meanin g
"worm"49. This term was adopted by Cobbold who combined it wit h
Dracunculus to name the worm Dracunculus loa 19. Nevertheless, many other
authors retained it in the genus Filaria and following the lead of Aitken i n
18661, the worm was known as Filaria loa for many years. In 1905, Stiles and
Hassall placed the parasite in the subgenus Loa of the genus Filaria 89, then
Castellani and Chambers in 1913 erected the genus Loa to house the worm
which has since that time been known as Loa loa 16.
DISCOVERY OF THE MICROFILARIA AND DETERMINATION OF

ITS RELATIONSHIP WITH THE ADULT LOA LOA
In 1890, Stephen Mackenzie of the London Hospital found microfilariae in the

blood of an African from the Con go named Mandombi who was suffering from
sleeping sickness (trypanosomiasis); the aetiology of this condition was no t
understood at that time. Mackenzie noticed that the microfilariae differed i n
several respects from the well-known forms now called Wuchereria bancrofti.
In particular, the parasites did not have nocturnal periodicity and could thus be
found by day and by night, and secondly, the microfilariae did not all appear to
be of the same size. In view of these pecularities, Mackenzie invited Partrick
Manson to see the patient. When Manson examined Mandombi's blood on the
evening of 2 December 1890, he confirmed that the parasites were of two sizes.
One of them resembled the microfilariae of W. bancrofti and at that time,
Manson had no doubts that that was precisely what it was. The other form was
about two thirds of the size and had more active motions. The patient died the
next day, but no adult worms could be found at autopsy. A few days later ,
Manson had the opportunity of seeing another patient of Mackenzie's; he also
came from the Congo and had been placed in a lunatic asylum because of a
mental disorder. On examination of this patient's blood, only the smaller forms
were found, thus proving that one type of microfilaria was not a transitiona l
form of the other. Manson then examined the blood of two blacks from Ol d
Calabar who were patients of Dr Grattan Guiness. In one, he found the small
forms, but in the other he saw bot h of the types that he had seen in Mandombi's
blood. As with that patient, microfilariae were circulating in the blood during
the day. Manson scrutinized parasites from this patient very carefully, looking
for differences from those of microfilaria bancrofti (this was before the
introduction of Romanowsky stains) but found only minor variations, bot h
forms being of the same size and provided with a sheath. However, Manso n
now thought that the large microfilariae from the African subjects wer e
different from those of microfilaria bancrofti in that the sheath was mor e
delicate, the oral movements were more marked, and that there was an absence
of granular material around the middle of the body. He examined the periodicity
of these microfilariae in detail. In both patients, the smaller worm could b e
found throughout the 24 hours, but in the patient with the large microfilariae,
these parasites reached a peak in the middle o f the day and were absent at night.
Manson wrote:
the law of periodicity for the appearance of the major embryo is just the reverse of
that which has hitherto been found to apply to the filaria sanguinis hominis of
Lewis.67
As a result of all these observations, he concluded that "man is liable to be the
host of at least two, if not three, distinct species of filarial haematozoa" 67.
Manson may not have been quite so definite in his remarks, however, if these
observations had been made after the discovery of the diurnal periodicity of W.
bancrofti in the Pacific by Thorpe in 1896. In order to differentiate these new
microfilariae from the Filaria sanguinis hominis of Lewis, Manson called them
Filaria sanguinis hominis major (i.e. bigger) and Filaria sanguinis hominis
minor (i.e. smaller)67. Later that year at the Seventh International Congress on
Hygiene and Demography held in London he renamed these parasites on th e
basis of their periodicity. Filaria sanguinis hominis became Filaria sanguinis
hominis nocturna, Filaria sanguinis hominis major became Filaria sanguinis
hominis diurna, and Filaria sanguinis hominis minor became Filaria
sanguinis hominis perstans to reflect night-time periodicity, daytim e
periodicity, and persistence of microfilaria throughout the 24 hours ,
respectively 68. These names subsequently became shortened to Filaria
nocturna, F. diurna and F. perstans.
Although it was apparent that there was at least one and probably two new
species of microfilariae, the nature of the parent worms was not immediately
clear. With the perspicacity of a true savant, Manson suggested that Loa loa
was a likely candidate, although he made one important error initially. Afte r
recalling that the subcutaneous and subconjunct ival migrations of this worm did
not seem propitious for transfer of t he parasite to a new host and noting that the
embryos in the circulation might have a much greater opportunity of migrating
Loiasis 645
via a blood-sucking insect in a fashion analogous to W. bancrofti in

mosquitoes, and perhaps misled by Leuckart's observation that adult Loa loa
contained embryos which had a general resemblance to those of W. bancrofti
except that they were smaller, he wrote: "Might it not be that the smaller o f
these new haematozoa is the embryo of the filaria loa?" 67. Manson's error, of
course, was in thinking that it was the smaller microfilaria which was th e
embryo of Loa loa (this is now known to be the embryo of Mansonella
perstans). Later, however, when it became apparent that F. perstans was
endemic in both Africa and South America whereas the acquisition of F. loa
was restricted to Africa, he corrected this mistake and related F. diurna to F.
loa 69.
Two ways of confirming this hypothesis were to compare the embryo s
within an adult Loa loa with microfilariae of F. diurna in the bloodstream, and
to look for F. diurna in the bloodstream of patients with clinical evidence o f
infection with the adult Loa loa. An opportunity for undertaking both of these
options presented itself to Argyll-Robertson in 1894-1895. He removed a
female Loa loa from the eye of a patient and s ent it to Manson but unfortunately
the investigation was not conclusive, with Manson writing:
The uterine tubes are stuffed with embryos at all stages of development. The more
mature embryos resemble in size and shape those of F. nocturna and F. diurna, but
in consequence of the method of mounting, it is impossible to say if they are
possessed of a sheath or not. If they are possessed of a sheath, I should say that they
are practically indistinguishable from the parasites mentioned. 71
Similarly, examination of the pat ient's blood failed to reveal microfilariae 5. The
absence of F. diurna from the blood of a patient with adult Loa loa infection
had also been documented previously by Dr. Logan in Liverpool. Occasional
patients were noted in whom both F. loa were recovered from the eye an d
microfilaria diurna were seen in the blood 11,15, but since many more patient s
had had only one or the other, the association remained uncertain. Indeed ,
Annett, Dutton and Elliot studied microfilaria diurna in its natural habitat in
West Africa and concluded in 1901 that Manson's hypothesis that thes e
microfilariae were the embryos of F. loa was erroneous. Rather, they contended
that microfilaria diurna was none other than microfilaria bancrofti, and that the
normal periodicity had been disturbed by the peculiar habits of West African
negroes who, they claimed, spent their nights in orgies 2.
Eventually, however, examination of more adult worms revealed that th e
enclosed embryos were sheathed and seemed very similar to both microfilaria
nocturna (= W. bancrofti) and microfilaria diurna. George Low then made
careful measurements of microfilaria nocturna and microfilaria diurna and
concluded that the former measured 0.21-0.28 mm in length whereas the latter
were 0.29-0.32 mm long, and that the location of the V spot (excretory pore)
in these two forms was different. Furthermore, he made measurements on 30
embryos expressed from an adult Loa loa that had been sent to him by D r
Currie in Lagos and found that they were the same as those of microfilari a
diurna. Finally, in contrast to nocturnally periodic microfilaria bancrofti, Low

was unable to reverse the diu rnal periodicity by inverting the sleep habits of an
infected patient. He believed, therefore, that there was no question of th e
identity of Loa loa and microfilaria diurna and declared that the time had come
for abolishing the name microfilaria diurna and substituting in its place th e
term microfilaria loa 64. Low's views were supported by Huffman who studied
in detail the embryos in a living Loa loa 50 and by Foley who found simila r
differences in the measurements of microfilaria bancrofti and microfilaria
diurna in the peripheral blood 36. In 1912, Fülleborn clinched the matter when
he reported that in microfilariae stained with haematoxylin or Azur II, nuclei
extended to the extreme end of the tail in the case of microfilaria diurna, but
only for 95% of the length of the worm in the case of microfilaria bancrofti.
Furthermore, this characteristic was identical in microfilaria diurna and in
microfilariae obtained from adult Loa loa 37,39. Fülleborn's observations were
confirmed soon afterwards by Fol ey36 and then by Meinhof 74. A few years later,
Dyce Sharp reported characteristic differences among microfilaria loa,
microfilaria bancrofti and microfilaria perstans when stained with supravital
dyes and when fixed organisms were examined after different stainin g
preparations 33.
FURTHER OBSERVATIONS ON DIURNAL PERIODICITY
Sensitized by their previous interest in the nocturnal periodicity of microfilaria

bancrofti, Mackenzie and Manson showed from the very beginning that Loa
loa microfilaraemia had a peak in the middle of the day. Indeed, this was one
of the means by which Manson differentiated the new species and provided the
basis of his name for it. Mackenzie, then others, had shown that microfilari a
bancrofti nocturnal periodicity could be reversed by inverting the sleepin g
habits of a patient. As already indicated, Low mentioned in 1910 that in 1904
he had been unable to achieve such a reversal in a patient with Loa loa
microfilaraemia 64. He repeated this experiment in 1921 on a 28 year old man
who had acquired loiasis in Nigeria and confirmed this observation by having
him sleep by day and remain awake at night for six days and nights 66.
The mechanism of diurnal periodicity in Loa microfilaraemia was and
remains as much of a mystery as does the nocturnal periodicity of W. bancrofti
microfilaraemia. One theory which had been put forward by Lane was that W.
bancrofti female adult worms released microfilariae in a cyclical fashion (see
chapter 23). This theory, in loiasis at least, was negated by a potentiall y
disastrous experience undertaken by Gönnert in 1941 (disastrous in the sense
that Gonnert could have given himself a fatal transfusion reaction or infected
himself with, for example, hepatitis B virus). In 1912, Fülleborn had reported
that he had injected Loa microfilariae into mice and monkeys but had failed to
Loiasis 647
recover any worms from either the peripheral or lung blood 38. Gönnert in
Hamburg took this idea and collected 160 ml of blood from a patient from the
Cameroon with a heavy Loa microfilaraemia and injected it intravenously into
his own bloodstream almost immediately. He calculated that he transferre d
1,640,000 microfilaria loa and 112,000 microfilaria perstans. He suffered from
an unanticipated transfusion reaction but examined his blood at intervals and
found that a definite diurnal periodicity persisted over the next few days .
Clearly, the periodicity was dependent upon the microfilariae themselves, o r
upon an interaction between them and the host rather than upon the adul t
worm41.

OF THE TABANID INTERMEDIATE HOST
The manner of transmission of Loa loa was a complete mystery to the earl y
observers who saw the adult worm. When Manson first described the micro-
filariae that eventually turned out to be those of Loa loa, he predicted that the
vector would be a blood-sucking insect of limited distribution in Africa an d
with day-biting habits. He wrote: "Some naturalists may be able, even at this
early stage of the investigation, to indicate these animals" 67.
The failure to find microfilariae in the blood of many such patients ,
however, misled other investigators into thinking that some other mode o f
transmission must be operative. Thus, Argyll-Robertson postulated tha t
embryos may be ingested in contaminated water, although he cautioned that:
the chief difficulty consists in determining how these embryo filariae escape from
the bodies of those affected with the disease, and get deposited in the impure water
and thus propagate the disease....Possibly the embryo parasites may be discharged
along with some of the excreta from the body, and from faulty sanitary
arrangements find their way into drinking water. 5
Argyll-Robertson must have later changed his mind, possibly after conversation
with Manson, however, for he recorded in a subsequent report that his patient,
who had returned to Old Calabar, had sent specimens of mosquitoes an d
sandflies which he and Manson had examined but had failed to detect an y
developing filarial larvae 6. Subsequently, Manson 72 then Sambon 84 suggested
that the intermediate host of Loa loa should be looked for amongst the larg e
blood-sucking flies of the family Tabanidae which bite by day and were known
popularly as mangrove flies or horse flies. Fülleborn reported in 1912 that he
had tried to infect mosquitoes with Loa loa but to no avail 38. In the latter part
of that year, Robert Leiper, funded by a bequest to the London School o f
Tropical Medicine by the late Lord Wandsworth, went to West Africa an d
undertook a series of studies designed to identify the vector of Loa loa. He fed
the bedbug, Cimex rotundatus, the flea, Pulex irritans, many species of
mosquitoes, and various other flies including Stomoxys calcitrans, S. migrans,
Glossina palpalis, Tabanus par, T. socialis, T. fasciatus and T. secundus on

a patient with Loa loa microfilaraemia but with negative results. A sligh t
degree of infection was observed with Haematopota cordigera and
Hippocentrum trimaculatum , but the development was slow and asynchronous.
In Chrysops dimidiata and C. silacea, however, development was rapid an d
uniform60. Leiper sent a telegram from Calabar to the London School o f
Tropical Medicine on 27 December 1912 which was reported in The Times
and the British Medical Journal of the following week: "The metamorphosis
of Filaria loa has been proved to take place in the salivary glands in a fl y
belonging to the genus Chrysops"61. Leiper had to abort his studies in January
1913, however, because of a lack of f lies with which to work. He was informed
that Chrysops had a marked seasonal incidence at Calabar in Nigeria and that
they would not reappear in abundant numbers until June. Perhaps because he
intended to extend his studies later, Leiper does not appear to have published
details of his observations on the development of microfilariae in Chrysops.
Nevertheless, his discovery was confirmed and this omission rectified by a
number of subsequent investigators.
In 1915, Kleine reported the results of his investigations in a heavil y
endemic area at Eseka in the German Cameroons (now called Cameroon). He
examined 600 wild-caught female flies (500 C. dimidiata and 100 C. silacea)
and found that 5.3% were infected, with fully mature infective larvae bein g
present in nine flies. Kleine considered that microfilariae perforated the gu t
wall, then development took place in the fatty tissue surrounding the tracheae
in the abdominal cavity. Later, they migrated to the cephalic end of the body of
the insect, and in two cases he was abl e to demonstrate emergence of the larvae
from the proboscis 57. This work was criticised by Cockin, however, on th e
grounds that the nature of the hosts o n which the flies had fed was unknown, no
illustrations or descriptions of the larvae were provided, and no attempt wa s
made to transmit infection by means of infected flies 20. While the first criticism
was valid, the second could also have been levelled at Leiper, and the third was
manifestly unfair in view of its impracticability and the doubtful ethics of such
a procedure. This was, of course, at the height of World War I, a time which
was not propitious for extended investigations on Kleine's part, and perhaps a
little xenophobia coloured C ockin's comments. These criticisms were certainly
not applied by an editorial writer in The Lancet 4 commenting on the report in
1921 by Dr. A. Connal in which he described the findings on more than 2,000
Chrysops which were caught over eight months in 1917 near Lagos and then
were dissected by his wife. She observed that 0.8% of 2,255 C. silacea and
2.4% of 249 C. dimidiata were infected; the larvae were usually present in the
muscles - in one insect, 427 worms were present 21. Subsequently, the Connals
conducted many feeding experiments on cases of loiasis with large numbers of
flies. They reported that the majority of embryos reached the abdomina l
muscles within 24 hours of feeding, although others proceeded to the head and
thorax. Growth was rapid so that by the fifth day they were seen coiled i n
Loiasis 649
whorls in the musculature, particularly of the abdomen. Ten to twelve days after
infection, larvae migrated towards the head, accumulated at the root of th e
proboscis and the labium and exited via the labella. Finally, evidence wa s
procured which indicated that flies could remain infective for five to si x
days22,23. Soon afterwards, however, they had to modify these comments since
histological sections of infected flies prepared by Dr AC Stevenson had made
it clear that most of the larvae were not in muscles but in fatty tissue, th e
so-called "fat body". Connal and his wife concluded that the forms found b y
Kleine in abdominal fatty tissue were almost certainly, as he presumed, stages
in the development of Loa loa 24.
This question was re-investigated many years later by Lavoipierre and by
Lebied. The former author considered that the young larvae invaded the cells
of the fat body then, after bursting o ut of them, migrated to the thorax, neck and
head58, while the latter believed that fatty cells in the haemocoele surrounded
the larvae and fused to form a syncitium 59.
Gordon and Crewe studied the mechanism of feeding of C. silacea and
C. dimidiata and concluded that they fed from a pool of blood formed in th e
deeper layers of the skin as a result of several thrusts of the fascicle, durin g
which action the anticoagulant in the insect's saliva prevented clotting. The y
showed that the infective larvae escaped from the proboscis during the act of
feeding44 then Lavoipierre indicated later that the infective larvae escape d
through a rupture in the delicate labio-hypo-pharyngeal membrane 58. Gordon
and Crewe also reported that the infective larvae could not penetrate the intact
skin, and presumably entered through the wound made by the biting fly.
Although Loa loa has never been transferred to humans experimentally ,
Orihel and Moore in 1975 infected two patas monkeys ( Erythrocebus patas)
and a baboon (Papio anubis). They used infective larvae obtained fro m
C. silacea that had fed on a patient in the British Cameroons and found a
prepatent period of 146 days in the baboon and 135 and 148 days in th e
monkeys. Microfilaraemia persisted for more than 40 weeks in the monkeys but
began to decline after three months in the baboon 80.
The most dramatic clinical manifestations of loiasis were attended by th e

appearance of a worm in the eye. Sometimes the parasite caused little trouble
except perhaps a minor irritation or watering, whereas on other occasions i t
produced a severe stabbing pain or overt conjunctivitis 8,62,75. A detailed
description was provided in 1895 by Argyll-Robertson who recounted th e
symptomatology in a 32 year old English lady who had spent eight years at Old
Calabar in Nigeria on the West Coast of Africa. She told him that:
the worm frequented both eyes, but showed a preference for the left one, sometimes
coursing over the surface of the eye under the conjunctiva, sometimes wriggling
under the skin of the eyelids - causing a tickling, irritating sensation but not real
pain, occasionally causing the eye to become bloodshot, and the eyelids to swell and
blacken slightly.5
Furthermore, the patient noticed that she was troubled much more when sh e
was febrile (from malaria) or remained indoors in a warm room or sat near a
fire, and that the worm seemed to disappear to the deeper parts when her face
was exposed to the cold. Finally, Argyll -Robertson was able to observe a worm
in the eye after the application of a warm cloth to her orbit:
I observed the worm moving in a tortuous, wriggling manner under the conjunctiva,
the surface of which became slightly elevated as it moved along. It passed with a
pretty quick movement over the surface of the sclerotic at the distance of about
5mm from the outer margin of the cornea. There was increased lachrymation and
slightly increased injection of the conjunctiva.5
Argyll-Robertson also drew attention to the other characteristic feature of
loiasis which came to be known as "fugitive swellings" or "Calabar swellings".
He remarked that his patient complained of:
ill-defined swellings under the skin of the forearm a little above the wrists, over the
dorsal surface of the radius, more marked generally in the right arm. The surface of
the swellings was not quite uniform, but did not give one the idea of being produced
by a coiled-up worm. The swellings measured about half an inch in diameter. They
were not painful, but occasioned a feeling of stiffness....The swellings occurred at
irregular intervals.5
Moreover, his patient told him that the natives of Calabar and others who had
been resident there for some time were also subject to these swellings on the
forearms and wrists; they were termed " ndi tot" meaning "swelling" by the local
populace5.
The pathogenesis of these lesions was a matter of considerable debate .
Argyll-Robertson managed to extract an adult Loa from deep within the tissues
of a similar swelling in the temple of a patient 5. Manson (1910) thought i t
unlikely that the mere presence and movement of worms caused these lesions
for he cited a patient whose blood was teeming with microfilaria loa and who
amused himself by harpooning adult worms with a needle as they wriggled their
way under the skin of his chest or abdomen, yet who rarely suffered fro m
Calabar swellings. Manson postulated that the oedema might be caused b y
lymphatic obstruction, the secretion of irritating glandular products, th e
excretion of faecal material by the worm, or the periodical emptying of th e
contents of the uterus of a gravid female worm into the connective tissues of the
host. Of these various hypotheses, he favoured the last, and supported thi s
thesis by instancing his discovery of microfilariae in an aspirate of one of these
lesions70. This could not be confirmed by Low, however; he aspirated swellings
of two patients who, in contrast to Manson's case, did not have a microfil -
araemia, and failed to find any embryos; he thought it more likely that th e
lesions were due to a toxic reaction to the worms, possibly dead ones 65.
Less definite were the suggestions of an association between Loa infection
and cerebral disease. The patient in whom Manson first observed the micro -
filariae died of sleeping sickness and the second patient was insane, so Manson
Loiasis 651
canvassed the possibility that the two conditions were connected 68. Later
authors12,87 described a variety of neurological problems in patients with Loa
infections, but these turned out to be coincidental, while trypanosomes wer e
shown to be the cause of sleeping sickness. Other conditions which have been
associated with loiasis include endomyocardial fibrosis 52 and nephrotic
syndrome93.
Several reports have been given by physicians of their own, personal ,
naturally-acquired infections. Rogers described fugitive swellings, especially
around the joints, which were painless yet occasioned stiffness, and recounted
the migratory habits of the adult worm 82. Similarly, Johnstone recorded his own
experiences:
I first noted the gradual onset of a swelling above the right wrist. This was
pronounced to be a sprain, but the swelling gradually spread to involve the whole
of the right hand, and writing for more than a few minutes caused cramp....playing
any games which involved holding a handle was impossible. At this stage, and
lasting about ten days, a severe neuralgia in the distribution of the right median
nerve came on every night and at no time....did I manage to sleep more than 20
minutes at a time....The swelling of the wrists and hand persisted for at least 6-8
weeks. Within a few weeks of the appearance of the first swelling, a regular crop of
swellings kept coming and going. In one week....I had 16 swellings, 3 coming on
in one day. At times they were irritating and the overlying skin red; at other times
they appeared to be situated more deeply, causing an ache which usually felt like a
bruise and lasted 24 hours. By far the greatest number developed on the forearms,
but few parts of my body have so far escaped.54
Johnstone then went on to recount the removal of an adult worm from his eye
on four separate occasions 54.
It was noted that the natural history of this infection may occupy man y
years. A number of months usually passed after exposure before the first sign
of infection appeared. Meinhof reported the case of a female German mission-
ary who went to the German Cameroons in 1903 and developed Calaba r
swellings two years later. These recurred, together with headaches, for another
six years until an adult Loa was first seen 74. On the other hand, Dyce Shar p
demonstrated that clinical manifestations (Calabar swellings) could appea r
soon after exposure, for he recounted a case in which such problems began 61
days after the earliest conceivabl e date of infection and one week after the most
probable infective date 34. The adult worms may be very long-lived fo r
instances have been recorded in which adult worms have persisted for at least
17 years73,95.
The diagnosis of loiasis is obvious when a worm is seen moving around th e

subconjunctival tissues of the eye. Neverthel ess, there have been countless tales
of sceptical but ill-informed doctors who found the story that their patient told
them too incredible. An alternative method of diagnosis was apparent whe n

Manson and Mackenzie discovered microfilaria loa and means were evolved
for differentiating them from other filarial parasites, as has already bee n
discussed. The chances of making the diagnosis in this way were improved by
various concentration techniques. The methods used in W. bancrofti infections
were equally efficacious in loiasis, and are discussed in chapter 23. It needs to
be remarked, however, that the first concentration technique was applied i n
cases of loiasis and filariasis by Smith and Rivas. They reported in 1914 that
the diagnosis could be enhanced by mixing 0.1-1.0 ml of blood in 5 ml of 2%
acetic acid, shaking and centrifuging the mixture, then finding microfilariae in
the sediment87. Rarely, Loa microfilariae have been recovered from urine ,
sputum and cerebrospinal fluid 53.
It was realized gradually, however, that many patients with a history o f
eyeworm had no microfilaraemia and, vice versa, that many patients with Loa
microfilaraemia had no such history. Worse, many patients with Calaba r
swellings had neither evidence of an adult worm nor the presence of micro -
filariae in the bloodstream. Although these lesions were very puzzling initially
(even Rogers, a doctor with experience himself in the endemic area, wa s
misdiagnosed in 1907), clinicians began to recognize them as characteristic, if
not pathognomonic, of Loa infection, and realized that parasitological con -
firmation of the diagnosis was likely if the patient was followed for lon g
enough. In such circumstances, reliance had to be placed upon pointers t o
infection with Loa loa. Eosinophilia was a characteristic finding 74 but although
it tended to be higher than in other helminthiases, was too non-specific to be
diagnostic. Slightly more specific were immunoassays. Fairley 35 and Rodhain
and Dubois81 showed that intradermal injection of Dirofilaria antigen produced
an immediate hypersensitivity reaction in patients with loiasis, but noted that
this test did not differentiate among the various filariases; immunologica l
reactions to Dirofilaria have also been seen, for example, in Mansonella
perstans 85 and Wuchereria bancrofti 13 infections.
The management of loiasis is essentially s urgical when the opportunity presents

itself. The French naval surgeons, Mongin and Bajon, were among the firs t
Europeans to report surgical extraction of the parasite, although witch-doctors
and their kin had been performing suc h procedures for centuries. Mongin made
it appear simple, merely remarking: "In order to remove it, I opened th e
conjunctiva and extracted the worm through that incision" 75. Bajon was more
expansive in detailing the problems he encountered:
After reflecting upon the ways in which I could extract it, I believed that by making
a small opening in the conjunctiva near the side of the head of the small animal,
then after stimulating it to move, it would come out by itself. I put this plan to
Loiasis 653
action, but instead of coming out through the aperture I had made, it passed to the
side and went to the region opposite the incision. Seeing that this tentative method
was not of any use, I grabbed hold of it at the middle of its body with small forceps
as well as the conjunctiva; I then made a small hole at the side of its body with the
point of a lancet, and with an ordinary needle, I pulled it out; after this operation, the
negress was well within 24 hours.8
A century later, when local anaesthesia was available, Argyll-Robertso n
recounted his technique:
I at once placed my finger on the surface of the globe in such a manner as to prevent
the parasite passing backwards until the conjunctiva was pretty well anaesthetised
by the application of cocaine. I then got my friend Dr. Maddox, who was present,
to apply his finger while the necessary preparations were hastily made for an
operation. She was placed on a couch and the speculum applied, when the pressure
of the finger having been removed the wriggling movements of the worm resumed,
as briskly as before application of the cocaine. I now grasped with a pair of toothed
fixing forceps a good fold of conjunctiva over the centre of the wriggling worm,
taking care to include in the fold all the structures superficial to the sclerotic. I next
made with a pair of scissors an incision through the conjunctiva a little nearer the
cornea, in such a manner as to lift up a small flap of conjunctiva, and after a little
careful separation of the tissues, found one extremity of the worm, which I seized
with a pair of iris forceps. On now relaxing the fixing forceps, the parasite came
away readily.5
In the following year, Roth told of his unfortunate experiences. He tried many
times to remove a worm from the eye of a 15 year old girl, but never succeeded
in catching the elusive creature. The same sequence befell his next tw o
patients, and he remarked rather optimistically that they had probably bee n
cured by his application of cocaine 83. Roth noted in passing that it was a
common practice amongst the local inha bitants to treat the infection by packing
small pieces of onions around the eye; this was said to either retain the worm
on the sclera where it could be picked off with a needle, or drive it away (and
he postulated that it passed through the nasal duct and was then eithe r
swallowed or spat out!).
A number of drugs were tried in loiasis. Aubert and Heckenroth (1913 )
investigated the actions of aniline, vari ous arsenicals and tartar emetic in loiasis
but found them to be useless7. Although most authors agreed that there was no
effective drug for the medical treatment of this infection, evanescent claim s
were made for salvarsan (arsenic) 76, anthiomaline (antimony) 17 and picric
acid77.
In 1947, diethylcarbamazine was introduced for the treatment of bancroftian
filariasis (see chapter 23), then this drug was soon tried in loiasis. A number
of investigators reported clinical improvement in many but not all patients with
loiasis79,86,88,90. Some patients developed an itchy morbilliform or urticarial rash
after treatment (possibly due to concurrent occult infection with Onchocerca).
Most of these patients had no Loa microfilaraemia. In Murgatroyd and Wood-
ruff's series, for example, only three of the 17 patients had microfilariae in the
bloodstream, and no mention was made of the longterm effects of the drugs on
the microfilaraemia 79. Woodruff later reported the liver biopsy finding in a
patient in whom diethylcarbamazine treatment had caused the parasites t o
disappear from the peripheral blood; microfilariae in the biopsy wer e
surrounded by phagocytes, thus suggesting that the action of the drug was t o
sensitize the microfilariae which were then destroyed by the cells of th e
reticulo-endothelial system 94. Subsequent experience has shown that although
this drug may be useful in patients with loiasis, it cannot be relied upon t o
eradicate the infection.
Although cases of loiasis were described initially from both Africa and fro m
South America, its universal occurrence in black slaves in the latter area and
its spontaneous disappearance from that regi on indicated that Loa infection was
endemic only in parts of West and Central Africa. The factors influencing the
distribution and intensity of infection could b e ascertained only when the central
role of Chrysops flies in the transmission of infection had been ascertained .
Sporadic attempts were made over the next few decades to both define th e
prevalence and severity of disease in infected populations, and to study th e
habits of the vectors, but the most intensive efforts were made during the late
1940's and the 1950's.
Gordon and his colleagues reported their investigations in a town in th e
British Cameroons in which a quarter of the population were infected .
C. siliacea and C. dimidiata were both found, though the former was muc h
more common. They observed that the female flies bit once every two weeks
or so, usually between the hours of 8.30 a.m. and 4.30 p.m., were found indoors
as well as outdoors, hunted probably by sight, preferring the well-lighte d
houses of Europeans to the d ark houses of the Africans, and had infection rates
of up to 12%. Chrysops larvae were found in densely-shaded streams, localized
in the stagnant parts and in mud beneath decaying vegetation 43,45. It became
clear that infection was limited chiefly to the rain forest or its immediat e
environs56 with the adult flies occupying the canopy of the forest. Furthermore,
monkeys in those forests were infected with a strain of Loa loa which, although
it had certain morphological differences and had nocturnal periodicity, wa s
possibly transmissible to man 27,42. Duke then showed that smoke from woo d
fires increased greatly the biting rate and may be an important factor i n
attracting flies from the forest to feed in houses28, and also suggested that the
flies were attracted by movement 29.
Loiasis 655
THE DEVELOPMENT OF PREVENTIVE AND CONTRO L

MEASURES
Attempts to control loiasis became feasible with discovery of the tabani d

vector, but such measures have not proved very satisfactory. Persona l
prophylaxis is dependent upon wearing long-sleeved and long-legged clothes
and the use of insect repellents to inhibit biting when outdoors, as well as the
screening of houses to prevent biting indoors. Control of the vector itself i s
usually impractical although clearing of vegetation to eliminate resting places
for adult flies and canalization of streams to enhance the free flow of water or
the use of insecticides in streams to reduce breeding larvae have bee n
advocated43,92.
Control by mass treatment with diethylcarbamazine to reduc e
microfilaraemia and repeated prophylactic administration of the drug have been
proposed32. This latter idea was suggested by the demonstration by Duke i n
monkeys30 and in humans 31 that diethylcarbamazine appeared to kill infective
larvae. The main difficulty wi th these approaches, however, has been to ensure
the cooperation of the population. This has proved almost impossible in areas
where concurrent onchocerciasis increased greatly the incidence and severity
of toxic reactions to the drug.
REFERENCES
1. AITKEN W. Parasitic diseases. In, Science and practice of medicine, London, volume 1,
pp 799-900, 1866
2. ANNETT HE, DUTTON JE, ELLIOT JH. Report of the malaria expedition to Nigeria
of the Liverpool School of Tropical M edicine and Medical Parasitology. Part II. Filariasis.
Thompson Yates Laboratory Reports, volume 4, 1901. Abstracted in Journal of Tropical
3. ANONYMOUS. Filaria loa. British Medical Journal i: 39-40, 1913
4. ANONYMOUS. Filaria loa and its insect host. Lancet i: 606, 1921
5. ARGYLL-ROBERTSON DM. Case of Filaria loa in which the parasite was remove d
from under the conjunctiva. Transactions of the Ophthalmological Society of the United
Kingdom 15: 137-167, 1895
6. ARGYLL-ROBERTSON DM. Note of the further history of the case of Filaria loa
previously reported to the Society. Transactions of the Ophthalmological Society of the
United Kingdom 17: 227-232, 1897
7. AUBERT P, HECKENROTH F. Action de divers médicaments sur les Microfilari a
perstans et diurna. Bulletins de la Société de Pathologie Exotique et de ses Filiales 6 :
457-459, 1913
8. BAJON B. Mémoires pour servir à l'histoire de Cayenne et de la Guyane française etc.,
Paris, two volumes, pp 878, 1777-1778. Partly translated by DI Grove
9. BLANCHARD R. La filaire sous-conjonctivale ( Filaria loa Guyot). Progrès Médical ,
Paris, series 2, 4: 591-593, 611-612, 1886
10. BLOT. Cited in 47
11. BRUMPT EJ. La Filaria loa Guyot est la forme adulte de la microfilaire désignée sous
le nom de Filaria diurna Manson. Comptes Rendus Hebdomadaires de la Société d e
Biologie 56: 630-632, 1904
12. BRUNETIERE. La filaire de l'oeil (Filaria loa) peut-elle déterminer des complications
cérébrales? Gazette Hebdomadaire des Sci ences Médicale de Bordeaux 34: 351-353, 1913
13. BRUYNOGHE G. Recherches sur les propriétés antigeniques des microfilaires d e
Dirofilaria immitis. Annales de la Société Belge de Médecine Tropicale 19: 335-353 .
1939
14. de BRY D, de BRY J. India orientalis, two volumes, Frankfurt, 1597-1598
15. BURROWS D. The relationship of microfilaria diurna to Filaria loa. Journal of Tropical
16. CASTELLANI A, CHALMERS AJ. Manual of tropical medicine, second edition .
Bailliere, Tindall and Cox, London, pp 1747, 1913
17. de CHOISY H. Observation d'un cas de microfilariose Loa traité par
l'antimonio-thiomalate de lithium. Revue de Médecine et Hygiene Tropicale 29: 294-296,
1937
18. CLOT A. Dragonneau. Archives Générales de Médecine 30: 573, 1832
19. COBBOLD TS. An introduction to the study of helminthology with reference, mor e
particularly, to the internal parasites of man, Groombridge and Sons, London, pp 480 ,
1864
20. COCKIN RP. Commentary on 57. Tropical Diseases Bulletin 7: 362, 1916
21. CONNAL A. Observations on filaria in Chrysops from West Africa. Transactions of the
Royal Society of Tropical Medicine and Hygiene 14: 108-109, 1921
22. CONNAL A, CONNAL SL. A preliminary note on the development of Loa loa (Guyot)
in Chrysops silacea (Austen). Transactions of the Royal Society of Tropical Medicine and
Hygiene 15: 131-134, 1921
23. CONNAL A, CONNAL SL. The development of Loa loa (Guyot) in Chrysops silacea
(Austen) and in Chrysops dimidiata (Van der Wulp). Transactions of the Royal Society
24. CONNAL A, CONNAL S L. (The development of Loa loa [Guyot] in Chrysops silacea
[Austen] and in Chrysops dimidiata [Van der Wulp].) Correspondence. Transactions of
the Royal Society of Tropical Medicine and Hygiene 16: 437, 1923
25. DUBINI A. Entozoografia umana per servire di complemento agli studii di anatomi a
patologia etc. Annali Universali di Medicina gia Compilati dai Dottore Annibale Omodei,
Milano, 35: 502-578, 1850
27. DUKE BO. The development of Loa in flies of the genus Chrysops and the probable
significance of the different species in the transmission of loiasis. Transactions of th e
28. DUKE BO. Studies on the biting habits of Chrysops. II. The effect of wood fires on the
biting density of Chrysops silacea in the rain-forest at Kumba, British Cameroons. Annals
29. DUKE BO. Studies on the biting habits of Chrysops. III. The effect of groups of persons,
stationary and moving, on the biting density of Chrysops silacea at ground level in the
rain-forest at Kumba, British Cameroons. Annals of Tropical Medicine and Parasitology
49: 362-367, 1955
30. DUKE BO. Studies on the chemoprophylaxis of loiasis. I. Experiments on monkeys with
special reference to diethylcarbamazine (Banocide). Annals of Tropical Medicine an d
31. DUKE BO. Studies on the chemoprophylaxis of loiasis. II. Observations o n
diethylcarbamazine citrate (Banocide) as a prophylactic in man. Annals of Tropica l
32. DUKE BO, MOORE PH. A trial of Banocide as a means of controlling the transmission
of loiasis on a rubber estate in Nigeria. Annals of Tropical Medicine and Parasitology 55:
263-277, 1961
33. DYCE SHARP N A. Filaria bancrofti and Loa loa. A note on some methods o f
Loiasis 657
differentiation of their embryos. Transactions of the Royal Society of Tropical Medicine

and Hygiene 17: 177-191, 1923
34. DYCE SHARP N A. Loa loa infections. A case with rapid onset of symptoms. Lancet ii:
765-766, 1929
35. FAIRLEY NH. Serological and intradermal tests in filariasis. A preliminary report .
36. FOLEY H. Études morphologiques sur les microfilaires à Gaine (Mf. bancrofti et Mf.
diurna). Observations faites chez les tirailleurs Sénégalais d'Algérie. Annales de l'Institut
Pasteur 27: 50-68, 1913
37. FÜLLEBORN F. Untersuchu ngen über Filarien. Archiv für Schiffs- und Tropen-Hygiene
16: 439-440, 1912
38. FÜLLEBORN F. Beiträge zur Biologie der Filarien. Centralblatt für Bacteriologie ,
39. FÜLLEBORN F. Beiträge zur Morphologie und Differentialdiagnose der Microfilarien.
40. GERVAIS P, van BENEDEN PJ. Zoologie médicale. Exposé méthodique du règn e
animal, basé sur l'anatomie, l'embryogénie, et la paléontologie; comprenant la description
des espèces employées en médecine, de celles quie sont vermineuses et de celles qui sont
parasites de l'homme et des animaux, Paris, two volumes, pp 959, 1859
41. GÖNNERT R. Zur Lebensdauer omenschlicher Mikrofilarien. Zentralblatt fü r
Bakteriologie 149: 75-81, 1942
42. GORDON RM. A brief review of recent advances in our knowledge of loiasis and o f
some of the still outstanding problems. Transactions of the Royal Society of Tropica l
43. GORDON RM. CHWATT LJ, JONES CM. The results of a preliminary entomological
survey of loiasis at Kumba, Britis h Cameroons, together with a description of the breeding
places of the vector and suggestions for future research and possible methods of control.
44. GORDON RM, CREWE W. The deposition of the infective stage of Loa loa by Chrysops
silacea, and the early stages of its migration to the deeper tissues of the mammalian host.
45. GORDON RM, KERSHAW WE, CREWE W, OLDROYD H. The problem of loiasis
in West Africa with special reference to recent investigations at Kumba in the Britis h
Cameroons and at Sapele in southern Nigeria. Transactions of the Royal Society o f
46. GRUNTZIG J, JENNES B. Historical note on Loa loa: a reinterpretation. America n
47. GUYON. Note sur des vers observés entre la sclérotique et la conjonctive, chez un e
négresse de Guinée, habitant l a Martinique. Comptes Rendus Hebdomadaires des Séances
de l'Académie des Sciences 7: 755-756, 1838
48. GUYON. Sur un nouveau cas de filaire sous-conjonctival, ou Filaria oculi des auteurs
observé au Gabon (côte occidentale d'Afrique). Comptes Rendus Hebdomadaires de s
Séances de l'Académie des Sciences 59: 743-748, 1864
49. GUYOT. Ophthalmie produite par des vers dans les yeux à la côte d'Angole. Abstracted
in J N Arrachart's Mémoires, Dissertations et Observations de Chirurgie, Paris, p p
228-233, 1805. (Originally presented to the Academy of Surgery in Paris in 1778)
50. HUFFMAN OV. The embryos of Filaria loa. Parasitology 4: 75-82, 1911
51. HUFFMAN OV, WHERRY B. A description of four Filaria loa from the same patient.
52. IVE FA, WILLIS AJ, IKEME AC, BROCKINGTON IF. Endomyocardial fibrosis and
filariasis. Quarterly Journal of Medicine 36: 495-516, 1967
53. JANSSENS PG, van BOGAERT L, TVERDY G, WANSON M. Réflexions sur le sort
des microfilaires de Loa loa l'organisme humain parasite. Manifestations viscérale s
provoquées par leur infiltration dans les tissus. Bulletin de la Société de Pathologi e
Exotique 51: 632-645, 1958

54. JOHNSTONE RD. Loiasis. Lancet i: 250-252, 1947
56. KERSHAW WE, KEAY RW, NICHOLAS WL, ZAHRA A. Studies on th e
epidemiology of Loa loa and Acanthocheilonema perstans in West Africa, with special
reference to the British Cameroons and the Niger Delta. Annals of Tropical Medicine and
57. KLEINE FK. Die Uebertragung vo n Filarien durch Chrysops. Zeitschrift für Hygiene und
Infektionskrankheiten 80: 345-349, 1915
58. LAVOIPIERRE MM. Studies on the host-parasite relationships of filarial nematodes and
their arthropod hosts. I. The sites of devel opment and the migration of Loa loa in Chrysops
silacea, the escape of the infective forms from the head of the fly, and the effect of th e
worm on its insect host. Ann als of Tropical Medicine and Parasitology 52: 103-121, 1958
59. LEBIED B. Iconographie de l'évolution intrasyncitiale de Loa loa chez Chrysops. (Note
préliminaires sur les facteurs, interne et externe, déterminants du cycle évolutif de s
Filariata (Scrjabin) chez leurs hôtes intermédaires. Annales de la Société Belge d e
Médecine Tropicale 37: 641-645, 1957
60. LEIPER RT. Report of the helminthologist, London School of Tropical Medicine, for the
half-year ending April 30th 1913. Report to the Advisory Committee of the Tropica l
Diseases Research Fund, Colonial Office, 1913. Abstracted in Tropical Diseases Bulletin
2: 195-196, 1913
61. LEIPER RT. Cited in 3
62. LONEY W. Extirpation of dracunculi from the eye. Lancet i: 308, 1844
63. LOOSS A. Zur Kenntnis des Baues der Filaria loa Guyot. Zoologischer Jahrbücher .
Abteilung für Systematik, Oekologie und Geologie der Tiere, Jena 20: 549-574, 1904
64. LOW GC. Discussion of 70. Transactions of the Royal Society of Tropical Medicine and
Hygiene 4: 251-253, 1910
65. LOW GC. The aetiological relationship of Loa loa to Calabar swellings. Journal o f
66. LOW GC, O'DRISCOLL EJ. Observations upon a case of Filaria (Loa) loa infection.
Lancet i: 798-800, 1921
67. MANSON P. The Filaria sanguinis hominis major and minor, two new species of
haematozoa. Lancet i: 4-8, 1891
68. MANSON P. The geographical distribution, pathological relations and life history o f
Filaria sanguinis hominis diurna and Filaria sanguinis hominis perstans in connexion
with preventive medicine. Transactions of the Seventh International Congress on Hygiene
and Demography, London, August 10-17, 1891, 1: 79-97, 1892. Abstracted in Medical
Press and Circular 103, new series 52: 202-205, 1891 and Semaine Médecine 11: 342 ,
1891
69. MANSON P. Tropical diseases. A manual of the diseases of warm climates, Cassell and
70. MANSON P. On the nature and origin of Calabar swellings. Transactions of the Society
73. MANSON-BAHR P. On the longevity of the Loa loa and some hitherto undescribe d
manifestions of this infection. Archiv für Schiffs- und Tropen-Hygiene 29: 222-224, 1925
74. MEINHOF H. Zur Klinik und Morphologie der Filaria und Mikrofilaria loa (diurna) .
75. MONGIN. Sur un ver trouvé sous la conjonctive, à Maribarou, isle Saint-Domingue .
Journal de Médecine, Chirurgie, Pharmacie etc. 32: 338-339, 1770. Translated in 55
76. MORLOT, ZUBER. Neosalvarsan et Filaria loa. Comptes Rendus Hebdomadaires des
Séances de la Société de Biologie 77: 475-476, 1914
Loiasis 659
77. MÜHLENS. Zur Behandlung der Filariasis. Archiv für Schiffs- und Tropen-Hygiene 25:
247-248, 1921
78. MÜLLER OF. Verzeichniss der bisher entdeckten Eingeweidewürmer, der Thiere, i n
welchen sie gefunden Worden, und besten Schriften, die derselben erwähnen .
Naturforscher, Halle 22: 33-86, 1787
79. MURGATROYD F, WOODRUFF AW. Loiaisis treated with Hetrazan (Banocide) .
Lancet ii: 147-149, 1949
80. ORIHEL TC, MOORE PJ. Loa loa: Experimental infection in two species of Africa n
primates. American Journal of Tropical Medicine and Hygiene 24: 606-609, 1975
81. RODHAIN J, DUBOIS A. A contribution to the study of intradermal reactions in human
filariasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 25 :
377-382, 1932
82. ROGERS W. A note on a cas e of Loa loa. Annals of Tropical Medicine and Parasitology
7: 363-365, 1913
83. ROTH F. Filaria loa. Lancet i: 764-765, 1896
84. SAMBON LW. Remarks on the individuality of Filaria diurna. Journal of Tropical
85. SCHOFIELD FD. The complement-fixation reaction in loiasis and Acanthocheilonema
perstans infections. Journal of Tropical Medicine and Hygiene 60: 170-172, 1957
86. SHOOKHOFF HB, DWORK KG. Treatment of Loa loa infections with Hetrazan .
87. SMITH AJ, RIVAS D. Notes upon human filariasis ( Filaria loa Guyot, and Filaria
bancrofti Cobbold). American Journal of Tropical Diseases and Preventive Medicine 2:
361-377, 1914
88. STEFANOPOULO GJ, SCHNEIDER J. Essais de traitement de la filariose à F. loa par
la 1-diéthyl-carbamyl 4-methylpipérazine. Comptes Rendus Hebdomadaires des Séances
de l'Académie de Biologie 142: 930-931, 1948
89. STILES CW, HASSALL A. The determination of generic types, and a list of roundworm
genera, with their original and type species. Bureau of Animal Industry, United State s
Department of Agriculture, Bulletin 79, pp 1-150, 1905
90. WANSON M. Essai de traitement avatif de la filariose à Loa loa et de la filariose
apériodique par les dérivés de la pipérazine. Annales de la Société Belge de Médecin e
Tropicale 29: 73-80, 1949
91. WARD H B. The earliest record of Filaria loa. Zoologische Annalen 1: 376-384, 1905
92. WILLIAMS P, CREWE W. Studies on the control of vectors of loiasis in West Africa.
V. The effects of DDT, dieldrin, aldrin and gamma-BHC in the mud of natural tabani d
breeding-sites in the rain-forest of the Cameroons. Annals of Tropical Medicine an d
93. WILLIS AJ. Adult nephrotic syndrome at Ibadan; aetiological considerations. Journal of
94. WOODRUFF AW. Destruction of microfilariae of Loa loa in the liver in loiasis treated
with Banocide (Hetrazan). Transactions of the Royal Society of Tropical Medicine and
Hygiene 44: 479-480, 1951
95. ZIEMANN H. Ein Fall von Filaria-loa-I nfektion mit mindestens 17 jähriger Dauer. Archiv
für Schiffs- und Tropen-Hygiene 30: 626-628, 1926
Table 24.1. Landmarks in loiasis

___________________________________________________________________
BC Adult worms migrating through the eye were recognized by inhabitants of

West and Central Africa and were removed by local practitioners
1768 Bajon removed an adult worm from the eye of a girl
1770 Mongin published an account of the adult worm and the clinical features it
caused
1890 McKenzie found unusual microfilariae in the blood of a patient with sleeping
sickness
1891 Manson investigated several patients and differentiated a microfilaria of the
same size as microfilaria bancrofti but which had diurnal periodicity and
ill-defined morphological changes (= microfilaria loa) and a smaller
microfilaria with no periodicity (= microfilaria perstans)
1895 Argyll-Robertson in collaboration with Manson gave a detailed description of
the morphology of male and female adult worms
Manson suggested that microfilaria diurna may be the embryo of L. loa
1912 Leiper discovered that microfilariae developed in flies of the genus Chrysops
1914 Smith and Rivas described a concentration technique for the demonstration
of microfilariae in the blood
1921-3 Connal and Connal described in detail the development of larvae in Chrysops
1948 Stefanopoulos and Schneider described the results of treatment with
diethylcarbamazine
1975 Orihel and Moore infected two monkeys and a baboon experimentally using
infective larvae developed in a fly fed on a human with loiasis
__________________________________________________________________
Chapter 25
Onchocerca volvulus and ONCHOCERCIASIS
SYNOPSIS
Common name: the convoluted filaria causing river blindness

Major synonyms: Filaria volvulus, Filaria volvulxus, Onchocerca caecutiens
Distribution: West, Central and East Africa, Central and northern South America
Life cycle: the adult worms, 20-50 cm long by 0.15-0.40 mm in diameter, mostly live
coiled tightly in subcutaneous nodules. Microfilariae are produced and migrate
through the dermis and into the cornea, anterior chamber and uveal tract of the eye.
When microfilariae are ingested by blackflies of the genus Simulium, they develop
over a week or so into infective larvae which pass to the mouthparts and infect the
next host at the following blood meal
Definitive host: humans (gorilla, spider monkey)
Major clinical features: subcutaneous nodules, dermatitis, keratitis, iridocyclitis,
choroidoretinitis, leading to blindness
Diagnosis: observation of microfilariae in the cornea or anterior chamber (best with a slit
lamp), finding microfilariae on skin biopsy, demonstration of worms in excised
nodules
Treatment: diethylcarbamazine, ivermectin, suramin
DISCOVERY OF THE MICROFILARIA
In 1874, John O'Neill, a British n aval surgeon attached to HMS Decoy at Cape
Coast Castle in the Gold Coast (Ghana) became intrigued by an irritating and
intractable skin disease somewhat resembling scabies which afflicted man y
people living in parts of the West Coast of Afr ica. He determined to look for the
cause of this peculiar condition, which was known locally as "craw-craw", by
studying a number of patients in Addah Fort Hospital under the care of D r
Thompson of the Glover Expedition. The condition was characterized b y
papules, vesicles and pustules. O'Neill examined the contents of pustules and
vesicles under a microscope but found nothing other than leucocytes. When he
turned his attention to papules, success attended his efforts for he found a n
organism which he had no doubt was the cause of the complaint. He reported
in 1875:
I was induced to bestow much time on its microscopic examination, and succeeded
at length in discovering a filaria which I believe to be the immediate cause of the
complaint.102
When specimens were examined in a drop of water under a microscope ,
microfilariae that were easily detectable by virtue of their violent contortions
661
were often seen:

Thread-like in form, at one time undulating, and now twisted as if into an inexplic-
able knot, then, having rapidly untwined itself, it curls up into many loops....
measuring it now we find its length about 1/100 inch, and its breadth about 1/2000
inch, and with the exception of the abruptly pointed tail the filaria is of nearly equal
breadth throughout its entire length. At the head, or blunted extremity, two small
dots are noticed, but their nature could not be determined. 102
It is possible that the same parasites were also seen in 1875 by Dr da Silva
Araujo in a negro in Bahia, Brazil. This patient had been troubled wit h
recurrent attacks of a skin complaint, also labelled "craw-craw". This term, of
course, was imprecise and does not necessarily indicate the same affliction as
that described by O'Neill. Nevertheless, da Silva Araujo recovered from th e
skin of this patient microfilariae which he named Filaria dermathemica 129.
Whether the microfilariae found by da Silva Araujo were in fact O. volvulus or
blood-borne embryos of another species which had contaminated the ski n
biospsies is uncertain; if they were, then a case could be made for designating
the worm now known as Onchocerca volvulus as Onchocerca dermathemica .
The discovery and publication of the finding of the adult O. volvulus was a
strange and tortuous affair. It 1890, an unnamed German doctor working in the
Gold Coast (Ghana), West Africa, removed two tumours, each about the size
of a pigeon's eggs, one from the scalp and the other from the chest, from two
of the local inhabitants. On examining the specimens, he found that the y
contained worms and sent them to Rudolf Leuckart in Germany for identific-
ation. Both tumours contained several female and male worms, the forme r
being about 6-70 mm in length and the latter about half that size; they wer e
coiled together to form a ball which was very difficult to unravel. This mass of
worms was situated in a cavity which contained fluid laden with embryos .
Leuckart did not publish news of this discovery, but informed Patrick Manson
in a personal communication 82. It was left to Manson to publish a skimpy notice
of the parasite, with due to acknowledgem ent to Leuckart, in a chapter he wrote
on skin diseases in the tropics for Davidson's book Hygiene and disease o f
warm climates89. The section on this parasite was labelled Filaria volvulxus,
the latter apparently being a mistranscription of "volvulus" (from the Lati n
"volvo volvere" = to roll or turn round ); whether this was Leuckart's or Manson
designation was not indicated in the text, but was presumably intended to draw
attention to the twisted and coiled intertwining of the worms.
Leuckart had also sent Manson an histological section containing a
fragment of the uterus of one of the worms. Manson remarked:
It was stuffed with outstretched embryos, resembling in shape and dimensions
F. diurna and F. nocturna. Possibly, compared to these parasites, the embryo of
Onchocerciasis 663
F. volvulxus was somewhat shorter, and also somewhat broader proportionately, and
more abruptly truncated at the cephalic end....One important feature of F. diurna
and F. nocturna I did not see represented in the embryo of F. volvulxus, viz., the
sheath. Professor Leuckart makes the same remark. 89
On the basis of the absence of a sheath, Manson concluded that these worms
were not the parental forms of microfilaria diurna (i.e. loa), and were certainly
not the mature W. bancrofti. He made no mention of the micro-filaria e
discovered in skin by O'Neill nearly 20 years earlier, and may well have been
unaware of the report. Somewhat wistfully, he concluded:
beyond the facts just stated, we possess very little information on the subject.
Observations on this and allied matters are very much wanted. From the numerous
discoveries, notwithstanding very limited opportunities, made in recent years in
African pathology and helminthology, it is evident that many novelties await the
investigator of diseases in that country.89
Six years later (1899), Labadie-Lagrave and Deguy described a youn g
female worm found in a nodule removed from a French soldier who had been
on an expedition to Dahomey in West Africa; they called the parasite F.
volvulus 78. In 1901 Prout described the worms recovered from tumour s
removed from two frontier policemen by Dr Hood, District Surgeon in Sierra
Leone. Prout examined the blood and aspirates from a lymph node of th e
second of these patients, but was unable to find any microfilariae. Concerning
the tumour, he wrote:
The tumour was about 1 in. in length by about 3/4 in. in breadth. On making an
incision, a greenish, semipurulent-looking fluid about the consistency of cream
escaped from the cyst. This, on microscopical examination, was found to contain
numerous filarial embryos. The capsule of the cyst consisted of dense fibrous tissue,
lined internally by a layer of soft, caseous-looking material, which could be easily
scraped off. This was composed of granular material, flat nucleated epithelial cells,
and contained free embryos. The interior of the cyst was filled with adult filariae,
lying in loops twisted up in the most confusing fashion, entering the cyst wall,
running along shallow tunnels, and re-entering the cyst. Owing to this and the
softness and brittleness of the worm, it was a matter of the greatest difficulty to
dissect it out, and I found it impossible to do so without breaking it. Eventually,
however, I succeeded in isolating a complete unbroken adult male, and the head, tail
and intermediate fragments of a female. These two worms formed the whole
contents of the cyst.108
Prout then went on to give the first detailed description of the male and female
adult worms, and described t he microfilariae. Further examples of onchocercal
infection with recovery of adult worms were reported by Brumpt (1904) 25,
Fülleborn (1908) 52 and Parsons (1908) 107. Parsons had in fact seen five patients
and wrote:
very little was known or taught of this particular nematode when (in 1903)....I
became a government official in Northern Nigeria. While other members of the
Filaridae have received a good deal of attention during the present decade, Filaria
volvulus seems to have been comparatively ignored. I am inclined to think, however,
that this Filaria is far more common in certain parts of Africa than is generally
supposed.107
In 1910, Railliet and Henry111 transferred the worm from the genus Filaria
of Müller98 to the genus Onchocerca which had been erected by Diesing i n
1841 to house O. reticulata, a parasite of the horse, donkey and mule i n
Europe42. The name Onchocerca was derived from a combination of the Greek
words (ONCHOS) meaning "hook" and (KERKOS, CERCOS)
meaning "tail".
In 1916, Rodolfo Robles in Guatemala removed a tumour from the forehead
of a boy and on opening it found that it contained:
a fine worm, white and ball-shaped, with the characteristics of a filaria....The
dissection of the parasite was extremely difficult because it seemed to be sewn into
the tumor itself. Extremely fragile, it broke at the slightest pull. However, after a
laborious effort, I extracted a whole piece that measured almost 30 cm (sic)....The
thick cuticle and the very obvious transverse striations made me think it was of the
genus Onchocerca; however, not having the head, the tail, or a male, I was unable
to identify the parasite fully.114
Subsequently, Robles removed other cysts and obtained isolated worms b y
digesting them in a dog's stomach for five hours. Although he thought that the
worm resembled O. volvulus, he thought that some characteristics did no t
coincide exactly. His discovery was first reported in a newspaper, La
Republica, on 29 December 1916, then the formal description appeared in La
Juventud Médica in 1917114. Most of the copies of the issue were destroyed in
an earthquake, but the article was republished in French in 1919 115. In an
accompanying article, Brumpt gave a detailed description of the parasite, and
after comparing it with the specimens collected by him in the Congo, decided
that it was a different species which h e named O. caecutiens to indicate that the
parasite caused blindness (from the Latin "caecus" = blind) 26. Calderón 34
concurred with this opinion. Fülleborn believed that O. volvulus and O. caec-
utiens were morphologically indistinguishable, but considered that there were
differences in the clinical manifestations caused by the two parasites 54,55.
Subsequent studies by Sandground 125 in which more material was examined,
however, showed that there were considerable variations among the specimens
and that no consistent differences existed between the American and African
forms of the worm. An editorial in the British Medical Journal in 1935
describing the latter's work, undertaken as part of the Harvard Department of
Tropical Medicine expedition to Guatemala, accepted this opinion:
Another important result of the expedition has been the final decision, after careful
examination of numerous adult filariae removed from the tumours, that the Central
American form does not differ in any way from the long-known type from the old
world, a conclusion which means that the name O. caecutiens is merely a synomym
of O. volvulus.3
CORRELATION OF O'NEILL'S MICROFILARIA WITH THE ADULT

Onchocerciasis 665
O. VOLVULUS AND ONCHOCERCAL DERMATITIS
When O'Neill in 1875 first described microfilariae in the skin of patients with
craw-craw, the microfilariae of Wuchereria bancrofti had been discovered only
13 years before, Lewis had de monstrated their presence in the blood only three
years earlier, and the parent worm of microfilaria bancrofti was still unknown.
Furthermore, none of the other microfilariae which may be found in human s
(Loa loa, Mansonella perstans etc.) had at that time been discovered. Th e
microscopical facilities and staining techniques available during that perio d
were not advanced sufficiently to permit a detailed description of th e
morphology of these parasites. The major difference between the microfilaria
described by O'Neill and that found by Lewis was the presence of a sheath in
the latter's case. O'Neill's omi ssion of any mention of the absence of this sheath
in the skin microfilariae that he saw 102 implies that he had not seen Lewis' s
paper and may well have bee n unaware of it. This is not particularly surprising
since he was a naval surgeon on the high seas and away from current librar y
facilities. Leuckart and Manson 89 were the first to recognize this characteristic
absence of a sheath in O. volvulus microfilariae, but failed to speculate on the
relationship between O. volvulus and the parasite described by O'Neill. Many
years were to pass before such a relationship was established definitely.
When Prout described the morphology of adult O. volvulus in 1901, he also
compared in tabular form the salient diagnostic features of microfilaria diurna
(= loa), microfilaria nocturna (= bancrofti), microfilaria perstans and the
Onchocerca microfilaria; he showed that they were all distinct from each other
in one respect or another 108. Like Manson, however, Prout did not relate these
worms to the microfilariae of craw-craw that had been described by O'Neill.
In 1913, Ouzilleau reported that in the re gion of Mbomu, French Equatorial
Africa, O. volvulus infections were very common (as were Loa loa and
Mansonella perstans, but Wuchereria bancrofti was absent). This provided an
opportunity for examining a large number of patients with onchocerciasis .
Ouzilleau confirmed Prout's observation that microfilariae were not present in
the blood; he found a microfilaria similar to those aspirated from a n
onchocercal cyst only once in 200 blood examinations, but did find them o n
many occasions in lymph node aspirates 103. This finding was criticized by Low
who felt that they must have been W. bancrofti microfilariae 83, but Ouzilleau
was supported later that year by Fülleborn and Simon56. Simon had found large,
unsheathed microfilariae in the inguinal lymph nodes and in the blood of a
patient with large onchocercal nodules on the superior iliac spine. He believed
that they might be microfilariae of O. volvulus so submitted them to Fülleborn
who could discern no differences between them and those prepared from O.
volvulus adult worms. This observation was confirmed when Simon the n
obtained lymph nodes from another patient with onchocerciasis who wa s
operated upon for a femoral hernia. Careful measurements of the size an d
location of various landmarks on the microfilariae proved conclusively that the

microfilariae from the lymph nodes and from O. volvulus were identical, and
were different from those of W. bancrofti and Loa loa. Finally, Simon also
showed that although the blood contained no microfilariae, O. volvulus-type
microfilariae could be obtained in blood specimens if excessive pressure was
applied to the skin, perhaps squeezing them out in the lymph. Thes e
observations satisfied Low who now wrote:
it is at once seen that the embryos found in the lymph glands and blood of the native
infected with volvulus cysts correspond with - or one might say, are the same as -
the real embryos of O. volvulus.84
Ouzilleau's views were again confirmed in 1916 by Rodhain and van de n
Branden in Leopoldville, Belgian Congo (Zaire) and by Dubois in the Well e
(Uele) district of the same country, by Robles in Guatemala, and later b y
Montpellier and colleagues 97. Despite repeated and intensive investigations ,
including the use of concentrating techniques, Rodhain and van den Branden
failed to find any microfilariae in the blood of 29 patients with clinica l
onchocerciasis yet were able to find microfilariae in 11 of 28 patients after the
single puncture of a femoral or inguina l lymph node 119. Similarly, Dubois wrote
that microfilaria volvulus was present in inguinal lymph nodes and stated that
he had never succeeded in finding them in the blood 43 and Robles in Guatemala
only once observed an infection when he pricked skin near a nodule 114.
Nevertheless, it was still not realized that these microfilariae were also found
commonly in the integument and were the same as O'Neill's parasites.
Montpellier and Lacroix in 1920 were first to put forward this view. They
reported that many native troops from Africa complained of a skin affection or
itch which was most marked on the buttocks, flanks and lumbar regions, and
was associated with inguinal lymp hadenopathy and an eosinophilia. Systematic
examination of these lesions resulted in the discovery of the constant presence
of microfilariae in the dermal layer of the skin, independent of the vascula r
system. Montpellier and Lacroix considered the microfilariae to be embryos of
O. volvulus or a very closely related species. Further investigation, moreover,
revealed the presence of fibrous cysts in some patients, one of which upo n
excision yielded a male and female O. volvulus. These investigators regarded
the condition as identical with the craw-craw described by O'Neill in 1875 and
concluded that this condition, which they called gale filarienne (filarial itch) ,
was a dermal manifestation of onchocerciasis 95.
At the conclusion of their paper which they presented to La Société d e
Pathologie Exotique in France, however, Brumpt challenged Montpellier and
Lacroix's proposition on the grounds that the distribution of craw-craw an d
onchocerciasis were different27. Not to be outdone, Montpellier and colleagues
reaffirmed their views in another paper pub lished later that year, remarking that
craw-craw or filarial itch used in the restricted sense of O'Neill corresponded
in geographical distribution with O. volvulus and reported that, except in rare
Onchocerciasis 667
instances, all their patients with filarial itch had onchocercal tumours, and that
all persons with one of these nodules had the eruption characteristic of filarial
itch94. This failed to convince Brumpt who again asserted that any role for O.
volvulus in the causation of filarial itch was doubtful 28.
In the following year, Ouzilleau and colleagues in the Congo (Brazzaville),
studied a village in which 16 of the 27 inhabitants were afflicted wit h
onchocercal nodules, with five having cutaneous lesions in addition. Thes e
investigators examined the skin lesions and concluded that subjects infecte d
with O. volvulus nodules always had microfilaria volvulus in the dermis, and
that these parasites elicited an inflammatory reaction which caused th e
cutaneous lesions, yet unaccountably, they did not consider that "craw-craw "
was connected with onchocerciasis 105. This elicited another response fro m
Montpellier and Lacroix 96 who discussed the advisability or otherwise o f
retaining the term craw-craw as a dis tinct condition. They reiterated their belief
that the skin lesions were due to itching whereas Ouzilleau and colleagues had
ascribed the skin reactions directly to the action of the microfilariae. In fact ,
both groups of investigators were probably partly right, with microfilaria e
stimulating an inflammatory reaction which, amongst other things, cause d
itching and scratching which in turn exacerbated the condition. Th e
observations of the French workers were confirmed by Macfie and Corson in
Accra, Ghana. They found that not only were O. volvulus microfilariae present
in the skin of patients with Onchocerca nodules, but that examination of skin
biopsies taken from 50 health y men selected at random revealed larvae in 34%
of them. Finally, MacFie and Corson showed at autopsy of three infecte d
individuals that parasites were p resent in widely separated areas of the skin but
were absent from the mucous membranes and internal organs 86.
Thus, by the middle of the 1920's, it was becoming clear that th e
unsheathed microfilariae in lymph node aspirates which looked the same a s
those obtained from O. volvulus adults were indeed derived from that parasite,
as were the same microfilariae seen in th e skin. Finally, despite the reservations
of some sceptics such as Brumpt, it seemed c ertain in retrospect that the filariae
seen in the skin 50 years earlier by O'Neill were indeed O. volvulus
microfilariae.

OF THE BLACKFLY INTERMEDIATE HOST
When Manson first described O. volvulus, he wrote that "Judging also from the
absence of sheath, it may be that the life history of this parasite is somewha t
different in character from that of F. diurna or F. nocturna" 89. Nevertheless,
Manson probably had in mind the likelihood that infection was transmitted by
some blood-sucking insect in the same way as he had shown with W. bancrofti.
When MacFadden and Leiper in 1911 reported on the contamination wit h

Onchocerca gibsoni of Australian beef imported into Britain (when ,
incidentally, they first coined the term onchocerciasis to describe the diseas e
caused by infection with Onchocerca), they speculated that the vector wa s
probably a blood-sucking muscid fly such as Stomoxys, Hipposbosca or a
tabanid, or an ixodid tick 85. In the same year, Breinl in Australia reported that
he had been unable to infect Stomoxys calcitrans, the mosquitoes Culex
fatigans (= quinquefasciatus), Stegomyia fasciata (= Aedes aegypti) and
Mansonia uniformis, the leech Hirudo medicinalis, or the copepod (crust-
acean) Cyclops pallidus with O. gibsoni 24. In 1913, Leiper tried to infect the
flies Stomoxys nigra and S. calcitans with the human parasite, O. volvulus,
when he was in Nigeria. He fed them upon the juice of onchocercal nodules and
although there was food initially in the stomach contents, dissection at late r
dates provided no evidence of i nfection of the flies 81. Similar experiments were
tried unsuccessfully by a numb er of subsequent investigators: Rodhain and van
den Branden (1916) with the mosquito Aedes aegypti and the bedbug Cimex
rotundatus 119, Calderón (1920) with lice, mosquitoes and various flies34 ,
Macfie and Corson (1922) with the tse-tse fly Glossina palpalis 86, and
Blanchard and Laigret (1924) with the tick Ornithodorus moubata and the
bedbug C. lectularis 22.
Meanwhile, Robles in Guatemal a, by a masterly series of observations, had
come very close to the truth as early as 1917. He ruled out transmission o f
infection via water by showing that the disease was common in plantation s
above 2,000 feet but not in people living at lower altitudes who drank the same
water which had flowed through the infection areas. Further, he noted that in
one farm which had two ranches, one situated at 2,000 feet (610 metres) and
the other at 2,300 feet, all the inhabitants of the higher site were infected, but
among the people living at the lower village, only those workers who picked
coffee by day at heights varying between 2,300 and 2,500 feet were infected.
These individuals slept at home at the lower ranch and their wives, wh o
remained there, were never infected. He also observed that with tw o
exceptions, the same blood-sucking insects were found above and below 2,000
feet, and they were present in considerable numbers at both locations. Th e
exceptions were two flies (which he erronously called mosquitoes):
From a careful investigation, we deduce that only two mosquitoes of the genus
Simulium: the S. samboni and the S. dinelli, exist between 2,000 and 4,000 feet
above sea level. In the places where these insects were numerous, the largest
number of ill patients was found....they bite for five minutes, sucking blood to the
point where you can see the abdomen fill progressively, giving them a red
coloration. When they are completely full, they become so heavy they can hardly fly,
and many times fall to the earth.114
On one of the farms where the flies abounded in great numbers, Roble s
exposed two largely naked children at 10 a.m. and watched the insects bite. The
majority rested on the ears, cheek and neck with the occasional one on th e
Onchocerciasis 669
forehead and chest. Unfortunately, Robles did not catch and dissect these flies,
but he wrote: "I believe I can hypothesize that these are the intermediate hosts.
At any rate, it is necessary to demonstrate this, and it has not been done" 114.
In 1923, the Briton, Donald Blacklock, began to investigate the mode o f
transmission of onchocerciasis in Sierra Leone. Since the microfilariae were not
in the blood but in the skin, he postulated that any arthropod capable o f
transmitting the worms must be able to da mage the skin and dislodge the larvae
in its efforts to reach blood. Accordingly, he first looked at the Congo floo r
maggot, Auchmeromyia luteola , which was common in the houses, but n o
signs of the parasite were found. In December 1923 and January 1924, h e
observed that the blackfly prophetically named Simulium damnosum was biting
viciously and in great numbers near the streams supplying several of th e
villages in an endemic area. Furthermore, he noticed that the insect was slow
in drawing blood, which reinforced his idea that it must be inflicting sever e
damage. He therefore caught 100 specimens and examined them for larvae in
the gut, but finding nothing, abandoned the search temporarily. In 1925, h e
resumed this operation at another vill age, this time with success. 780 flies were
captured while biting randomly selected boys and 2.6% of the insects contained
larvae morphologically identical with O. volvulus microfilariae in their gut .
Thereupon, he submitted two men who were known to have O. volvulus
microfilariae in their skin, bu t were not infected with any other filarial parasite,
to the flies and found that 17% of Simulium contained microfilariae in thei r
intestinal tract. When flies were then permitted to bite only on a 4 inch ban d
around the patients' body, this area in cluding nodules near the trochanters, 80%
of the insects became infected. Meanwhile, 1,320 wild Simulium were
dissected and 1.1% were found to contain developmental forms of som e
nematode, which was in all probability the larva of O. volvulus, in the thorax.
Wild flies were then fed upon infected persons and kept alive for as long a s
possible, with the result that up to 82% were found harbouring larvae in th e
thorax, although only one worm was found in the head. In 1926, he undertook
a further series of experiments to study the development of filariae within the
flies. He found that development took about ten days to complete an d
summarized his findings:
The skin forms taken into the gut of Simulium accumulate at the margin of the
blood coagulum lying between this and the gut wall. They are very active and the
majority pass out of the gut within 24 hours and may be found in the posterior part
of the thoracic muscles in 48 hours. They have altered completely in shape....they
have also lost a great deal of their mobility. Several moults appear to occur before
the form is reached which is capable of invading the head. 20
Blacklock found that when worms reached the proboscis they entered th e
labium where they remained coiled up waiting for an opportunity to emerge. He
then inoculated two monkeys with infective larvae, one intradermally and the
other subcutaneously, the first in the flank and the second in the head, but was
unsuccessful in transmitting infection. Details of Blacklock's work wer e
published in 192618,19 and summarized in the British Medical Journal in

192720.
Blacklock's findings were confirmed by other workers in Africa. Bequaert
(1928) described the insect carrier of O. volvulus in Liberia14, then Gibbons
and Loewenthal investigated S. damnosum and onchocerciasis in Uganda 61.
Van den Berghe (1941) showed that S. damnosum was an important vector in
the Belgian Congo (Zaire) 16. Earlier (1932), Hisette had shown that in certain
regions of the same country, S. neavei was the vector 69, then this was confirmed
in 1940 by McMahon in Kenya 87. Eventually, Wanson, Henrard and Peel 141 in
1945 successfully infected laboratory-bred S. damnosum with O. volvulus.
In the Americas, Hoffman in Mexico reported in 1930 that although tw o
blackflies, S. mooseri (= callidum) and S. ochraceum ingested microfilariae,
development proceeded only in the latter 71. On the other hand, Strong i n
Guatemala showed in the next year that S. mooseri, S. ochraceum and
S. avidum were all vectors131. Giaquinto Mira believed that S. ochraceum was
the most important species in view of its preference for biting man 60 then
Vargas studied the development of O. volvulus larvae in S. callidum 137.
O. volvulus has not been transmitted experimentally to humans by infected
flies, but epidemiological evidence suggests that the prepatent period i s
between three to 18 months. The adult worms may live for 15 years and ar e
capable of producing microfilariae for up to ten years 113, while microfilariae
may persist for from 6 months to 3 years 46.
RECOGNITION OF THE CLINICAL FEATURES AND DESCRIPTION

OF THE PATHOLOGY
SKIN DISEASE
Once the adult onchocercal worms were recognized within subcutaneou s

nodules, it was obvious that these lesions were a cardinal manifestation o f
onchocerciasis. Nevertheless, only scattered reports describing this condition
in one or several patients appear ed during the twenty years following Manson's
first description. The first person to record a large series of patients wit h
nodules was Ouzilleau in 1913. He noted that the cysts, which varied in siz e
from very small to as large as an apple, were generally superficial in location.
Although the skin could usually be moved over them, they were often tethered
to the underlying muscles or bones. Nearly 80% of the cysts were situated on
the lateral aspects of the chest, while the remainder were usually seen ove r
bony surfaces or joints, especially the iliac crest, greater trochanter, knee ,
olecranon, and frontal, parieta l and occipital regions of the scalp 103. Ouzilleau's
findings were largely confirmed several years later by Dubois who collected an
enormous series of 1,449 patients. He did f ind, however, a different distribution
Onchocerciasis 671
of nodules in the body with 30% being locate d over the trochanters, 29% on the
iliac crests, 21% on the sides of the thorax and 19% either on different or two
or more sites 43. Similar findings were then found by many investigators, with
the distribution of nodules tending to follow more the pattern described b y
Dubois.
Desoil and Benoit studied the histological appearances of an excise d
onchocercal nodule and found a granulomatous inflammatory reaction around
the adult worms and microfilariae migrating throughout the tissues of th e
"tumour"40. Similar observations, with the addition of oedema, eosinophili c
infiltration, endothelial proliferation and fibrosis were noted by subsequen t
investigators90,101. From time to time, nodules became infected secondarily with
bacteria and presented as abscesses, the original problem being realized only
when onchocercae were recovered from the abscess contents 77,122.
While the relationship of O. volvulus to nodules was clear, considerabl e
controversy surrounded the role of O. volvulus microfilariae in producing other
skin lesions. As has already been recounted, it was not until 1920 that O' Neill's
description of filarial worms in craw-craw was exhumed from the librar y
archives and equated with O. volvulus by Montpellier and Lacroix. O'Neil l
described craw-craw as an itchy, papulo-vesiculo-pustular eruption which was
most marked in the clefts of the fingers, front of the wrists, and back of th e
elbows. This distribution is classical of scabies as he himself remarked, and it
may well be that he was dealing with a dua l infection. O'Neill discoursed on the
natural history of the condition:
The papules arise singly and at irregular intervals, increase to the size of a pin's head,
feel firm to the touch, and appear of the same colour as the surrounding integument.
In some cases, the papules arrange themselves in a crescentic form, like
ringworm.....In about two days' time the papule becomes converted into the vesicle,
with very little increase in size, and in the course of a couple of days the pustule is
developed, rapidly enlarging, and uniting with those in its immediate
neighbourhood. In the height of his suffering the patient tears the pustules, and their
liberated and dessicated contents produce large and unsightly crusts. 102
It was the itching and consequent scratching which led to the rediscovery b y
Montpellier and Lacroix of microfilariae in the tegument 95. In addition to the
papules, vesicles and pustules, Ouzilleau and his colleagues in 1921 recognised
thickening of the skin variously described as pseudo-ichthyosis, ichthyosi s
simplex and lichenization. Their histological studies of these lesions revealed
the presence of microfilaria volvulus in the dermis and subdermal tissues ,
infiltration with mononuclear cells, hyperkeratosis of the epidermis, often with
infiltration of the basal layers by leucocytes, enlarged dome-like papillae i n
lichenoid zones and in pruriginous regions with the addition in the latte r
location of blisters and ulceration. In leucodermic areas, the pigment wa s
lacking, the horny layers of skin were thinner than usual and there was a n
increase in fibrous tissue with an absence of blood vessels and glands 105. In
contrast, Montpellier and Lacroix 95 did not emphasize the inflammator y
reaction, nor did Dyce Sharp who found that microfilariae were not usuall y
associated with inflammation, although there was sometimes a layer of definite
inflammatory change49. These differences in severity were probably due t o
biopsies being taken from areas of skin with differing severities of disease .
Harris summarized the natural history of the skin lesions by remarking that the
first skin affection was an itching rash which then either became elephantoid,
often with enlarged lymph nodes, or became atrophic 65.
One of the major objections which Brumpt had raised about th e
onchocercal nature of these lesions was the frequent absence of onchocerca l
nodules. Although these criticisms were no longer tenable when man y
investigators demonstrated the unequivocal presence of microfilariae identical
with those of O. volvulus in the skin, explanations were furnished by th e
discovery in autopsies of two humans of clinically occult adult worms whic h
were free in the tissues unencumbered by a fibrous, nodular reactions15, then
the realization that nodules might be located in the deep, inaccessible tissues.
Another problem which was the subject of some controversy was whether
or not onchocercal infection caused elephantiasis. Ouzilleau (1913) had found
that up to 3% of the populati on he surveyed had this condition, yet Wuchereria
bancrofti was absent, only O. volvulus, M. perstans and L. loa being present.
Since he had found O. volvulus microfilariae in aspirates from enlarged lymph
nodes, he suggested that this parasite may be the cause of elephantiasis 103.
Ouzilleau was supported by Dubois who proved onchocercal infection in over
90% of 53 patients with elephantiasis 43. Ouzilleau returned to this theme i n
1923104, then was echoed by Dyce Sharp who found O. volvulus microfilariae
in hydrocele fluid 49. In order to explain the pathogenesis of elephantiasis i n
Onchocerca infection, Rodhain put forward the hypothesis that obstruction to
lymph flow was caused by microfilariae in the lymphatic capillaries 118. On the
other hand, Dubois eventually modified his views and concluded that while O.
volvulus favoured the appearance of elephanti asis, W. bancrofti was its primary
cause44. Nevertheless, Kirk (1947) found that hydrocele and scrota l
elephantiasis were very common in patients with onchocerciasis in the Sudan
in an area where bancroftian filariasis was rare 76, so that the matter is not yet
completely resolved. Finally, a form of pseudoelephantiasis called "hangin g
groin", in which a sac of atrophic skin containing sclerosed glands in a matrix
of connective tissue and lymph exudate, was described by Nelson as bein g
frequent in persons heavily infected with Onchocerca in Uganda99.
Variations on these themes were seen in onc hocerciasis in Central America,
perhaps partly due to the light skin colour of many of the infected persons and
the biting habits of the vectors. In Guatemala, there was a condition known as
"Erisipela de la Costa" (erysipelas, i.e. red skin inflammation of the coast). In
1915, Robles was consulted by a woma n concerning recurrent erysipelas of the
face which was accompanied by fever, a burning sensation, pruritus and poor
vision, but he did not know the cause. Afterwards he saw a boy with the same
features:
Onchocerciasis 673
There was edema of the eyelids, the forehead, and the superior lip. The cheeks were
puffed up with shiny, dry, scaly lesions that resembled chronic eczema; also there
was a greenish coloration of both cheeks as you would see in ecchymosis of several
days' duration. When touched, the edema was hard leaving no digital impression.
The ears were much increased in size with the external ear pushed forward; the lobe
was edematous, scaly, dry and whitish.114
On his forehead was a tumour the size of a cherry; it was this nodule tha t
Robles excised and first discovered the adult Onchocerca in the Americas and
later remarked: "I understood then that the 'erysipelas' lesions surely were due
to the presence of this parasite" 114.
Robles collected a large series of patients and noted that the nodules were
found most commonly on the head. They were generally situated in the sub -
cutaneous tissues but were occasionally tethered to underlying structures .
Indeed, in four of 500 patients on whom he operated, the nodules ha d
perforated the cranium and were resting on the meninges. He noted too, that the
adult worms could be long-lived, for he found living worms in a cyst which he
removed from a patient who had been living out of an endemic area for seven
years.
Apart from the skin nodules, Robles observed two forms of skin disease .
Some patients developed acute inflammation in which the skin became:
smoothy, shiny, red, tense and warm simulating erysipelas....After three to four days
the fever falls slowly and the patient enters a chronic stage. The swellings persist
much longer, for days, up to months in the same stage; but usually at the end of 20
days they diminish notably.114
In the chronic stage, however, he wrote that when the face was involved:
the cheeks are always indurated, the skin eczematous, pigmented and lustrous, with
an absolutely typical greenish livid color; elephantiasis of the ears, which are
doubled in size, bent forward with skin wrinkled and scaly.....On the limbs of the
body there is a uniform swelling with induration as seen in the elephantiasis of the
Arabs. However, the typical greenish color suggests the diagnosis instantaneously.114
Robles observations were confirmed by Calderón 34 and by Strong 131,132. A few
years late, Goldman and Ortiz classified the dermatitis into three forms :
pigmentation dermatitis or "mal de morado" (= purple disease) in which th e
skin became purplish in colour, a lic henoid form, and an eczematous dermatitis
in which the lesions were papulo-vesicular, excoriated, papillomatous an d
hyperkeratotic62. Although Robles had commented upon elephantiasis of th e
limbs, subsequent investigat ors were agreed that this condition was very rarely
seen in American onchocerciasis.
EYE DISEASE
The early investigators of onchocerciasis in Africa made no mention at all of

eye disease. This is not altogether surprising as the most obvious feature was
the presence of nodules, which were not usually situated on the head. Bein g
aware of microfilariae in lymph nodes, they were more concerned with th e

possibility of the organism causing elephantiasis. Furthermore, they were not
aware of onchocercal microfilarial skin disease which, had they known of it ,
might have sensitized them to look for other manifestations of illness caused by
microfilariae. Finally, they were devoid of the technical equipment necessary
for a full recognition of onchocercal eye disease; it is doubtful if any of the m
even had a simple ophthalmoscope. In contrast, the clinical presentation t o
Robles in Guatemala was completely different. Nodules were common on the
head and produced a distinctive sk in disease, often located on the face. Further,
the patients often complained of an associated eye trouble. Robles' first, bu t
undiagnosed, patient complained o f losing her sight, and ophthalmic symptoms
and signs were marked in the boy from whom he first recovered an adul t
Onchocerca:
The ocular symptoms consisted of redness of the conjunctiva and iritis; the usually
brilliant and transparent corneas were now dull and without glossiness; there were
scattered small leucomas as if the patient had suffered from an ulcerative keratitis;
there were periorbital pains....and very notable diminution of visual acuity. The boy
complained of cloudy vision. Photophobia was so intense that the little boy always
walked with the brim of the hat pulled down to shade his eyes from the light; at
midday he experienced burning and pruritis (sic) in the eyes which felt as though
they were full of sand.114
What really convinced Robles of the relationship between the eye disease and
infection was the remarkable resolution following removal of onchocerca l
nodules from his forehead:
the child's appearance the following day was completely different; the edema as well
as redness of the conjunctiva had disappeared. . The clouding of his vision had
disappeared so that now he could see perfectly; the light did not bother him any
longer; the pruritis (sic) and gritty sensation were no longer present. 114
As with the skin disease, Robles recognized two forms of eye involvement. In
acute ophthalmic onchocerciasis, he described periorbital pain, sensations of
having foreign bodies in the eyes, and wrote that "the cornea has the char -
acteristics of a punctate keratitis" 114. Further, he noted that a dangerous iriti s
could complicate the picture, but remarked that examination of the fundus by
Dr Pachecho Luna had not revealed any abnormality of that part of the eye. In
chronic cases, Robles found photophobia, pte rygia, punctate keratitis, a dull iris
with a deformed and constricted pupil, and progressive loss of visual acuity .
These features were echoed by Pachecho Luna who thought that the punctate
keratitis was due to a microfilarial toxin as eyesight improved rapidly whe n
nodules were removed:
For this reason, it is presumed that all the symptoms are due to the secretion from
a parasite in the human organism, of a toxic substance, which produces at times
appreciable lesions in the eyes.106
Pachecho Luna never saw any microfilariae in the eye itself. Similarly ,
Calderón commented upon punctate keratitis, corneal leucoma, acute o r
chronic iritis, photophobia, pigmentation of the sclera, and considerabl e
Onchocerciasis 675
impairment of vision34. A number of other authors also remarked upon th e

rapid disappearance of acute symptoms after removal of a nodule, althoug h
such statements were criticiz ed by Guerrero (1922) on the ground that patients
were not followed up to see if the problems recurred and he contended that a
"post hoc propter hoc" interpretation of the relationship could be fallacious 64.
Doubts were also expressed by Fülleborn, who together with Zschukke, found
nodules in 70% of labourers on one Guatemala plantation yet found objective
evidence of diminution of vision in only two. He concluded that the carriers of
Onchocerca that they had seen were perfectly healthy individuals and h e
deprecated the prophylactic removal of parasitic cysts which had bee n
proposed recently54,55. His view did not endure, however, and many author s
confirmed the relationship between O. volvulus infection and eye disease 36,80.
The first persons to mention onchocerciasis of the eye in Africa wer e
Ouzilleau and his colleagues who recorded that one of the 16 infected persons
they had found in a village of 27 inhabitants had keratitis 105. Publication of the
observations in Central America stimulated a search for eye disease in African
onchocerciasis but it seemed to be largely absent; thus, Blacklock in 192 7
reported that he could find no evidence of eye disease in patients wit h
onchocerciasis in Sierra Leone 20. It was not until 1931 that Hisette reported that
in a focus of onchocerciasis in the Belgian Congo (Zaire), 20% of the patients
with onchocerciasis were blind and that 50% of the population suffered from
eye troubles. The disease differed from onchocerciasis as generally described
in Africa in that large numbers of cysts were located on the head, although there
was no erysipelas-like lesions. Further, he found that removal of the nodule s
often ameliorated the symptoms 68. Hisette amplified his findings in a long paper
published in the following year where, in addition to a description of anterior
eye disease, he drew attention to an association with choroidoretinitis 69. His
findings prompted renewed efforts to find ocular complications o f
onchocerciasis in other parts of Africa and in 1935 Bryant reported tha t
blindness was appallingly common in a part of the Sudan where the infection
was endemic. Some of this was due to anterior eye disease with onchocerca l
punctate keratitis and corneal sclerosis, but most people were blind because of
a gross choroidoretinitis with optic atrophy. Whereas the first condition wa s
clearly due to Onchocerca infection, there was some doubt about the second,
for microfilariae could not be found in histologically-sectioned eyes, but h e
provided statistical and epidemiological evidence to support his thesis 29. In
1945, Ridley showed that slightly more than one third of patients wit h
onchocerciasis in a region of the Gold Coast (Ghana) had evidence of eithe r
anterior or posterior disease, with nearly half of them being blind or nearl y
blind. He concluded on the basis of slit lamp examinations and a review of the
literature of the pathology of the disease that living microfilariae caused n o
tissue reaction but that the lesions were a response to dead microfilariae 112. In
the same year, Puig Solanes and his colleagues in Mexico came to the sam e
conclusion 109.
Histological studies of infected eyes were slow in coming because o f

difficulties in obtaining material. In 1928 and again in 1930, Ochoteren a
described the findings in an eye excised from a blind man. The eye was fixed
entire and serial sections made; microfil ariae were seen particularly in the outer
one third of the cornea and in the optic nerve 100. Silva (1932) found
microfilariae in the choroid and posterior two thirds of the cornea in sections
of eyes128 and Hisette in the same year found microfilariae throughout the eye 69.
Giaquinto Mira in 1934 also described microfilariae in the optic nerve 59 then
in the same year, Strong and his colleagues indicated that in a study of 11 eyes
removed at operation, microfilariae were found in the cornea, iris, ciliary body
and choroid132. Bryant (1935) then showed that in patients with anterio r
onchocerciasis, microfilariae could be found throughout the anterior eye, th e
cornea was vascularized, the ciliary body inflamed and fibrotic, and the sclera
and choroid were infiltrated with plasma cells although he could no t
demonstrate microfilariae therein 29.
Most investigators have agreed that whether or not eye disease is likely to
occur depends, at least in part, on the distribution and density of microfilariae
in the body. It was realized e arly that the propensity of flies in Central America
to bite near the head and for nodules to form there increased the relativ e
frequency of eye disease in that region compared with Africa. Kershaw and his
colleagues working in Africa described in 1954 a technique for quantifying the
microfilarial density in various parts of the body. They showed that there was
a clear relationship between heavy microfilarial counts in the skin, particularly
of the upper parts of the body, and eye lesions with blindness:
The occurrence of anterior segment lesions is related to the presence of microfilariae
in the anterior chamber and the head region consequent upon a spread of
microfilariae from the lower parts of the body. This spread is associated with a high
intensity of infection in the human host and this in turn probably reflects the
duration and intensity of the exposure to which the host has been subjected
throughout his life....Blindness due to anterior-segment lesions, when expressed as
a percentage of infected persons, is 23 times higher in these heavily infected
communities than in lightly infected ones....the incidence of blindness due to
choroido-retinal lesions amongst infected persons is only six times higher. 75
These observations were then confirmed by Rodger and Brown 116.
While the vast majority of observers accepted that onchocercal infectio n
could cause devastating eye disease, there were still some sceptics. Choyc e
(1958) considered that there was no good evidence that posterior lesion s
(retinal degeneration and optic atrophy) were due to onchocerciasis and, on the
basis of his experience in the Cameroons, believed that the anterior diseas e
(keratitis commonly, iritis mor e rarely), although admittedly due to O. volvulus
infection, did not often lead to more than a slight interference with vision 38. In
reviewing this opinion, a commentator in The Lancet wrote: "If this is correct,
there is little to justify the growing reputation of onchocerciasis as a blinding
affection"4. Woodruff and his colleagues therefore investigated the questio n
further in Uganda and concluded that many other factors than the mer e
Onchocerciasis 677
presence of microfilariae were necessary for the production of eye disease 142.
At this point, so much uncertainty and controversy surrounded the question of
onchocercal eye disease, that a reviewer in The Lancet in 1963 wrote:
The relation between infection with these worms and damage to the eyes is by no
means straightforward....Everyone agrees that microfilariae invading the cornea may
cause conjunctivitis and keratitis, both punctate and sclerosing; but such lesions
rarely cause complete blindness. Blindness is likelier to be due to lesions in the
posterior part of the eye, but opinions differ as to whether such lesions are really
caused by microfilariae or whether they arise from genetic effects and excessive
inbreeding.5
Choyce in 1964 then compared the ocular manifestations of onchocerciasis in
endemic areas in Central America, in Africa, and in expatriates in Britain. He
now concluded that in American onchocerciasis blindness was due to anterior
lesions, posterior lesions being rare, while in the African form of the disease
choroidoretinal lesions were present as well as anterior eye involvement .
Nevertheless, Choyce still held that the posterior eye lesions were due to other
factors such as vitamin B deficiency or inheritance 39. On the other hand, Quere
and his colleagues in Africa, from observations of a large series of patients ,
concluded that both anterior and posterior regions of the eye were involved in
a typical sequence of inflammatory processes caused by the microfilariae 110.
This view is now generally accepted.
The diagnosis of onchocerciasis can be established by finding the parasite in a

number of ways. The most obvious of these is excision of the nodule an d
finding the adult worms therein, as was done in Africa by the medica l
missionary who sent the original specimens to Leuckart, and by Robles i n
Central America. Alternatively, a nod ule can be aspirated with a needle and the
contents examined 103. Van den Berghe used this technique in a large series of
405 nodules and found eggs liberated by damage to the female worm by th e
needle in 60%, a few larvae but no eggs in 30%, and neither eggs nor larvae in
the remaining 10% 17. Microfilariae may also be aspirated from draining lymph
nodes as was shown by Ouzilleau 103.
Another way of demonstrating the presence of microfilariae was described
by O'Neill in 1875 but was forgotten until the technique was resurrected b y
Montpellier and Lacroix in 1920. O'Neill wrote:
I find the readiest way to procure the filaria is to take between the finger and thumb
a fold of the skin, so that the papule will be the highest point, then with a very sharp
scalpel slice off the epidermis, which may be discarded; now take another slice,
which will remove the base of the papule and the cutis vera. This film, moistened
with a drop of water, and magnified about 100 diameters, will very likely contain at
least one filaria, easily detected in the field by its violent contortions. 102
Fülleborn and Simon then showed that the diagnostic morphological features
of O. volvulus microfilariae could be demonstrated by staining them wit h

Romanowsky stains 56.
The presence of microfilariae in the eye can be discerned in a number o f
ways. Silva in 1925, merely by illuminating the fundus with a flat mirror, saw
a very mobile, refringent body with a golden reflection which he believed was
a filaria in the vitreous; with the Gullstrand ophthalmoscope he saw its shadow
on the retinal surface 128. Subsequently, Torroella first used the slit lamp an d
saw microfilariae migrating along the corneal surface and moving in a spira l
fashion through the anterior chamber 135. Torroella's observations wer e
confirmed in 1932 in the Congo (Zaire) by Hisette 69 and also in Uganda by
Boase (1935). The latter described his slit lamp findings:
prolonged examination revealed many of these organisms....The manner in which
they propelled themselves through the aqueous immediately suggested to my mind
the well-known antics of the mosquito larvae, though I think a better description of
their movements would be to say that they tied themselves into knots and untied
themselves with amazing rapidity....their length....is about a third of a millimetre. 23
In the same year, Bryant reported that microfilariae could be found in aqueous
fluid obtained by puncture of the anterior chamber under local anaesthetic with
a syringe, but this method clearly has its disadvantages and dangers 29. A few
years later, Torres Estrada compared vari ous means of visualizing microfilariae
in the eye with different types of ophthalmic equipment and emphasized that the
parasite seemed to be more abundant in the vitreous than in the anterio r
chamber and could be seen in the former site early in the disease 134.
A number of observers noted that blood eosinophil levels were increased
in onchocerciasis, but this was clearly a nonspecific finding. Many attempt s
were therefore made to develop more specific immumoassays. Rodhain and van
den Branden in 1916 looked for complement fixing antibodies using a n
O. volvulus antigen preparation but found them in only 18% of patients 119.
Fifteen years later, Rodhain together with Dubois described a skin test using a
similar antigen but found cross-reactivity with other nematodes 120, then
reported the same phenomenon with Fairley's preparation of Dirofilaria
immitis antigen121. Greater specificity was claimed by van Hoof usin g
O. volvulus antigen prepared in a different manner in an assay to detec t
complement fixing antibodies 72.
Finally, Mazzotti in 1948 drew attention to the fact that a presumptiv e
diagnosis of onchocerciasis could be made if pruritus with or without a ras h
appeared following the administration of diethylcarbamazine (the Mazzott i
reaction - see section on treatment) for this was almost invariable i n
onchocerciasis but was absent in filariasis 91. The usefulness of this phenomenon
was then emphasized by Burch 32.
Onchocerciasis 679
The management of onchocerciasis has been approached from both surgica l

and medical standpoints. The surgical excision of nodules containing adul t
worms was shown to be effective 69,114, but its feasibility depended upon th e
availability of facilities and the number and locations of the nodules to b e
removed.
Many attempts have been made to improve the medical therapy o f
onchocerciasis since O'Neill first tried sulphur (which was often useful i n
scabies) and found it ineffective. He also noted that "the nostrums of the native
'medical man' have frequently failed to bring relief after six months '
application"102. The same might be said for the modern medical man whos e
therapeutic armamentarium is not that much m ore effective. Dyce Sharp (1926)
tried a Bayer preparation, B1916, in a single case and claimed excellen t
results49. Certain antimony compounds and plasmochin were found to have an
effect on microfilariae but were discarded as they had no action on the adul t
worms which rapidly replenished the supply of microfilariae 1. Enzer (1942) in
a preliminary paper investiga ted euflavine, tryparsemide (arsenic) and suramin
(the latter two being anti-trypanosomal compounds) and thought that they may
be of some value if combined with protein shock (T.A.B.) therapy 50.
In 1947, van Hoof and his colleagues took up the further investigation of
suramin which had first been u sed in the treatment of trypanosomiasis in 1921.
They gave 1 gram a week for seven to ten weeks and considered that it wa s
always successful73. On the other hand, Ruiz Reyes tried the same drug bu t
without appreciable benefit 123. Burch tried suramin with some success bu t
experienced troublesome side-effects 31 then Ashburn and colleagues showed
that suramin had a definite lethal effect on adult worms 8.
At around the same time as these re sults were reported, diethylcarbamazine
was introduced for the treatment of filariasis (see chapter 24) then was soo n
tried in onchocerciasis. The first results were reported in 1948 by Mazzotti and
Hewitt who found some reduction in the numbers of microfilariae in the skin,
but in contrast to when suramin was used, nodules extirpated subsequently still
contained living adult worms and microfilariae 93. This was followed by th e
observation of Mazzotti that although the numbers of skin microfilaria e
decreased initially, they often increased again a few months later 92. These
effects, i.e. a failure to kill adult Onchocerca and only a transient reduction in
microfilarial numbers were confirmed by many investigators 8,31,33,45,66,138.
Mazzotti had earlier noted that allergic attacks with fever and local induration
of the skin may occur in onchocerciasis, then found that such reactions wer e
commonly precipitated by the administration of diethylcarbamazine, th e
severity of the reaction being dependent upon the intensity of infection 91. This
phenomenon came to be known as the Mazzotti reaction. Hawking and Laurie
described it graphically, even when small doses of the drug were given:
even a single dose of 50 mg hetrazan citrate almost always produced a violent
reaction which was well marked in 16 hours. There was usually swelling, oedema
and tenderness of the skin, especially of the buttocks and thighs. Sometimes the
prepuce, penis and scrotum were swollen. Intense itching was always widespread.
Sometimes there was a thick papular rash over the trunk and limbs. The
lymph-glands were generally enlarged and tender....There was always pyrexia. 66
The initial encouraging reports with suramin and with diethylcarbamazine
were followed by comparative trials 33 and with the combination of the tw o
drugs37,126. Although each drug has had its advocates, suramin has largely been
abandoned because of its occasional severe toxicity, especially on the kidneys,
even though it kills adult worms, while diethylcarbamazine suffers from th e
twin disadvantages of having only a transitory effect and producing unpleasant
side-effects associated with killing of the microfilariae. Attempts have bee n
made to improve the effectiveness of the latter drug, for example, b y
administering the drug in a skin lotion 6, but these efforts have bee n
unrewarding. Duke in 1981 summarized the difficulties:
The outstanding problem in onchocerciasis remains in the treatment of patients,
particularly those whose eyes are at risk. We are still dependent upon two drugs,
DEC-C (diethylcarbamazine citrate) and suramin whose actions were discovered
more than 30 years ago and which are far from satisfactory in use....What is now
needed above all is a non-toxic drug, which has a convenient dosage schedule and
which can kill or permanently sterilise the adult worms of O. volvulus without
producing a microfilaricidal reaction.48
Duke then remarked that towards this end, The United Nations Development
Fund/World Bank/World Health Organization Spec ial Programme for Research
and Training in Tropical Diseases has set in train a programme to develop new
filaricidal drugs effective against O. volvulus, which:
Given adequate funds, sufficient brains, patience, and some luck, it is hoped...may
pay off within the next 10-15 years developing a new drug to improve the prospects
of treatment of those threatened with or suffering from ocular onchocerciasis. 48
While these words were being written, a promising drug was bein g
developed. In 1978, Blair and Campbell had reported that ivermectin, a
macrocyclic lactone derived from a new species of actinomycete, Streptomyces
avermitilis, had exceptional potency against the nematodes Ancylostoma
caninum 21 and Dirofilaria immitis 35. In 1982, Aziz and his colleagues showed
that the density of skin microfilari ae was greatly reduced in Senegalese patients
treated with ivermectin 12. Subsequent double-blind studies in West Africa have
compared ivermectin with diethylcarbamazine and placebo in patients wit h
high skin microfilarial density, most of whom had ocular involvement .
Ivermectin was shown to be superior to diethylcarbamazine in both safety and
efficacy; ivermectin resulted in a more sustained microfilaricidal effect, wit h
skin microfilarial levels 12 months after treatment being 2-10% o f
pre-treatment levels compared with a value of 10-45% for patients treated with
diethylcarbamazine 9,63,79.
Onchocerciasis 681
Early workers in Africa observed an association between onchocerciasi s

and rivers, particularly smaller waterways. Thus, Ouzilleau found that the
infection was common around the headwaters of the Ubangi 103. Dubois
observed onchocerciasis around waterways in the lower Welle (Uele )
district43 and Rodhain showed that the condition was prevalent along other
tributaries of the Congo117. Similar terrain was present in the Konno district
of Sierra Leone where Blacklock first demonstrated transmission by S.
damnosum:
It is a hilly region drained by several large rivers and a multiplicity of small streams;
the hills are in most cases clothed with dense bush right to the summit. Each village
has in its immediate vicinity several streams; swampy areas produced by silting up
and overflow of the streams are numerous and biting insects are plentiful. 20
This association was explained when the vector was discovered and its breed-
ing habits discerned. Robles in Guatemala had earlier described some aspects
of the biting behaviour of Simulium in Guatemala, showing that those species
preferred to bite by day and around the head (see earlier). After Blackloc k
proved that S. damnosum was the intermediate host, he began to study it s
behaviour. He demonstrated that the flies were present in the bush in th e
vicinity of water, that female flies bit by da y, usually from the waist downwards,
and preferred shade and humidity. Like Robles, Blacklock observed that they
took from one to five minutes to feed then became so distended that they had
difficulty in flying 20. Similar observations were made by van den Berghe in the
Congo16. Wanson and Henrard, also in that country, later showed that female
worms commonly migrated several miles (even up to 45 miles) along rapidly
flowing sections of rivers. They found that breeding took place in these rivers,
with larvae and pupae attached to submerged stones, plants and various other
impedimenta submerged in fast-moving water. They determined that the period
for development from egg to adult took about nine days, and that the adul t
females lived for about three weeks 140. Studies of the behaviour of simuliid flies
in Central America gave broadly similar results.
In East Africa (Kenya), McMahon reported in 1940 that S. neavei was the
vector 87 then he and van Someren showed that the larva of this specie s
developed on the carapace of a freshwater crab 130.
Both Dubois43 and Rodhain117 in the early part of this century noted that the
distribution of onchocerciasis was very p atchy, with the frequency varying from
one location to another. Subsequent studies showed that in some regions, up to
100% of the population was infected. In general, the frequency of infection was
observed to rise with increasing age. In West Africa, onchocerciasis wa s
present in parts of both the northern arid savannah and in the southern rai n
forest, but eye disease was much less common in the latter location. Duke and
his colleagues then showed that this difference may be due to the presence of
different strains of both parasite and vector in those two regions 47.
In many parts of Central America, onchocerciasis is often associated with
the growing of coffee. The infection was first described in Guatemala, as has
already been recounted. In 1923, Fülleborn suggested that onchocerciasis may
also be present in Mexico 53, then this was confirmed by Larumbe80 .
Subsequently, foci of infection were reported in other parts of northern South
America.
Two hypotheses have been promulgated concerning the origins of oncho-
cerciasis in America 70. The first postulates that the infection did not exist in the
Western Hemisphere prior to its introduction by infected persons from Africa.
The most obvious source of such infection is among the negro slaves carried
from West Africa124, but other suggestions have been made. For example ,
Torroella considered that the infection may have been introduced into Mexico
by a battalion of Sudanese troops sent to assist the French invasion troops of
Napoleon III in 1862 136. The alternative hypothesis is that onchocerciasis i s
autochthonous to the Americas. This seeme d quite tenable when Brumpt's view
that O. caecutiens was different to O. volvulus was accepted. This idea wa s
supported by Diaz who found a small number of pre-Columbian skulls wit h
erosions and perforations which he attributed to onchocercal nodules 41. This,
of course, was a non-specific finding, as are the various examples of earl y
Spanish literature citing regions where blindness was common, that have been
quoted by Figueroa Marroquin in support of this latter thesis 51.
Although natural infections with O. volvulus have been found in the gorilla
in the Congo and in the spider monkey in Me xico, there is no evidence that they
are a significant reservoir of zoonotic onchocerciasis.
When Gibbins and Loewenthal reported their own studies of onchocerciasis in

Uganda in 1933, they wrote that since huge tracts of extremely fertile country
had been rendered uninhabitable through the ravages of Simulium flies, and as
the lives of those still living there had been made miserable by irritation from
their bites, the question of suppression of these insects was urgent .
Interestingly, they were concerned only with skin disease and made thi s
judgement without any consideration of the ophthalmic complications of th e
infection. They were not sanguine about the prospects, however, remarking that
it was futile to attempt to attack the flies in their breeding grounds, bu t
suggested that trapping may prove feasible 61. A few years later, Buckley found
in Kenya that discriminative clearing of bush along the banks of two infected
rivers, together with removal of surrounding undergrowth, greatly reduced fly
numbers30.
The outlook was changed drastically, however, with the discovery in 1941
Onchocerciasis 683
by Müller and his team at Geigy in Switzerland of the insecticide, DDT .

Garnham and McMahon in 1949 used this ne w chemical to attack the fly in one
of the three areas in Kenya endemic for onchocerciasis where S. naevei bred in
limited stretches of two rivers. They app lied emulsions of DDT in oil and water
at 10-14 day intervals for six to seven months and succeeded in eradicating the
flies57. Seven years later they reported that the flies were still absent and that
although transmission of onchocerciasis had ceased, the disease still lingered
on58. Eighteen years after eradication of the flies, Roberts and colleague s
reported that all the adult O. volvulus had disappeared by about the sixteenth
year113. A similar result was obtained following a campaign of sprayin g
vegetation along the river banks with DDT from the air in the Congo 139. In
1967, McMahon reviewed the information available about the control o f
Simulium vectors of onchocerciasis. He concluded that larviciding was th e
most efficient means of control and indicated that intermittent control of S.
damnosum had been achieved in various parts of West Africa and that S.
naevei had been eradicated from Kenya and parts of Uganda 88. These results
encouraged the World Health Organization in collaboration with the Food and
Agriculture Organization, the United Nations Development Programme and the
World Bank to embark upon a multi-million dollar programme in the Volt a
River Basin of West Africa with the objective of eradicating blackflies wit h
larvicides. Since 1974, the biodegradable organophosphate insecticide ,
temephos, has been applied from the air repeatedly to 14,000 km of river s
covering an area of nearly one million square kilometres and encompassin g
seven countries (Benin, Burkina Faso [Upper V olta], Ghana, Ivory Coast, Mali,
Niger and Togo) with a popul ation of ten million people. This programme was
based upon the premise that by keeping S. damnosum out of the control area
for 10-15 years, transmission will be interrupted for long enough for th e
infection to die out. The initial two phases of the Onchocerciasis Contro l
Programme carried out between 1974 and 1985 cost US $162 million. A third
phase, at an estimated cost of US $133 million, is to be undertaken betwee n
1986 and 1991, and will be extended westwards into Guinea, Guinea-Bissau,
Senegal and Sierra Leone; it is thus hoped to prevent reintroduction of th e
disease into treated areas by migratory blackflies and provide protection to an
additional eight million people 7.
In contrast to the experience in Africa, the breeding places of Simulium in
Central America are largely inaccessible and McMahon concluded that control
by larviciding was difficult 88. A different approach has been taken in that area
for many years, however. Mass campaigns for the removal of head nodule s
have been mounted with a considerable reduction in microfilarial density ,
morbidity and onchocercal transmission 131,133.
An alternative approach which has been tried in both Africa and th e
Americas has been the repeated administration of diethylcarbamazine; this has
met with little success because the frequency of side-effects has ensured poor
cooperation by the populace6. Nevertheless, the introduction of ivermectin has

provided new hope. As already mentioned, this drug is less toxic and mor e
effective, and may be better tolerated than diethylcarbamazine when given as
a mass prophylactic in endemic areas 11.
OTHER SPECIES OF ONCHOCERCA
In 1965. Siegenthaler and Gübler reported finding an Onchocerca (probably

O. gutturosa) in a nodule removed from the knee of a 25 year old Swis s
woman127. In the same year, Azarova and colleagues described the recovery of
an Onchocerca from the conjunctiva and cornea of a 15 year old girl in th e
Crimea (USSR) 10. In 1973, Ali-Khan and Meerovitch reported the removal of
an Onchocerca from a wrist swelling of a middle-aged woman from Ontario,
Canada2, then Beaver and his colleagues discu ssed another such worm removed
from a similar site in a woman in Illinois, USA 13.
REFERENCES
1. ADAMS AR. A case of onchocerciasis (filarial blinding) with manifestations developing
in Britain. Lancet i: 545-548, 1938
2. ALI-KHAN Z, MEEROVITCH E. The first reported case of a zoonotic Onchocerca sp.
in Man. 48th Annual Meeting of the Ameri can Society of Parasitologists, Toronto, 29 June
1973
3. ANONYMOUS Study of a filarial infection, British Medical Journal i: 1271-1272, 1935
4. ANONYMOUS. Ocular lesions in onchocerciasis. Lancet i: 1165-1166, 1958
5. ANONYMOUS. Control of filarial worms. Lancet i: 589-590, 1963
6. ANONYMOUS. Diethylcarbamazine citrate lotion and onchocerciasis. Lancet ii :
1232-1233, 1980
7. ANONYMOUS. Onchocerciasis Control Programme enters a third phase, Parasitology
Today 2: 81, 1986
8. ASHBURN LL, BURCH TA, BRADY FJ. Pathologic effects of suramin, hetrazan and
arsenamide on adult Onchocerca volvulus. Boletin del Oficina Sanitaria Panamericana 28:
1107-1117, 1949
9. AWADZI K, DADZIE KY, SCHULZ-KEY H, GILLE S HM, FULFORD AJ, AZIZ MA.
The chemotherapy of onchocerciasis XI. A double-blind comparative study of ivermectin,
diethylcarbamazine and placebo in human onchocerciasis in Northern Ghana. Annals of
10. AZAROVA NS, MIRETSKY OY, SONIN MD. (The first instance of detection o f
nematode Onchocerca Diesing 1841 in a person in the USSR.). Meditsinskay a
Parasitologiya i Parasitarn e Bolezni 34: 156-158, 1965. In Russian
11. AZIZ MA. Ivermectin vs. onchocerciasis. Parasitology Today 2: 233-235, 1986
12. AZIZ MA, DIALLO S, DIOP IM, LARIVIERE M, PORT A. Efficacy and tolerance of
ivermectin in human onchocerciasis. Lancet ii: 171-173, 1982
13. BEAVER PC, HORNER GS, BILOS JZ. Zoonotic onchocerciasis in a resident of Illinois
and observations on the identification of Onchocerca species. American Journal o f
14. BEQUAERT J. The insect carrier of Onchocerca volvulus in Liberia. Proceedings of the
Onchocerciasis 685
Fourth International Congress of Entomology 2: 605-607, 1928

15. van den BERGHE L. Note préliminaire sur la localisation extraoculaire de Onchocerca
volvulus chez l'homme. Annales de la Société Belge de Médecine Tropicale 16: 549-551,
1936
16. van den BERGHE L. Recherches sur l'onchocercose au Congo Belge. Ier mémoire. L a
transmission d'Onchocerca volvulus par les Simulies. Annales de la Société Belge d e
Médecine Tropicale 21: 63-76, 1941
17. van den BERGHE L. Recherches sur l'onchocercose au Congo Belge. IIe mémoire. Les
vers adultes et leur localisation chez l'homme. Annales de la Société Belge de Médecine
Tropicale 21: 167-187, 1941
18. BLACKLOCK DB. The development of Onchocerca volvulus in Simulium damnosum .
19. BLACKLOCK DB. The further development of Onchocerca volvulus in Simulium
damnosum Theob. Annals of Tropical Medicine and Parasitology 20: 203-218, 1926
20. BLACKLOCK DB. The insect transmis sion of Onchocerca volvulus (Leuckart 1893), the
cause of worm nodules in man in Africa. British Medical Journal i: 129-133, 1927
21. BLAIR LS, CAMPBELL WC. Efficacy of avermectin against Ancylostoma caninum in
22. BLANCHARD M, LAIGRET J. Recherches sur la transmission d' Onchocerca volvulus
par divers parasites hématophages. Bulletins de la Société de Pathologie Exotique et de
ses Filiales 17: 409-417, 1924
23. BOASE AJ. Ocular filariasis. East African Medical Journal 11: 326-328, 1935
24. BREINL A. Investigation of the morphology and life history of Onchocerca gibsoni .
Report for the year 1911, Australian Institute of Tropical Medicine, pp 5-17, 1911
25. BRUMPT E. À propos de la Filaria volvulus. Revue de Médecine et d'Hygiene Tropicale
1: 43, 1904
26. BRUMPT E. Une nouvelle filaire pathogèn e parasite de l'homme ( Onchocerca caecutiens ,
n. sp.). Bulletins de la Société de Pathologie Exotique et de ses Filiales 12: 464-473, 1919
27. BRUMPT E. Discusssion of 95. Bulletins de la Société de Pathologie Exotique et de ses
Filiales 13: 314-315, 1920
28. BRUMPT E. Au sujet des rapports entre l' Onchocerca volvulus et la gale filarienne.
29. BRYANT J. Endemic retino-choroiditis in the Anglo-Egyptian Sudan and its possibl e
relationship to Onchocerca volvulus . Transactions of the Royal Society of Tropica l
30. BUCKLEY JJ. Studies on human onchocerciasis and Simulium in Nyanza Province,
Kenya. II. The disappearance of S. neavei from a bush-cleared focus. Journal o f
31. BURCH TA. Experimental therapy of onchocerciasis with suramin and hetrazan. Boletin
del Oficina Sanitaria Panamericana 28: 233-248, 1949
32. BURCH TA. Prurito producido por el Hetrazán como una prueba de diagnóstico para la
oncocercosis. Revista de Colegia Médica de Guatemala 2: 53-57, 1951
33. BURCH TA, ASHBURN LL. Experimental therapy of onchocerciasis with suramin and
hetrazan; results of a three year study. American Journal of Tropical Medicine 31 :
617-623, 1951
34. CALDERÓN VM. Contribución al estudio del filárido onchocerca sp. Sr. Robles 1915,
y de las enfermedades que produce. Doctoral thesis, 1919, Tipografia Sanchez & d e
Guise, pp 107, 1920
35. CAMPBELL WC, BLAIR LS. Efficacy of avermectins against Dirofilaria immitis in
36. CASTELLANI A. Observations on some dis eases of Central America. Journal of Tropical
37. CHERRY JK. The treatment of onchocerciasis. E ast African Medical Journal 37: 550-558,
1960
38. CHOYCE DP. Some observations on the ocular complications of onchocerciasis and their
relationship to blindness. Transactions of the Royal Society of Tropical Medicine an d
Hygiene 52: 112-121, 1958
39. CHOYCE DP. Ocular onchocerciasis in Central America, Africa and British Isles (with
a note on equine periodic ophthalmia). Transactions of the Royal Society of Tropica l
40. DESOIL, BENOIT. Considérations sur l'onchocercose à propos d'un cas observé dans une
tumeur du fascia lata chez un soldat nègre. Comptes Rendus Hebdomadaires des Séances
et Mémoires de la Société de Biologie 83: 685-687, 1920
41. DIAZ F. Oncocercosis de Robles. Boletin de la Oficina Sanitaria de Guatemala 6: 1020,
1027, 1935
42. DIESING C. In 67
43. DUBOIS A. Le rôle pathogène de Onchocerca volvulus , Leuckart. Bulletins de la Société
44. DUBOIS A, FORRO M. Contribution à l'étiologie de l'éléphantiasis congolais. Annales
de la Société Belge de Médecine Tropicale 19: 13-21, 1939
45. DUKE BO. The reappearance, rate of increase and distribution of the microfilariae o f
Onchocerca volvulus following treatment with diethylcarbamazine. Transactions of th e
46. DUKE BO. The effects of drugs on Onchocerca volvulus . I. Methods of assessment ,
population dynamics of the parasite and the effects of diethylcarbamazine. Bulletin of the
World Health Organization 39: 137-146, 1968
47. DUKE BO. Onchocerciasis. British Medical Bulletin 28: 66-71, 1972
48. DUKE BO. The six diseases of WHO. Onchocerciasis. British Medical Journal ii :
961-962, 1981
49. DYCE SHARP NA. A contribution to the study of Onchocerca volvulus Leuckart, with
some observations on its prevalence in Nigeria. Transactions of the Royal Society o f
50. ENZER J. A preliminary report on the treatment of onchocerciasis. East African Medical
Journal 19: 134-135, 1942
51. FIGUEROA MARROQUIN H. Historia de la enfermedad de Robles en America y de su
descubrimiento en Guatemala. Separata anticipada de la obra enfermedad de Robles de la
Academia de Ciencias Médicas Fisicas y Naturales de Guatemala, 1963
52. FÜLLEBORN F. Ueber Filaria volvulus Leuckart. Archiv für Schiffs- un d
53. FÜLLEBORN F. Kommt "Kusten-Erysipel" und Onchocerca caecutiens ausser in
Guatemal auch in Mexiko vor? Archiv für Schiffs- und Tropen-Hygiene 27: 386-390 ,
1923
54. FÜLLEBORN F. The "blinding filaria" of Guatemala ( Onchocerca caecutiens , Brumpt
1919). Proceedings of the International Conference on Health Problems in Tropica l
Countries, United Fruit Company, Boston, Mass., pp 241-255, 1924. Abstracted i n
55. FÜLLEBORN F. Zur Onchocerca-caecutiens-Frage. Archiv für Schiffs- un d
56. FÜLLEBORN F, SIMON. Untersuchungen über das Vorkommen der Larven vo n
Onchocerca volvulus in Lymphdrüsen und in der Zirkulation. Archiv für Schiffs- un d
Tropen-Hygiene 17: 501-514, 843-844, 1913
57. GARNHAM PC, McMAHON JP. The eradication of Simulium neavei Roubaud, from an
onchocerciasis area in Kenya Colony. Bulletin of Entomological Research 37: 619-628,
1947
58. GARNHAM PC, McMAHON JP. Final results of an experiment on the control o f
onchocerciasis by eradication of the vector. Bulletin of Entomological Research 45 :
Onchocerciasis 687
175-176, 1954
59. GIAQUINTO MIRA M. Sulla presenza delle microfilarie di " Onchocerca caecutien s
Brumpt" nel nervo ottico. La Riforma Medica 50: 858, 861, 1934
60. GIAQUINTO MIRA M. Contributo agli studi dul problema della transmissione dell a
onchocercosi nel Guatemala. Annali d'Igiene 47: 109-125, 1937
61. GIBBINS EG, LOEWENTHAL LJ. Cutaneous onchocerciasis in a Simulium
damnosum-infested region of Uganda. Annals of Tropical Medicine and Parasitology 27:
489-496, 1933
62. GOLDMAN L, ORTIZ LF. types of dermatitis in American onchocerciasis. Archives of
Dermatology and Syphilis 53: 79-83, 1946
63. GREENE BM, TAYLOR HR, CUPP EW, MURPHY RP, WHITE AT, AZIZ MA ,
SCHULZ-KEY H, D'ANNA SA, NEWLAND, HS, GOLDSCHMIDT LP, AUER C ,
HANSEN AP, FREEMAN SV, REBER EW, WILLIAM S PN. Comparison of ivermectin
and diethylcarbamazine in the treatment of onchocerciasis. New England Journal o f
Medicine 313: 133-138, 1985
64. GUERRERO P. Juicio critico sobre el estudio de la onchocercosis Guatemalteca. L a
Juventad Médica 19: 460-467, 1922
65. HARRIS BP. Clinical aspects of onchocerciasis in the South Kavirondo district of Kenya
Colony. Transactions of the Royal Society of Tropical Medicine and Hygiene 34 :
233-249, 1940
66. HAWKING F, LAURIE W. Action of hetrazan on filariasis and onchocerciasis. Lancet
ii: 146-147, 1949
67. HERMANN J. Trichina bei einem Pferde gefunden. Osterreichische medicinisch e
Wochenschrift, pp 199-200, 1841
68. HISSETTE J. Sur l'existence d'affections oculaires importantes d'origine filarienne dans
certains territoires du Congo. Annales de la Société Belge de Médecine Tropicale 11 :
45-46, 1931
69. HISSETTE J. Mémoire sur l'Onchocerca volvulus "Leuckart" et ses manifestation s
oculaires au Congo Belge. Annales de la Société Belge de Médecine Tropicale 12 :
433-529, 1932
70. HOEPPLI R. Parasitic diseases in Africa and the Western Hemisphere. Acta Tropic a
Supplementum 10, pp 240, 1969
71. HOFFMANN XX. Ueber Onchocerca im Süden von Mexico und die Weiterentwicklung
ihrer Mikrofilarien in Eusimulium mooseri. Archiv für Schiffs- und Tropen-Hygiene 34:
461-472, 1930
72. van HOOF L. Serological reactions in onchocerciasis. Transactions of the Royal Society
73. van HOOF L, HENRARD C, PEEL E, WANSON M. Sur la chimiothérapie d e
l'onchocercose (Note préliminaire). Annales de la Société Belge de Médecine Tropicale
27: 173-177, 1947
75. KERSHAW WE, DUKE BO, BUDDEN FH. Distribution of microfilariae of O. volvulus
in the skin. Its relation to the skin changes and to eye lesions and blindness. British Medical
Journal i: 724-729, 1954
76. KIRK R. Observations on onchocerciasis in the Bahr-el-Ghazal province of the Sudan .
77. KULZ L, BACH FW. Beiträge zur Kenntnis von Onchocerca volvulus Leuck., 1893.
Centralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten, Abteilun g
originale 23: 321-326, 1913
78. LABADIE-LAGRAVE, DEGUY. Un cas de Filaria volvulus. Archives de Parasitologie
2: 451-460, 1899
79. LARIVIERE M, VINGTAIN P, AZIZ M, BEAUVAIS B, WEIMANN D, DEROVIN F,
GINOUX J, SCHULZ-KEY H, GAXOTTE P, BASSET D, SARFATI C. Double-blind

study of ivermectin and diethylcarbamazine in African onchocerciasis patients with ocular
involvement. Lancet ii: 174-177, 1985
80. LARUMBE J. Bulletin del Departmento de Salubridad Publica, 1926. Also, L a
onchocercosis en Oaxaca. Anales de la Sociedad Mexicana de Oftalmología y
Oto-Rhino-Laryngología, series 2, 8: 16-26, 1930
81. LEIPER RT. Report of the helminthologis t, London School of Tropical Medicine, for the
half-year ending April 30th, 1913. Report to the Advisory Committee of the Tropica l
Diseases Research Fund, Colonial Off ice, 1913. Abstracted in Tropical Diseases Bulletin
2: 195-196, 1913
83. LOW GC. Tropical Diseases Bulletin 1: 420, 1913
84. LOW GC. Tropical Diseases Bulletin 3: 102, 1914
85. MacFADDEN AJ, LEIPER RT. Reports to the local government board on public health
and medical subjects on a parasitic conditio n (onchocerciasis) met with in Australian beef.
Food Reports No. 11, H.M. Statione ry Office, pp 16, 1911. Partially reprinted in Journal
86. MacFIE JW, CORSON JF. Observations of Onchocerca volvulus . Annals of Tropical
87. McMAHON JP. Onchocerca volvulus and its vector in the South Kavirondo Districts of
Kenya. Transactions of the Royal Society of Tropical Medicine and Hygiene 34: 65-83,
1940
88. McMAHON JP. A review of the control of Simulium vectors of onchocerciasis. Bulletin
of the World Health Organization 37: 415-430, 1967
89. MANSON P. Diseases of the skin in tropical climates; Filaria volvulxus. In, Hygiene and
diseases of warm climates, AH D avidson, (Editor), Young J Pentland, London, pp 1016,
1893
90. MARTÍNEZ-BAEZ M. Sur la struct ure histologique des nodules à Onchocerca volvulus
et O. caecutiens. Annales de Parasitologie Humaine et Comparée 13: 207-230, 1935
91. MAZZOTTI I. Posibilidad de utilizar como medio diagnostico auxiliar en l a
oncocercosis, las reacciones alergicas consecutivas a la administracion del "Hetrazan".
Revista del Instituto Salubridad y Enfermedades Tropicales, Mexico 9: 235-237, 1948
92. MAZZOTTI L. Estudio ucerca del trata miento de la oncocercosis. Medicina, Mexico 29:
1-5, 1949
93. MAZZOTTI L, HEWITT R. Tratamiento de la oncocercosis por el cloruro d e
1-dietilcarbamil-4-metilpiperazina (Hetrazan). Medicina, Mexico 28: 39-42, 1948
94. MONTPELLIER J, DEGUILLON, LACROIX A. La gale filarienne est-elle bien une
manifestation de volvulose? Bulletins de la Société de Pathologie Exotique et de se s
Filiales 13: 530-535, 1920
95. MONTPELLIER J, LACROIX A. L e craw-craw ou gale filarienne; son origine dans les
kystes sous-cutanées à Onchocerca volvulus . Bulletins de la Société de Pathologi e
96. MONTPELLIER J, LACROIX A. Nouvelle note au sujet de la "gale filarienne" .
97. MONTPELLIER J, LACROIX A, BOUTIN P. Note hématologique concernant le s
sujets infestés par Onchocerca volvulus . Bulletins de la Société de Pathologie Exotique
et de ses Filiales 14: 653-654, 1921
98. MÜLLER OF. Verzeichniss der bisher entdeckten Eingeweidewürmer der Thiere, i n
welchen sie gefunden Worden, und besten Schriften, die derselben erwähne n
99. NELSON GS. "Hanging groin" and hernia, com plications of onchocerciasis. Transactions
100. OCHOTERENA I. Contribución para el conocimiento de la onchocercosis en Mexico.
Onchocerciasis 689
Arbeiten über Tropenkrankheiten, Festschrift Bernard Nocht, pp 386-389, 1928. Also,

Anales del Instituto Biologia. Universidad Nacional de Mexico 1: 59-62, 1930
101. OCHOTERENA I. Contribución para el conocimiento de la onchocerciasis en Mexico.
Proceso histologico de formación de los fibromas onchocercosos. Anales del Institut o
Biología. Universidad Nacional de Mexico 2: 109-115, 1931
102. O'NEILL J. On the presence of a filaria in "craw-craw". Lancet i: 265-266, 1875
103. OUZILLEAU F. Les filaires dumaines de la Région du M'Bomou (Afrique équatoriale
française). Pathogénie de l'éléphantiasis de cette region. Rôle de la Filaria volvulus.
104. OUZILLEAU F. L'éléphantiasis au C ongo et l'Onchocerca volvulus . La Presse Médicale
31: 617-622, 1923
105. OUZILLEAU, LAIGRET, LEFROU. Contribution a l'étude de l' Onchocerca volvulus .
106. PACHECHO LUNA R. Disturbances of vision in patients harboring certain filaria l
tumors. American Journal of Ophthalmology 1: 122-125, 1918
107. PARSON AC. Filaria volvulus Leuckart, its distribution, structure and pathologica l
effects. Parasitology 1: 359-368, 1908
108. PROUT WT. A filaria found in Sierra Leone. ? Filaria volvulus (Leuckart). British
109. PUIG SOLANES M, FONTES A, QUIROZ J. Investigación oftalmológica en la zona
oncocercosa de Chiapas. Salubridad y asistencia. Organo de la Secretaria de Salubridad
y Asistencia. Reforma y Lieja, Mexico 2: 69-86, 1945
110. QUERE MA, BASSETT A, LAR IVIERE M, BASSETT M, RAZAFINJATO R. Étude
statistique sur la fréquence et la spéc ificité des complications oculaires de l'onchocercose.
Bulletin de la Société Médicale d'Afrique Noire Langue Francaise 8: 1-26, 1963
111. RAILLIET A, HENRY AC. Remarques à l'occasion de la note de M. le Dr. Antoine .
112. RIDLEY H. Ocular onchocerciasis, including an investigation in the Gold Coast. British
Journal of Ophthalmology, Monograph Supplement 10, pp 58, 1945
113. ROBERTS JM, NEUMANN E, GÖCKEL CW, HIGHTON RB. Onchocerciasis i n
Kenya 9, 11 and 18 years after elimination of the vector. Bulletin of the World Health
114. ROBLES R. Enfermedad nueva en Guatemala. La Juventud Médica 17: 97-115, 1917.
Translated in 74
115. ROBLES R. Onchocercose hu maine au Guatémala produisant la cêcité et "l'érysipéle du
littoral" (Erisipela de la costa). Bulletins de la Société de Pathologie Exotique et de ses
Filiales 12: 442-460, 1919
116. RODGER FC, BROWN AJ. Assessment of the density of infection with onchocerciasis
and the probable level of safety from its ocular complications. Transactions of the Royal
117. RODHAIN J. Observations diverses concernant Onchocerca volvulus . Bulletins de la
118. RODHAIN J. Les filaires de l'Afrique tropic ale; rôle pathogène. Les réactions allergiques
qu'elles provoquent et le diagnostic de celles-ci. Bulletins de la Société de Pathologi e
119. RODHAIN J, van den BRANDEN F. Recherches diverses sur la Filaria (Onchocerca)
volvulus. Bulletins de la Société de Pathologie Exotique et de ses Filiales 9: 186-198 ,
1916
120. RODHAIN J, DUBOIS A. Obser vations de cas de parasitisme par Onchocerca volvulus
chez l'Européen. Réactions cutanées. Allergie dans la filariose volvulose et la filariose
loa. Revue Belge des Sciences Médicales 3: 613-623, 1931
121. RODHAIN J, DUBOIS A. A contri bution to the study of intradermal reactions in human
filariasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 25 :
377-382, 1932
122. ROUBAUD E, JAMOT E. Présence d' Onchocerca volvulus dans un abcès suspubien.
Quelques précisions morphologiques sur l e parasite. Bulletins de la Société de Pathologie
123. RUIZ REYES F. Tratamiento experimental en la oncocercosis con el "Naphurid e
sodium". Medicina, Mexico 27: 475-477, 1947
124. RUIZ REYES F. Datos historicos sobre el origen de la onchocercosis en America .
Revista Médica Mexicana 32: no. 645, pp 49-56, 1952
125. SANDGROUND JH. Part II. In, Onchocerciasis, with special reference to the Central
American form of the disease, by R P Strong, J H Sandground, J C Bequaert and M M
Ochoa, Harvard University Press, Cambridge, Massachussetts, pp 234, 1934
126. SARKIES JW. Antrypol in the treatment of onchocerciasis. Transactions of the Royal
127. SIEGENTHALER R, GÜBLER R. Pararticuläres Nematodengranulom (einheimische
Onchocerca). Schweizerische medizinische Wochenschrift 95: 1102-1104, 1965
128. SILVA R. Ocular onchocerciasis. Southern Medical Journal 25: 113-117, 1932
129. da SILVA ARAUJO AJ. Memoria sobre a filariose ou a molestia produzida pro um a
nova especie de parasita cutanea, Bahia, pp 36-86, 1875
130. van SOMEREN VD, McMAHON J. Phoretic association between Afronurus and
Simulium species, and the discovery of the early stages of Simulium neavei on
fresh-water crabs. Nature, London 166: 350-351, 1950
131. STRONG RP. Onchocerca investigations in Guatemala. Report of progress of th e
Harvard expedition. New England Journal of Medicine 204: 916-920, 1931
132. STRONG RP. Part I. In, Onchocerciasis, with special reference to the Central American
form of the disease, by R P Strong, J H Sandground, J C Bequaert and M M Ochoa ,
Harvard University Press, Cambridge, Massachussetts, pp 234, 1934
133. de la TORRE I. Sur l'onchocercose au Mexico. Bulletin de l'Office International e
d'Hygiene Publique 23: 2017-2020, 1931
134. TORRES ESTRADA A. Ophthalmoscopic observation of microfilariae in the vitreous
of patients infected with onchocerciasis. American Journal of Ophthalmology 25 :
1445-1448, 1942
135. TORROELLA JL. Contribución al estudio de la onchocercosis de sus manifestiaciones
oculares. Anales del Instituto de Biología. Universidad Nacional de Mexico 1: 201-203,
1930
136. TORROELLA JL. Batallon del ejercito fraces , como probable origen de la onchocercosis
de Mexico y Guatemala. Salud Publica de Mexico Epoca V, vol. 6, no. 3, May-June ,
1964
137. VARGAS L. Algunas consideraciones sobres el desarrollo de Onchocerca volvulus en
los Simulidos. Revista del Instituto de Salubridad y Enfermedades Tropicales, Mexico
3: 57-65, 1942
138. WANSON M. L'Hetrazan dans la période d'invasion de l'onchocercose. Annales de l a
139. WANSON M, COURTOIS L, LEBIED B. L'éradication du Simulium damnosu m
(Theobald) à Leopoldville. Annales de la Société Belge de Médecine Tropicale 29 :
373-403, 1949
140. WANSON M, HENRARD C. Habitat et comp ortement larvaire du Simulium damnosum
Theobald. Recueil des Travaux des Sciences Médicales au Congo Belge 4: 113-121 ,
1945
141. WANSON M, HENRARD C, PEEL E. Onchocerca volvulus Leuckart. Indices
d'infection des simulies aggressives pour l'homme. cycle de développement che z
Simulium damnosum Theobald. Recueil des Travaux des Sciences Médicales au Congo
Belge 4: 122-138, 1945
142. WOODRUFF AW, BARNLEY GR, HOOLAND JT, JONES DE, McCRAE AW ,
Onchocerciasis 691
McLEAN DS. Onchocerciasis and the eye in Western Uganda. Transactions of the Royal
Table 25.1. Landmarks in onchocerciasis

___________________________________________________________________
1875 O'Neill discovered microfilariae in skin biopsies in West Africans with a skin
condition known as "craw-craw"
1893 Manson reported the personal communication to him by Leuckart of the
discovery by a German doctor in Ghana of adult worms in nodules removed
from the subcutaneous tissues
1916 Robles discovered Onchocerca infection in Guatemala
1917 Robles postulated on epidemiological grounds that Simulium flies may be the
vector of Onchocerca in Guatemala, and suggested a relationship between this
infection and eye disease
1920 Montpellier and Lacroix in Africa once more drew attention to the presence
of microfilaria volvulus in the skin and related this infection to dermatitis
1925 Silva observed a microfilaria in the eye with an ophthalmoscope
1926 Blacklock in Africa described the development of microfilaria volvulus into
infective larvae in S. damnosum, but failed to transmit infection
experimentally to monkeys
1928 Ochoterena demonstrated histologically the presence of microfilariae in the
eye and optic nerve
1930 Torroella observed microfilariae in the cornea and anterior chamber with a slit
lamp
1930 Hoffman showed that species of Simulium were the vectors in Central
America
1931 Hisette emphasized the ocular manifestations of onchocerciasis in Africa
1947 Van Hoof and his colleagues showed that suramin killed adult worms but
various workers found this drug to be very toxic
1948 Mazzotti and Hewitt reported that skin microfilarial density fell after treatment
with diethylcarbamazine, although adult worms were not killed
1948 Mazzotti suggested that the precipitation of a rash by diethylcarbamazine
could be used as a diagnostic method
1949 Garnham and McMahon eradicated flies from a limited focus in Kenya by
applying DDT to streams
1982 Aziz and his colleagues indicated that ivermectin greatly reduced the density
of skin microfilariae
___________________________________________________________________
Chapter 26
Dracunculus medinensis and GUINEA WOR M

DISEASE
SYNOPSIS
Common names: Guinea worm, Medina worm, dragonneau, causing dracunculiasis,

dracontiasis
Major synonyms: Filaria medinensis, Fuellebornius medinensis, Gordius medinensis
Distribution: West, North and East Africa, Middle East, Indian subcontinent
Life cycle: First-stage larvae released from gravid female worms into water are ing-
ested by small crustaceans (Cyclops) in the body cavity of which they moult twice
to become infective forms. When humans ingest water containing infected Cyclops,
the larvae escape from the crustacean and migrate through the duodenal wall into
the retroperitoneal connective tissues. There they mature and mate. The female
worms migrate through the connective tissues, usually to the lower limbs, and the
female worm, about 1 metre long, appears in the base of an ulcer approximately one
year after ingestion of the parasite
Definitive hosts: humans (dogs, cats, monkeys, raccoons)
Major clinical features: ulcer, secondary infection
Diagnosis: macroscopic appearance, larvae in discharged fluid
Treatment: metronidazole, niridazole, thiabendazole suppress inflammation and aid in
mechanical extraction of the worm
Guinea worms have been known since antiquity in parts of Africa and th e
Middle East. The parasite is probably mentioned in the Egyptian Papyrus
Ebers (c.1550 B.C.) 99. Thus, Hoeppli49 believed that the following selectio n
from this papyrus is possibly a description of the treatment of an infection with
Guinea worm; "-----" represents the lesion and cannot be translated wit h
certainty:
If thou examinest a swelling of ----- in any limb of a man, then thou shalt apply a
bandage to it. If thou findes that it goes and comes, piercing through the flesh which
is under it, then thou shalt say concerning it; ----- has entered (?). Thou shalt
perform an operation for it, the same being split with a....knife and seized with an
....instrument (forceps); that which is in its interior is seized with a forceps and then
thou shalt remove it....That which is like the head is seized. 29
It is certainly true that dracunculiasis was endemic in Egypt at the time for the
calcified remains of a Dracunculus have been identified in the mummy of a
693
teenage girl entombed around 1,000 BC 22.

The theory was advanced in 1855 by Küchenmeister 59 that the "fiery ser-
pents" which attacked the children of Israel in the desert during their exodu s
from Egypt (c.1250 BC) were in reality Dracunculus medinensis , thus making
the Mosaic passage in Numbers 21: 6 (th ought to be written in 8th century BC)
one of the earliest recorded references to the worm: "Then the Lord sent fiery
serpents among the people, and they bit the people, so that many people o f
Israel died" (Revised Standard Version). Küchenmeister's postulate has been
accepted with enthusiasm by some but rejected by others 5,6,124.
The affliction was mentioned by Agatharchides of Cnidus (2nd quarter of
the 2nd century BC), a geographer and teacher of one of the sons of Alexander
Ptolemy VII. The original manuscript has now been lost but Plutarch (c.46-120
AD) refers to him in the eight book of his Symposiacon (Table talk) where he
makes him narrate:
The people who live near the Red Sea are tormented by an extraordinary and
hitherto unheard of disease. Small worms issue from their bodies in the form of
serpents which gnaw their arms and legs; when these creatures are touched they
withdraw themselves and insinuating themselves between the muscles give rise to
horrible sufferings.1
The condition was also known, either by experience of as a result of hearsay,
to a number of other Greek and Roman writers including Pliny (23-79 AD) ,
Soranus of Ephesus (c.100), Julius Pollux (c.185), Galen (129-c.200), Aetius
of Amida (c.550) and Paulus Aegineta of Alexandria (c.840). It was described
by a number of Persian-Arab physicians including Rhazes (died 928) an d
Avicenna (980-1037). Among the first Europeans from non-endemic areas to
come in contact with the worm were Amatus Lusitanius, van Linschoten ,
Alexei de Abreu, Edward Wotton, Thomas de Veiga, Joh. Gorraeus, Mercur-
ialis and Ingrassia, all in the sixteenth century.
Considerable uncertainty surrounded the nature of the affliction. Som e
authors including Aetius, Paulus Aegineta, Rhazes, Amatus Lusitanius, Alexei
de Abreu, Wotton and de Veiga apparently regarded it as a worm. Others ,
however, thought it was a corrupt nervous substance (Soranus, Pollux, Galen,
Paré), a tumour or abscess (Gorraeus, Aldrovandi, Montranus), an elongated
vein (Guy de Chauliac), black bile (Tagentiu s), fibrous concretions (Richerand)
or atrophied cellular tissue (Larrey).
It is also not always clear precisely what some of the early writers thought
was the nature of the worm. The Persian-Arabic physician, Avicenna (= Abu
Ali al Husain ibn Abdallah ibn Sina) is a case point. According to Hoeppli 49,
Avicenna denied its animal n ature, believing it to be a vein. Amatus Lusitanius
(1511-1568) was also of this view, f or he wrote in Latin (translated by Singer):
A certain Ethiopian slave....was seized with pain in the leg. An ulcer developed, in
which vein-like structures became prominent....The Arabian physicians especially
Avicenna....describe it as the Medina vein.9
On the other hand, Singer provides the following English translation of a Latin
Dracunculiasis 695
rendition by Velschius of Avicenna's text:

In the meanwhile a vermicular movement can be distinguished beneath the skin as
though some live thing were there, and indeed as we shall see, a worm is present,
for so at least some regard the thing that has arisen. 8
From the overall sense, it seems pretty certain that Avicenna was indee d
referring to a worm, but the difficulty apparently lies in the accurate translation
of the original Arabic (Ark, Aerk, Irk or Erk Almedini) which the Greek and
Latin translators of the Middle Ages, having no opportunity of seeing th e
creature, rendered as "Vena seu Nervus medinensis" (vein or nerve fro m
Medina). Thus, Andry (1700) wrote: "Avicenna calls this Worm by the name
of Vena by reason that it resembles a small vein" 3. According to Hoeppli again,
the work Ark simply means something long, thin or filariform 49.
Küchenmeister, however, quoted one autho rity in support of the suggestion that
perhaps it meant "to corrode" or " to gnaw away", thus indicating that it referred
to a worm which gnawed away at the flesh 59. Because of this uncertaintly ,
different translators have therefore used different words in their translations ,
depending upon their personal preferences.
Examples of these various opposing views are provided by Paré and by de
Veiga: "This little dragon is not a worm, nor indeed any living Thing, but only
a Swelling and an Imposthum e occasioned by too hot Blood" 101 compared with
"Whoever entertains such Doubts has taken a narrow view of 'em. 'Tis certain
this worm moves" 132.
Such confusion lasted for many cent uries for as late as 1824 superintending
Surgeon Milne of Bombay, India wrote:
The substance in question cannot be a worm because its situation, functions and
properties are those of a lymphatic vessel and hence the idea of its being an animal
is an absurdity.85
Nevertheless, the opinion that the pathology in question was due to a worm
gradually gained ground. Amatus Lusitanius (1551-1568) left no doubt as to
his own views when he wrote:
Authors are in doubt whether this is a nerve, a vein or a worm. But I have seen the
condition with my own eyes, and can bear witness that a thin, white worm in many
coils was drawn forth.2
In 1674, Georg Hieronymous Velschius (Welsch) wrote a large monograph of
456 pages on the single subject of dracunculiasis. He saw drancunculi every-
where including on ancient Roman emblems, in the signs of the zodiac, among
marine nemertines and polychaetes, in Arabic lettering, in many Gree k
sculptures and in the emblem of the medical profession (serpents coilin g
around the staff of Aesculapius which he interpreted as a Guinea worm jus t
extracted by entwining it around a piece of wood) but asserted that dracunculi
were definitely alive and verminous 133.
Amongst those who accepted the verminous nature of disease, there wa s
considerable confusion concerning the morphology of the creature. Thus ,
Nicholas Andry wrote in 1741:
Two things have to be pointed out concerning this worm: 1. It has two heads: not
one at the side of the other, but one situated at one end, the other one at the other
end, as in some caterpillars. 2. Always one of the two heads appears dead, whereas
the other one appears alive.3
Linnaeus recognized it as a worm and in 1758 in his Systema Naturae, class-
ified the parasite in his Class Vermes, Order Intestina, naming it Gordius
medinensis 71. The specific name, as already inferred, was derived from it s
prevalence around the Arabian city, Medina, as was recorded by Avicenna :
"The disease is commonest at Medina, whence it takes its name" 8.
In the revision by Gmelin of Systema Naturae (thirteenth edition) published
in 1788, the worm was transferred from the free-living species of Gordius to
the genus Filaria of Müller (see chapter 23) and it became known as Filaria
medinensis for some years 43.
Any lingering doubts as to the animal nature, specifically the helminthi c
nature, of the parasite should have been dispelled by the discovery in the early
nineteenth century of the embryos (lar vae) released by the parent worm (as will
be described later). The first detailed description of the worm's anatomy was
published in 1868 by the Englishman, Henry Bastian, and put paid to an y
lingering reservations that D. medinensis was in fact a worm. He examined six
specimens which had been taken from the lower extremities of a Britis h
surgeon in Bombay by a native of that Indian city. The parasites varied i n
length from 18 inches to three feet and macroscopically were:
of a milk-water colour....mostly quite smooth,....cylindrical, more or less flattened
laterally and tapering gradually towards both extremities. About 1/20 of an inch
from the posterior extremity the body becomes more abruptly narrowed, and
terminates usually in a sharply curved tail or point....No vulva discoverable; and
aperture doubtful....The integuments are so elastic, that the worm may be stretched
to nearly twice its natural length.10
Bastian then described the appearance under the low power microscope of the
small head, the lamellar nature of the chitinous integument, four powerfu l
longitudinal muscles, two delicate ganglionated chords extending the whol e
length of the worm, four longitudinal "circulatory vessels" and the gut. All the
worms were female and viviparous. He found th at the reproductive organs were
huge:
The genital apparatus consists of a large, highly organized sac or uterus, distended
with young Filariae and a little fine granular matter. It occupied the whole of the
peritoneal cavity....except from one to two and a half inches from the anterior
extremity and about a quarter of an inch or less from the tail. Both anteriorly and
posteriorly, this sac terminated abruptly in a small tube twisted several times around
the intestine, or forming a knotted glandular-looking mass. 10
In 1879, Fedchenko improved upon the description of the anatomy of the
worm. He found a basal granular layer in the hypodermis which formed th e
outer layers of the integument, discovered some transverse muscle fibres ,
discussed the morphology of the head, excretory system and gut, layin g
particular attention upon the oesophagus and surmising that the worm ingested
food, and concluded that the uterine appendages were ovaries 36.
Dracunculiasis 697
Bastian was intrigued by the failure to find any male worms and speculated
that either the males never attained any great size and therefore failed to attract
attention whereas the enormous development of the genitalia of the female s
made them so large that they became palpable in superficial situations, o r
possibly, that the male worms, in contrast to the females, never entered th e
body. The former hypothesis was proven correct when RH Charles at las t
discovered the male worm. During an autopsy in Lahore, India in 1892, h e
found two nematode worms in the subperitoneal tissues which he regarded as
immature D. medinensis. He went on to say
On examining two....I was struck by seeing something growing from the side of
each of them. This 'something' I found to be a roundworm with the characters of
that to which it was attached. On drawing upon it with forceps I found, to my
astonishment, that it was possible to pull it out of the body of the larger worm from
a small opening near its middle....I did not completely pull it out and only withdrew
it about 1 cm.18
Charles was of the opinion that the "something" was a male Dracunculus but
failed to provide convincing evidence to support his case. A contemporar y
commenator wrote in the British Medical Journal :
Before subscribing to Dr. Charles's views, we should like to see a more detailed
account of the structure of this "something"....Dr. Charles gives no account of the
head, tail, testicle, alimentary canal, spicules, papillae, or any of those features
characteristic of male nematodes. Until these are fully supplied we suspect that
helminthologists will be inclined to regard Dr. Charles's supposed male filaria
medinensis as being probably a hernia or the uterus or alimentary canal of the
female....It is quite possible however, that Dr. Charles in right of his views; but in
bringing them forward the least he could have done, in justice to himself and in the
cause of science, was to use every means in his power to justify the position he
assumes and to make it unassailable. It is not too late yet if he has the interesting
specimens he so meagrely describes in his possession. 7
Subsequently, Leiper (1906) found two male worms about 22 cm long in
an infected monkey 61. Surprisingly, he never provided a detailed description of
their morphology yet he did not encounter the censure that Charles ha d
received. The first substantial account of the morphology of the mal e
Dracunculus was provided in 1937 by Moorthy 86.
In his discussion of the anatomy of the Guinea worm in 1863, Bastia n
remarked that he doubted the propriety of considering the worm as a species
of the genus Filaria. Of the many names which had been used to designate the
worm previously such as "de vena medinensis" 133, "de dracunculo Persarum" 57
and "de verme medinensis" 46, two of these "dracunculus" (derived from th e
Latin word "draco" meaning "snake", "serpent" or "dragon") and "medinensis"
were adopted into binary nomenclature (i.e. Dracunculus medinensis ) by
Cobbold in his text book of the following year 20. In 1915 by Opinion 66, th e
International Commission on Zoological Nomenclature approved this name ,
Dracunculus medinensis being the type of species of the genus Dracunculus 53.
The first person to use the name "Dracunculus" after 1758 (the starting point
for binary nomenclature following the appearance of the tenth edition o f
Linnaeus's Systema Naturae) had been Reichard in 1759 115, and it was this
name which was given official sanction. This was later disputed by Leiper ,
however, on the ground that Reichard only used it in a vernacular sense in his
thesis. Leiper applied the same criticism to the use by Gallandat in his thesis in
177342 of the term "medinensis" to modify "dracunculus". Despite Leiper' s
objections and his attempt to change the name to Füllebornius medinensis 65,
the official name Dracunculus medinensis (Linnaeus 1758) Gallandat 177 3
still stands.
With respect to its common name of Guinea worm, Sir James Tennent ,
Colonial Secretary of the British Government in Ceylon (Sri Lanka) wrote:
these pests in all probability received their popular name of Guinea worm from the
narrative of Bruno or Braun, a citizen or surgeon of Basle, who about the year
1611, made several voyages to that part of the African Coast, and on his return,
published amongst other things, an account of local diseases. 127
EARLY THEORIES ON THE MODE OF TRANSMISSION
The belief that Guinea worm was acquired from water was embedded deeply
in the folk-lore of the inhabitants of many endemic areas. This was accepte d
and reported by a number of European adventurers who began visiting suc h
regions in the sixteenth century. The Dutch navigator, Jan van Linschoten ,
journeyed to the East Indies and on his return to Holland wrote a number o f
books which became very popular and were translated into many Europea n
languages. In 1584, he had visited Hormuz (Ormus, Ormusz) in the Gulf o f
Oman (Persian Gulf) and wrote: "There is in Ormus a sickness or commo n
plague of wormes, which growe in their legges, it is thought that they proceede
of the water they drink"73. Van Linschoten also noted that the place was so hot
that the inhabitants slept at night immersed except for their heads in troughs of
water and "Thus it comes about that they are infected by worms, which grow
in their legs, and are two or three feet long" 73. Thus, not only did Linschote n
recognize an association with water, but he appears to have canvassed the two
ideas which were to become a recurring theme over the next three centurie s
concerning the acquisition of infection - ingestion of worms and penetration of
worms through the skin.
About the middle of the seventeenth century, Monseigneur de la Mott e
Lambert, Bishop of Beirut, undertook a pastoral tour of the Middle East and a
record of his experience was published. He found that in the town of Lau i n
Persia (Iran):
the water....is very bad and the cause of severe and mortal diseases. To this bad
water supply throughout the country between Lau and Gomeron may be attributed
worms of a prodigious length which engender in their thighs and legs 12
In the latter part of the same centu ry, a British traveller to the East Indies stated
in the Philosophical Transactions , concerning the Guinea worm with whic h
he had been afflicted: "These worms are bread by the water, between Gomroom
Dracunculiasis 699
and Schiraz, especially that about Laur" 74.

The resemblance of Guinea worms to the free-living Gordius aquaticus or
"hairworm" inhabiting ponds and rivers led some 18th century writers such as
Meyer to suppose that the entozoon was really the latter worm which ha d
penetrated the cellular tissues 84. Similarly, Linnaeus thought that the Guine a
worm normally lived outside the human body, but when pathogenic, introduced
itself through the skin of the legs 72.
The Englishman James Lind (w ho introduced citrus fruits as a prophylactic
against scurvy at sea) showed much more insi ght into the mode of transmission,
however, when in 1768 he wrote:
and thus supposing the guinea worm to be generated from animalcula or their ova
contained in the waters of the country, their production in the human body may
probably afterwards be prevented by drinking those waters only that have been
rendered perfectly sweet by undergoing a previous putrefaction. 68
Lind achieved this purification by first sealing containers of pond water from
the endemic areas in West Africa until microscopical examination indicate d
that all the animals were dead, and then foll owing this with sieving of the water.
At around the same period, the Frenchman, Gallandat, also favoured th e
theory that infection was acquired by ingestion of water because his observ -
ations led him to believe that those who drank no water in Guinea escape d
infection41. Likewise, the Briton, Colin Chisolm (1795) in Grenada noted with
respect to Guinea worms that "the cause of this singular disease....seems to be
confined to the water of some wells" 19. Chisolm found strange animalcules in
such water and showed that the disease could be prevented by the filling in of
the wells. Similarly, Ferg in Surinam rep orted that an outbreak of Guinea worm
infection had occurred on a plantation in Surinam in 1801 and noted that both
the field-hands and the household slaves, who had nothing in common except
the water supply, became infected 37.
On the other hand, there were several anecdote s which seemed to go against
the theory that infection was acquired from ingestion of contaminated water .
Küchenmeister59 quotes two such instances. While in Curaçao (Netherland s
Antilles), Jacquin, who drank much water remained free from infection ,
whereas his companion who consumed only spirituous liquors was affected .
Similarly, a Dutch general in Angola a te and drank nothing but food and bever-
ages brought with him from Europe yet acquired the worm. Similarly, several
observations by British medical offic ers in India also seemed to militate against
the water ingestion theory. In 1806, Bruce claimed that watercarriers in India
who carried leather bags on their backs suffered from dracunculiasis chiefly in
those same parts 14. This claim was supported by Scott but rejected by a number
of other observers including Smyttan, Morehead and Ewert. In 1816, Heat h
reported that in an outbreak of dracunc uliasis amongst the crew of a ship which
had lain for a long time in the port of Bombay, only the crew became infected
whereas the officers remaine d free of the infection; both groups drank from the
same water supply, but only the officers wore shoes while on shore 47.
Consequently, these events were interpreted as indicating that infection wa s

acquired from water through the skin.
All this remained mere speculation, however, and no significant advances
could be made until the offspring of the Guinea worm were identified. Th e
embryos of D. medinensis, and the fact that female worms were viviparous ,
were discovered and first reported in 1819 by Rudolphi in his major work ,
Entoozorum Synopsis, wherein he wrote: "Filariae nostrae prole quasi farctae
sunt, quod si harum longitudinem illius vero minutiem spectas, foetuum multa
millium milklia singulis tribuit" 121 which may be translated roughly as saying
that if the longitudinal organs of the worm are in fact observed closely, many
thousands of individual embryos may be discerned.
This remark lay buried among so much other data, however, that littl e
notice appears to have taken of the observation and the phenomenon had to be
rediscovered several times before the fact became known widely. The firs t
person to do this was Jacobson in Copenhagen who examined a Guinea worm
removed from a 13-14 year old b oy who had been born on the coast of Guinea;
he recounted his findings in a letter send to M. Blainville in Paris in 1834 55. In
the following year, Duncan in Calcutta, India also found on microscopica l
examination of Guinea worms that the uteru s was packed full of embryos 27. The
presence of embryos was soon verified in that country by Forbes 38 and by
McLelland75. The existence of embryos was then reaffirmed in Europe by the
Parisian surgeon Maisonneuve in 1844. In 1840, Maisonneuve had examined
a 28 year old patient who had spent two and a half years soldiering in Senegal
and had contracted dracunculiasis. During extraction of the worm, a few drops
of white fluid, like whey, escaped and microscopical examination disclose d
myriads of small cylindrical, amazingly active worms with pointed tails 80.
Furthermore, continued observation revealed that they remained alive for one
to two days. Maisonneuve commented that when the time for reproducin g
arrived, the worm makes an ef fort to perforate the skin in order to discharge its
young into the external environment.
As already mentioned, the question which followed naturally from all o f
these observations concerned the manner in which infection was transmitted to
another host. Once Duncan had found embryos in the Dracunculus uterus, he
was stimulated to search the envi ronment. He reported that "the soils and pools
abound in the rains with a worm smaller and more slender, but otherwis e
exceedingly like (Guinea worm)" 27. Likewise, Forbes in Darwar, India als o
looked in water for worms and may well have found larvae liberated by female
worms for he wrote:
I examined several of the tanks in the neighbourhood and found the mud on their
banks and in their half dry beds abundantly supplied with animalcules, some of them
resembling very much those produced by the guinea worm when infecting the
human limb....Two kind of these animalcules may be detected in the soft mud: one
kind seven to eight times the size of the guinea worm animalcules, the other exactly
resembling it.38
In the same vein, Brett (1840) claimed to have found Dracunculus in the
Dracunculiasis 701
flood-plains on the banks of the river near Dhun in India 13.

It seemed likely, therefore, that the released embryos were carried through
the medium of water, in which case t wo modes of entry seemed possible; either
the worms could be ingested in contaminated water or the larvae coul d
penetrate the skin when humans waded in infected water. The first person t o
investigate these possibilities experimentally appears to have been Forbes in
India in 1838. He obtained fr esh larvae from the leg of a sepoy (Indian soldier)
then gave them to two pups. On examination of the dogs, one 4 hours and the
other 24 hours later, he foun d the worms dead in the mucus of the stomach and
duodenum38. This seemed to oppose the ingestion theory and gave credence to
the idea that infection was acquired by worms penetrating the skin.
In 1855, Carter in Bombay, India published some epidemiological observ-
ations which he also interpreted as supporting this latter concept. Over th e
period of a year, 21 out of 50 boys in the School of Industry in Bombay ha d
been infected with Guinea worm, although none who had been admitted to the
school within the last year had b een so afflicted. The boys lived in an enclosure
bounded on three sides by the sea and on the fourth side by a cliff. Within the
enclosure were two wells, one three feet and the other six feet in depth; th e
former was used for providing drinking water and the latter for bathing. I n
addition to the boys, the wife of the sergeant who superintended the school was
also infected; she bathed in the well but obtained her drinking water fro m
elsewhere. Carter examined these tanks and found minute worms closel y
resembling the young of guinea worms. In ano ther school, where dracunculiasis
was absent, he could not find these "tankworms" and concluded that infection
was acquired by bathing in, not by th e drinking of, water which contained these
"tankworms" 17.
The idea of skin penetration gained ground, and despite the fact that nothing
had been proven, an anonymous writer in The Lancet of 1867 asserted
dogmatically:
The most contradictory opinions have been expressed by correspondents in the daily
journals on the subject of guinea-worm disease. The real facts of the case are simply
these. In certain tropical parts, minute worms abound in stagnant pools and swampy
ground. These have the power of penetrating the skin, in virtue of their "boring"
properties, and subsequently grow to a large size, causing, after a few months, local
irritation and the formation of a quasi-abscess, which is a provision of nature to aid
expulsion of the worm. The lower limb is the part most usually attacked, and the
worm makes its way thither via the feet of natives, and simply because they are
commonly unprotected and in contact with the bare ground. But Europeans would
be equally liable to guinea-worm disease did they go about with bare feet. 4
Several years later, however, all this was to change with the epocha l
discovery of Fedchenko.

OF THE CRUSTACEAN INTERMEDIATE HOST
In the three years between 1868 and 1871, The Russian naturalist, Alekse j
Fedchenko, and his wife lived in Turkestan , Samarkand and Tashkent in central
Asia. It was during this period that he made his original observations on D.
medinensis. Fedchenko made arrangements in 1869 with one of the loca l
doctors to provide him with Guinea worms extracted recently from infecte d
persons. His first attempt to study the fate of the embryos failed when he killed
them by adding fresh well water which was rather cold and was rich in lim e
salts. He then told how:
an incident helped me in my research....On the 5th of July, in the small bottle in
which (the doctor) had brought a guinea worm, I noticed a pair of small water
crayfish - the Cyclops. Placing them under the microscope, I saw in each one several
familiar looking embryos of the guinea worm.36
In order to convince himself that the embryos of the Guinea worm reall y
entered the Cyclops, he performed an experiment. He punctured a Dracunculus
and placed the embryos in a watch glass. He then added water and Cyclops
which he had assured himself were free of any larvae. Although he did no t
succeed in determining whether the embryos were ingested or whether the y
penetrated the cuticle of the Cyclops, he discovered that "after several hours a
significant number of embryos appeared in most of them, especially in males
and particularly in young specimens" 36. Fedchenko found that there wer e
usually five or six larvae lodged in the body cavity of each minute crustacean.
He watched the evolution in the appearance of the worms over the succeeding
weeks. During the first few days, the gut became more developed, then afte r
two weeks the larva moulted and lost it s tail. By three weeks, the differentiation
of the internal organs had become more pronounced with the rudiments of the
reproductive organs appearing. Finally, Fedchenko provided an illustration of
a larva after a sojourn of one month in the crustacean. He presented his findings
to a meeting of the Imperial Society of Friends of Natural Sciences ,
Anthropology and Ethnography in Moscow on 21 January 1870, his pape r
being published later that year in the Proceedings of the Society 36
Fedchenko wrote that at the beginning of his studies he had placed Drac-
unculus larvae in a small aquarium containing different water animals in th e
hope that Guinea worm, like so many other parasites, would live first in some
such animal then pass on to man. He made no mention in his paper, however,
that he had been advised by others to follow any particular line of enquiry .
Indeed, by recounting the incident of 5 July, he implies that his initia l
observation with Cyclops was serendipitous. This does not seem to be a n
accurate portrayal of the preceding events, however, for Leuckart 67 remarked
that he had met Fedchenko in 1868 and had advised him to look for th e
development of D. medinensis in Cyclops because of the similarity between its
Dracunculiasis 703
embryo and that of Cucullanus elegans, a parasite of perch, the life cycle o f
which Leuckart had already work out and publis hed in 1865. Cobbold, who had
met Fedchenko when the latter visited London in 1873 later wrote:
It is only fair to add that the Russian traveller was led up to his discovery by the
previous investigations of Leuckart concerning the young of Cucullanus. The
Leipsig helminthologist had, indeed, specially instructed Fedschenko as to the
probable source of Dracunculus. It is often thus that science makes its clear
advances, since a master-mind is needed to set others on the right track. 21
A more important, but undoubtedly erroneous, criticism of Fedchenko' s
contribution was expressed by Manson-Bahr in his textbook in 1966 when he
wrote:
Fedchenko (1869) is credited with the discovery of the transmission of the guinea
worm, but probably Manson was the original observer (1895). Leiper believes that
the stages figured by the former are those of Cucullanus (a parasite of fish), not of
D. medinensis.83
In fact, Leiper had been much more circumspect than this. He had merel y
observed that Fedchenko's paper, published in Russian in 1870, was ver y
inaccessible and that two of the illustrations of purported Dracunculus given
in Leuckart's textbook 67 were undoubtedly based upon a specimen of a
Cucullanus larva66. Manson-Bahr's statement brought forth a response fro m
Hughes in defence of Fedchenko. He arranged for Fedchenko's paper to b e
translated and summarized it by saying that w hatever the defects in Fedchenko's
drawings, his written account was convincing enough 52. Final confirmation of
the validity of Fedchenko's discovery was provided shortly thereafter whe n
Muller published a reproduc tion of Fedchenko's original drawings and showed
that it undoubtedly represented a D. medinensis third stage larva 92.
Although Fedchenko discovered that D. medinensis larvae grew and
moulted in the crustacean, Cyclops, he was unable to complete the cycle o f
transmission. He posed a rhetorical question, then went on to postulate, with
accurate foresight, the subsequent course of events:
What then happens to the embryos at a later stage? It seems to me that, taking into
consideration the known facts concerning the development of other roundworms,
one can state the following: Cyclops, with the embryo, enter the stomach of man
through drinking water; here, under new conditions, further development occurs
pertaining primarily to the genitals. The differentiation of males and females occurs,
and copulation takes place. Thereafter, the males die; however, the females, to
develop their offspring, take off by unknown means, toward the skin where they
place themselves subcutaneously.36
In support of this hypothesis, Fedechenko drew attention to a multiplicity
of diverse observations: all specimens studied so far were female; Pruner i n
Egypt had discovered a worm in the liver; the head of the worm pointe d
towards the skin; the fact that in Asia the infection occurred only where th e
inhabitants were forced to drink stagnant water and that these people, i n
contrast to the Hindus of India, did not go barefoot and rarely bathed but, i n
accordance with Muslim custom, washed their face and hands five times each
day with their hands. He concluded by saying that:

Now, experimentation is needed - similar to the feeding experiments conducted in
studying tapeworm or other parasitic worms - to prove whether the Cyclops, with
the embryo of Filaria, swallowed by a human being, is the cause of guinea-worm
disease.36
According to Cobbold 21, Fedchenko himself did later undertake some desultory
experiments in this regard but without success. He fed infected crustaceans to
dogs and cats, but failed to rear dracunculi in these animals. This did not put
Cobbold off for he remarked:
Clearly, these carnivora were unsuitable hosts. Could Fedchenko have experimented
on man the results would probably have been very different. Arguing from what
happens in the case of Cucullanus amongst fishes, and Trichina in man, there can
be little doubt that all further and final changes undergone by the larvae are
accomplished within the human host.21
Rather surprisingly, more than 20 years were to pass before anyon e
repeated Fedchenko's important experiments. In 1894, Patrick Manson had a
patient with Guinea worm infection in the Seaman's Hospital in London. H e
collected a supply of embryos from this patient and mixed them with a number
of Cyclops procured from neighbouring ponds. Twelve hours or so later, h e
found that nearly every one of the copepods had 10-20 larvae coiled an d
wriggling within the body cavity. He believed that infection had taken place by
penetration of the joints in the integument. Over the ensuing weeks he watched
the slow metamorphosis of the worms. He repeated the experiment in th e
following year and found that, in contrast to Fedchenko's belief, the enclosed
larvae moulted not once but twice 81.
In 1905, Leiper studied dracunculiasis on the Gold Coast (Ghana) of West
Africa and performed a new series of experiments in which Cyclops was
infected. He thought it probable that the crustaceans were infected via their oral
cavity; this view was later to be proven correct by Turkhud 129 and by
Roubaud119. Furthermore, Leiper found that once metamorphosis was complete,
the larvae lay quiescently within the crustacean for several weeks. Whe n
hydrochloric acid was added to simulate t he acidity of gastric juice, the Cyclops
were killed but the Dracunculus larvae regained their former activity an d
escaped from the disintegrating intermediate hosts. He interpreted thes e
observations as indicating that once the worms were set free in the stomach of
the human host, they were able to proceed with further development within the
human body 60.
The species of Cyclops which Fedchenko in the USSR and Leiper in West
Africa used are uncertain. That used by Manson in England was probabl y
C. quadricornis. Other species, including C. leuckarti 119, C. hyalinus 87 , C.
nigerianus 96 and C. vernalis 125 as well as other carnivorous species of Cyclops
were later shown to be infected.
While still in West Africa, Leiper turned his attention to attempting t o
complete the life cycle of the parasite. In 1898, Plehn in the German Camer-
Dracunculiasis 705
oons (Cameroon) had claimed to have found a female worm, indistinguishable

from the Medina worm, in a monkey eight months after feeding it banana s
containing first-stage larvae 102. In the light of hindsight, however, it must b e
concluded that the relationship between these two events cannot be causal. In
order to prove whether or not an intermediate host was necessary, Leipe r
induced a monkey to swallow thousands of newly-liberated embryos, but n o
sign of infection could be found at a utopsy six months later. He must have been
convinced absolutely that a vector was required for he applied living embryos
to the dorsum of his own hand; no erythema or itching occurred and no patent
infection developed subsequently 62. He then fed a monkey on bananas wit h
Cyclops that had been infected with D. medinensis for five weeks. Six months
later, he and Dr. Daniels made a careful post-mortem examination and found
five worms which possessed all the characteristics of D. medinensis. Three
were immature females about 30 cm long, and the other two were small male
worms 22 mm in length 61,62. He concluded that:
these results point strongly to the truth of the theory that infection of man takes
place from the drinking of water containing infected cyclops....The finding of both
male and female forms in the connective tissues relieves us of the more improbable
alternatives previously open to us....The view that larvae at once make their way
through the gut wall and become sexually differentiated later in the tissues of their
host, brings the after-development of the parasite much more into line with that of
other filariae62
In discussing the great frequency of infection in the lower limbs of humans ,
Leiper noted that in his experimental monkey, the female worms had made their
way into the limbs, being found in the forearm, axilla and popliteal space. He
remarked that "geotropism" seemed to him to provide the most likel y
explanation for the distribution of the parasite.
Several years later, Turkhud in the Bombay Bacteriological Laboratory in
India attempted to repeat this experiment. Numbers of monkeys were infected
orally with living first-stage larvae or with infected Cyclops, while others were
given embryos by subcutaneous injection. Post-mortem examinations wer e
made up to one and a half years later, but no dracunculi were ever found 130,131.
Consequently, five "volunteers" ingested five infected Cyclops containing a
total of 6-8 D. medinensis larvae on 5 April 1913. On 18 March 1914 (38 4
days later), one of the volunteers, a laboratory assistant who had remained well
during the interval, developed a small blister on his right foot together wit h
fever, vomiting and diarrhoea. On the 30th of that month, the blister was found
to contain D. medinensis embryos. None of the other four subjects developed
patent infections131. Turkhud may well have completed the life cycl e
experimentally, but this report must be viewed with some circumspection as the
area was endemic for dracunculiasis and the infection could have been acquired
naturally.
Several other unsuccessful attempts were made to repeat Leiper's exper -
iment with monkeys 32,119 until Brug in the Dutch East Indies in 1930 recovered
a full-grown female worm from the calf of a gibbon 15. Four years later, Issajev
in the Soviet Union reported that in a series of experiments between 1927 and
1932, he had infected 42 dogs orally and obtained female worms from 27 o f
them54. In 1936, Moorthy and Sweet confirmed this result by indicating tha t
they had produced patent infections in a number of dogs. Furthermore, the y
recovered a large number of male and female worms 88,90. It was this latter
experiment which finally provided a definitive description of the male worm,
thus completing all the major links in the life-history of D. medinensis.
It remained to define the route of migration of worms within the body of the
definitive host. Onabamiro (1956) could find no trace of worms in dogs until
43 days of infection, when he found them par ticularly in the axillae and inguinal
regions, thus suggesting that they may have migrated there via the lymphati c
system97. Muller then investigated the early route of infection in dogs, cats and
monkeys; he found larvae in the duodenal wall 13 hours after infection, in the
abdominal mesentery for up to twelve days, then in the thoracic and abdominal
muscles at two weeks. He thought it likely that a moult took place and th e
worms migrated to the axillary and inguinal subcutaneous tissues. The mal e
worms died between three and five months after infection and became encysted
while the female worms began moving down the extremities between the eighth
and tenth months 93,94
DETERMINATION OF THE INCUBATION PERIOD
The time required for development of worms in these experimental infections

was consistent with the period thought to be necessary for the development of
patent infections in humans. It had long been known that a number of months
were required for clinical expression of the infection. Kuchenmeister (1855 )
remarked that the infection was asymptomatic for a long time 59 and
Moquin-Tandon (1861) wrote that the incubation period varied between two
months and a year or more 91. In 1880 G Mackay, a retired Deputy Surgeon -
General of the Indian Army, recorded that a regiment of native infantry arrived
at Madras in February 1860 when dracunculiasis was rampant. In Februar y
1861, the first cases of Guinea worm infection amongst the troops wer e
admitted to the regimental hospital; during the following four months, 13 5
cases, being 25% of the strength of the regiment, occurred. Mackay wrote:
Having had many opportunities of observing the origin and progress of this most
troublesome and often formidable parasite, I believe that a period of from eight to
twelve months is necessary for the full development of the worm in the human
system79
Cases which occurred in expatriates aft er leaving endemic areas provided more
certain evidence of the minimum time required. In 1879, Fox reported th e
instance of a young Englishwoman in whom a Gu inea worm had appeared eight
months after leaving India 40. In 1909, Manson recorded the occurrence o f
Dracunculiasis 707
infections in two Englishmen who had been exposed in the Sudan twelve plus
or minus several months previously 82. In the following year, Powell reported an
event in which 16 Indians were exposed during a three day period from 20-22
April 1902. The first worm appeared in the first patient on 3 April 1903 (h e
discharged eight more over the next three months). Six more of the party were
similarly afflicted between 1 May and 20 May 1903, giving incubation periods
ranging between 345 and 437 days104. A somewhat shorter pre-patent period
was reported by Wurtz and Sorel. In March 1911, they paid a visit of thre e
hours to a village in the Ivory Coast where they noticed many cases of drac -
unculiasis; 260 days later, two of their se rvants were found to be infected 134. All
these observations left little doubt that a period of approximately one year was
required between acquisition of infection and the presentation of the adul t
female worm.
The clinical manifestations of dracunculiasis have been apparent for all to see
since time immemorial. At the beginning of the second millenium AD ,
Avicenna succinctly described the condition:
The signs of this condition are as follows. A pustule first appears and swells up, but
afterwards contracts down again to a mere bleb. Soon, however, the bleb perforates
and dark red matter is continuously exuded. In the meanwhile a vermicular move-
ment can be distinguished beneath the skin. For the most part it is the legs that are
involved, but I have seen cases in which the hands and even the sides are affected....
Should the worm be ruptured, much pain and trouble ensue, and even if rupture
does not take place, the condition is tiresome enough. 8
In the late seventeenth century, Lister, an English traveller recounted vividly his
own experiences. He related that he had known some sufferers who had been
bed-bound for up to ten months, and that there were some who had lost their
legs, or even their lives. He recognized that the severity of the disease wa s
increased enormously if the worms were broken during their extraction:
A few days after my arrival....the fruit of my journey showed themselves; for a little
below the instep of my left foot, a worm put out his head....When mine first came
out, for about 40 to 50 days, it came out every day little by little, without putting me
to too much pain, but that I could go up and down till it was come out about a yard
and a quarter; but afterwards, one day stirring too much, I hurt the worm and
enraged him, so that he broke off of himself, and going in, caused my foot and leg
(up to the calf) to swell till the skin was ready to burst, which kept me sleepless and
cast me into a fever. I had a chirurgeon and kept my bed for about 20 days in which
time I had several fits of the said fever.74
One thing above all struck most observers, and that was the remarkabl e
frequency with which the worms presented in the feet. In 1805, McGregor in
India reported that in 87% of h is series of 181 patients the worms were located
in such a situation78, and this observation has more or less held true in al l
subsequent reports. For example, Forbes reported his experiences as a medical

member of the Anglo-French Boundary Commissi on in the Gold Coast (Ghana)
and French West Africa (Ivory Coast) colonies in 1902-1903. Forty percent of
the 400 native carriers were afflicted wi th Guinea worm, the sites of emergence
being the lower limb in 77% (feet in 22%), upp er limb in 9%, scrotum in 4.5%,
abdominal wall in 4%, back or buttocks in 3.5%, face in 1% and penis in 1%.
Nearly half of his patients had multiple infect ions, most of them having between
two and ten worms39. Occasionally, massive numbers of worms are present ;
Trewn reported the instance of a person who ha d 55 worms at one time 128. This,
however, was not the general experience; more typical was the finding b y
Fairley and Liston that the average number of worms per person in their series
of 140 patients was 1.9 33 and the observation of Rao that 2,086 of 3,12 9
patients had only one worm 112.
It has long been realized that most persons were quite unaware of th e
presence of the worm during the prepatent period. In one large recent series,
only one third of patients were a ware that anything was amiss before the blister
appeared, and most of these patients only discerned a palpable worm several
days earlier113. As the time for presentation of the worm approached, there was
not infrequently urticaria, vomiting, fever, abdominal pain and sometime s
dyspnoea, possibly produced by a toxin released by the worm 31,33. One
somewhat racist commentator wrote in 1914:
the patients being for the most part, in Africa at least, people of limited intelligence
this testimony is unreliable. My opinion is that premonitory symptoms are not the
rule; nevertheless they have been not infrequently described and are probably more
common in Europeans.76
More objective investigators, however, have found that such symptom s
occurred in 30-90% of their patients 16,26,33.
In simple cases of Guinea worm infection, it was apparent that worm s
extruded gradually over a period of four to six weeks, then the ulcer heale d
leaving a scar. It was also realized from the earliest times 8 that if the worm
ruptured, then severe inflammation was likely to follow. Secondary bacteria l
infection often supervened; in a series of 218 cases, septic complications were
present in nearly half of the patients 33. Sometimes, the worms failed to surface
and became encysted and calcifie d in the tissues where they remained for many
years23,114,118. Occasionally, the dracunculi were observed to enter a joint ,
especially the knee, where they sometimes liberated larvae into the synovia l
fluid and precipitated a severe arthritis.
Susceptibility to infection and resistance to reinfection is a vexed topic .
Trewn, who had the experience of removing 526 guinea worms during th e
space of three years, noted that some people never became infected eve n
though they used the same water sources as did others who got yearly infect-
ions, thus implying that the former were immune, whether for constitutional or
immunological reasons, whereas the latter had acquired no resistance t o
infection128. This was confirmed by Rao who surveyed some 11,000 villagers
Dracunculiasis 709
in India and found almost 30% infected. Nearly two thirds of these people had
had more than one attack, and 10% of them had had ten or more attacks over
the years112. Similarly, Reddy and colleagues studied 10,000 villagers in th e
South Indian Deccan where infection rates ranged between 11 and 53%. They
found that multiple infections, reinfections, and superinfections were frequent,
thus suggesting that no immunity developed 113.
The diagnosis of Guinea worm infection is usually obvious when the wor m
makes it appearance in the ulcer. If any doubt remains, some fluid exuded by
the worm can be obtained and examined microscopically for the pathog -
nomonic larvae. Patrick Manson in 1895 described the remarkable manner in
which such a collection may be obtained:
Squeeze a little cold water from a sponge so that the stream should fall on the sound
skin within an inch or two of the guinea-worm ulcer; at the same time watch the
little hole....at the centre of the ulcer. In a few seconds a droplet of whitish fluid will
be seen to well up in the little hole, or a delicate tube will be protruded from it for
an inch or more, and then suddenly rupture.81
Manson believed that the worm pro lapsed a portion of its uterus an inch or two
at a time through the mouth then it burst but Leiper denied this, saying that the
uterus protruded through an opening just outside the circumoral ring o f
papillae62.
Diagnosis in the stage before rupture of the blister and presentation of the
head of the worm may be made, as was done by Turkhud in his experimental
infections of a human, by aspiration of fluid from the blister then examining it
for the presence of larvae 131.
Calcified worms may be seen on radiographs as shown by Connor 23 and by
Dimier and Bergonie 25, both in 1918, but localization of living worms i s
unsatisfactory as they are radiolucent. Hudellet (1919) rendered them radio -
opaque by injection of 10% collargol into the worm 51, then Roussel achieved
a similar effect by the injection of lipiodol 120.
As in other systemic helminth infections, eosinophilia is characteristic o f
dracunculiasis, this first being shown by Billet in 1896 11. A variety of
immunological assays have been described, with Ramsay introducing an intra-
dermal test in 1935 110 and a complement fixation test being described i n
1940126.
The time-honoured method of treating dracunculiasis has been by winding the

worm around a stick and pulling it out slowly. Amatus Lusitanius wrote in the
sixteenth century that the Arabian physicians, especially Avicenna an d

Avenzoar, had taught the following method:
First the patient ties the end of the vein or nerve round a small piece of wood, and
this he winds little by little till the last part of the worm is drawn out. As the
structure is often three cubits long [1 cubit = approximately 50 cm], the treatment
may last many days before the sufferer is altogether free of pain and inconvenience.
Many adapt a cataplasm [i.e. a poultice or plaster] or cold suffusion. 9
Van Linschoten soon afterwards in 1596 provided the first known illustration
of this process 73, then nearly a century later Velschius published a number of
illustrations of the same procedure 133.
In a review in 1880 of the treatment of Guinea worm in India, Dick re -
marked that the native experts practised treatment along four lines - stink the
worm out, coax it out, suck it out and pull it out - then summarized his ow n
investigations. Stinking the worm out with assafoetida poultices failed, while
coaxing it out by prolonged immersion in running water was little mor e
successful. He had no experience of sucti on with the traditional trumpet-shaped
sucking tube, but determined t hat many days of slow winding could be avoided
frequently by incising the skin ove r the worm and then pulling it out by traction
in the space of a few minutes 24. In doing this, he merely legitimized the practice
of many native barber-surgeons. In 1884, JW Reynolds, a former Britis h
surgeon in Bombay described how one of them had removed a number o f
worms from his own feet in 1861. (It is certain that he was the host to th e
worms that Bastian used in his description, for Reynolds remarked that he later
gave the worms to Harley, and Bastian in turn stated that he had received his
specimens from an infected Bombay surgeon via Harley).
A barber took five out of my legs very cleverly; most of them were extracted at one
sitting, but two (one in each foot) held on with their hooks, and he had to leave them
until the next day, when he got them out. His stock of instruments consisted of a
needle and a razor; he commenced operations by finding, as near as he could guess,
the centre of the worm; then he raised the skin over the centre of the worm with the
point of the needle, passed the razor under it, and snipped off a tiny bit of cuticle,
making an almost circular cut the size of a large pin's head. By raising almost
invisible pieces of skin and tissue, and slicing them away with the razor, he
deepened, but did not increase, the area of the whole, till he saw the white worm at
the bottom; then passed the eye of the needle (like a tentaculum) under it, and
brought up a loop. He pulled on the two sides alternatively till he got one end out,
then he dealt with the other. When he found the hook had been made use of, he
applied heat and friction to make it yield its hold.116
In 1883, Faulkner, a civil surgeon in Aden, claimed that electrolysis with
a galvanic current was effective 35, to which Reynolds replied that galvanis m
had been in use for at least 25 years 116.
Most practitioners hoped that drugs would aid in the extraction of Guinea
worms. Around 1895, the injection of mercuric perchloride was recommended,
but this did not find lasting favour. A rather drastic method was tried in India
in 1903; a number of Indian soldiers infected with Guinea worm each con -
sumed more than a pound of sugar a day for three days. The sugar made th e
Dracunculiasis 711
patient unbearably thirsty, but the dehydration made it easy to wind out th e
worm unruptured 117. In 1919, Jeanselme gave three intravenous injections of
novarsenobenzol to a young Senegalese soldier then a few days later a dea d
worm was extracted. He was uncertain whether the arsenic had a direct action
on the worm, however, as no trace of the metal could be found in the worm 56;
arsenicals did not prove subsequently to be effective. Macfie (1920) though t
that intravenous injections of tartar emetic (sodium antimony tartrate) recently
introduced for the therapy of schistosomiasis had a beneficial effect 77, but
Fairley and Liston later showed that the drugs had no action on either the adult
worm or the embryos contained therein 34. In 1942, Elliot claimed that injections
of phenothiazine (which had recently been recommended for the treatment of
enterobiasis) each week for four weeks assisted in the removal of worms 30, but
this therapy did not become generally accepted either.
No significant advances were made until Raffier in 1965 showed that oral
niridazole cured 70% of 71 patients on the Ivory Coast within seven days 106,107.
Two years later, he also showed that thiabendazole was useful in the treatment
of 234 patients in the same country 108. In 1970, Pardanani and Kothari found
that metronidazole appeared useful 100. Muller then investigated the actions of
these drugs and found that the worms appeared normal on histologica l
examination and that the larvae developed normally in Cyclops. He concluded,
therefore, that their effective ness was due to an anti-inflammatory action which
facilitated the mechanical removal of the worms 95. More recently, Shafei
showed that mebendazole was effective in dracunculiasis, but that its actio n
differed from the other drugs because it killed the worm 123.
Many of the epidemiological observations o ver the past several centuries which
led to the formulation of various theories on the mode of transmission o f
dracunculiasis have been discussed. These occurrences became comprehens-
ible with the demonstration that Guinea worm infection was transmitte d
through the agency of a water crustacean. Although species of Dracunculus
closely related to D. medinensis have been described in various animals ,
humans seem to be the only important host of this worm.
Dracunculiasis is now restricted to parts of Africa, the Middle East and the
Indian subcontinent. In former times, however, it was prevalent in the Wes t
Indies and parts of South America. Hirsch (1885) wrote concerning thes e
countries:
All the authorities....agree that dracontiasis was quite unknown before the
importation of the negro. With the suppression of the slave trade, the disease fell to
a minimum or disappeared altogether.48
The first person to draw attention to the infection in the Western Hemisphere
appears to have been Don Diego Rodriguez de Valdes y de la Vanda, Spanish
governor of Rio de la Plata in 1599 (Argentina/Uruguay) 98. In some regions, it

seems that transmission occurred for a number of years as evidenced, fo r
example, by the description by Ferg of an epidemic in Surinam in 1801 37. For
uncertain reasons, the infection appears to have now died out in these areas. A
similar situation occurred in the Dutch East Indies (Indonesia). Occasiona l
exotic infections were imported into that country and Brug in 1930 from such
a case, succeeded in infecting the local C. leuckarti and then producing an
infection in a monkey. He attributed the free dom of the country from indigenous
infection to the habit of the inhabitants of drinking running rather than stagnant
water15.
In many endemic areas, it has bee n found that the incidence of infection has
a seasonal pattern which some times coincided with the rainy season and some-
times did not, local habits and physical factors determining the distribution of
infection throughout the year. While such events have been recognized fo r
many years, it is only in the last century that the reasons for the phenomenon
have been understood. Thus, in Rajasthan, India, transmission occurred during
the rainy season because water was then obtained from surface ponds rathe r
than from deep wells 70. In contrast, in Iran where water is obtained fro m
cisterns, transmission took place during the dry season because the concen -
tration of Cyclops was reduced by the large volume and turbidity of wate r
during the rainy season 69.
An ideal physical arrangement for the transmission of infection are th e
stepwells so common in India. This was recognized in 1879 by Mr. Chunder
Dutt, an assistant surgeon at a colliery in Chonda in the Central Provinces of
India, who observed 180 cases in one village. Water for drinking and washing
purposes was obtained from the only well in the vicinity of the village. Thi s
well had a flight of stone stairs down which the people descended to fill their
pots with water. All that could be glea ned as to the cause of the outbreak of the
disease was that men from a neighbouring village where dracunculiasis was
rife the year before, used to go down into the well for drawing water whils t
suffering from mature Guinea worms in their feet and legs. In the curren t
outbreak, he found that the field-labourers, to whom the infection was largely
limited, had the habit of drinking from the well on their returning from th e
fields, descending one or two steps into the water to dip their hands o r
water-vessels therein28. Despite the clarity of his observations, the precis e
mechanism by which infection occurred was not apparent to him, however, pre-
sumably because he had no access to recent literature reporting Fedchenko' s
discovery. The importance of these wells was repeatedly recognized. Fo r
example, Rao reported in in 1942 that he had examined 434 wells and found
that 158, most of them step wells, contained Cyclops 112.
When epidemics of dracunculiasis occurred, the infection sometimes had
significant economic effects. Atten tion was drawn repeatedly to this by medical
officers in charge of troops so afflicted in colonies in endemic areas. Mor e
important, however, were the e ffects on rural villages where a large proportion
Dracunculiasis 713
of the work-force were incapacitated temporarily, thus having a deleteriou s

action on agricultural production.
Effective methods of avoiding Guinea worm infection were suggested by some

observers even when the modes of transmission were understood only dimly.
De Bourges (1666), in his narrative of the Bishop of Beirut's journey wrote :
"the way to avoid this worm is to drink only wine or if water is used, only such
as has been carefully filtered through linen" 12. Similarly, the method o f
purifying water adopted by Lind (1768) 68 has already been referred to, as has
the discovery by Chisolm (1795) 19 that the disease could be prevented by filling
in of the wells (although this seems a drastic and impractical suggestion).
The elucidation of the central role of Cyclops in transmission provided solid
ground for the evolution of control techniques. Leiper summarized the problem
by remarking: "the isolation of infective man from healthy cyclops and o f
infected cyclops from man must be the object of any organized effort to stamp
out dracontiasis" 62. These efforts encompassed physical, biological an d
chemical approaches.
Concerning physical measure s, WM Graham, a medical officer in the West
African Medical Service, wrote in 1905 that Cyclops can be removed readily
by straining water through a fine handkerchief. Since he did not believe that this
was a practical proposition for the indigenous inhabitants, he advocate d
structural alterations to existing wells to convert them into concrete trough s
with conduction away of outflow water 44. In a similar vein, Leiper (1907 )
prophesied:
it is evident that dracontiasis will disappear from the Coast towns when the
provision of a properly-controlled water supply, obtained either from artesian wells
or through pipes from some rapidly-flowing stream, permits the filling-in of the
surface collections of rain water and the shallow wells upon which the natives now
rely for their supplies.62
The efficacy of such measures was shown in many areas. In a part of India, for
example, replacement of step wells by draw wells in a number of village s
reduced greatly the incidence of infection 111. Another physical metho d
suggested by Leiper was the heating of well water with steam, but this did not
prove a viable technique 63
In 1912, Leiper returned to West Africa and found that in certain place s
Cyclops appeared to be kept under control by the innumerable small fish living
in the water sources, with a consequent absence of dracunculiasis 64. This
concept was investigated in detai l by Moorthy and Sweet in India in 1936; they
found that fish of the genus Barbus were a potent destroyer of Cyclops 89
A third approach has been to try chemical treatment of water. A number of
chemicals have been suggested including potassium permanganate (1914) 131,
lime (1930) 105, DDT (1953)109 , zinc dimethyldithiocarbamate (1956) 45 and

chlorination (1968) 122. Such measures have had on occasion some success in
certain limited areas.
Currently, the best hope for controlling dracunculiasis lies in the Inter -
national Drinking Water Supply and Sanitation Decade due to end in December
1990. Since there is no significant animal reservoir of infection, successfu l
implementation of safe water su pplies could theoretically lead to elimination of
Guinea worm infection within several years, much as in the same way as has
been achieved with smallpox 50. Whether or not these hopes are realized ,
however, only time will tell.
REFERENCES
1. AGATHARCHIDES. De mari rubra. Cited in 103

2. AMATUS LUSITANIUS. Medici physici praestantissimi: curationum medicinaliu m
centuria quatuor etc., B Constantinus, Venetiis, pp 645, 1557. Partly translated in 124
3. ANDRY de BOISREGARD N. De la génération des vers dans le corps de l'homme etc.,
Laurent d'Houry, Paris, pp 1190, 1741. Partly translated in 49
4. ANONYMOUS. The Guinea-worm disease. Lancet ii: 314, 1867
5. ANONYMOUS. The Guinea-worm. British Medical Journal i: 488, 1880
6. ANONYMOUS. Book review of "The diseases of the Bible" by Sir Risdon Bennett .
7. ANONYMOUS. Supposed discovery of the male of Filaria medinensis . British Medical
8. AVICENNA. Libri in re medica omnes, qui hacte nus ad nos pervenere. Id est, libri canonis
quinque, De viribus cordis, De removendis nocumentis in regimine sanitas, De sirup o
acetosa et cautica, translated by JP Mongio Hydruntino et J Costaeo Laudensi, V
Valgrisius, Venetiis, pp 966, 1564. Original Arabic version "Al Canon fi Al Tib", c. 1000
AD. Partly translated in 124
9. AVICENNA. Ibidem. Cited in 2
10. BASTIAN HC. On the structure and nature of the Dracunculus of Guinea worm.
Transactions of the Linnean Society 24: 101-134, 1863
11. BILLET A. Eosinophilie dans un cas de filariose sous cutanée de Médine. Compte s
Rendus Hebdomadaires et Mémoires des Séances de la Société de Biologie 9: 18, 1896
12. de BOURGES J. Relation du voyage de Mgr. l'Evéque de Beryte, vicaire apostolique du
Royaume de la Cochinchine, par la Turquie, la Perse, les Indes etc., jusqu'au Royaume
de Siam et autres lieux, D Bechet, Paris, pp 245, 1666
13. BRETT FH. A practical essay on some of the principle surgical diseases of India, W
Thacker and Co., Calcutta, pp 506, 1840
14. BRUCE N. Remarks on the dracunculus, or Guinea worm, as it appears in the peninsular
of India. Edinburgh Medical and Surgical Journal 2: 145-150, 1806
15. BRUG SL. Dracunculus medinensis in the Dutch East Indies. Mededeelingen van de n
16. CARAYON A, CAMAIN R, GUIRAUD R, HAURET P. Aspects chirurgicaux de s
helminthiasies en Afrique de l'ouest (ascaridiose, dracunculose, filariose, bilharziose). II.
Pathologie de migrations habituelles aberrantes ou manquées de la filaire de Médine (À
propos de 25 localisations chirurgicales). Médecine Tropicale 21: 538-549, 1961
17. CARTER HJ. Note on dracunculus in the island of Bombay. Transactions of the Medical
and Physical Society of Bombay, new series, 2: 45-56, 1855
18. CHARLES RH. A contribution on the lif e-history of the male Filaria medinensis removed
Dracunculiasis 715
from the abdominal cavity of man. Scientific memoirs by medical officers of the Army of
India 7: 51-56, 1892. Abstracted in British Medical Journal ii: 1151, 1892
19. CHISOLM C. An essay on the malignant pestilential Fever introduced into the Wes t
Indian Islands from Boullam, on the coast of Guinea as it first appeared in 1793, 1794,
1795 and 1796, second edition, two volumes, pp 105, 1801. Also, On the Mali s
Dracunculus or Guinea-worm (in Grenada). Edinburgh Medical and Surgical Journal 11:
145-164, 1815
20. COBBOLD TS. Entozoa: an introduction to the study of helminthology with reference,
more particularly, to the internal parasites of man, Groombridge and Sons, London, p p
480, 1864
22. COLE J. Buried treasure. British Medical Journal ii: 1412-1413, 1979
23. CONNOR FP. Notes on cases of surgical interest. I. Inflammatory conditions due t o
calcified remains of Guinea-worms. Indian Medical Gazette 53: 297-299, 1918
24. DICK F. The treatment of Guinea-worm. British Medical Journal ii: 207-208, 1880
25. DIMIER, BERGONIE J. Recherche du filaire de Médine par la radiographie. Archives
d'Électricité Médicale et de Physiotherapie 26: 337-341, 1918
26. DUKE J. Note on the symptoms of Filaria medinensis or Guinea worm. Indian Medical
Gazette 30: 64-65, 1895
27. DUNCAN A. Observations on Dracunculus. Transactions of the Medical and Physica l
Society of Calcutta 7: 273-281, 1835
28. DUTT C. Cited in British Medical Journal i: 488-489, 1880
29. EBBELL B. The Papyrus Ebers, the greatest Egyptian medical document, translated by
B Ebbell, Levin and Munksgaard, Copenhagen, pp 135, 1937
30. ELLIOT M. A new treatment for dracunculiasis. Transactions of the Royal Society o f
31. FAIRLEY NH, LISTON WG. Studies in the pathology of dracontiasis. Part I. India n
32. FAIRLEY NH, LISTON WG. Studies in the transmission of Dracunculus medinensis -
a negative experiment. Part II. Indian Journal of Medical Research 12: 93-104, 1924
33. FAIRLEY NH, LISTON WG. Studies in dracontiasis. Part IV. The clinical picture. An
analysis of 140 cases. Indian Medical Gazette 12: 351-367, 1924
34. FAIRLEY NH, LISTON WG. Studies in dracontiasis. Part V. Observations an d
reflections on intravenous medication with special reference to tartar emetic. India n
Medical Gazette 12: 369-374, 1924
35. FAULKNER AS. Electrolysis in the treatment of Dracunculus. British Medical Journal
ii: 1280-1281, 1883
36. FEDCHENKO AP. (Concerning the structure and reproduction of the Guinea wor m
[Filaria medinensis L.].) Izvestiia Imperatorskago Obshchestva Liubitelei Estestvoznaniia
Antropologii i Ethnografii - Mo skva, 8 columns 71-81, 1870. In Russian. Translated in 58
37. FERG. Jahrbuch der deutschen Medicin p 151, ?1801. Cited in 48
38. FORBES D. Extracts from the half yearly reports of the diseases prevailing at Dharwar
in the 1st grenadier regiment, N.I. for the year 1836. Transactions of the Medical an d
Physical Society of Bombay 1: 215-225, 1838
39. FORBES JG. Medical report of the Anglo-French Boundary Commission on the western
frontier of the Gold Coast Colony, Janu ary 1902-May 1903. Saint Bartholomew's Hospital
Reports, London 39: 171-187, 189-205, (1903) 1904
40. FOX T. Notes on unusual or rare forms of skin disease. I. Case of Guinea-worm disease.
Lancet i: 330-331, 1879
41. GALLANDAT DH. Lettre sur le dragonneau, ou veine de Médine et sur l'usage d u
sublime corrosif dans cette maladie. Journal de Médecine, Chirurgie, Pharmacie etc. 12:
24-28, 1760
42. GALLANDAT DH. Dissertio de dracunculo sive vena medinensis. Nova Act a
Physico-Medica Academiae Caesareae Leopoldino-Carolino Naturae Curiosorum ,

Norimb. 5: 103-116, 1773. (Manuscript dated 1771)
43. GMELIN JF. Systema naturae per regna tria naturae secundum classes, ordines, genera,
species cum characteribus, differentiis, synonymis, locis, 13th edition, G E Beer, Lipsiae,
eight volumes, pp 3021-3909, 1788-1793
44. GRAHAM WM. Guinea-worm and its hosts. British Medical Journal ii: 1263-1265, 1905
45. GRETILLAT S. Le dimethyldithiocarbamate de zinc dans la prophylaxie de l a
dracunculose. Médecine d'Afrique Noire, Dakar 12: 93-96, 1965
46. GRUNDLER. Cited in 20
47. HEATH GT. Observations on the generation of Guinea worm. Edinburgh Medical an d
Surgical Journal 12: 120-121, 1816
48. HIRSCH A. Handbook of geographical and historical pathology. volume 2. Chroni c
infective, toxic, parasitic, septic and constitutional diseases, translated from the secon d
German edition by C Creighton, The New Sydenham Society, London, pp 681, 1886
of Malaya Press, pp 526, 1959
50. HOPKINS DR. Guinea wo rm and the decade. World Health, November, pp 22-23, 1984
51. HUDELLET G. Extirpation totale du ver de Guinée après diagnostic de position par les
rayons X. Bulletin de la Société Médico-Chirurgicale Française de l'Ouest-Africain 1 :
17-19, 1919
52. HUGHES MH. A historical note on the transmission of dracontiasis. Transactions of the
Smithsonian Institution Publication 2359, Washington, DC, pp 171-176, 1915
54. ISSAJEV L. (Experimentelle dracunculosis beim Hunde). Meditsinskaya Parazitologiya
i Parazitarn e Bolezni 3: 231-238, 1934. In Russian, with German summary
55. JACOBSON. Extrait d'une lettre à M. Blainville, Naturelles Archives du Museum 3: 80,
1834
56. JEANSELME. Note sur un cas de ver de Guinée radicalement guéri par l e
novarsénobenzol en injections intraveineuses. Bulletin de l'Académie de Médecine, third
series, 81: 156-158, 1919
57. KÄMPFER. Cited in 20
58. KEAN B H, MOTT KE, RUSSELL AJ. Tropical medicine and parasitology. Classi c
group Entozoa, translated by E Lankester, The Sydenham Society, London, pp 452, 1857
60. LEIPER RT. The influence of acid on Guinea worm larvae encysted in Cyclops. British
61. LEIPER RT. Some results of the infection of monkeys with Guinea worm. Report of the
British Association for the Advancement of Science 76: 200, 1906
62. LEIPER RT. The etiology and prophylaxis of dracontiasis. British Medical Journal i :
129-132, 1907
63. LEIPER RT. A method for dealing with town wells infected with Guinea worm. Journal
of the London School of Tropical Medicine 1: 28-30, 1911
64. LEIPER RT. Report of the helminthologist, London School of Tropical Medicine, for the
half-year ending April 30th, 1913. Abstracted in Tropical Diseases Bulletin 2: 195-196,
1913
65. LEIPER RT. Discussion on the validity of certain generic names at present in use i n
medical helminthology. Archiv für Schiffs- und Tropen-Hygiene 30: 484-491, 1926
Dracunculiasis 717
66. LEIPER RT. Landmarks in medical helm inthology. Journal of Helminthology 7: 101-118,
1929
68. LIND J. An essay on diseases incidental to Europeans in hot climates, with the method of
preventing their fatal consequences etc., T Becket and PA de Hondt, London, pp 348 ,
1768
69. LINDBERGH K. Dracunculose en Iran. Archiv für Schiffs- und Tropen-Hygiene 40 :
330-342, 1936
70. LINDBERGH K. Dracunculose dans l'état de Djodhpour (Radjpoutana), Inde. Bulletin de
la Société de Pathologie Exotique 39: 318-328, 1946
71. LINNAEUS C. Systema naturae per regna triae naturae, secundum classes, ordines ,
genera, species, cum characteribus, differentiis, synonymis, locis, tenth edition, L Salvii,
Holmiae, two volumes, pp 823, 1758
72. LINNAEUS C. Cited in 91
73. van LINSCHOTEN JH. Vera descriptio regni par s Indiae Orientalis in qua Johan. Hugonis
Linstscotani navigatio in Orientem. Teucrides Annaeus Lonicer, Frankfort, 1599. Original
Dutch edition, Voyage ofte Schripaert van JHLvL naer Oost ofte Portugaels Indiens etc.,
Amstelredam, 1596. Partly translated in 124
74. LISTER M. Part of a letter from Fort St. George, in the East Indies, giving an account of
the longworm which is troublesome to the inhabitants of those parts. Philosophica l
Transactions of the Royal Society of London 19: 417-418, 1697
75. McCLELLAND. Remarks on Dracunculus. Calcutta Journal of Natural History 1 :
359-371, 1840
76. McCONNELL RE. Dracontiasis or dracunculias is: a review. Journal of Tropical Medicine
and Hygiene 17: 337-340, 1914
77. MacFIE JW. Intravenous injection of tartar emetic in Guinea-worm infections. Lancet i:
654-655, 1920
78. McGREGOR J. A memoir on the state of health of the 88th regiment, and of the corp s
attached to it, from the 1st June 1800 to the 31st May 1801 as originally presented to the
Medical Board, Bombay. Edinburgh Medical and Surgical Journal 1: 266-289, 1805
79. MACKAY G. The Guinea-worm. British Medical Journal i: 610, 1880
80. MAISONNEUVE JG. Note sur un dragonneau observé à Paris, et présenté à la Société
de Chirurgie. Archives Générale de Médecine 6: 472-480, 1844. Abstracted in Lancet i:
153-153, 1845
81. MANSON P. On the Guinea-worm. British Medical Journal ii: 1350-1351, 1895
82. MANSON P. The life-span of Filaria medinensis . British Medical Journal ii: 10, 1903
83. MANSON-BAHR PH. Manson's Tropical diseases, sixteenth edition, Baillière, Tindall
and Cassell, London, pp 1131, 1966
84. MEYER. Cited in 91
85. MILNE J. In, Extracts from a correspondence on the Filaria medinensis among some of
the medical officers of the Honourable East India Company's service at Bombay; with a
letter from Dr. Robert Grant, professor of comparative anatomy in the University o f
London. Edinburgh Medical and Surgical Journal 35: 112-118, 1831
86. MOORTHY VN. A redescription of Dracunculus medinensis . Journal of Parasitology 23:
220-224, 1937
87. MOORTHY VN. Observations on the development of Dracunculus medinensis larvae in
Cyclops. American Journal of Hygiene 27: 437-460, 1938
88. MOORTHY VN, SWEET WC. A note on the experimental infection of dogs wit h
dracontiasis. Indian Medical Gazette 71: 437-442, 1936
89. MOORTHY VN, SWEET WC. A biological method for the control of dracontiasis. Indian
90. MOORTHY VN, SWEET WC. Further notes on the experimental infection of dogs with
dracontiasis. American Journal of Hygiene 27: 301-310, 1938

91. MOQUIN-TANDON A. Elements of medical zoology, translated by R T Hulme ,
Baillière, London, pp 423, 1861
92. MULLER RL. A historical note on the transmission of Dracunculus. Transactions of the
93. MULLER R. Studies on Dracunculus medinensis (Linnaeus). I. The early migratio n
route in experimentally infected dogs. Journal of Helminthology 42: 331-338, 1968
94. MULLER R. Experimental dracontiasis in animals. Parasitology 58: 7p-8p, 1968
95. MULLER R. the possible mode of action of some chemotherapeutic agents in guine a
worm disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 65:
853-854, 1971
96. ONABAMIRO SD. The diurnal migration of Cyclops infected with the larvae o f
Dracunculus medinensis (Linnaeus) with some observations on the development of the
larval worms. West African Medical Journal 3: 189-194, 1954
97. ONABAMIRO SD. The early stages of the development of Dracunculus medinensi s
(Linnaeus) in the mammalian host. Annals of Tropical Medicine and Parasitology 50 :
157-166, 1956
98. OTTSEN H. Journaal van de Reis naar Zuid-America (1598-1601). (Journaal van d e
voyagie na Rio de Plata), 'S-Gravenhage, pp 253, 1918
99. PAPYROS EBERS. Das hermetische Buch über die Arzneimittel der alten Aegypter in
hieratischer Schriften Herausgegeben mit Inhaltsangabe und Einleitung versehen vo n
Georg Ebers, two volumes, Leipzig, 1875. The Papyrus Ebers, translated from th e
German version by CP Bryan, Geoffrey Bles, London, pp 167, 1930
100. PARDANANI DS, KOTHARI ML. Metronidazole in dracunculiasis. A preliminar y
report of a therapeutic trial. Indian Journal of Medical Science 24: 359-360, 1970
101. PARÉ A. Cited in 3
102. PLEHN F. Die Kamerun-Kuste. Studien zur Klimatologie, Physiologie und Pathologie
in der Tropen, August Hirschwald, Berlin, pp 363, 1898
103. PLUTARCH. Oeuvres de Plutarque, traduites du Grec par J Amyot, Paris, 22 volumes,
1783-1787. Partly translated in 91
104. POWELL A. The life span of the Guinea-worm. British Medical Journal i: 73, 1904
105. PRADHAN YM. Observations on experiments designed to combat dracontiasis in a n
endemic area by Col. Morison's method of "liming" wells. Indian Journal of Medica l
Research 18: 443-465, 1930
106. RAFFIER G. Note préliminaire sur l'activité du CIBA 32644-Ba dans la dracunculose.
Acta Tropica 22: 350, 1965
107. RAFFIER G. Preliminary note on the activity of a new antihelminthic agent i n
dracunculosis. Médecine Tropicale 26: 39-46, 1966
108. RAFFIER G. Activité du thiabendazole dans la dracunculose. Médecine Tropicale 27:
673-678, 1967
109. RAMAKRISHNAN NR, RATHNASWAMY GK. Use of DDT for control of Cyclops
breeding and as an anti-dracontiasis measure. Indian Medical Gazette 88: 386-390, 1953
110. RAMSAY GW. Observations o n an intradermal test for dracontiasis. Transactions of the
111. RAO CK REDDY GV. Dracontiasis in West Godavari and Kurnool districts, Andhr a
Pradesh. Bulletin of the Indian Society of Malariology and Communicable Diseases 2:
275-293, 1965
112. RAO SR. Some epidemiological factors of Guinea-worm disease as noticed in a recent
survey of Osmanabad district. Journal of the Indian Medical Association 11: 329-337,
1942
113. REDDY CC, NARASAIAH IL, PARVATHI G. Epidemiological studies o n
guinea-worm infection. Bulletin of the World Health Organization 40: 521-529, 1969
114. REDDY CC, SIVAPRASAD MD, PARVA THI G, CHARI PS. Calcified guinea worm:
clinical, radiological and pathological study. Annals of Tropical Medicine an d
Dracunculiasis 719

115. REICHARD CW. Dissertatio de pediculus inguinalibus insectis et vermibus homin i
molestis, Erfuti, pp 51, 1759
116. REYNOLDS JW. Electrolysis in the t reatment of dracunculiasis. British Medical Journal
i: 138, 1884
117. RICHARDS WG. Note on Dracunculus medinensis (Guinea worm). Parasitology 14:
307-308, 1922
118. ROLLESTON HD. Guinea-worm embedded for 21 years under the skin of the calf of
the leg. Transactions of the Pathological Society of London 43: 152, 1892
119. ROUBAUD E. Observations sur la biologie du ver de Guinée: infection intestinale des
Cyclops. Bulletins de la Société de Pathologie Exotique et de ses Filiales 6: 281-288 ,
1913
120. ROUSSEL B. Radiographie du ver de Guinée (filaire de Médine) après injectio n
intrasomatique de lipiodol. Bulletins de la Société de Pathologie Exotique et de se s
Filiales 21: 103-104, 1928
121. RUDOLPHI CA. Entozoorum synopsis cui accedunt mantissima duplex et indice s
locupletissima, Sumtibus August Rücker, Berolini, pp 811, 1819
122. SABOKBAR R. Dracunculose en Iran. VIIIth International Congress of Tropica l
Medicine and Malaria, Tehran, pp 938-939, 1968
123. SHAFEI AZ. Preliminary report on the therapeutic effect of mebendazole in guine a
worm infection. Journal of Tropical Medicine and Hygiene 79: 197-200, 1976
124. SINGER C. On certain early referen ces to dracontiasis, the guinea-worm disease. Annals
125. SOUTHWELL T, KIRSHNER A. Some observations on guinea worm larvae. Annals
126. STEFANOPOULO GJ, DANIAUD J. Réaction de fixation du complément et intra -
dermo-réaction au course de la fila riose humaine à Dr. medinensis. Bulletin de la Société
de Pathologie Exotique 33: 149-153, 1940
127. TENNENT JE. Sketches of the natural history of Ceylon with narratives and anecdotes
illustrative of the habits and instincts of the Mammalia, birds, reptiles, fishes, insects etc.,
including a monograph of the elephant, and a description of the modes of capturing and
training it, Longmans, London, 1868
128. TREWN HS. Guinea worm. Indian Medical Gazette 72: 606-609, 1937
129. TURKHUD DA. Proceedings of the Second All-India Sanitary Conference, 1912 ,
Government Central Branch Press, Simla, pp 118-120, 1913
130. TURKHUD DA. In, Report of the Bombay Bacte riological Laboratory for the year 1912,
presented by Major WG Liston, Government Central Press, Bombay, pp 32-36, 1913
131. TURKHUD DA. In, Report of the Bombay Bacte riological Laboratory for the year 1913,
presented by Major WG Liston, Government Central Press, Bombay, pp 14-16, 1914 .
Republished as, Prophylaxis of dracontiasis. Indian Journal of Medical Research, special
number, pp 217-225, 1919
132. de VEIGA T. Cited in 3
133 VELSCHIUS GH. Exercitatio de Vena Medinensi, ad mentem Ebnisinae sive d e
dracunculi veterum. Specimens e xhibens novae versionis ex Arabico, cum commentarion
uberiori, cui accedit altera de vermiculus capillaribus infantium, Theophili Goebelli ,
Augustae Vindelicorum, pp 456, 1674
134. WURTZ, SOREL. Note sur la durée de l'incubation du ver de Guinée. Revue d e
Médecine et d'Hygiene Tropicale 9: 123-124, 1912
Table 26.1. Landmarks in dracunculiasis

___________________________________________________________________
BC Guinea worms have been known since antiquity in endemic areas but their nature was
controversial. Mechanical extraction was practised
1819 Rudolphi described the larvae (embryos) of Dracunculus
1834 Jacobson rediscovered the first-stage larvae
1868 Bastian made a detailed description of the anatomy of the adult female worm
1869 Fedchenko observed that embryos developed with the body cavity of the crustacean,
Cyclops
1880 Mackay described an epidemic of dracunculiasis in Indian troops and suggested that the
incubation period was 8-12 months
1892 Charles claimed to find male adult worms in the retroperitoneal tissues at autopsy
1894 Manson confirmed Fedchenko's observations on development withinCyclops
1906 Leiper showed that hydrochloric acid, simulating gastric juice, stimulated the activation
of larvae and their release from Cyclops
1906 Leiper fed infected Cyclops to monkeys and recovered 3 immature female and 2 small
male Guinea worms at autopsy 6 months later
1914 Turkhud administered infected Cyclops to 5 volunteers; one person developed
dracunculiasis one year later
1937 Moorthy provided the first detailed account of the male adult worm
1956 Onabamiro studied the route of migration of parasites in experimentally infected
animals
1965 Raffier showed that niridazole assisted the extraction of worms
1967 Raffier showed that thiabendazole assisted the extraction of worms
1970 Pardanani and Kothari reported that metronidazole assisted the extraction of worms
1976 Shafei claimed that mebendazole kills Guinea worms
___________________________________________________________________
Chapter 27
NEMATODE INFECTIONS OF LESSE R

IMPORTANCE
INFECTION WITH ANATRICHOSOMA CUTANEA
This Capillaria-like parasite of the skin and nasal mucosa of monkeys in Asia
and Africa was discovered by Swift, Boots and Miller in 1922 and name d
Trichosoma cutaneum 327. In 1958, it was renamed Anatrichosoma cutaneum
by Chitwood and Smith 67. A human case of creeping eruption of the skin due
to infection with this worm was reported by Morishita and Tani in Japan i n
1960225.
INFECTION WITH ANCYLOSTOMA SPECIES
A. BRAZILIENSE
This parasite was first recovered from the intestine of dogs and cats b y
Gomes de Faria in Brazil in 1910 who called it Ancylostomum braziliense 130.
With the acceptance of Ancylostoma as the generic name for this group o f
hookworms, it became known as Ancylostoma braziliense . For many years,
there was controversy concerning the relationship between this worm an d
A. ceylanicum, with the eventual acceptance that they were different specie s
(see chapter 20).
Contrary to A. duodenale, A. ceylanicum and Necator americanus,
A. braziliense does not complete its development in humans, but it is the major
cause of the clinical syndrome called cutaneous larva migrans. This syndrome
appears to have been first described by Robert Lee in an address to the Clinical
Society of London in 1874, although the worm involved in that particular case
will never be precisely known:
The morbid appearance consists of a fine line on the left side of the abdomen, which
stretches in a convoluted manner across the side. It appears to consist of a narrow,
reddish, slightly-elevated line, much resembling to the touch what would be
produced by a bristle underneath the epidermis....It was said to have begun as a fine
line on the right ankle, which gradually travelled up the thigh on to the abdomen,
where it was at first in the right side, and during the last three weeks has travelled
across to the left.172
The anonymous reporter in The Lancet who wrote the above also commented
that this was:
721
a remarkable case of Skin Disease in a child, the nature of which had given rise to
much diversity of opinion amongst those who had seen it, and on which there was
not much light thrown by the members of the Society. 13
and concluded that a commission had been appointed to investigate the cause.
In 1892, Crocker also in England, saw a similar case and, suspecting that an
insect larva may be the cause, proposed the term "creeping eruption" 80. In
1895, Samson-Hammelstjerne showed that the larva of the fly, Gasterophilus,
was one cause of this condition 292.
The disease was particularly prevalent in the southeastern United States of
America and in 1926, Kirby- Smith and his colleagues held a clinic in Jackson-
ville, Florida and saw 179 cases in the space of ten days. More than half o f
these patients were thought to have acquired their infection at the beach. A
larval nematode was seen in skin biopsies; they named it Agamonematodium
migrans pending the discovery of the adult worm 162. The histological sections
were submitted to Ransom at the US Bureau of Animal Industry and he gave
the guarded opinion that they were third-stage larvae of the super-famil y
Strongyloidea. White and Dove then implicated A. braziliense as the cause of
the condition by studies in animals and by applying A. braziliense larvae to
human skin experimentally 345, then this was confirmed by Shelmire wh o
infected 18 volunteers experimentally 303. The distribution of infection on th e
body noted many years before by Lee was typical, for Dove (1932) reviewed
301 cases in Florida and showed that the lo wer limbs were afflicted in 76%, the
hand and arms in 14% and the trunk in 9% of cases. He noted that movement
of the larvae was very slow, each one moving only several millimetres per day,
and sometimes continuing for weeks or months 97. In 1953, Muhlesein reported
that eventually the cutaneously-migrating larvae may pass to the deeper tissues
and cause pneumonitis 228.
Initially, the condition was treated, usually with success, by freezing o r
cauterizing the skin overlying the advancing larva. In 1943, Smith claimed that
antimony (Fouadin) was effective in a child with multiple infections 309 but
Blank could not confirm this observation 40. Burks and Kingery believed tha t
chloroquine was valuable 48 but it was supplanted by thiabendazole when th e
efficacy of this drug was demonstrated by Stone and Mullins in 1965 321.
A. CANINUM
This hookworm parasite of dogs was first described by Ercolani in 1858 a s

Sclerostoma caninum 105, then renamed Ancylostoma caninum by Hall in
1913 135 . There have been several claims, beginning with Manalang in th e
Philippines199, that it has completed its development in humans. Severa l
workers have shown that this worm does not usually cause cutaneous larv a
migrans in humans although it might cause ground itch 149,346.
Miscellaneous Nematode Infections 723
A. MALAYANUM
This hookworm was first recovered from a bear and described as Helarctos
malayanus by Alessandrini in 1905 7. Infection in humans has been reporte d
once357.
ANGIOSTRONGYLIASIS
ANGIOSTRONGYLUS CANTONENSIS
In 1935, Chen recovered thi s worm from the respiratory tract of a rat caught in
Canton, China and named it Pulmonema cantonensis 64. In 1946, Dougherty
transferred it to the genus Angiostrongylus of Kamensky158 naming it
Angiostrongylus cantonensis 96. The generic name is derived from a
combination of the Greek words (ANGEON) and
(STRONGYLOS) meaning "vessel" and "round", respectively. The life cycle
was first described by Mackerras and Sandars in Australia in 1955. The y
reported that eggs hatched in the lungs of the rodent host then the larva e
migrated up the trachea and were swallowed then expelled in the faeces. The
larvae then infected a molluscan intermediate host within which they became
infective larvae in about two weeks. When ingested by the definitive host, the
infective larvae migrated to the brain and moulted twice. The young worm s
about 2 mm long, then migrated to the lungs and began laying eggs about four
weeks after infection 196. Many species of slugs and several species of lan d
snails as well as a planarian, crabs, fresh-water prawns and frogs have bee n
found infected with third-stage larvae, these non-molluscs serving as paratenic
hosts. Most human infections are thought to have been acquired by ingestion
of undercooked specimens of the giant African land snail, Achatina fulica.
The first infection in a human was repo rted by Nomura and Lin (as Haemo-
strongylus ratti) in Taiwan in a 15 year old boy with suspected meningitis from
whom six young adult worms were identif ied in the cerebrospinal fluid, but this
report was buried in the Japanese literature for many years 28,238. The first
well-documented fatal case in a human was reported by Rosen and hi s
colleagues in 1962287 following the investigations of Rosen into the cause o f
eosinophilic meningitis in Tahiti and Hawaii. The circumstances surrounding
the implication of A. cantonensis in this condition have been a subject of recent
controversy8,286. By 1979, 259 cases were known to have occurred in Taiwan 63.
The worm is a common cause of eosinophilic meningitis, most cases having an
incubation period of about three weeks and being relatively mild in severity and
self-limiting in duration. Occasionally, worms have been visualized in the eye,
either in the anterior chambe r or vitreous 260. Rarely, worms have been found in
human lung355, but patent infections with production of eggs and excretion of
larvae have not been reported thus far. The diagnosis is best made by recovery
of the worm. Alicata and Brown were of the op inion that skin testing was useful
in ruling out the diagnosis but that a positive reaction could not be relied upon
because of cross-reactivity with other helminths 9. Treatment is largely
symptomatic, headache often being relieved by removal of cerebrospinal fluid
at lumbar puncture. Thiabendazole was reported as being active against these
worms in experimental animals 82, but did not seem to be effective in humans 152.
In any case, it has been suggested that killing the worms could exacerbate the
inflammatory reaction with undesirable consequences in infected patients .
Worms have been removed surgically from the eye.
A. COSTARICENSIS
In 1967, Céspedes and his colleagues published two papers describing th e

clinical features and pathology of an illness which had been seen in 31 patients
in Costa Rica between 1952 and 1967. The m ain features were pain in the right
lower quadrant of the abdomen, often associated with a palpable mass and with
an eosinophilia ranging from 8-60%. Two yo ung children died from perforative
ileitis. In histological sections of these and other resected tissues, portions of
a worm were found and eggs were seen in the midst of a granulomatou s
inflammatory reaction and eosinophilic vasculitis. Céspedes and colleague s
believed the worm to be a metastrongylid parasite of mammals which ha d
infected humans by accident 52,53
In 1971, Morera and Céspedes described the causative worm which they
named Angiostrongylus costaricensis 223. In the following year, Chabau d
erected a new genus, Morerastrongylus, to house this worm 54, but Anderson
in 1978 reduced it back to Angiostrongylus 11. Also in 1971, Morera reported
the discovery of the adult worms in natural definitive hosts, the rats Sigmodon
hispidus and Rattus rattus 220, and he and Ash recorded the finding of infective
larvae in the tissues of the slug Baginulus plebeius 222. Since then, many other
species of mammals have been found infected and human infections have been
recorded from other parts of Central and northern South America. In 1973 ,
Morera described the life cycle of the worm; first stage larvae were passed in
the faeces of an infected rat, ingested by the slug intermediate host, the n
migrated to its mantle and foot and moulted twice to become infective after two
to three weeks. When the infected slug was eaten by a rat, the larvae were freed
from the digested mollusc and migrated into the lymphatics of the gut mucosa,
moulted twice, then migrated to the ileocaecal region where they entered th e
arterioles and small arteries and the adult worms, which reached 2-4 cm i n
length, began to lay eggs which hatched with larvae appearing in the faece s
about three weeks after infection 221. Larvae are not discharged in the faeces of
humans although eggs and larvae may be seen in specimens of bowel. Th e
diagnosis is therefore generally made by biopsy, although a precipitin test has
been described recently by Sauerbrey 297. The mode of infection in humans i s
uncertain since raw slugs are not generally eaten in endemic regions. They may
be consumed accidentally or possibly larvae may leave the slug in the mucus
and thus contaminate fruit and vegetables. Treatment with thiabendazole has
been recommended by Loria-Cortes and Lobo-Sanahuja 189.
ANISAKIASIS
In 1845, Dujardin erected the genus Anisakis to house certain species o f

nematodes found in the stomach of marine mammals 99. It is now known that
when eggs of these worms are passed in the host's faeces, they embryonate and
hatch in the water and the free-swimming larvae may survive for up to thre e
months 138. The freeliving larvae may be ingested by shrimp-like crustacean s
(Euphausiidae) in which they develop int o infective larvae. The infective larvae
may in turn be eaten by fish and squid in which they migrate into the peritoneal
cavity and tissues; after death of the fish, they tend to migrate to the muscles 310.
The infective larvae may then be transferred from fish to fish and are finall y
eaten by whales, porpoises and dolphins and embed in the gastric mucosa of
these mammals to produce tumours 330.
In 1960, Rodenburg and Wielinga 284 and Kuipers and colleagues 167 in Hol-
land described an acute abdominal illnes s in humans due to inflammation of the
small intestine caused by larvae, identified at that time as Eustoma rotundatum,
which had been acquired by ingestion of slightly salted herring. Later in tha t
year, van Thiel and colleagues report ed 11 such cases, in most of whom worms
were discovered at laparotomy for relief of intestinal obstruction; one patient
developed peritonitis and two patients died 331. The identification of thes e
worms was changed to Anisakis marina by van Thiel 330 then altered to A.
simplex by Davey in his revision of the genus 91. The infection was first
recognized in Japan in 1965 by Asami and colleagues 16. By 1979, more than
500 cases had been recorded there 358.
CAPILLARIASIS
CAPILLARIA AEROPHILA
This common parasite of the respiratory mucosa of cats, dogs, foxes and some
other carnivores in many parts of the world was found in a fox and described
as Trichosoma aerophilum by Creplin in 1839 78. It was renamed Thominx
aerophila by Dujardin in 1845 99 then transferred to the genus Capillaria of
Zeder359 by Travassos in 1915 to become Capillaria aerophila 333. The generic
name is derived from the Latin word "capillus" meaning "hair'. The eggs ar e
coughed up, swallowed and discharged in the faeces; after six week or so they
become infective and infection of a new host occurs after their ingestion .
Infection in humans is rare, the first documented cases being reported in th e

USSR by Skrjabin and his colleagues in 1957 308. The most common clinica l
manifestation is asthma. The diagnosis is made by finding eggs in sputum or in
faeces, though one patient was diagnosed after finding the worm in a lun g
biopsy. This patient responded to treatment with diethylcarbamazine, thia -
bendazole and corticosteroids 6.
C. HEPATICA
This worm was discovered in the liver of a mouse in Australia in 1893 b y

Thomas Bancroft who named the parasite Trichocephalus hepatica 18. In 1916,
Hall erected the genus Hepaticola and transferred it to this genus naming i t
Hepaticola hepatica 136. In the preceding year, however, Travassos had placed
it in the genus Capillaria of Zeder359, where it is now considered to lie, so the
correct name is Capillaria hepatica 333. The parasite is common in rodents ,
especially rats, but has also been found in many other species of mammals in
all continents. Transmission occurs between carnivorous, especially canna -
balistic animals. Nishigori showed that after ingestion of eggs, larvae passed
to the liver, mainly via the portal system a nd matured over four weeks or so; the
adult worms produced eggs which were deposited in the liver parenchyma and
were not normally excreted in the faeces 237. Although the adult worms soo n
died, the eggs sometimes remained viable for about two years 334. When the
infected liver of the host was eaten by a predatory or scavenging animal, th e
eggs passed through the gut and were excreted in the faeces. When deposited
on damp soil, they developed into the infective stage; these may then b e
ingested in food, drink or soil 352.
The first case in humans was reported by MacArthur in India in 1924. At
the post-mortem examination of a 20 year old Br itish soldier who had died from
pneumonia, multiple abscesses were found scattered widely in both lungs and
in the liver. Masses of C. hepatica eggs were found microscopically in close
proximity to the liver abscesses 194. Infection has since been diagnosed in a
number of humans, either at autopsy or by finding eggs in the liver biopsies ,
often in patients who have presented with hepatomegaly and eosinophilia 246.
Occasionally, spurious instances of infection have been reported after finding
eggs in the faeces 306; presumably the ova had been ingested and passed directly
through the alimentary tract 116.
Effective treatment has not yet been devised; two children treated wit h
antimony recovered, but this may have been coincidental 76,304.
C. PHILIPPINENSIS
In 1963, eggs of a Capillaria species were found in the faeces of a man who
had been admitted to hospital in the Philippines with malabsorption syndrome.
He died three days later and autopsy revealed worms in the small and larg e
intestines68. In 1967, an illness causing seve re disease and sometimes death was
reported in Ilocos Sur Province of the Philippines; subsequent investigations
revealed Capillaria eggs in the stools of most patients 49. This led to Chitwood,
Valesquez and Salazar in the following year describing the adult worms, 3-4
mm long, and naming the parasite Capillaria philippinensis 69. In 1973, a focus
of infection was discovered in Thailand 256. In 1972, Cross and his colleagues
indicated that monkeys had been infected experimentally by feeding the m
freshwater fish and suggested that autoinfection may occur 81. It was shown that
eggs passed in the faeces required almost two weeks to embryonate and tha t
development to the infective larval stage in the fish intestinal mucosa took at
least three weeks 35,81. In humans, the adult worms together with larvae and eggs
have been found in the small intestine, especially the jejunum, and in heav y
infections a severe enteropathy with malabsorption and wasting is produce d
which not infrequently leads to death in a few weeks to months 50,90. Whalen and
his colleagues showed that thiabendazole was partially effective in intestina l
capillariasis344, then Singson and co-workers found that mebendazole wa s
considerably more effective 305.
INFECTION WITH CHEILOSPIRURA SPECIES
This genus was erected by Diesing in 1861 94. The worm has been recovere d
once from a human; it was found in a conjunctival nodule in a Filipino farmer 4.
INFECTION WITH CONTRACAECUM OSCULATUM
In 1912, Railliet and Henry raised the genus Contracaecum to house certain
species of nematode parasites of reptiles and fish 275. In 1967, Schaum and
Müller described larvae, identified as Contracaecum osculatum , in an
eosinophilic granuloma in the intestine of a patient in Germany who ha d
symptoms of peritonitis. The infection was thought to have been acquired by
eating imperfectly cooked fish in the Baltic. Cure was obtained wit h
thiabendazole 298.
INFECTION WITH CYCYLODONTOSTOMUM PURVISI
This hookworm parasite of the large intestine of rats was described by Adams
in Malaya in 1933 2. Infection in a human has been reported once 34.
INFECTION WITH DIOCTOPHYMA RENALE
This parasite, commonly known as the giant kidney worm, was known t o
Redi279 but was described by Goeze in 1782 and called Ascaris renalis by
him126 . Goeze's specimen was recovered from a dog but the worm has sinc e
been found in many carnivores. In 1802, Collet-Meygret called it in a
vernacular fashion, a dioctophyme 77. Rudolphi in 1802 labelled it Strongylus
gigas 289 then in 1851 Diesing renamed it Eustrongylus gigas 93. It was known
by this designation for many years. In 1901, Stiles argued that it should b e
called Dioctophyma renale 318, and despite some opposition, his view event-
ually prevailed when it was endorsed by the American Society of Parasitol -
ogists in 1941 (Journal of Parasitology 27: 279, 1941).
Eggs are excreted in the urine and are ingested by aquatic oligochaetes in
which they develop to the infective larval stage. Mammals can be infecte d
directly by ingestion of infected oligochaetes, but more commonly they ar e
taken up first by amphibia or fishes which are in turn ingested by the definitive
host197.
Only a small number of humans have been infected with this worm which
measures up to a metre in length and is ab out 5 mm in diameter. In 1860, Beale
in his review of parasitic infections of the urinary tract wrote:
The parasite appears to have been found in the human kidney on one occasion,
although Küchenmeister comes to the conclusion that it has never been met with.
The specimen is preserved in the College of Surgeons. 23
Blanchard reviewed the literature in 1886 and regarded only nine human cases
as authentic. One of the first presumptive cases reported in the Englis h
literature was described by Cannon in 1887 51. Most proven cases have bee n
diagnosed at autopsy or a worm has been expelled through the urethra. On e
case has been reported in which an immature worm was identified in a nodule
on the chest wall 30.
INFECTION WITH DIPETALONEMA SPECIES
The genus Dipetalonema was erected by Diesing in 1861 94. Immature worms
have been found in humans on several occasions including in an arm nodule 27
and in the eye26. These parasites may have been D. arbuta described by Highby
in 1943143 or D. Sprenti described by Anderson in 1935. In 1932, Owen and
Hennessey in Uganda reported the presence of small yellow nodules in th e
bulbar conjunctiva together with proptosis and periorbital oedema in som e
patients247. Poltera255 considered that these were Loa infections, but they may
have been Dipetalonema or Mansonella parasites 25.
INFECTION WITH DIPLOSCAPTER SPECIES
This genus was erected by Cobb in 1913 73 to house certain species of free -
living worms which live in decaying organic matter. Humans are infected very
rarely. Yokogawa found D. coronata in the urine of an elderly patient 356.
Chandler observed this species in the stomach contents of 9 achlorhydri c
patients58 who had presumably ingested them in decaying vegetable matter.
DIROFILARIASIS
DIROFILARIA IMMITIS
This worm was found in the heart of a dog and described as Filaria immitis by
Leidy in 1856 in the United States of America 173. The microfilariae reported in
dog blood by Gruby and Delafond in 1843 132 and later named by them Filaria
papillosa haematica canis domestica 133 may have been D. immitis 340,341 . In
1911, Raillet and Henry 272 erected the genus Dirofilaria and transferred the
parasite to it, it thus becoming known a s Dirofilaria immitis. The generic name
is derived from a combination of the Latin words "dirus" and "filarium "
meaning "cruel" and "ball of thread", respectively. It is transmitted b y
mosquitoes including Anopheles maculipennis 131 and Culex quinquefasciatus
(= fatigans)19. Occasional infections have occurred in humans with incomplete
development of the worm. Faust and his colleagues first described this in 1941
following the discovery of a worm in the vena cava of a woman in Ne w
Orleans111. In most cases since then, however, worms have been lodged in a
branch of the pulmonary artery and many have been found by a routine chest
X-ray70. They have rarely been found in the abdominal cavity 328, the eye95, and
subcutaneous tissues 37.
D. TENUIS
This parasite of the cutaneous tissues of the raccoon in the United States o f
America was described by Chandler in 1942 59. Many infections of the eye or
eyelid reported from the USA as due to D. conjunctivae may have been really
due to D. tenuis 241. In a number of other patients, the worms have presented as
subcutaneous tumours (reviewed in 115).
D. REPENS
This parasite of the subcutaneous tissues of dogs was described by Railliet and
Henry in 1911274. It is transmitted by mosquitoes such as Aedes aegypti33 .
Human infection was first reported b y Skrjabin and his colleagues in the USSR
in 1930; a worm was recovered from a subcutaneous nodule near the eye 307.
Many cases of D. conjunctivae infections reported from Europe and Asia may
in fact have been D. repens infections.
D. URSI
This parasite of the subcutaneous tissues of bears was described by Yamaguti

in 1941353 and was reviewed by Anderson in 1978 10. The vectors are simuliid
blackflies. The first human infection sus pected as being due to this parasite was
removed from the breast of a woman in Washington State, United States o f
America342.
INFECTION WITH EUSTRONGYLIDES SPECIES
Adult worms of various species of the genus Eustrongylides, which was

erected by Jaegerskiöld in 1909 151, are parasites of the anterior gut o f
fish-eating birds. The infective larvae develop in small fish and amphibia i n
which they may reach up to 10 cm in length. Unencapsulated, migrating larvae
may be found in the tissues of mammals that have eaten infected fish. Thre e
fishermen in the United States of A merica swallowed live bait minnows and all
developed severe abdominal pain; two required operative intervention t o
remove worms migrating into the peritoneal cavity 134.
GNATHOSTOMIASIS
GNATHOSTOMA SPINIGERUM
This parasite was discovered by Richard Owen in 1836 in the stomach wall of
a tiger which had died in the London Zoological Gardens. He erected a ne w
genus, Gnathostoma, derived from a combination of the Greek words
(GNATHOS) and µ (STOMA) meaning "jaw and "mouth", respectively,
to house this species which he named Gnathostoma spinigerum ; the specific
epithet reflects the rings of spines on the parasite's head 248.
Almost 100 years were to pass before inroads were made into an under -
standing of the life cycle of this worm. In 1912, Mitter found the parasite in a
cat, dog and leopard 212, then Chandler in 1925 reported finding the worm i n
10-30% of cats examined post-mortem in India 56. He also noted finding
encysted larvae in the mesentery of Indian snakes (rock python and cobra) 57.
Several years later, Heydon described the development in water of G. spini-
gerum eggs obtained from an infected cat and observed spontaneous hatching
of larvae142. In 1933, Prommas and Daengsvang in Thailand reported that they
had shown experimentally that Cyclops was the first intermediate host; th e
larvae forced their way into the body cavity of the copepod and moulted after
10-14 days to become second-stage larvae 257. They were unable to infect cats
with infected Cyclops but showed that a second intermediate host was required.
When the freshwater fish, Clarias batrachus, ingested infected Cyclops, the
second-stage larvae escaped and migrated to the tissues where they moulte d
again to become infective third-stage larvae 258. They then completed the lif e
cycle experimentally by infecting cats with infected fish 259. Africa and his
colleagues in the Philippines then re ported (in a paper dated October 1936, but
which seems to have been published somewhat later since it did not arrive at
the Bureau of Hygiene and Tropical Diseases in London until 17 March 1938)
that they had found encysted gnathostome larvae in the flesh of three species of
naturally-infected freshwater fi sh, then recovered adult G. spinigerum from the
stomach nodule of a presumably "clean" cat which had been fed larvae obtained
from an infected fish, Glossobius giurus 5. Daengsvang and Tansurat i n
Thailand then showed that natural inf ections occurred in over 90% of the frogs,
Rana rugulosa, 80% of the eel, Monopterus albus, and 30-40% of the
freshwater fishes, Ophiocephalus striatus and Clarias batrachus, that they
examined86. Miyakazi indicated in 1954 that he had found infective larvae i n
crayfish, crabs, amphibia, reptiles, fish and many mammals that had eaten fish
flesh, but that the larvae only matured to the adult stage in the stomach of dogs
and felines after a migration through the tissues 213. The various hosts of
infective third-stage larvae, probably including man, may become infecte d
either by ingestion of infected Cyclops or by the consumption of anothe r
infected vertebrate (i.e. a paratenic host) 84. Humans are thought to be usually
infected by eating poorly-cooked infected fish or domestic birds (ducks an d
chickens). In Thailand, many living infective larvae are found in a kind o f
fermented food made from the raw flesh of freshwater fish which is a favourite
dish of Thai women 83, while in Japan, "sashimi", the sliced raw flesh of animals
or fish, is enjoyed frequently 214.
The first human infection with this parasite was described by Levinson in
1889. The worm was remove d from an abdominal tumour in a Thai woman by
Dr Deunzer in Bangkok and forwarded to Levinson who named it Cheir-
acanthus siamensis 183. It was transferred to the genus Gnathostoma, becoming
G. siamense, by Railliet in 1893 263, and was then shown to be synonymous with
G. spinigerum by Leiper180. The larvae may migrate throughout the huma n
body. Their presence may become manifest when they appear superficially ,
either causing an abscess 204,293, or migrating through the subcutaneous tissues
producing a form of cutaneous larva migrans 142,329 or migratory oedema 283. The
worm often attempts to extrude itself, often through the skin, but also via the
mucous membrane of the oral cavity 283, respiratory tract and urinary tract. I n
one patient who had transient swellings for seven years and then had a worm
removed from an abscess in his right hand, swellings continued intermittently
for another ten years until a second worm was extracted; Maplestone and Rao
thought it likely that the worm had lived for 17 years 205. In 1945, Mukerji and
Bhaduri reported the extraction of a worm from the anterior chamber of a n
eye229, then the same patient seems to have b een described by Sen and Ghose 302.
When the parasites migrate through the deeper tissues, they may produc e
visceral larva migrans. The first fatal case recorded was described b y
Chitanondh and Rosen in 1967; a Thai woman developed a progressiv e
ascending paralysis and a worm was found in the spinal cord at autopsy 65.
Larvae may also migrate through the brain to produce an eosinophili c
meningoencephalitis 47,261.
The diagnosis is made by recovery of the worm but immunoassays, partic-
ularly skin tests, may be valuable 214. Treatment is by surgical removal. Effective
chemotherapy has not yet been demonst rated although ancylol, a compound not
available for human use, has been shown to be effective against migratin g
larvae in cats 85.
G. HISPIDUM
This parasite found in the stomach of pigs was described by Fedchenko i n

1872112. It rarely infects humans 224.
INFECTION WITH GONGYLONEMA PULCHRUM
This consmopolitan parasite of ruminants was first described by Molin i n

1857 215. The name is derived from a combination of the Greek word s
(GONGYLOS) and µ (NEMA) meaning "round" and "thread",
respectively. The adult worm, up to 6 cm in length, lives in the mucosa an d
submucosa of the oral cavity and oesophagus of animals. Eggs are passed in the
faeces and ingested by dung beetles or cockroaches; they hatch in the intestine
and the larvae burrow into the body cavity and encapsulate. The definitive host
becomes infected by swallowing an infected insect 22.
The first human infection was recorded in Italy in 1864 by Pane who called
the worm Filaria labialis 249. In 1916, Ward described the extraction of a worm
from beneath the mucosa of the lower lip of a 16 year old girl; the patient had
stated that she had seen the worm on three occasions during its migratio n
between the lips and the fauces 339. About 30 human cases have now bee n
reported. Most worms have be en found in the buccal cavity or its environs, but
Feng and colleagues have recorded one patient w ith oesophageal localization 114.
The worms have been removed surgically; anthelmintic therapy is uncertain.
INFECTION WITH HAEMONCHUS CONTORTUS
In 1803, Rudolphi described Strongylus contortus as a parasite of sheep 290. In

1898, Cobb erected the genus Haemonchus and transferred this parasite into
it, the worm thus becoming known as Haemonchus contortus 72. The generic
name is derived from a combination of the Greek words µ (HAIMA) and

(ONCHOS) meaning "blood" and "spear", respectively. Infection i s
rare in humans. de Magalhaes recorded the infection once in Brazil 198 and
Sweet described the infection in three aborigines in Western Australia 326.
INFECTION WITH LAGOCHILASCARIS MINOR
This species was first described by Leiper in 1909 who received the specimen
obtained from a human infected in Trinidad 177. The name is derived from a
combination of the Greek words (LAGOS), (CHEILOS), and
(ASKARIS, ASCARIS) meaning "hare-lipped" and "worm" ,
respectively; this reflects the deep median depression in each lip which gives
the parasite the form of a harelip. This worm has not yet been identified i n
animals and the life cycle is uncertain. The infection has been reported i n
humans a number of times. In most instances it has been recovered from th e
tissues of the head and neck with colonies of adult worms, eggs and larvae in
various stages of development being found in abscesses or nodules whic h
develop over months or years 42. Recently, a fatal case of encephalitis has been
described285. Variable success has been achieved with diethylcarbamazine 98,171,
thiabendazole 217,239 and levamisole 42.
INFECTION WITH MAMMOMONOGAMUS LARYNGEUS
This parasite of the upper respiratory tract of cattle and felines, commonl y
known as "gapes" was recovered from an ox and described by Railliet in 1899
who named it Syngamus laryngeus, the specific epithet reflecting its location
in the host265. In 1948, Rizhikov transferred the worm to the genu s
Mammomonogamus 282. The life cycle of this worm is uncertain. In 1913 ,
Leiper recorded the discovery by King in St. Lucia, West Indies of a male and
female worm which were coughed up by a woman, with a chronic cough .
Leiper named the parasite Syngamus Kingi 179,180. It was later considered to be
synonymous with M. laryngeus, although Buckley believed S. Kingi to be
synonomous with S. nasicola von Linstow, 1899 45. Hoffman in 1931 recounted
removing a red object from the posterior wall of the pharynx of a patient who
had had a continuous cough since visiting a farm several weeks previously; it
proved to be a pair of M. laryngeus in copula 144. Mornex and colleagues have
recently reviewed human Mammomonogamus infections and indicated that 78
cases have been reported, mostly from Central America and the Caribbean 226.
MANSONELLIASIS
MANSONELLA OZZARDI
For a number of years, Patrick Manson in London corresponded with friends

and acquaintances all over the w orld in an endeavour to collect statistics on the
various species of filariae. Filaria sanguinis hominis (= F. nocturna =
Wuchereria bancrofti) was well-known and Manson himself had described two
new species, microfilaria diurna (= Loa loa) and microfilaria perstans (=
Mansonella perstans) in 1891. In 1897, he presented his findings to the annual
meeting of the British Medica l Association held in Montreal, Canada, in which
he concluded that there were another two species of human filariae 202. In 1893
and again in 1895, Dr Newsham of St. Vincent, West Indies, had sent him a
large number of blood films prepared from residents of that island. In six o f
them, Manson found microfilaria bancrofti, but in ten of them he discovered:
an entirely new filaria which at Blanchard's suggestion, I have named filaria
Demarquayi. This new filaria is shaped exactly like filaria nocturna and filaria diurna
but is very much smaller. I do not feel justified in giving the measurements of the
dried organisms, the only specimens available, as in consequence of the shrivelling
the parasites have undergone, the dimensions may be materially altered; suffice it
to say that filaria Demarquayi is less then half the size of filaria nocturna. Filaria
Demarquayi has no sheath, but, like filaria perstans, is naked in the blood . . it
exhibits no diurnal periodicity whatever, being present in the peripheral blood both
during the day and during the night.202
In early 1897, Dr Ozzard in British Guiana (Guyana) had sent Manson 6 3
slides prepared from people living in the interior of that country. Manson found
no evidence of W. bancrofti infection, but in 27 of them he discovered tw o
different microfilariae:
One of these minute filariae closely resembled filaria Demarquayi of St. Vincent,
being minute and sharp-tailed and without a sheath; the other closely resembled, if
it was not identical with, filaria perstans a parasite which hitherto I had found only
in West African blood.202
Manson decided that of these two microfilariae (which he referred to a s
"Demerara filaria" - Demerara bein g a town in British Guiana), the blunt-tailed
form was indeed F. perstans, but from reasoning that is difficult to follow ,
wrote:
I do think the sharp-tailed Demerara filaria is a new species and not identical with
filaria Demarquayi....this new filaria of Demerara....I propose to call provisionally
filaria Ozzardi.202
CW Daniels in British Guiana, however, was less certain, for one year later he
reported to the British Medical Association: "If the sharp-tailed embryo s
represent another species, it has yet to be decided whether it is a new one or the
f. demarquayi" 88.
Otto Galgey, colonial assistant surgeon in St. Lucia, West Indies, was even
more forthright. He noted considerable variability in size of the F. demarquayi
he had found in St. Lucia, and after comparing them with specimens o f
F. ozzardi concluded that they were one and the the same worm:
I am inclined to believe that all are filaria Demarquayii; that is to say, that the filaria
Demarquayii of St. Vincent, and that discovered by me in St. Lucia, and the
sharp-tailed form of filaria Ozzardi (British Guiana) are identical. 120
In 1899, Daniels reported finding an adult female worm and a portion of a n
adult male worm which differed from the adult F. perstans (which he had
described the previous year) at the autopsy of patient who had had microfilaria
perstans and microfilaria ozzardi in his peripheral blood. They were foun d
lying free in the subperitoneal connective tissues of the anterior abdomina l
wall. He described the parasites, comparing them with F. bancrofti and F.
perstans and concluded:
The differences observed both in the male and female are sufficient, I consider, to
differentiate this from the other described adult filariae. The name 'Filaria Ozzardi'
might be retained for the new species.89
Later that year Galgey found two parental forms of F. demarquayi in the
mesentery of an infected patient in St Lucia 121. He sent them to Ozzard i n
British Guiana for identification, but owing to imperfections in the specimens,
Ozzard was not able to come to any definite conlusion. In 1902, Low reported
that he had compared microfilaria demarquayi from St. Lucia, Dominica and
St. Vincent and microfilaria ozzardi from British Guiana, and had concluded
that they were identical 190. With the recognition that F. demarquayi and
F. ozzardi were synonymous, the correct name appeared to be Filaria
demarquayi since Manson had described this parasite first in his original 1897
paper. Since this name had already been used for W. bancrofti by Zune361,
however, Railliet proposed the designation F. juncea 266. Leiper pointed out,
however, that the second name given by Manson, F. ozzardi, had priority 180. In
1914, Biglieri and Araoz found a microfilaria in persons living in the province
of Tucumán in northern Argentina, and named it microfilaria tucumani 36; this
parasite was also later shown to be synonymous with microfilaria ozzardi 337.
In 1929, Faust erected the genus Mansonella in honour of Manson, with this
parasite as the type and only species 108. When Chabaud and Bain reclassified
the Dipetalonema group in 1976, they omitted M. ozzardi as they considered
it insufficiently known for taxonomic consideration 55. In 1982, Orihel and
Eberhard redescribed the species and redefined the genus using materia l
obtained by infection of experimental monkeys ( Erythrocebus patas)242.
Low in 1901 attempted to determine the vector of the parasite by exposing
infected patients to Culex fatigans (= quinquefasciatus), Stegomyia fasciata
(= Aedes aegypti), C. taeniatus and Anopheles albipes, but found that they
were refractory to infection. Subsequently, he caught and dissected a variety of
blood-sucking insects feeding on inhabitants in a heavily endemic area o f
British Guiana, but with negative results 190. In 1933, Buckley in St. Vincen t
indicated that microfilaria ozzardi was taken up by and developed in gnats of
the genus Culicoides 45, especially C. furens 46. Many years later, Nelson and
Davies showed that C. phlebotomus was a vector in Trinidad 231, while the
blackflies, Simulium species, were implicated in transmission in parts of South

America332,335.
Manson had written in 1897 that although he did not known what the y
were, he had no doubt that the pa rasite had some pathological consequences 202.
In the following year, however, Daniels declared that there was as yet n o
evidence of a pathological role for these worms as most infected person s
seemed to be in good health, even when the worms were numerous 88. This view
was echoed by Low in 1902:
The presence of the parental and embryonic forms of filaria Demarquayii seems to
give rise to no pathological effects or clinical symptoms. As the habitat of the parent
is in the loose connective tissue of the peritoneum, with perhaps the exception of
setting up some slight local inflammation on its death, it cannot do much harm, as
it does not implicate important structures.190
This latter concept has since stood the test of time. Diagnosis depends upo n
recovery of microfilaria from the blood, or less frequently, in skin samples 184.
Treatment is unnecessary; in any case, none in available.
M. PERSTANS
The blunt-tailed microfilaria of M. perstans was found by Mackenzie an d

Manson in 1890 in the same patient (who later died from sleeping sickness) in
whom they discovered what turned out to be microfilaria loa. These events and
the naming by Manson of the parasite first Filaria sanguinis hominis mino r
(because of the smaller size of the microfilaria when c.f. microfilaria loa)200,
then its designation as Filaria sanguinis hominis perstans (later F. perstans
to meet the needs of binomial nomenclature) because it had no periodicity in
contrast to the nocturnal periodicity of microfilaria bancrofti and the diurnal
periodicity of microfilaria loa 201 have been described in chapter 23. Th e
finding by Manson in 1897 of a similar microfilaria in blood sent to him from
Central America 202 is recorded in the section on M. ozzardi. This observation
stimulated C W Daniels in British Guiana to search for the parent worm. I n
December 1897, he was rewarded with success in finding male and femal e
worms in the mesentery and in subpericardial fat in two individuals who had
had both microfilaria perstans and microfilaria ozzardi in their blood during
life. He described the morphology of the worms, and since all the female worms
had blunt-tailed larvae, it seemed likely that they were the parental form o f
microfilaria perstans. Daniels wrote:
Although this is undoubtedly a new species of filaria I do not propose at present to
give it a name, seeing that it may turn out to be the parental form of one of the
already known and named species of nematode embryos described by Manson. Very
probably it may be the parental form of filaria perstans. 87
In 1898, Manson described two Congoles e patients with sleeping sickness who
were also infected with F. perstans 203. One of them soon died, and Mr O'Neill
of the Charing Cross Hospital found a mature filaria in the connective tissu e
behind the abdominal aorta. Manson comp ared this with the nematode from the
Americas described by Daniels and determined that they were the one and the
same, thus proving that Daniels had indeed discovered the adult form of F.
perstans 14. This opinion was supported soon afterwards by Low 191.
Thereafter, changes in the nomenclature of this parasite became rather like
a game of musical chairs. In 1912, Railliet, Henry and Langeron 276 transferred
it to the genus Acanthocheilonema which had been raised in 1870 b y
Cobbold75, thus becoming Acanthocheilonema perstans . However, Yorke and
Maplestone357 considered that Acanthocheilonema was a synonym of Dipetalo-
nema erected by Diesing in 1861 94, so it became known as Dipetalonema
perstans. In 1935, Faust 109 described the genus Tetrapetalonema and Yeh354
then Chabaud and Bain in 1976 55 placed it in this genus, the worm thus being
described as Tetrapetalonema perstans . This fashion was evanescent ,
however, for in 1982, Orihel and Eberhard redefined the genus Mansonella
and transferred this worm into that genus 242; it is therefore known currently as
Mansonella perstans.
Analogy with other filarial parasit es suggested that this worm was probably
transmitted by insect intermediate hosts but a number of years were to pas s
before this was proven. An interesting but odd exchange over the transmission
of infection took place at the beginning of the present century. The unorthodox
Charlton Bastian postulated that F. perstans was really a member of the genus
Tylenchus which contained nematode parasites of plants, and suggested tha t
infection was acquired by eating bananas 20. This brought a fulsome response
from Low who may have thought that Bastian himself was bananas: "filari a
perstans has nothing to do with the genus Tylenchus nor do bananas play any
part in the distribution or spread of this filaria" 192. Not to be outdone, Bastian
returned to the fray adducing various arguments 21 which were once more
refuted by Low 193.
In 1908, Fülleborn succeeded in achieving some development of microfil-
ariae in Anopheles maculipennis 118. In 1921, Sergent and Gouillon reported
unsuccessful attempts to infect Culex pipiens 301, but in 1927 Dyce Sharp in a
preliminary note announced the development of F. perstans in Culicoides
grahami 103. In the following year, he provided a more formal and detaile d
description of the events, with the product ion of infective larvae eight days after
experimental infection of C. austeni 104. In 1952, Hopkins and Nicholas showed
that C. grahami was a possible but poor vector when compared with C.
austeni 146.
Initially, Manson ascribed no pathological consequences to M. perstans
infection, but then transiently entertained the idea that it might be the cause of
sleeping sickness200,201. This possibility was banished, however, when th e
different geographical distributions of the two conditions were established and
the trypanosomal aetiology of the illness was ascertained. In 1903, Low wrote:
Filaria perstans, like filaria Demarquayii, gives rise to no pathological symptoms, the
position of the worms in the connective tissues of the mesentery apparently causing
no harm.191
Although there have been occasional claims to the contrary 71,219,227,323, most
commentators have upheld this view. The diagnosis is made by finding th e
microfilariae in the blood. Diethylcarbamazine has little action on the worm 139
but mebendazole may be active 338.
M. STREPTOCERCA
In 1922, JW Macfie and TF Corson on the Gold Coast (Ghana) found micro-
filariae in the skin of 22 out of 50 healthy adults which could be distinguished
from those of Onchocerca volvulus by having a slender body, crook-shape d
posterior end, and a blunt tail. Sections of the skin showed that they were lying
in the dermis and were surrounded by a slight degree of cellular infiltration .
MacFie and Corson placed these worms in the genus Agamofilaria of Stiles320
and named them Agamofilaria streptocerca 195. The same parasites were found
later by Dyce Sharp in 1927 in the British Cameroons (Cameroon) 102 then by
other observers in West and Central Africa. Like M. perstans, this parasite has
had a complex nomenclatural history. In 1949, Faust 110 transferred it to the
genus Acanthocheilonema of Cobbold 75 thus naming the worm
Acanthocheilonema streptocerca. Meanwhile, Peel and Chardome 251 in 1946
had reported the discovery of two female worms and a fragment of a mal e
worm in a chimpanzee (Pan paniscus) in the Belgian Congo (Zaire) and had
placed the parasite in the genus Dipetalonema of Diesing94, naming it
Dipetalonema streptocerca. In 1976, Chabaud and Bain 55 transferred it to the
genus Tetrapetalonema of Faust109 to become Tetrapetalonema streptocerca .
Finally, Orihel and Eberhard 242 in 1982 considered that Tetrapetalonema was
synonymous with Mansonella and renamed the parasite Mansonella
streptocerca.
The adult female worm was first di scovered in human tissue by Meyers and
his colleagues in 1972 209, then they found the adult male in 1977 211.
Chardome and Peel showed in 1949 that this parasite was transmitted by
Culicoides grahami 60, then Duke100 proved that C. milnei was also a vector.
The infection may be asympyomatic but some dark skinned persons presen t
with itching and hypopigmented macules. Meyers and colleagues reported that
diethylcarbamazine kills microfilariae in the tissues and produces degenerative
changes in adult worms 210.
INFECTION WITH MENINGONEMA PERUZZII
In 1973 Orihel and Esslinger described Meningonema peruzzii which had been
collected from three monkeys (Cercopithecus talaporn )243. The generic name
is derived from a combination of the Greek words µ (MENINX) and
µ (NEMA) meaning "membrane" and "thread", respectively. The sam e
worms had been reported by Peruzzi in 1928 in Uganda 253. Orihel240 then
suggested that these worms were the true cause of the meningoencephaliti s
attributed by Dukes and his colleagues to Dipetalonema (= Mansonella)
perstans 101.
INFECTION WITH METASTRONGYLUS ELONGATUS
In 1845, Dujardin described Strongylus elongatus, a parasite of the respiratory

tract of pigs99. In 1911, Railliet and Henry 273 transferred this worm to the genus
Metastrongylus which had been erected by M olin in 1861 216. The generic name
is derived from a combination of the Greek words µ (META) and
(STRONGYLOS) meaning "with" and "round", respectively .
Infections in humans are very rare, the first being described by Dujardin in the
respiratory tract of a six year ol d boy99. Chatin in 1888 reported infection in the
gastrointestinal tract of a pork vendor 61.
INFECTION WITH MICROFILARIA SPECIES (Adult worm undescribed)
M. BOLIVARENSIS
This unsheathed microfilaria was found i n the blood of American Indians living
in a remote part of Venezuela and reported by Godoy and colleagues in 1980 125.
M. RODHAINI
This infection was first described from the chimpanzees Pan paniscus and Pan
satyrus by Peel and Chardome in Zaire in 1946 251. Microfilaria indistinguish-
able from this parasite were seen in skin biopsies of people in Gabon b y
Richard-Lenoble and colleagues in 1982 281.
M. SEMICLARUM
In 1974, Fain reported the finding of a dis tinctive unsheathed microfilaria in the
blood of 52 inhabitants in three villages in Zaire. He named this parasit e
microfilaria semiclarum because it had a long, clear region on the posterior half
of the body106. The adult worms, reservoir host, and life cycle are unknown.
INFECTION WITH MICRONEMA DELETRIX
This species was described by Anderson and Bemrick in 1965 from thousands
of worms found in bilateral tu mours in the nares of a horse in the United States
of America 12. The generic name is derived from a combination of the Gree k
words µ (MIKROS, MICROS) and µ (NEMA) meaning "small" and
"thread", respectively. Three fatal cases with this parasite or a M. deletrix-like

worm have been recorded, the first being reported by Hoogstraten and Young
in 1975; a 5 year old boy in Canada died from meningoencephalitis caused by
the worm after he passed through a manure spreader and sustained multipl e
lacerations 145.
INFECTION WITH NECATOR SUILLIS
This hookworm parasite of pigs was designated Necator suillis by Ackert and
Payne in 19231. Buckley in 1932 infected himself on 11 separate occasion s
with infective larvae (about 80 worms each time) prepared from eggs obtained
from N. suillis recovered from pigs at an abbatoir in Trinidad. Eggs were first
seen 54 days after the first application to his skin and continued to be passed
over the next four months. Only three adult worms were recovered afte r
treatment with oil of chenopodium 44.
INFECTION WITH OESOPHAGOSTOMUM SPECIES
A number of species of the genus Oesophagostomum, raised by Molin in

1861216, are parasites of subhuman primates, swine and sheep. The generi c
name is derived from a combination of the Greek words
(OESOPHAGOS) and µ (STOMA) meaning "gullet" and "mouth" ,
respectively. These parasites are often called "nodular worms" since the y
produce large nodules in the wall of intestine, especially in the caecum an d
colon. Included amongst those which may occa sionally infect humans are O. bi-
furcum described by Creplin in 1849 79, O. aculateum by von Linstow in
1879 185, O. apiostomum by Willach in 1891 348
, O. bifurcum by Creplin in
1849 , O. brumpti by Raillet and Henry in 1905 268 and O. stephanosum des-
79
cribed by Stossich in 1905 322; some of these may be synonyms of each other.
The first human infection was found in a person from the Omo River in East
Africa 268, then Leiper reported O. apiostomum infection in man after the
parasite was collected by Foy in Nigeria 178. More recently, Anthony an d
McAdam reviewed 34 cases seen in Uganda. The most common presentation
was as a mass in the ileocaecal re gion although nodes or abscesses, usually 1-2
cm in diameter, may be seen in other parts of the small and large bowel 15.
Operative intervention may be necessary to effect the diagnosis or to reliev e
intestinal obstruction. No anthelmintics have yet been shown to be effective.
INFECTION WITH OSTERTAGIA SPECIES
In 1890, von Ostertag described a parasite recovered from cattle which h e

named Strongylus convolutus 244. Two years later, Stiles renamed it Strongylus
ostertagi 317. In 1894, Stadelmann described a similar parasite in sheep which
he named Strongylus circumcincta 315. In 1907, Ransom erected the genu s
Ostertagia and transferred these worms into it, the parasites thus becomin g
known as Ostertagia ostertagi and Ostertagia circumcincta 277. In 1941,
Kasimov recorded finding two male sp ecimens of O. circumcincta in the stools
of a patient after administration of anthelmintics 159 then reported the discovery
of a single O. ostertagi in the small intestine of a man at autopsy 160. Lapage
noted in a comment on these papers that it was possible that these worms might
have been ingested in uncooked or partly cooked abomasum of cattle, sheep or
goats169.
INFECTION WITH PELODERA SPECIES
Pelodera strongyloides, described in 1866 by Schneider 299, is a parasite of the

orbit of wild rodents, and the skin of dogs, horses, cattle and sheep. Huma n
infection has been reported once when it was found infecting the skin of an 11
year old Polish girl 250.
INFECTION WITH PHYSALOPTERA CAUCASICA
This worm was found in the ileum of a patient in the Caucasus and name d
Physaloptera caucasica by von Linstow in 1902 186. The generic name is
derived from a combination of the Greek words (PHYSALIS) and
(PTEROO) meaning "bubble" and "wing", respectively. In 1907 ,
Leiper also described a worm that had been removed from the stomach of a
person in Uganda and named it P. mordens 176. He later suggested that monkeys
may be the reservoir of infection180. The worms, 2-10 cms long, live with their
head embedded in the mucosa of the alimentary tract anywhere between th e
oesophagus and the ileum, but they may also be found in the liver. The infection
is rare in humans although Vandepitte and colleagues in 1964 reported finding
five cases in Zaire in one year. These patients complained of vomiting an d
epigastric pain and eggs were found in their faeces336. Another patient has been
described recently in whom worms that were probably Physaloptera caused
gangrene of the distal small bowel 235. The life cycle of this worm is unknown
and the treatment of the infection is uncertain.
INFECTION WITH RHABDITIS SPECIES
The genus Rhabditis was erected in 1845 by Dujardin 99 to house a number of

species of free-living nematodes which live typically in decaying organic matter
but which may occasionally be found temporarily on damaged human tissue or
in the lumen of various organs. Rhabditis species found in faeces have usually
been ingested in contaminated food or water and have passed through th e
alimentary tract or have contaminated faecal droppings deposited on the soil.
Kobayashi reported finding a Rhabditis which he called R. hominis in 17
students in Japan and noted that there were no ill-effects; the worms wer e
expelled spontaneously in 2-3 months 163. Rhabditis species have also been
found in urine 113 and in skin 236.
INFECTION WITH RICTULARIA SPECIES
This genus was erected by von Frölich in 1802 117. The worms are normall y
parasites of rodents and bats but an adult female worm has been seen in New
York in a human appendix 161.
INFECTION WITH SPIROCERCA LUPI
This parasite of wolves and dogs was named Strongylus lupi by Rudolphi 291 in
1809 then transferred to the genus Spirocerca of Raillet and Henry 273.In 1959,
Biocca reported the case of an infection of a baby who had been born on e
month prematurely and had developed intestinal obstruction and peritonitis as
a consequence of worms embedded in her terminal ileum 38. It is believed that
the mother must have ingested an infected beetle while pregnant.
INFECTION WITH TERNIDENS DEMINUTUS
This parasite of the large intestine of several simian species was described as
Triodontophorus deminutus by Raillet and Henry 267 in 1905 then renamed
Ternidens deminutus by them in 1909 270. The generic name Ternidens is
derived from a combination of the Latin words "ter" and "dens" meanin g
"thrice" and "tooth", respectively, and indicates the presence of three complex
teeth in the buccal cavity.
Infection of a woman with this parasite was reported by Leiper in 1908 175.
In 1929 Sandground recovered T. deminutus-like eggs from the faeces of a
medical missionary who had spent 25 years in Africa, cultured larvae, an d
produced an experimental infection in a vo lunteer, although he failed to recover
adult worms after carbon tetrachloride treatment 294. In a subsequent survey in
Southern Rhodesia (Zimbabwe), he found that in some regions more than 50%
of the population were infected 295. He attempted to transfer infection to more
humans and to subhuman primates but failed, as did Goldsmid many year s
later 127. Sandground used carbon tetrachloride and tetrachlorethylene i n
treatment. More recently, thiab endazole128 and pyrantel embonate 129 have been
shown to be effective.
INFECTION WITH TERRANOVA SPECIES
This genus was erected by Leiper and Atkinso n in 1914 to house certain worms
collected by Atkinson during the ill-fated British Antarctic Expedition o f
1910-1913 led by Captain Scott 182. The genus was named after the ship (itself
named "Terra Nova" meaning "new land") which took the party to th e
Antarctic. The life cycle is probably similar to that of Anisakis.
The first human infections were reported in Japan in 1972 by Suzuki and
his colleagues who described 5 patients in whom a larva was seen penetrating
the gastric mucosa 325. Koyama and colleagues then described the morphology
of the larvae removed from these patients 166. The infections were thought t o
have been acquired by eating raw fish. A number of similar cases have bee n
reported since. Some of these may b e due to infection with Phocanema species
since the larvae of this genus, erected by Myers 230 in 1959, are
indistinguishable from those of Terranova.
INFECTION WITH THELAZIA
T. CALLIPAEDA
This worm, 5-17 mm in length, which was found in a dog, was described b y
Railliet and Henry271 in 1910. The generic name is derived from the Gree k
word (THELAZO) meaning "to suck". In 1917, Stuckey 324 and
147
Houghton in China described infections of the human eye with a worm they
identified as Filaria palpebralis. Leiper, however, considered that the parasite
was almost certainly T. callipaeda 181, an opinion which was shared by Faust 107,
the latter describing the male worm for the first time and showing that rabbits
were a host. The life cycle is uncertain but other species of Thelazia use flies
(Musca, Fannia) as intermediate hosts. According to Kagei and colleagues, 30
cases have now been reported from Japan 155. The worm usually causes littl e
conjunctivitis but often stimulates marked tear production. Movement over the
corneal surface can cause corneal opacities. The worm may be removed with
forceps after anaesthesia of the eye.
T. CALIFORNIENSIS
This species has been recovered from a number of animal and bird hosts i n
California. It was first described by Kofoid and Williams 164 in 1935 after two
worms, 10-13 mm long, were removed from the eye of a doctor wh o
complained of an irritation in his eye; he remembered that some flying insect
had hit his eye ten days previously. Several cases have been reported since.
TOXOCARIASIS
TOXOCARA CANIS
This ascarid parasite of dogs was described by Werner in 1782 as Ascaris

canis 343. In 1907, Leiper erected the genus Belascaris and, holding that
Ascaris canis was synonymous with Fusaria mystax of the cat described by
Zeder359, called it Belascaris mystax 174. In 1916, however, Johnston transferred
the worm to the genus Toxocara, which had been erected by Stiles in 1905 319,
and named it Toxocara canis 154. The name Toxocara is derived from a
combination of the Greek words (TOXON) and (KARA, CARA)
meaning "bow" and "head", respectively.
There are rare records of the infection in humans by the adult form of this
parasite, but they are questionable, probably being in reality immature Ascaris
lumbricoides 39,350. In dogs, infection is usually acquired across the placenta or
via the mother's milk, although infective egg s in soil or larvae in paratenic hosts
may be ingested 314. When paratenic hosts are infected, larvae migrate into the
tissues, fail to mature and become encapsulated. This fate also befalls T. canis
larvae in humans. In monkeys, such lar vae have been shown to remain alive for
at least nine years 24.
In 1947, Josephine Perlingiero and Paul György of the Philadelphia General
Hospital reported the case of a two year old black boy admitted to hospital in
1944 with fever, weight loss, cough, vomiting, transient diarrhoea ,
hepatomegaly and marked eosinophilia. Because the vomiting continued and
abdominal distension developed, he was subjected to laparotomy and the liver
was found "to have small, gray-white lesions scattered over the smooth surface
of all lobes"252. Biopsy revealed focal necrotic lesions with numerou s
polymorphonuclear and eosinophilic granulocytes and giant cells. In view of the
fact that he "improved remarkably" after he vomited a single male A. lum-
bricoides, the illness was ascribed to infection with this parasite 252. A similar
case was described by Zuelzer and Apt two years later 360, then in 1950 Mercer
and colleagues found nematode larvae which they indentified as A. lumbri-
coides in lesions in the liver of a patient with a similar condition 208, as did
Behrer in the following year 31.
Meanwhile, in 1950, Helenor Wilder of the United States Armed Force s
Institute of Pathology had described an ocular disease which she called nema-
tode ophthalmitis. She discussed a large series of cases, mostly of children ,
from whom an eye had been enucleated because of a suspected diagnosis o f
retinoblastoma. Histological examination, however, revealed eosinophili c
granulomas, and in 24 of 46 such specimens, nematode larvae were found in
serial sections. A number of the m were examined by BG Chitwood who wrote:
"So far as can be determined on the basi s of the material at hand, the specimens
are third stage hookworm larvae" 66. Wilder remarked sagaciously, however ,
that the fact that the larvae in these cases had been identified as being probably
those of hookworms did not rule out other nematodes such as Strongyloides
and Ascaris as possible causes of this endophthalmitis. Most of the childre n
came from the southeastern USA and Wilder concluded:
The findings of intraocular larvae by serial sectioning and the identification of the
specific pathologic reaction that they evoke has led to the conclusion that nematodes
play an important and hitherto unrecognized role in blindness in children 347
In 1952, Beaver and his colleagues, Snyder, Carrera, Dent and Lafferty, in
New Orleans described three patients with hepatomegaly, anaemia and eosin-
ophilia, in one of whom a larva was seen in a liver biopsy. Consequently, they
coined the term "visceral larva migrans" to distinguish it from cutaneous larva
migrans caused by larvae of Ancylostoma braziliense and other parasites in the
skin. By utilizing serial sections, it was pos sible to reconstruct almost the whole
of the worm and it was concluded that it "resembled the infective stage o f
Toxocara canis or T. cati" 29. Mice were thereupon infected with T. canis and
T. cati eggs and worms similar to that found in the human case wer e
demonstrated subsequently in histological sections 29. In the following year, "by
means of an experiment which cannot be commended" 349, Smith and Beaver
produced the disease experimentally in humans. They administered orally 200
embryonated eggs of T. canis to two mentally defective children aged two and
three years, respectively; both developed eosinophilia and some degree o f
hepatomegaly311. This result was confirmed in a human volunteer by Chaudhuri
and Saha in 1959 62. In 1956, Nichols re-examined five of Wilder's cases and
identified the larvae in the eyes as those of Toxocara 233,234, then in 1959, Irvine
and Irvine reported finding T. canis larvae in the eye of a child in California 150.
By 1981, over 1900 cases of toxocariasis had been reported from many parts
of the world and most of these have been due to T. canis but a few have been
caused by T. cati 124.
Infection in humans is usually acquired by ingestion of eggs in the soil .
Toxocara ova were found in soil samples of 45% of dooryards in New Orl -
eans140 and in 24% of public parks in Britain 41. Infection is therefore common
in children who ingest soil (pica). The diagnosis may be established by finding
larvae in biopsy specimens but this is often difficult. Immunodiagnostic assays
are therefore valuable. A precipitin test was described in 1956 by Heiner and
Kevy141 and a skin test a few years later 351. More recently, Matthes and Buch-
walder considered a microprecip itation test using live larvae as the most useful
immunodiagnostic procedure 207. There have been scattered reports that th e

infection responds to treatment with thiabendazole 232, but this has not always
been the experience 17. Similar contradictory results have followed treatmen t
with diethylcarbamazine 312. Photocoagulation of the eye lesions is sometimes
possible148.
T. CATI
This ascarid parasite of cats was described as Ascaris cati by Schrank in

1788300. Zeder in 1800 named it Fusaria mystax359 , then Rudolphi renamed
it Ascaris mystax 288 and Leiper in 1907 used it as the type species of his new
genus, Belascaris, calling it Belascaris mystax 174. Railliet and Henry in 1911
reverted to the specific description of Schrank, naming it Belascaris cati 274. In
1927 Brumpt transferred it to the genus Toxocara of Stiles319, it thus being
designated Toxocara cati 43. Cats acquire the infection by ingesting embryo -
nated eggs or larvae in paratenic hosts. In contrast to T. canis, transplacental
transmission does not occur but t ransmammary transmission is common. Some
larvae complete their development to for m adult worms in the gut of young cats
but most larvae migrate to the muscles in older cats 313. Complete development
in humans is rare. The first such patient was possibly reported by Pickells in
Ireland in 1824254 then more probably by Bellingham O'Brien32 in the same
country a few years later then by Cobbold in England in 1863 74. According to
von Reyn and colleagues, there have been 20 reports of infection in humans 280,
but many of these may be spurious o r follow the ingestion by a child of a young
adult worm. More commonly, T. cati may cause visceral larva migrans.
TRICHOSTRONGYLIASIS
In 1892, Giles in India recov ered a worm which he named Strongylus colubri-
formis from nodules in the intestine of a sheep 123. In the following year, Railliet
described S. instabilis 263 then in 1896 he also described S. probulurus 264. In
1905, Looss erected the genus Trichostrongylus, transferred S. instabilis and
S. probulurus into it, and described a new species, T. vitrinus 188. The generic
name is derived from a combination of the Greek words (THRIX)
[combining form - (TRICHO-)] and (STRONGYLOS)
meaning "hair" or "thread" and "round", respectively. In 1911 Ranso m
transferred S. colubriformis into the genus Trichostrongylus 278. Other species
described were T. axei 269, T. orientalis 153, T. skrjabini 157 and T. brevis 245. All
of the above species are now known to infect humans.
In 1925, Koino reported that T. orientalis infections in mice seemed t o
follow the same route through the lungs as do hookworms. Although infection
could be established percutaneously, he believed that oral infection was th e
usual and more efficient mode of infection 165. Monnig218 then Hasegawa137
showed, however, that after oral infection, s ystemic migration did not occur; the
larvae migrated into the mucosa and matured in about three to four weeks.
The first human infection with a Trichostrongylus species was reported by
Looss in 1895 who described infection with the worm he named Strongylus
subtilis 187. Later Lane168 showed that S. subtilis was synonymous with S.
colubriformis described by Giles in 1892 123 so Looss's name lapsed in favour
of T. colubriformis. Initially, such infections were regarded as accidental i n
those who kept close proximity with animals. Eventually, however, it wa s
realized that human infection was much more frequent in many parts of th e
world than had hitherto been suspect ed. For example, Kalantarian found a 15%
prevalence in Armenia 156, Stewart showed that 70% of the population in one
part of Iran was infected 316, Lawless and colleagues reported a 70% infection
rate in an Egyptian village 170, and Otsuru observed a frequency of 40% in parts
of Japan245. Infection may persist for years; Sandground described one patient
in whom the infection had laste d for at least 8.5 years 296. These various surveys
revealed that in the vast majority of patients, infection produced no ill-effects.
The diagnosis of trichostrongyliasis is made by finding eggs in the faeces,
although specific identification depends upon recovery of the adult worms .
Otsuru showed in 1962 that bephenium hydroxynaphthoate was effective 245,
then thiabendazole 206 and pyrantel pamoate 122 were also found to be useful.
INFECTION WITH UNCINARIA STENOCEPHALA
This hookworm parasite of dogs was described by Railliet in 1885 262. Patent
infections do not develop in humans but Fülleborn in 1927 showed by exper-
imental infection of his own skin that it may cause cutaneous larva migrans 119.
REFERENCES
1. ACKERT JE, PAYNE FK. Investigations on the control of hookworm disease. XII .
Studies on the occurrence, distribution and morphology of Necator suillis including
descriptions of the other species of Necator. American Journal of Hygiene 3: 1-25, 1923
2. ADAMS AR. Report on a collection of nematodes from the Federated Malay States .
3. ADDARIO C. Su di un nem atode dell'occhio umano. Annali di Ottalmologia, Milano 14:
135-148, 1885
4. AFRICA CM, GARCIA EY. A new nematode parasite ( Cheilospirura sp.) of the eye of
man in the Philippines. Journal o f the Philippine Islands Medical Association 16: 603-607,
1936
5. AFRICA CM, REFUERZO PG, GARCIA EY. Further observations on the life cycle of
Gnathostoma spinigerum. Philippine Journal of Science 61: 221-225, 1936
6. AFTANDELIANS R, RAFAAT T, TAFFAZOLI M, BEAVER PC. Pulmonary capillariasis
in a child in Iran. American Journal of Tropical Medicine and Hygiene 26: 64-71, 1977
7. ALESSANDRINI GC. Su di alcune uncinariae parasite dell'uomo e di altri vertebrati.
Bolletino della Società dei Naturalisti in Napoli, second series, 6: 23-48, 1905
8. ALICATA JE. Priority in determining the cause and method of human infection in cases of
eosinophilic meningitis in Tahiti. Tropical Medicine and Hygiene News 35: 111-114, 1986
9. ALICATA JE, BROWN RW. Preliminary observations on the use of an intradermal test
for the diagnosis of eosinophilic meningoencephalitis in man caused by Angiostrongylus
cantonensis. Canadian Journal of Zoology 40: 119-124, 1962
10. ANDERSON RC. Description and relationships of Dirofilaria ursi Yamaguti, 1941 and
a review of the genus Dirofilaria Railliet and Henry, 1911. Transactions of the Roya l
Canadian Institute 29: 25-64, 1952
11. ANDERSON RC. Keys to genera of the superfamily Metastrongyloidea. CIH keys to the
nematode parasites of vertebrates, No. 5, Commonwealth Agricultural Bureaux, Farnham
Royal, Slough, U.K., 1978
12. ANDERSON RV, BEMRICK WJ. Micronema deletrix, n. sp., a saprophagous nematode
inhabiting a nasal tumour of a horse. Proceedings of the Helminthological Society o f
Washington 32: 74-75, 1965
13. ANONYMOUS. Lancet ii: 803, 1874
14. ANONYMOUS. The parental form of Filaria perstans. British Medical Journal i: 429,
1899
15. ANTHONY PP, McADAM IW. Helminthic pseudotumou rs of the bowel: thirty four cases
of helminthoma. Gut 13: 8-16, 1972
16. ASAMI K, WATANUKI T, SAKAI H, IMANO H, OKAMOTO R. Two cases o f
stomach granuloma caused by Anisakis-like larval nematodes in Japan. American Journal
17. AUR RJ, PRATT CB, JOHNSTON WW. Thiabendazole in visceral larva migrans .
American Journal of Diseases of Children 121: 226-229, 1971
18. BANCROFT TL. On the whipworm of the rat's liver. Journal and Proceedings of th e
Royal Society of New South Wales 27: 86-90, 1893
19. BANCROFT TL. On some further observations on the life-history of Filaria immitis,
Leidy. Journal and Proceedings of the Royal Society of New South Wales 37: 254-257,
1903. Reprinted in British Medical Journal i: 822-823, 1904
20. BASTIAN HC. Note on the probable mode of infection by the so-called Filaria perstans,
and on the probability that this organism really belongs to the genus Tylenchus (Bastian).
Lancet i: 286-287, 1904
21. BASTIAN HC. The anatomical characters of the so-called Filaria perstans and on the
mode of infection thereby. Lancet i: 643-644, 1904
22. BAYLIS HA, PAN TC, SAMBON JE. Some observations and experiments in northern
Italy. A preliminary note. Journal of Tropical Medicine and Hygiene 28: 413-419, 1925
23. BEALE L. A course of lectures on urine, urinary deposits and calculi. IV. Third class of
urinary deposits: entozoa. British Medical Journal ii: 1007-1008, 1860
24. BEAVER PC. Zoonoses, with particular reference to parasites of veterinary importance.
In, Biology of parasites, E.J. Soulsby (Editor), Academic Press, New York, pp 215-227,
1966
25. BEAVER PC, JUNG RC, CUPP EW. Clinical parasitology, ninth edition, Lea an d
Febiger, Philadelphia, pp 825, 1984
26. BEAVER PC, MEYER EA, JARROLL EL, ROSENQUIST RC. Dipetalonema from the
eye of a man in Oregon, U.S.A. American Journal of Tropical Medicine and Hygiene 29:
369-372, 1980
27. BEAVER PC, ORIHEL TC. Human infection with filariae of animals in the United States.
28. BEAVER PC, ROSEN L. Memorandum o n the first report of Angiostrongylus in man, by
Nomura and Lin, 1945. American Journal o f Tropical Medicine and Hygiene 13: 589-590,
1964
29. BEAVER PC, SNYDER CH, CARRERA GM, DENT JH, LAFFERTY JW. Chroni c
eosinophilia due to visceral larva migrans. Pediatrics 9: 7-19, 1952
30. BEAVER PC, THEIS JH. Dioctophymatid larval ne matode in a subcutaneous nodule from
a man in California. American Journal of Tropical Medicine and Hygiene 28: 206-212,
1979
31. BEHRER MR. Hypereosinophilia with eosino philic granuloma of the liver associated with
Ascaris infection. Journal of Pediatrics 38: 635-640, 1951
32. BELLINGHAM O'BRIEN. On an undescr ibed species of human intestinal worms. Dublin
Medical Press 1: 103-104, 1839
33. BERNARD PN, BAUCHE J. Conditions de la propogation de la filariose sous-cutanée
du chien. Stegomyia fasciata hôte intermédaire de Dirofilaria repens . Bulletins de la
34. BHAIBULAYA M, INDRANGARM S. Man, an accidental host of Cyclodontostomum
purvisi (Adams, 1933), and the occurrence in rats in Thailand. Southeast Asian Journal of
Tropical Medicine and Public Health 6: 391-394, 1975
35. BHAIBULAYA M, INDRANGARM S, ANANTHAPRUTI M. Freshwater fishes o f
Thailand as experimental intermediate hosts for Capillaria philippinensis . International
Journal for Parasitology 9: 105-108, 1979
36. BIBLIERI R, ARAOZ JL. Contribución al estudio de una nueva filariosis human a
encontrada en la Républica Argentina (Tucumán) ocasionado por la "Filaria tucumana".
Primera Conferencia de la Sociedad Sud-Americana de Higiene, Microbiología y
Patología, Buenos Aires, 17-24 Septiembre, 1916, Buenos Aires, 1917
37. BILLUPS J, SCHENKEN J R, BEAVER PC. Subcutaneous dirofilariasis in Nebraska.
Archives of Pathology and Laboratory Medicine 104: 11-13, 1980
38. BIOCCA E. Infestazione umana prenatale da Spirocerca lupi (Rud. 1809). Parassitologia
1: 137-142, 1959
39. BISSERU B, WOODRUFF AW, HUTCHINSON RI. Infection with adult Toxocara
canis. British Medical Journal i: 1583-1584, 1966
40. BLANK H. Use of fuadin in creeping eruption. Journal of the American Medica l
Association 123: 989-990, 1943
41. BORG OA, WOODRUFF AW. Prevalence o f infective ova of Toxocara species in public
places. British Medical Journal iv: 470-472, 1973
42. BOTERO D, LITTLE MD. Two cases of human Lagochilascaris infection in Colombia.
43. BRUMPT EJ. Précis de parasitologie, fourth edition, Librairie de l'Académie d e
44. BUCKLEY JJ. Necator suillis as a human infection. British Medical Journal i: 699-700,
1933
45. BUCKLEY JJ. Some observations on two West Indian parasites of man. Proceedings of
the Royal Society of Medicine 27: 134-135, 1933
46. BUCKLEY JJ. On the development in Culicoides furens Poey of Filaria (Mansonella)
ozzardi Manson, 1897. Journal of Helminthology 12: 99-118, 1934
47. BUNNAG T, COMER D S, PUNYAGUPTA S. Eosinophilic myeloencephalitis caused
by Gnathostoma spinigerum . Neuropathology of nine cases. Journal of Neurologica l
Science 10: 419-434, 1970
48. BURKS JW, KINGERY FA. Treatment of creeping eruption with chloroquin e
diphosphate. A preliminary report. Southern Medical Journal 49: 1290-1292, 1956
49. CABRERA BD, CANLAS B, DAUZ U. Human intestin al capillariasis. III. Parasitological
features and management. Acta Medica Philippina, series 2, 4: 92-103, 1967
50. CANLAS B, CABRERA BD, DAUZ U. Human intestinal capillariasis. II. Pathological
features. Acta Medica Philippina, series 2, 4: 84-91, 1967
51. CANNON R. Case of Strongylus gigas. Lancet i: 264, 1887
52. CÉSPEDES R, SALAS J, MEKBEL S, TROPER L, MÜLLNER F, MORERA P .
Granuloma entéricos y linfáticos con intensa eosinofilia tisular producidos por u n
estrongilídeo (Strongylata: Railliet y Henry, 1913). I. Patología. Acta Médic a
Costaricensis 10: 235-255, 1967
53. CÉSPEDES R, SALAS J, MEKBEL S, TROPER L, MÜLLNER F, MORERA P .
Granuloma entéricos y linfáticos con intensa eosinofilia tisular producidos por u n

estrongilídeo (Strongylata: Railliet y Henry, 1913). II. Aspecto parasitológico (not a
previa). Acta Medica Costaricensis 10: 257-265, 1967
54. CHABAUD AG. Description de Stefanskostrongylus dubosti n. sp. parasite du
potamogale et essai de classification des nématodes Angiostrongylinae. Annales d e
Parasitologie Humaine et Comparée 47: 735-744, 1972
55. CHABAUD AG, BAIN O. La lignée Dipetalonema. Nouvel essai de classification .
Archives de Parasitologie Humaine et Comparée 51: 365-397, 1976
56. CHANDLER AC. The helminthic parasites of cats in Calcutta and the relation of cats to
human helminthic infections. Indian Journal of Medical Research 13: 213-227, 1925
57. CHANDLER AC. A contribution to the life-history of a gnathostome. Parasitology 17:
237-244, 1925
58. CHANDLER AC. Diploscapter coronata as a facultative parasite of man, with a general
review of vertebrate parasitism by rhabditoid worms. Parasitology 30: 40-45, 1938
59. CHANDLER AC. The helminths of raccoons in East Texas. Journal of Parasitology 28:
255-268, 1942
60. CHARDOME M, PEEL E. La répartition des filaires dans la région de Coquilhatville et
la transmission de Dipetalonema streptocerca par Culicoides grahami . Annales de la
61. CHATIN JC. Le strongyle paradoxale chez l'homme. Bulletin de l'Académie de Médecine
52: 482-491, 1888
62. CHAUDHURI RN, SAHA TK. Tropic al eosinophilia. Experiments with Toxocara canis.
Lancet ii: 493-494, 1959
63. CHEN ER. Angiostrongyliasis and eosinophilic meningitis on Taiwan: a review. In ,
Studies on angiostrongyliasis in Eastern Asia and Australia, J.H. Cross (Editor), Special
Publication, U.S. Naval Medical Research Unit No. 2, Taipei, pp 57-73, 1979
64. CHEN HT. Un nouveau nématode pulmonaire, Pulmonema cantonensis n.g., n.sp. des
rats de Canton. Annales de Parasitologie Humaine et Comparée 13: 312-317, 1935
65. CHITANONDH H, ROSEN L. Fatal eosinophilic encephalomyelitis caused by th e
nematode Gnathostoma spinigerum . American Journal of Tropical Medicine and Hygiene
16: 638-645, 1967
66. CHITWOOD BG. Cited in 347
67 CHITWOOD MB, SMITH WM. A redescri ption of Anatrichosoma cynomolgi Smith and
Chitwood, 1954. Proceedings of the Helminthol ogical Society of Washington 25: 112-117,
1958
68. CHITWOOD MB, VALESQUEZ C, SALAZAR NG. First International Congress o f
Parasitology, Rome, 1964
69. CHITWOOD MB, VELASQUEZ C, SALAZAR NG. Capillaria philippinensis sp. n.
(Nematoda: Trichinellidae) from the intestine of man in the Philippines. Journal o f
70. CIFERRI F. Human pulmonary dirofilariasis in the United States: a critical review .
71. CLARKE V de V, HARWIN RM, MacDONALD DF, GREEN CA, RITTEY DA .
Filariasis: Dipetalonema perstans infections in Rhodesia. Central African Journal o f
Medicine 17: 1-11, 1971
72. COBB N A. Extract from MS report on the parasites of stock. Agricultural Gazette o f
New South Wales 9: 296-321, 1898
73. COBB NA. New nematode genera found inhabiting fresh water and non-brackish soils.
Journal of the Washington Academy of Science 3: 432-444, 1913
74. COBBOLD TS. On the occurrence of Ascaris mystax in the human subject. Lancet i :
31-34, 1863
75. COBBOLD TS. Description of a new generic type of entozoon from the aard wol f
(Proteles); with remarks on its affinities, especially in reference to the question o f
parthenogenesis. Proceedings of the Zoological Society of London i: 9-14, 1870
76. COCHRANE JC, SKINSTEAD E E. Capillaria hepatica in man - followup of a case.

South African Medical Journal 34: 21-22, 1960
77. COLLET-MEYGRET GF. Mémoire sur un ver trouvé dans le rein d'un chien. Journal
de Physiologie, Paris 55: 458-464, 1802
78. CREPLIN FHC. Eingeweidewürmer, Binnenwürmer, Thierwürmer. In, Allgemein e
Encyclopädie der Wissenschaften und Künste etc., J S Ersch und J G Gruber, (Editors),
Leipzig, 32: 277-302, 1839
79. CREPLIN FHC. Nachträge von Creplin zu Gurlt's Verzeichnisse der Thiere, in welchen
Endozoen gefunden worden sind. Archiv fü r Naturgeschichte, Berlin, 15J, 1: 52-80, 1849
80. CROCKER HR. Creeping eruption. Annals of Dermatology 3: 1184, 1892
81. CROSS JH, BANZON T, CLARKE MD, BASCA-SERVILLA V, WATTEN RH ,
DIZON JJ. Studies on the experimental transmission of Capillaria philippinensis in
monkeys. Transactions of the Royal Society of Tropical Medicine and Hygiene 66 :
819-834, 1972
82. CUCKLER AC, EGERTON JR, ALICATA JE. Therapeutic effect of thiabendazole on
Angiostrongylus cantonensis infections in rats. Journal of Parasitology 51: 392-396, 1965
83. DAENGSVANG S. Human gnathostomiasis in Siam with reference to the method o f
prevention. Journal of Parasitology 35: 116-121, 1949
84. DAENGSVANG S. A monograph on the genus Gnathostoma and gnathostomiasis in
Thailand, Southeast Asian Medical Information Centre, Tokyo, 1980
85. DAENGSVANG S. Chemotherapy of feline Gnathostoma spinigerum migration stage
with multiple subcutaneous doses of ancylol. Southeast Asian Journal of Tropica l
86. DAENGSVANG S, TANSURAT P. A contribution to the knowledge of the secon d
intermediate host of Gnathostoma spinigerum Owen 1836. Annals of Tropical Medicine
and Parasitology 32: 137-140, 1938
87. DANIELS CW. Discovery of the parental form of British Guiana blood worm. British
88. DANIELS CW. Filariae and filarial disease in British Guiana. British Medical Journal
ii: 878-880, 1898
89. DANIELS CW. The probabl e parental form of the sharp-tailed filaria found in the blood
of aboriginals of British Guiana. British Medical Journal i: 1459-1460, 1899
90. DAUZ U, CABRERA BD, CANLAS B. Human intestinal capillariasis. I. Clinica l
features. Acta Medica Philippina, series 2, 4: 72-83, 1967
91. DAVEY JT. A revision of the genus Anisakis Dujardin, 1845 (Nematoda: Ascaridata).
92. DESPORTES C. Filaria conjunctivae Addario 1885, parasite accidental de l'homme, est
un Dirofilaria. Annales de Parasitologie Humaine et Comparée 17: 380-404, 515-532,
1940
93. DIESING CM. Systema helminthum, Wilhelmum Braumüller, Vindobonae, tw o
volumes, pp 1267, 1849-1851
94. DIESING CM. Revision der Nematoden. Sitzungsberichte der Akademie de r
Wissenschaften in Wien. Mathematisch-naturwissenschaftliche Klasse 31: 42: 595-736,
1861
95. DISSANAIKE AS. Zoonotic aspects of filarial infection in man. Bulletin of the World
Health Organization 57: 349-357, 1979
96. DOUGHERTY EC. The genus Aelurostrongylus Cameron, 1927 (Nematoda :
Metastrongylidae) and its relatives; with descriptions of Parafilaroides, gen. nov., and
Angiostrongylus gubernaculatus , sp. nov. Proceedings of the Helminthological Society
of Washington 13: 16-25, 1946
97. DOVE WE. Further studies on Anchylostoma braziliense and the etiology of creeping
eruption. American Journal of Hygiene 15: 664-711, 1932
98. DRAPER JW. Infection with Lagochilascaris minor. British Medical Journal i: 931-932,
1963

100. DUKE BO. The intake of the microfilariae of Acanthocheilonema streptocerca by
Culicoides milnei, with some observations on the potentialities of the fly as a vector .
101. DUKES DC, GELFAND M, GADD KG, CLARKE VdeV, GOLDSMID JM. Cerebral
filariasis caused by Acanthocheilonema perstans. Central African Journal of Medicine
14: 21-27, 1968
102. DYCE SHARP NA. A note on Agamofilaria streptocerca MacFie and Corson, 1922.
103. DYCE SHARP NA. Development of Microfilaria perstans in Culicoides grahami : a
preliminary note. Transactions of the Royal Society of Tropical Medicine and Hygiene
21: 70, 1927
104. DYCE SHARP NA. Filaria perstans: its development in Culicoides austeni .
105. ERCOLANI GB. Nuovi elementi teorico-pratici di medicina veterinaria, Bologna, p p
550, 1858
106. FAIN A. Une nouvelle microfilaire parasitant le sang de deux muridae sauvages e n
République du Zaire (Nematoda: Filarioidea). Acta Zoologica et Pathologic a
Antverpiensis 58: 103-108, 1974
107. FAUST EC. Thelazia infection of man and mammals in China. Transactions of the Royal
108. FAUST EC. Human helminthology. A manual for clinicians, sanitarians and medica l
zoologists, Lea and Febiger, Philadelphia, pp 616, 1929
109. FAUST EC. Notes on helminths from Panama. III. Filarial infection in the marmosets,
Leontocebus geoffroyi (Pucheron) and Saimiri örstedii örstedii (Reinhardt) in Panama.
110. FAUST EC. Human helminthology. A manual for physicians, sanitarians and medica l
zoologists, third edition, Lea and Febiger, Philadelphia, pp 744, 1949
111. FAUST EC, THOMAS EP, JONES J. Discovery of human heartworm infection in New
Orleans. Parasitology 27: 115-122, 1941
112. FEDTSCHENKO (FEDCHENKO) AP. (Zoological ob servations. 2. G. hispidum, a new
parasite of swine.) Izvestiia Imperatorskago Obshchestva Liubitelei Estestvoznaniia ,
Antropologii i Etnogafii Moskva 10: 106-111, 1872. In Russian
113. FENG LC, LI F. Two human cases of urinary infection with Rhabditella axei (Cobbold
1884) Chitwood, 1933. Peking Natural History Bulletin 18: 195-202, 1933
114. FENG LC, TUNG MS, SU SC. Two Chinese cases of Gongylonema infection. A
morphological study of the parasite and a clinical study of the cases. Chinese Medical
Journal 73: 149-162, 1955
115. FONT R, NEAFIE RC, PERRY HD. Subcutaneous dirofilariasis of the eyelid. Report
of six cases. Archives of Ophthalmology 98: 1079-1082, 1980
116. FOSTER AO, JOHNSON CM. An explanation for the occurrence of Capillaria hepatica
ova in human faeces suggested by the finding of three new hosts used as food .
117. von FROELICH JA. Beyträge zur Naturgeschichte der Eingeweidewürmer .
118. FÜLLEBORN F. Untersuchunge n an menschlichen Filarien und deren Uebertragung auf
Stechmücken. Archiv für Schiffs- und Tropen-Hygiene 12: 357-388, 1908
119. FÜLLEBORN F. Durch Ha kenwurmlarven des Hundes ( Uncinaria stenocephala ) beim
Mewnschen erzeugte "Creeping Eruption". Abhandlungen aus dem Gebiet de r
Auslandskunde, Hamburg Universität (Festschrift Nocht) 26: 121-133, 1927
120. GALGEY O. Filaria Demarquayii in St. Lucia, West Indies. British Medical Journal i:
145-146, 1899
121. GALGEY O. St. Lucia, Colonial Report, 1899
122. GHADIRIAN E, ARFAA F. Present status of trichostrongyliasis in Iran. America n

123. GILES GM. On nodular disease of the intestine in sheep. Scientific Memoirs of Medical
Officers of the Army of India, part 7, pp 31-44, 1892
124. GLICKMAN L, SCHANTZ PM. Epidemiology and pathogenesis of zoonoti c
toxocariasis. Epidemiological Reviews 3: 230-250, 1981
125. GODOY GA, ORIHEL TC, VOLCAN GS. Microfilaria bolivensis : a new species of
filaria from man in Venezuela. American Journal of Tropical Medicine and Hygiene 29:
545-547, 1980
126. GOEZE JF. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper,
127. GOLDSMID JM. Ternidens deminutus: a parasitological enigma in Rhodesia. Research
Lecture Series No. 4, Faculty of Medicine, University of Rhodesia, 1971
128. GOLDSMID JM. Thiabendazole in the treatment of human infections with Ternidens
deminutus (Nematoda). South African Medical Journal 46: 1046-1047, 1972
129. GOLDSMID JM, SAUNDERS CR. Preliminary trial using pyrantel pamoate for th e
treatment of human infections with Ternidens deminutus . Transactions of the Roya l
Society of Tropical Medicine and Hygiene 66: 375, 1972
130. GOMES de FARIA J. Contribução para a sistematica helmintolojica brazileira. 3 .
Ancylostomum braziliense n. sp. Parazito dos gatos e cais. Memorias do Institut o
Oswaldo Cruz 32: 40-45, 1910
131. GRASSI B, NOÈ G. The propagation of the filariae of the blood exclusively by means
of the puncture of peculiar mosquitoes. British Medical Journal ii: 1306-1307, 1900
132. GRUBY D, DELAFOND HM. Note sur une altération vermineuse de sang d'un chien
determiné par un grand nombre d'hématozoaires du genre filaire. Comptes Rendu s
Hebdomadaires des Séances et Mémoires de l 'Académie des Sciences 16: 325-325, 1843.
Abstracted in Lancet i: 265, 1843
133. GRUBY D, DELAFOND HM. Tr oisième mémoire sur le ver filaire qui vit dans le sang
du chien domestique. Comptes Rendus Hebdomadaires des Séances et Mémoires d e
l'Académie des Sciences 24: 9-14, 1852. Abstracted in Quarterly Journal o f
Microscopical Sciences 2: 33-35, 1854
134. GUNBY P. One worm in the minnow equals too many in the gut. Journal of th e
American Medical Association 248: 163, 1982
135. HALL MC. A new nematode, Rictularia splendida, from the coyote, with notes on other
coyote parasites. Proceedings of the United States National Museum 46: 73-84, 1914.
Preprinted, Washington, pp 73-84, 1913
136. HALL MC. Nematode parasites of mammals of the orders Rodentia, Lagomorpha and
Hyracoidea. Proceedings of the United States National Museum 50: 1-258, 1916
137. HASEGAWA T. (Über die Entwicklung des Trichostrongylus instabilis und
experimental infektion. Taiwan Igakkai Zas shi No. 239, 1929.) In Japanese, with German
summary
138. HATSUSHIKA R. An experimental study on development and hatching of eggs o f
Anisakis physeteris (Nematoda: Ascaridata). Kawasaki Medical Journal 5: 1-7, 1979
139. HAWKING F. the chemotherapy of filarial infections. Pharmacological Reviews 7 :
279-299, 1955
140. HEADLEE WH. Epidemiology of human ascariasis in metropolitan area of Ne w
Orleans, Louisiana. American Journal of Hygiene 24: 479-521, 1936
141. HEINER DC, KEVY SV. Visceral larva migrans. Report of the syndrome in thre e
siblings. New England Journal of Medicine 254: 629-636, 1956
142. HEYDON GM. Creeping eruption or larva migrans in north Queensland and a note on
the worm Gnathostoma spinigerum . Medical Journal of Australia i: 583-591, 1929
143. HIGHBY PR. Dipetalonema arbuta n. sp. (Nematoda) from the porcupine, Erethizon
dorsatum (L). Journal of Parasitology 29: 239-242, 1943
144. HOFFMAN WA. Gapeworm in man. Porto Rico Journal of Public Health and Tropical
Medicine 6: 381-383, 1931

145. HOOGSTRATEN J, YOUNG WG. Menin goencephalomyelitis due to the saprophagous
nematode, Micronema deletrix . Canadian Journal of Neurological Science 2: 121-126,
1975
146. HOPKINS CA, NICHOLAS WL. Culicoides austeni , the vector of Acanthocheilonema
perstans. Annals of Tropical Medicine and Parasitology 46: 276-283, 1952
147. HOUGHTON HS. Note upon fil arial parasites from the conjunctival sac. China Medical
Journal 31: 25-26, 1917
148. HUISMANS H. Über das Solitärgranulom bei okularer Toxocara canis Infektion
(Hundespulwurm). Ophthalmologica 174: 10-13, 1977
149. HUNTER GW, WORTH CB. Variations in response to filariform larvae of Ancylostoma
caninum in the skin of man. Journal of Parasitology 31: 366-372, 1945
150. IRVINE WC, IRVINE AR. Nematode endophthalmitis: Toxocara canis. Report of one
case. American Journal of Ophthalmology 47: 185-191, 1959
151. JAEGERSKIOLD LA. Zur Kenntnis der Nematoden-Gattungen Eustrongylides und
Hystrichis, Uppsala, pp 48, 1909
152. JENNY B, BIOT J, FOUQUET M, THOMAS J, MAFART Y. La méningite à
éosinophile. Étude de 62 cas, dout 51 chez des sujets translantés à Tahiti. Médecin e
Tropicale 29: 330-340, 1969
153. JIMBO K. Ueber eine neue Art von Trichostrongylus aus dem Darme des Menschen in
Japon (Trichostrongylus orientalis n. sp.). Annotationes Zoologicae Japonenses 8 :
459-465, 1914
154. JOHNSTON TH. The endoparasites of the dingo, Canis dingo, Blumb. Proceedings of
the Royal Society of Queensland 28: 96-100, 1916
155. KAGEI N, HAYASHI S, ISHIDA T, YAMAGUTI T, ASAMI K, TAKEUCHI T. (A
case of thelaziasis callipaeda in Tokyo.) Japanese Journal of Parasitology 30: 337-344,
1981. In Japanese, with English summary
156. KALANTARIAN H. Trichostrongylosen des Menschen in Armenien. In, Sammlun g
Helminthologischer Arbeiten, K I Skrjabin, (Editor), Moscow, pp 84-96, 1927
157. KALANTARYAN EV. (On the fauna of the Trichostrongylids of sheep of Armenia) .
"Proceedings of the State Instit ute of Experimental Veterinary Medicine" 5: 40-57, 1928.
In Russian
158. KAMENSKY. (La position systématique des genres Metastrongylus Wost. et
Protostrongylus g. n. parmi les autres Strongylides.) Sbornik Trudov Khar'kouskag o
Veterinarnago Instituta, Kharkov 7: 15-17, 1905. In Russian, with French summary
159. KASIMOV GB. (The first case of ostertagiasis in man). Meditsinskaya Parazitologiya
i Parazitarn e Bolezni 10: 121-123, 1941. In Russian. Abstracted in Tropical Diseases
Bulletin 40: 326, 1943
160. KASIMOV B. (First case of Ostertagia ostertagi in man in Azerbaidjan.) Meditsinskaya
Parazitologiya i Parazitarn e Bolezni 12: 81, 1943. In Russian. Abstracted in Tropical
161. KENNEY M, EVELAND LK, YERMAKOV V, KASSOUMY DY. A case o f
Rictularia infection of man in New York. American Journal of Tropical Medicine and
Hygiene 24: 596-598, 1975
162. KIRBY-SMITH JL, DOVE WE, WHITE GF. Creeping eruption. Archives o f
Dermatology and Syphilology 13: 137-173, 1926
163. KOBAYASHI H. On a new species of rhabditoid worms found in the human intestines.
164. KOFOID CA, WILLIAMS OL. The nematode Thelazia californiensis as a parasite of
the eye of man in California. Archives of Ophthalmology 13: 176-180, 1935
165. KOINO H. Studies on the development and structure of the larvae of Trichostrongylus
orientalis, and their migratory course in the host. Transactions of the Sixth Biennia l
Congress of the Far Eastern Association of Tropical Medicine, Tokyo 1: 467-470, 1925
166. KOYAMA R, KUMADA M, SUZUKI H, OHNUMU H, KARASAWA Y ,
OHBAYASHI M, YOKOGAWA M. Terranova (Nematoda: Anisakidae) infection i n

man. II. Morphological features of Terranova sp. larva found in human stomach wall.
167. KUIPERS FC, van THIEL PH, ROSKAM ET. Eosinofiele flegmone van de dunn e
darm, verooraakt door een niet aan het lichaam van de mens aangepast worm .
Nederlandsch Tijdschrift voor Geneeskunde 104: 422-427, 1960. Also, Lancet ii :
1171-1173, 1960
168. LANE C. Trichostrongylus colubriformis (Giles 1892), a human parasite. Indian Medical
Gazette 48: 129-132, 1913
169. LAPAGE G. Tropical Diseases Bulletin 42: 50-51, 1945
170. LAWLESS DK, KUNTZ RE, STRONE CP. Intestinal parasites in an Egyptian village
of the Nile valley with emphasis on protozoa. American Journal of Tropical Medicine and
Hygiene 5: 1010-1014, 1956
171. de LEÃO RN, LEÃO FILHO J, BRA GADIAS L, CALHERIOS L B. Infeccão humano
pelo Lagochilascaris minor Leiper, 1909. Registrado de um caso observado no Estado
do Pará (Brasil). Revista do Instituto de Medicina Tropical de Sao Paulo 20: 300-306,
1978
172. LEE RJ. Creeping eruption. Transactions of the Clinical Society of London 8: 44-45 ,
1874. Abstracted in Lancet ii: 803, 1874
173. LEIDY J. Worms in the heart of a dog. (Abstract). Proceedings of the Academy o f
Natural Science, Philadelphia 8: 2, 1856
174. LEIPER RT. Two new genera of nematodes occasionally parasitic in man. Britis h
175. LEIPER RT. The occurrence of a rare sclerostome of man in Nyasaland. Journal o f
176. LEIPER RT. Physaloptera mordens : a new intestinal parasite of man. Transactions of
the Society of Tropical Medicine and Hygiene 1: 76-82, 1908. Presented 20 December
1907; Abstracted in Lancet i: 102, 1908
177. LEIPER RT. A new nematode worm from Trinidad, Lagochilascaris minor , sp. n.
Proceedings of the Zoological Society of London, Abstract 74, pp 35-36, 1909
178. LEIPER RT. The occurrence of Oesophagostomum apiostomum as an intestinal parasite
of man in Nigeria. Journal of Tropical Medicine and Hygiene 14: 116-118, 1911
179. LEIPER RT. Gapes in man, an occasional helminthic infection: a notice of its discovery
by Dr. A. King in St. Lucia. Lancet i: 170, 1913
180. LEIPER RT. Observations on certain helminths of man. Transactions of the Roya l
181. LEIPER RT. Thelaziasis in man: a summary of recent reports on "circumocular filariasis"
in Chinese literature, with a note on t he zoological position of the parasite. British Journal
of Ophthalmology 1: 546-549, 1917
182. LEIPER RT, ATKINSON EL. Helminthes of the British Antarctic Expedition ,
1910-1913. Proceedings of the Zoological Society of London pp 222-226, 1914
183. LEVINSON GM. Om en ny Rundorm hos Me nnesket Cheiracanthus siamensis , nov. sp.
Videnskabelige Meddelelser fra Dansk Naturhistorisk Forening i Kjøbenhavn (1889) 5
Aartis, 1: 323-326, 1890
184. LIGHTNER LK, EWERT A, CORREDOR A, SABOGAL E. A parasitologic survey
for Mansonella ozzardi in the Comisaria del Vaupes, Colombia. American Journal o f
185. von LINSTOW OF. Helminthologische Untersuchungen. Jahreshefte des Vereins fü r
Vaterländische Naturkunde in Württemberg, Stuttgart 35: 313-342, 1879
186. von LINSTOW OF. Zwei neue Parasiten des Menschen. Centralblatt für Bakteriologie
und Parasitenkunde, Abteilung originale 31: 768-771, 1902
187. LOOSS A. Strongylus subtilis n. sp., ein bisher unbekannter Parasit des Menschen i n
Egypten. Centralblatt für Bakteriologie und Parasitenkunde, Abteilung originale 18 :
161-169, 1895
188. LOOSS A. Das Genus Trichostrongylus n.g., mit zwei neuen gelegentlichen Parasiten
des Menschen. Centralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten,
189. LORIA-CORTES R, LOBO-SANAHUJA JF. Clinical abdominal angiostrongyliasis. A
study of 116 children with intestinal eosinophilic granuloma caused by Angiostrongylus
costaricensis. American Journal of Tropical Medicine and Hygiene 29: 538-544, 1980
190 LOW GC. Notes on Filaria Demarquayii . British Medical Journal i: 186-187, 1902
191. LOW GC. Filaria perstans. British Medical Journal i: 722-724, 1903
192. LOW GC. Filaria perstans and the suggestion that it belongs to the genus Tylenchus
(Bastian). Lancet i: 420-421, 1904
193. LOW GC. "Filaria perstans:. Lancet i: 752-753, 1904
194. MacARTHUR WP. A case of infestation of human liver with Hepaticola hepatic a
(Bancroft 1893) Hall 1916, with sections from the liver. Proceedings of the Royal Society
of Medicine 17: 83-84, 1924
195. MacFIE JW, CORSON JF. A new species of filarial larva found in the skin of natives
in the Gold Coast. Annals of Tropical Medicine and Parasitology 16: 465-471, 1922
196. MACKERRAS MJ, SANDARS DF. The life-history of the rat lung-worm ,
Angiostrongylus cantonensis (Chen) (Nematoda: Metastrongylidae). Australian Journal
of Zoology 7: 1-21, 1955
197. MACE TF, ANDERSON RC. Development of the giant kidney worm, Dioctophyma
renale (Goeze, 1782) (Nematoda: Diocto phymatoidea). Canadian Journal of Zoology 53:
1552-1568, 1975
198. de MAGALHÃES PS. Note s d'helminthologia brésilienne. Neuvième série. Archives de
Parasitologie 12: 283-286, 1908
199. MANALANG C. Studies on ankylostomiasis in the Philippines. Transactions of the Sixth
Congress of the Far Easten Association of Tropical Medicine, Tokyo, pp 3512-368, 1925
200. MANSON P. The Filaria sanguinis hominis major and minor, two new species of
haematozoa. Lancet i: 4-8, 1891
201. MANSON P. The geographical distribution, pathological relations and life history o f
Filaria sanguinis hominis diurna and Filaria sanguinis hominis perstans in connexion
with preventive medicine. Transactio ns of the Seventh International Congress on Hygiene
and Demography, London, August 10-17, 1891, 1: 79-97, 1982. Abstracted in Medical
Press and Circular 103, new series, 52: 202-205, 1891, and Semaine Médecine 11: 342,
1891
202. MANSON P. On certain new species of nematode haematozoa occurring in America .
203. MANSON P. A clinical lecture on sleeping sickness. British Medical Journal ii :
1672-1677, 1898
204. MAPLESTONE PA. A case of human infection with a gnathostome in India. India n
205. MAPLESTONE PA, RAO SS. A case of gnat hostomiasis with some interesting features.
Indian Medical Gazette 74: 479-480, 1939
206. MARKELL EK. Pseudohookworm infection - trichostrongyliasis. Treatment wit h
thiabendazole. New England Journal of Medicine 278: 831-832, 1968
207. MATTHES HF, BUCHWALDER R. Untersuchungen zum Larvenprazysitationest mit
Ascaris suum- und Toxocara canis-larven. Angewandte Parasitologie 23: 1-8, 1982
208. MERCER RD, LUND HZ, BLOOMF IELD RA, CALDWELL FE. Larval ascariasis as
a cause of chronic eosinophilia with visceral manifestations. American Journal o f
Diseases of Children 80: 46-58, 1950
209. MEYERS WM, CONNOR DH, HARMANN LE, FLESHMAN K , MORIS R, NEAFIE
RC. Human streptocerciasis. A clinico-pathologic study of 40 Africans (Zairians) ,
including identification of the adult filaria. American Journal of Tropical Medicine and
Hygiene 21: 528-545, 1972
210. MEYERS WM, MORIS R, NEAFIE RC, CONNOR DH, BOURNLAND J. Strepto-
cerciasis: degeneration of adult Dipetalonema streptocerca in man following

diethylcarbamazine therapy. American Journal of Tropical Medicine and Hygiene 27 :
1137-1147, 1978
211. MEYERS WM, NEAFIE RC, MORI S R, BOURLAND J. Streptocerciasis: observation
of adult male Dipetalonema streptocerca in man. American Journal of Tropical Medicine
and Hygiene 26: 650-657, 1977
212. MITTER SN. Note on Gnathostoma spinigerum . Parasitology 5: 150, 1912
213. MIYAZAKI I. Studies on Gnathostoma occurring in Japan (Nematoda :
Gnathostomatidae). II. Life history of Gnathostoma and morphological comparison of
its larval forms. Kyushu Memoirs of Medical Science 5: 123-140, 1954
214. MIYAZAKI I. On the genus Gnathostoma and human gnathostomiasis with specia l
reference to Japan. Experimental Parasitology 9: 338-370, 1960
215. MOLIN R. Notizie elmintologiche. Atti der Reale Istituto Veneto di Scienze, Lettere ed
Arti, third series, 2: 146-152, 1857
216. MOLIN R. Il sottordine degli acrofalli ordinato scientificamente secundo i risultamenti
delle indagini anatomiche ed embriogeniche. Memorie del Reale Istituto Veneto d i
Scienze, Lettere ed Arti 9: 427-633, 1861
217. MONDRAGON H, CANO RM, BOTERO D. Primer caso de infeccion humana po r
Lagochilascaris minor en Colombia. Antioquia Medica 23: 463-464, 1973
218. MONNIG H. The life histories of Trichostrongylus instabilis and T. rugatus of sheep in
South Africa. Eleventh and Twelfth Report of the Director of Veterinary Education and
Research, pp 231-251, 1926
219. MORENAS L. Un cas de filariose dû à Acanthocheilonema perstans avec manifestations
clinique et grosse éosinophile. Bulletins de la Société de Pathologie Exotique et de ses
Filiales 22: 325-330, 1929
220. MORERA P. Investigación del huésped definitivo de Angiostrongylus costaricensi s
(Morera y Céspedes, 1971). Boletín Chileno de Parasitologia 25: 133-134, 1971
221. MORERA P. Life history and redescripti on of Angiostrongylus costaricensis Morera and
Céspedes 1971. American Journ al of Tropical Medicine and Hygiene 22: 613-621, 1973
222. MORERA P, ASH LR. Investigacion del huésped intermediario de Angiostrongylus
costaricensis (Morera y Céspedes, 1971) . Boletín Chileno de Parasitologia 25: 135, 1971
223. MORERA P, CÉSPEDES R. Angiostrongylus costaricensis n. sp. (Nematoda:
Metastrongyloidea), a new lungworm occurring in man in Costa Rica. Revista d e
Biologia Tropical 18: 175-185, 1971
224. MORISHITA K. A pig nematode, Gnathostoma hispidum Fedtschenko, as a huma n
parasite. Annals of Tropical Medicine and Parasitology 18: 23-36, 1924
225. MORISHITA K, TANI T. A case of Capillaria infection causing creeping eruption in
man. Journal of Parasitology 46: 79-83, 1960
226. MORNEX JF, MAGDELEINE J, de THORE J. La syngamose humaine ( Mammomon-
ogamus nasicola) cause de toux en Martinique: 37 observations récentes. Nouvell e
Presse Médicale 9: 3628, 1980
227. MOSLER H. Filaria perstans. Archiv für Schiffs- und Tropen-Hygiene 43: 130, 1939
228. MUHLEISEN JP. Demonstration of pulmonary migration of the causative organism of
creeping eruption. Annals of Internal Medicine 38: 595-600, 1953
229. MUKERJI AK, BHADURI NV. Gnathostome infection of the eye. Indian Medica l
Gazette 80: 126-128, 1945
230. MYERS BJ. Phocanema, a new genus for the anisakid nematode of seals. Canadia n
Journal of Zoology 37: 459-465, 1959
231. NELSON GS, DAVIES JB. Observations on Mansonella ozzardi in Trinidad.
232. NELSON JD., McCONNELL TH, MOORE DB. Thiabendazole therapy of viscera l
larva migrans: a case report. American Journal of Tropical Medicine and Hygiene 15 :
930-933, 1966
233. NICHOLS RL. The etiology of visceral larva migrans. I. Diagnostic morphology o f
infective second-stage Toxocara larvae. Journal of Parasitology 42: 349-362, 1956
234 NICHOLS RL. The etiology of visceral larva migrans. II. Comparative larva l
morphology of Ascaris lumbricoides , Necator americanus, Strongyloides stercoralis , and
Ancylostoma caninum . Journal of Parasitology 42: 363-399, 1956
235. NICOLAIDES NJ, MUSGRAVE J, McGUCKIN D, MOORHOUSE DE. Nematod e
larvae (Spirurida: Physalopteridae) caus ing infarction of the bowel in an infant. Pathology
9: 129-135, 1977
236. NIELLY M. Un cas de dermato se parasitaire non encore observée en France ( Anguillula
leptodera). Bulletin de l'Académie de Médecine, Paris 46: 395-402, 1882
237. NISHIGORI M. (On the life history of Hepaticola hepatica . Second report). Taiwa n
Igakkai Zasshi No. 247, 1925. In Japanese, with English summary
238. NOMURA S, LIN H. (First clinical case of Hemostrongylus ratti Yokogawa in man.)
Taiwan No Ikai 3: 589-592, 1945. In Japanese. Translated in 28
239. OOSTBURG BF, VERMA AA. Lagochilascaris minor infection in Surinam. Report of
a case. American Journal of Tropical Medicine and Hygiene 17: 548-550, 1968
240. ORIHEL TC. Cerebral filariasis in Rhodesia - a zoonotic infection? American Journal
241. ORIHEL TC, BEAVER PC. Morphology and relationship of Dirofilaria tenuis and
Dirofilaria conjunctivae. American Journal of Tropical Medicine and Hygiene 14 :
1030-1043. 1965
242. ORIHEL TC, EBERHARD ML. Mansonella ozzardi: a redescription with comments on
taxonomic relationships. American Journal of Tropical Medicine and Hygiene 31 :
1142-1147, 1982
243. ORIHEL TC, ESSLINGER JH. Meningonema peruzzii gen. et sp. n. (Nematoda :
Filarioidea) from the central nerv ous system of African monkeys. Journal of Parasitology
59: 437-441, 1973
244. von OSTERTAG R. Ueber eine neue Strongylus-Art im Labmagen des Rindes .
Vorläufige Mittheilung. Centralblatt für Bakteriologie und Parasitenkunde, Abteilun g
originale 8: 457-460, 1890
245. OTSURU M. Trichostrongylus brevis sp. nov. from man (Nematoda :
Trichostrongylidae). Acta Medica et Biologica 9: 273-278, 1962
246. OTTO GF, BERTHROND M, APPLEBY RE, RAWLINS JC, WILBUR O .
Eosinophilia and hepatomegaly due to Capillaria hepatica. Bulletin of the Johns Hopkins
Hospital 94: 319-336, 1954
247. OWEN HB, HENNESSEY RS. A note on some ocular manifestations of helminthi c
origin occurring in natives of Uganda. Transactions of the Royal Society of Tropica l
248. OWEN R. Anatomical descriptions of two speci es of Entozoa from the stomach of a tiger
(Felis tigris Linn), one of which forms a new genus of Nematoidea (Gnathostomata) .
Proceedings of the Zoological Society of London (47) part 4, pp 123-126, 1836
249. PANE C. Note sopra di un elminto nematoide. Annali dell'Accademia degli Aspirant i
Naturalisti di Napoli, series 3, 4: 32-34, 1864
250. PASYK K. Dermatitis rhabditosa in an 11-year old girl. A new cutaneous parasiti c
disease of man. British Journal of Dermatology 98: 107-112, 1978
251. PEEL E, CHARDOME M. Sur des filarides de chimpanzes "Pan paniscus" et "Pa n
satyrus" au Congo Belge. Annales de la Société Belge de Médecine Tropicale 26 :
117-156, 1946
252. PERLINGIERO JG, GYÖRGY P. Chronic eosinophilia. Report of a case with necrosis
of the liver, pulmonary infiltrations, anemia and Ascaris infestation. American Journal of
Diseases of Children 73: 34-43, 1947
253. PERUZZI M. Cerebral filariasis in five monkeys infected with trypanosoma l
meningoencephalitis. League of Nations Organization. Final Report of the International
Commission on Human Trypanosomiasis, pp 309-313, 1928
254. PICKELLS W. Case of a young woman who has discharged and continues to discharge,
from her stomach, a number of insects in different stages of their existence. Transactions
of the Kings and Queens College of Physicians of Ireland 4: 189-214, 441-446, 1824
255. POLTERA AA. The histopathology of ocular loiasis in Uganda. Transactions of th e
256. PRADATSUNDARASAR A, PECHARANOND K, CHINTANAWONGS C ,
UNGTHAVORN P. The first case of intestinal capillariasis in Thailand. Southeast Asian
Journal of Tropical Medicine and Public Health 4: 131-134, 1973
257. PROMMAS C, DAENGSVANG S. Preliminar y report on the life-cycle of Gnathostoma
spinigerum. Journal of Parasitology 19: 287-292, 1933
258. PROMMAS C, DAENGSVANG S. Further report of a study on the life-cycle o f
Gnathostoma spinigerum . Journal of Parasitology 22: 180-186, 1936
259. PROMMAS C, DAENGSVANG S. Feeding experiments of cats with Gnathostoma
spinigerum larvae obtained from the second intermediate host. Indian Medical Gazette
23: 115-116, 1937
260. PROMMINDAROJ K, LEELAWONGS N, PRADATSUNDARASAR A. Huma n
angiostrongyliasis of the eye in Bangkok. American Journal of Tropical Medicine an d
Hygiene 11: 759-761, 1962
261. PUNYAGUPTA S. Recent knowledge on clinical gnathostomiasis. Journal of th e
Medical Association of Thailand 50: 686-695, 1967
262. RAILLIET A. Éléments de zoologie médicale et agricole, Paris, pp 586, 1885
263. RAILLIET A. Traité de zoologie médicale et agricole, second edition, Paris, pp 736 ,
1893
264. RAILLIET A. Sur les variations morphologiques des strongyles de l'appareil digestif, et
sur un nouveau strongyle du dromadaire. Comptes Rendus Hebdomadaires des Séances
et Mémoires de la Société de Biologie 48: 540-542, 1896
265. RAILLIET A. Syngame laryngien du boeuf. Comptes Rendus Hebdomadaires de s
Séances et Mémoires de la Société de Biologie 51: 174-176, 1899
266. RAILLIET A. In, Précis de parasitologie humaine. Maladies parasitaires dues à de s
végétaux et à des animaux, fo urth edition, M Neveu-Lemaire, (Editor), J Lamarre, Paris,
pp 712, 1908
267. RAILLIET A, HENRY AC. Le Triodontophorus deminutus , nouveau sclérostomie n
parasite de l'homme, et la cachexie africaine. Bulletin du Muséum d'Histoire Naturelle,
Paris 11: 269-272, 1905
268. RAILLIET A, HENRY AC. Encore un nouveau sclérostomien ( Oesophagostomu m
brumpti nov. sp) parasite de l'homme. Comptes Rendus Hebdomadaires des Séances et
269. RAILLIET A, HENRY AC. Sur la classification des Strongylidae. I. Metastrongylinae.
Comptes Rendus Hebdomadaires de s Séances et Mémoires de la Société de Biologie 66:
85-88, 1909
270. RAILLIET A, HENRY AC. Sur la classifica tion des Strongylidae. II. Ankylostomatinae.
Comptes Rendus Hebdomadaires de s Séances et Mémoires de la Société de Biologie 66:
167-171, 1909
271. RAILLIET A, HENRY AC. Nouvelles observations sur les thélazies, nématode s
parasites de l'oeil. Comptes Rendus Hebdomadaires des Séances et Mémoires de l a
Société de Biologie 68: 783-785, 1910
272. RAILLIET A, HENRY AC. Sur une filaire péritonéale des porcins. Bulletins de l a
273. RAILLIET A, HENRY AC. Helminthes du porc recueillis par M Bauche en Annam .
274. RAILLIET A, HENRY AC. Recherches sur les ascarides des carnivores. Compte s
1911
275. RAILLIET A, HENRY AC. Quelques nématodes parasites des reptiles. Bulletins de la

276. RAILLIET A, HENRY AC, LANGERON. Le genre Acanthocheilonema Cobbold, et
les filaires péritonéales des carnivores. Bulletins de la Société de Pathologie Exotique et
de ses Filiales 5: 392-395, 1912
277. RANSOM BH. Notes on parasitic nematodes, including descriptions of new genera and
species, and observations on life histories. Circular (116), Bureau of Animal Industry ,
United States Department of Agriculture, pp 7, 1907
278. RANSOM BH. The nematodes parasitic i n the alimentary tract of cattle, sheep, and other
ruminants. Bulletin (127), Bureau of Animal Industry, United States Department o f
Agriculture, pp 132, 1911
279. REDI F. Opusculorum pars secunda, sive experimenta circa varias res naturales ,
speciatim illas quae ex indiis afferuntur etc., pp 312; opusculorum pars tertia, sive d e
animalculis vivis, quae in corporibus animalium vivorum reperiuntur observationes. In,
Opuscula varia physiologica, T Haak et S Luchtmans, Lugduni Batavorum, thre e
280. von REYN CF, ROBERTS TM, OWEN R, BEAVER PC. Infection of an infant with
an adult Toxocara cati (Nematoda). Journal of Pediatrics 93: 247-249, 1978
281. RICHARD-LENOBLE D, KOMBILA M, BAIN O. Foyer de filariose humaine a u
Gabon à microfilaire dermique indifférenciable de microfilaria rodhaini. Annales d e
Parasitologie Humaine et Comparée 57: 506, 1982
282. RIZHIKOV KM. (Phylogenetic relationships within the nematode family Syngamidae,
with revision and systematic fin dings.) Dokladi Akademii Nauk SSR 62: 733-736, 1948.
In Russian, with English summary
283. ROBERT L. La gnathostomose humaine, oedème ambulant siamois dû à Gnathostoma
spinigerum (R. Owen, 1835). Bulletins de la Société de Pathologie Exotique et de ses
Filiales 15: 854-860, 1922
284. RODENBURG W, WIELINGA WJ. Eosinfiele flegmone van de dunne darme ,
veroorzakt door een worm. Nederlandsch Tidjscrift voor Geneeskunde 104: 417-421 ,
1960
285. ROSEMBERG S, LOPES MB, MASUDA Z, CAMPOS R, VIEIRA BRESSAN MC.
Fatal encephalopathy due to Lagochilascaris minor infection. American Journal o f
286. ROSEN L. Reply to 8. Tropical Medicine and Hygiene News 35: 114-117, 1986
287. ROSEN L, CHAPPELL R, LAQUEUR GL, WALLACE GD, WEINSTEIN PP .
Eosinophilic meningoencephalitis caused by a metastrongylid lungworm of the rat .
288. RUDOLPHI CA. Fortsetzung der Beobachtungen über die Eingeweidewürmer. Archiv
für Zoologie und Zootomie 2: 1-67, 1802
289. RUDOLPHI CA. Beschreibung von Strongylus gigas. In, Beyträge zur Anatomie und
Physiologie der Thiere, JA Albert, (Editor), Bremen, Heft 1, pp 115-116, 1802
290 RUDOLPHI CA. Neue Beobachtungen über die Eing eweidewürmer. Archiv für Zoologie
und Zootomie 3: 1-32, 1803
291. RUDOLPHI CA Entozoorum, sive vermium intestinalium historia naturalis, Treuttel &
292. SAMSON-HIMMELSTJERNE CV. (Concerning a new disease of the skin.) Vratsch 16:
1364, 1895. In Russian
293. SAMY PC. Gnathostoma siamense or Gnathostoma spinigerum . Indian Medical Gazette
53: 436, 1918
294. SANDGROUND JH. Ternidens deminutus (Railliet and Henry) as a parasite of man in
Southern Rhodesia, together with observations and experimental infection studies on an
unidentified nematode parasite of m an from this region. Annals of Tropical Medicine and
295. SANDGROUND JH. Studies on the life-history of Ternidens deminutus , a nematode
parasite of man, with observations on its incidence in certain regions of southern Africa.

296. SANDGROUND JH. On the potential longevity of various helminths with a record of
a species of Trichostrongylus in man. Journal of Parasitology 22: 464-470, 1936
297. SAUERBREY M. A precipitin test for the diagnosis of human abdomina l
angiostrongyliasis. American Journal of Tropical Medicine and Hygiene 26: 1156-1158,
1977
298. SCHAUM E, MÜLLER W. Die Heterocheilidiasis. Eine Infektion des Menschen mi t
Larven von Fisch-Ascariden. Deutsche medizinische Wochenschrift 92: 2230-2233, 1967
299. SCHNEIDER AF. Monographie der Nematoden, pp 357, Berlin 1866
300. SCHRANK FP. Verzeichnisse der b isher hinlängich bekannten Eingeweidewürmer nebst
einer Abhandlung über ihre Anverwandtschaften, München, pp 116, 1788
301. SERGENT E, GOUILLON P. Essais d'inocul ation à un singe d'une filariose humaine par
des piqûres de Culex pipiens. Archives des Instituts Pasteur de l'Afrique du Nord 1: 85,
1921
302. SEN K, GHOSE N. Ocular gnathostomiasis. British Journal of Ophthalmology 29 :
618-626, 1945
303. SHELMIRE B. Experimental creeping eruption from a cat and dog hookworm ( A.
braziliense). Journal of the American Medical Association 91: 938-943, 1928
304. SILVERMAN NH, KATZ JS, LEVIN SE. Capillaria hepatica infestation in a child.
South African Medical Journal 47: 219-221, 1973
305. SINGSON CN, BANZON TC, CROSS JH. Mebendazole in the treatment of intestinal
capillariasis. American Journal of Tropical Medicine and Hygiene 24: 932-934, 1975
306. SKRJABIN KI, POJDAPOLSKAYA WP, SCHICHOBALOWA NP. (Neue Fälle der
Hepaticolosis beim Menschen.) "Russian Journal of Tropical Medicine" 7: 449-450 ,
1929. In Russian, with German summary
307. SKRJABION KI, ALGANSES AJ, SCHOULMANN ES. (Premier cas de Dirofilaria
repens chez l'homme.) Tropickeskaya Meditsina i Veterinariya, Moscow 2: 9, 1930. In
Russian, with French summary
308. SKRJABIN KI, SHIKHOVALOVA NP, ORLOV IV. (Essentials of nematodology. VI.
Trichocephalidae and Capillariidae of animals and man and diseases caused by them ,
Academy of Sciences of USSR, Moscow, pp 420-423, 1957.) In Russian. Englis h
translation, Israel Progam for Scientific Translation, Jerusalem, pp 416-419, 513-515 ,
1970
309. SMITH DC. the treatment of creeping eruption with sodium antimony biscatecho l
(Fuadin). Journal of the American Medical Association 123: 694-695, 1943
310. SMITH JW, WOOTTEN R. Experimental studie s on the migration of Anisakis sp. larvae
(Nematoda: Ascaridida) into the flesh of herring, Clupea harengus L. International
Journal for Parasitology 5: 133-136, 1975
311. SMITH MH, BEAVER PC. Persistence and dis tribution of Toxocara larvae in the tissues
of children and mice. Pediatrics 12: 491-496, 1953
312. SNYDER CH. Visceral larva migran s - ten years' experience. Pediatrics 28: 85-91, 1961
313. SPRENT JF. The life history and development of Toxocara cati (Schrank) 1788) in the
domestic cat. Parasitology 46: 54-78, 1956
314. SPRENT JF. Observations on the development of Toxoocara canis (Werner 1782) in the
dog. Parasitology 48: 185-198, 1958
315. STADELMAN H. Ueber Strongylus circumcinctus , einem neuen Parasiten aus de m
Labmagen des Schafes. Sitzungsberichte der Gesellschaft Naturforschender Freunde zu
Berlin, pp 142-146, 1894
316. STEWART IS. Human infestation with Trichostrongylus in South Persia. British Medical
Journal ii: 737-739, 1949
317. STILES CW. A word in regard to the Filaridae found in the body cavity of horses and
cattle. Journal of Comparative Medicine and Veterinary Archives 13: 143-147, 1892
318. STILES CW. A discussion of certain questions of nomenclature as applied to parasites.
Zoologische Jahrbücher, Abteilun g für Systematik, Oekologie und Geographie der Tiere,
Jena 15: 157-208, 1901

319. STILES CW. The determination of generic types, and a list of roundworm genera with
their original and type species, CW St iles and A Hassall, Bulletin (79), Bureau of Animal
Industry, United States Department of Agriculture, pp 1-150, 1905
320. STILES CW. Agamofilaria georgiana n. sp., an apparently new roundworm parasite ,
from the ankle of a negress. Hygiene La boratory, United States Public Health and Marine
Hospital Service, Bulletin 34, pp 9-30, 1907
321. STONE OJ, MULLINS JF. Thiabendazole effectiveness in creeping eruption. Archives
of Dermatology 91: 427-429, 1965
322. STOSSICH M. Sopra alcuni nematodi. Annuario del Museo Zoologico della Real e
Universita di Napoli, new series, 1: 1-4, 1904
323. STOTT G. Pathogenicity of Acanthocheilonema perstans . Journal of Tropical Medicine
and Hygiene 65: 230-232, 1962
324. STUCKEY EJ. Circumocular filariasis. China Medical Journal 31: 24-25, 1917
325. SUZUKI H, OHNUMA H, KARASAWA Y, OHBAYASHI M, KOYAMA T ,
KUMADA M, YOKOGAWA M. Terranova (Nematoda: Anisakidae) infection in man.
I. Clinical features of five cases of Terranova larva infection. Japanese Journal o f
326. SWEET WC. The intestinal parasites of man in Australia and its dependencies as found
by the Australian Hookworm Campaign. Medical Journal of Australia i: 405-407, 1924
327. SWIFT HF, BOOTS RH, MILLER CP. A cutaneous nematode infection in monkeys.
328. TADA I, SAKAGUCHI Y, ETO K. Dirofilaria in the abdominal cavity of a man i n
Japan. American Journal of Tropical Medicine and Hygiene 28: 988-990, 1979
329. TAMURA H. (On creeping disease.) Hifu-Ka Oyobi Hinyoôki-Ka Zasshi pp 827-834,
891-910, 1919. In Japanese . Abstracted in Tropical Diseases Bulletin 18: 116-117, 1921
330. van THIEL PH. the final hosts of the herringworm Anisakis marina. Tropical and
Geographical Medicine 18: 310-328, 1966
331. van THIEL PH, KUIPERS FC, ROSKAM TH. A nematode parasitic to herring, causing
acute abdominal syndromes in man. Tropical and Geographical Medicine 12: 97-113 ,
1960
332. TIDWELL MA, TIDWELL M, MUÑOZ de HOYOS P. Development of Mansonella
ozzardi in a black fly species of the Simulium sanguineum groups from eastern Vaupes,
Colombia. American Journal of Tropical Medicine and Hygiene 29: 1209-1214, 1980
333. TRAVASSOS LP. Contribui ções par o conhecimento da fauna helmintolojica brasileira.
V. Sobre as especies brasileiras do genero Capillaria, Zeder, 1800. Memorias d o
Instituto Oswaldo Cruz 7: 146-172, 1915
334. TROISIER J, DESCHIENS R. L'hépatic oliase. Annales de Médecine 27: 414-425, 1930
335. UNDIANO C. Importancia y actualización del nuevo concepta da la patogenicidad de
la mansoneliasis. Revista de la Faculdad de Ciencias Médicas de la Universidad Nacional
de Cordoba 24: 183-189, 1966
336. VANDEPITTE J, MICHAUX JL, FAIN A, GATTI F. Premières observation s
congolaises de physaloptérose humaine. Annales de la Société Belge de Médecin e
Tropicale 44: 1067-1076, 1964
337. VOGEL H. Ueber Mikrofilaria demarquayi und die Mikrofilaria aus Tucuman i n
Argentinien. Abhandlungen aus dem Gebiet der Auslandkunde, Hamburg Universität 26:
573-578, 1927
338. WAHLGREN M. The successful treatment of Dipetalonema perstans filariasis with
mebendazole. Annals of Tropical Medicine and Parasitology 76: 557-559, 1982
339. WARD HB. Gongylonema in the role of a human parasite. Journal of Parasitology 2 :
119-125, 1916
340. WELCH FH. On a species of filaria fo und in the interior of the vascular system of a dog:
relative to the filaria in the blood, and the ova and larvae of a nematode worm in th e
urine, of man. Lancet i: 336-338, 1873
341. WELCH FH. Haematozoa. Lancet i: 508, 1873

342. WELTY RF, LUDDEN TE, BEAVER PC. Dirofilariasis in man: report of a case from
the state of Washington. American Journal of Tropical Medicine and Hygiene 12 :
888-891, 1963
343. WERNER PC. Vermium intestinalium praesertim taeniae humano, brevis expositionis
continuatio, SL Crusium, Lipsiae, volume 1, part 2, pp 28, 1782
344. WHALEN GE, ROSENBERG EG, STRICKLAND GT, GUTMAN RA, CROSS JH,
WATTEN RH, UYLANGCO C, DIZON JJ. Intestinal capillariasis. A new disease of
man. Lancet i: 13-16, 1969
345. WHITE GF, DOVE WE. The causation of creeping eruption. Journal of the American
346. WHITE GF, DOVE WE. A dermatitis caused by larvae of the Ancylostoma caninum .
Archives of Dermatology and Syphilology 20: 191-200, 1929
347. WILDER HC. Nematode ophthalmitis. Transactions of the American Academy o f
Ophthalmology and Otorhinolaryngology 55: 99-109, 1950
348. WILLACH P. Sclerostoma apiostomum nov. sp. Ein neuer und gefährlicher Parasit der
Affen. Archiv für Wissenschaftliche und practische Tierheilkunde 17: 340-346, 1891
349. WOODRUFF AW. Toxocariasis. British Medical Journal ii: 663-669, 1970
350. WOODRUFF AW. Not an i nfection with adult Toxocara canis. British Medical Journal
283: 1124, 1981
351. WOODRUFF AW, THACKER CK, SHAH A I. Infection with animal helminths. British
352. WRIGHT KA. Observations on the life cycle of Capillaria hepatica (Bancroft, 1893)
with a description of the adult. Canadian Journal of Zoology 38: 167-182, 1961
353. YAMAGUTI S. Studies on the h elminth fauna of Japan. Part 35. Mammalian nematodes
II. Japanese Journal of Parasitology 9: 409-439, 1941
354. YEH LS. On a filarial parasite, Deraiophoronema freitastenti n. sp., from the giant
anteater Myrmecophaga tridactyla from British Guiana, and a proposed reclassification
of Dipetalonema and related genera. Parasitology 47: 196-205, 1957
355. YII CY, CHEN CY, FRESH JW, CHEN T, CROSS JH. Human angiostrongyliasi s
involving the lungs. Chinese Journal of Microbiology 1: 148-150, 1968
356. YOKOGAWA S. A human case of accidental parasitism of Diploscapter coronat a
(Cobb, 1893) Cobb, 1913. Zoological Magazine, Tokyo 48: 507-512, 1936
357. YORKE W, MAPLESTONE RA. The nematode parasi tes of vertebrates, J&A Churchill,
358. YOSHIMURA H, AKAO N, KONDO K, ONISHI Y. Clinicopathological studies on
larval anisakiasis, with special r eference to the report of extra-gastrointestinal anisakiasis.
359. ZEDER JG. Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer von J A E
Goeze mit Zusätzen und Anmerkungen herausgegeben von Zeder, Siegfried Lebrech t
Crusius, Leipzig, pp 320, 1800
360. ZUELZER W, APT L. Disseminated visceral lesions associated with extrem e
eosinophilia. American Journal of Diseases of Children 78: 153-181, 1949
361. ZUNE A. Urine chyleuses et hématochyleuses, Paris, pp 82, 1891
Chapter 28
MISCELLANEA
IMAGINARY WORMS AND PSEUDOPARASITES
Imaginary parasites, usually worms, have been dreamt up and claimed as the
cause of disease in many societies until, and including, recent times. Worm s
were frequently found in the viscera and tissues of animals killed for culinary
purposes so it was a logical step to assume that similar worms must occur in
humans and were likely to produce illness. It was not until autopsies of humans
became commonplace that erroneous ideas of fantastic parasites wer e
expunged. In addition to these imaginary parasites, which were purely an d
simply figments of the imagination, pseudop arasites were also described. These
arose from misguided interpretations of pathological changes such a s
coagulated blood or necrotic tissue or secondary infestation of human tissues
and excretions by non-parasitic organisms.
IMAGINARY PARASITES
Imaginary parasites are well-described in the ancient literature. Thus, Ra, the
sun-god of Egypt, was supposed to have fallen sick when a worm arose from
his sputum and bit on the heel (cited in 24). The Indian medical work, th e
Sushruta Samhita, written around the first century AD, alleged that there were
three types of worms living in humans. Th e first arose in the faeces and of these
there were said to be seven varieties - some of these were undoubtedly real. Six
worms were thought to arise in the sputum. They were all imaginary, bein g
thought to be hairy with spots and tails; it was considered that they fed on the
bone marrow and penetrated into the eyes, palate and ears. Finally, seve n
imaginary worms arose from the blood, some of which were believed to feed
on the roots of hairs which fell out as a consequence 93.
A number of imaginary worms are detailed below. Undoubtedly th e
imaginary worms which were most widely held to exist were the toothworms,
but a number of others were frequently alleged such as eyeworms, earworms,
nasal worms, corpse worms, umbilical worms and echo worms.
Toothworms
The belief that toothache and dental disease are caused by worms in or around
the teeth goes back to ancient times. Perhaps the earliest literary reference to
765
such parasites is in an Egyptian papyrus (Anastasi IV, 13.7) of the twentiet h

dynasty (c.1200-1100 BC) in which an unhappy official at a desert outpost is
recorded as complaining that a worm gnawed at this teeth 95. Such ideas were
also prevalent in Mesopotamia. An Assyrian tablet in the library o f
Asur-bani-pal (c.500 BC) mentions t oothworms and describes charms for their
removal. Moreover, the tablet described the origins of these worms and their
modus operandi:
After Anu made the heavens,
The earth made the rivers
The rivers made the canals
The canals made the marsh
The marsh made the Worm.
The worm came weeping unto Samas,
Came unto Ea, her tears flowing,
'What wilt thou give me for my food,
What wilt thou give me to destroy?'
'I will give thee dried figs and apricots.'
'Forsooth, what are dried figs to me, or apricots?
Set me amid the teeth and let me dwell in the gums,
That I may destroy the blood of the teeth,
And of the gums chew their marrow.
So shall I hold the latch of the door.'"(cited in 95)
Similarly, the Syriac Book of Medicine, written in the ninth century AD but
largely a translation of Galen's De locis affectis (second century AD), contains
prescriptions for the treatment of teeth with worms in them 101. Likewise, Scrib-
onius Largus, physician to the Roman emperor, Claudius, associated worm s
with dental disease in his De compositione medicamentorum 66. In the same
manner in the Indian text, the Sushruta Samhita, it was considered that dental
caries arose when the teeth were eaten by worms 93. Toothworms were also
generally accepted in China. For example, a writer of the Ming dynasty (16th
century AD) believed that worms recovered from patients with longstandin g
toothache had black heads whereas those seen in acute cases had red heads 64.
This concept that toothworms caused dental dise ase was accepted in Europe
until the eighteenth century and was recorded in various leechbooks and books
of herbal remedies 96. In the present century, such beliefs are still prevalen t
among the poorly-educated in many parts of the world. It seems likely that these
ideas arose spontaneously and independently in different places althoug h
Townend96 has suggested that this notion ma y have begun in the Nile valley and
spread from there to other communities.
A variety of techniques have been used down the ages in diverse places in
an attempt to deal with these mythical creatures. Many herbal remedies have
been employed but the pride of place goes to henbane ( Hyoscamus species).
The Assyrians recommended that it be p laced on a hollow tooth and Scribonius
Largus described fumigation with the smoke of its burning seeds in order t o
drive the worms out of decayed teeth. Similarl y, this formula was extolled in the
Miscellanea 767
Anglo-Saxon leechcraft:
For toothworms, take acorn meal and henbane seed and wax of all equally much,
mingle these together, work into a wax candle and burn it, let it reek into the mouth,
put a black cloth under it, then will the worms fall on to it. 31
Other plants which have been recommende d from time to time included myrtle,
tamarisk, sumach, leeks, onions, raisins and roses. A seventeenth centur y
English poem mentions come of these:
If in your teeth you hap to be tormented,
By means some little wormes therin do breed,
Which pain (if heed be tane) may be prevented,
By keeping cleane your teeth, when as you feede;
Burne Francomsence (a gum not evil sented),
Put Henbane into this, and Onyon seed,
And with a tunnel to the tooth that's hollow,
Convey the smoke thereof, and ease shall follow. 8
In many instances, it seems that when seeds wer e heated, they cracked open and
plant embryos were scattered and mistaken for worms. Meanwhile, hyo -
scyamine and related drugs, constituents of henbane, dulled the pain.
As well as plants, various small animals including worms, caterpillars ,
weevils, ladybirds and small b eetles were used to "cure" toothache. This seems
to have been based upon the principle of "similis similibus curantur", i.e. that
the administration of worms or some such would cure the disease caused b y
worms in the teeth. Thus, the Assyrian sufferer from toothache was recom -
mended to crush a caterpillar on the afflicted tooth while a Greek physicia n
suggested that earthworms boiled in oil cured toothache.
An alternative ploy was to invoke charms and incantations. This approach
was based upon the belief that toothworm infection was associated wit h
invasion and possession by a demon which could be driven out by invocation.
For example, the pagan Brandenburgians supplicated the moon:
Little moon, decrease,
Go away from us,
Little worm, go away
And do me no more harm.9
Many of the toothache incantations had a Christian flavour:
Abraham said to Jesus Christ
As they walked on the slope of Bethris:
'I have not the power of walking
Or of riding because of toothache'
Said Jesus Christ to Abraham:
'Toothache will not be in that head;
Out of the toothache! Out of the toothache!
Known in heaven, known on earth.
Known to thy King is thy disease.
Toothworms and toothache to be placed under the earth.' 10
Besides being spoken, charms were sometimes written on paper or parchment
and worn as an amulet.
Gradually, however, doubts grew about toothworms. Jacques Houllie r

(1498-1562) wondered whether they really existed and condemned th e
widespread practice of fumigations (cited in 52). Pierre Fauchard (1690-1761)
in his classical work on dental surgery described how he had tried to find these
worms and had failed. Others confirmed his observations and toothworm s
passed into the realms of mythology.
Eyeworms, Earworms and Nasal Worms
There have been many descriptions of worms in the orbital, aural and nasa l
cavities. Some of these may not have been imaginary at all as it is well-known
that flies may deposit eggs in these places from time to time and the resultant
maggots may have been mistaken for worms. Indeed, some of those in the eye
may have been true worms (Loa, Thelazia). Many, however, were imaginary
and have been described by numerous authors since the time of Galen. In the
case of the orbit, for example, blepharitis (inflammation of the eyelids) ma y
have caused crusts which had the appearance of parasites. Moreover, som e
enterprising quack "eye-specialists" have been known to breed fly larvae then
insert them into the conjunctival sac thus permitting their removal from tha t
site16.
Many techniques have been described for flushing worms out of thes e
domains and indeed may be the means of producing objects resembling worms.
Thus, the Syriac Book of Medicine remarked concerning:
Worms in the ears....boil strong onions in the urine of children, and drop the liquor
into the ears. Or pound and mix together sumach, goat's milk, rings of
pomegranates, and raisins with honey, heat the mixture and drop it into the ears. .
Or pour juice of absinthe and old oil which is cloudy into the ears and the worms
will come out.101
Another popular method for driving out the worms was fumigation and i s
described under toothworms.
Urine Worms
Macroscopic worms have rarely been passed in u rine but sometimes coagulated
blood in elongated form has been mistaken for worms.
Umbilical worms
This worm was thought to live within the umbilicus of small children and cause
weakness and failure to thrive. Its presence could be "proved" by fastening a
small fish to the umbilicus in the evening then noting whether some of it had
been "eaten" in the morning. In reality, parts of the fish had been rubbed off by
the movements of the child. Andry in 1741 recounted Ettmuller's technique for
eradicating such parasites. Half of a nutsh ell containing a mixture of honey with
Miscellanea 769
powdered glass and juniper is fastened to the umbilicus then "the worm comes
as usual and attracted by the honey eats of this mixture from which it dies" 3. A
rather similar worm was the "Amao" described by Lusitanius (1575-1642 )
which was supposed to live in the intestinal canal of children and graduall y
consume their strength so they died if the worm was not expelled by the proper
treatment72.
Corpse Worms
These worms were also sometimes known as "food worms" or "phthisi s

worms". In ancient China it was believed that up to 80,000 of these worm s
were present in each human body and that without them the human body could
not exist. It was believed that they began their life with the birth of their host.
Furthermore, they were thought to undergo transformations in their appearance
during six generations. For example, Ku Chin Yi T'ung Ta Chu'an described
and illustrated the following:
1. Worms of the first generation: resembled an infant with hair on its back, a
ghost or a frog.
2. Second generation: a ball of hair, a centipede, a lizard, a shrimp or a crab.
3. Third generation: a mosquito, an ant, a mantis, a hedgehog or a caterpillar.
4. Fourth generation: a ball of thread, a grub, the lungs of a pig or a snake.
5. Fifth generation: a hairless mouse.
6. Sixth generation: a tortoise, the t ail of a horse or a bird. Furthermore, it was
believed that worms of this generation had either wings or feet and could
therefore reinfect people at a distance of a thousand miles 64.
Echoing Worms
In ancient China, it was sometimes believed that people were made sick b y
echoing worms which were supposed to produce an echo when the parasitized
person spoke. These worms were thought to be expelled or killed when th e
relevant part of the Chinese pharmacop oeia was read and the appropriate herbs
taken. For similar reasons, some Chinese anthelmintic prescriptions required
that silence should be maintained while preparing the medicines otherwise the
worm may hear and not be expelled 54.
Furia infernalis (Höllenwurm, Mordwurm)
This parasite was listed by Linnaeus in his Systema Naturae and discussed by
a number of writers including Solander 90 and Pallas79 . The parasite was
supposed to be a very small worm, the thickness of a hair, yellowish-white in
colour with one dark end, and have a single row of minute spines. It wa s
thought to be carried by the wind and be found in northern Sweden, Lapland
and Russia. It was said to attack humans, horse s and cattle in summer and cause
a burning feeling like a mosquito bite. This was followed by the development
of a painless swelling, central necrosis and death within several hours to days.
It is likely that in fact the writers were des cribing a number of bacterial diseases
such as anthrax, glanders, tularaemia or plague 54.
PSEUDOPARASITES
Pseudoparasites seemed just as real as imaginary parasites. For example ,

Ambroise Paré (1510-1590), a famous French military surgeon, described and
illustrated numerous fantastic creatures that had allegedly developed i n
abscesses or had been passed from the gut. Thus, he cited a specime n
recovered from a patient by Benenius, a physician in Florence:
A worm the size of four fingers, with a red round head the size of a large weight; it
had a body covered with downy hair, a bifid tail in crescent shape and altogether four
feet, two before and two behind.80
In addition, many pseudoparasites wer e free-living animals that were thought
to be found in the human stomach and intestines , the urinary bladder, the female
genital tract, or in abscesses. These included frogs, salamanders, snakes ,
lizards, leeches and lice. They were supposedly vomited, passed in stool o r
urine, or escaped in some othe r way. Some found their way into human excreta
by chance while others were placed there by hysterics, mendicants o r
charlatans. For example, an Ascaris may look like a snake to the uninitiated .
Others are quite inexplicable in this way such as the extraordinary claims that
a Russian vomited a dog and that a young boy passed a pup in his faeces 58.
Normal or pathological human structures have al so been mistaken for worms.
These include the secretions of sebaceous glands 3, hydatidiform moles in the
vagina27 and even spermatozoa 69.
Besides members of the animal kingdom, plants have also been thought to be
worms. Thus, Seltzer of Strasbourg in a thesis described "worms" which h e
found in the stools of a 26 year old woman that turned out to be the seeds o f
Morus nigra 92.
PARASITOPHOBIA
Parasitophobia or, more properly, a delusion that a person is infected wit h

parasites was apparently first described in 1872 (cited in 104). Some patients are
convinced that they harbour parasites in the skin; these are usually confuse d
with entomological ectoparasites. Others are certain that they are infected with
internal parasites, frequently worms. This condition may be seen in the setting
of a primary psychiatric disorder or in conjunction with a variety of organi c
illnesses including vitamin deficiencies, chronic renal failure and toxi c
psychosis. Those with primary psychiatric disorders may have parasitophobia
as an isolated problem while in others it is part of a schizophrenic, depressive
or compulsive illness.
Miscellanea 771
Wykoff104 reviewed cases reported in the literature and added many of hi s

own. He remarked that this condition is seen most frequently between the ages
of 40 and 60 years and occurs more commonly in females. Response t o
treatment has been poor.
EARLY ILLUSTRATIONS OF WORMS
Very few worms parasitic in humans we re known when printing became estab-
lished in Europe in the latter half of the fifteenth century. Initially, illustrations
were produced with the aid of woodcuts but during the seventeenth centur y
copper engravings which permitted the renderin g of finer details were gradually
introduced. In the early nineteenth century the new technique of lithograph y
was adopted.
FIFTEENTH AND SIXTEENTH CENTURIES
Perhaps the first illustration of a parasitic worm is to be found in the Hortus

Sanitas of Jacob Meydenbach published in Ma in, Germany, in 1491. This book
had 1066 illustrations with one of them showing a man in a squatting position
from whose anus large worms, presumably Ascaris, were passing out (cited
in28). The first simple illustration of a tapeworm (without a head) was provided
by Cornelius Gemma in 1575 46. This picture was copied by many author s
including Aldrovandi 1, Spigelius (van der Spiegel) 91, Clericus 29 and Andry3. In
1596, The Dutch explorer van Lins choten illustrated the extraction of a Guinea
worm70.
SEVENTEENTH CENTURY
The liver fluke, Fasciola hepatica, was figured by Redi in 1668 82 then by
Ruyschius in 1691 86 and Bidloo in 1698 13. Velschius in 1674 showed Dracunc-
ulus medinensis protruding from various parts of the human body but gave no
details of the parasite 100. He also drew filariae obtained from birds. In 1683 ,
Edward Tyson illustrated the anatomy of Ascaris lumbricoides 97 then in the
same year he drew a Taenia saginata and reproduced the scolex of a dog tape-
worm98. In the following year, Redi described 108 different parasites an d
produced copper plates in wh ich he illustrated amongst other things Eustrong-
ylus gigas, Cysticercus pisiformis , the reproductive organs of Ascaris
lumbricoides, and the dog and cat tapeworms, each of the latter with a head 83.
In 1691, Tyson illustrated Cysticercus tenuicollis from the omentum of an
antelope99.
EIGHTEENTH CENTURY
Andry gave illustrations of fragments of Taenia and Diphyllobothrium in 17002

and again in subsequent editions of his book in 1718 and 1741 3. Clericus in
171529 copied the figures of previous authors in 14 plates. Included amongst
them was a reproduction of Enterobius vermicularis by Contoli who had re-
garded it as a minute fish. In 1762, Roederer and Wagler 84 provided a simple
drawing of Trichuris trichiura. A variety of worms were illustrated in 44 plates
by Goeze in 178248 and in 10 plates by Bloch in the same year 17
. In 1789,
Fischer drew Cysticercus cellulosae in the choroid plexus 42.
NINETEENTH CENTURY
Good illustrations of a number of worms were provided by Joerdens (1801) 58,

Brera (1811) 22 and Bremser (1819)20. The last author illustrated Coenurus and
Echinococcus. Owen drew the larvae of Trichinella spiralis in 183578 then
Dubini illustrated Ancylostoma duodenale in 184337. Schistosoma haemat-
obium was figured by Bilharz in 1852 14. Crude drawings of the worms sub -
sequently called microfilaria bancrofti and microfilaria volvulus were made by
Demarquay (1863) 36 and O'Neill (1875)77 , respectively. Clonorchis sinensis
was drawn by McConnell in 1875 73 then a figure of an adult Wuchereria was
published by Cobbold in 1877 30 from material provided by Bancroft.
UNORTHODOX MODES OF TREATMENT
Massage
Massage of the abdomen has been recommended for the treatment of intest-
inal worms in many countries but particularly in China. As a consequence of
this procedure, worms were supposed to be passed in the stools:
Abdominal pain in children accompanied by a palpable mass in the abdomen is due
to worms. In this case, no drug is necessary: simply advise the parents to massage the
abdominal mass for half a day. This kills the worms which will be passed out in the
faeces.25
Acupuncture
Acupuncture has been practised in China as a means of treating worms for
many years:
Heartache caused by the three kinds of worms is attended by profuse salivation and
inability to turn the body into a recumbent position. In this case, the pit of the stomach
is the proper place for acupuncture.56
This practice is based upon the theory that the inserted needles will transfe r
energy to different parts of the body along hypothetical lines or "meridians".
Moxibustion
In this procedure, cones of the plant Artemisia (worm-wood) are applied to
Miscellanea 773
the skin and ignited. The smouldering fire burns into the skin and produces a
blister. It was sometimes used in China as an anthelmintic measure 54.
Music
Music was advocated occasionally for the treatment of worms in Europe in
the eighteenth century. According to Goeze 48, tapeworms could be expelled by
the noise of a Jew's harp. Others believed that intestinal worms could sens e
sound and recommended the use of certain musical instruments to mollif y
tapeworms and thus relieve symptoms 21.
Magic
In diverse countries down the ages, magic in the form of incantations o r
charms has been invoked to induce the expulsion of intestinal worms. Many of
the incantations had quasi-religious overtones while charms were objects with
written or engraved magic signs or words.
THE MOON AND WORMS
For many centuries and in many parts of the world, the moon has been held to
have an influence on worms, particularly upon the efficacy of anthelminti c
therapy. One of the first authors to deal with this subject was Nicola s
Myrepsus, a Greek physician who lived in the thirteenth century. He advised
that anthelmintics be given only during the waning of the moon 76. Andry at the
beginning of the eighteenth century was sceptical at first about such an effect
but then, following an investigation, gave some credence to the phenomenon.
He treated 100 persons with intestinal worms during the days of the wanin g
moon and found that more than 80% were cured. In contrast, the result wa s
reversed if the therapy was given on the other days 2. Similarly, Hoffman55
advised giving anthelmintics when the moon changed its phase.
Such ideas were not confined to Europe. Some ea rly Chinese writers believed
that intestinal worms had their heads turned upwards during the first half of the
lunar month and downwards in the second half. Further, they thought tha t
anthelmintic therapy was more effective if the head of the worms was turned
upwards 54. In recent times in Ruanda in Africa, it has been the practice t o
administer anthelmintics when the moon is full 68.
Some authors believed that the moon also i nfluenced symptomatology. Rosen
de Rosenstein85 thought that the symptoms were worse in children wit h
tapeworm infections during the waning moon and at the time of the new moon.
Likewise, Wawruch 102 claimed that Taenia segments appeared in stools more
regularly at this period. Some authors contended that Ascaris was more likely
to be discharged around this time and believed that there may be a simila r
influence on Enterobius. Küchenmeister, who was infected with these las t
parasites, however, sought a relationship between the numbers of worm s
discharged and the phases of the moon but could find no connection 63.
WORMS AS THERAPEUTIC AGENTS
The roundworm, Ascaris lumbricoides, has from time time been a popula r
therapeutic device in both the Occident and the Orient. Pulverized, drie d
worms were commonly used by both the medical profession and the populace
at large in Europe as an anthelmintic. In China, worm extracts were recom -
mended for the treatment of a wide range of conditions such as ulcerativ e
blepharitis, painful ophthalmitis, anal fistula, cancrum oris and boils e.g. "An
Ascaris worm, washed clean, baked dry over a tile on a fire, and ground into a
powder will, when applied to pustules and furuncles, effect a quick cure" 26.
It was even used as an aphrodisiac:
Grind the above (Ascaris) into powder, mix with grease and roll into pills of the size
of barley seeds. Before coitus, introduce one pill into the urethra; it will help enlarge
and stiffen the penis and prolong its periods of erection. 89
WORMS AND IMMUNITY
In 1862, Casimir Davaine highlighted the phenomenon of natural resistance to

helminth parasites. he took ov a of the common roundworm of humans, Ascaris
lumbricoides, and fed them, first to a cow, then to rats. He failed subsequently
to find adult worms in the intestine of these animals and concluded that, i n
contrast to humans, they were not susceptible hosts to this parasite:
Eggs of A. lumbricoides develop outside the body of man, but the embryo only
hatches when it is brought by food or drink....in whichever animal supplies these
conditions, the egg hatches if it remains in the intestine long enough; however, the
embryo does not linger if the animal is not of the kind where the worm can acquire
its final form.35
The accumulation of such data led to the development of two important con-
cepts - the host specificity of a parasite and the parasite fauna characteristic of
a given host species. Both of these aspects interact and ultimately ar e
determined genetically. Despite over 100 years of investigation since the time
of Davaine, we are little wiser as to the reasons why these variations in hos t
responsiveness occur or as to what the mechanisms are by which suc h
responses are generated.
A variation on this theme is the effect of age on susceptibility to firs t
infection. This probably applies to human s although it has never been definitely
shown. This phenomenon was alluded to by Looss in 191171 then Ransom in
192181 observed that young chickens were infected easily with the gapeworm,
Syngamus trachealis, while old chickens were difficult to infect. Likewise, it
has been shown with a number of parasites that the sex of the host influences
the susceptibility to infection with male animals in general being more prone
to infection.
The idea of acquired immunity to a worm, i.e. the development of resistance
to a particular parasite following prior exposure was floated by Weinberg and
Julien in 1911 103. They carried out experiments on ascarid infections in horses
Miscellanea 775
and concluded that horses infect ed with a certain number of parasites gradually
immunized themselves against the actio n of the secretions of these worms. Five
years later, Fujinami in a paper entitled (in translation) "Immunity t o
macroparasitic disease: can it be acquired?" recorded the acquisition o f
immunity against Schistosoma japonicum in horses45. In 1921, the
development of acquired immunity against Trichinella spiralis was shown in
rats by Ducas38. Blackwell and Thompson in 1923 observed that immunit y
could be acquired by both man and animals against the larva of the tumbu fly,
Cordylobia anthropophaga, which causes cutaneous larva migrans 15. Whether
significant acquired immunity develops in most human helminth infections has
been a matter of intense debate ever since, with the probability being that i t
develops only to a limited degree 50. How worms manage to evade the host' s
responses and persist has been a subject of earnest but largely unproductiv e
speculation18. The possibility of developing vaccines against helminths has now
been floated for a number of years 6,32 but success has hitherto eluded everyone's
grasp.
The development of immune responses, particularly the appearance of anti-
bodies and skin reactivity has been put to diagnostic purposes for man y
decades. The era of immunodiagnosis in human helminthology was probably
ushered in by Isaac and von den Velden in 1904 when they reported th e
presence of a precipitin reaction in the serum of a person with Diphyllo-
bothrium latum infection and compared this with a negative in an uninfected
control individual57. In the same year, Fleckseder and von Stejskal 43
found
antibodies against Taenia saginata in the serum of immunized rabbits bu t
Langer65 could not find such antibodies in humans infected with T. solium or
T. saginata infections. In 1906, Ghedini described a complement fixation test
for antibody directed against fluid from human hydatid cysts 47. In the following
year, Fleig and Lisbonne 44 described a test for precipitating antibody i n
echinococcosis.
In 1911, Casoni described a skin test for echinococcosis in which delaye d
hypersensitivity reactions occurred in infected persons after intraderma l
injection of fluid obtained from a sheep hydatid cyst 23. Sophisticated
immunological techniques have been developed in recent years and are no w
frequently being employed in the immunodiagnosis of human helminthiases 7.
Reactions to ascarids were described by Miram, Cobbold, Huber, Leuckart,
Bastian, Railliet and many others in the nineteenth century. In 1910, Gold -
schmidt again described features r esembling hay fever after exposure to human
and horse Ascaris and recognized its allergic nature49. The relationship between
helminthiasis and the atopic d isorders, asthma, hay fever and eczema, has been
a thorny one for many years. Herrick in 1913 may have been the first t o
recognize an association between asthma and worm infection when he wrote:
Common to both bronchial asthma and Ascaris infection is an increase of the
eosinophils in the blood. One may well ask the significance of the eosinophilia in this
association.53
Paul Erlich had described these peculiar white cells in 1879 then Müller and
Rieder in 189175 observed that they were increased in number in hookwor m
infection. Similar findings were then made in other worm infections. Neverthe-
less, little attention was paid to this association until Johansson in 1967 59
discovered a new class of immunoglobulin (initially called IgND, now IgE) and
found that increased levels were seen in the serum of patients with asthma. In
the following year, he observed increased levels of the same antibody i n
Ethiopian schoolchildren with Ascaris infection60. Similar elevations were then
seen in a variety of helminth infections. These discoveries provided a further
nexus between helminthiasis and atopy. A number of hypotheses wer e
advanced including a belief that worms caused asthma, the concept that worm
infection ameliorated asthma, and the proposition that atopic individuals ar e
able to generate increased resistance to worms 51.
The first major textbook of helminth immunology was written in 1929 b y
Taliaferro who produced a 414 page work entitled The immunology of
parasitic infections "94. This was followed in 1941 by Culbertson with hi s
Immunity against animal parasites "33.
WORMS AND CANCER
Eli Metchnikoff, the generally-recognized discoverer of the phenomenon o f

phagocytosis, in his Harben Lectures of 1906 advanced the proposition tha t
there may be a relationship between entozoa, in particular intestinal worms, and
cancer:
Even in certain tumours the role of the entozoa would appear very probable....Might
not the entozoa serve as gates for entry for the hypothetical parasites of those
tumours?74
He drew attention to the recent studies of Borrel 19 who had described the
presence of intestinal worms in the centres of intestinal tumours of mice an d
had correlated cysticercosis and tumours in rats. Metchnikoff then went of to
advocate a campaign against intestinal worms in order to prevent cancer in the
same manner as the war which had just begun against disease-carryin g
insects74.
In 1913, Fibiger in Copenhagen claimed that a newly-recognized worm ,
Spirometra neoplastica (= Gongylonema neoplasticum), in rats from the West
Indies and South America caused cancer of the stomach and suggested tha t
cockroaches may be the intermed iate hosts39. He revived this idea in 1920 with
further studies40,41. Nevertheless, an editorial writer in the British Medical
Journal cautioned:
It must not be assumed that spontaneous tumours of rats and mice are commonly
caused by the ingestion of food containing Spiroptera neoplastica, still less that
cancers of higher animals and man are produced by a similar, indeed by any, parasite.4
Nevertheless, this idea was taken up by enthusiasm by Sambon and Bayliss
who, under the auspices of the Cancer Field Commission of the Tropica l
Disease Prevention Association, investigated the relationship betwee n
Miscellanea 777
Gongylonema and cancer in certain districts in Italy. This led to the concept of
"cancer houses" with the theory that Gongylonema was transmitted from
person to person by cockroaches, resulting in cancer 87. This hypothesis was
attacked by Leiper and a heated correspondence followed 11,67,88. In the event,
Leiper was proven correct when it was finally concluded that Fibiger's tumours
were in fact non-malignant 5.
Nevertheless, time has been a little kinder in favouring associations between
cancer and two parasites - Schistosoma haematobium and bladder cancer (see
chapter 8), and Clonorchis sinensis and carcinoma of the bile ducts (se e
chapter 6)
THE GOD, "VERMINUS"
The Romans apparently had a god of worms and worm diseases name d
"Verminus". The little that is known about this deity derives from an inscription
on an altar found near Rome in 1876. The inscription said:
"Vermino
A. Postumius A.F.A.N Albi
Duovir lege Plaetoria"
which has been translated as:
"To Verminus
Aulus Postumius Albinus, son of Aulus
grandson of Aulus Duovir by the Plaetorian law"
Apparently, the increasing seriousness of worm infections had caused thi s
shrine to be erected and dedicated by the consul, Aulus 54.
REFERENCES
1. ALDROVANDI U. De animalibus insectis libri septem denuo impressum, Ferronius ,
Bononiae, pp 767, 1602
2. ANDRY R. De la génération des vers dans le corps de l'homme. Avec trois lettres sur les
sujets des vers, les deux premières....par M. Nicolas Hartsoeker et l'autre....par M .
Georges Baglivi, Laurent d'Houry, Paris, pp 468, 1700. An account of the breeding o f
worms in human bodies etc., translated by H Rhodes and A Bell, pp 266, 1701
3. ANDRY R. De la génération des vers dans le corps de l'homme, third edition, Lauren t
d'Houry, Paris, pp 1190, 1741. Partly translated in 54
4. ANONYMOUS. Helminths in cancer. British Medical Journal i: 777-778, 1920
5. ANONYMOUS. Fibiger's tumour of the rat's stomach. Lancet i: 735-736, 1938
6. ANONYMOUS. Immunisation against helminths. Lancet i: 685, 1960
7. ANONYMOUS. Immunodiagnosis in parasitic diseases. British Medical Journal 283 :
1349-1350, 1981
11. BAYLISS HA. Gongylonema and cancer. British Medical Journal ii: 503-504, 1926
12. BERDOE E. The origin and growth of the healing art. A popular history of medicine in
all ages and countries, Swan Sonnenschein and Co., pp 509, 1893
13. BIDLOO G. Observatio, de an imalculis, in ovino aliorumque animantium hepate detectis,

J Luchtmans, Lugduni Batavorum, 1698
14. BILHARZ T., von SIEBOLD CT. Ein Beitrag zur Helminthographia humana, au s
brieflichen Mittheilungen des Dr. Bilharz in Cairo, nebst Bemerkungen von Prof. C. Th.
von Siebold in Breslau. Zeitschrift für wissenschaftliche Zoologie 4: 53-76, 1852-1853
15. BLACKLOCK DB, THOM PSON MG. Study of tumbu-fly, Cordylobia anthropophaga
Gruneberg in Sierra Leone. Annals of Tropical Medicine and Parasitology 17: 443-510,
1923
16. BLANCHARD R. Charlatans et pseudo-parasites: les "vers des yeux". Bulletins de l a
17. BLOCH ME. Abhandlung von der Erzeugung der Eingeweidewürmer und den Mittel n
wider dieselben, Sigismund Friedrich Hesse, pp 54, 1782
18. BLOOM B. Games parasites play: how parasites evade immune surveillance. Nature 279:
21-26, 1979
19. BORREL A. Tumeurs cancére uses et helminthes. Bulletin de l'Académie de Médecine de
Paris 41: 141-144, 1906
Aertze. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. Nebst eine m
Anhang über Pseudo-helminthen, Carl Schaumburg et Comp., Wien, pp 248, 1819
21. BRERA VL. Medizinische-practische Vorlesungen ueber die vornehmste n
Eingeweidewürmer des menschlichen lebenden Koerpers und die sogennante n
Wurmkrankheiten. Aus dem Italienischen uebersetz und mit Zusaetzen versehen von FA
Weber, Breitkopf und Haertel, Leipzig, 1803
22. BRERA VL. Memorie fisico-mediche sopra i principali vermi del corpo umano vivente
etc., Antonio Ronna, Crema, pp 452, 1811
23. CASONI T. La diagnosa biologica dell'echinococcosi umana mediant e
l'intradermoreazione. Folia Clinica Chemica e Microscopica 4: 5-16, 1911
24. CASTIGLIONI A. A history of medicine. Translated from the Italian and edited by E.B.
Krumbhaar, second edition, Alfred A. Knopf, New York, pp 1192, 1947
25. CH'EN FU-CHENG (A comp ilation of pediatrics.), 1750. In Chinese. Partly translated in
54
26. CH'I FAND LEI CHU (A classified collection of unusual prescriptions.) In Chinese .
27. delle CHIAIE S. Compendio di elintografia umana, second edition, Dalla Stamperia e
Cartiera del Fibreno, Napoli, 1833
28. CHOULANT L. Graphische Icunabeln für Naturgeschichte und Medicin, Leipzig, 1858
29. CLERICUS D (LE CLERC). Historia naturalis et medica latorum lumbricorum intr a
hominem et alia animalia, nascentium etc., Fratres de Tournes, Genevae, pp 449, 1715.
A natural and medicinal history of worms bred in the bodies of men and other animals etc.,
translated by J Browne, printed for J Wilcox at the Green-Dragon, Little Britain, pp 436,
1721
30. COBBOLD TS. Discovery of the adult representative of microscopic filariae. Lancet ii:
495-496, 1877
31. COCKAYGNE O. Leechdoms, wort cunning and starcraft of early England etc. ,
Longman, London, three volumes, 1864-1866
32. COX FE. Specific and nonspecific immunisation against parasitic infections. Nature 273:
623-626, 1978
33. CULBERTSON JH. Immunity ag ainst animal parasites, Columbia University Press, New
York, pp 274, 1941
34. DAVAINE C. Traité des entozoaires et des maladies vermineuses de l'homme et de s
animaux domestiques, J B Baillière et fils, Paris, pp 838, 1860
35. DAVAINE CJ. Nouvelles recher ches sur le développement et la propogation de l'ascaride
lombricoïde et du trichocéph ale de l'homme. Comptes Rendus Hebomadaires des Séances
de l'Académie des Sciences, série 3, 4: 261-265, 1862. Translated in 62
Miscellanea 779
36. DEMARQUAY JN. Helminthologie. Gazette Médicale de Paris 18: 665-667, 1863
37. DUBINI A. Nuovo verme intestinal umano ( Agchylostoma duodenale ) costituente un sesto
genere dei nematoidei proprii dell'uomo. Annali Universali di Medicina 106: 5-13, 1843
38. DUCAS R. L'immunité dans la trichinose. Thèse, Paris, Jouve et Cie, 1921
39. FIBIGER J. Ueber eine durch Nematoden ( Spiroptera sp. n) hervorgerufene papillomatöse
und carcinomatöse Geschwulstbildung im Magen der Ratte. Berliner klinisch e
Wochenschrift i: 289-298, 1913
40. FIBIGER J. Sur la transmission aux rats de la Spiroptera neoplastica (Gongylonema
neoplasticum). Méthode pour la production expérimentale du cancer. Comptes Rendu s
41. FIBIGER J. Carcinome spiroptér ien de la langue du rat. Comptes Rendus Hebdomadaires
42. FISCHER JL. Taeniae hydatigenae in plexu chorioideo nuper inventae historia etc., J
Haasio, Lipsiae, 1789
43. FLECKSEDER R, von STEJSKAL K. Biologische Reaktionen mit Bandwurmextrakt.
Wiener klinische Wochenschrift 17: 793, 1904
44. FLEIG C, LISBONNE M. Recherches sur un sérodiagnostic du kyste hydatique par l a
méthode des precipitins. Comptes Rendus Hebdomadaires des Séances et Mémoires de
la Société de Biologie 62: 1198-1201, 1907
45. FUJINAMI A. (Immunity to macroparasitic disease, can it be acquired?), 1916. I n
Japanese. Abstracted in China Medical Journal 31: 81, 1917
46. GEMMA C. De naturae divinis characterismis seu raris et admirandis etc., Antverpiae, pp
225, 1575
47. GHEDINI G. Ricerche sul siero di sangue di individuo affetto da cisti da echinococco e
sul liquid in essa contenuto. Gazzetta degli Ospedali et delle Cliniche 27: 1616-1617, 1906
48. GOEZE JA. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper ,
49. GOLDSCHMIDT R. Die Aska risvergiftung. Münchener medicinische Wochenschrift 57:
1991-1993, 1910
50. GROVE DI. Immunity in human helminth infections. In, Biology and control o f
endoparasites, L.E. Symons, A.D. Donald and J.K. Dineen (Editors), Academic Press ,
Sydney, pp 375-400, 1982
51. GROVE DI. What is the relationship between asthma and worms? Allergy 37: 139-148,
1982
52. GUERINI V. A history of dentistry from the most ancient times until the end of th e
eighteenth century, Lea and Febiger, Philadelphia, pp 355, 1909
53. HERRICK WW. Experimental eosinophilia with an extract of an animal parasite: it s
relation to anaphylaxis and certain clinical features. Archives of Internal Medicine 11 :
163-186, 1913
55. HOFFMANN FH. Opera omnia physico-medica etc. et supplementa, Genevae, pp 508,
1740-1753
56. HUAND-FU MI. (The classics of acupuncture and moxibustion.) In Chinese. Partl y
translated in 54
57. ISAAK S, von der VELDEN. Eine spezifische Präzipitinreaktion bei Bothriocephalus
latus behergergenden Menschen. Deutsche medizinische Wochenschrift 30: 982, 1904
58. JOERDENS JH. Entomologie und Helminthologie des menschlichen Koerpers etc., G A
Grau, Hof, two volumes, pp 473, 1801-1802
59. JOHANSSON SG, BENNICH H. Immunological studies of an atypical (myeloma )
immunoglobulin. Immunology 13: 381-394, 1967
60. JOHANSSON SG, MELLBIN T, VAHLQUIST B. Immunoglobulin levels in Ethiopian
pre-school children with special reference to high concentrations of IgE (IgND). Lancet
i: 1118-1121, 1968
61. KANNER L. Folklore of the teeth. Dental Cosmos 67: 259, 1926
group Entozoa, translated by E Lankester, The Syndenham Society, London, pp 452, 1857
64. KU CHIN YI T'UNG CHU'AN. Cited in 54
65. LANGER J. Zur Frage der Bildung spezifischer Antikörper im Organismus vo n
Bandwurmwirten. Münchener medizinische Wochenschrift 52: 1665-1665, 1905
66. LARGUS S. Cited in 52
67. LEIPER RT. Gongylonema and cancer. British Medical Journal ii: 504, 1926
68. LESTRADE. La médecine indigène au Ruanda. Académie Royale des Science s
Coloniales. Classe des sciences morales et politiques. Nouvelle série, tome VIII, fasc. l.
(Ethnographie), Bruxelles, 1955. Cited in 54
69. LEUCKART FS. Zoologische Bruckstucke, Stuttgart, Freiburg, three volumes, 1819
70. van LINSCHOTEN JH. Vera descriptio regni pars Indiae orientalis in qua Johann .
Hugonis Lintscotani navigatio in orientem etc., Teucrides Annaeus Lonicer, Frankfort ,
1599. Original Dutch edition, 1596
71. LOOSS A. The anatomy and life h istory of Agchylostoma duodenale Dub. A monograph.
Part II. The development in the free state. Translated from the German by M Bernhard.
Records of the School of Medicine, Egyptian Ministry of Education 4: 163-613, 1911
72. LUSITANIUS. Cited in 29
73. McCONNELL JF. Remarks on the anatomy and pathological relations of a new species
of liver-fluke. Lancet ii: 271-274, 1875
74. METCHNIKOFF E. The Harben lectures for 1906. II. The hygiene of the alimentar y
canal. Lancet i: 1554-1555, 1906
75. MÜLLER HF, RIEDER H. Ueber vorkommen und klinische Bedeutung der eosinophilen
Zellen, Ehrlich, im circulirenden Blute des Menschen. Deutsche Archiv für klinisch e
Medicin 48: 96-121, 1891
76. MYREPSUS N. De antid., sect. I, cap. 298. Cited in 35
77. O'NEILL J. On the presence of a filaria in "craw-craw". Lancet i: 265-266, 1875
78. OWEN R. Description of a microscopic entozoon infesting the muscles of the huma n
body. London Medical Gazette 16: 125-127, 1835
79. PALLAS PS. Einige Erinnerungen die Bandwürmer bettrefend: in Beziehung auf de s
zwölfte und vierzehnte Stück des N aturforschers. Neue nordische Beyträge physickalische
und geographische Erd- und Volkerbeschriften 1: 113-131, 1781
80. PARÉ A. Les oeuvres d'Amroise Paré, onzième edition. Avec les voyages qu'il a faits en
divers lieux: et les pourtraits & figures, tant l'anatomie que des instruments de chirurgie,
& de plusiers monstres, Chez Pierre Rigaud, Lyon, pp 854, 1651. Partly translated in 54
81. RANSOM BH. United States Department of Agriculture Bulletin No. 939, 1921
82. REDI F. Esperienze intorno alla generazione del'insetti, Carlo Dati, Firenze, pp 177, 1668
83. REDI F. Osservazione intorno agli animali viventi che si trovano negli animali viventi ,
Piero Matini, Firenze, pp 244, 1684
84. ROEDERER JG, WAGLER CG. De morbo mucoso liber singularis, quem nupe r
speciminis inauguralis loco ediderunt, B Bossigelium, Goettingae, pp 211, 1762
85. ROSEN de ROSENSTEIN N. Traité des maladies des infans etc. Traduit du Suédois par
Le Febvre de Villebrune, P G Cavelier, Paris, pp 582, 1778
86. RUYSCHIUS (RUYSCH) F. Observationum anatomico-chirurgicarum centuria etc., H
et T Boom, Amstelodami, pp 138, 1691
87. SAMBON LW. Observations and researches o n epidemiology of cancer made in Holland
and Italy (May-September, 1925). Journal of Tropical Medicine and Hygiene 29 :
Miscellanea 781
233-287, 1926
88. SAMBON LW. Refutation of statements made by Professor R.T. Leiper M.D., D.Sc.,
F.R.S., concerning African schistosomes, "American Gongylonemes", zoo vermin and
Italian cancer houses. Journal of Tropical Medicine and Hygiene 29: 314-322, 1926
89. SHÊH SHENG TSUNG YAO. (Essentials of Hygiene. A curious book on coitus.), 1638.
In Chinese. Partly translated in 54
90. SOLANDER DC. Furia infernalis, vermis et ab eo concitari solitus morbus, descripti .
Nova Acta Regiae Societatis Scientarum Upsaliensis 2: 44, 1775
91. SPIGELIUS (van der SPIEGEL) A. De lumbrico lato liber cum eiusdem lumbrici icone
et notis, L Pasquati, pp 88, 1618
92. SULTZER C. Dissertation sur un ver intestinal nouvellement découvert et décrit sous le
nom bicorne rude, JA Fischer, Strasbourg, pp 52, 1801
93. SUSHRUTA SAMHITA. An English translation, edited by Kaviraj Kunja La l
Bhishagratna, Calcutta, 1911
94. TALIAFERRO WH. The immunology of parasitic infections, The Century Co, Ne w
York, pp 414, 1929
95. THOMPSON RC. Assyrian medical texts, Pro ceedings of the Royal Society of Medicine
19: 29-78, 1926
96. TOWNEND BR. The story of the toothworm. Bulletin of the History of Medicine 19:
37-58, 1944
97. TYSON E. Lumbricus teres, or some anatomical observations on the round worm bred
in human bodies. Philosophical Transactions of the Royal Society 13: 153-161, 1683
98. TYSON E. Lumbricus latus, or a di scourse read before the Royal Society, of the joynted
worm etc. Philosophical Transactions of the Royal Society 13: 113-144, 1683
99. TYSON E. Lumbricus hydropicus: or an essay to prove that Hydatides often met with
in morbid animal bodies, are a species of worm, or imperfect animals. Philosophica l
Transactions of the Royal Society 17: 506-510, 1691
100. VELSCHIUS GH. Exercitatio de Vena Medinensi, ad mentem Ebnsinae sive dracunculis
veterum etc., Theophili Goebelli, Augustae Vindelicorum, pp 456, 1674
101. WALLIS BUDGE EA. Syriac anatomy, pathology and therapeutics or, "The book o f
medicines etc.", two volumes, Oxford University Press, London, 1913
102. WAWRUCH. Réflexions tirées de deux cent six o bservations de ténias. Gazette Médicale
de Paris 9: 633, 1842. Extracted from Medizin Jahrbuch des Oesterreich Staates
103. WEINBERG M, JULIEN A. Sub stances toxiques de l'Ascaris megalocephala . Comptes
1911
104. WYKOFF RE. Delusions of parasitosis: a review. Reviews of Infectious Diseases 9 :
433-437, 1987
Chapter 29
BIOGRAPHIES
ALEIXO de ABREU (1568-1630)

Aleixo de Abreu was born in Alcáçovas, Portugal in 1568. He entered Evora
University and graduated with a bachelor of arts degree in 1583. He then studied
medicine at Coimba University and graduated seven years later. He first practised in
Lisbon then in 1594 he was appointed physician to the governor of Angola. In 1604 he
went to Brazil with the governor of that province, Diogo Botello. During this period he
developed dysentery and jaundice which necessitated his return to Lisbon in 1606. In
1612 he was appointed physician to the treasury officials, a position which he held until
1629. During a serious illness in 1621 he began writing his Tratado de las siete
enfermedades etc. (Treatise of the seven diseases), the first text on tropical medicine.
It was published in 1623, partly in Latin and partly in Spanish, and described, amongst
other things, the worms now known as Trichuris trichiura and Dracunculus
medinensis. He died in Lisbon in 1630.
NICOLAS ANDRY de BOISREGARD (1658-1742)

Andry was born in Lyons, France in 1658. He studied medicine then later became
professor of philosophy and dean of the faculty of medicine at the University of Paris.
He was a man of letters and made notable contributions to both the humanities and
science. He wrote the first textbook of orthopaedics, and indeed coined the word which
is derived from the Greek words referring to straightening and the rearing of children.
He also wrote on phlebotomy and helminthology, the latter book being an attempt to
refute the doctrine of the spontaneous generation of worms. He died in 1742, one year
after the last edition of his textbook on helminths. (Plate 1)
ARETAEUS THE CAPPADOCIAN (c. 50 AD)

Aretaeus was born in the Roman province of Cappadocia in Asia Minor, probably in
the first century AD. He studied medicine at Alexandria in Egypt and became a prolific
writer. His work, De causis et signis morborum [On the causes and signs of diseases],
however, is the only extant treatise. Aretaeus was the first person to describe cardiac
murmurs and may have been the first to practise direct auscultation of the chest. (Plate
2)
DOUGLAS MORAY COOPER LAMB ARGYLL-ROBERTSON (1837-1909)

Argyll Robertson was born in Edinburgh, Scotland, the son of an ophthalmic surgeon
and lecturer in the medical school. He was educated at the Edinburgh Institution, at
Neuwied in Germany, and at the Universities of Edinburgh, St. Andrews and Berlin. He
graduated in medicine from St. Andrews in 1857 and became a fellow of the Royal
College of Surgeons of Edinburgh in 1862, having studied ophthalmology under von
Arlt in Prague and von Graefe in Berlin. From the beginning of his career, he devoted
himself exclusively to ophthalmic surgery, becoming assistant ophthalmic surgeon
783
(1867) then ophthalmic surgeon (1870) to the Edinburgh Royal Infirmary until 1897
when he became consulting surgeon. He investigated the role of an extract of the Cal-
abar bean (physostigmine) in the treatment of certain eye conditions and in 1869 and
1879 published papers describing the pupillary changes in tabes dorsalis (syphilis) which
now bear his name (Argyll Robertson pupil). He described the appearances of the adult
Loa loa. He became president of the Royal College of Surgeons of Edinburgh in 1886
and was awarded the honorary degree of LL.D. by the University of Edinburgh in 1897.
He married Miss Fraser in 1882 but had no children. He was a keen golfer, archer,
shooter and fisherman. When he retired in 1904, he retired to the island of Jersey on
account of its milder climate. In November 1908 he travelled to India to visit an old
friend, the Thakur of Gondal. He died suddenly in Gondal on 3 January 1909. (Plate 3)
ARISTOTLE (384-322 BC)

Aristotle was born in Stagira, Macedonia, the son of a Greek physician. At the age of
17 he became a pupil of Plato at the Academy in Athens. He was a tutor to Alexander
the Great who probably endowed a museum which allowed Aristotle to collect botanical
and zoological specimens. Around 347 BC he moved to Asia Minor and married
Pythias. After a period on the island of Lesbos, he returned to Athens in 335 BC and set
up a school in a grove sacred to Apollo Lyceus, the school becoming known as the
"Lyceum". He wrote many works on a wide range of subjects including logic, biology,
psychology, physics, metaphysics, ethics, political science, aesthetics and literary
criticism. In 323 BC he was forced to leave Athens because of anti-Macedonian feelings
and he died at Chalcis in Euboea in the following year.
BAILEY KELLY ASHFORD (1873-1934)

Ashford was born in Georgetown, USA, the son of the professor of surgery there. He
joined the United States Army and graduated from the Army Medical School and
Georgetown University. The Spanish-American War took him to Puerto Rico where he
met then married Maria Asuncion Lopez, daughter of the Marques de Villar, by whom
he had a son and two daughters. He was at Ponce when a devastating hurricane struck
and the Army was left to succour 800,000 persons. It was this that led him to define
hookworm infection as the cause of much anaemia on the island. Ashford rose to the
rank of colonel in the United States Army. He spent many years trying to establish a
school of tropical medicine in Puerto Rico. He was eventually successful in 1926 and
was appointed professor of tropical medicine and mycology, a post which he held until
his death. Meanwhile, he had been a member of the Rockefeller Commission (on
hookworm) to Brazil in 1916 and had sailed with the American Army to France in 1917.
Subsequently, he became particularly interested in sprue and in candidiasis. He died in
1934 at the age of 61 years. (Plate 4)
MAX ASKANAZY (1865-1940)

Askanazy was born in Stalliponen, Germany in 1865. He studied medicine at Kön-
igsberg (Kaliningrad), now in the USSR (Lithuania), where he later became professor
of pathology. In 1905 he was appointed director of the Institute of Pathology in Geneva,
Switzerland. He held this post for 35 years until his death in 1940.
Biographies 785
EDWARD LEICESTER ATKINSON (1882-1929)

Atkinson was born in England in November 1882. He studied medicine at St. Thom-
as's Hospital, London and qualified as a member of the Royal College of Surgeons and
a licentiate of the Royal College of Physicians in 1906. He joined the Royal Naval
Medical Service as a surgeon in 1908. He was medical officer to Captain Scott's ill-fated
expedition to the South Pole in 1910, was left in charge of the base camp, and led the
rescue team which found Scott's last remains. He was promoted to Staff Surgeon in
1913, and went with Leiper on his expedition to the Orient in 1914. Atkinson was
wounded severely in July 1917 while serving with the Howitzer Brigade in France. In
May 1918 he was awarded the Distinguished Service Order. In September 1918 he was
awarded the Albert Medal for gallantry in saving life at sea following an explosion on
H.M.S. Glatton ; he was gravely injured in the process and his life was despaired of for
some time. He was a keen bacteriologist and parasitologist; he invented a method of
disinfecting and deodorizing urinals in ships. His official biography recorded that his
zeal, tact, kindly disposition and consideration made him a friend to all, and that his
cheery optimism, versatility, pluck and determination brought him through many
vicissitudes. In November 1928, he was placed on the retired list as medically unfit with
the rank of Surgeon Captain, but died at sea on 2 February 1929 at the age of 46 years.
(Plate 5)
ERWIN OTTO EDUARD von BAELZ (1849-1913)

Baelz was born in Bietigheim in Württemberg, (in present-day West) Germany on 13
January 1849, the son of a builder. From his youth, he was interested in natural history
and travel and became fluent in French and English and read Italian and Spanish. He
began tertiary studies at the University of Tübingen at the age of 17, but in 1869 he
transferred to the University of Leipzig. At the outbreak of the FrancoPrussian War
(1870), he joined the artillery and became a medical auxiliary. Baelz returned to Leipzig
then graduated in medicine in 1872. Subsequently, he studied pathology at the Leipzig
Polyclinic, went to Vienna where he became an assistant in pathology, then returned to
Leipzig where he worked for four years under Wunderlich who at that time had the most
famous clinic in Germany. While working there, he came in contact with some Japanese
post-graduate students, and in April 1876 he went to the newly-created medical
department at Tokyo Imperial University, Japan, where he later became professor of
medicine. He married a Japanese woman and remained in that country for the next 29
years. Baelz made original observations on paragonimiasis, clonorchiasis, beriberi and
leprosy. He was decorated both in Japan and in Germany. Von Baelz returned to
Germany in 1905 and died in Stuttgart on 31 August 1913 at the age of 64 years. (Plate
6)
JOSEPH BANCROFT (1836-1894)

Bancroft was born on a farm at Stretford, near Manchester, England, the only son of
Peter Bancroft and Mary Lane in 1836. He began his medical training as an apprentice
of Dr Jeremiah Shaw in Sale, Cheshire. He then continued his studies at the Manchester
Royal School of Medicine and Surgery and at the Manchester Royal Infirmary. He
qualified as a member of the Royal College of Surgeons and a licentiate of the Royal
Society of Apothecaries in London in 1859 then received a doctorate in medicine from
the University of St Andrews. While still a medical student he married Ann Oldfield by
whom he had three children, one daughter dying in infancy. Following graduation he
practised in Nottingham for five years. He was a keen naturalist and was for three years
president of the Nottingham Naturalists' Society. Because of illness (possibly nephrotic
syndrome), he moved to the warmer climate of Queensland, Australia in 1864, settling
on the outskirts of Brisbane in 1867. He became visiting surgeon to the Brisbane
Hospital in 1867 then in 1868 he was appointed house surgeon, a post similar to that of
medical superintendent. Two years later he resigned this post and became a visiting
surgeon once more and developed a thriving private practice. He wrote on a variety of
clinical topics, especially snake-bite, tick paralysis, typhoid fever, leprosy and filariasis.
He was a keen horticulturist and was intrigued by the medicinal possibilities of
Australian plants. He was interested in public health and was for a number of years
Health Officer for Brisbane. He was said to be a kindly and approachable man, yet on
the other hand it has been remarked that he was direct of speech and at times could be
rather irascible. He died suddenly from a myocardial infarction on 16 June 1894 aged
58 years. (Plate 7)
THOMAS LANE BANCROFT (1860-1933)

Bancroft was born in Nottingham, England, the son of Dr Joseph Bancroft and Ann
Oldfield in 1860. When he was four years of age he migrated to Brisbane, Australia with
his family aboard the "Lady Young". He was educated at Brisbane Grammar School
then in 1877 went with his father to Britain to begin training as a medical student in
Edinburgh. Following his graduation in 1883, he returned to Brisbane and entered
practice. He practised there until 1894 when he moved to Deception Bay 40 kilometres
north of Brisbane where he managed a property inherited from his father that included
a meatworks and experimental farm. When the meatworks closed in 1904 he returned
to Brisbane. While at Deception Bay, he had considerable time to devote to research.
Like his father, he was a devoted, talented and many-sided doctor-naturalist, making
many contributions to knowledge of the Australian fauna and flora. He died in 1933.
(Plate 8)
CLAUDE HEMAN BARLOW (1876-1969)

Barlow was born in Lyons, Michigan, United States of America and graduated with
a doctorate in medicine from Northwestern University in l906. He married Grace Haw-
ley in the following year and had four daughters. In 1908, he went to Huchow, China
as a medical missionary for the Baptist Foreign Missions Society. From 1911-1925 Bar-
low was located mostly in Shaohsing (= Shaoxing), although he had a spell (as a patient)
in a tuberculosis sanatorium at Saranac Lake, New York in 1913 and attended the
London School of Tropical Medicine in 1914. He was released by the Society from his
other duties in 1922 in order to pursue his researches on fasciolopsiasis in China using
facilities provided by Johns Hopkins University. Between 1925 and 1928 he was
appointed port physician for the Chinese Maritime Customs in Ningpo (= Ningbo). In
1929 he joined the International Health Division of the Rockefeller Foundation and
went to Egypt where he worked on the snail control of schistosomiasis. Barlow remain-
ed with the Foundation for the next 21 years, apart from a period spent in South Africa
where he also was concerned with schistosomiasis control. He died in New York State,
USA, on 9 October 1969 aged 92 years.
HENRY CHARLTON BASTIAN (1837-1915)

Bastian was born at Truro in Cornwall, England on 26 April 1837. He received his
Biographies 787
education at University College, London graduating with the degree of master of arts in
1861, bachelor of medicine in 1863 and doctor of medicine in 1866. Shortly after
graduation he was elected assistant physician to St Mary's Hospital and lecturer in
pathology at its Medical School. In 1867 he was appointed professor of pathological
anatomy then in 1887 professor of medicine and clinical medicine at University College
Hospital, a post which he held until 1897. He was also a physician to the National
Hospital for the Paralysed and Epileptic from 1882-1912. He was elected a fellow of the
Royal Society in 1868 when only 31 years of age for his contributions to parasitology,
having published two monographs on free-living nematodes in which he described 100
new species and investigated their physiology. His middle years were devoted to
neurology but in his early and later years he was primarily concerned with the origin of
life, being a staunch advocate of heterogenesis (spontaneous generation). This latter
story is a remarkable example of misguided moral courage and scientific enthusiasm in
the face of hopeless odds. He died at home on 17 November 1915 at Chesham Bois,
Buckinghamshire aged 78 years leaving his widow, Julia (née Orane), three sons, and
a daughter. (Plate 9)
ARTHUR RÉNÉ JEAN BAPTISTE BAVAY (1840-?)

Bavay was born on 29 April 1840 at Lamballe in Côtes de Nord, France, the son of
François Bavay, a doctor, and his wife, Marguerite. He studied pharmacy between 1858
and 1860 and was appointed in the French Navy as pharmacist third class (1860),
pharmacist second class (1864) and pharmacist first class (1869), serving in Brest and
Lorient in France, New Caledonia in the South Pacific (1864-1869), and Guadeloupe
in the Caribbean (1869-1875). In 1868 he married Anna Coz. In 1875 he was appointed
professor of botany and natural history in Toulon. In 1877 he was made a Chevalier de
la Légion d'Honneur (knight of the legion of honour). In 1881 he was appointed
professor of pharmacy and therapeutics in Brest, becoming chief pharmacist in 1883.
In 1896 he was transferred to the Conseil Supérieur de Santé (high council of health).
He remained there until he retired in 1902. It is uncertain when he died.
PAUL C BEAVER (1905-)

Beaver was born in Indiana in the United States of America in 1905. He obtained the
degrees of master of science and doctor of philosophy from the University of Illinois. He
joined the department of parasitology at Tulane University in New Orleans, Louisiana
in 1945, rising to the rank of professor of parasitology and director of the university's
international centre for medical research in Cali, Colombia. He served as editor of the
"American Journal of Tropical Medicine and Hygiene" for twenty years.
(Plate 10)
PIERRE JOSEPH van BENEDEN (1809-1894)

PJ van Beneden was born on 19 December 1809 at Mechelen (Malines) in Belgium.
He graduated in medicine in 1831 from the University of Louvain having first been ap-
prenticed to Louis Stöffels, a great collector of natural history specimens, who inspired
van Beneden to become a zoologist. In 1835 he was appointed professor of zoology and
comparative anatomy at the Catholic University of Louvain then became curator of the
Natural History Museum in that city. In 1843 he established, at his own expense, a
marine aquarium which was one of the first of its kind. Van Beneden made many
contributions to the knowledge of the biology of parasitic worms. He was much
esteemed for his high character and was the recipient of many honours, including being
elected president of the Royal Belgian Academy in 1881, a foreign corresponding
member of the Royal Society of Britain, and being made a Grand Officer of the Order
of Leopold in 1886. His son, Edouard, became professor of zoology at Liège in 1870;
he was an embryologist who discovered the phenomenon of meiosis. The elder van
Beneden died at Louvain on 8 January 1894, aged 84 years. (Plate 11)
CHARLES ALBERT BENTLEY (1873-1949)

Bentley was born at Chipping Norton, England on 25 April 1873. He studied first in
Liverpool then in Edinburgh where he graduated with the degrees of bachelor of
medicine and master of chirurgie in 1898. After two years as a resident at the Royal
Southern Dispensary in Liverpool, he went to India for a number of years as chief
medical officer for the Empire of India and Ceylon Tea Company in Assam. Not only
did he discover the cause of "ground-itch", but he showed that the recently-discovered
Leishman-Donovan bodies were present in kala azar, thus showing for the first time the
true nature of this deadly disease. He took a diploma in public health from Cambridge
and a diploma in tropical medicine and hygiene in 1905. In 1909 he undertook an
extensive investigation of malaria in Bombay. In 1915 he was appointed director of
public health in Bengal. In 1916 he married Gwendoline Harper by whom he had two
sons and two daughters. The University of Calcutta conferred an honorary doctorate of
medicine on him in 1931. In 1931 he left India for Egypt on being appointed professor
of hygiene in the Egyptian University in Cairo. He remained there until 1937 when he
retired to England. He was created a Companion of the Order of the Indian Empire
(CIE) in 1929 and made a Commandant of the Order of the Nile in 1937. He died at
Carshalton, England on 23 November 1949 at the age of 76 years after a short illness.
GODEFRIDUS GOVERT BIDLOO (1649-1713)

Bidloo was born in Amsterdam, Holland in 1649. He studied medicine at the Uni-
versity of Leiden and eventually became professor of anatomy, first at the Hague and
then at Leiden. For a time he was physician to William of Orange, later King William
III of England, and in 1692 became Inspector of Military Hospitals in England. Bidloo
published an Atlas of Anatomy in Amsterdam in 1685 with 105 plates by the artist
Gerard de Lairesse. These plates were plagiarized by the English anatomist and surgeon,
William Cowper in his Anatomy of Human Bodies published in 1698 in Oxford. Two
years later, an irate Bidloo wrote a scathing attack on the latter in a tract entitled
"Guglielmus Cowper, criminis literarii citatus". Bidloo died in Leiden, Holland in 1713.
THEODOR BILHARZ (1825-1862)

Bilharz was born on 23 March 1825 at Sigmaringen on the Danube in Württemberg,
(present-day West) Germany. He was the eldest of nine children and showed his taste
for natural history as a youngster, collecting plants, insects and minerals. In 1843 he
entered the University of Freiberg, then in 1845 transferred to Tübingen where he began
the study of medicine. After his graduation in 1849, Bilharz returned to Freiberg where
he was appointed prosector at the Anatomical Institute; there he was able to study the
comparative anatomy of lower animals and to attend von Siebold's lectures on
helminthology. In June 1850, he went to Egypt as an assistant to another former teacher,
Wilhelm Griesinger, who had been appointed, amongst other things, physician to the
Viceroy of Egypt. When Griesinger departed from Egypt in 1852, Bilharz became
Biographies 789
successively chef-de clinique in the surgical division of Kasr-el-Aini Hospital, chief

surgeon of the division for internal diseases, professor of medicine and professor of
comparative anatomy (1856), then in 1861 he moved to the department for syphilis and
diseases of the skin. In 1862, Bilharz accompanied the Duchess of Saxe-CoburgGotha
and her party to Massaua (also Massowah, now Mesewa) on the Red Sea in the Eritrean
province of Ethiopia, while the Duke and his companions went on an expedition to the
interior. While in Massaua, Bilharz attended a German lady who was living in that place
and who was suffering from a febrile illness, variously recorded as being typhus and
typhoid. Bilharz contracted the disease himself, returned to Cairo and died there shortly
afterwards on 9 May 1862 at the age of 37. Bilharz remained unmarried, was a modest
man and painfully shy in the presence of strangers, but was a valued friend to many. Not
only did he make major contributions to helminthology (schistosomiasis, hookworm
infection, heterophyiasis, taeniasis nana), but he was also an authority on the fauna
(describing, for example, the electric organ of the eel) and flora of Egypt, and on its
inhabitants and their customs. (Plate 12)
DONALD BREADALBANE BLACKLOCK (1879-1955)

Blacklock was born at Oban in Argyllshire, Scotland on 7 January 1879, the son of
the Rev. John Blacklock, a presbyterian minister. He was educated at the University of
Edinburgh where he graduated with the degrees of bachelor of medicine and bachelor
of chirurgie in 1902. He practised for a few years in South Africa. He took the diploma
in public health (London) in 1907, degree of doctor of medicine (Edinburgh) in 1909,
and diploma in tropical medicine (Liverpool) in 1911. In that same year he was
appointed research assistant to the Liverpool School of Tropical Medicine's research
laboratory and worked mostly on trypanosomiasis. In 1914 he was made director of the
laboratory and was later appointed lecturer in parasitology. During World War I he
served in the Royal Army Medical Corps. In 1921 he was created professor of the
tropical diseases of Africa by the University of Liverpool and appointed first director of
the Sir Alfred Lewis Jones Research Laboratory in Freetown, Sierra Leona where he
remained for the next eight years. In 1922 he married Dr Mary Georgina Thompson;
they had no children. In 1929 he returned to Liverpool as professor of parasitology, then
from 1934 until his retirement in 1945 he was professor of tropical hygiene. In 1940
during World War II he was sent as a Surgeon-Captain in the Royal Navy Volunteer
Reserve to Freetown, Sierra Leone to control a malaria outbreak which was threatening
shipping convoys; for these services he was made a Commander of the Order of St
Michael and St George (C.M.G.) He retired to Cornwall and died at his home at
Mawnan on 10 June 1955 at the age of 76 years. (Plate 13)
RAPHAEL ANATOLE BLANCHARD (1857-1919)

Blanchard was born on 28 February 1857 at Sainte-Christophe (Indre-et-Loire) in
France. His father, a poet and author, died at the age of 26, but his grand-uncle, Jean
Pierre Blanchard, was famous for devising the first parachute and for having been the
first person to cross the English Channel in a balloon (1785). Blanchard began the study
of medicine and natural science at the University of Paris in 1875, graduating as a doctor
of medicine in 1882. He was appointed associate professor of medicine at the Paris
Faculty of Medicine in 1883. In 1876, Blanchard had helped found the Société
Zoologique de France, of which he became the secretary-general and moving spirit for
twenty years. He and Milne-Edwards organized the first International Congress of
Zoology, and Blanchard was appointed president of the International Commission on

Zoological Nomenclature in 1898. In the previous year he had been appointed professor
of medical zoology, a title which was changed in 1906 to parasitology. He founded the
Archives de Parasitologie in 1898, then became the first president of the Société
Française d'Histoire Médicale and helped found the Institut de Médecine Coloniale in
1902. He was a prolific author, publishing 603 books, brochures, original papers, notes
and articles. He had a considerable command of languages and was an eloquent speaker,
an indefatigable researcher and a good organizer. He had many warm friends but, as one
biographer wrote, "that he should have some enemies is natural for such is the fate of
most leaders of men". He died suddenly on 7 February 1919 at the age of 62 years.
(Plate 14)
LUDWIG HEINRICH BOJANUS (1776-1827)

Bojanus was born on 16 July 1776 at Buchsweiler in Elsass, Germany, now Alsace,
France. He studied medicine at Jena and graduated there in 1797. After travelling for a
year studying natural science, he began medical practice in Darmstadt where he was
admitted as a member of the College of Medicine in 1801. In 1806 he was appointed
professor of veterinary medicine in Wilna (now Vilnius, Lithuania, USSR), becoming
professor of anatomy there in 1816. His major work was a monograph on the anatomy
of tortoises, which remained an essential zoological text for many years. He died in
Darmstadt on 2 April 1827 aged 50 years.
CHARLES BONNET (1720-1793)

Bonnet was born in Geneva, Switzerland on 13 March 1720. He was the son of weal-
thy parents, his family having emigrated from France during the persecution of the
Huguenots. As a young person he was hindered by increasing deafness. He studied law
and was elected to the council of his native city, but he also had a lively interest in nat-
ural science and eventually devoted himself entirely to that pursuit. He made major
contributions to the understanding of insect biology and was the first person to describe
the phenomenon of parthenogenesis when he showed that each female aphid produced
95 offspring without mating (1746). Likewise he studied regeneration and showed that
each section of Lumbriculus worms when cut into many pieces became perfectly
reconstituted into an adult worm. A serious eye disease, however, compelled him to give
up making direct observations, and he spent the rest of his days engaged in theoretical
speculations, frequently with effusive religious overtones, about natural science and
philosophy. In 1756 he married Jeanne-Marie de la Rive, the daughter of a wealthy
landowner. He died at his estate near Geneva on 20 May 1793 at the age of 73 years.
MAXIMILIAN GUSTAV CHRISTIAN CARL BRAUN (1850-1930)

Braun was born in Germany in 1850. He was educated at the Universities of Greifs-
wald and Würzburg where he studied zoology and medicine. He graduated with the
degree of doctor of medicine from Wurzburg in 1874 then three years later he was
awarded a doctorate of philosophy. In 1880 he was appointed a professor in comparative
anatomy at the University of Dorpat (now Tartu in Estonia, USSR) then in 1883 was
made professor of zoology in that institution. In 1886 he moved to Rostock then in
1891 he was appointed professor of zoology and comparative anatomy and director of
the zoological museum at the University of Königsberg (now Kaliningrad, Lithuania)
where he remained until his retirement in 1922. After a number of years of ill health he
Biographies 791
died on 19 February, aged 80 years. (Plate 15)
JOHANN GOTTFRIED BREMSER (1767-1827)

Bremser was born on 19 August 1767 at Wertheim, (present-day West) Germany. He
studied zoology at Jena and graduated in 1792. He then undertook further studies in
medicine in Vienna, Austria. In 1806 he became associated with the museum of natural
history in Vienna, and in 1811 was appointed its curator. In 1815 he went to Paris in
order to pursue studies in his field of interest. Apart from helminthology, Bremser
published papers on a number of infectious diseases including scarlet fever, cowpox and
measles. He died in Vienna on 21 August 1827, aged 60 years.
JEAN de BRIE (1349-?)

Jean de Brie was born at Villiers-sur-Rougnons, near Coulommiers, France in 1349.
He had the reputation of being one of the best breeders of sheep and cattle in the
country. He was commissioned by King Charles V of France to write a book on the
proper management of sheep and the best means of wool production. This was com-
pleted in 1379, and in it de Brie described the liver fluke.
JOHN JOSEPH CRONIN BUCKLEY (1904-1971)

Buckley was born in Dublin, Ireland in 1904, the son of J J Buckley, the acting dir-
ector of the National Museum of Ireland. He graduated with the degree of master of
science from the National University of Ireland then went to the London School of
Tropical Medicine in 1928. While in the West Indies between 1931 and 1933 he
worked out the life cycle of Mansonella ozzardi. He studied onchocerciasis in Kenya
in 1938 and in the 1950s undertook a number of experiments with Brugia, inoculating
himself on three occasions with B. malayi and concluding that he had developed tropical
eosinophilia. In 1963 he developed a lower limb paresis associated with intolerable pain.
His biographer has said that his modesty was such that he belittled his own
achievements and he invariably gave more credit than was really due to his collaborators.
He died in 1971.
GEORGE BUSK (1807-1886)

Busk was born on 12 August 1807 in St Petersburgh (Leningrad), Russia, (USSR)
where his father was a merchant in the English colony. He was educated at Dr Hartley's
school in Yorkshire, England, then was apprenticed for six years to George Beaman,
being articled at the Royal College of Surgeons. He spent some time at St Thomas's
Hospital, then graduated in 1830. In 1832, Busk was appointed Assistant Surgeon to the
Grampus, the Seamen's Hospital ship at Greenwich, and afterwards to the Dreadnought
which replaced it. He served in this capacity for 25 years, during which time he made
important observations on cholera and scurvy. He was elected a fellow of the Royal
Society in 1850. He resigned his post as surgeon to the Dreadnought in 1855 and
became Hunterian professor of anatomy and physiology at the Royal College of
Surgeons between 1856 and 1859. Busk turned his attention to more general aspects
of biology, paying particular attention to the Bryozoa and becoming interested in eth-
nology. He was the first Home Office Inspector under the Cruelty to Animals (Vivi-
section) Act, a post which he held with tact and impartiality. He married his cousin Ellen
in 1843 and had two daughters. A biographer wrote that "Busk was full of knowledge,
an unwearying collector of facts, a devoted labourer in the paths of science, and cautious
in the conclusions he drew from his observations. He was a man of unaffected simplicity
and gentleness of character, without a trace of vanity, a devoted friend, and an upright,
honest gentleman". He died at his home in Harley Street, London on 10 August 1886,
aged 79 years. (Plate 16)
JOHN CATTO (1878-1908)

Catto was born in August 1878 in Britain. He studied medicine at the University of
Aberdeen and graduated with the degrees of bachelor of medicine and bachelor of
chirurgie in 1900 and he later obtained a diploma in public health from the University
of London. While employed as a resident medical officer in Singapore, he obtained the
specimen in which he eventually found Schistosoma japonicum adult worms. He re-
turned to England in 1904, then joined the Indian Medical Service as a lieutenant on 1
September 1905. He died of cholera at Imphal, Manipur State, India on 7 May 1908
aged 29 years.
AULUS CORNELIUS CELSUS (30 BC-50 AD)

Celsus lived during the reign of Tiberius Caesar at the height of Roman civilization
immediately after the founding of the Empire. He was a landowner, nobleman and
medical historian. He was probably a scholar with limited clinical experience, but he held
most of the contemporary knowledge of medicine within his grasp. He wrote an
encyclopaedia, "De artibus", which contained sections on agriculture, military arts,
rhetoric, philosophy and jurisprudence. Only the last section, De medicina, is extant; it
was re-discovered in 1443 when a copy of the manuscript was found in the papal library
in Milan. (Plate 17)
ADELBERT von CHAMISSO (1781-1838)

Von Chamisso (also known as Charles Adélaïde Chamisso) was born, the son of a
count, at Schloss Boncourt in the Champagne district of France on 30 January 1781. In
1798 he entered military school in Berlin and was commissioned in the Prussian Army
as a lieutenant in 1801. Following the surrender of his regiment in 1806, he returned to
France. His interests lay in the realms of writing lyrics and in natural science. In 1812
he went back to Berlin to study medicine and science. In 1815 he sailed around the
world as naturalist with the Russian, Captain Otto von Kotzebue on the brig Rurik,
following which he wrote a book on his experiences and observations. In 1819 he was
appointed adjunct curator of the Royal Botanical Gardens in Berlin, then became curator
in 1833. In 1820 he married Antonie Piaste by whom he had seven children. Von
Chamisso was elected a member of the Academy of Science in 1835 and died in Berlin
on 21 August 1838 aged 57 years.
RICHARD HAVELOCK CHARLES (1858-1934)

Charles was born in 1858. He was educated at Queen's College in Cork, Ireland then
entered the Indian Medical Service in 1882. He was soon appointed to the Afghan
Boundary Commission then at an early age was made professor of anatomy and surgery
at the Lahore Medical College. Subsequently he became professor of surgery in
Calcutta. He reached the rank of Major-General in the Indian Medical Service and was
appointed medical adviser to the Indian Office. He was knighted in 1912. He was said
to have a forceful personality but was a good friend to all who gained his confidence.
Biographies 793
After several years of failing health he died on 27 October 1934, his wife having
pre-deceased him by several years. (Plate 18)
JOHN BRIAN CHRISTOPHERSON (1868-1955)

Christopherson was born at Bakley, Yorkshire, England on 30 April 1868, the son of
a clergyman. He went to Cambridge University then continued his medical studies at St.
Bartholomew's Hospital, London. After graduating in 1893, he took several resident
positions in that hospital, gained the fellowship of the Royal College of Surgeons in
1897 and proceeded to the degree of doctor of medicine from Cambridge in the fol-
lowing year. Between 1896 and 1902 he was on the surgical staff of the Albert Dock
Hospital, but then went to South Africa as surgeon to the Imperial Yeomanry Hospital
during the Boer War. In 1902 he was appointed physician to the Governor-General of
the Sudan, then two years later became Director of Medical Services to the Sudan
Government. In 1909 he resigned these appointments to become Director of the Civil
Hospitals in Khartoum and Omdurman. Meanwhile, his main clinical interests had
evolved from surgery to medicine; he took the membership of the Royal College of
Physicians in 1905 and was elected a fellow of that College in 1913. In 1912 he married
Joyce Ormerod, a daughter of one of the physicians at St Bartholomew's Hospital. In
1916 during World War I he went with a Red Cross unit to Serbia (now part of Yugo-
slavia) but was taken prisoner-of-war by the Austrians. On his release shortly afterwards,
he went to France, serving as the secretary to the War Office Commission on Medical
Establishments in the British Expeditionary Force. Near the end of that year, he returned
to the Sudan where he was to make his observations on the efficacy of antimony in the
treatment of schistosomiasis. He settled in London after the war and was honoured by
being made a Commander of the Order of British Empire (C.B.E.) in 1919. Although
he did not lose interest in tropical medicine, he turned his attention to respiratory
diseases and became a member of the staff of the London Chest Hospital. He was
described as being a kind, considerate soul with a keen, inquisitive look and an enquiring
mind. He died at his home in Lydney-on-Severn in Gloucestershire, England on 21 July
1955 at the age of 87 years. (Plate 19)
THOMAS SPENCER COBBOLD (1828-1886)

Cobbold was born on 28 May 1828 at Ipswich, Suffolk, England, the son of Richard
Cobbold, a well-to-do clergyman. At the age of 16, he became apprenticed to J G
Crosse, a surgeon in Norwich, for three years then in 1847 he went to Edinburgh to
study medicine and graduated with the degree of doctor of medicine in 1851. After a
short period in Paris, he became curator of the Anatomical Museum of the University
in Edinburgh and remained there for several years while working on comparative anat-
omy. In 1852 he married a Miss Amyss of Suffolk by whom he eventually had several
daughters and a son. In 1856 he went to London and was appointed lecturer in botany,
zoology and comparative anatomy, first at St. Mary's Hospital and then (1861) at the
Middlesex Hospital Medical School. Cobbold did not practise medicine for many years
but in 1865, following the success of his book, began a consultative practice in hel-
minthology. He wrote the first major English textbook on parasitic diseases: Entozoa:
an introduction to the study of helminthology, more particularly to the internal para-
sites of man which was published in 1864. In the same year he was elected a fellow of
the Royal Society, then was appointed professor of geology at the British Museum in
1868 and professor of botany and helminthology at the Royal Veterinary College in
1872. He was said to be of a kind and affectionate disposition (although his often
dogmatic writings at times appear to belie this), made and kept many friends, was de-
voted to music, and possessed a remarkable alto voice. He died from cardiac disease in
London on 20 March 1886 at the age of 57 years. (Plate 20)
CHARLES WILBERFORCE DANIELS (1862-1927)

Daniels was born on 9 May 1862, the third son of the Rev. Thomas Daniels, rector
of Hulme near Manchester, England. He was educated at Trinity College, Cambridge
and at the London Hospital, graduating from the University of Cambridge with the
degree of bachelor of medicine in 1886. After three years in various posts in the London
Hospital, he entered the Colonial Medical Service in 1889 and was sent to Fiji. In 1894
he was transferred to British Guiana (now Guyana). In 1899 he went to Calcutta on
behalf of the Royal Society to study Ross's work on the transmission of malaria then
later that year he proceeded to Nyasaland (Malawi) as a member of the Royal Society's
Commission on blackwater fever. On his return to London he was made superintendent
of the London School of Tropical Medicine but two years later he was sent to Malaya
(Malaysia) to direct the new Institute of Medical Research in Kuala Lumpur. In 1905
he retired from the Colonial Service and returned to the London School of Tropical
Medicine as Director. In 1912 he was appointed adviser to the Colonial Office where
he remained until 1920 when ill health forced him to retire. A progressive and disabling
illness dogged his last years in Ilford until his death on 6 August 1927, aged 65 years.
He never married. (Plate 21)
CASIMIR JOSEPH DAVAINE (1812-1882)

Davaine was born on 19 March 1812 at Saint-Amand-les-Eaux in France, the sixth
child of Benjamin Joseph Davaine, a distiller. He entered the Collège of Tournai in 1828
then moved to Lille. In 1830 he went to Paris to study medicine, spending his clinical
years at the Paris Hospital. He received his doctorate in 1837 for a thesis on
haematocoele in the tunica vaginalis. He began the practice of medicine in Paris but
developed an interest in natural history, especially parasitology; for example, he pub-
lished a paper on lice in 1839. In 1844 he wrote a work on the development of the fetal
human brain between the ages 5 weeks and 7 months. He was elected a member of the
Société de Biologie in 1848 and became its treasurer and archivist. The first edition of
his great textbook of parasitology appeared in 1860 and the second edition was
published in 1877. Davaine described the causative organism of anthrax and was the
first to recognize the pathogenic role of bacteria. In 1869, 14 years before Metchnikoff,
he described phagocytosis by human leucocytes. All this research was carried out while
Davaine practised medicine for he never had a laboratory of his own, nor did he hold an
official university position. Because of his fame, he was appointed physician to the
French Emperor. In 1869 he married an Englishwoman, Maria Forbes, by whom he had
a son. Outside of medicine, he was a rose-fancier. He died in Garches from an
abdominal malignancy on 14 October 1882, aged 70 years. (Plate 22)
JEAN NICHOLAS DEMARQUAY (1814-1875)

Demarquay was born in Longueval, a small village in the department of Somme,
France in 1814, the son of a farmer. He graduated in medicine and specialized in surgery
becoming a famous exponent of the art. He was surgeon to the Maison Municipale de
Santé and a member of the Academy of Medicine in Paris. Demarquay never married,
Biographies 795
and although born of poor parents, died a millionaire. He was a man of literary pursuits
and possessed a very extensive library. He invented many surgical devices and published
papers on surgery, pharmacology and hypnosis. Because of his contributions, he was
made a Commandant of the Legion of Honour. He died in Longueval, having left Paris
two weeks earlier, of cancer of the stomach on 21 June 1875, aged 60 years.
FÉLIX DÉVÉ (1872-1951)

Dévé was born at Beauvais, France on 10 November 1872. He studied medicine at
Paris, and while there in 1900 began his long series of investigations on echinococcosis.
In 1902 he went to Rouen and entered clinical practice. During the first World War he
joined the French Army Medical Service. In 1924 he was appointed professor of clinical
medicine in Rouen. He wrote three books and more than 300 articles on hydatid disease.
He received much recognition for his work; he was a member of the Academy of
Medicine in Paris and corresponding member for the academies in Rome, Lima and
Buenos Aires and was an honorary professor of the Faculty of Medicine in Montevideo,
Uruguay. He died suddenly in Paris on 1 September 1951 aged 78 years.
(Plate 23)
HAROLD ROBERT DEW (1891-1962)

Dew was born in Melbourne, Australia on 14 April 1891. He studied medicine at the
University of Melbourne and graduated in 1914. He immediately joined the Royal Army
Medical Corps and served in Palestine and France. In 1920 he took the fellowship of the
Royal College of Surgeons. In 1923 he was jointly appointed to the surgical staff of the
Royal Melbourne Hospital and made assistant director of the adjacent Walter and Eliza
Hall Institute of Medical Research. He wrote his classic monograph on echinococcosis
in 1928 then two years later he was appointed to the Royal Prince Alfred Hospital as the
first full-time professor of surgery in Australia by the University of Sydney. He became
president of the Royal Australasian College of Surgeons in 1954-55, was knighted in
1955, and retired in 1956. He died on 17 November 1962, aged 71 years. (Plate 24)
ANGELO DUBINI (1813-1902)

Dubini was born, of a poor family, in Milan, Italy on 8 December 1813. He studied
medicine at the University of Pavia and received his degree in 1837. He spent the next
two years at the Milan Hospital (Ospedale Maggiore), during which time he discovered
hookworm, then in 1840 was appointed an assistant in the Medical Clinic of the Uni-
versity of Pavia. In 1841 he travelled to Paris, London, Vienna and Heidelberg in order
to study French, English and German. He took his microscope with him on his travels
and expanded his interest in pathology. He returned to Milan and was appointed as an
assistant at the Ospedale Maggiore. In 1847, he was promoted to become head of the
pathological services in the hospital, and in 1849 was appointed a member of a
commission for the study of rabies. In 1865, he became chief physician and head of the
department of dermatology in the same hospital and remained there until his retirement
in 1878. In his retirement, he wrote a cookbook which received popular acclaim, and
another work on the keeping of bees. He spent the last few years of his life at Cassano
Magnago where he indulged these hobbies. He fractured a femur and died in that place
on 28 March 1902, aged 88 years. (Plate 25)
FÉLIX DUJARDIN (1801-1860)

Dujardin was born at Tours in France on 5 April 1801, the son of a watchmaker. He
was a versatile and gifted person who applied his talents to a number of vocations, be-
coming an engineer, bookseller, then professor of geometry then of chemistry at the
University of Tours from 1826. In 1823 he had married Clémentine Gregoire. He did
not turn his attention to zoology until he was over 30 years of age. In 1839 he was ap-
pointed professor of geology in Toulouse but in the following year he was called to the
chair of zoology and botany at Rennes; he remained there until his death. Being a person
of catholic and wide-ranging interests, he made important contributions in a number of
areas. He improved the performance of the microscope by developing a system of lenses
beneath the stage which became the fore-runner of the modern condensor. He proved
that sponges were animals and first observed the motility of leucocytes. He made a
number of contributions to parasitology, the most notable being his book, Histoire
naturelle des helminthes ou vers intestinaux. He spent the last few years of his life
almost as a recluse, having been persecuted by his colleagues. He died in Rennes on 8
April aged 59.
PAUL VAN DURME (1877-1947)

Van Durme was born in Ghent, Belgium in 1877. He graduated in medicine from the
University of Ghent in 1901 then studied at the Liverpool School of Tropical Medicine
in England. He visited the centres of tropical medicine in London, Hamburg, Marseilles
and Paris. He was appointed a professor of legal medicine in 1910 and professor of
medicine in 1919. He retired in 1934, dying 13 years later in 1947.
NEIL HAMILTON FAIRLEY (1891-1966)

Fairley was born in Melbourne, Australia in 1891 and graduated in medicine from the
University of Melbourne in 1915. Almost immediately, he joined the Army and was
posted to Egypt with the Australian Expeditionary Force. While in the Middle East he
made original observations on schistosomiasis, cerebrospinal fever, dysentery and
typhus. He returned to Australia but in 1921 was appointed professor of tropical med-
icine in Bombay where he researched on tropical sprue. In 1924 he returned to the
Walter and Eliza Hall Institute of Medical Research in Melbourne and worked on snake
bite. In 1928 he went to London as physician to the Hospital for Tropical Diseases.
During World War II he was commissioned a brigadier in the Australian Army and was
appointed director of the Land Headquarters Medical Research Unit at Cairns,
Queensland where he proved that mepacrine was a valuable prophylactic for malaria.
After the war he was appointed to the chair of clinical tropical medicine in the University
of London, but illness forced him to retire in 1948. He was knighted in 1950. He died
in Sonning, England on 19 April l966 leaving a widow and three sons, one of whom
became a well-known oncologist before he was killed by a terrorist bomb in London.
(Plate 26)
ERNEST CARROLL FAUST (1890-1978)

Faust was born in Carthage, Missouri in the United States of America on 7 September
1890. He obtained a bachelor of arts degree from Oberlin College, Ohio in 1912 then
went to the University of Illinois to study parasitology. He was awarded a master of arts
degree in 1914 and obtained the doctorate of philosophy in 1917. He served as an
instructor in the same institution for the next two years then went to the Peking Union
Biographies 797
Medical College in China in 1919. He remained there until 1928, rising to the rank of
associate professor of parasitology. During this period he wrote classic monographs on
clonorchiasis and schistosomiasis japonica. In 1928 he returned to the United States as
professor of parasitology at Tulane University in New Orleans, Louisiana. In 1947 he
was appointed professor of tropical diseases and hygiene in that institution. He is
perhaps best remembered for his text on helminthology which became incorporated into
Craig and Faust's Clinical Parasitology, still the bible of medical parasitology. He
married Lola Swift by whom he had one daughter. He died in New Orleans on 2
November 1978, aged 88 years.
ALEKSEJ PAWLOWICH FEDCHENKO (FEDTSCHENKO) (1844-1873)

Fedchenko was born on 7 February 1844 at Irkutsk near Lake Baikal in Russia
(USSR). After the death of his father, his mother sold the estate and moved to Moscow
to facilitate the family's education. Following graduation, he taught at Moscow
University then in 1866 became assistant dean of the student body. He married a fellow
student, OA Armfeld, then travelled to Scandinavia where he collected insects and
worked on the measurement of Finnish skulls. He studied for a short period with
Leuckart then between 1868 and 1871 sojourned with his wife, in Turkestan, Samar-
kand and Tashkent in south central USSR. He visited Cobbold in London in 1873 then
went to the French Alps. On 15 September 1873 he was killed, aged 29 years, in an
accident while climbing Mont Blanc; he is buried in the English cemetery at Samoëns.
The Fedchenko glacier in Turkestan is named after him. He was the first explorer of
Central Asia and his work on the geology, flora and fauna of the region was published
posthumously between 1873 and 1876 as Fedchenko's Journeys in Turkestan.
(Plate 27)
WINTHROP DAVENPORT FOSTER (1880-1918)

Foster was born in the United States of America in 1880. He worked as a zoologist
at the Bureau of Animal Industry, United States Department of Agriculture. He died in
1918.
AKIRA FUJINAMI (1870-1934)

Akira Fujinami (also known as Kan Fujinami) was born in the Aichi prefecture of
Japan in 1870. He graduated from the Faculty of Medicine of the Tokyo Imperial Uni-
versity in 1895, then spent the next four years studying pathology in Germany. In 1899
he was appointed professor of pathology at the Imperial University of Tokyo and held
this position until his retirement in 1930. In 1918 he was awarded the prize of the
Imperial Academy of Japan for his researches in schistosomiasis. He was said to be a
man of fine character and delightful personality and was admired by his students and
colleagues. He died on 18 November 1934. (Plate 28)
FRIEDRICH FÜLLEBORN (1866-1933)

Fülleborn was born on 13 September 1866 at Kulmbach in (present day West)
Germany. He studied medicine at Berlin University. He was a voluntary assistant in
anatomy with Virchow and studied anthropology. In 1894 he went to North America
to study the embryology of certain fishes on behalf of the Royal Prussian Academy of
Science. Between 1896 and 1900 he was a medical officer in the German Colonial
Army in German East Africa (now Tanzania, Uganda). During this period he studied the
fauna and ethnology of the Nyasa and Kinga mountains. This was to lead to books on
the Nyasa tribes and the people of Tanganyika (Tanzania). In 1901 he joined the
newly-formed Institute for Naval and Tropical Diseases in Hamburg, Germany. In
1908-9 he led an expedition to the South Pacific to make anthropological observations.
On the outbreak of World War I he was called up for military service and shortly
afterwards was severely wounded at Mons in France. Thereafter he was appointed an
expert on malaria and hygiene to the German troops operating in Macedonia. In 1920
he undertook research in the West Indies and South America while later travels carried
him to East Africa, India and Japan. In 1930 he was appointed director of the Hamburg
Institute and professor in the University of Hamburg. Fülleborn was a great raconteur
and linguist, a fine cook and a persistent smoker. He married relatively late in life and
died on 9 September 1933, aged 66 years. (Plate 29)
GALEN (129-c.200 AD)

Galen was born in 129 AD at Pergamum in Turkey, the son of Nicon, a landowner,
architect and mathematician. Galen was taught in the local temple of Aesculapius, an
institution for medical teaching and healing, then studied in succession in Smyrna,
Corinth and Alexandria. He returned to Pergamum and began the practice of medicine,
being appointed surgeon, amongst other things for the gladiators at their summer games.
Subsequently, he became more interested in anatomy, experimental physiology and
general medicine. Eventually, he was summoned to Rome by the emperor to become
his personal physician. He was a prolific writer on medicine, philosophy, mathematics
and grammar. Such was his authority, that he was quoted endlessly and with finality for
the next 1400 years until the dawn of modern clinical investigation.
(Plate 30)
KONRAD GESNER (1516-1565)

Gesner was born in Zurich, Switzerland on 26 March 1516. His father was a protes-
tant artisan who fell at the battle of Kappel in 1531 in which the civic guard of Zurich
under Zwingli were defeated by the Catholics. Subsequently, his friends sent him to
study at their expense in Basle, Paris and Montpellier, where he read many subjects
including classical and oriental languages, natural science and medicine. He was pro-
fessor of Greek at the Lausanne Academy from 1537-1540, then was appointed the first
town-physician of Zurich. He had a quiet nature and a constant struggle with financial
difficulties but his energy was marvellous. He wrote on many subjects but his
masterpiece was his immense four volume Historia animalium in which the animal
world was arranged according to the principles of Aristotle. He died on 13 March 1565,
aged 48 years, of the plague that ravaged Zurich in that year.
JOHANN AUGUST EPHRAIM GOEZE (1731-1793)

Goeze was born in Ascherleben, (East) Germany on 28 May 1731. He studied theol-
ogy in Halle between 1747 and 1951 and was a preacher in Quedlinburg (East Germ-
any). He became a hospital chaplain in 1755, then in 1762 he was appointed minister
to the protestant church of St. Blas in Quedlinberg. In 1786 he was made dean of the
cathedral in that city. Goeze acquired a microscope and made major contributions to the
knowledge of natural history, particularly in the fields of entomology and helminthology.
His great work on parasitic worms was submitted to the Academy of Science in
Copenhagen in response to its call for communications on the origins of intestinal
Biographies 799
worms and received second prize (silver medal). He died in Quedlinberg on 27 June
1793 aged 62 years.
GIOVANNI BATTISTA GRASSI (1854-1925)

Grassi was born on 27 March 1854 in the small Italian town of Rovellasca in Lomb-
ardy. In 1872 he entered the Faculty of Medicine at the University of Pavia to both learn
the practice of medicine and to embark upon a career in research. While still a medical
student in 1878, he found that hookworm infection could be diagnosed by finding eggs
in the faeces. Following his graduation, he turned to research rather than clinical
practice. In 1880 Grassi won a scholarship to the University of Messina to study
zoology. Subsequently, he went to Heidelberg and Würzburg in Germany to study under
first, the anatomist, Gegenbauer, then the zoologist, Butschli. It was in Germany that he
met his future wife, Maria Koenen. In 1883 Grassi returned to Italy and was appointed
professor of zoology, comparative anatomy and physiology at the University of Catania.
In 1895 he moved to the same chair in Rome. He and Ronald Ross had a great
controversy over which of them first discovered that malaria was transmitted by
Anopheles mosquitoes. Grassi has been eulogised as an "indefatigable (who) showed
great enthusiasm and perseverance in his work and granted first-hand importance to
originality, truthfulness, zeal and exactness" by some, but damned as a plagiarist, liar and
fraud by others. In 1908 Grassi was appointed a Senator of the Kingdom of Italy for life.
He died in Rome on 4 May 1925 aged 71 years and was buried in the small village of
Fiumicino where he had conducted a malaria control campaign for the last seven years
of his life. (Plate 31)
WILHELM GRIESINGER (1817-1868)

Griesinger was born on 29 July 1817 in Stuttgart, (present day West) Germany. He
began his medical studies at Tübingen University in 1834 but, because he was a mem-
ber of a banned student organization, had to move to Zurich in 1837 to complete his
training. He began a practice at Friedrichschafen at Bodensee (Lake Constance) in 1839
then a number of appointments in Paris, Winnenthal (where he received his psychiatric
training), and Stuttgart followed. In 1843 he returned to Tübingen. In 1845 he
published a major textbook Die Pathologie und Therapie der psychischen Krankeiten
(Pathology and treatment of psychiatric illness), which was to have a seminal role in
neuropsychiatry. In 1847 he was appointed lecturer in pathology, materia medica and
the history of medicine in Tübingen. In 1849 he was appointed professor of pathology
and therapeutics at the University of Kiel. At this time, a political change of great
importance occurred in Egypt; the francophile Viceroy, Mehemed Ali, died and his
successor, Abbas, replaced Clot Bey and other French administrators and teachers with
persons of German nationality. The triple post of Director of the Medical School,
President of the Sanitary Council, and personal physician to the Viceroy was offered to
Griesinger who went to Cairo in 1850. Although he made major contributions to the
knowledge of hookworm disease and schistosomiasis, his time there was not altogether
a happy one and he returned to Germany in 1852. Subsequently, he became a major
force in psychiatry, especially in the linking of that discipline to physiology and internal
medicine. He was professor of medicine in Zurich from 1860-1864, then devoted the
last three years of his life to full-time psychiatric practice. He died on 26 October 1868
aged 51 years. (Plate 32)
JOHN HARLEY (1833-1921)

Harley was born in Shropshire, England in 1833. He received his medical education
from King's College, London and qualified in 1858. He was elected an assistant phys-
ician to King's College Hospital in 1863 and held this post until he was appointed to the
same position at St. Thomas's Hospital. He was promoted to full physician at the latter
institution in 1879 and was created consultant physician in 1893. He also served on the
staff of the London Fever Hospital. He received a doctorate of medicine from the
University of London and was elected a fellow of the Royal College of Physicians in
1867. He expounded views on the origins of certain diseases that were entirely un-
warranted by contemporary discoveries in pathology and bacteriology with the result that
he lost the respect of his professional colleagues. His habit of smiling, bowing and
shaking hands on every possible occasion with every acquaintance that he met became
an easily caricatured joke. Outside of medicine, he was interested in botany and geology.
He died in Sussex on 9 December 1921.
PHILIPP JACOB HARTMANN (1648-1707)

Hartmann was born in Stralsund in Pomerania, Prussia (now East Germany) in 1648.
He studied letters, theology and medicine in Königsberg, East Prussia (now Kaliningrad,
USSR) from 1669 and received his degree in the last subject in 1678. He travelled
through France, Holland and England in order to further his knowledge. He returned to
Königsberg and was appointed, successively, professor of history and of medicine. In
1685 he was elected to the Academia Naturae Curiosorum under the pseudonym of
Aristotle II. He made many contributions to comparative medicine and wrote a history
of anatomy. He died in Königsberg in 1707.
WILLIAM HARVEY (1578-1657)

Harvey was born at Folkestone in Kent, England on 1 April 1578, the son of a yeo-
man farmer. He was educated at King's School in Canterbury then entered Caius Coll-
ege, Cambridge, where he graduated with a bachelor of arts in 1597. He then travelled
through France and Germany to Padua, Italy where he received a doctorate in arts and
medicine in 1602. He then returned to England and received the degree of doctor of
medicine from the University of Cambridge. In 1604 he married Elizabeth Browne but
had no children. In 1607 he was admitted to the College of Physicians then in 1609 he
was appointed to the staff of St Bartholomew's Hospital in London. In his Lumleian
Lecture of April 1616, "Exercitatio anatomica de motu cordis et sanguinis in anim-
alibus" (Study on the motion of the heart and blood in animals), he described the circ-
ulation of the blood; this work was not published until 1628. In 1851 he published his
treatise on embryology, Exercitationes de generatione animalium (Studies on the gen-
eration of animals). Even though he was one of the greatest physiologists of all time, he
was also a successful practitioner and was appointed physician to King James I and his
son Charles I. He died near London on 3 June 1657, aged 79 years, probably from a
stroke. (Plate 33)
ERNST FRIEDRICH GUSTAV HERBST (1803-1893)

Herbst was born in Göttingen in present-day West Germany in 1803. He was educ-
ated at the University of Göttingen and spent most of his professional life in that city. He
died in 1893.
Biographies 801
HIPPOCRATES (c.460-375 BC)

Hippocrates was born on the Greek island of Cos, the son and grandson of physicians,
and was himself to be given the accolade of "Father of Physic". He rejected mysticism
and emphasized the role of clinical observation in the study of disease. A large number
of writings have appeared under his name but they probably represent the labours of
many. Adams's translation, "The genuine works of Hippocrates", contains Prognostics,
Aphorisms, First and third books of epidemics, Regimen on acute diseases, On airs,
waters and places, On the articulations, On fractures, On wounds of the head, The
oath, and The law. Hippocrates' lectures were said to be given under a plane tree in a
village on the island of Cos. He was accorded honorary Athenian citizenship and is
believed to have died in Thessaly. A marble bust of Hippocrates was found in 1940 near
the ruins of Ostia Antica, the seaport of imperial Rome. (Plate 35)
ISAO IJIMA (1861-1921)

Ijima was born in Hamamatsu, Shizouka prefecture in Japan in 1861. He studied
zoology at the University of Tokyo and graduated in 1882. He went to Germany for
post-graduate studies, then returned to his own university where he became professor
of zoology and director of the Marine Experimental Station at Misaki, Kanawaga pre-
fecture. He was awarded the degree of doctor of science in 1892. He made many con-
tributions to ornithology and the study of sponges. He published an Outline of Zoology
in 1918 and is generally considered to be the father of Japanese parasitology. (Plate 36)
CONSTANTIN JANICKI (1876-1932)

Janicki was born in Moscow, Russia (USSR) in 1876, the son of a famous engineer.
He began his studies at the University of Warsaw, Poland, but Russian domination was
so oppressive to him that he went to Leipzig in 1894. Here he fell under the influence
of Leuckart and studied there for four years. He then moved to Freiburg, Germany and
finally to Basel, Switzerland where he received his doctorate in 1906. Following
working in Grassi's laboratory in Italy for five years, he went back to Basel as privat-
docent in 1911. In 1919 he returned to Warsaw to take up the post of professor of
zoology. He committed suicide in 1932. (Plate 37)
FUJIRO KATSURADA (1867-1946)

Katsurada was born in Japan in 1867, the son of a samurai. He studied at Ishikawa
Prefecture School of Medicine and was licensed in 1887. He then continued his educ-
ation at the Faculty of Medicine of the Tokyo Imperial University. He spent several years
in Germany and received the degree of doctor of medicine from the University of
Freiburg in 1901. He was appointed professor of medicine at Okayama Medical College
in 1903 and remained there until 1914. Subsequently, he became director of the
Seamen's Institute in Kobe and director of the Japanese Hospital for Tropical Diseases.
(Plate 38)
KENJI KAWANISHI (1868-1927)

Kawanashi (also known as Kasai) was born in Japan in 1868. He began the study of
medicine at the Tokyo Imperial University but in 1889 was drafted into military service
during the Sino-Japanese War. He then resumed his medical studies at Kyoto Imperial
University. He remained in the army as a medical officer and was stationed in Taiwan,
Manchuria, and Germany. In 1908 he received the degree of doctor of medicine. He
became head physician of the South Manchurian Railway Hospital in Dairen, then was
appointed the first director of the South Manchurian Medical School.
COENRAAD KERBERT (1849-1927)

Kerbert was a student in Amsterdam, Holland then undertook post-graduate studies
with Rudolf Leuckart in Leipzig in present-day East Germany. In 1876 he wrote a dis-
sertation on reptile skin, then in the next year was appointed as an assistant at the
Zoology Laboratory in Amsterdam. He became a lecturer at the University of Amster-
dam and chief curator of the Aquarium. In 1890 he succeeded CF Westerman (after
whom he had named Distoma westermanni) as director of the Royal Zoological Society.
MOHAMED KHALIL (1895-?)

Khalil was born in Cairo, Egypt on 23 May 1915. He studied medicine at the Gov-
ernment Medical School in Cairo and graduated in 1918. He was appointed as a clinical
assistant at the Kasr-el-Aini Hospital in Cairo in that year, then spent between 1920 and
1922 at the London School of Tropical Medicine. In 1922 he was appointed sub-director
for parasitic diseases at the Public Health Laboratories in Cairo, then in 1925 he was
made professor of parasitology at the Cairo Medical School. (Plate 39)
HARUJIRO KOBAYASHI (1884-1969)

After graduating from the Kyoto Imperial University in Japan, Kobayashi studied
schistosomiasis japonica at the University of Tokyo. In 1916 he went to Korea where
he made a number of original investigations on clonorchiasis, paragonimiasis, tricho-
strongyliasis and malaria. He published several books on parasitology, including an
account of the parasites of Korea. He died in 1969. (Plate 40)
SHIMESU KOINO (1897-1971)

Koino was born in 1897 at Tomiyama-cho, Awagun in Chiba Province near Tokyo,
Japan. He studied medicine at the University of Manchuria, graduating in 1920. He
investigated plague then returned to the department of parasitology of the Keio Uni-
versity Medical School in Tokyo. In 1927 he joined the department of paediatrics in
Keio University Hospital. He began private practice in pediatrics in 1929. He died in
1971.
GOTTLOB FRIEDRICH HEINRICH KÜCHENMEISTER (1821-1890)

Friedrich Küchenmeister was born on 22 January 1821 in Buchheim near Lausigk
in Saxony, (present day West) Germany, the son of a protestant pastor. Initially, he was
destined for the ministry and began the study of theology, but then changed to medicine
which he studied first in Leipzig, then later in Prague. In 1846 he began the practice of
medicine in Zittau (East Germany) and became particularly expert in the fields of
obstetrics and gynaecology. In 1859 he moved to Dresden (East Germany) where he
continued both his medical practice and his research; here he was given the title of
"medicinalrat" or medical councillor. All of his experiments were done at his own behest
and without the benefits and facilities of a university environment. He was a dynamic
man of catholic interests. Parasitology was never the same after his demonstrations of
the importance of experimentation. His experiences led him to write his famous textbook
of parasitology. He introduced the operation of ovariotomy to Germany and displayed
considerable ingenuity in inventing and modifying surgical instruments; perhaps the best
Biographies 803
known of these was an apparatus for plugging the nostrils in epistaxis. He was one of
the first advocates of the official inspection of meat and meat markets. He investigated
the propagation and treatment of cholera, and the frequency of consumption in Saxony.
For some years he edited a journal of his own entitled Periodical of Epidemiology. He
popularized the treatment of diphtheria with lime water, investigated the toxins of
mushrooms and the grafting of fruit trees, and was an avid bee-keeper. His study was
said to be littered with theological texts and he was a masterly exponent of the scriptures.
He wrote papers on Luther's last illness and on the latter's famous hymn "A mighty
fortress is our God". During the last fifteen years of his life he came much before the
public eye as an ardent apostle of cremation; in Dresden in 1874 he began the practice
of the placement of ashes in urns. He gave the appearance of being a rough person, but
underneath he was said to have a heart of gold and, as a doctor, was much loved and
respected. He died in Dresden on 30 April 1890, aged 69 years. As he wished, he was
cremated at Gotha in the crematorium of which he was a founder. (Plate 41)
CLAYTON ARBUTHNOT LANE (1868-1948)

Lane studied medicine at St. Mary's Hospital in London, England and graduated with
the degree of bachelor of medicine in 1893. He obtained a doctorate in medicine in 1895
and entered the Indian Medical Service, rising to the rank of lieutenant-colonel. He died
in London on 2 January 1948. (Plate 42)
EDWIN LANKESTER (1814-1874)

Lankester was born on 23 April 1814 at Melton, in Suffolk, England. He was articled
to a surgeon then studied medicine at University College, London between 1834 and
1837. He was appointed lecturer in materia medica and botany at St. George's Hospital
Medical School in 1843 and was elected a fellow of the Royal Society in 1845. In 1850
he was made professor of natural history at New College, London. In 1862 he was
appointed coroner for Central Middlesex, a post which he held until his death. He was
a voluminous writer on aspects of natural history and, amongst other things, translated
Küchenmeister's two volume text Animal Parasites from the German, and in an
appendix to that work named the fluke now called Fasciolopsis buski. He died from
diabetes and a carbuncle on 30 October 1874 aged 60 years.
DANIEL LE CLERC (CLERICUS) (1652-1728)

Le Clerc was born in Geneva, Switzerland in 1652, the son of a doctor. He studied
in Montpellier and in Paris, France, then received the degree of doctor of medicine from
the University of Valencia, Spain. He returned to Geneva and began to practise, but his
great interest was in medical history, his History of Physick being published in 1696. He
wrote a monograph in Latin on helminthology in 1715 which was translated to English
as well as a monograph with Manget on anatomy. He became a councillor of state in
1702 and held this position until his death in 1728. (Plate 43)
ANTONY van LEEUWENHOEK (1632-1723)

Van Leeuwenhoek was born in Delft, Holland on 24 October 1632, the son of Philips
Thoniszoon, a prosperous basket-maker. Antony took his surname (Lion's corner) from
the house near the Leeuwenpoort (Lion's gate) at Delft owned by his father. As a boy
he was sent to Amsterdam to receive a business training while he worked in the cloth
trade. When he was 22 years old, he returned to his native town and began work as a
shopkeeper. In 1660 he received a sinecure office with the municipal authorities as City
Chamberlain of Delft. This employment provided him with ample leisure to indulge in
his scientific interests. He taught himself the art of lens grinding and used simple
biconvex lenses to magnify the world around him. It is said that, at his death, more than
400 microscopes and magnifying glasses were found. He was extremely jealous of his
inventions and never sold or lent them to anyone, although he did allow visiting
scientists to use them. He never received a formal scientific training and could not write
or read Latin, the medium in which most natural philosophers of his day published their
works. He communicated many of his findings in letters to friends and published many
of his original observations in the Proceedings of the Royal Society of London, of which
he became a foreign member in 1680. He made numerous observations of biological
interest, discovering spermatozoa, erythrocytes, the capillary circulation, Infusoria and
Rotifera in water, and was the first to demonstrate a parasitic protozoon when he found
Giardia lamblia in his own stools. He married Barbara de May, the daughter of a
merchant in Norwich, England in 1654, by whom he had five children. She died in
1666 then he married Cornelia, the daughter of a Calvinist minister, in 1671. He died
in Delft on 26 August 1723 at the great age of 90 and lies buried in the Oude Kerk.
(Plate 44)
JOSEPH LEIDY (1823-1891)

Leidy was born in Philadelphia in Pennsylvania, United States of America in 1823,
the son of a prosperous hatmaker of German parentage. He began the study of medicine
at the University of Pennsylvania and took the degree of doctor of medicine in 1844
with a thesis on the comparative anatomy of the eye of vertebrates. In 1845 he was
appointed a prosector in anatomy then in 1853 he was made professor of anatomy.
Shortly afterwards, the disciplines of zoology and comparative anatomy were added to
this position. He published widely in a number of areas ranging from the structure of the
liver to the fossil horse of America. Indeed, he became the father of palaeontology in the
United States. In 1853 he advanced a theory of natural selection, anticipating Darwin
by several years. He was a modest and retiring man, but popular with his students. In
1886 he was awarded the degree of doctor of laws by the University of Harvard. He died
after a short illness in 1891. (Plate 45)
ROBERT THOMSON LEIPER (1881-1969)

Leiper was born at Kilmarnock, Scotland on 17 April 1881. He began the study of
biology and medicine at the University of Birmingham but then transferred to Glasgow
where he graduated with bachelor degrees in science, medicine and surgery in 1904. He
obtained the degree of doctor of science from that University in 1911 and its doctorate
of medicine in 1917. His interest in helminthology began soon after graduation. He
joined the staff of the London School of Tropical Medicine in 1905 to found the
department of helminthology. He visited the Gold Coast (Ghana) in 1905, worked with
Looss in Egypt in 1907 and visited Uganda in the same year, worked in Nigeria in 1912
and went on an expedition to China and Japan in 1914. Between 1912 and 1914 he was
Wandsworth Scholar at the London School. Following the outbreak of World War I, he
was sent to Egypt in 1915 with the rank of lieutenant-colonel in the Royal Army
Medical Corps to investigate the mode of transmission of schistosomiasis and advise on
prophylaxis for the troops. In this task he was successful, finding the snail vectors of
Egyptian schistosomiasis. Soon afterwards, he was appointed to the chair of hel-
Biographies 805
minthology in the University of London; he held this position until his retirement in
1946. He founded and edited the Journal of Helminthology and Helminthological
Abstracts, was director of the Institute of Agricultural Parasitology at St. Albans, and
made many other contributions to helminthology, including discovery of the insect
vector of Loa loa. He was elected a fellow of the Royal Society in 1921 and was made
a Companion of the Order of St Michael and St George (C.M.G.) in 1941. He married
Ceinwen Jones in 1908 and had a son and two daughters. It has been said that he had
an unpredictability that was the delight of his friends and the despair of his opponents.
His biographers have written that he was a man of gentle voice and charm of manner
who had a great sense of humour, but also remarked that he did not suffer fools gladly
and that at times his criticisms could be acidulated. His dedicated and unparalleled career
over half a century inspired a fierce loyalty among his countless students and colleagues.
He died on 21 May 1969 aged 88 years. (Plate 46)
NATHANIEL GOTTFRIED LESKE (1751-?)

Leske was born on 22 October 1751 at Muskau in lower Lausitz. He studied in Leip-
zig then was appointed successively professor of natural history in 1775 then professor
of economy in 1778 in the University of Leipzig.
KARL GEORG FRIEDRICH RUDOLF LEUCKART (1822-1898)

Leuckart was born on 7 October 1822 in Helmstadt in Brunswick, (present-day West)
Germany where his father was a business man. He began his studies in Göttingen in
1842 and graduated with a medical degree in 1845. In 1847 he was appointed a lecturer
in zoology at Göttingen. In 1850 he became associate professor of zoology at Giessen
and married soon after his arrival. He remained in Giessen until 1869 when he took the
chair of zoology at Leipzig; in 1880 he established a new Zoological Institute which
became famous. He made major contributions to the comparative anatomy and
classification of many invertebrates but became attracted particularly to parasitic worms,
perhaps through the influence of his uncle, FS Leuckart (1794-1843), who was
professor of zoology in Freiburg. Much of Leuckart's original work is contained in his
Die Parasiten des Menschen und die von ihnen herrührenden Krankheiten (Parasites
of Man) which was partly translated into English. Among his important contributions
were his observations on the life cycles of Trichinella spiralis, Fasciola hepatica and
Strongyloides stercoralis and the recognition of Onchocerca volvulus. He attracted a
large number of brilliant pupils to Leipzig, including Fedchenko, Janicki, Kerbert, Looss
and Lutz. He was a helpful, warm-hearted and good-humoured man, and was univers-
ally praised by his colleagues and former students after his death in Leipzig on 6 Feb-
ruary 1898, aged 75 years. (Plate 47)
TIMOTHY RICHARD LEWIS (1841-1886)

Lewis was born at Llanboidy in Carmarthenshire in Wales on 31 October 1841. After
leaving school at the age of 15, he was apprenticed to a pharmacist in Narbeth. Four
years later he went to London as a dispenser in the German Hospital but also attended
classes at University College between 1863 and 1866. He then went to Aberdeen and
graduated in 1867 with the degrees of bachelor of medicine and master of chirurgie. In
1868 he was commissioned as an assistant surgeon in the Medical Department of Her
Majesty's Army, being promoted to surgeon in 1873 and surgeon-major in 1880. Lewis
and DD Cunningham, having received the highest marks for the British Army and
Indian Medical Services, respectively, were sent to Germany for 3 months then to India
to study the cause of cholera. He worked on this and other subjects in India from 1869
until 1883, usually in conjunction with Cunningham until the latter's appointment as
professor of physiology in the University of Calcutta. Many of his findings were pub-
lished as appendices to the Annual Reports of the Sanitary Commissioner with the
Government of India. In 1879 he married and had two children. In 1883 he was ap-
pointed assistant professor of pathology at the Army Medical School, Netley, England.
In 1886 he was recommended for election as a fellow of the Royal Society. Two weeks
later, on 7 May 1886, he died at his home in Woolston in Southampton, aged 44 years,
from pneumonia and septicaemia following an accidental wound which he received
while performing a post-mortem examination. (Plate 48)
CARL LINNAEUS (1707-1788)

Linnaeus, the first child of Nils and Christina Linnaeus, was born at Råshult in
Sweden on 23 May 1707. His father came of peasant stock from the province of Små-
land and had no family name early in life, as was common with many rural people in
that country. While at school, Nils Ingemarsson adopted the name Linnaeus after a great
linden tree which was regarded as sacred and grew near his home. After much
tribulation, Nils was ordained a minister in 1704 and appointed curate of Råshult in
1706. This permitted him to indulge himself in horticulture and a study of herbs, and he
established a large garden filled with many rare and exotic plants. This interest and
enthusiasm was transmitted to his son Carl and provided him with an opportunity for
developing his powers of observation. One of his teachers, recognizing his talent for
natural science, urged his family to allow him to study medicine rather than theology.
In 1727 Linnaeus began to study medicine at the University of Lund, but in the follow-
ing year he moved to Uppsala. There he secured patrons and, although not a graduate,
obtained permission to lecture in botany and attracted large audiences. With financial
assistance from his future father-in-law, a wealthy physician in Falun, he travelled to
Holland and took the degree of doctor of medicine from the University of Harderwijk.
He remained in that country for three years, publishing a number of works, including
his Systema Naturae (1735), which brought him immediate fame. After visiting Eng-
land and France, he returned to Stockholm where he practised as a physician until he
was appointed to the chair of botany at Uppsala University in 1741. There Linnaeus
devoted himself to teaching, the reorganization of the botanical gardens, and to the
production of scientific works. He never attempted to formulate any elaborate theory of
the phenomena of life, but conceived nature as being created by God for His honour and
for the blessing of mankind. He was far more interested in systematics than in
mechanisms and, even in the twelfth edition of his Systema Naturae, still averred that
the universe consisted of the four ancient elements of fire, air, water and earth. Further,
his systematic classification of the animal kingdom was less successful than his
arrangement of the botanical world. Nevertheless, by establishing the concept of species,
which he regarded as immutable, he laid down the foundations for the modern system
of classification and he facilitated its implementation by developing the binary system
of nomenclature, first for plants in 1753, then for animals in 1758. He became
acknowledged throughout Europe as an authority on natural sciences. When his own
Biographies 807
country ennobled him, he took the name of von Linné. Illness progressively impaired his
powers from the 1750's, then during the eighth decade of his life he was subjected to
repeated strokes which dulled his intelligence and finally paralysed him entirely. He died
in Uppsala on 10 January 1778 aged 70 years, and is buried in its cathedral. Following
his death, there was an acrimonious dispute between his son, who had unfortunately
been appointed his successor, and the rest of his family over his herbarium, library and
correspondence. They were eventually sold to England where they were preserved by
the Linnean Society which was founded for that purpose. (Plate 49)
ARTHUR LOOSS (1861-1923)

Looss was born at Chemnitz in Saxony, (present day East) Germany on 16 March
1861, the son of a local manufacturer. In 1880 he entered the University of Leipzig
where he studied natural science for four years under a number of authorities, including
Leuckart. He received a doctorate of philosophy in 1885 for his thesis on certain
trematodes. He lectured at the University of Leipzig for some years and in 1889 pre-
sented a thesis on the role of phagocytes in the degeneration of the tadpole's tail as a
prelude to his appointment as Privat-docent in the Faculty of Philosophy. In 1891 he
married Elise Lohse, but remained childless. He visited Egypt in 1893 although he did
not settle there until 1896 when he accepted an invitation from the government to re-
main in Cairo as professor of biology and parasitology, a post created especially for him
in the Egyptian Government School of Medicine. He was particularly concerned with
trematodes, but he made the major discovery of showing that hookworm larvae
penetrated the intact skin. Looss remained in Cairo for 18 years until he was dismissed
in November 1914 following the outbreak of World War I. He volunteered for military
service and appears to have spent some time in Belgium as a captain. In 1919 a post was
found for him as an assistant in the Zoological Institute at Giessen. In 1921 he became
an honorary doctor of medicine of the University of Giessen. His dogmatic manner and
acrid, controversial style brought him into conflict in turn with Railliet, Stiles, Manson,
Leiper and Sambon, but in private life Looss was said to be a man of simple and lovable
character who had many friends of many nationalities. He was an accomplished linguist
and philatelist. In his later years he was troubled greatly with asthma and he died at
Giessen on 4 May 1923 at the age of 62 years. (Plate 50)
GEORGE CARMICHAEL LOW (1872-1952)

Low was born at Monifieth in Forfarshire, Scotland in 1872. He studied medicine at
the University of Edinburgh, qualifying in 1897 and obtaining the degree of doctor of
medicine in 1912. He was a resident at the Royal Infirmary in Edinburgh then went to
London to study under Manson. In 1900 Low, together with LW Sambon and Signor
Terzi, a well-known artist, lived for 3 months in a screened hut erected at Ostia near
Rome, Italy, in order to demonstrate that malaria could be prevented by sleeping by night
in a mosquito-proof house. In 1901 he travelled to the West Indies and British Guiana
(Guyana) to study filariasis then in 1903 he went to Uganda with the Royal Society's
Commission to seek the cause of sleeping sickness. Shortly afterwards he was appointed
superintendent of the London School of Tropical Medicine, where he remained for the
next 34 years. Together with Sir James Cantlie, he founded the (Royal) Society of
Tropical Medicine and Hygiene in 1907. He was a keen ornithologist. In 1906 he
married Elizabeth Nash but remained childless. He died at his home in London on 21
July 1952, aged 79 years. (Plate 51)
ADOLPHO LUTZ (1855-1940)

Lutz was born in Rio de Janeiro, Brazil in 1855 into a family which had emigrated
from Switzerland in 1849. He was the fifth of ten children and was taken to Switzerland
when two years old. He studied medicine at Berne University where he graduated in
1878. He studied for short periods in Paris, Leipzig and London then in 1881 returned
to Brazil and began to practise in São Paulo. In 1889 he went to Hawaii in charge of the
leprosy colony on Molokai. It was there that he met his future wife, Ann Fowler, an
English nurse; they were married in 1891 and had a son and a daughter. In 1892 he
returned to São Paulo where he was appointed director of the Bacteriological Institute.
In 1908 he became chief of the department of medical zoology of the Instituto Oswaldo
Cruz in Rio de Janeiro where he remained until 1938 when he was forced to retire after
a series of strokes and failing health. He died in 1940 following an attack of influenza.
(Plate 52)
JAMES FREDERICK PARRY McCONNELL (1848-1895)

McConnell was born in Agra, India, the son of a Scot, James F McConnell, on 13
January 1848. He studied medicine at Aberdeen University and at St. George's Hospital
and graduated with the degrees of bachelor of medicine and master of chirurgie with
high honours in 1869. Subsequently he acquired a doctorate of medicine from that
University. He became a member of the Royal College of Surgeons and in 1888 was
elected a fellow of the Royal College of Physicians. In 1870 he joined the Indian Med-
ical Service in Bengal where he served for the remainder of his life, rising to the rank of
surgeon lieutenant-colonel. His first post was as house surgeon at the Calcutta Medical
College and his last was as professor of pathology and physician at that same institution.
He died in Calcutta on 24 August 1895 aged 47 years.
STEPHEN MACKENZIE (1844-1909)

Stephen Mackenzie was born on 14 October 1844 in Leytonstone, England, the sev-
enth child of Stephen Mackenzie, a surgeon, and his wife, Margaret Frances, née
Harvey. He began his medical training as an apprentice in Wellingborough then entered
medical school at the London Hospital. He qualified as a member of the Royal College
of Surgeons in 1869 but then continued his studies at the University of Aberdeen,
graduating with the degree of bachelor of medicine and master of chirugie in 1873. He
proceeded to the degree of doctor of medicine of that University in 1875 and became a
member (1874) then fellow (1879) of the Royal College of Physicians. After a period
in Berlin, he became assistant physician to the London Hospital, being in charge of the
skin department in 1874, lecturer in pathology in 1877, physician and lecturer in
medicine in 1886 and consulting physician in 1905. In addition, he was physician to the
London Ophthalmic Hospital (Moorfields) from 1884-1905 and was one of the first to
make routine use of the ophthalmoscope. He became an authority of diseases of the skin
and of the blood. He married Helen Dulley, the daughter of the doctor with whom he
had served his apprenticeship, and had two sons and a daughter. He was knighted in
1903 as had been his older brother Morell who was also on the staff of the London
Hospital. Stephen Mackenzie developed chronic lung disease in middle age which
greatly restricted his activities and he was forced to spend the winters in Egypt. He died
at Dorking in Surrey on 3 September 1909 aged 64 years.
Biographies 809
MARCELLO MALPIGHI (1628-1694)

Malpighi was born at Crevalcore near Bologna, Italy where his father was a small
landowner, in 1628. At the age of 17, he began the study of philosophy and medicine
at the University of Bologna. He graduated in 1653 and remained in Bologna for several
years. In 1656 he accepted the chair of theoretical medicine (equivalent to physiology)
in Pisa then in 1662 moved to the University of Messina. In 1666 he returned to
Bologna. He made many contributions to medicine and science including observations
on the circulation of blood through the lungs, the structure of the kidney (Malpighian
corpuscles) and the liver, recognition of lymphadenopathy, and studies of the anatomy
of fishes and silkworms. He maintained a regular correspondence with the Royal Society
in England and was elected a fellow in 1668. In 1691 he went to Rome as personal
physician to Pope Innocent XII. He died there in 1694, his body being subjected to
post-mortem examination at his own request; it disclosed a scarred kidney, a small
bladder calculus, left ventricular hypertrophy, and an old cerebral infarction.
(Plate 53)
PATRICK MANSON (1844-1922)

Manson was born on 3 October 1844 in Oldmeldrum, Aberdeenshire in Scotland, the
second son of nine children, his father being laird of Fingask and manager of the local
branch of the British Linen Bank. At school, he was said to be studious but not brilliant
and fond of cricket, fishing and carpentry. At the age of fourteen he was apprenticed at
the ironworks of his mother's relatives, Messrs Blaikie Bros. in Aberdeen, but developed
curvature of the spine and paresis of the right arm so was committed to bed for five
months, during which time he studied natural history. In 1860 he entered the medical
course at the University of Aberdeen and graduated with the degrees of bachelor of
medicine and master of chirurgie in 1865. In 1866 he was assistant medical officer at
the Durham Lunatic Asylum in England and during this time wrote a doctoral thesis
entitled A peculiar affection of the internal carotid artery in connexion with diseases
of the brain. Later that year he joined the Chinese Imperial Maritime Customs and was
posted to Takao, Formosa (Taiwan) where his duties were to inspect ships at port, treat
crews, maintain a meteorological record, attend the native missionary hospital and
conduct a private practice. In 1875 he went on leave to England and married Henrietta
Isabella Thurburn, by whom he had two sons and three daughters. On his return to the
Orient, he was posted to Amoy in China. Despite a lack of professional and literary
contact, Manson carried out many important helminthological studies while in Amoy;
he observed the development of Wuchereria bancrofti microfilariae in mosquito
intermediate hosts, found periodicity of microfilaraemia in the blood, discovered
Spirometra mansoni and was associated with the recognition of Paragonimus
westermani. He went on leave to Britain in 1882 then moved to Hong Kong in 1883.
He took a leading part in the foundation of the Hong Kong College of Medicine for the
Chinese and was appointed its Dean in 1887. In 1889 he returned to England and
commenced practice in London the following year. In 1891 he discovered the
microfilariae of Loa loa and of the worm now known as Mansonella perstans. He was
appointed physician to the Albert Dock Hospital of the Seamen's Hospital Society in
1892 and medical adviser to the Colonial Office in 1897. Shortly afterwards he des-
cribed Filaria ozzardi, was intimately associated with Ronald Ross between 1894 and
1898 in the discovery of the mosquito transmission of malaria, founded the famous
London School of Tropical Medicine in 1899 and drew attention to the lateral spines of
the eggs later recognized as Schistosoma mansoni in 1902. In 1898 the first edition of
his Manual of tropical diseases appeared; successive editions have continued to appear
down to the present day. Manson was the first president of the Society of Tropical
Medicine and Hygiene (now the Royal Society) and has been acclaimed frequently as
the "father of tropical medicine". He was made a Companion of the Order of St Michael
and St George (C.M.G.) in 1900 then was knighted in 1903. He was elected a fellow
of the Royal Society in 1900 and received honorary doctorates from the Universities of
Aberdeen (LL.D., 1886) and Oxford (D.Sc., 1904). For the last thirty years of his life
he was affected by recurrent attacks of gout. Manson was, by all accounts, a most
impressive man in appearance, intellect and personality who was universally mourned
after his death in London on 9 April 1922 at the age of 77 years.
(Plate 54)
YONEJI MIYAGAWA (1885-1959)

Miyagawa was born in Japan in 1885. He graduated in medicine from the Tokyo
Imperial University in 1917 then was an assistant for four years at the Hospital Clinic.
He then transferred to the Government Institute for Infectious Diseases. In 1921 he was
appointed clinical director to the hospital of the Institute, then in 1927 he was made
professor of medicine at the University of Tokyo. In 1934 he became director of the
Government Institute for Infectious Diseases. (Plate 55)
KEINOSUKE MIYAIRI (1865-1946)

Miyairi was born in Nagano-Ken, Japan in 1865. He studied medicine at the Tokyo
Imperial University and graduated in 1890. He worked in public health for a number of
years then was sent to Germany between 1902 and 1904. Upon his return to Japan, he
was appointed professor of Hygiene at the Fukuoku College of Medicine of the Kyoto
Imperial University. (Plate 56)
GIOVANNI BATTISTA MORGAGNI (1682-1771)

Morgagni was born in Forli, Italy on 25 February 1682. He studied medicine in Bol-
ogna where he graduated in 1801. He remained in Bologna until 1707 when he moved
to Venice. In 1909 he returned to Forli and practised medicine with great success. At the
age of 29 in 1711 he was elected to the chair of theoretical medicine (equivalent to
physiology) at Padua then four years later he was appointed professor of anatomy in the
same University, a position which he was to hold for over 50 years. He was a scholar,
teacher, physician, philosopher, medical historian and pathologist. He published widely
but his greatest work was De sedibus et causis morborum per anatomen indagatis (The
seats and causes of diseases, investigated by anatomy) which appeared when he was 79
years old; it summarized a lifetime study of clinical observations and of pathological
studies. Morgagni was the founder of the discipline of pathological anatomy. He died
at Padua on 5 December 1771, aged 89 years. (Plate 57)
OTTO FREDERIK MÜLLER (1730-1784)

Müller was born on 2 March 1730 in Copenhagen, Denmark, where his father was
a musician. Although he grew up in poverty, he was able to study theology then juris-
prudence at the University of Copenhagen by working as a tutor for certain aristocratic
families. During visits to their estates he became interested in natural history and
acquired a collection of insects. While tutor of a young count, he journeyed through
Biographies 811
Europe, increasing his knowledge and widening his collections. Upon his return to
Denmark, he married into money and thereafter was able to devote himself to scholarly
pursuits until his death at the age of 54 years in Copenhagen on 26 December 1784. He
was generally regarded as an amiable, kind-hearted but somewhat vain man.
MASATOMO MUTO (1886-1967)

Masatomo Muto (also known as Shochi Muto) was born in Yamanashi prefecture,
Japan in 1886. He studied medicine at the Aichi Prefectural College of Medicine, grad-
uating from there in 1913. He studied pathology in Kyoto and later became professor
of pathology at Aichi University. He died in 1967. (Plate 58)
KOAN NAKAGAWA (1874-1959)

Nakagawa graduated in 1894 from the department of medicine, Fourth High School
(which was the predecessor of the Kanazana Medical College). He practised medicine
in Tokyo, Japan until 1904 when he entered the medical service of the Formosan (Tai-
wanese) Government. By 1926 he was chief medical officer to the Government and
director of the largest hospital on the island. He died in 1959. (Plate 59)
BERNHARD NAUNYN (1839-1925)

Naunyn was born in Germany in 1839, the son of a well-to-do Berlin burgomaster.
He apparently suffered from hydrocephalus as a child and did not learn to speak until he
was four years of age. He began his university training at Bonn, intending to prepare for
the law. He turned his attention to physics and chemistry, however, and in 1860
returned to Berlin to begin the study of medicine. In 1862 he presented his inaugural
thesis for the degree of doctor of medicine on the development of Echinococcus in the
dog. After several early appointments, he joined the department of medicine at
universities in Dorpat (1969), Bern (1871), Königsberg (now Kaliningrad) (1872),
Strasbourg (1888) and retired to Baden-Baden in 1904 as professor emeritus. He was
recognized as one of the great clinical teachers in Germany. He made major
contributions to the understanding of diabetes mellitus, but his interests were catholic
and he wrote on many clinical subjects, especially the nature of jaundice and the
formation of gallstones. He made little attempt to develop a private practice, preferring
instead to devote his great energies to the furthering of the understanding of diseases
which could be studied in animals and by quantitative chemical procedures at the
bedside and in the experimental laboratory. He died in 1925. (Plate 60)
ALEXANDER von NORDMANN (1805-1866)

Von Nordmann was born of a Germanized Finnish family in Wiborg, Finland in 1805.
He studied at Åbo (now Turku) then went to Berlin where he became a pupil of
Rudolphi. While in Berlin, he wrote Mikrographische Beiträge which dealt chiefly with
parasitic crustaceans but which also considered certain parasitic trematodes. Following
this he was called to a chair in Odessa where he investigated the living and fossilized
world of South Russia. In 1849 he was appointed a professor in the University of
Helsingfors (Helsinki) and he died there in 1866.
LOUIS ALEXIS NORMAND (1834-1885?)

Normand was born on 7 September 1834 at Clermont in Argonne, France, the son
of a music teacher. He enrolled in the Naval Medical School and became successively
a surgeon, third class (1855), surgeon second class (1861), physician first class (1865)
and principal physician (1878). His first appointment in 1855 was in the Naval Hospital
(Hôpital de la Marine) in Toulon. Between 1855 and 1880 he served on 20 warships.
He had 20 periods of service on land including at Toulon, Cherbourg, Paris, Marseille,
Rochefort and Lorient. He was made a Chevalier de la Légion d'Honneur (knight of the
legion of honour) in 1863. He served with distinction against two epidemics of yellow
fever on the Normandy and the Massena and took part in campaigns in the Crimea, Italy
and Mexico. He retired at his request in 1884 while based at Lorient and is thought to
have died in 1885.
JOHN O'NEILL (1848-1913)

O'Neill was born on 31 July 1848. He undertook his medical studies at Queen's Col-
lege in Cork, Ireland, graduating with the degrees of doctor of medicine and master of
chirurgie in 1870. In 1872 he entered the Royal Navy, serving in the Ashanti War of
1873-1874. On 30 September 1875 he joined the Indian Medical Service as a surgeon,
being promoted to surgeon-major in 1887 and surgeon lieutenant-colonel in 1895. Most
of this period was spent in civil service in the Punjab Sanitary Service. In 1883 he led
a team of surgeons from the Bengal Army that was sent to Egypt during the cholera
outbreak of 1883. He retired from the Indian Medical Service in 1896. He died in
England on 15 October, 1913, aged 65 years.
RICHARD OWEN (1804-1892)

Owen was born at Lancaster, England on 20 July 1804, the son of a West Indies
merchant who died while his son was still an infant. He was apprenticed for four years
to a doctor in Lancaster then matriculated as a medical student at the University of
Edinburgh in 1824. He left Edinburgh prematurely, however, not taking his degree. He
became a prosector for surgical lectures at St Bartholomew's Hospital in London and
two years later became a member of the Royal College of Surgeons. Although he set up
in practice in 1826, his first love was anatomy and in the same year he became assistant
conservator of the Hunterian museum of the Royal College of Surgeons. At around the
same time, he also became lecturer on comparative anatomy at St Bartholomew's
Hospital. In 1836 he was made Hunterian professor of anatomy and physiology at the
College. In 1856 he resigned to become the first superintendent of the natural history
department of the British Museum, and oversaw its transfer to new premises in South
Kensington. He became famous in the eyes of the British public for his work on fossils.
Owen attacked Darwin in 1860 over the theory of evolution, but he defended
creationism in terms so ambiguous that no-one understood him. He was knighted in
1884, having retired in the previous year to a residence in Richmond Park that had been
donated by Queen Victoria. A biographer has recorded that he was a tyrant and a prima
donna possessed of deviousness, duplicity and ambiguity. He died in London in
December 1892, aged 88 years. (Plate 61)
ALBERT TRONSON OZZARD (?-1929)

Ozzard became a member of the Royal College of Surgeons in 1886 and a licentiate
of the Society of Apothecharies in the following year. He joined the Colonial Medical
Service and spent 40 years from 1887-1927 in British Guiana (Guyana) holding various
posts including district medical officer and resident surgeon to the Suddie and George-
Biographies 813
town Public Hospitals. However great the demands of work, he always found time to
call in the aid of his microscope in the diagnosis of obscure cases. He lived a strenuous
life in a tropical climate, broken by attacks of grave illness. His last work was the
investigation of a severe epidemic of malaria in the upper reaches of the Demerara
River. Unfortunately he contracted the infection and he remained in poor health until
his death on 1 February 1929, leaving his widow, daughter, and two sons.
JAMES PAGET (1814-1899)

Paget was born at Great Yarmouth in Norfolk, England in 1814, the eighth child of
the 17 children of Samuel and Sarah Paget. His father was a brewer and shipowner and
mayor of the town. In 1839 he was apprenticed to Mr Charles Costerton, a surgeon in
Yarmouth. In 1834 at the age of 21 he entered St. Bartholomew's Medical School in
London then in 1836 he became a member of the Royal College of Surgeons. The next
few years were very difficult for him financially; he was curator of St. Bartholomew's
museum and did much writing including being sub-editor of the Medical Gazette and
translating medical articles from German, French, Dutch and Italian. In 1839 he nearly
died of typhus. In the same year he was appointed demonstrator in morbid anatomy then
in 1841 he became surgeon to the Finsbury Hospital. From 18431851 he was warden
of St. Bartholomew's College. In 1844 he married Lydia North, the daughter of an
Anglican minister. In 1847 he was appointed assistant surgeon to St. Bartholomew's
Hospital, having been made a fellow of the Royal College of Surgeons when the
fellowship was instituted. From 1847-1852 he was professor of human anatomy and
surgery. He was appointed surgeon to St. Bartholomew's and kept that post until he
resigned in 1871 following a near fatal attack of cellulitis which left him weakened. In
that year he was knighted. He described Paget's Disease of the Nipple in 1874 and
osteitis deformans (Paget's Disease of Bone) in 1877. He was president of many learned
societies. He died after two years of enfeebling illness on 30 December 1899, aged 85
years. (Plate 62)
PETER SIMON PALLAS (1741-1811)

Pallas was born in Berlin in Germany on 3 October 1741, the son of a doctor. He
studied medicine at the universities of Halle, Göttingen and Leiden. He received his
degree from the last university in 1760 with a thesis on intestinal worms. He then spent
some years in Holland and England working on zoological collections from the tropics.
In 1767 he was invited by the Russian government to take part in an expedition which
was being sent to explore Siberia. He spent six years from 1768-1774 travelling in that
region, then went to St. Petersburgh (now Leningrad) where he worked, as professor of
natural history, on the immense quantity of scientific material that he had brought back
with him. In 1793 he was sent to explore the Crimean district which had just then
become a part of Russia and he stayed there for a long time living on an estate that the
Empress Catherine II had given him. Pallas was also an accomplished linguist and
geologist. Finally, he moved back to Berlin in order to be in closer touch with the
scientific world and he died there on 20 Septemer 1811, aged 69 years. (Plate 63)
LOUIS PASTEUR (1822-1895)

Pasteur was born at Dole in Jura, France on 22 December 1822, the son of a tanner
and a retired sergeant in Napoleon's Army. He studied at the University of Besançon,
where he received the degree of bachelor of arts in 1842. He continued his education
in the physical sciences in Paris at the École Normale Supérieure, from which he re-
ceived a doctorate of philosophy in 1848, and at the Sorbonne. In 1849 he was ap-
pointed professor of physics at the Lyceum in Dijon. In 1852 he moved to Strasbourg
as professor of chemistry. In 1854 he became professor of chemistry and dean of the
Faculty of Sciences in Lille. It was here that he studied fermentation and showed that
yeast cells were required for the production of alcohol. In 1857 he was recalled to Paris
to direct the scientific studies of the École Normale. It was during this period that he
established the causal relationship of micro-organisms with infectious diseases. In 1863
he was professor of geology and chemistry at the École des Beaux Arts, then from 1867
to 1899 he was professor of chemistry at the Sorbonne. When only 46 years of age in
1868 he had a stroke which left him partially paralysed on one side of his body, and with
impaired speech. As the years passed, he became more interested in infectious diseases,
identifying Staphylococcus aureus in boils and Streptococcus pyogenes fever, and
developed a vaccine against rabies. In 1888 the Pasteur Institute was opened as a
monument to Pasteur funded by public subscriptions. He died seven years later on 28
September 1895, aged 72 years, at the Chateau Villeneuve-l'Étang near Paris. (Plate 64)
EDOARDO PERRONCITO (1847-1936)

Perroncito was born on 1 March 1847 at Viale d'Asti in Italy. He studied at the Uni-
versity of Turin and received a degree in veterinary medicine in 1867. He was appointed
professor of veterinary pathological anatomy in the University of Turin in 1874 and
remained there until his retirement 48 years later in 1922. He studied a variety of
parasites, particularly hookworm, Taenia saginata, Echinococcus and Trichinella. After
he left the University, he served as director of the International Museum for the study
of bees and wine-making. He died in Pavia, Italy on 4 November 1936, aged 89 years.
(Plate 65)
MANOEL AUGUSTO PIRAJÁ DA SILVA (1873-1961)

Pirajá da Silva was born in the town of Camamn near Bahia, Brazil in 1873. His early
education was undertaken in Salvador then he studied medicine at the University of
Bahia. After a period of private practice he was appointed professor of clinical medicine
in the University of Salvador in 1902. A few years later he was appointed professor of
parasitology in the medical school in Bahia, where he remained until his retirement in
1935. His interests were wide-ranging and in addition to parasitology he studied a
variety of microbiological and botanical problems. He died in 1961.
FELIX PLATTER [PLATERUS] (1536-1614)

Platter was born in Basel, Switzerland, the son of a well-known printer in October
1536. After receiving a classical education, he began the study of medicine in Mont-
pellier, France in 1552 and graduated in 1556 as a bachelor of medicine. He then toured
France and Germany before returning to Basel where he conducted a public dissection
and received the degree of doctor of medicine in 1557. In 1571 he was appointed to the
chair of the practice of medicine, then his election to the position of city physician made
him overseer of the public health and director of the city hospitals. In this capacity, he
displayed exceptional courage during successive outbreaks of plague. He sponsored a
botanical garden and established chairs in anatomy and botany at the University in Basel.
He was a prolific author on medical subjects, proposed a classification of psychiatric
disorders (unlike most of his contemporaries, he refused to consider mental disturbances
Biographies 815
to be the work of demons), and described cretinism, amongst many other observations.
He died in Basel on 28 July 1614, aged 77 years.
(Plate 66)
FRANZ PRUNER (1803-1882)

Pruner was born on 8 March 1803 at Pfreimdt in Oberfalz, Germany, the son of a
civil servant. He studied medicine in Munich from 1826, graduating in 1830. He trav-
elled to Paris then in 1832 was appointed professor of anatomy and physiology in Cairo,
Egypt. Two years later he became the director of the Military Hospital in Esbegyeh near
Cairo then subsequently director of the Kasr-el-Aini Central Hospital in Cairo where he
was also professor of ophthalmology. He died on 29 September 1882, aged 79 years.
(Plate 67)
BRAYTON HOWARD RANSOM (1879-1925)

Ransom was born in Iowa, United States of America in 1879. He was educated at the
University of Nebraska from where he received the degree of doctor of philosophy in
1908. In 1902 he moved to George Washington Medical School in Washington, D.C.
He then joined the Bureau of Animal Industry, United States Department of Agriculture,
becoming chief of the zoology division in 1906. He was a reticent person and fastidious
about his appearance. He died in 1925. (Plate 69)
WILLIAM HENRY RANSOM (1823-1907)

Ransom was born at Cromer, England on 19 November 1823, the son of Henry Ran-
som, a master mariner. He went to school in Norwich, then after an apprenticeship with
a doctor at King's Lynn, studied at University College, London where he graduated with
the degree of bachelor of medicine in 1848. After travelling through France and
Germany on a study tour, he settled in Nottingham in 1850 and became physician to the
General Hospital between 1854 and 1890. During this period he gained the degree of
doctor of medicine from the University of London and was elected a fellow of the Royal
College of Physicians in 1869. In 1860 he married Elizabeth Branwell by whom he had
four sons and one daughter. During the early years of his practice, he devoted much of
his spare time to studying the embryology of fishes and the development of galls in
plants; for this work he was elected a fellow of the Royal Society in 1870. He died in
Nottingham on 16 April 1907 at the age of 83 years. (Plate 70)
FRANCESCO REDI (1626-1697)

Redi was born at Arezzo, Tuscany in Italy on 18 February 1626, the son of a doctor.
When he was a boy he was educated in the Jesuit schools then he took the degrees of
doctor of medicine and doctor of philosophy from the University of Pisa in 1647. He
spent the next five years in travelling, studying languages, and writing poetry. He
became an intimate of the court of the Grand Duke of Tuscany at the age of 26, but was
not made "medico primo" until 1666 when his father died. He was a wise and skilful
physician and had a healthy scepticism about the value of many of the therapeutic agents
then available. His greatest work, however, lay in other directions. He was a great man
of science and a brilliant investigator. He was the first to experiment with snake venom,
finding that it was innocuous by mouth but toxic when applied parenterally. He proved
that worms in rotting meat arise, not in consequence of putrefaction, but from eggs laid
by flies on the meat. Some of Redi's experiments were inconclusive and he accepted that
certain intestinal worms and gall-flies may arise by spontaneous generation. According
to his translator, Bigelow, his "constant friendship for the Jesuits must have had a
maleficent effect on (his) mind, as it exacted blind faith and put a limit to his logic". Redi
never married. During the last nine years of his life he suffered much from epilepsy, and
his death occurred suddenly on the night of 28 February 1697 when he was with the
court at Pisa. He was accorded a public funeral and was buried in the church of San
Francesco at Arezzo, aged 71 years. (Plate 71)
RODOLFO ROBLES (1878-1839)

Robles was born in Quezaltenago in Guatemala in 1878. Most of his schooling was
undertaken in Guatemala but he spent a brief period in California, United States of
America. He studied medicine in France, graduating in 1904. Here he came under the
influence of the famous French parasitologist, Émil Brumpt. He returned to his home
town to practise but in 1911 moved to Guatemala City where he carried on a private
practice while holding various positions in the Faculty of Medicine. He died in 1939.
JOHANNES GEORGE ROEDERER (1726-1763)

Roederer was born in Strasbourg, France in 1726. He studied medicine in Paris, grad-
uating in 1750. Subsequently he studied in England and Holland. He returned to Stras-
bourg as an obstetrician. In 1754, he was appointed professor of obstetrics at the Uni-
versity of Göttingen in (West) Germany. He died in Strasbourg in 1763.
CARL ASMUND RUDOLPHI (1771-1832)

Rudolphi was born in Stockholm, Sweden of German parents on 14 July 1771. His
father was a schoolmaster who later became a pastor near Stralsund in the part of
Pomerania which was then within the Swedish kingdom (now East Germany). He stud-
ied at Greifswald University where he took the doctorate of philosophy in 1793. He then
studied medicine in Jena, Dresden, Erlangen and Göttingen, then presented his thesis
entitled Sur les vers intestinaux for the degree of doctor of medicine at Griefswald. In
1801, having finished a course at the Berlin Veterinary School, he was appointed a
professor in the Veterinary Institute in Griefswald. He was appointed professor of
medicine at that University in 1808, then was called to Berlin as professor of anatomy
and physiology in 1810. Here he founded the Berlin Zoological Museum and under his
influence Berlin became a great centre for the study of human and comparative
anatomy. He could never persuade himself to perform vivisections, but laboured hard
for the abolition of the mysticism that natural philosophy had introduced into biology.
He made important contributions in three main areas - parasitology, comparative
anatomy, and physiology. His first parasitological opus, Entozoorum, sive vermium
intestinalium historia naturalis, appeared between 1808 and 1810, then his
Entozoorum Synopsis was published in 1819, but his most important work may have
been his textbook on physiology, Grundriss der Physiologie, which occupied his old
age and was still unfinished at his death. Rudolphi married twice, first to his cousin,
Friederike Eleonore Wilhelmi, by whom he had two daughters. She died in 1801, then
he later married Charlotte Friederike Wilhelmie Meyer, the eldest daughter of the
Burgomaster of Greifswald. After his second wife died in 1821, Rudolphi's own health
became poor and he died in Berlin on 29 November 1832, aged 61 years. (Plate 73)
Biographies 817
LOUIS WESTENRA SAMBON (1866-1931)

Sambon was born in London, England in 1866, the son of an Englishwoman and a
Frenchman. He received his preliminary medical training at St. Bartholomew's Hospital
in London but then went to the University of Naples where his father had Italian rel-
ations. He graduated from there with the degree of doctor of medicine in 1891. While
still a student in Naples, he worked through a terrible cholera epidemic which afflicted
the city; for this service he was decorated by both the French and Italian governments.
He began his professional career as a gynaecologist in Rome, but the lure of England
proved too strong and he went to London, much against the wishes of his father. There,
he met Manson and a strong friendship sprang up between them. He nearly ruined his
career at the outset by publishing an article on acclimatization in which he held, contrary
to universal opinion at the time, that parasites, and not the climate, killed the white man
in the tropics. He was eventualy vindicated in this matter, but time did not deal so kindly
with his attempts to prove that pellagra was caused by an insect-borne parasite, or in his
beliefs concerning the parasitic nature of cancer and in the existence of cancer houses
and cancer streets. Nevertheless, he was an accomplished epidemiologist and, according
to a biographer, a warm-hearted and courteous man. He died suddenly in Paris on 31
August 1931 at the age of 65 years. (Plate 75)
CARL THEODOR ERNST von SIEBOLD (1804-1885)

Von Siebold was born on 16 February 1804 at Würzburg, (present day West) Germ-
any, the son of Adam Elias von Siebold, a famous obstetrician who was later to found
the Lying-in Hospital in Berlin. He studied medicine at Göttingen and Berlin and took
his degree from the latter university in 1828. After the death of his father he had
financial problems and practised medicine for some years at Heilsberg, East Prussia
(now Lidzbark, Poland). In 1831 he married Fanny Nöldechen; she died in 1854 and in
the following year he married her younger sister, Antoynie. In 1834 went to Königsberg
(Kaliningrad) but after a short period he became director of the midwifery school in
Danzig where he remained for six years. During this period he devoted much of his
spare time to zoological studies and the collection of insects and helminths. In 1836 he
discovered ciliated epithelium in man when examining an extirpated nasal polyp. In
1840 he was called to Erlangen as professor of zoology, comparative anatomy and vet-
erinary medicine. In 1845 he established the class Protozoa which he characterized as
unicellular animals. In the same year he moved to Freiburg as professor of zoology,
comparative anatomy, physiology and special physiology. There he founded in 1848,
with Albert Kölliker, the journal Zeitschrift für wissenschaftliche Zoologie. In 1850 he
became professor of physiology and director of the Physiological Institute at Breslau,
Germany (now Wroclaw, Poland), then moved to Munich where a chair of physiology
and comparative anatomy was established in 1856. After some years of ill-health with
his mental faculties gradually deteriorating, he died in Munich on 7 April 1885, aged 81
years. (Plate 76)
PROSPERO SONSINO (1835-1901)

Sonsino was born on 6 August 1835 at Tunis, Tunisia of Italian parents. While still
young he went with his family to Italy then studied medicine at the University of Pisa.
Between 1860 and 1864 he practised in Turkey and other parts of Asia minor. He then
settled in Florence, working in public health and editing a medical journal called
Imparziale. In 1873 he went to Cairo, Egypt and studied aspects of parasitology at the
Khedivial Laboratory. He worked heroically during the cholera epidemic of 1882, being
one of the few Europeans who refused to leave Cairo. He left Egypt in 1885 and
travelled as a ship's doctor to South America and eastern Asia. He then returned to
Africa to study schistosomiasis and in 1897 he once more visited Egypt. He finally
retired to Montepiano in Italy, where he died on 19 November 1901, aged 66 years.
(Plate 77)
LAZZARO SPALLANZANI (1729-1799)

Spallanzani was born in Scandiano in northern Italy on 12 January 1729, the son of
a lawyer. He attended the Jesuit College at Reggio where he was ordained a priest; he
was eventually made an abbott. He then studied law at the University of Bologna but his
interest turned to science and he became a brilliant investigator in geology, biology and
experimental physiology. He studied the Infusoria with the microscope and rejected the
theory of spontaneous generation. These investigations led to a chair in natural history
at the University of Pavia in 1769. His interests were catholic and his investigations
widespread. He made many contributions to medical science including observations on
the digestive power of saliva and gastric juices and he discovered the passage of blood
through the capillaries. He died in Pavia on 11 February 1799, aged 70 years. (Plate 78)
DIMTRY F SSINITZIN (1871-1937)

Ssinitzin was born in Symferolpol in the Crimea in the Russian Empire (now Simfer-
opol, USSR) in 1871. He studied at the University of Warsaw, which was then part of
Russia, and later received his doctorate in zoology from the University of St. Peters-
burgh (Leningrad). He was appointed a professor in Shanjasky University in Moscow,
then became Chancellor of Nijny-Novgorod University from 1918-1919. Political
change forced him to leave the USSR in 1923 and he sought asylum in the United
States of America at the age of 52 years. He lived in poverty for some time but then
obtained employment as a technician at the American Museum of Natural History.
Later, he became an associate zoologist at the Bureau of Animal Industry in
Washington, D.C. Finally, he moved to California where he engaged in private research.
He died in 1937.
JOHANNES JAPETUS SMITH STEENSTRUP (1813-1897)

Steenstrup was born, the son of a minister, at Vang in Jutland in Denmark on 8
March 1813. He studied in Copenhagen then became a schoolmaster for some years.
He took no university degree but undertook journeys of exploration in Ireland, Scotland,
Jutland and Norway in which he gathered material for his courses on mineralogy and
botany at the Soro Academy where he taught for six years. In 1842 he published two
books which brought him fame; the first was a classic work on Scandinavian bog
research and the second was his Alternation of Generations (Om Fortplantning og
Udvikling gjennem vexlende Generations Raekker, en saeregen Form for Opfostringen
i de lavere Dyreklasser) in marine life and trematode worms. In 1846 he was appointed
professor of zoology at the University of Copenhagen, then in 1848 became director of
the Museum of Natural History. He was an extraordinarily gifted and many-sided
investigator, working in diverse fields of research, including botanical, geological and
archaeological studies of peat moss and the discovery of ancient Stone Age shell
mounds. He died on 20 June 1897. (Plate 80)
Biographies 819
FRANCIS HUGH STEWART (1879-1951)

Stewart was born in 1879. He studied medicine at the University of St Andrews and
at the University of Edinburgh from which he graduated in 1904 with the degrees of
bachelor of medicine and bachelor of chirurgie. He immediately joined the Indian
Medical Service. He was medical officer to a number of regiments and saw active serv-
ice on the northeastern frontier of India from 1911-1912 and in several Asian and
African fronts during World War I. He was Officer Commanding of the Indian Station
Hospital in Quetta (now in Pakistan) before his retirement from the Service in 1921. He
died in 1951.
CHARLES WARDELL STILES (1867-1941)

Stiles was born in the United States of America in 1867, the son of a methodist min-
ister. His tertiary education was undertaken in a number of institutions in America and
Europe including the Wesleyan University in Connecticut (1885-1886), and Leipzig
(1889-1890). He obtained his doctorate of philosophy in 1890 in the last-named, having
worked under Leuckart. Subsequently he spent some time at the Trieste Zoological
Institute and the Pasteur Institute. He then returned to the United States in 1892 as a
zoologist in the Department of Agriculture's Bureau of Animal Industry. In 1898 he
returned to Berlin for two years as a scientific attaché. In 1902 he joined the United
States Public Health Service, ultimately becoming its medical director in 1930. He
served as secretary of the International Commission on Zoological Nomenclature for
many years. His time abroad, especially in Germany had stamped a military bearing on
him, together with a delight in wearing uniforms adorned with a sword and other
embellishments. He died in 1941. (Plate 81)
JAN SWAMMERDAM (1637-1680)

Swammerdam was born in Amsterdam, Holland on 12 February 1637, the son of an
apothecary who was also a keen student of natural history. He studied medicine at the
University of Leiden and qualified as a candidate in medicine in 1663 but was plagued
by chronic ill-health. In 1665 he visited France seeking a cure then returned to Holland
to continue his studies and graduated with the degree of doctor of medicine in 1667. He
did not practise medicine but continued the collection and anatomical investigation of
lower forms of life, especially insects, of which he classified more than 3,000 forms. He
was a skilled sketcher and those drawings formed the basis of his masterpiece General
History of Insects. He anticipated Galvani in an experiment that was not published until
many years later, in which he showed that stimulation of the nerve caused contraction
of an isolated frog muscle. Five years or so before his death, he came under the spell of
a religious fanatic and renounced science, destroying many manuscripts. He was
disinherited by his father, and died in Amsterdam of a wasting disease at the early age
of 43 years on 17 February 1680. (Plate 82)
WILLIAM ST. CLAIR SYMMERS (1863-1937)

Symmers was born of Scottish parents in South Carolina, United States of America
in 1863. When he was seventeen years of age he followed in his father's footsteps and
was sent to Aberdeen University to study medicine. While in Aberdeen, his sight became
affected and he had to depend upon lectures and his fellow students reading to him. He
qualified in 1887, then assisted a country practitioner in Shaftesbury, Dorset. He
subsequently worked at Pasteur's laboratory in Paris, in Birmingham, and at the Lister
Institute. While employed as an assistant bacteriologist at the latter institution, he was

sent to Egypt to study the problem of cattle plague, being allowed l8,000 pounds sterling
per annum for his laboratory and all his expenses. In 1897 he was appointed professor
of pathology and bacteriology at the Government Medical School in Cairo and
pathologist to the government hospital. He returned to the United Kingdom in 1904 and
was appointed professor of pathology at Queen's College, Belfast in Ireland. He was a
voracious reader and had an amazing memory, being able, for example, to recite most
of the Aeneid in Latin. His students nicknamed him "The Man". He died in Belfast at
the age of 70 years. (Plate 83)
ALGERNON PHILLIPS WITHIEL THOMAS (1857-1937)

Thomas was born in England in 1857 and received his training in biology at the Uni-
versity of Oxford. While a demonstrator there, he discovered the intermediate host of
Fasciola hepatica, independently of Leuckart. Shortly afterwards, he was appointed as
the first professor of biology and geology at the University in Auckland, New Zealand,
where he remained for the next thirty years. Shortly before his death in 1937, he was
knighted for his contributions to education. (Plate 84)
DYNESHVAR ATMARAN TURKHUD (1868-1926)

Turkhud was born in India in 1868 but studied medicine at the University of Edin-
burgh, Scotland. Between 1908 and 1915 he held a number of appointments as doctor
on plague duty at the Bombay Bacteriological Laboratory, at the Matunga leprosarium,
and as professor of bacteriology at the Grant Medical College. In 1916 he became
officiating director of the Bombay Bacteriological Laboratory and in 1926 was acting
director of the King Institute of Preventive Medicine in Madras. He died later that year.
EDWARD TYSON (1650-1708)

Tyson was born in Bristol, England on 20 January 1650 (according to the English cal-
endar of that period, or 30 January 1651 in the Gregorian calendar). He entered Oxford
University in 1667 and graduated with a bachelor of arts (1670), then master of arts
(1673). He then studied medicine and graduated as a bachelor of medicine in 1677.
Thereupon he went to London to practise medicine, was elected a fellow of the Royal
Society in 1680, and received the degree of doctor of medicine from Cambridge
University in the same year. In 1684 he was appointed reader in anatomy at Surgeon's
Hall and appointed physician to Bethlehem and Bridewell Hospitals. Tyson made major
contributions to medicine, human anatomy, and comparative anatomy, perhaps the most
important publication in the last discipline being his monograph on the orang-utan. In
this work, published in 1699, Tyson distinguished for the first time the anthropoid apes
as a group separate from both monkeys and man. Tyson died, a bachelor, on 18 August
1708 in London, aged 58 years, and is buried in St. Dionis Backchurch, Lime St.,
London. (Plate 85)
VILLANOVANUS (ARNALD OF VILLANOVA, ARNAULDT DE

VILLENEUVE) (c.1240-1311)
Villanovanus was born in Aragon, Spain around 1240 AD. As a young man, he stud-
ied in Montpellier, France. By 1281 he was physician to Peter III of Aragon. In 1291 he
took up residence in Monpellier but was called back repeatedly to Spain. He translated
many works, including those of Galen and Avicenna from Arabic into Latin. His
Biographies 821
commitment to medicine was gradually replaced by a concern for theological matters

and he spent much time travelling between Provence and Rome. In 1305 he became an
adviser to Pope Clement V. His principal work, the Parabolae, contains many
aphorisms. He died on 6 September 1311 at sea off Genoa, Italy.
RUDOLPH VIRCHOW (1821-1902)

Virchow was born in Schivelbein in Pomerania in present day East Germnay on 13
October 1921. He graduated in medicine from the University of Berlin in 1843 then
served as a house officer and assistant to Froriep at the Charité Hospital in Berlin. In
1847 he was appointed prosector at the same hospital. In the same year Virchow and
Reinhardt founded the Archiv für pathologische Anatomie und Physiologie and fü r
klinische Medicin; in 1852 Reinhardt died and Virchow continued the journal on his
own. In 1859 he accepted the chair of pathological anatomy at the University of Würz-
burg then in 1866 he returned to Berlin as professor of pathology and director of the
Pathological Institute. Virchow championed the principle of cellular pathology, the
fundamental concepts of which were embedded in his 1858 work, Cellular Pathology.
He advanced the ideas that the basic components of tissues and organs were cells, that
cells begat cells, and that diseased cells were altered in structure and biochemistry. These
views revolutionized pathology and he became known as the "Father of Modern
Pathology". In 1848 he had participated in an uprising in Berlin. His liberal political
leanings led him into politics and in 1862 he joined the Prussian Lower House. He
served in the Reichstag from 1880 to 1893. He died in Berlin on 5 September 1902,
aged 80 years. The Virchow Institute and the Virchow Hospital in Berlin are memorials
to him. (Plate 86)
JOHANN JACOB WEPFER (1620-1695)

Wepfer, the son of a Canton councillor, was born at Schaffhausen, Switzerland on 23
December 1620. He studied humanities and medicine at Basel and Strasbourg and spent
two years in Italy before receiving his medical degree from Basel University in 1647. He
returned to Schaffhausen, was appointed city physician, and was allowed to perform
post-mortem examinations. He also became an army medical officer and personal
physician to the Duke of Wirtemberg and other notables. He described the anastomotic
blood vessels at the base of the brain, later known as the circle of Willis, and showed that
cerebral haemorrhage was a cause of apoplexy (stroke). In formulating his deductions
from the pathological findings, Wepfer rejected the speculations of his predecessors and
developed an admirable scientific approach, correlating clinical features with
pathological findings. He was elected as Machaon III of the Academia Naturae
Curiosorum. He died at Schaffhausen on 26 January 1695, aged 74 years. (Plate 87)
HELENOR CAMPBELL WILDER (1895-)

Wilder was born at Baltimore in Maryland, United States of America. She worked for
thirty years in the section of ophthalmic pathology of the Armed Forces Institute of
Pathology until her retirement in 1953. Not medically qualified, she was made an
honorary member of the American Academy of Ophthalmology and Otorhinology in
view of her contributions to eye pathology.
OTTO EDWARD HENRY WUCHERER (1820-1873)

Wucherer was born in Oporto, Portugal on 7 July 1820. His mother was Dutch and
his father was German. The family had a business in Brazil and he lived in Bahia for
seven years as a young child. He was educated in Hamburg, Germany where he took up
an apprenticeship in pharmacy. He then studied medicine at the University of Tübingen
where he received his doctorate in 1841. He was then an assistant for a short period at
St. Bartholomew's hospital in London, England following which he practised in Lisbon,
Portugal then in Nazareth, then Cachoeira, Brazil. In 1847 he returned to Bahia as the
doctor to the German colony there. He was confronted by epidemics of yellow fever
(1849) and cholera (1855). His wife, Dorothea Frederica Louiza, died of yellow fever
in 1854. He wrote on hookworm, filariasis, ainhum and poisonous snakes. After 24
years in Bahia, he returned to Germany in 1871 and went to Stuttgart where his second
wife (a sister of the first) and son were living. Possibly because of financial difficulties,
he returned to Bahia in 1873. He was said to be of noble character, serious, modest and
caring. He suffered a stroke while attending a patient in labour, and died soon afterwards
on 7 May 1873, aged 52 years. He is buried next to his first wife in the cemetery for
foreigners in Salvador, Brazil. (Plate 88)
SADAMU YOKOGAWA (1883-1956)

Yokogawa was born in Okayama Prefecture in Japan in 1883. He graduated with
honours from Okayama Medical College in 1908. After working for some time in
Okayama, he went to Formosa (Taiwan) as a lecturer in pathology, becoming professor
of pathology there in 1918. He died in 1956. (Plate 89)
FRIEDRICH ALBERT ZENKER (1825-1898)

Zenker was born in Dresden in present day East Germany in 1825. He studied med-
icine in both Leipzig and Heidelberg. He received an appointment in the department of
pathology in the University of Leipzig but returned eventually to Dresden where he was
appointed professor of pathology in the Medical-Surgical Academy. In 1862 he became
professor of pathology at Erlangen where he remained until his retirement in 1895. He
died in 1898. (Plate 90)
PERSON INDEX
Numbers in bold refer to the page on which a biography can be found.
Abbotts-Smith 405, 460 Annett 613, 645 Baellstaedt von - see

Abdallah 531 Anthony 740 Albertus Magnus
Abildgaard 41, 106, Apt 744 Baelz 142, 161-2, 171-2,
400-1, 480 Araoz 735 176, 279, 785
Abreu de 455-6, 783 Aretaeus 320, 338 783 Baer von C 11, 43, 108
Ackert 740 Argyll-Robertson 643, Baer J 414, 426
Actuarius 455 645, 647, 649-50, 653, Baermann 528, 530
Adams 727 783 Baglivi 38
Aetius 356 Arinus 119 Baillet 432
Africa 310-1, 731 Aristophanes 362 Bain 735, 737-8
Agatharchides 694 Aristotle 3, 30, 32, 356, Bajon 642, 652
Aitken 643 362, 439, 469, 784 Baker 516
Akashi 427 Arizono 300 Balfour 199
Al-Qazwini 31 Arme 631 Bancroft J 14, 601-4,
Albarran 207 Arthur 558 608-9, 772, 785
Albertus Magnus 31-2 Artigas 309 Bancroft T 55, 610-1,
Albrecht 408 Arzube 177 613, 726, 786
Alcock 609 Asada 59, 300, 304, 479 Barbier 288
Aldrovandi 771 Ash 59, 605 Barbot 616
Alessandrini 723 Ashburn 87, 579, 604 Barlow C 131-8, 210,
Alexinsky 335 Ashford 500, 515, 529, 221, 786
Ali-Khan 684 784 Barlow N 558
Alicata 724 Ashton 119 Barry 441
Allan 195-6, 213 Askanazy 306-7, 551, Barton 629
Alves 216 554, 784 Basch 302
Amato Neto 487 Aspöck 461 Bascome 618-9
Amatus Lusitanius 471, Atkinson 56, 145, 372-4, Basnuevo 85
694-5, 709, 769 743, 785 Bastian 53, 606, 696-7,
Amin 629 Attygale 514-5 710, 737, 786
Anaxagorus 32 Aubert 653 Batsch 325, 433
Anazawa 301 Auchincloss 625 Baumler 81
Anderson R 724, 730, Augustine 517, 528 Bavay 544-6, 550, 787
739 Austin 90, 526 Baylis 203, 286, 776
Anderson W 486 Austrageliso 509 Beal 560
Ando 166, 168-70, 172, Avicenna 4, 31, 77, 356, Beale 728
301 439, 444, 480, 521, Beaujean 149
Andreev 335 694-5, 707, 709 Beaurepaire Aragão de
Andrews 520, 526 Azarova 684 624
Andry 37-8, 356, 359, Aziz 680 Beaver 16-7, 252, 461,
386, 398, 695, 768, 684, 745, 787
771-3, 783 Babione 618 Beer 463
Annandale 203, 275 Bacigalupo 425, 433 Behrer 744
823
Bekhti 91 306, 308, 311, 389, Brown H 485, 487, 526,

Belleli 246, 248 421-4, 426, 441, 474- 561
Bellingham 460, 746 5, 500, 551, 642, 668, Brown N 129
Bemrick 739 728, 734 789 Brown P 374-5
Beneden van 25, 46-7, Bloch 40, 305, 387, 422, Brown R 562, 572, 724
328-9, 331, 361, 368, 772 Brown TR 585
424, 580, 643, 787 Boase 678 Browne 33
Bennington 311 Bobillier 339 Bruce 699
Benoit 671 Boerhaave 39 Brudastov 483
Bentley 83, 509, 524, Bojanus 42, 107-8, 790 Brug 16, 283, 300, 604,
788 Bonetus 338 613, 618, 705, 712
Bequaert 203, 275, 670 Bonnal 431 Brugmans 91
Bérenger-Férand 392 Bonne 300-1, 629 Brumpt, 289, 431, 487,
Berghe van den 670, Bonnet 386, 399, 790 521, 663-4, 666-7,
677, 681 Bonnsdorf von 405, 672, 682, 746
Bergouie 709 409-10 Bruning 81, 524
Berkeley 484 Bonyun 617, 625 Brunner 485
Berkowitz 150-1, 252 Bordeu de 33 Bry de 641-2
Bernard, 207 Borel 105 Bryant 675-6, 678
Bernstein 346 Borrel 776 Bucholz 105, 298
Berrio 81 Borrichius 370 Buchwalder 745
Berry 281 Bour 197 Buckley 287, 605, 630,
Bertolus 400-1 Bourges de 713 682, 733, 735, 740,
Bhaduri 731 Bourne 603 791
Bhalerao Boycott 516-7, 519 Budd 127
Bidloo 37, 104-7, 115, Bozzolo 514, 524, 527 Bueding 87
771, 788 Brackett 287 Buffon 5, 39
Biermer 407 Brady 445 Bui-Quoc-Hong 487,
Biggam, 519 Branden van den 666, 526
Biglieri 735 668, 678 Bumbalo 90
Bijlmer 444 Braun 15, 25, 54, 108, Bunnag 136, 308
Bilharz 13, 22, 187-9, 163, 309, 401-3, 405, Burch 678-9
191-2, 205-8, 211-2, 790 Burrass 90
233-4, 245, 251, 303, Bray 86 Busk 127-8, 601, 789
424, 500, 506, 772, Brayer 78 Bylund 92
788 Bremser, 9-10, 41-2,
Billet 709 105, 325, 365, 388, Caelius Aurelianus 480
Biocca 502, 742 399, 440-2, 448, 470, Caius 525
Bischoff 772, 791 Calandruccio 54, 458,
Bishop 525 Brenes 178 463, 473-4
Blackie 288, 562 Brera 772 Calderón 664, 668, 673-
Blacklock 58, 204, 669- Breton 550 4
70, 675, 681, 789 Brett 701 Caldwell 462, 490, 509
Blackwell 775 Brie de 103-4, 114, 119, Cameron 59
Blair 84, 92, 216, 680 121, 791 Campbell A 429
Blanchard E 360 Bright 335 Campbell W 92, 574,
Blanchard R 14, 17, Brock 195 585, 680
121, 142, 267, 303, Brown A 676 Camuset 500, 513
Person Index 825
Cannon 728 Chow 152, 170 500, 725, 740

Capp 88 Choyce 676-7 Crevaux 599
Cardanus 31 Christenson 286 Crewe 649, 177
Cardoso 243 Christopherson 83, 214, Crilly 523
Carneri de 463 221, 793 Crocker 722
Carnochan 625 Chu 136 Cross 59, 726
Carter H 247, 629, 701 Chuckerbutty 600 Cruz 519
Casaux 429 Chung 88-9, 173, 177-8 Cuckler 585
Casoni 337, 775 Church 471 Culbertson 776
Castellani 302, 643 Ciurea 58, 301, 305, 307 Cunha 526
Castle 409, 519 Claparède 441 Cunningham 309, 599
Catto 266-7, 278, 283, Clericus - see Le Clerc Cupp 16-7
792 Clot 642 Currie 645
Cawston 203-4, 211 Cobb 729, 732 Curtis 218
Celsus 3, 30, 356, 469, Cobbold 12-3, 22-3, 25, Cuvier 6
792 121, 128, 130, 135,
Cerf 89, 217 142, 160-1, 189-90, D'Alessandro 346
Cerqueira Falção de 371, 390, 399, 441, Da Cruz Ferreira 89
240 447-8, 500, 575-6, Dacunha 252
Céspedes 724 588, 599, 602, 606, Daengsvang 59, 730-1
Ch'en 177-8, 297 608-10, 614, 618, 643, Daland 560
Chabaud 724, 735, 737- 703-4, 737, 772, 793 Dalgetty 509, 530
8 Cockin 201 Danaraj 85, 629
Chabert 106, 118, 218 Codvelle 121 Daniels 266, 427, 604,
Chaia 526 Cole 134 705, 734-7, 794
Chambers 302, 643 Coleman 214 Darling 530, 549, 558
Chamisso von 43, 109, Coles 212 Date 445, 460, 482
792 Collet-Meygret 728 Davaine 3, 13-4, 50, 77,
Chandler 221, 287, 427- Colomiati 514 128, 334, 370, 372,
8, 517, 729-30 Coneato 522 397, 410, 426-7, 458,
Chang 302 Connal 56, 648-9 461, 472, 484, 598,
Chapin 311 Connor 709 774, 794
Chardome 58, 738-9 Conor 197 Davey 725
Charles 697-8, 792 Contoli 440, 772 David 605
Chastang 545, 550 Conyngham 311 Davies 736
Chatin 739 Cook 250 Davis 449
Chaudhuri 745 Corre 599 Day 213-4, 247, 526
Chauvin 545-6 Correa 464 Deguy 663
Chen 723 Corson 667-8, 738 Delafond 729
Cherry 195 Cort 177, 286, 303-4, Delpert 588
Chesterman 288 479, 485, 528 Demarquay 14, 597-600,
Children 572 Coulaud 92 619, 623, 772, 794
Chisolm 699, 713 Coulet St. 439 Democritus 32
Chitanondh 732 Coulston 429 Deschiens 550
Chitwood 721, 726, 745 Coventry 485 Desnos 218
Cho 449 Craig 604 Desoil 671
Choi 151 Cram 421 Desowitz 90
Chopra 626 Creplin 43, 108, 400, Deunzer 731
Dévé 333-6, 339, 341, Ebell 520 Ferg 699, 712

344-5, 795 Eberhard 735. 737-8 Ferguson 207, 246, 247
Dew 333-5, 337, 344-5, Edeson 58, 605, 615 Fernán-Nuñez 460
795 Edgar 280 Ferrara 402
Dhayaguda 629 Edwards 613 Fibiger 776-7
Diamantis 212, 215-6 Ehrenberg 243 Fiedler 581
Diaz 682 Elgood 195 Figueroa Marroquin
Dick 710 Elliot 711 682
Diesing 3, 11, 110, 162, Elliotson 446, 448, 461, Filippi de 108
189-90, 325, 399, 428, 485 Finlayson 266
431, 500, 578, 664, Elmes 310 Finsen 335
726, 728, 737, 738, Enzer 679 Fischer 529, 772
Dietz 299-300, 305, 309 Epicurus 32 Fisher 288
Dimier 709 Epstein 474 Fitch 616
Dinnik 463 Ercolani 722 Fitzherbert 104, 114,
Dioscurides Anazarbeus Erian 216 117, 119, 121
77 Erlich 776 Fleckseder 775
Do Nascimento 91, 487, Eschricht 44, 342, 360, Fleig 337, 775
Dobson 514-5 399 Flu 239
Doeveren van 359 Espejo 92 Foley 646
Dollfus 297, 427 Esslinger 738 Forbes D 46, 700-1
Dougherty 722 Ettmuller 768 Forbes J 707-8
Douglas 212 Eustis 560 Foster 90, 253, 477-8,
Dounon 550 797
Dove 722 Fain 739, 310, 432 Fox 620, 706
Drebbel 36 Fairley 203, 208, 212, Foy 740
Dryden 338 242, 244, 248, 373, França 204
Dubini 499-500, 502, 624, 652, 678, 708, Friedheim 215
512, 643, 772, 795 711, 796 Friedreich 584
Dubois 423, 652, 666, Falção 298 Frimodt-Müller 629
670, 672, 678, 681 Farber 104, 114 Fritz 485
Ducas 775 Faria de 502, 721 Froelich von 301, 742
Dujardin 3, 10, 45, 298, Farid 210 Fromman 104
327, 361, 365, 424, Farquet 213 Fujii Y 279
489, 577, 643, 725, Farre 572-3, 576-7, 582 Fujii D 268, 279, 283-4
739, 742, 796 Fauchard 768 Fujinami 56, 266, 268-
Duke 655, 680-1, 738 Faulkner 710 70, 273, 284, 775, 797
Dukes 739 Faust 16, 86, 153, 243-4, Fukutuni 284
Duncan 700 267, 275, 277-9, 285, Fülleborn 459, 478-9,
Dunsterville 190 429, 431, 549-50, 556, 510, 517, 519, 552-4,
Dunus 397 561, 729, 735, 737-8, 556-8, 615, 646-7,
Duque Lince 462 743, 796 663-5, 675, 678, 682,
Durme van 55, 552, 796 Fayard 87, 486 737, 747, 797
Dutcher 622 Fayrer 620 Gabucinus 31, 104
Dutt 712 Fedchenko 51, 696, Gage 554-5, 558, 560
Dyce Sharp 58, 646, 702-4, 732, 797 Galen 3, 30, 319-20, 356,
651, 671-2, 679, 737-8 Fehr 357 439, 443,
Feng 613, 732 469, 694, 766, 798
Person Index 827
Galgey 734-5 Gonzalez 244 Handley 625

Gallandat 698-9 Goodsir 334 Harada 522
Galli-Valerio 404 Goodwin 487, 526 Hardy 212
Galliard 147, 559 Gordon 91, 216, 517, 649, Harinasuta 177, 308
Galvin 489 654 Harley 189-90, 193-4,
Garcia 310-1 Gorter 625 209, 212, 234, 606,
Garnham 683 Goto 277 710, 799
Garrison 300, 427 Gouillon 737 Harris 672
Gault 629 Gouvêa de 121 Harrison 207
Gayer 603 Graefe von 371 Hartmann 321, 331,
Gelpi 483 Graham C 446 362-3, 402, 800
Gemma 104, 119, 771 Graham W 713 Hartsoeker 38
George de St. 49 Grassi 54, 402, 422-5, Hartz 459, 559
Gerritson 210 441, 458, Harvey 21, 800
Gervais 432, 544, 643 473-4, 503, 506, 521, Harwood 87
Gesner 104, 362, 798 524, 546, 549-50, 553, Hasegawa 459, 747
Ghalioungi 519 560, 611, 799 Hassal 163, 176, 303,
Ghedini 337, 485, 522, Gravière de la 544 308, 421, 470, 550,
775 Greany 252 643
Ghose 732 Grene 286 Hatch 197
Giaquinto Mira 670, 676 Grenet 513 Haubner 333, 368-9
Gibbins 682 Grew 36 Hawking 84, 626, 679
Gibbons 670 Griesinger 190, 192, 205- Heanley 129, 144, 148-9
Giles 505-6, 508, 515, 6, 208, Heath 699-700
746-7 211-2, 234, 245, 500, Heckenroth 653
Gillet 289 512-3, 521, 799 Héricourt d' 78
Girardeau 562 Gros 443, 472 Heiner 745
Girges 247, 249-50 Grove 559 Heller 368, 446, 476,
Giroud 87, 449 Gruby 729 579
Gleichen-Rusworm 399 Grüntzig 642 Henle 575
Gmelin 6, 363, 696 Gubler 684 Hennessy 728
Goddard 129, 133 Guerrero 674 Henrard 681
Godfrey 617 Guillemard 195, 213 Henry 431, 664, 726,
Godoy 739 Guiness 644 729, 739-40, 742-3,
Goebel 442 Gulland 623 746
Goeze 5, 40, 48, 106, Gullstrand 678 Herbst 50, 578-81, 800
324-5, 327-8, Guret 578 Herman 524
334, 337, 359-60, 363, Guyon 641-3 Herrick 581, 584, 775
365, 370, 386-8, 400, Guyot 642-3 Hewitt 85, 626, 679
426, 432, 440, 456, György 744 Heydon 730
728, 772-3, 798 Hien 288
Goldberger 312 Häckel 52-3 Highby 728
Goldman 673 Hairston 627 Hilton 575
Goldsmid 743 Hales 92 Hinchcliffe 287
Goldsmith 253 Hall 83, 87, 432, 446, Hinman 559
Golgi 549-50 525, 722 Hippocrates 3, 30, 32,
Gönnert 89, 216, 375, Hallez 474 319, 356, 444, 469,
646-7 Hampton 525 480, 521, 800
Hirasawa 299 Ishii 178 Kawanishi 270, 279,

Hirsch 176, 711 Issajev 705 283, 801
Hisette 670, 675-6, 678 Iturbe 243-4 Keller 430, 479
Hjaltelin 335, 340, 342 Iwata 429 Kellicott 176
Ho-Thi-Sang 487 Kennard 611
Hodgkin 605 Jacobson 700 Kenney 464
Hoekenga 462 Jacoby 515 Kérangel 513
Hoelz 424 Jaegoerskiöld 730 Kerbert 162, 163, 174,
Hoeppli 149, 480, 693-5 James 55, 611, 613 802
Hoffman 408 Janeway 581, 584 Kerr 128, 308
Hoffman F 733 Janicki 58, 403-5, 801 Kershaw 676
Hoffman W 624, 733 Janson 302 Kevy 745
Hoffmann 670 Jayewardene 487 Khalil 215, 221, 304,
Holcomb 239 Jeanselme 711 521, 525, 802
Hollenbach 367 Jefferys 129 Kholokowsky 306
Hood 663 Jener 374 Kikuiko 173
Hoof van 87, 679 Jennes 642 Kikuth 85, 561
Hoogstraten 740 Jiménez-Galán 178 Kimuri 170
Hooke 36 Joannidès 213 King 733
Hopkins 737 Johansson 776 Kingery 309
Houghton 144-5, 431, Johnson 281 Kirby-Smith 722
743 Johnston 425, 744 Kirchner 298
Houllier 767 Jophnstone G 128 Kirk 672
Howard 510 Johnstone R 651 Kitchener Lord 200
Hsia 177 Joyeux 423-5, 507 Kleine 56, 648-9
Hsieh 172 Judas 389 Klemm 344
Hsu 146-7, 152 Julien 774 Kloetzel 251
Huart 519 Jung 16-7, 460 Knoch 400-1
Huber 389 Junod 84 Knott 624-5
Hudullet 709 Knox 389-90
Huffman 643, 646 Kagei 743 Kobayashi Harujiro 57,
Humbert 48, 367 Kahane 460 144-7, 152-3, 168,
Humphreys 221 Kakami 168 304-6, 429, 742, 802
Hungerford 164, 166 Kalantarian 747 Kobayashi Hisao 166,
Hunter 335, 338 Kalm 81 169, 176
Hutcheson 281 Kamo 178, 422 Koch 443-4
Hutchinson H 248 Kan 281 Kofoid 449
Hutchinson J 339 Kartulis 246 Koford 744
Huxley 53 Kasai - see Kawanishi Koino 478, 482-3, 485,
Kasimov 741 489, 746, 746
Ibn Sina - see Avicenna Katamine 173 Kölliker 400
Ijima 143, 152, 422, Kato 252 Kondo 173, 479
430, 831 Katsurada 15, 174, 264- Kondoléon 625
Ikeda 173 -8, 271, 305, 801 Koppisan 248
Imai 281 Katsuta 303 Kosaka 426
Imamura 173 Katz 90, 217, 251, 253 Kosuge 552
Inouye 174 Kau 170 Kothari 711
Irvine 745 Kawamura 172 Kouri 119
Isaac 775
Person Index 829
Kouwenaar 525, 629 Laveran 545, 550 Lewis 14, 55, 362, 599-
Koyama 743 Lavoipierre 649 601, 603, 606, 609,
Krabbe 322, 341-2 Lawless 747 619, 623, 665, 805
Krause 523 Laurie 679 Li 146-7, 302
Krehl 357 Lawrie 625 Libby 282
Kreis 549 Lawton 249 Libermann 545, 550
Krull 59, 116, 298 Le Bas 405-6 Lichtenstein 16, 302,
Küchenmeister 11-3, Le Clerc 38, 82, 771-2, 309
24-5, 46-9, 110, 118, 803 Lie 301
325, 327-30, 332-3, Leach 440 Lim 90
342, 364-70, 372-3, Leared 342 Lin 723
376, 388, 392, 400-1, Lebeder 335 Lind 699, 713
410, 432-3, 441, 445, Lebied 649 Linnaeus 1, 4, 18, 40,
448, 457-8, 481, 483, Lee R 721-2 105-6, 359, 362, 286,
500, 579, 584, 694-5, Leeuwenhoek 25, 33, 422, 440, 457, 469-70,
699, 706, 773, 802 36, 104-7, 803 696, 769, 806
Kudiche 85, 261 Leichtensern 54, 504-5, Linné von - see
Kuhne 589 507, 549, 618 Linnaeus
Kuipers 725 Leidy 128, 423, 577-8, Linschoten van 616,
Kumagawa 274 729, 804 641, 698, 710, 771
Kurata 281 Leiper 23-4, 56, 129, Linstow von 298, 473,
Kurimoto 264, 422 145, 190, 195, 201-4, 562, 740-1
Kurlow von 554 218, 220, 239-42, 255, Lisbonne 337, 775
Kuwabara 151 264, 272-4, 301, 305, Lister 707
Kwan 129 308-9, 406, 431, 440, Liston 708, 711
Kynsey 505, 515 470, 502, 506, 527, Little 605
647-8, 668, 697-8, Liu 89
Labadie-Lagrave 663 703-5, 709, 713, 731, Livois 325
Lacroix 666-7, 671, 677 733, 735, 740-4, 746, Lobo-Sanahuja 725
Laennec 325 776, 804 Locke 338
Laigret 668 Lemoine 598 Loeper 83
Lambert 87, 217 Lentz 447 Löffler 483
Lambinet 510 Leon 301 Logan 283, 645
Lämmler 89 LeRoux 288 Lombard 527
Lamson 86-7, 486, 525 Leske 432, 805 Loney 642
Lane 303, 309, 488, 502, Leuckart F 11 Looss 54-5, 129, 142-3,
517, 522, 524-6, 615, Leuckart R 48-51, 53-4, 163, 195, 197, 199-
747, 803 110-1, 113, 115, 120, 200, 218, 220, 236-40,
Langen de 86, 510, 560- 128-9, 161, 163, 325, 298, 301-3, 500, 502,
1 333, 357, 367, 369, 504-11, 518, 527, 548,
Langer 775 388-90, 400-1, 422-4, 552, 553, 643, 746-7,
Laning 280 427, 441, 446, 458, 774, 807
Lankester 127, 130, 803 472-4, 502-3, 547-8, Lopez 642
Lapage 741 575, 581-3, 609-10, Loria-Cortes 725
Lapierre 288 662, 665, 677, 702, Lortet 196-7, 199
Larumbe 682 805 Lotsy 212
Lasbrey 214 Levine 89 Low 55, 288, 611-2, 622,
Lautner 205 Levinson 731 645-6, 650, 665-6,
735-7, 807 609, 622, 703 Meydenbach 771

Lowenthal 670, 682 Mantey 196 Meyers 629, 738
Lu 171 Mapes 59, 298 Meyner 421
Lucretius Carus 616 Maplestone 86, 510, Mhaskar 525
Ludlow 170 605, 731, 737 Milne 695
Lühe 309, 399, 422 Maren 84 Milton 218, 251, 253
Luschka 577 Margolis 414 Minchin 58, 425
Lyle 195 Markovic 309 Minet 212
Lýsek 490 Martin de la Calle 118 Minett 622
Martin 118, 173, 252 Minning 281, 483
MacArthur 371, 726 Martinéz Báez 178 Minot 409
MacCowen 561 Martins 244 Mitter 730
MacCowen 88 Martirani 91, 561 Miura 252, 485
MacDonald 505 Matsuura 270 Miyagawa 272, 276-7,
MacFadden 668 Matthes 745 289, 510, 810
MacFie 667-8, 711, 738 Maung 479 Miyairi 56, 168, 268,
MacKay 706 Mauss 216 270-2, 274, 281, 284,
Mackenzie 614, 643, Maxwell 621 810
646, 652, 736, 808 May 365 Miyakai 422
Mackerras 59, 723 Mayer 216 Miyazaki 177-8, 731
Mackie 207, 235, 248-9, Mazzotti 85, 678-9 Molin 500, 732, 739-40
252 McAdam 740 Mongin 642, 652
MacLaurin 339 McConnell 15, 141-3, Monnig 746
Maddern 210-1, 246, 146, 149, 302, 514, Monson 178
249, 508 722, 808 Monti 549-50
Maegraith 285 McCoy 136 Montpellier 666-7, 671,
Magalhães de 255, 604, McDonagh 215 677
733 McGregor J 707 Moore 59, 196, 649
Magath 337, 374-5, 413 McGregor W 142-3, Moorthy 697, 706, 713
Maisonneuve 700 148 Moquin-Tandon 189,
Maitland 625 McKinley 622 361, 706
Majima 263, 278, 301 McLelland 700 Morenas 118
Malebranche de 33 McMahon 681, 683 Morera 59, 724
Malpighi 33, 36, 105, McMullen 310 Morgagni 322, 456, 810
322, 359, 363, 808 Mebius 149 Mori 522
Manalang 722 Medicus 33 Morin 344
Mann 280 Meerovitxh 684 Morishita 299
Manson 15, 55, 159-62, Mehlis 43, 105, 108 Moriyasu 172
164, 171-2, 175, 235- Mehrez 87, 449 Mornex 733
6, 252, 254, 267, 428, Meillon de 627 Mosler 50, 390, 473,
508, 530, 603-4, 606- Meinhof 646, 651 482, 585
11, 613-5, 619-20, Mekel 423 Mossbrugger 460
622-3, 626, 643-7, Meleney 267, 275, 277- Motte Lambert de la
650-2, 662-3, 665, 9, 282 698
667-8, 670, 677, 704, Melnikov 422 Moty von 445
706, 709, 734-7, 809 Mercer 744 Moura de 513
Manson-Bahr 87, 203, Mercurialis 31 Mouriquand 449
242, 449, 599, 604-5, Metchnikoff 445, 776 Mozley 221
Person Index 831
Muangmanee 308 Nomura 723 Pachecho Luna 674

Muhleisen 722 Nordmann von 43, 108, Paget 572-6, 582, 813
Mühlens 305 811 Pagliani 514, 527
Mukerji 86, 731 Normand 543-6, 550, Pallas 40-1, 105, 323-4,
Mukoyama 147-8 553, 556-9, 560, 811 364-5, 386, 769, 813
Müller H 523, 776 Nouffer 77. 373 Palmer E 423
Müller J 426, 430-1 Noya Benitez 253 Palmer ED 86
Müller O 41-2, 107, Nwako 178 Pampiglione 562
664, 810 Nwokola 178 Panarolus 362, 471
Muller R 703 Nybelin 485 Pane 732
Müller W 727 Nyberg 410 Paracelsus 31, 33, 78
Mullins 722 Pardani 711
Murgatroyd 653 O'Connor 622 Paré 31, 695, 770
Murphy 409 O'Neill 661-5, 671-2, Parona C 503
Musgrave 460 677, 681, 812 Parona E 423, 503, 524,
Mustafa 483 Ochoterena 676 546, 553
Muto 57, 145-6, 148, Odhner 129, 171, 300 Parsons 663
151-2, 306, 811 Ogata 276 Pasco 59, 300
Myers B 743 Ogawa 555 Pasteur 51-2, 813
Myers W 614, 625 Ohba 478 Paulus Aegineta 356,
Myrepsus 773 Oisio 510 480, 694
Okada 510 Payne A 176
Nag 525 Oken 42, 108 Payne F 489-90, 740
Naganori - see Majima Okumura 428-9 Payne G 538
Nakagawa 57, 130, 132, Oleinikov 446 Peacock 575
137, 165-7, 169, 811 Oliver 48, 391 Peel 58, 738-9
Nakahama 162-4 Oliver-Gonzalez 85, 487 Peiper 510
Nakamura 56, 268, 269, Onabamiro 706 Pellegrino 217
270, 284, 422 Onji 57, 303-4, 310-1 Pene 91
Napier 520 Onuigbo 178 Penner 287
Narabayashi 276 Ophüls 551, 556 Perez 309
Natterer 162 Oribasius 30 Perez-Santiago 92
Naunyn 332, 334, 811 Orihel 59, 649, 735, Perlingiero 744
Needham 39 737-9 Perrin 84
Neghme 86 Ortiz 673 Perroncito 49, 376, 391,
Nelson 273, 672, 735 Ostertag von 741 393, 503-4, 514, 521,
Newsham 734 Östling 410 524, 529, 546, 560,
Nicholas 737 Otsuru 747 562, 814
Nicholl 58, 425 Ottesen 630 Peruzzi 739
Nicholls 525 Otto 84, 479 Pesigan 281-2
Nickerson 411 Oudendal 459 Petrushewsky 413
Nicolai 388 Owen H 728 Philpot 443
Nietzsch 42, 107, 282 Owen R 572-7, 582, Pickells 746
Nishigori 303, 555-6, 730, 772, 812 Pigafetta 642
726 Ozaki 301, 304 Pigoulewski 121
Nishio 57, 303-4, 310-1 Ozzard 506, 734-5, 812 Pilsbry 203, 243
Noè 611 Pirajá da Silva 239, 243,
Nöller 298 Pachecho 59 255, 814
Pirie 522 484, 815 Rodenwaldt 129

Planck 53 Rao 301, 605-6, 708, Rodger 676
Plato 32 712, 731 Rodhain 652, 666, 668,
Platter 398, 405, 471, Rathouis 129 672, 678, 681
814 Ratz von 299 Rodrigues 91, 309, 561
Plehn 704 Rausch 345-6, 414 Roederer 456-7, 459,
Pliny 3, 30, 77, 356, 469, Recio 421 461, 480, 772, 816
694 Reddy 709 Rogers 651-2
Plutarch 694 Redi 33-5, 104, 108, Rook de 613
Podjapolskaja 311 114, 320-1, 351, 469, Rose 221
Poirier 128, 308 728, 771, 815 Rosen 58, 403-5, 723,
Poltera 728 Redlich 404 732
Pons 250 Reichard 698 Rosenberg 402
Porter 204, 242 Reinhard 601 Rosenblatt 605
Posselt 344-5 Reinus 642 Rosenstein 359, 773
Potiez 243 Rendall 484 Rosi 86
Pouchet 49, 52-3, 330-1 Renoult 209 Ross 461, 476, 612-3
Powell 707 Rep 502 Roth 373, 653
Poynton 605 Requine 3 Roubaud 704
Pratt 311 Retzius 106 Roupell 571
Priestley 599 Reyher 407-8 Roussel 709
Priston 282 Reyn von 746 Roux 150, 545, 550
Proffit 485 Reynolds 710 Rovelli 54, 422-3, 549
Prommas 59, 730-1 Rhazes 694 Rudolphi 2, 8-9, 41, 82,
Prout 622, 663, 665 Rhind 43, 480 298, 300, 308, 325,
Pruner 500, 703, 814 Rhoads 519 331, 363, 365, 387,
Puig Solanes 675 Ricciardi 562 431-3, 456-7, 459,
Richard-Lenoble 739 461, 480, 728, 732,
Quénu 339 Richards 213 742, 746, 772, 816
Quere 677 Richter 472 Ruffer 209
Ridley 675 Ruiz Reyes 679
Radomyos 300 Rieder 523, 776 Rumler 362
Raffier 711 Rim 151, 174, 306 Runeberg 407-8
Ragni 393 Ringer 15, 159 Ruyschius 771
Railliet 54, 121, 129, Ripert 174 Ryuzi 151
302, 422, 426-7, 431, Rivas 652
458, 500, 664 726, Rivikka 86 Saboia 604
729, 731, 742, 733, Rivolta 306 Saeki 425
735, 737, 739-40, 742- Rizhikov 733 Sagredo 459
3, 746-7, Ro 173 Saha 745
Rake 518 Robbins 462 Saito 144
Raleigh 625 Roberts J 683 Salzer 584, 586
Ramsay G 710 Roberts W 602 Salzmann 423
Ramsay W 2 Robles 58, 664, 668-9, Sambon 16, 236-8, 611,
Ransom B 13, 393, 477- 672-4, 681, 816 647, 776, 816
8, 727,741, 746, 774, Roche 520 Sambuc 149
815 Rockefeller 529 Samson-Hammelstjerne
Ransom W 372, 461, Rodenburg 725 722
Person Index 833
Sandares 59, 723 108-10, 128, 187-8, Stejksal von 775

Sanders 282 234, 303, 327-31, 360, Stekhoven 555
Sandground 300, 310, 365, 424, 442, 500, Stevenson 649
449, 549, 557-8, 664, 577-8, 817 Stewart F 444, 475-8,
742-3, 747 Siegenthaler 684 818
Sandwith 304, 506, 508 Silva 676, 678 Stewart I 747
Sangalli 506 Silva Araujo 55 Stiles 163, 176, 303,
Santiago-Stevenson 85, Silva Lima da 598-9 308, 312, 421, 424,
626 Simon 665-6, 678 428, 430, 470, 500,
Santos 282 Simonds 108, 120 516-8, 528-9, 550,
Sasa 604 Singer 694 643, 728, 738, 741,
Sawada 88 Singson 726 744, 746, 819
Schapiro 87 Sisinitsin - see Ssinitzin Stock 213
Schaudinn 511 Skrjabin 299, 311, 726, Stoll 87, 412, 512
Schaum 726 729 Stone 722
Schenone 91 Smillie 517 Stossich 740
Schiller 345 Smith A 500, 652 Stransky 281
Schinz 485 Smith D 309 Straub 525
Schmidt 446 Smith M 745 Stricker 443
Schneider A 741 Smith W 721 Ströbel 585
Schneider H 375 Soemmering 440, 448 Strom 299
Schrank 301, 457, 746 Solander 769 Strong 670, 673, 676
Schraufstätter 89, 375 Sommer 360 Stuckey 743
Schrecker 213 Sonsino 195, 198-9, 234, Stunkard 59, 287, 421
Schreiber 42, 86 287, 302, 422, 505, Suga 162
Schubart 400 514, 550, 601, 610, Suganumu 624
Schüffner 81, 443, 447, 817 Sui - see Koino
524 Sooley 283 Suyeyasu 276
Schulthess 504 Sorel 707 Suzuki 56, 268, 270-2,
Scott 743 Sorenson 445 274, 285, 743
Scott H 517 Spallanzani 39, 817 Swammerdam 33, 35-6,
Scowden 559 Spiegel van der - see 819
Scribonius Largus 766 Spigelius Swartzwelder 87, 90,
Seifert 547-8, 560 Spigelius 32, 357, 398, 460, 483, 561
Seltzer 770 771 Swayne 484
Sen 732 Spillman 483 Sweet 706, 713, 733
Senn 190 Spooner 424 Swellengrebel 443, 447
Serapion 4, 256 Spöring 399-400 Swift 721
Sergent 737 Sprent 489 Symmers 246-8, 819
Servantie 118 Spruit 462 Szidot 411
Seurat 604 Ssinitzin 115-6, 818 Taillandier 560
Shaftesbut, Earl of 338 Stadelmann 741 Takata 490
Shaldon 247 Standen 449 Takemoto 276-7
Shaw 215 Stanley 573 Talaat 89
Shillinger 87 Steenstrup 13, 44-5, Taliaferro 485, 624, 776
Shimura 555 109, 327, 361, 400, Talyzin 487
Shirai 114, 116 818 Tanabe 299, 310
Sibthorpe 603 Stein von 48, 328, 401 Tang 427
Siebold von 43-5, 47-8,
Tansurat 731 Uchimara 425 Ward 118, 129, 176-7

Tarassov 407, 413 Ulrich 461, 484 309, 642, 732
Tardieux 150 Unterberger 473 Warren E 203-4
Tayler-Jones 428 Upatham 308 Warren K 249
Taylor 286 Wassell 431
Teissier 553 Vaillant 426 Watkins-Pitchford 203
Tennent 698 Vallisnerius 38, 386 Watson 311
Termakov 464 Vanda de la 711 Watson-Wemyss 149
Tesch 283, 300 Vandepitte 310 Wawruch 388, 733
Thayer 551 Vandyke Carter 614 Webb 629-30
Theophrastus 77, 356 Veglia 288 Webbe 221
Théoridès 91 Veiga de 695 Wedl 484
Thiel van 725 Velden van den 775 Weinberg 118, 337, 373,
Thienpont 91 Velschius 694-5, 710, 774
Thira 555, 558 771 Weingarten 629
Thomas A 53, 110-3, Verloren 400 Weinland 110, 128, 190,
115, 119-21, 820 Verrier 49, 330-1 423-4
Thomas H 92 Vervoort 486 Welch 92
Thomas J 332, 324 Vialleton 197, 199 Weller 445
Thompson 201, 204, Vic-Dupont 288 Wepfer 105, 323, 432,
661, 775 Vilela 561 821
Thoonis 87 Viljoen 377 Werner 363, 744
Thorensen 340 Villanovanus 31, 356, Westerman 162-3
Thorpe 674 820 Weston 92
Tiedemann 575 Villeneuve de - see Whalen 726
Todokoro 284 Villanovanus Wharton 362
Tomita 562 Virchow 50-1, 344, 579- Wherry 643
Topley 526 81, 589, 820 White A 449
Toroella 678, 682 Virik 310 White G 722
Torres Estrada 678 Vix 441 White R 449
Tötterman 409 Voelker 177-8 Whitmarsh 622
Travassos 297, 725-6 Voge 288 Wielinga 725
Trent 618 Vogel 59, 177-8, 281, Wilder 744-5, 821
Trewn 708 298, 305, 307, 345, Wiley 215
Tsamis 216 483 Willach 740
Tsao 178 Vogt 11 Williams C 515
Tsujuki 169 Williams F 212
Tsykalas 216 Wagener 50, 109 Williams O 744
Tubangui 59, 275, 300-1 Wagler 327, 370, 456, Willius 114
Tukalewski 463 459, 772 Wilms 54, 549, 552
Tullis 485 Wakeshima 168
Tulp 357 Waldeck 584
Turkhud 56, 704-5, 709, Walker B 275
820 Walker J 130, 135-6
Turner 615 Walther 583
Tyson 35, 80, 321-2, Walton 485
357-9, 364, 369, 469, Wang 151, 172
471, 771, 820 Wanson 670, 681
Person Index 835
Wilson 615 600, 623, 821 Yoshimoto 281

Wiltschur 408 Wundt 442 Yoshino 369-70
Winogradoff 306 Wurtz 707 Young 740
Winter 629 Wykoff 59, 308, 771
Witenberg 311 Zancarol 207, 235, 245
Wolff 197 Yamada 172, 428 Zeder 6-7, 325, 363,
Wolffhüggel 433 Yamagiwa 169, 172, 432, 457, 726, 744,
Wolfs 289 264 746
Wolphius 398 Yamaguti 730 Zenker 50, 442-4, 447,
Wood 582 Yarwood 310 579, 581, 583-4, 586-
Woodland 425 Yeh 737 7, 725, 822
Woodruff 653, 677 Yokogawa M 168, 173, Zimmerman 422
Wordsworth 368 176 Zschukke 675
Wormald 571, 573 Yokogawa S 56-7, 166- Zuelzer 744
Wright 86, 445 70, 173, 275, 303-6, Zune 735
Wrisberg 456 510, 555, 729, 822 Zurn 432
Wu 170 Yorke 737
Wucherer 81, 500, 502- Yoshida 119, 166, 169,
3, 513, 523, 526, 598- 275, 428-9, 477-9, 554
SUBJEC T
INDEX
- - disease 209, 520 discovery 499-501

Abiogenesis 29 epidemiology 527-8
Abramis 307 landmarks 540-1
Acanthocephala 2, 8 life cycle 502-10
Acanthocheilonema perstans 16, 737 nomenclature 500-1
Acanthocheilonema streptocerca 738 pathology 510-20
Acantogobius 304 prevention 528-31
Acerina 402 synopsis 499
Achatina 723 treatment 523-7
Achillurbania nouveli 297, 311 Ancylostoma malayanum 723
Achillurbania recondita 297 Ancylostomiasis 499-541
Acis 423 Ancylostomum duodenale 501
Acriflavine 216 Angiostrongylus cantonensis 723-4
Acupuncture 772 Angiostrongylus costaricensis 724-5
Aedes 605, 613 Anguillula intestinalis 13, 545-6
Afroplanorbis 243 Anguillula stercorale 544
Agamofilaria streptocerca 738 Anguillula stercoralis 13, 544-6
Agchylostoma duodenale 500 Anisakiasis 725
Agchylostomum ceylanicum 502 Anisakis marina 725
Alaria 297 Anisakis simplex 725
Albendazole 91 Anisus 301
Alocima - see Bithynia Ankylostoma duodenale 12, 501
Alternation of generations 43-5, 109, Annelida 2
327 Anopheles 612-3
Alyselminthus crassiceps 432 Anthelmintics
Amphimerus pseudofelineus 309 see also individual anthelmintics
Amphistomum hominis 302 traditional 75-82
Anacardium, oil of - see cashew nut 1800-99 82
oil 1900-24 82-4
Anaemia, iron deficiency 512-20 1925-49 84-8
Anaemia, pernicious 407-10 1950-74 88-92
Anatrichosoma cutanea 721 1975+ 92
Anchylostoma duodenale 13 Anthiomaline - see antimonials
Anchylostomum duodenale 501 Antimonials 83, 214-6, 282, 711
Ancylostoma braziliense 502, 721-2 Ants 298, 427
Ancylostoma caninum 510-1, 722 Aphanius 304
Ancylostoma ceylanicum 502 Arecha catechu 80, 374
Ancylostoma duodenale Arion ater 111
anaemia 512-22 Armigerus 244
clinical features 520-2 Arsenicals 84, 213, 711
diagnosis 522-3 Artemisia 77
836
Subject Index 837
Artyfechinostomum mehrai 309 Bilharzia polonica 202, 286

Artyfechinostomum sufratyfex 309 Biogenesis 53
Ascariasis 469-97 Biomphalaria - see Heliosoma,
Ascaridia columbae 473 Planorbis
Ascaris canis 744 Bismuth 83
Ascaris lumbricoides Bithiniol 88, 119, 173
clinical features 480-4 Bithynia 146-7, 307
diagnosis 484-5 Blackflies 667-670
discovery 469-71 Blanfordia 275-6
epidemiology 487-8 Blasenwürmer 7
landmarks 497 Blicca 307
life cycle 471-4 Bosmina 403
nomenclature 470, 473-4 Bothriocephalus latus 9-10, 390
pathology 474-80 Bothriocephalus liguloides 428
prevention 488-9 Bothriocephalus mansoni 428
synopsis 469 Bothriocephalus tropicus 388
treatment 485-7 Bradybaena 302
Ascaris maculosa 473 Brugia malayi
Ascaris marginata 473 discovery 604-5
Ascaris megalocephala 473 Brugia pahangi 528
Ascaris mystax 473, 746 Brugia patei 605
Ascaris suum 489-90 Brugia timori 605
Ascaris trichiura 457 Bulimus 146
Ascaris vermicularis 4, 440, 470 Bulinus - see Bullinus
Ascaris vermicularis cauda subulata 5 Bullinus 202-3, 241, 287-8
Aspidium, oleoresin of - see male fern Bythinella 178, 308
Australorbis 244
Avian schistosomes 286-7 Cambarus 177
Cambendazole 91, 561
Baermann technique 428 Camphora 82
Baginulus 724 Cancer 776
Bandwürmer 7 Capillaria aerophila 725-5
Barbus 307 Capillaria hepatica 726
Beetles 423 Capillaria philippinensis 726-7
Belascaris cati 746 Carbon tetrachloride 83-4, 132, 134,
Belascaris mystax 744, 746 136, 486, 524
Bephenium 88, 487, 526 Carcinus 311
Bertia studeri 421 Cardiocondyle 427
Bertiella mucronata 421 Cashew nut oil 84
Bertiella polyordna 421 Cephalocotylea 11
Bertiella satyri 421 Ceratocephyllus 423, 425
Bertiella studeri 421 Cercaria 42, 107, 109-10, 286-8
Betanaphthol 83, 136, 486, 524 Cestoda 2, 9
Betel nut - see Areca Cestoidea 9
Bible 30, 209, 588, 694 Cheilospirura 727
Bilharzia crassa 197 Cheiracanthus siamensis 731
Bilharzia haematobia 12, 189-91 Chenopodium, oil of 81, 462, 486, 524
Bilharzia magna 189 Chloroform 524
Chloroquine 85, 173 Cysticercus crispus 328

Chloxyl - see Hetol Cysticercus ex taenia mediocanellata
Chrysanthemum 78, 374 390
Clarias 731 Cysticercus fasciolaris 321, 323-4, 327-
Classification 1-28 9, 333, 433
Clonorchiasis 141-57 Cysticercus finna 7
Clonorchis endemicus 143 Cysticercus longicollis 432
Clonorchis sinensis Cysticercus pisiformis 320, 329-30, 333,
clinical features 149-50 365-6
diagnosis 151-1 Cysticercus tenuicollis 320-1, 324, 330
discovery 141-3
epidemiology 152-3 Davainea formosana 427
landmarks 157 Davainea madagascariensis 426-7
life cycle 143-7 Demerera filaria 734
nomenclature 142 Diaptomus 403-4, 412
pathology 147-9 Dibothriocephalus latus 399
prevention 153 Dibothrium latum 11, 399
synopsis 141 Dichlorophene 88, 136
treatment 151 Dicrocoelium dendriticum 297-0
Coenurosis 431-2 Dicrocoelium hospes 299
Coenurus cerebralis 329-30, 332-3, 432 Diethylcarbamazine 85, 487, 626, 653-
Coenurus glomerulatus 431 4, 679-80
Coenurus tenuicollis 324, 329, 389 Dioctophyma renale 728
Conocephalus 302 Dioplongonoporus fukuokaensis 422
Contracaecum osculatum 727 Dipetalonema arbuta 728
Corpse worms 769 Dipetalonema ozzardi 735
Crabs 165-6, 174, 177-8, 311 Dipetalonema sprenti 728
Crayfish 174 Dipetalonema streptocerca 738
Crustaceans 403-5, 428-9, 702-6, 711-3, Diphetarsone 462
731 Diphyllobothriasis 397-419
Ctenocephalides see Pulex Diphyllobothrium cordatum 428
Cucullanus 704 Diphyllobothrium dalliae 414
Cucurbita pepo 80, 374 Diphyllobothrium decipiens 430
Culex 604, 607, 609-11, 613, 626 Diphyllobothrium dendriticum 414
Culicoides 735-8 Diphyllobothrium erinacei 430-1
Cyclocheilichthys 308 Diphyllobothrium houghtoni 430
Cyclodontostomum purvisi 727 Diphyllobothrium lanceolatum 414
Cyclops 403-4, 428, 702-6, 711-3, 731 Diphyllobothrium latum
Cyprinus 307 clinical features 405-10
Cystica 9 diagnosis 410
Cysticercosis 355-83 differentiation 397-9
Cysticercus 363 epidemiology 411-3
Cysticercus bovis 390, 393 landmarks 419
Cysticercus cellulosae life cycle 399-405
clinical features 371-2 nomenclature 399
discovery 322, 362-3 pernicious anaemia 407-10
life cycle 364-9 prevention 413
nomenclature 8, 363 synopsis 397
see also Taenia solium treatment 410-1
Subject Index 839
Diphyllobothrium mansoni 429 Dithiazanine 88-9, 462, 561

Diphyllobothrium mansonoides 430 Dobium erinacei-europaei 431
Diphyllobothrium okumari 430 Dochmius ankylostomum 501
Diphyllobothrium pacificum 414 Dochmius trigonocephalus 502, 507
Diphyllobothrium ranarum 430 Dracontiasis - see dracunculiasis
Diphyllobothrium reptans 430 Dracunculiasis 693-720
Diphyllobothrium ursi 414 Dracunculus loa 12, 643
Diplocanthus 424 Dracunculus medinensis
Diplogonoporus grandis 422 clinical features 707-9
Diploscapter coronata 729 diagnosis 709
Dipterex - see metrifonate discovery 693-8
Dipylidium caninum 331, 364, 422-3 epidemiology 711-3
Dipylidium cucumerinum 422 incubation period 706-7
Dirofilaria conjunctivae 729 landmarks 720
Dirofilaria immitis 612, 729 life cycle 698-706
Dirofilaria repens 729 nomenclature 697-8
Dirofilaria tenuis 729 prevention 713-4
Dirofilaria ursi 730 synopsis 693
Distoma - 106, see also Distomum treatment 709-11
Distoma - see also Distomum Dryoptera filix mas - see male fern
Distoma buski 14, 160 Ducks 41
Distoma compactum 162
Distoma conjunctum 309 Earworms 768
Distoma cygnoides 109 Ebers papyrus - see Papyrus Ebers
Distoma endemicum 152 Echinochasma perfoliatus 299
Distoma haematobium 12, 188-9 Echinococcosis 319-53
Distoma hepaticum 7 Echinococcus altricipariens 12, 326, 332
Distoma hepatis endemicum sive Echinococcus alveolaris 433-4
innocuum 142 Echinococcus granulosus
clinical features 335-6
Distoma hepatis endemicum sive
diagnosis 337-8
perniciosum 142
discovery 319-26
Distoma heterophyes 14, 303
epidemiology 340-1
Distoma japonicum 14
landmarks 353
Distoma nodulosum 111
life cycle 326-33
Distoma pancreaticum 302
nomenclature 325
Distoma pulmonale 162
pathology 333-5
Distoma pulmonalis 162 prevention 342-3
Distoma rathouisi 129 synopsis 319
Distoma ringeri 14, 160 treatment 338-40
Distoma rude 162 Echinococcus hominis 325-5
Distoma sinense 14 Echinococcus hydatidosa 326
Distoma spathulatum 142 Echinococcus multilocularis 343-6
Distoma trigonocephalum 111 Echinococcus polymorphus 325
Distoma viverrini 308 Echinococcus scolicipariens 12, 326
Distoma westermanni 163 Echinococcus simiae 325
Distomum capense 190 Echinococcus simplex 326
Distomum crassum 13, 128 Echinococcus veterinorum 325-6, 331
Distomum hians 108 Echinococcus vogeli 346-7
Echinoparyphium paraulum 299 Fasciola melis 301

Echinoparyphium recurvatum 299 Fasciola revoluta 301
Echinostoma hortense 300 Fascioletta ilocanum 300
Echinostoma ilocanum 300 Fascioliasis 107-26
Echinostoma jassyense 301 Fasciolopsiasis 127-40
Echinostoma lindoense 300 Fasciolopsis buski
Echinostoma malayanum 309 clinical features 133-5
Echoing worms 769 diagnosis 135-6
Eliocharis 132 discovery 127-9
Emboitement 33, 38 epidemiology 136-7
Emetine 173, 216, 281 landmarks 140
Enterobiasis 439-54 life cycle 130-2
Enterobius vermicularis nomenclature 129
clinical features 444-5 pathology 133-8
diagnosis 445-6 prevention 137
discovery 439-40 synopsis 127
epidemiology 446-7 treatment 136
landmarks 454 Fasciolopsis fülleborni 129
life cycle 440-3 Fasciolopsis goddardi 129
nomenclature 440 Fasciolopsis spinifera 129
pathology 443-4 Fermentation 52
prevention 447-9 Ferrisea 205
synopsis 439 Ficus 81
treatment 447-9 Filaria bancrofti 15, 602
Entozoa 2 Filaria demarquayi 734-6
Epigenesis 32 Filaria dermathemica 662
Equivocal generation 29 Filaria diurna 15, 644
Eriocheir 165-6 Filaria immitis 729
Esox 401, 412 Filaria labialis 732
Eucalyptus, oil of 524 Filaria lacrymalis 10, 643
Euparyphium melis 301 Filaria loa 14, 643
Eurytrema pancreaticum 302 Filaria malayi 604
Eustoma rotundatum 725 Filaria medinensis 6
Eustrongyloides 730 Filaria nocturna 614, 644
Eustrongylus gigas 728 Filaria oculi 643
Eyeworms 768 Filaria oculi humani 10, 643
Filaria ozzardi 15
Fasciola gigantica 121 Filaria palpebralis 743
Fasciola hepatica Filaria papillosa haematobia canis
clinical features 116-8 domestica 729
diagnosis 118 Filaria perstans 15, 644
discovery 103-6 Filaria philippinensis 604-5
epidemiology 119-20 Filaria sanguinis hominis 13, 601, 603
landmarks 126 Filaria sanguinis hominis diurna 644
life cycle 106-14 Filaria sanguinis hominis major 644
prevention 121 Filaria sanguinis hominis minor 644,
synopsis 103 736
treatment 118-9 Filaria sanguinis hominis nocturna 644
Fasciola hominis 6 Filaria sanguinis hominis perstans
Subject Index 841
644, 736 Haplorchis pumilio 303

Filaria subconjunctivalis 643 Haplorchis tachui 303
Filaria volvulus 15 Haplorchis yokogawai 303
Filaria volvulxus 662-3 Helicella 298
Filariasis 597-640 Helicorbis 302
Filix mas - see Male fern Heliosoma 243
Fish 41, 144-5, 299, 304-8, 400-2, 731 Helminal 486
Fleas 423, 425 Helminth, derivation of term 2-3
Fluke 104 Helminthocorton 82
Formica 208 Hepaticola hepatica 726
Frogs 299, 301-2, 429 Heterakis maculosa 473
Furia infernalis 769-70 Heterobilharzia 287
Fusaria dispar 7, 457 Heterodera radicicola 449-50
Fusaria lumbricoides 7 Heterogenesis 52
Fusaria mystax 744, 746 Heterogony 505-6
Fusaria vermicularis 7 Heterophyes aegyptiaca 303
Heterophyes brevicaeca 311
Galumna 421 Heterophyes heterophyes 303-4
Galvinism 710 Heterophyes katsuradai 304
Gambusia 304 Heterophyes nocens 303
Gastrodiscoides hominis 302 Heterophyes yokogawai 305
Geese 44, 108 Hetol 89, 307
Gentian violet 85-6, 499, 561 Hexachlorophene 89
Gigantobilharzia 287 Hexylresorcinol 86, 136, 462, 486, 525
Glossobius 731 Himasthla muehlensi 305
Glottis 361 Hippeutis - see Planorbis
Gnathostoma hispidum 732 Höllenwurm 769-70
Gnathostoma pulchrum 732, 776-7 Hookworm - see Ancylostoma,
Gnathostoma siamense 731 Necator
Gnathostoma spinigerum 730-2 Hookworm disease 499-541
Gnathostomiasis 7302 Hycanthone 86, 217
Goeffroea surinamensis cortex 82 Hydatid - see Echinococcus
Gordius medinensis 4 Hydatigera granulosus 325
Grasshoppers 302 Hydatigera taeniaeformis 433
Gregarina 161-2 Hymenolepis diminuta 423-4
Ground-itch 509 Hymenolepis fraterna 425
Guinea worm - see Dracunculus Hymenolepis longior 425
medinensis Hymenolepis nana 424-6
Guinea worm infection - 693-720 Hypoderaeum conoidea 305
Gynaecophorus haematobia 189-90 Hypoloberca 177
Gyraulus 300
Idus 307
Haemonchus contortus 732 Illustrations of worms, early 771-2
Haemostrongylus ratti 723 Imaginary worms 765-70
Hagenia abyssinica 78, 374 Immunity 37, 774-6
Hakenwürmer 7 Indoplanorbis 301, 309
Halysis lata 7 Inermicapsifer madagascariensis 426
Halysis solium 7 Infection 26
Hampala 308 Infestation 26
Infusoria 39 Maggots, generation of 33-5

Intestina 4 Magic 773
Iron deficiency anaemia 512-20 Male fern 76-7, 213, 301, 373, 375, 524
Isalopotamon 177 Mallotus philippinensis 80, 374
Iulus 473 Mammomonogamus laryngeus 733
Ivermectin 92, 561, 680 Mansonella ozzardi
Mansonella perstans 736-8
Jericho 209 Mansonella streptocerca 738
Mansonia 613
Kahun papyrus 209 Massage 772
Kamala 80, 374 Mastigodes hominis 7
Katayama disease 279 Mebendazole 91, 340, 449, 462, 487,
Katayama - 273 526, 727
Kosso - see Kousso Melania 145-6, 164, 166, 306
Kousso 78-9 Menichopholan - see Niclofolan
Meningonema peruzzii 738
La dauve 114 Mepacrine 86-7, 375, 426
Lagochilascaris minor 733 Mesocestoides lineatus 426
Latex of higueron - see Leche de higueron Mesocestoides variabilis 926-7
Leche de higueron 81-2, 462, 523 Metagonimus 174
Leptodera 544 Metagonimus yokogawai 305
Leuciscus 307, 473 Metastrongylus elongatus 739
Leucobia 144 Metrifonate 89, 217, 253
Levamisole 91, 487 Metronidazole 119, 711
Lice 422 Microfilaria bolivarensis 739
Ligula mansoni 428 Microfilaria rodhaini 739
Limnea 110-3 - see also Lymnaea Microfilaria semiclarum 739
Limneus 110-3 - see also Lymnaea Micronema deletrix 739-40
Lithoglyphosis 288, see Tricula Microscope 36
Loaches 300 Miracils - see hycanthone, lucanthone
Loa loa Misgurnus 300
clinical features 649-51 Mites 421
diagnosis 651-2 Molluscicides 221
discovery 641-6 Monkey 189, 197
epidemiology 654 Monostomum flavum 108
landmarks 660 Monostomum mutabile 108-9
life cycle 647-9 Moon 773
nomenclature 643 Mordwurm 769-70
periodicity 643-7 Morerastrongylus costaricensis 724
prevention 655 Mosquitoes 606-613
synopsis 641 Moxibustion 772-3
treatment 652-4 Mugil 304
Loiasis 641-60 Multiceps longihamatus 433
Lota 401, 412 Multiceps multiceps 432
Loxotrema ovatum 305 Multiceps serialis 432
Lucanthone 86, 216, 282 Music 370, 773
Lumbricus 3-4, 322, 324 Mytilus 305
Lymnaea 107, 286, 301, 305 - see also Myzelmintha 11
Limneus, Limnea
Subject Index 843
Nanophyes salmincola 311 Opisthorchis guayaquilensis 309

Nanophyetus salmincola 311 Opisthorchis noverca 308-9
Nanophyetus schickhobalovi 311 Opisthorchis sinensis 142
Nasal worms 768 Opisthorchis tenuicollis 308
Nasturtium officinale 120 Opisthorchis viverrini 308
Necator americanus Orientobilharzia 287
discovery 501 Ornithobilharzia 287
nomenclature 501 Ostertagia circumcincta 741
see also Ancylostoma duodenale Ostertagia ostertagi 741
Necator suillis 740 Oxamniquine 90, 253
Nematoda 1, 8 Oxantel 90
Nematomorpha 2 Oxytrema 311
Niclofolan 174 Oxyuris "incognita" 449
Niclosamide 89, 375, 411, 426 Oxyuris vermicularis 10, 440
Niridazole 89-90, 217, 253, 282, 711
Nomenclature, rules of zoological 16 Papyrus Ebers 75-6, 209, 355, 439,
-24 469, 520, 693
Nomenclature 1-28, see also individual Parafossarulus - see Bithynia
worms Paragonimiasis 159-85
Notropis 144 Paragonimus africanus 177
Paragonimus ecuadoriensis 177
Odontobutis 306 Paragonimus heterotremus 177
Oesophagostomum apiostomum 740 Paragonimus hueitungensis 177
Oesophagostomum bifurca 740 Paragonimus kellicotti 176-7
Oesophagostomum brumpti 740 Paragonimus mexicanus 178
Oesophagostomum stehpanosum 740 Paragonimus miyazakii 178
Oleum animali Dippelis 82 Paragonimus peruvianis 178
Oleum cajeputi 82 Paragonimus szechuanis 178
Oleum chaberti 82 Paragonimus tuanshahensis 177
Oleum terebinthicae 82 Paragonimus westermani
Olive oil 448 clinical features 171-2
Onchocerca dermathemica 662 diagnosis 172
Onchocerca gutturosa 684 differentiation 177
Onchocerca volvulus discovery 159-63
clinical features 670-7 epidemiology 174-5
diagnosis 677-8 landmarks 185
discovery 661-4 life cycle 164-9
epidemiology 681-2 nomenclature 163
landmarks 691 pathology 169-70
life cycle 667-70 prevention 175-6
nomenclature 664 synopsis 159
pathology 665-7, 670-7 treatment 172-4
prevention 682-4 Parascaris equorum 473
synopsis 661 Parasitism 24-5
treatment 679-80 Parasitophobia 770
Onchocerciasis 661-91 Paromomycin 90
Oncomelania - see Blanfordia, Parthenogenesis 549
Katayama Paryphostomum sufratyfex 309
Opisthorchis felineus 306-7 Pelodera strongyloides 741
Perca 402 Pyrvinium - see Viprynium

Periodicity 613-5
Pernicious anaemia 407-10 Quinacrine - see Mepacrine
Phenothiazine 87, 449
Philophthalmus 309 Raillietina celebensis 427
Phocanema 743 Raillietina demerariensis 427
Physaloptera caucasica 741 Raillietina madagascariensis 426
Physaloptera mordens 741 Rats 724
Physopsis 203-4 Rattus 724
Piperazine 87, 439, 486-7 Redia 108
Pirenella 304 Rhabditis 502, 544, 546, 742
Plagiorchis 309 Rhabdonema intestinale 14
Plagiorchis congolensis 310 Rhabdonema strongyloides 548
Plagiorchis javensis 310 Rictularia 742
Plagiorchis muris 310 Rockefeller Foundation 222, 517, 529
Plagiorchis philippinensis 310 -30
Planaria latiuscula 103 Royal yellow worms 107-8
Planorbarius 204 Rules of zoological nomenclature 16
Planorbina 244 -24
Planorbis 132, 137, 202-4, 241, 341-4, Rundwürmer 7
289, 300-1
Platyhelminthes 1 Salmo 306, 412
Plectoglossis 305-6 Salpae 109
Plerocercoides prolifer 430 Salvarsan - see Arsenicals
Polycephalus echinococcus 7, 325 Santonin - see Semen-contra-vermes
Polycephalus hominis 7, 325 Saugwürmer 7
Polysarcus 163 Scannus 423
Pomatiopis 177 Scheloribates 421
Pomegranate 76, 374 Schistosoma bovis 202, 287
Potadoma 177 Schistosoma cattoi 267
Potamon 165-8 Schistosoma haematobium
Praziquantel 92, 119, 136, 151, 217, clinical features 208-11
282, 307, 375, 411, 426 dams and 219
Preformation 33 diagnosis 211-2
Priority, law of 18, 22-4 discovery 187-9, 191
Proglottis 361 epidemiology 218-9
Prontosil - see Sulphonamides landmarks 231
Pseudasbora 144, 146 nomenclature 189-91
Pseudoparasites 770 pathology 205-8
Pseudorhabditis stercoralis 547 prevention 220-2
Pulex 422-3, 425 synopsis 187
Pulmonema cantonensis 723 treatment 212-8
Pumpkin seeds 80, 374 Schistosoma incognitum 287
Punica granatum 76, 374 Schistosoma intercalatum 287
Punta 308 Schistosoma japonicum
Purgatives 82, 485-6 clinical features 279-81
Pygidiopsis summa 310-1 diagnosis 281
Pyrantel 90, 449, 487, 526 discovery 263-8
Pyrgophyla 202 epidemiology 283-4
Subject Index 845
landmarks 295 Spirocerca lupi 742

life cycle 268-76 Spirometra 430
pathology 276-9 Spirometra erinacei 431
prevention 284-6 Spirometra houghtoni 430-1
synopsis 263 Spirometra neoplastica 776-7
treatment 281-2 Spirometrosis 430-1
Schistosoma mansoni Spontaneous generation 29-53
clinical features 249-51 Stannum 82
diagnosis 251-3 Stellanctchasmus falcatus 312
discovery 233-40 Stephanolecithus parvus 168
epidemiology 254 Stibocaptate - see Antimonials
landmarks 262 Stibophen - see Antimonials
life cycel 240-4 Stilbazium 90
nomenclature 236 Stizolobium 82
pathology 244-9 Stizostedeon 412
prevention 220-2 Stomachida lumbricoides 470
synopsis 187 Strobilos 361-2
treatment 217-8 Strongyloides intestinalis 15
Schistosoma margrebowiei 288 Strongyloides stercoralis
Schistosoma matthei 288 clinical features 557-9
Schistosoma mekongi 288 diagnosis 559-60
Schistosoma rodhaini 289 discovery 543-50
Schistosome dermatitis 286-7 epidemiology 562
Schistosomes, avian 286-7 landmarks 569-70
Schistosomiasis haematobia 187-231 life cycle 551
Schistosomiasis japonica nomenclature 546
Schistosomiasis mansoni 233-62 pathology 550-1, 553-7
Sclerostoma caninum 722 prevention 562
Sclerostoma duodenale 12, 501 synopsis 543
Scolex 362 treatment 560-1
Segmentina 130-2, 137 - see also Strongyloidiasis 543-70
Planorbis Strongylus colubriformis 746
Semen-contra-vermes 77, 486 Strongylus contortus 732
Semisulcospira - see Melania, Thiara Strongylus convulutus 741
Sesarma 166 Strongylus elongatus 739
Sheep rot 116-7, 119-20 Strongylus fülleborni 562
Simulium 668-70 Strongylus fülleborni-like 562
Siropotamon 177 Strongylus gigas 728
Slugs 724 Strongylus intestinalis 546
Snails - see individual genera Strongylus lupi 742
Snails 49, 106-14, 130-2, 143-7, 164-9, Strongylus ostertagi 741
198-205, 240-4, 270-6, 298, 300-2, Strongylus probulurus 746
304-5, 307, 309, 311, 723 Strongylus quadridentatus 501
Snakes 429, 730 Strongylus subtilis 747
Sparganosis 428-30 Sudanautes 177
Sparganum erinacei-europaei 431 Sulphonamides 173
Sparganum mansoni 428 Suramin 87, 679
Sparganum proliferum 430 Syngamus kingi 733
Spelotrema brevicaeca 311 Syngamus laryngeus 733
Syngenesis 33 nomenclature 3-4, 388-9

Systema Naturae 1, 5, 18, 362-3, 386, prevention 393
440, 469 synopsis 385
treatment 392
Tabanids 647-9 Taenia sans épine 386, 398
Taenia à épine 398 Taenia secunda Plateri 398
Taenia alveolaris 344 Taenia serialis 431-2
Taenia brauni 431-2 Taenia serrata 330, 365-6
Taenia canina 14, 422 Taenia solium
Taenia cateniformis 331 clinical features 369-72
Taenia cellulosae 6 diagnosis 372-3
Taenia crassiceps 329, 432-3 discovery 355-63
Taenia crassicollis 328-30, 332, 433 epidemiology 376
Taenia cucumerina 331, 364, 422 landmarks 383
Taenia cucurbitina grandis saginata 5, life cycle 364-9
386-7 nomenclature 3-4, 6, 356-7, 361-2
Taenia cucurbitina plana pellucida 5, prevention 376-7
386-7 synopsis 355
Taenia demerariensis 427 treatment 373-5
Taenia dentata 388 Taeniarhynchus saginata 389
Taenia echinococcus 12, 331-3 Taeniasis saginata 385-396
Taenia egyptiaca 424 Taeniasis solium 355-83
Taenia elliptica 12 Taenia taeniaeformis 324, 328, 433
Taenia ex cysticerco tenuicollo 365-6 Taenia vesicularis, cerebrina,
Taenia flavopunctata 12 multiceps 432
Taenia hydatigena 320, 324, 365 Taenia visceralis 6
Taenia hydatigena granulosa 325 Taenia visceralis socialis granulosus 5,
Taenia inerme 388 325-6
Taenia infantis 457 Taenia vulgaris 6
Taenia intestinorum 398 Tanaceti vulgaris semina 82
Taenia lata 4 Taphius 244
Taenia longihamatus 433 Tartar emetic - see Antimonials
Taenia madagascariensis 427 Tenebrio 328, 423, 425
Taenia mediocanellata 12, 388 Ternidens deminutus 742-3
Taenia multiceps 332, 431-2 Terranova 743
Taenia murina 424 Tetrachlorethylene 87, 136, 525
Taenia nana 12, 331 Tetramisole 91, 487
Taenia osculis marginalibus oppositus Tetrapetalonema perstans 737
422 Tetrapetalonema streptocerca 738
Taenia pellucida 388 Thecosema 189
Taenia pisiformis 329 Thelazia californiensis 744
Taenia prima Plateri 398 Thelazia callipaeda 743
Taenia saginata Theology 38
clinical features 392 Thiabendazole 91, 449, 487, 526, 561,
diagnosis 392 586, 727
discovery 385-9 Thiara 145-6 - see also Melania
epidemiology 393 Thomas, curse of 616
landmarks 396 Thominx aerophila 725
life cycle 389-91 Thymobenzene 213
Subject Index 847
Tilapia 304 Trichosoma cutaneum 721

Tin 78, 374 Trichostrongyliasis 746-7
Tinca 307 Trichostronyglus axei 746
Toothworms 765-8 Trichostrongylus brevis 746
Toxocara canis 473, 744 Trichostrongylus colubriformis 746
Toxocara cati 473, 746 Trichostrongylus orientalis 746
Toxocariasis 744-6 Trichostrongylus skrjabini 746
Transmission of worms 29-74 Trichostrongylus vitrinus 746
early times 29-33 Trichuriasis 455-68
1650-1699 33-7 Trichuris suis 463
1700-1749 37-9 Trichuris trichiura
1750-1799 39-41 clinical features 459-61
1800-1824 41-3 diagnosis 461-2
1825-1849 43-6 discovery 455-7
1850-1874 46-53 epidemiology 463
1875-1899 53-5 landmarks 468
1900-1924 55-8 life cycle 457-8
1925+ 68-9 nomenclature 456-7
landmarks 70-3 pathology 458-9
see also Individual worms prevention 463
Trapa 132 synopsis 455
Treatment, unorthodox 772-3 treatment 462
Treatment, worms as 774 Trichuris vulgaris 457
Trematoda 1, 8-9 Trichuris vulpis 463-4
Trichina affinis 10, 457 Tricula 177-8, 288
Trichina spiralis 10, 573 Troglotrema salmincola 311
Trichinella spiralis Tropical eosinophilia 629-30
clinical features 582-4 Tropicorbis 243
diagnosis 584-5 Turpentine 374, 448, 462, 486
discovery 571-80 Tylenchus 737
epidemiology 586-8 Tympanotonus 304
landmarks 596
life cycle 578-80 Umbilical worms 768-9
nomenclature 573 Uncinaria americana
pathology 580-2 15Uncinaria duodenale 501
prevention 588-91 Uncinaria duodenalis 501
synopsis 571 Uncinaria stenocephala 501-2, 747
treatment 585-6 Unio 193
Trichinosis 571-96 Univocal generation 36
Trichobilharzia 286 Unorthodox treatment 772-3
Trichocephalos 5
Trichocephalus affinis 458
Trichocephalus crenatus 458
Trichocephalus depressiusculus 458-9
Trichocephalus dispar 11, 457, 579
Trichocephalus hominis 6
Trichocephalus trichiurus 15
Trichodectes 422
Trichosoma aerophilum 725
Urine worms 768 epidemiology 626-7

landmarks 640
Vermes 1 life cycle 606-13
Verminus 777 nomenclature 604
Vermis 1, 4 pathology 618-23
Viprynium 92, 449 periodicity 613-5
Vitamin B12 409-10 prevention 627-8
synopsis 597
Water caltrop 132, 136-7 treatment 624-6
Water chestnut 132, 136-7 Wuchereria malayi 605
Watercress 120 Wuchereria pahangi 605
Watsonius watsoni 311-2
Worm, derivation of term 1 Xenopsylla 423, 425
Wormseed oil - see Oil of
Chenopodium Zebrina 298
Wuchereria bancrofti Zoological nomenclature 16-24
clinical features 615-23 Zoophyta 4
diagnosis 623-4
discovery 597-605

Book Der Fru

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Book Der Fru

Uploaded by

Copyright:

Available Formats

A HISTORY OF HUMAN

Department of Clinical Microbiology and Infectious Diseases

Tel: Wallingford (0491) 32111

©C.A.B International 1900. All rights reserved. No part of this

British Library Cataloguing in Publication Data

Printed and bound in the UK by Bookcraft (Bath) Ltd

1. The nomenclature and classification of worms 1

2. Understanding the origin and transmission of worms 33

3. The discovery and development of anthelmintics 75

4. Fasciola hepatica and fascioliasis 103

5. Fasciolopsis buski and fasciolopsiasis 127

6. Clonorchis sinensis and clonorchiasis 141

7. Paragonimus westermani and paragonimiasis 159

8. Schistosoma haematobium and schistosomiasis haematobia 187

9. Schistosoma mansoni and schistosomiasis mansoni 233

10. Schistosoma japonicum and schistosomiasis japonica 263

11. Trematode infections of lesser importance 297

12. Echinococcus granulosus and echinococcosis or hydatid

13. Taenia solium and taeniasis solium and cysticercosis 355

14. Taenia saginata and taeniasis saginata 385

15. Diphyllobothrium latum and diphyllobothriasis 397

16. Cestode infections of lesser importance 421

17. Enterobius vermicularis and enterobiasis 439

18. Trichuris trichiura and trichuriasis 455

19. Ascaris lumbricoides and ascariasis 469

20. Anyclostoma duodenale, Necator americanus and

21. Strongyloides stercoralis and strongyloidiasis 543

22. Trichinella spiralis and trichinosis 571

23. Wuchereria bancrofti, Brugia species and filariasis 597

24. Loa loa and loiasis 641

25. Onchocerca volvulus and onchocerciasis 661

26. Dracunculus medinensis and Guinea worm disease 693

27. Nematode infections of lesser importance 721

28. Miscellanea 765

29. Biographies 783

Person index 823

Subject index 836

In his History of Tropical Medicine published in 1939, HH Scott wrote :

THE NOMENCLATURE AND CLASSIFICATIO N

THE NATURE OF WORMS

Worms are multicellular invertebrate animals, each of which belongs to one of

The early physicians and naturalists, however, regarded parasitic worms a s

AWARENESS OF PARASITIC WORMS DOWN THE AGES

Classis Vermes CURRENT NAME

lumbricoides, "lumbricus latus" ("latus" = "broad, wide") for Taenia species,

Table 1.2. Classification of worms infecting humans according to Goeze, 1782 21

Genus CURRENT NAME

Ascaris lumbricoides Ascaris lumbricoides

Table 1.3. Classification of worms infecting humans according to Gmelin, 1788-1793 20

Classis Vermes CURRENT NAME

Zeder, 1800 Zeder, 1803 CURRENT NAME

ed to be a revision of Goeze's work (Erster Nachtrag zur Naturgeschichte der

Table 1.5. Classification of worms infecting humans according to Rudolphi. 1808-1810 39

Ordo Nematoideorum CURRENT NAME

Gmelin (Table 1.4). He divided (incorrectly) Gmelin's Taenia cellulosae into

Table 1.6. Classification of worms infecting humans according to Bremser, 1819 10

Nematodeorum CURRENT NAME

rived from the Greek word µ (TREMATODES) meanin g

Table 1.7. Classification of worms infecting humans according to Dujardin, 1845 17

Nématoides CURRENT NAME

changes to the parasites infecting humans in this volume, other than hi s

Table 1.8. Classification of worms infecting humans according to Diesing, 1849-1851 16

Nematoidea CURRENT NAME

Table 1.9. Classification of worms infecting humans according to Küchenmeister,