Professional Documents
Culture Documents
2002 Null
2002 Null
2002 Null
Edited by
Gagandeep Singh
and
Sudesh Prabhakar
Department of Neurology
Postgraduate Institute of Medical Education and Research
Chandigarh, India
CABI Publishing
A catalogue record for this book is available from the British Library,
London, UK.
Contents
Contributors ix
Preface xiii
Abbreviations xiv
SECTION I TAENIA SOLIUM CYSTICERCOSIS: BASIC SCIENCE
v
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vi Contents
Contents vii
Contributors
x Contributors
Oscar H. Del Brutto, Department of Neurology, Luis Vernaza Hospital, Guayaquil, Ecuador.
Louis Dongmo, School of Medicine, Yaoude, Cameroon.
Michel Druet-Cabanac, Institut d’Epidémiologie Neurologique et de Neurologie Tropicale,
EA 3174 (Neuroparasitologie et Neuroépidémiologie Tropicale) Faculté de Médecine, 2 rue
du Dr Marcland, 87025 Limoges, France.
Michel Dumas, Institut d’Epidémiologie Neurologique et de Neurologie Tropicale, EA 3174
(Neuroparasitologie et Neuroépidémiologie Tropicale) Faculté de Médecine, 2 rue du Dr
Marcland, 87025 Limoges, France.
Alfonso Escobar, Instituto de Investigaciones, Biomedicas, National Autonomous University
of México, Ciudad Universitaria 04510, México DF, México.
Carlton A.W. Evans, Imperial College, Department of Infectious Diseases, Hammersmith
Hospital, Du Cane Road, London W12 0NN, UK.
Ana Flisser, Departmento de Microbiologia y Parasitologia, Facultad de Medicina, National
Autonomous University of México, Ciudad Universitaria, San Angel, México 04510 DF,
México.
Orestes V. Forlenza, Laboratory of Neuroscience (LIM-27), Department and Institute of
Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Hector H. García, Departments of Transmissible Diseases, Microbiology, and Pathology,
Universidad Peruana Cayetano Heredia, Lima, Peru.
José Garcia-Noval, Centro de Investigaciones de las Ciencias de la Salud, Facultad de
Ciencias Medicas, Universidad de San Carlos, Zona 12, Guatemala City, Guatemala.
Ravindra K. Garg, Department of Neurology, King George’s Medical College, Lucknow,
226 003, Uttar Pradesh, India.
Robert H. Gilman, Department of International Health, Johns Hopkins School of Public
Health, Johns Hopkins University, 615 N Wolfe St, Room W 3501, Baltimore, Maryland
21205, USA.
Armando E. Gonzalez, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de
San Marcos, Lima, Peru.
Dinora F. González-Esquivel, Laboratorio de Neuropsicofarmacologia, Instituto Nacional de
Neurologia y Neurocirugia, México City, México.
Rakesh K. Gupta, Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of
Medical Sciences, Rae Bareli Road, Lucknow 226 014, Uttar Pradesh, India.
W. Allen Hauser, Department of Neurology and Public Health, College of Physicians and
Surgeons, Columbia University, GH Sergievsky Center, 630 West 168th Street, New York
10032, USA.
Akira Ito, Department of Parasitology, Asahikawa Medical College, Midorigaoka-Higashi
2-1-1-1, Asahikawa 078-8510, Hokkaido, Japan.
Satish Jain, Department of Neurology, Neurosciences Center, All India Institute of Medical
Sciences, New Delhi, 110 029, India.
Helgi Jung, Laboratorio de Neuropsicofarmacologia, Instituto Nacional de Neurologia y
Neurocirugia, México City, México.
Alok M. Kar, Department of Neurology, King George’s Medical College, Lucknow, 226 003,
Uttar Pradesh, India.
Atul Kumar, Dr Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of
Medical Sciences, Ansari Nagar, New Delhi 110 029, India.
Teresa Lopez, Laboratorio de Micribiologia y Parasitologia, Facultad de Medicina
Veterinaria, Universidad Nacional Mayor de San Macos, Cdra. 29 Av. Circunvalacion s/n
San Borja, Lima, Peru.
Mahesh C. Maheshwari, Department of Neurology, Neurosciences Center, All India Institute
of Medical Sciences, New Delhi, 110 029, India.
Olga Mata-Ruiz, Departmento de Biotecnologia, Instituto de Diagnostico y Referencia
Epidemiologicos, Secretaria de Salud, México DF, México.
Contributors xi
xii Contributors
Bhawani S. Sharma, Department of Neurosurgery, CN Center, Room 720, All India Institute
of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.
Namrata Sharma, Dr Rajendra Prasad Center of Ophthalmic Sciences, All India Institute of
Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.
Gagandeep Singh, Department of Neurology, Dayanand Medical College and Hospital,
Ludhiana, 141 001, Punjab, India.
Bhim S. Singhal, Department of Neurology, Bombay Hospital Institute of Medical Sciences,
12 Marine Lines, Mumbai, 400 0020, India.
Achal Srivastava, Department of Neurology, Neurosciences Center, All India Institute of
Medical Sciences, New Delhi, 110 029, India.
Raquel Tapia-Romero, Departmento de Biotecnologia, Instituto de Diagnostico y Referencia
Epidemiologicos, Secretaria de Salud, México DF, México.
Patricia Tato, Department of Microbiology and Parasitology, Faculty of Medicine, National
Autonomous University of México, México DF 04510, México.
Judy M. Teale, Department of Microbiology, The University of Texas Health Science Center at
San Antonio, San Antonio, Texas 78229, USA.
Manjari Tripathi, Department of Neurology, Neurosciences Center, All India Institute of
Medical Sciences, New Delhi, 110 029, India.
Victor C.W. Tsang, Division of Parasitic Diseases, National Center for Infectious Diseases,
Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
Manuela Verastegui, Laboratorio de Parasitologia, Facultad de Ciencias, Universidad
Peruana Cayetano Heredia, Av. Honorio Delgado s/n Urbanizacion Ingeniera, San Martin
de Porres, Lima, Peru.
Noshir H. Wadia, Director of Neurology, Jaslok Hospital and Research Center, Mumbai,
India.
Karen M. Weidenheim, Division of Neuropathology, Montefiore Medical Center, AECOM,
YU111, East 210th Street, Bronx, New York 10467, USA.
A. Clinton White Jr, Infectious Disease Section, Department of Medicine, Baylor College of
Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Patricia P. Wilkins, Division of Parasitic Diseases, National Center for Infectious Diseases,
Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
Marianna Wilson, Division of Parasitic Diseases, National Center for Infectious Diseases,
Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
Hiroshi Yamasaki, Department of Parasitology, Asahikawa Medical College, Midorigaoka-
Higashi 2-1-1-1, Asahikawa, 078-8510, Hokkaido, Japan.
Preface
Neurocysticercosis and the macroparasite Taenia solium, which causes it, have been known
about for time immemorial. Through history, one can follow the development of concepts
regarding the aetiology, pathology, clinical science and treatment of the disorder. Recent
times have however been complicated by accumulating knowledge regarding molecular biol-
ogy, immunology and genetics of the disorder. The relationship between the molecular labo-
ratory and bedside clinical practice is becoming increasingly powerful. In these times of
molecular advances, a review of neurocysticercosis and T. solium that focuses on past accom-
plishments, current understanding and future hopes seems appropriate. A number of scien-
tific antecedents mean that the goals of effective treatment and, more importantly, eradication
are foreseeable. This alone prompted the genesis of this textbook, which symbolizes the spirit
of unity between basic researchers, clinicians and field workers. Since the book involved a
large number of subspeciality areas including parasitology, immunology, biology, genetics,
epidemiology and public health, clinical neurology, radiology and veterinary medicine, it
was impossible for two authors alone to write such a volume. Therefore, we solicited the con-
tribution of a number of experts, each with great depth of knowledge and experience in their
respective areas. The contributors to this book are its principal strength and we are indebted
to them for their time and effort spent not only in writing their respective chapters but also
for the years of painstaking work that led to the realization of knowledge through basic, clini-
cal or field research. It is because of their involvement, that the book turns out what it was
meant to be, a ‘one-stop shop for T. solium cysticercosis’.
We express our appreciation of several associates among the contributors, who gave
invaluable suggestions while planning the book project and were also involved in stimulat-
ing discussions: James Allan, Peter Schantz, Ana Flisser, Patricia Wilkins, Hector García,
Akira Ito, Phillip Craig, Arturo Carpio, Carlton Evans and Svetlana Agapejev. Davinder
Singh and Arun Gupta provided excellent editorial assistance with the text and illustrations,
respectively. Finally, this book is a tribute to those millions afflicted by the disorder. They
have contributed in their own way to the understanding of the disorder. It is our fervent
hope that the recent accomplishments in scientific understanding brought out in this volume
will ultimately lead to the goal of complete global eradication of the parasite, T. solium.
Abbreviations
Abbreviations xv
HU Hounsfield units
ICH intracranial hypertension
ICP intracranial pressure
IDEMSC intradural extramedullary spinal cysticercosis
IEF immunoelectrophoresis
IFN interferon
IgG immunoglobulin G
IgM immunoglobulin M
IHA indirect haemagglutination assay
IL interleukin
ILAE International League Against Epilepsy
IMOA intramuscular oncosphere assay
IMSC intramedullary spinal cysticercosis
IP intraperitoneal
IV intravascular
IVNC intraventricular neurocysticercosis
LLGP lentil lectin-bound glycoproteins
LrRNA large subunit rRNA
MAb monoclonal antibody
MF metacestode factor
MoAb monoclonal antibody
MRI magnetic resonance imaging
mtDNA mitochondrial deoxyribonucleic acid
NADH reduced nicotinamide-adenine dinucleotide
NADPH nicotinamide-adenine dinucleotide phosphate (reduced form)
NC neurocysticercosis
Nd:YAG neodymium:yttrium alminium-garnet
NOD-SCID non-obese diabetic-severe combined immunodeficiency
Pc corrected P value
PCR polymerase chain reaction
PD proton density
PoAb polyclonal antibody
PRA participatory rural appraisal
Rnase ribonuclease
RR relative risk
rRNA ribosomal ribonucleic acid
SCG solitary cysticercus granuloma
SDS-PAGE sodium dodecyl sulphate-polyacrylamide gel electrophoresis
SrRNA small subunit rRNA
SSECTL single small enhancing CT lesion
sTS synthetic Taenia solium
TCD transcranial doppler
Th T helper cell
TNF tumour necrosis factor
tRNA transfer ribonucleic acid
VPS ventriculoperitoneal shunt
Zbigniew S. Pawlowski
No animal has been responsible for more hypotheses, discussions and errors than the tapeworm
Casimir Joseph Davaine, 18601
2 Z.S. Pawlowski
comprises 11 genera of small to large sized nata, and less frequently T. solium adult
tapeworms. They have a holdfast organ – tapeworms have been noted, often giving
the scolex – and an elongated-segmented rise to taxonomic confusion in the past. The
tape-like body. Each segment has intri- taxonomic revision of genus Taenia, pub-
cately developed sexual organs but does lished by Verster, recognizes only two
not have an alimentary canal. The genus species of Taeniidae, namely, T. solium and
Taenia has about 20 species; important T. saginata as capable of parasitizing the
among these are T. solium (pork tapeworm), human gut8,9. The so called Asian Taenia,
T. saginata (beef tapeworm), T. crassiceps first described in 1980s in Taiwan, was ini-
(rodent tapeworm), T. hydatigena (canine tially proposed to be a new species but is
tapeworm), T. ovis (canine tapeworm) and now accepted to be a subspecies of T. sagi-
T. pisiformis (canine tapeworm). Only a few nata namely, T. saginata asiatica (see Chapter
species among Taeniidae present potential 5)10,11. The adult stage of T. solium needs to
health hazards to humans: Taenia solium, T. be differentiated from other Taeniidae, par-
saginata, Echinococcus granulosus and E. mul- ticularly the closely related T. saginata (Table
tilocularis. In addition, there are anecdotal 1.1, Fig. 1.1). Differences between scolices of
reports of human infection with T. crassi- T. solium and T. saginata were recognized as
ceps, T. hydatigena and T. multiceps. Few early as in the 17th century7. T. solium scol-
other zoonotic species, e.g. T. taeniaeformis, ices are armed with hooks, while T. saginata
T. ovis and T. hydatigena are good models scolices are not. This easily visible criterion
for laboratory and field studies; the latter is now of little routine diagnostic value as
can hardly be performed with T. solium on intact scolices can rarely be found after
account of its high pathogenic risk poten- treatment with modern anthelminthics (that
tial. Therefore, studies of related species cause considerable damage to the worm). In
constitute a useful source of information on general, the adult T. solium is smaller and
biology and transmission of T. solium. more delicate than T. saginata. For nearly
Although the ‘Standardized Nomenclature 150 years, gravid proglottides of T. solium
of Animal Parasitic Diseases’ recommended and T. saginata were differentiated by count-
the use of the term ‘taeniosis’ (T. solium tae- ing the number of lateral uterine branches.
niosis, T. saginata taeniosis), the term, ‘taeni- In 1967, Verster questioned this criterion
asis’ continues to be widely used6. The term, and proposed three morphological charac-
‘cysticercosis’ denotes infection with the teristics for distinguishing T. solium from T.
metacestode stage (cysticercus) of Taenia. It saginata, namely the presence of an armed
was as late as 1853 that cysticerci were rostellum, three-lobed ovary and the
demonstrated to be a developmental stage absence of a vaginal sphincter (Table 1.1,
of T. solium and not a separate parasite Fig. 1.1)8. These differences are rarely
species as was previously held7. The terms, observed in routine diagnostic parasitol-
‘cysticercus cellulosae’ and ‘cysticercus ogy practice as scolices and mature
bovis’ were introduced in the 18th century; proglottides are not commonly available
these are of historic value only and should and counting ovarian lobes as well as find-
never be used in a generic fashion. In med- ing the vaginal sphincter requires fixation
ical literature, the expression ‘cysticercosis’ and staining of mature proglottides, which
synonymously denotes T. solium metaces- is an arduous procedure.
tode infection unless otherwise specified, Enzyme electrophoresis for the differentia-
e.g. bovine cysticercosis. tion of Taeniidae was elaborated in the early
1970s; it has been replaced by DNA finger-
printing in the 1990s12,13. Specific DNA probes
Differences between T. solium, T. saginata for T. solium and T. saginata are now avail-
and T. saginata asiatica able13. Intraspecific DNA differences were
demonstrated between T. solium tapeworms
Several morphological abnormalities of originating from various continents (reviewed
strobila or individual proglottides of T. sagi- in Chapter 5)14. These molecular studies also
Table 1.1. Morphological differences between T. solium, T. saginata and T. saginata asiatica (compiled from references 10, 18, 37 and 46).
4/9/02
Intermediate host Pig, wild boar Cattle, reindeer Pig, cattle, goat, some wild mammals
Metacestodes
4:37 pm
Adult tapeworm
Scolex
Diameter (m) 0.6–1.0 1.5–2.0 0.8
Number of suckers 4 4 4
Diameter of suckers (mm) 0.4–0.5 0.7–0.8 0.24–0.29
Rostellum Present Absent Present
Number of hooks 22–32 Absent Absent
Proglottides
Length (mm) 1.5–8 4–12 c. 3.5
Maximal breadth (mm) 7–10 12–14 c. 9.5
Basic Biology and Transmission
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4 Z.S. Pawlowski
0.5 mm
(a) (b) (c)
2 mm
(d) (e)
(f) (g)
ut
5 mm
Fig. 1.1. Diagrammatic representation of the comparative morphological features of adult T. solium (a, d,
f, h), T. saginata (b, g, i) and T. saginata asiatica (c, e, j) (adapted from references 8, 10, 47). Note that
tri-lobed ovary in the mature proglottid of T. solium (d), in comparison to two lobes in the mature
proglottid of T. saginata and T. saginata asiatica (e), the presence of the vaginal sphincter in the atrium
genitale of T. saginata (g). Note also the differences in the branching pattern of the uterus of T. solium
(h), T. saginata (i) and T. saginata asiatica (j) proglottides.
6 Z.S. Pawlowski
*Human taeniasis
HUMANS
(Gravid Several in a
proglottids) week
ENVIRONMENT
PIGS
elongated (20 5 mm) and each is packed testes; each connected to the sperm duct
with a uterus full of eggs. The gravid proglot- (vas deferens) leading to the genital pore.
tids detach from the strobila by ‘apolysis’ The female reproductive system comprises
either individually or in groups of two to five, of a vagina, also located within the genital
and are passed in the faeces a few times in a pore, a receptaculum seminis, an oviduct, a
week20. Discharged proglottides remain active trilobed ovary and a vitelline gland. Both
and may show some movements. self- and cross-fertilization may occur.
The tapeworm is a protoandrous her- Spermatozoa formed in the testes are con-
maphrodite4. Its reproductive system is veyed through the sperm duct to the genital
intricately developed. Within each mature pore and thereafter to the vagina to finally
proglottid, a centrally located ovary, a reach the receptaculum seminis and the
vitelline gland and uterus, surrounded by oviduct. The ovary discharges eggs in to the
numerous testes can be seen. The male oviduct, where the latter are fertilized by
reproductive organs include numerous spermatozoa. The fertilized eggs acquire
Fig. 1.3. Picture depicting the entire length of the adult T. solium tapeworm. (Source: Ana Flisser,
National Autonomous University of México, México DF, México.)
8 Z.S. Pawlowski
yolk cells from a vitelline gland in the being noticed in the faeces. Usually, a single
oviduct itself and are relocated into the T. solium tapeworm parasitizes the human
uterus, where they are stored. As the uterus gut; however, multiple infections may occur.
tube is closed without any opening to out- Superinfection probably exists; it has been
side it develops several ramifications packed documented in experimental T. saginata
with eggs, thus occupying most of the infection27.
gravid proglottid. Besides the reproductive
system, the adult tapeworm has four major
organ systems: tegument, nervous system, Taenia solium eggs
osmoregulatory system and muscular sys-
tem. It has no digestive canal4. The eggs of T. solium are morphologically
While the tapeworm lives in human small indistinguishable from those of other Taenia
intestine, its scolex is temporarily fixed in the sp. (Fig. 1.4a). As with eggs of other
duodenum and the strobila is bent a few Taeniidae, the outer shell of T. solium eggs is
times21. However, it frequently moves up very delicate and is usually lost while leav-
and down, in synchrony with the passage of ing the uterus. What is found in the faeces is
incoming food. It adapts to the rather hostile an oncosphere covered by an embryophore,
intestinal environment, being mobile, anaer- characteristic for all Taenia. The embryophore
obic, and is able to withstand the varying pH is globular in shape and measures 31–43 m
and digestive enzymes within the intestine. in diameter28. It has a thick striated cover
The adult worm is believed to survive for a and contains an oncosphere armed with six
few years; new proglottides constantly typical embryonic hooklets (giving it the
replace those expelled. Studies performed by name, ‘hexacanth embryo’), usually visible
Yoshino in the 1930s are of interest22–26. He through the embryophore cover. The
himself swallowed three T. solium cysticerci embryophore protects the oncosphere
and noted passage of proglottides starting against various unfavourable environmental
from 2 months after infection and lasting for conditions but is easily broken in the gut of
2 years and 3 months26. A tapeworm that the intermediate host where the substance
dies naturally or after treatment is easily cementing the keratin-like prismatic ele-
digested and disappears quickly without ments of its cover is digested.
(a)
(b) (b)
(a)
Fig. 1.4. Taenia solium eggs (a) and oncospheres (b). The eggs are 40 30 m in size and surrounded
by a shell; in the centre of figure (a) is a disintegrating egg, showing the process of hatching of an
oncosphere. The oncospheres can be seen surrounding a single egg in (b); their size is smaller (30 20
m) and they contain characteristic embryonic hooklets. (Source: Akivo Ito, Asahikawa Medical College,
Asahikawa, Japan.)
10 Z.S. Pawlowski
censed pig dealers are not motivated to pass there is no significant wildlife reservoir and
pork through meat inspection because of finally a feasible intervention is available in
threat of condemnation. Furthermore, the the form of mass chemotherapy of human
lack of fuel as well as the local culinary taeniasis with safe and effective drugs
habits facilitate the consumption of raw or (reviewed in Chapter 41).
semi-cooked meat. These factors lead to the
transmission of the parasite from pig to man
in endemic areas42. The socio-ecological and Conclusions
economic factors strongly influence the
transmission of T. solium infection and are Six major stages of development have been
responsible for its concentration in certain recognized in the life cycle of T. solium. Man
areas, making short-term control with taenia- is a major reservoir, multiplier of the parasite
sis therapy possible (discussed in Chapter and disseminator of infection to both himself
41)43,44. and to the pig. The pig does not play the
most important role in spreading human
cysticercosis, as was believed until not long
Implications for control ago. The role of the external environment in
transmission of T. solium infection is incom-
In 1993, the Task Force for Disease pletely understood. The control of taenia-
Eradication (Centers for Disease Control, sis/cysticercosis depends much not only on
Atlanta, USA) itemized four diseases that the biological life cycle but also on the ‘eco-
were potentially eradicable in the future; nomic’ cycle of T. solium. Several factors
these included lymphatic filariasis, mumps, including inadequacies in pig husbandry,
rubella and T. solium taeniasis/cysticerco- sanitary facilities, meat inspection, personal
sis45. Several characteristics of T. solium hygiene and local feeding habits are
infection make it suitable for eradication, involved in the perpetuation of the life cycle
namely, adult tapeworm infection in of T. solium in the developing world. Control
humans is the only source of infection for strategies should be able to deal with these
intermediate hosts (pigs); the animal inter- deficiencies in order to be effective in eradi-
mediate host population can be managed; cating taeniasis/cysticercosis.
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16 A. Flisser et al.
*T cells are of the following two types: helper (Th, CD3+/CD4+) and cytotoxic (CTL, CD3+/CD8+). The
former produce molecules that regulate the immune response, while the latter lyse histocompatible infected
or transformed cells (Fig. 2.1). The type of response elicited by Th cells depends on the subtype they transform
themselves to after antigen priming, i.e. Th1 or Th2. The two responses are becoming increasingly difficult to
understand as knowledge about them accumulates. Nevertheless, it can generally be said that Th1 cells
produce cytokines [including tumour necrosis factor- (TNF-) and interferon-gamma (IFN-)] that promote
inflammation, macrophage activation, and intracellular destruction of infectious agents; they also stimulate
proliferation of CD8+ cells. Thus, this response is primarily ‘cellular’. On the other hand, Th2 cells stimulate
most of the antibody responses, as well as granulocyte proliferation, differentiation and chemotaxis. The
major cytokines produced by the Th2 cells are interleukin-4 (IL-4), IL-5, IL-10 and IL-13. This type of response
is primarily ‘humoral’. Each response reciprocally down-regulates the other, for instance, IFN- stimulates the
Th1 response and inhibits Th2, while IL-4 promotes Th2 response and down-regulates Th1 response.
CD8+
4/9/02
CTL
CD8+
Antigens
IFN-
Macrophage
IL-15 activation
Antigen- IL-12
presenting
cell (APC) Th1
Page 17
CD4+
MHC class II
Th0
CD4+
T helper
cells
IL-4 IL-4
Antibodies
Th2 IL-5
CD4+ IL-6 IgM
IL-13 IgG
New and Revisited Immunological Aspects
IgA
B cell IgE
Plasma cell
17
Fig. 2.1. Diagrammatic overview of the Th1 and Th2 host immune responses.
Subject to the CABI Digital Library Terms & Conditions, available at https://cabidigitallibrary.org/terms-and-conditions
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Singh - Chap 02 4/9/02 4:37 pm Page 18
18 A. Flisser et al.
immune responses to natural and experi- anticysticercal treatment and after vaccina-
mental cysticercosis are yet to be clarified. tion35,36. This suggests that eosinophils may
Studies so far have addressed molecular play an important role in the degenerative
components in the CSF, serum and the gran- phase in this parasitic infection. Another
uloma itself. Increased levels of interleukin study showed that IL-2 was synthesized by
(IL)-1 and IL-6 have been reported in CSF of the peripheral blood cells of 58% of individu-
patients with inflammatory NC27. High lev- als with untreated, recently diagnosed NC,
els of IL-6 in CSF of patients with subarach- while interferon- (IFN-), IL-4 and IL-10,
noid NC have also been reported; this were only found in 11%, 10% and 14%,
possibly represents an acute phase response. respectively25. Interestingly, only IFN- was
In addition, high levels of tumour necrosis increased in the group of patients as com-
factor-alpha (TNF-alpha) have also been pared to controls.
noted in CSF of children with active NC28. The macroscopic disappearance of killed
TNF-alpha was undetectable in controls and cysticerci takes about 2 months, but the
children with inactive NC. immunological processes that occur within
In asymptomatic humans, a single low the involuting granulomas are poorly under-
dose of the taeniacidal drug praziquantel, stood. Very few immunohistochemical stud-
given to treat intestinal parasites may cause ies of the inflammatory response within
sufficient damage to latent asymptomatic cysticercus granulomas located in the human
cysticerci that inflammation and seizures central nervous system have been performed,
result29. Similarly, full dose anticysticercal mainly due to limited specimen tissue37,38.
therapy administered in heavy infections Available reports suggest an intermixture of
has precipitated fatal cerebral inflamma- Th1 and Th2 responses in human brain cys-
tion30,31. An immunological study of NC ticercus granulomas. Observations made in
patients treated with praziquantel (without animals are of interest in understanding the
major adverse effects) reported elevated sol- complex phenomena that occur in granulo-
uble IL-2 in the CSF suggesting a Th1-type mas within the central nervous system.
immune response to therapy, in contrast Destruction of parasites in the natural inter-
with the Th2-type immune response found mediate host, the pig, is mediated by a gran-
in animal models of viable cysticerci32. It ulomatous eosinophil-rich inflammation
was therefore hypothesized that living cys- (driven by the Th2 response), followed by
ticerci facilitate immune evasion by induc- macrophage/lymphocyte-driven resolution
ing a Th2-type immune response until the (involving the Th1 response)35. In apparent
death of the larval parasite allows a Th1- discordance, a Th1 response prevails in
mediated inflammatory response to ‘early’ granulomas, that is, when metaces-
develop. This model however, is not consis- todes are intact in a rodent model of cysticer-
tent with some of the other findings listed cosis (T. crassiceps in mice)39. In the same
above and it seems likely that the regulation model, ‘late’ granulomas, wherein parasite
of immunity in T. solium cysticercosis is a destruction is complete, exhibit a mixture of
complex phenomenon. Th1 and Th2 cytokines (IL-4). It would seem
Increased levels of eotaxin and IL-5, both then that if the first antibody–complement
eosinophil-selective mediators, have been phenomenon does not destroy the onco-
found in the sera of patients with NC33. sphere, the latter develops into a metaces-
These cytokines are involved in recruiting tode, giving rise to a host–parasite
eosinophils locally as well as systemically. relationship that, while in equilibrium, has a
Interestingly, in the mouse model of more ‘silent’ Th1-like pattern (i.e. IL-2), with
Angiostrongylus cantonensis infection, abla- concomitant presence of antibodies mostly of
tion of IL-5 activity with anti-IL-5 mono- the IgG class. When this equilibrium is bro-
clonal antibody resulted in more severe ken, a pro-inflammatory granulomatous
intracranial disease34. Furthermore, the pres- Th2-like process provokes parasite destruc-
ence of eosinophils as the first attack cells tion. This would be followed by resolution of
was reported in porcine cysticercosis after the inflammatory reaction induced by Th1
20 A. Flisser et al.
Conclusions
NC and Neoplasia
It is known that antibodies and complement
A recent analysis of autopsy files suggested are protective against T. solium oncospheres
that NC might be a risk factor for human (Fig. 2.2), but if the pace of the host immune
cancer, specifically of the lymphoid response is slow, then the parasites develop
tissues65–68. Several data support this mechanisms to evade the latter. As a result,
hypothesis. Chromosome aberrations in metacestodes establish and antibodies and
peripheral blood lymphocytes are more com- complement are no longer effective in
mon in patients with NC and in cysticercotic destroying them. Thus, a race between
pigs as compared to those observed in the development of protective immune mecha-
same cases after anticysticercal treatment nisms by the host and evasive mechanisms
3 Phase III.
Resolution.
IR
0
0 5 10 15 20
Infection time
Fig. 2.2. Phases of cysticercosis in relation to immune response. The initial Phase I is characterized by
the development of immune mediated protective mechanisms in the host and the differentiation of the
oncosphere into a metacestode. Phase II is a period during which the parasite and the host coexist due
to the development of immune evasive mechanisms by the parasite. Finally, in Phase III, the
host–parasite equilibrium is broken and the parasite is destroyed by an immune reaction that sometimes
even damages the host. This final phase leads to resolution of the infection.
by the parasite occurs during the initial probably chemo-attracted to the site by
period of infection. Subsequently, an equili- lymphoid cells. It is surmised that this spe-
brated host–parasite relationship develops cific response is mediated by Th2 cytokines.
that may last for long periods of time and Finally, an intense granulomatous type of
maintains concomitant immunity. The inflammatory reaction occurs that leads to
immune response against T. solium cys- complete parasite destruction and resolu-
ticerci appears to have both Th1 and Th2 tion with fibrosis. This last mechanism is
components, although their precise roles probably of the Th1-type. Thus, it seems
remain controversial. Through not yet that the Th1 and Th2 cytokines play differ-
understood mechanisms, the parasite is ent roles during various stages of the
killed primarily by eosinophils, which are host–parasite relationship.
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68. Herrera, L.A., Ramírez, T., Rodríguez, U., et al. (2000) Possible association between Taenia solium cys-
ticercosis and cancer: increased frequency of DNA damage in peripheral lymphocytes from neuro-
cysticercosis patients. Transactions of the Royal Society of Tropical Medicine and Hygiene 94, 1–5.
69. Montero, R., Flisser, A., Madrazo, I., et al. (1994) Mutation at the HPRT locus in patients with neuro-
cysticercosis treated with praziquantel. Mutation Research 305, 181–188.
70. Flisser, A., González, D., Plancarte, A., et al. (1990) Praziquantel treatment of brain and muscle
porcine Taenia solium cysticercosis. 2. Immunological and cytogenetic studies. Parasitology Research
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71. Lightowlers, M.W. (1994) Vaccination against animal parasites. Veterinary Parasitology 54, 177–204.
72. Johnson, K.S., Harrison, G.B.L., Lightowlers, M.W., et al. (1989) Vaccination against ovine cysticerco-
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73. Mitchel, G.F. (1990) Vaccines and vaccination strategies against helminths. In: Agabian, N., Cerami,
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74. Harrison, G.B.L., Heath, D.D., Dempster, R.P., et al. (1996) Identification and cDNA cloning of two
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75. Lightowlers, M.W., Rolfe, R., Gaucci, C.G. (1996) Taenia saginata: vaccination against cysticercosis in
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Instituto Oswaldo Cruz 96, 353–356.
3
Molecular Determinants of
Host–Parasite Interactions: Focus on
Parasite
Ingestion of food or water contaminated with Host inflammatory response directed against
T. solium eggs is the most preliminary step in T. solium metacestodes is a major determinant
the development of human cysticercosis. of clinical symptoms and signs of NC. There
Hatched and activated oncospheres penetrate is great variability in its onset, duration and
intestinal tissues, perforate small intestinal severity. The seminal study by Dixon and
blood vessels, and reach the bloodstream. Lipscomb has established that metacestodes
Here, they passively migrate and finally remain in host tissues in a viable, non-degen-
lodge in target tissues and develop into erate state for variable and prolonged periods
metacestodes. Specific mechanisms underly- of time5. Eventually, usually after 4–5 years,
ing T. solium oncosphere penetration have not local and systemic immune responses against
pre-incubated with F1 was inhibited. This parenchymal tissues and tegument; the
study provided specific evidence for the hooks were dispersed in necrotic tissue.
probable existence of a RNA molecule, F1, Moderate inflammatory reaction sur-
whose principal site of action was shown to rounded the metacestodes.
be the lymphocyte.
Local inflammatory responses were also
evaluated using scanning electron
microscopy in the experimental protocol out-
Effect on local inflammatory reactions lined above21. Samples from metacestodes
removed at 6 and 12 days post-implantation
In vivo studies further examined the effects were studied.
of MF on the inflammatory reaction around At 6 days post-implantation, it was
implanted metacestodes in mice20. Female found that:
BALB/c syngeneic mice were divided into
four groups based upon the following 1. In control mice, metacestodes were disin-
experimental protocol. One group of mice tegrated and covered by an intense inflam-
was treated with 100 g of MF (one dose matory reaction (Fig. 3.1a).
every 96 h for 12 days). A second group 2. Metacestodes removed from mice treated
consisted of mice inoculated with metaces- with MF alone were intact and exhibited a
tode antigens (100 g as a single dose) scarce inflammation on the bladder tegu-
alone, while a third group was constituted ment (Fig. 3.1b).
by mice that were first inoculated with 3. An evaginated metacestode removed
metacestode antigens and then treated with from a mouse inoculated with metacestode
MF. In the fourth (control) group, mice were antigen alone displayed inflammatory reac-
inoculated with inert normal saline alone. tion on its scolex. Inflammatory cells were
Subsequently, mice in all four groups were disseminated on the double crown of hooks,
implanted with live T. solium metacestodes suckers and the neck tegument; whereas the
(six metacestodes/mouse), obtained from bladder wall tegument was covered by a
cysticercotic pig meat under sterile condi- dense net of fibrous material embedding
tions. Twelve days after the metacestode numerous inflammatory cells.
implantation, the mice were killed. 4. Metacestodes removed from mice immu-
Histopathological studies revealed that: nized with metacestode antigens and subse-
quently treated with MF exhibited few
1. Metacestodes implanted in control mice inflammatory cells on their bladder wall
were completely destroyed and their rem- teguments.
nants were surrounded by an intense inflam-
matory reaction predominantly made up of At 12 days post-implantation:
neutrophils and eosinophils. 1. Metacestodes removed from control mice
2. In metacestodes of mice that were treated were completely enmeshed in an intense
with MF alone, there were clearly identifi- inflammatory reaction, with a dense colla-
able and intact suckers, rostellum, tegument gen-like matrix embedding numerous
and hooks. Few neutrophils, plasma cells, inflammatory cells and covering the whole
lymphocytes and histiocytes were noted in bladder wall tegument.
spiral canals; eosinophils were not observed. 2. The inflammatory reaction surrounding
3. Metacestodes implanted in mice immu- metacestodes removed from mice treated
nized with metacestode antigens alone were with MF alone was more intense than that
completely destroyed; their caseous rem- observed on day 6. In one partially evagi-
nants were intensely surrounded and infil- nated metacestode, the scolex was apparently
trated by neutrophils and eosinophils. intact, with minimal amount of inflammatory
4. Finally, in mice immunized with infiltrate in the folds of its neck. At higher
metacestode antigens and subsequently magnification ( 1500), the microtriches were
treated with MF, there were clearly identifi- visibly intact with scarce inflammatory cells
able (albeit necrotic) rostellum, suckers, and eosinophil like-granules.
Fig. 3.1a. Scanning electron micrograph of a Taenia solium metacestode removed from a control mouse
at day 6. (Reproduced with permission from reference 21.) (ST, subtegument; T, tegument.)
Fig. 3.1b. Scanning electron micrograph of a metacestode removed from a MF-treated mouse at day 6.
(Reproduced with permission from reference 21.)
3. Metacestodes from mice immunized with different kinds of white cells, cell debris and
metacestode antigens exhibited much fibrinoid material was apparent.
stronger inflammatory reactions on the 4. In mice immunized with metacestode anti-
scolex tegument in comparison to day-6. gen and treated subsequently with MF, the
Copious inflammatory infiltrate was visible inflammatory reaction on the bladder wall
surrounding the tegument of an evaginated tegument was less extensive in comparison to
scolex (Fig. 3.2). Ruptures of different size immunized (with metacestode antigens) or
and depth were evident in the tegument and control groups. Very few inflammatory cells,
sub-tegumental suckers. At higher magnifi- cell debris and fibrous material were found
cation ( 1500), an intense accumulation of adherent to intact microtriches.
Fig. 3.2. Scanning electron micrograph of an evaginated scolex removed from an immunized mouse at day
12. An intense inflammatory reaction completely covers the scolex tegument. Note the large cell aggregates
and several ruptures of the sucker and rostellum teguments. (Reproduced with permission from reference 21.)
1.4
1.2
1.0
0.8
A (492)
0.6
0.4
0.2
0
0 100 200 300 400 500 600 700 800 900 1000
Dilutions
I IF IM
IFM C
Fig. 3.3. Antibody titres determined by ELISA in sera from mice inoculated with Taenia solium
metacestode antigens (I), inoculated with metacestode antigens plus MF (IF), inoculated with
metacestode antigens and implanted with six metacestodes (IM), inoculated with metacestode antigens
plus MF and implanted with six metacestodes (IFM), and inoculated with saline (C). Data are expressed
as mean values SE for each treatment (n = 4) (P0.05 for I versus IF, IM or IFM). (Reproduced with
permission from reference 20.)
10,000
9000
8000
(3H) Thymidine uptake cpm
7000
6000
5000
4000
3000
2000
1000
0
C CM I IF F IM IMF MF
Fig. 3.4. Effect of Taenia solium metacestode antigens on the proliferation of murine splenic
lymphocytes from the following groups of mice: (C) control; (CM) implanted with six metacestodes; (I)
inoculated with metacestode antigens; (IF) inoculated with metacestode antigens plus MF; (F) inoculated
with MF; (IM) inoculated with metacestode antigens and implanted with six metacestodes; (IMF)
inoculated with metacestode antigens plus MF and implanted with six metacestodes; and (MF)
inoculated with MF and implanted with six metacestodes. Bars represent mean values SE for thymidine
uptake by cells stimulated with 1 g of metacestode antigens (P0.05 for I and IM versus IF, IMF, CM or
C). (Reproduced with permission from reference 20.)
(a) (b)
150 25
100
15
50
5
C– C+ 10 20 C– C+ 10 20
(c) (d)
50 5
TNF- concentration (ng ml–1)
IL-4 concentration (U ml–1)
30 3
10 1
C– C+ 10 20 C– C+ 10 20
MF (g) MF (g)
Fig. 3.5. Effect of Taenia solium MF on the production of cytokines. IL-2, IFN- and IL-4 were measured in
supernatants of mouse spleen cells treated with 10 and 20 g of MF (measured as ribose) and stimulated
with Con-A. TNF-alpha was detected in supernatants of murine macrophage line (IC-21) treated with 10
and 20 g of MF and stimulated with lipopolysaccharide and recombinant IFN-. C are the cytokine
concentrations from cells incubated in RPMI medium; C+ are the cytokine values from cells stimulated with
Con-A or lipopolysaccharide/recombinant IFN-. (Reproduced with permission from reference 22.)
al., described cysteine, metallo- and serine T. solium metacestodes (96% viability) at
protease activities in acid extracts from 37°C for 2 h. Cells were separated, washed
lyophilized T. solium metacestodes. The and stained with monoclonal antibodies, anti-
authors reported IgG digestion by the extracts CD4 FITC (fluoresceinated) and anti-CD8 PE
in vitro26. We postulated that immunoglobulin (phycoerythrinated). Flow cytometric analysis
molecules behaved as target substrates and revealed significant decrease in CD4+ expres-
molecular nutrients for T. solium proteases. sion (Fig. 3.6). The cause and effect relation-
Supernatants of live metacestode cultures ship between protease activity and decrease
were evaluated for protease activity on pep- in CD4 expression was demonstrated when
tide substrates with T cell surface proteins27. human lymphocytes were cultured with
Substantial cysteine protease activity in addi- metacestode excretory–secretory products in
tion to metallo- and serine protease activities presence of L-cysteine, a reducing substance.
was found. Isolated human lymphocytes Cells were washed and stained and analysed
from volunteers were co-cultured with live by flow cytometry. Metacestode excretory–
104
104
a b c
103
103
103
FL2-H
FL2-H
FL2-H
CD8
102
102
102
101
101
101
100
100
100
100 101 102 103 104 100 101 102 103 104 100 101 102 103 104
FL1-H FL1-H FL1-H
CD4
Fig. 3.6. Flow cytometry analysis of human T cells co-cultured with 100 Taenia solium metacestodes after
cells were separated and stained with monoclonal antibody fluoresceinated anti-human CD4 and
phycoerythrinated anti-human CD8. (a) Control cells in RPMI 1640 medium without metacestodes. (b)
Cells co-cultured for 2 hours with 100 metacestodes. (c) Cells co-cultured for 2 hours with 100
metacestodes and 100 g of rabbit antiserum to metacestode excretory-secretory products. Values are
expressed as gated percentages of CD8+and CD4+cells. (Reproduced with permission from reference 27.)
secretory products pre-incubated with E-64 (a inhibit cytokine, particularly IFN- and IL-2,
specific inhibitor of cysteine protease) served and to a lesser degree IL-4 production in vitro.
as control material. A significant decrease in Live metacestodes also secrete cysteine, met-
CD4 expression, attributable to cysteine pro- allo- and serine proteases. Cysteine protease
tease activity was again demonstrated. activity significantly depletes CD4+ cells in
Furthermore, treatment with E-64 resulted in vitro. The elucidation of these molecules and
the reversion of the inhibitory effect on CD4 of their actions in experimental conditions
expression. have provided insights into the mechanisms
by which T. solium metacestodes evade host
immunological attack and are able to survive
Conclusions for long periods of time.
References
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9. Hammerberg, B., William, J.F. (1978) Interaction between Taenia taeniaeformis and the complement
system. Journal of Immunology 120, 1033–1038.
10. Suquet, C., Green, E.C., Leid, R.W. (1984) Isolation and partial characterization of a Taenia taeniae-
formis metacestode proteinase inhibitor. International Journal of Parasitology 14, 165–172.
11. Laclette, J.P., Shoemaker, C.B., Richter, D., et al. (1992) Paramyosin inhibits complement C1. Journal
of Immunology 148, 124–128.
12. Tato, P., Valles, Y., Rolon, R., et al. (1987) Effect of the immunization on immunodepressed hogs,
infected naturally by Cysticercus cellulosae. Revista LatinoAmericana de Microbiologia (México) 29,
67–71.
13. Molinari, J.L., Tato, P., Valles, Y. (1987) Immunodepression of T lymphocytes in hogs modulated by
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14. Dessaint, J.P., Camus, D., Fisher, E., et al. (1977) Inhibition of lymphocyte proliferation by factor(s)
produced by Schistosoma mansoni. European Journal of Immunology 7, 624–629.
15. Yin, F.D., Nowak, M., Copeman, B., et al. (1983) A low molecular weight immunosuppressive factor
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tor on cultured human lymphocytes stimulated with phytohemagglutinin. Annals of Tropical
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17. Molinari, J.L., Soto, R., Tato, P., et al. (1993) Immunization against porcine cysticercosis in an
endemic area in Mexico: a field and laboratory study. American Journal of Tropical Medicine and
Hygiene 49, 502–512.
18. Molinari, J.L., Tato, P., Reynoso, O.A., et al. (1989) Modulation effects on mice response to a
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induced by a small RNA purified from Taenia solium metacestodes. Parasitology Research 81, 181–187.
20. Tato, P., White, A.C. Jr, Willms, K., et al. (1996) Immunosuppression and inhibition of inflammation
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Parasitology Research 82, 590–597.
21. Molinari, J.L., Tato, P., Rodriguez, D., et al. (1998) Impairment of the inflammatory reaction on
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microscopy study. Parasitology Research 84, 173–180.
22. Arechavaleta, F., Molinari, J.L., Tato, P. (1998) A Taenia solium metacestode factor nonspecifically
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24. Hotez, P.J., Trang, N.L., McKerrow, J.H., et al. (1985) Isolation and characterization of a proteolytic
enzyme from the adult Ancylostoma caninum. Journal of Biological Chemistry 260, 7343–7348.
25. Chappel, C.L., Dresden, M.H. (1986) Schistosoma mansoni: proteinase activity of ‘hemoglobinase’
from the digestive tracts of adult worms. Experimental Parasitology 61, 160–167.
26. White, A.C. Jr, Molinari, J.L., Pillai, A.V., et al. (1992) Detection and preliminary characterization of
Taenia solium metacestode proteases. Journal of Parasitology 78, 281–287.
27. Molinari, J.L., Mejia, H., Clinton, A.C. Jr, et al. (2000) Taenia solium: a cysteine protease secreted by
metacestodes depletes human CD4 lymphocytes in vitro. Experimental Parasitology 94, 133–142.
hamsters (Mesocricetus auratus), tapeworms pigs are the natural intermediate host of the
developed and exhibited greater sexual devel- helminth. Most researchers employing this
opment, though mature and infectious oncos- model so far have used naturally infected
pheres were not produced14–16. Cysternal pigs21,22, although experimentally induced
infection with scolex and membranes from T. infections have also been studied (see also
solium cysticerci resulted in an intense granu- Chapter 15)23. The number of T. solium eggs
lomatous inflammatory response consisting of required for inducing experimental infection
lymphocytes in rabbits17. Interestingly, the varied between 1000 and 380,00023. The
most successful hosts to date for adult T. porcine model has provided information
solium tapeworms are chinchillas (Chin- related to progression of the parasitosis in
chillidae family of rodents), in which larvae liver, muscles and lungs. In parallel to human
develop into gravid proglottides, eventually CNS infections, histological studies in this
producing infective oncospheres. Infectivity of model revealed the presence of immature,
eggs obtained from the chinchilla model was mature, degenerate and calcified cysts in pig
demonstrated in pigs. Metacestodes were liver and muscle22,24. As yet, a detailed analy-
found in pig skeletal muscle, 12 weeks after sis of the specific immunological elements
oral infection with gravid proglottides recov- has not been described in the porcine model.
ered from chinchillas14. A major area of application of porcine
Immunosuppressive treatment with models has been the development of treat-
steroids (prednisolone and methyl pred- ment strategies to control porcine cysticerco-
nisolone) facilitates the establishment and sis with the ultimate goal of preventing
development of adult T. solium and a related human infection. Two of the drugs that are
cestode, T. crassiceps in experimental host currently used for treatment of human cys-
intestine14,18. The basis of the facilitatory ticercosis, albendazole and praziquantel,
effect of steroid treatment presumably relates have been used in several different protocols
to suppression of local mucosal inflamma- to determine their efficacy for treatment of
tory responses to worm attachment19. When porcine cysticercosis21, 22, 25, 26. Another drug,
T cells were depleted in vivo in Mongolian oxfendazole has been found effective in con-
gerbils (Meriones unguiculatus) infected with trolling swine cysticercosis (reviewed in
T. crassiceps ova, only destrobilated adult Chapter 43)27. These studies together with
worms were harvested in the faeces20. This the epidemiological studies are important for
indicated that T cells in some way prevented the development of interventions to eradi-
strobilar attachment to enteral mucosa. A cate T. solium infection28,29. However, the
similar effect was observed in prednisolone- scarcity of infected pigs in non-endemic
treated gerbils, arguably due to an effect of areas, and the difficulty in obtaining T.
prednisolone upon T cells20. solium eggs have limited the widespread use
The development of an experimental of the porcine model. Moreover, there are
model that allows the recovery of T. solium difficulties in handling pigs, and a high cost
eggs is likely to have a significant impact of support is involved. Therefore, other ani-
upon future research. Eggs will be available mal species have been used to develop
for antigen cloning, analysis and purification. experimental models for cysticercosis using
Further application of the chinchilla model related parasites.
will be valuable in the areas of vaccine design
and host–adult parasite interactions.
Experimental intraocular cysticercosis
intense inflammatory response in those rab- production of interleukin-2 (IL-2) and IFN-
bits that had been previously infected decreased and DTH was depressed, while
through the intraperitoneal route or had IL-4, IL-10, IgG2b and IgG1 production was
been inoculated with cysticercus antigen30,31. up-regulated. These results suggest that
A granulomatous response comprising there is a shift from an initial parasite-restric-
eosinophils and polymorphonuclear cells tive, Th1-type based response to a later para-
was noted. Naive rabbits and steroid treated site-permissive, Th2 response. While the
rabbits did not exhibit inflammatory ocular early response suppresses infection by
lesions30,31. These models are significant in metacestodes, the latter allows establishment
the understanding of immune reactions and growth of T. crassiceps metacestodes in
specifically involved in the intraocular com- murine hosts36,38.
partment as well as the treatment of ocular Analyses of the immunological response
cysticercosis. around peritoneal granulomas formed 3–14
weeks after infection indicate that early
granulomas are predominantly associated
T. crassiceps experimental cysticercosis with a Th1-type response, whereas later
granulomas, in which parasite destruction is
Two related cestode parasites, T. crassiceps complete, have a mixture of Th1- and Th2-
and Mesocestoides corti have been used exten- type responses39. These data suggest that
sively as animal models of cysticercosis. dying parasites can no longer modulate host
Their metacestodes are infectious to mice, immunological responses. The Th1 granulo-
and the larval stages of these parasites are matous response is likely to be involved in
easily maintained in the peritoneal cavity of the pathogenesis of symptomatic human
infected mice32,33. Intraperitoneal injection of infection in which active inflammation is a
either organism results in invasion of liver major cause of disease. As the parasite is
and peritoneum. Intraperitoneal inoculation, destroyed, the response shifts to involve
however, does not produce CNS lesions, a greater Th2-type cytokine expression, per-
major drawback of initial investigations with haps as a means of down-regulating inflam-
these models. Recently, however, infection mation39. Interestingly, it was demonstrated
with either organism was accomplished in that subcutaneous inoculation with larvae
the brain, thereby facilitating the study of induces protection against subsequent
infective mechanisms specific to the CNS34. intraperitoneal challenge. Parasite destruc-
T. crassiceps has a canine definitive host tion was associated with adherence of host
and a rodent intermediate host32,35. In nat- cells to the tegument of larvae. The crucial
ural infections, the larval form invades sev- effector population of host cells involved in
eral tissues including the peritoneal cavity of parasite death is not known40.
the rodent. In BALB/c mice, chronic infec- The T. crassiceps animal model has also
tion with T. crassiceps induced host immuno- been used to investigate mechanisms of
suppression. Analysis of the temporal course immunological regulation that the parasite
of the immune response in mice inoculated can exhibit in the host. T. crassiceps larvae
intraperitoneally with T. crassiceps, revealed release factors that are capable of down-reg-
a time dependent variation in the intensity of ulating both proliferative responses of and
Th1 and Th2 type responses (see Chapter 2 cytokine production by T cells41. These para-
for an overview of the Th1 and Th2 site factors were found to down-regulate
responses)36–38. In the early stages of infec- production of IFN- and IL-4 by mitogen
tion when few or no parasites could be stimulated spleen cells41. This inhibitory
recovered from the peritoneal cavity, mice effect was caused by excretory–secretory
exhibited a strong Th1 type of immuno- products from the larvae in the early stages
logical response characterized by high of infection. In contrast, excretory–secretory
interferon- (IFN-) production, IgG2a dom- products from larvae harvested late in
inated antibody response and delayed type infection were not suppressive40. Future
hypersensitivity (DTH). Late in infection, studies will be critical to elucidate immuno-
Fig. 4.1. Haematoxylin and eosin staining of a brain cryosection, 10 m in thickness. Mesocestoides
corti metacestode is present in parenchyma associated with small inflammatory infiltrate shown by the
long arrow. The short arrow demarcates a parasite in a lateral ventricle.
100
80
Percentage of parasites
P
60
EP
40
20
0
2 days 1 3 5 10 16
Time p.i (weeks)
Fig. 4.2. Distribution of Mesocestoides corti larvae in the brain of BALB/c mice. Haematoxylin and eosin
stained sections from infected mouse brains were analysed for the presence and location of larva.
Parasites were counted and classified as P (parenchymal) or EP (extraparenchymal, i.e. located in
ventricle, subarachnoid space or meninges). Each data point represents the average of three mice.
necrosis in brain parenchyma (Fig. 4.3). An larger and fewer organisms were able to
accumulation of inflammatory cells in the penetrate brain parenchyma.
ventricles and meninges was noted (Fig. In the mouse model, infection of CNS
4.4). Massive accumulation of gamma/delta appears to induce initially an innate type
T lymphocytes, macrophages, and to a of immunological response evidenced by
lesser extent, dendritic cells, NK cells, mast the presence of neutrophils, macrophages
cells and B cells was observed (Fig. 4.5). A and natural killer cells. By 3 days postin-
Th1 pathway of cytokine expression was fection, an early-induced response devel-
observed in the brain after M. corti infection ops with the added participation of large
with high levels of IL-2, IL-12, IL-15 and numbers of gamma/delta T cells. By 7
IFN- (Fig. 4.6). Importantly, Th2-related days postinfection, an adaptive immuno-
cytokines (IL-10 and IL-13) were either logical response is evident with parasite
undetectable or found in very low levels specific T and B cells.
(IL-4). Interestingly, gamma/delta T lym- The immunological response that devel-
phocytes were found in the CNS by 2 days ops in mouse brain has been evaluated in
postinfection. These cells co-localized to both infected BALB/c and C57BL/6 mice.
areas where Th1 cytokines were detected34. Little difference was found in the type of the
The immunological response in the CNS in cellular and cytokine response in the CNS in
mice infected with T. crassiceps was similar these two strains of mice. This is of interest
with the exception that this organism was since these two strains often differ dramati-
cally in their response to infectious organ-
isms such as Leishmania54,55.
(a)
(a)
(b)
(b)
3
Number of
cells
0
2 days 5 days 1 5 13
Time p.i (weeks)
CD19
Fig. 4.5. Immunological response in the brain after Mesocestoides corti infection. Two mouse brains
obtained after intracranial inoculation with M. corti metacestodes were analysed by immuno-
histochemistry for the presence of various cell types. Cells in the extraparenchymal regions were
counted, and the score given represents: 1–100 cells (1), 100–300 cells (2), 300–500 cells (3). The
results represent the average of two mice.
3
Number of
cells
0
2 days 5 days 1 5 13
Time p.i (weeks)
IL-12
IL-4
Fig. 4.6. Predominance of a Th1 pathway of cytokine response in the brain after Mesocestoides corti
infection. Results of immunohistochemical staining for IL-12 and IL-4 are shown. Cells were counted and
scores given as described in Fig. 4.5. The results represent the average of two mice.
Data from the mouse model are consistent Macrophages, NK cells and pro-inflamma-
with previous reports of the cellular tory cytokines predominate with little or no
immunological responses in human brain. detection of eosinophils, mast cells and IL-4
production8. Within the brain, host responses Two of these molecules are temperature-
to the parasite appears to be of Th1 inflam- induced heat shock proteins (hsps) of the hsp70
matory type in contrast to the Th2 response and hsp60 families58. Since gamma/delta T
which is a characteristic response to cells might be able to recognize whole proteins
helminths in peripheral extraneural tissue. in an antibody-like manner60,61, M. corti hsps
However, as disease progresses with granu- have a potential role in the development of an
loma formation, a mixed Th1 and Th2 inflammatory response in the CNS.
response is likely. Furthermore, phospholipids have been found
The presence of gamma/delta T cells in to induce specific expansion of human
large numbers predicts their important role gamma/delta T cells62–64. Future studies with
in NC. In lymphoid tissues, gamma/delta T M. corti lipids may help define the mechanism
cells represent a minor proportion of T cells by which the parasite induces an inflamma-
and their specific functions are uncertain56,57. tory response in the brain.
We hypothesized that gamma/delta T cells
play important immunoregulatory functions
by producing cytokines that modulate the Conclusions
development of inflammatory response in
CNS. Further studies in the animal model Animal models contribute to the areas of
may improve our understanding of the role parasite biology and immunology and are
of this T cell subset in the human disease. valuable for the recognition of new mecha-
The interactions between immunological nisms involved in the host–parasite relation-
cells and resident brain cells in the mouse ship during cestode infection. These models,
model are of interest with specific reference to and the data obtained from human studies
T cells. A question that needs to be answered will be critical for the understanding of the
is which antigens may be activating the progression of the disease in the human host.
gamma/delta T cell response? Previous stud- The animal models hitherto described have
ies have indicated that M. corti secretes a num- been instrumental in the understanding of
ber of molecules when propagated in vitro58,59. host–parasite interactions involved in NC.
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48 A. Ito et al.
E. multilocularis
1000
E. granulosus
T. crassiceps
T. pisiformis
0.02 T. taeniaeformis
H. diminuta
669
986 H. nana
H. microstoma
M. corti
M. expansa
D. caninum
1000 D. latum
D. ditremum
F. hepatica
Fig. 5.1. A neighbour-joining phylogenic tree of 17 cestodes based on the sequences of partial LrRNA
genes. Bootstrap values more than 500 are shown in the tree. The trematode, Fasciola hepatica served
as an outgroup. The cestodes examined were Echinococcus multilocularis, E. granulosus, Taenia
hydatigena, T. solium, T. saginata, T. asiatica, T. crassiceps, T. pisiformis, T. taeniaeformis, Hymenolepis
diminuta, H. nana, H. microstoma, Mesocestoides corti, Moniezia expansa, Dipylidium caninum,
Diphyllobothrium latum and D. ditremum.
a factor that may affect its potential to pro- (T. asiatica vs. variant of T. saginata (T. saginata
duce neurological symptoms. However, we asiatica)),9–11 and also with reference to its
have shown that larvae of the Asian Taenia potential to cause human cysticercosis12,13.
can develop to 10 mm or larger in diameter Mitochondrial DNA analysis15–18 and compara-
in non-obese diabetic-severe combined tive studies of morphology and development
immunodeficiency (NOD-SCID) mice14. of metacestodes of each species in experimen-
Secondly, while T. solium is neuro- and myo- tal animal models14,19–23 have provided prelim-
tropic, the Asian Taenia is hepato- and vis- inary insights into differences in the biological
cero-tropic. In other words, in swine and behaviour of the three human taeniids. Both
possibly in humans, metacestodes of the lat- suggest that the Asian Taenia is highly homolo-
ter are primarily found in the liver and vis- gous to T. saginata, and although there are bio-
cera and not in the brain and muscles, as is logical differences between the two9,14, T.
the case with T. solium. asiatica should not be classified as a new
Given the above background, controversy species but rather a subspecies of T. saginata,
exists with regard to speciation of Asian Taenia i.e., T. saginata asiatica16–18,23.
Fig. 5.2. The mitochondrial genome of Taenia solium. Arrows indicate the direction of transcription
(COI–III: cytochrome c oxidase subunits I–III; ND1–6 and 4L: NADH dehydrogenase subunits 1–6 and
4L; ATP6: ATPase subunit 6; LrRNA and SrRNA: large and small subunit rRNAs). Genes for tRNAs are
indicated as abbreviated capital letters for amino acids. The gene arrangement of T. solium mtDNA is the
same as those of Echinococcus multilocularis and T. crassiceps mtDNAs.
50 A. Ito et al.
Vertebrata
Mus musculus
(16,295 bp)
Echinodermata
S. purpuratus
(15,650 bp)
Arthropoda
D. yakuba
(16,019 bp)
Nematoda
Caenorhabditis
elegans
(13,794 bp)
Platyhelminthes
Taenia solium
(13,709 bp)
Fig. 5.3. The arrangements of protein and rRNA genes among representative metazoan mitochondrial
genomes. The sites of tRNA genes are omitted from this figure. Arrows indicate the direction of transcription.
UAA codon specifies tyrosine in the latter. are unpaired and replaced by loops of 6–9
The codon sequences are unified into the nt. This unorthodox structure, particularly
mitochondrial code of the entire phylum in tRNAArg and tRNACys, has not been found
Platyhelminthes, and its range is conceived to in any other metazoan mitochondrion so
cover all three classes: Turbellaria, Trematoda far28.
and Cestoda. The genetic code is similar to The cestode mtDNA contains genes for
that of echinoderm mitochondria5; however large and small subunit rRNAs (LrRNA and
it differs from the universal code27. Our SrRNA) of mitochondrial ribosomes. The
group28 recently found that GUG is an initiat- putative LrRNA and SrRNA genes are 983
ing methionine codon and UAA is a termi- and 704 nt long, respectively (M. Nakao et
nating codon (Table 5.1). al., Asahikawa, unpublished observations).
The length of these genes are similar to those
of their nematode counterparts29 but are
tRNA and rRNA genes shorter than those of other metazoan mito-
chondrial rRNAs, so far reported. It is specu-
Individual sizes of 22 tRNA genes identified lated that the compactness of the cestode
in the cestode mtDNA range from 58 to 73 rRNAs results from the pressure to minimize
nucleotides (nt). The variations in length are the size of the mitochodrial genome.
mostly due to differences in stem and loop Predicted secondary structures of cestode
sizes of the D and T arms (M. Nakao et al., LrRNA and SrRNA are more similar to those
Asahikawa, unpublished observations). The of nematodes30 and trematodes2.
nucleotide compositions of cestode and
nematode mtDNAs are similar. However,
the secondary structures of their tRNAs dif- Polymorphism of T. solium: global
fer from each other. A majority of cestode variations
tRNAs (18 out of 22) can be folded into con-
ventional four-arm cloverleaf structures, A comparison of sequences of complete COI
whereas the remaining four [tRNASer(AGN), genes in different isolates of T. solium from
tRNASer(UCN), tRNAArg and tRNACys] have Asia (China, India, Indonesia, Thailand),
unorthodox structures wherein their D-arms Africa (Mozambique, Tanzania) and Latin
Table 5.1. The flatworm mitochondrial genetic code modified for cestodes.
TTT Phe (F) TCT Ser (S) TAT Tyr (Y) TGT Cys ( C )
TTC Phe (F) TCC Ser (S) TAC Tyr (Y) TGC Cys ( C )
TTA Leu (L) TCA Ser (S) TAA Stop TGA Trp (W)
TTG Leu (L) TCG Ser (S) TAG Stop TGG Trp (W)
CCT Leu (L) CCT Pro (P) CAT His (H) CGT Arg ( R )
CTC Leu (L) CCC Pro (P) CAC His (H) CGC Arg ( R )
CTA Leu (L) CCA Pro (P) CAA Gln (Q) CGA Arg ( R )
CTG Leu (L) CCG Pro (P) CAG Gln (Q) CGG Arg ( R)
ATT Ile (I) ACT Thr (T) AAT Asn (N) AGT Ser (S)
ATC Ile (I) ACC Thr (T) AAC Asn (N) AGC Ser (S)
ATA Ile (I) ACA Thr (T) AAA Asn (N) AGA Ser (S)
ATG* Met (M) ACG Thr (T) AAG Lys (K) AGG Ser (S)
GTT Val (V) GCT Ala (A) GAT Asp (D) GGT Gly (G)
GTC Val (V) GCC Ala (A) GAC Asp (D) GGC Gly (G)
GTA Val (V) GCA Ala (A) GAA Glu (E) GGA Gly (G)
GTG* Val (V) GCG Ala (A) GAG Glu (E) GGG Gly (G)
*Initiation codon.
America (Mexico, Ecuador and Peru) was rare in Asia. On the other hand, racemose
undertaken18,24. Based upon the sequencing cysticercosis is comparatively more com-
data, it was apparent that the Asian isolates mon in Central and South America.
differed from the African and American iso- Similarly, muscular cysticercosis leading to
lates (Fig. 5.4)24. We surmised that the simi- pseudohypertrophy has almost exclusively
larities between African and American been reported from China and India and is
isolates could be related to a common ances- uncommon in Central and South America.
tor or origin. Indeed, pigs were exported Furthermore, serological analysis of puri-
from Europe (perhaps, Spain or Portugal) to fied glycoproteins33 and the antigenic com-
Africa and America from the 15th century ponents of cyst fluid of T. solium cysticerci34
onwards. Therefore, it is conceivable that have revealed differences in the
African and American isolates of T. solium immunoblot profile of isolates from
were introduced by European colonization. Ecuador and Mozambique on one hand
The hypothesized export phenomenon and Irian Jaya, Indonesia and China on the
draws a parallel to the recent export of T. other hand (Fig. 5.5; A. Ito et al.,
solium from Bali to Irian Jaya after the latter Asahikawa, unpublished data).
came under Indonesian control in 196911,31,32. An increasing amount of travel, immigra-
The confirmation of the above hypothesis tion and refugeeism in the world is likely to
requires an analysis of the mtDNA of T. dilute strict geographical predilections of
solium isolated from Europe and the demon- any supposed strains and their different clin-
stration of its similarity to American and ical and serological expressions. This is likely
African strains24. to interfere with the determination of a logi-
The demonstrated differences in the COI cal inference of phylogenic relationships
gene sequences between Asian and between substrains as well as the study of
American–African isolates may be surmised epidemiology based on mitochondrial
to translate into different clinical implica- genomics. This however does not prevent us
tions. Indeed, there are differences in the from forming a preliminary opinion that
clinical spectrum of NC between Asia and there are indeed at least two different sub-
South America. For instance, parenchymal strains of T. solium based on differences in
NC and subcutaneous cysticercosis are their mitochondrial genomes, biological and
common while racemose cysticercosis is clinical behaviour.
52 A. Ito et al.
Mexico
Peru
COI gene
(1620 bp)
Tanzania A
Mozambique
981
0.01 Da Ecuador
Thailand
1000
China 2 B
China 1
1000
Irian Jaya
Taenia saginata
1000
Taenia asiatica
Echinococcus multilocularis
Fig. 5.4. A neighbour-joining phylogenetic tree of various isolates of Taenia solium. The tree was
constructed from complete nucleotide sequences of COI genes. Bootstrap values are shown in the tree
(group A: the African and Latin American isolates; group B: the Asian isolates).
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11. Simanjuntak, G.M., Margono, S.S., Okamoto, M., et al. (1997) Taeniasis/cysticercosis in Indonesia as
an emerging disease. Parasitology Today 13, 321–323.
12. Ito, A. (1992) Cysticercosis in Asia-Pacific regions. Parasitology Today 8, 182–183.
13. Galan-Puchardes, M.T., Fuentes, M.V. (1999) Human cysticercosis and larval tropism of Taenia asiat-
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14. Ito, A., Nakaya, K., Sako, Y., et al. (2001) NOD-SCID mouse as an experimental animal model for
cysticercosis. Southeast Asian Journal of Tropical Medicine and Public Health 32 (Suppl.), 85–89.
15. McManus, D.P. (1990) Characterization of taeniid cestodes by DNA analysis. Revue Scientifique et
Technique 9, 489–510.
16. Bowles, J., McManus, D.P. (1994) Genetic characterization of the Asian Taenia, a newly described
taeniid cestode of humans. American Journal of Tropical Medicine and Hygiene 50, 33–44.
17. Zarlenga, D.S., George, M. (1995) Taenia crassiceps: cloning and mapping of mitochondrial DNA and
its application to the phenetic analysis of a new species of Taenia from Southeast Asia. Experimental
Parasitology 81, 604–607.
18. Okamoto, M., Nakao, M., Sako, Y., et al. (2001) Molecular variation of Taenia solium in the world.
Southeast Asian Journal of Tropical Medicine and Public Health 32 (Suppl.), 90–93.
19. Ito, A., Cheng, W.C., Chen, C.C., et al. (1997) Human Taenia eggs develop into cysticerci in SCID
mice. Parasitology 114, 85–88.
20. Ito, A., Ito, M., Eom, K.S., et al. (1997) In vitro hatched oncospheres of Asian Taenia from Korea and
Taiwan develop into cysticerci in the peritoneal cavity of female scid (severe combined immunodefi-
ciency) mice. International Journal for Parasitology 27, 631–633.
21. Ito, A., Ma, L., Sato, Y. (1997) Cystic metacestodes of a rat-adapted Taenia taeniaeformis established in
the peritoneal cavity of scid and nude mice. International Journal for Parasitology 27, 903–905.
22. Ito, A., Ito, M. (1999) Human Taenia in severe combined immunodeficiency (SCID) mice. Parasitology
Today 15, 64–67.
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the pork tapeworm Taenia solium worldwide. Parasitology 126 (in press).
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tionary origin of a tRNASerAGN that contains a dihydrouridine arm replacement loop, and of ser-
ine-specifying AGA and AGG codons. Journal of Molecular Evolution 28, 374–387.
26. Ohma, T., Osawa, S., Watanabe, K., et al. (1990) Evolution of the mitochondrial genetic code IV.
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deduced from cytochrome c oxidase subunit I gene sequences. Journal of Molecular Evolution 34,
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Biochemistry and Parasitology 111, 415–424.
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todes, Caenorhabditis elegans and Ascaris suum. Genetics 130, 471–498.
30. Okimoto, R., Macfarlane, J.L., Wolstenholme, D.R. (1994) The mitochondrial ribosomal RNA
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598–613.
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serodiagnosis of cycsticercosis in pigs naturally injected with Taenia solium. Journal of Helminthology
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291–294.
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6
Hereditary Factors in
Neurocysticercosis with Emphasis on
Single, Small, Enhancing CT Lesions
58 V. Padma et al.
ily members. The affected relatives with 13 in Arab patients14,19,20. Some ‘genes’ pre-
seizures in these families also were examined disposing to the susceptibility to seizures
in the same way as the affected relatives of may be located near the HLA locus. From
probands. The 41 patients (from a total 235) this viewpoint, seizures in association with
included for HLA-DR typing were unrelated SSECTL in Asian Indians may represent a
and randomly selected. HLA-DR typing also genetically determined predisposition to a
was performed on 154 healthy controls (from unique benign epileptic syndrome with par-
the same ethnic groups living in the same ticular imaging characteristics.
geographic region)18.
A history of seizures was documented
among first- and second-degree relatives of HLA Studies in Human
50 (21%) probands. A first-degree relative Neurocysticercosis
was affected in 35 and a second-degree rela-
tive in 15 probands. Thirty-eight (3%) of 1212 From a contrasting point of view to that pre-
first-degree relatives and 28 (0.8%) of 3379 sented above, HLA associations have been
second-degree relatives were affected. reported with other infective diseases such
Therefore, the ratio of affected first- as leprosy, tuberculosis and cysticerco-
degree : second-degree relatives was 4.3 : 1. sis7,21,22. Del Brutto et al. reported signifi-
Localization-related epilepsies were more cantly increased frequency of HLA-A28 and
common among first-degree relatives decreased frequency of HLA-DQW2 in a
(P0.05), whereas generalized epilepsies Mexican cohort with parenchymal NC7. The
were more often noted among second-degree authors surmised that HLA-A28 confers sus-
relatives (P0.01). Interestingly, seven of 35 ceptibility to NC, while HLA-DQW2 accords
first-degree relatives had seizures in associa- resistance. With a similar view, our results of
tion with SSECTL compared with only one HLA studies in the Indian probands with
of 15 second-degree relatives. Other syn- SSECTLs point to an increased susceptibility
dromes were almost equally distributed to an infective agent such as cysticercosis. It
among the relatives. Among affected first- is also possible that affected relatives of
degree relatives, seven had localization- individuals with SSECTLs were exposed to
related epilepsy, while five had SSECTL. the common causative agent (through food
Among 1587 first- and 3797 second-degree and water for cysticercosis). The high preva-
relatives of 212 controls with neurological lence of seizures among first-degree rela-
diseases other than epilepsy, 20 first- and tives could also be reflection of an exposure
four second-degree relatives had epilepsy. to a common environmental agent.
Affected probands had a significantly higher
frequency or a positive family history in
comparison to controls6. Experimental Evidence for a Genetic
HLA-DR B1*13 was expressed in 29.3% of Contribution
probands in comparison to 97% in healthy
controls (2 = 10.35; RR = 3.83). On the other Fragoso et al. investigated the influence of non-
hand, HLA-DR B1*09 was observed with an classic Class I MHC Qa-2 antigen expression
increased frequency in probands (7.3 vs. 1.3%; and acquisition of T. crassiceps cysticercosis in
2 = 4.69; RR = 6). None of the other class II mice8. The authors found that the
antigens tested revealed any significant devia- BALB/cAnN substrain of mice, which did not
tion in patients as compared to controls6. express Qa-2 antigen was highly susceptible to
Several previously published reports sug- infection, while another substrain BALB/cJ,
gest a role of the HLA system in different which expressed Qa-2 was resistant to T. crassi-
epileptic syndromes11,13,14,19,20. Juvenile ceps cysticercosis. In further experiments, Qa-2
myoclonic epilepsy was shown to be linked transgenic mice (C57BL/67/BALBcAnN) were
to the BF and HLA loci on human chromo- backcrossed to BALB/cAnN mice and then
some 6 in two population groups from the infected with T. crassiceps9. A significantly
United States and Germany, and HLA-DRW lower yield of cysticercus larvae was noted in
60 V. Padma et al.
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the human major histocompatibility complex. Nucleic Acids Research 29, 210–213.
2. Ruiz, N., Giudecelli, V., Ginestoux, C., et al. (2000) IMGT, the international immunogenetics data-
base. Nucleic Acids Research 28, 219–221.
3. Nepom, G.T., Nepom, B.S. (1992) Prediction of susceptibility to rheumatoid arthritis by human
leukocyte antigen genotyping. Rheumatic Diseases Clinics of North America 18, 785–794.
4. Subbah, I., Savola, K., Ebeling, T., et al. (2000) Genetic, autoimmune and clinical characteristics of
childhood- and adult-onset type 1 diabetes. Diabetes Care 23, 1326–1332.
5. Jain, S., Padma, M.V., Kanga, U., et al. (1997) Human leukocyte antigen studies in Indian probands
with seizures associated with single small enhancing computed tomography lesions and seizure
types in their family members. Journal of Epilepsy 10, 55–61.
6. Jain, S., Padma, M.V., Kanga, U., et al. (1999) Family studies and human leukocyte antigen class II
typing in Indian probands with seizures in association with single small enhancing computed
tomography lesions. Epilepsia 40, 232–238.
7. Del Brutto, O.H., Granados, G., Talamas, O., et al. (1991) Genetic pattern of the HLA system: HLA A, B,
C, DR, DQ antigens in Mexican patients with parenchymal brain cysticercosis. Human Biology 63, 85–93.
8. Frogoso, G., Lamoyi, E., Mellor, A., et al. (1996) Genetic control of susceptibility to Taenia crassiceps
cysticercosis. Parasitology 112, 119–124.
9. Frogoso, G., Lamoyi, E., Mellor, A., et al. (1998) Increased resistance to Taenia crassiceps murine cys-
ticercosis in Qa-2 transgenic mice. Infection and Immunity 66, 760–764.
10. Padma, M.V., Behari, M., Misra, N.K., et al. (1994) Albendazole in single CT ring lesions in epilepsy.
Neurology 44, 1344–1346.
11. Durner, M., Janz, D., Zingsem, J., et al. (1992) Possible association of juvenile myoclonic epilepsy
with HLA-DRw6. Epilepsia 33, 814–816.
12. Arali, J.A. (1993) Immunological aspects of epilepsy. Brain Development 15, 41–49.
13. van Engelen, B.G., de Waal, L.P., Weemeas, C.M., et al. (1994) Serologic HLA typing in cryptogenic
Lennox Gastaut syndrome. Epilepsy Research 17, 43–47.
14. Obeid, T., el Rab, M.O., Daif, A.K., et al. (1994) Is HLA-DRw13 (W6) associated with juvenile
myoclonic epilepsy in Arab patients? Epilepsia 35, 319–321.
15. Moen, T., Brodtkorb, E., Michler, R.P., et al. (1995) Juvenile myoclonic epilepsy and human leukocyte
antigens. Seizure 4, 119–122.
16. Oguni, H., Uehara, T., Fzumi, T., et al. (1995) Immunogenetic study of patients with severe
myoclonic epilepsy in infants and its variant. Epilepsia 36 (Suppl. 3), S9–10.
17. Suastegui, R.A., De la Rosa, G., Fonzalez-Austiazaran, A., et al. (1995) HLA – class II genetic markers
are involved in resistance/susceptibility for the expression of massive spasm. Epilepsia 36 (Suppl. 3),
S10.
18. Mehra, N.K., Verduijn, W., Taneja, V., et al. (1991) Analysis of HLA-DR2 associated polymorphism
by oligonucleotide hybridization in an Asian Indian population. Human Immunology 32, 246–253.
19. Greenberg, D.A., Delgado-Escueta, A.V., Widlitz, H., et al. (1988) Juvenile myoclonic epilepsy may
be linked to the BF and HLA loci on human chromosome 6. American Journal of Medical Genetics
31, 185–192.
20. Liu, A.W., Delgado-Escueta, A.V., Serratose, J.M., et al. (1995) Juvenile myoclonic epilepsy locus in
chromosome 6p21.2–p11: linkage to convulsions and electroencephalographic trait. American Journal
of Human Genetics 57, 368–381.
21. Zerva, L., Ciznam, B., Mehra, N.K., et al. (1996) Arginine at positions 13 or 70–71 in pocket 4 of
HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy. Journal of Experimental
Medicine 183, 829–836.
22. Rajalingam, R., Mehra, N.K., Jain, R.C., et al. (1996) Polymerase chain reaction-based sequence spe-
cific oligonucleotide hybridization analysis of HLA class II antigens in pulmonary tuberculosis: rele-
vance to chemotherapy and disease severity. Journal of Infectious Diseases 173, 669–676.
Peter M. Schantz
Introduction History
64 P.M. Schantz
demonstrated that he could produce cys- most of the rest of Western Europe, similar
ticerci in the muscles of pigs by feeding them or higher prevalence rates have been docu-
T. solium eggs obtained from tapeworm seg- mented recently in parts of Africa, Asia, and
ments passed by infected humans. Further Central and South America4. Improvements
studies confirmed that humans alone were in diagnosis (neuroimaging methods and
the definitive host of the worm and pigs specific antibody detection) have revolution-
were the only significant intermediate host; ized the antemortem recognition of this dis-
thus, the reasons for the well-recognized ease, thus improving our understanding of
paucity of infection in Moslems and Jews, for the nature of the disease and its true preva-
whom Mosaic laws forbade the ingestion of lence while large-scale migration of popula-
pork, could then be understood. Scattered tions in modern times have continued to
reports suggest that the infection was preva- expand its distribution.
lent in pigs and in humans in various parts
of the world; however, highest rates of trans-
mission most likely occurred in populations Geographic Distribution
with the poorest recorded medical documen-
tation. During the first half of the 19th Taenia solium infection is widely endemic in
century, approximately 2% of postmortem rural areas of developing countries in
examinations of humans conducted in Central and South America, Asia and Africa
Berlin, Germany, revealed cysticercosis and (Fig. 7.1). Published reports document the
details of the clinical and pathologic charac- occurrence of clinical NC in most of the
teristics of NC were extensively described in countries of the Americas (most notably
German medical literature by the turn of the Mexico, Guatemala, El Salvador, Honduras,
20th century3. Although the infection has Colombia, Ecuador, Peru, Bolivia and Brazil).
been virtually eliminated from Germany and The infection was reported to be present in
18 countries of South and Central America West Kalimantan, Sulawesi, Flores, East
whose combined populations represented Timor and Irian Jaya10,11. The cestode was
94% of the total 1980 population of the Latin apparently introduced into Irian Jaya in
American countries5. Of the American coun- recent times when swine from Bali were
tries, only Canada, the United States, translocated to (former) West New Guinea12.
Argentina and Uruguay appear to be free of Improvements in socio-economic conditions
transmission in the pig–human cycle; how- were associated with reduction or disappear-
ever, these latter countries are observing an ance of the infection in Japan, Taiwan, Hong
increase in imported and introduced infec- Kong, Singapore, and Thailand, where, in
tions related to immigration of persons from recent years, most cases diagnosed were
neighbouring countries where T. solium apparently imported.
infection is endemic4. No information is In Africa, T. solium is transmitted through-
available concerning the occurrence, or out most of the continent with the exception
absence, of infection in Guyana, Suriname of the strictly Muslim areas of North and
and French Guiana. sub-Saharan Africa. NC is an important
In Asia, most available data are from cause of neurological disability in regions of
clinic-based populations and, consequently, Africa in which it has been studied; epilepsy
are biased in terms of the true geographic in several countries has been documented to
origin and epidemiologic factors associated be caused by T. solium infection in 30–51% of
with transmission. Transmission in much of cases13. In Africa, as in Asia, subcutaneous
Asia is strongly influenced by prevailing cul- localization of cysticerci, concomitant with
tural practices and socio-economic condi- intracerebral infection, is common (30%);
tions. In India, for example, intestinal-stage this is in contrast to the infection in
T. solium infections occur mainly in pork-eat- American countries where subcutaneous
ing populations, particularly in rural popula- localization in patients with NC is relatively
tions and lower socio-economic classes; 78% rare4. Because of the limited development of
of children of pig farmers were reported to medical and sanitary infrastructure, the
be passing taeniid eggs6,7. Vegetarian popu- impact of the disease may be underestimated
lations are presumably exposed to cysticer- to a greater degree than in other regions. The
cosis through direct and indirect contact widespread absence of sanitary services,
with Taenia carriers. The vast majority of especially adequate disposal of human
clinical cases reported in India are of the sin- excrement, and the frequent practice of
gle-lesion variety with relatively mild symp- allowing pigs to roam free, permits transmis-
toms and benign outcome; these are believed sion of T. solium in most of the regions.
to be associated with exposure to eggs in Controlled slaughter of swine is rarely prac-
contaminated foodstuffs or other indirect tised and consequently cysticerci-infected
exposure to tapeworm carriers8. Curiously, pork is generally consumed by humans who
the greatest number of cases of the rare, mas- either ignore or are ignorant of its signifi-
sive, disseminated form of the disease have cance14,15. In South Africa, Zimbabwe and
also been reported from India; the explana- Madagascar where medical services are rela-
tions for these extremes are unknown9. As tively sophisticated, NC has long been a sub-
might be expected, there are no reports from ject of scientific reports16–19; from other
the strictly Moslem countries of Iran, regions, however, there are very limited data
Pakistan, Afghanistan and Bangladesh. because of the lack of diagnostic facilities.
Human NC is reported widely from China NC is reportedly a common clinical entity in
and parts of Korea. It is known to occur also, many countries of West Africa (Senegal,
although few published data are available, in Benin, Ivory Coast, Togo, Ghana) and
the Southeastern Asian countries of Central Africa (Zaire, Cameroon, Burundi
Myanmar, Cambodia, Laos, Vietnam and and Rwanda)20. Few reports of NC in
parts of the Philippines. In Indonesia, T. humans in East Africa have been docu-
solium infection is endemic in parts of mented; however, a recent report of T. solium
numerous islands including Sumatra, Bali, cysticercosis in 13% of pigs slaughtered in
66 P.M. Schantz
three abattoirs in Tanzania suggests that the diagnoses of NC have been reported from
cestode occurs in at least some regions21. many other countries; however, such statis-
There is increasing recognition that the med- tics are misleading because differences in
ical and economic costs of T. solium cysticer- availability of medical services and lack of
cosis are greatly underestimated in countries comprehensive and consistent reporting in
like Tanzania, Zambia, Zimbabwe and South most countries confound attempts to com-
Africa and efforts are underway to docu- pare incidence and prevalence between coun-
ment these costs and to organize effective tries and, within a country, between rural and
methods of prevention and control (A.L. urban areas. For example, extensive docu-
Willingham, Frederiksberg, Denmark and mentation in the medical literature on the
R.C. Krecek, Onderstepoort, South Africa, occurrence of NC in Mexico over many years
personal communication, 2000). might have suggested that the disease was
Historically, T. solium occurred widely in more prevalent there than in neighbouring
European countries; indeed, many of the ear- countries; however, recent surveys using
liest recorded observations about the parasite modern diagnostic techniques reveal that the
and its life cycle were reported by European prevalences of T. solium infection in some
authors2. In the mid-19th century, it was countries of the region exceed rates in Mexico
reported that cysticerci were observed in 2% by considerable margins (Table 7.1). In all
of autopsied human cadavers in Germany countries, improved diagnostic technology,
and infections were commonly observed in new options for treatment, and greater
swine at slaughter2. The same was apparently awareness of cysticercosis by the medical and
true in many countries of the continent. public health communities have resulted in
Today, as a result of improvements in swine documentation of increased numbers of cases
husbandry, sanitation and hygiene, the infec- diagnosed in traditional disease-endemic
tion has largely disappeared; however, locally areas as well as new disclosures of active
acquired infections are still occasionally transmission from regions where the disease
reported from Spain (Castilla, Extremadura was previously unrecognized or not
and Andalucia)22,23, northern Portugal24, reported. Recent surveys and epidemiologi-
southern Italy25 and Poland (Z. Pawlowski cal studies, using state-of-the-art diagnostic
and A. Ramisz, Poznan, Poland, personal methods26, have begun to document the
communication, 1997), indicating persisting occurrence of the infection and its impact on
foci of transmission in some regions. affected populations. Table 7.1 compares
recent prevalence estimates for T. solium cys-
ticercosis and taeniasis in humans and cys-
Prevalence Data ticercosis in pigs in surveys of
community-based population samples in
Until recently, the only available quantitative Latin America in which comparable diagnos-
data on cysticercosis from any country were tic methods were used27–40. Prevalence varied
clinic-based statistics on the frequency of NC among communities; however, a consistent
among hospital patients or autopsied cadav- relative pattern of prevalence ratios of the
ers. In Mexico, for example, NC has long different forms of infection has been
been considered to have an important impact observed. Prevalences of intestinal stage
on health services expenditures. Through the infection (taeniasis) are relatively low; how-
1980s, this diagnosis accounted for nearly 9% ever, rates of cysticercosis in humans and
of admissions in neurology and neurosurgi- pigs are usually related quantitatively to the
cal services and was the final diagnosis in rates of taeniasis. People in affected commu-
11–25% of patients operated on for removal nities are not usually aware that the parasitic
of brain tumours1. NC was found in 2.8–3.6% cysts they see in the meat of pigs is the cause
of all autopsies in Mexico City hospitals and of seizures and other neurological disorders;
was reported as the cause of death in however, use of modern serological and
0.6–1.5% of hospitalized patients. Similar sta- imaging diagnostic technology has identified
tistics documenting the frequency of clinical NC as the most important contributor to the
Table 7.1. Prevalence estimates of Taenia solium cysticercosis and taeniasis in humans and pigs in
Latin American communities.
Sero- Prevalence
prevalence of Prevalence
Sample (EITB1) taeniasis in pigs
Country Community size (%) (%) (%) Reference
Mexico Angahuan 1552 10.8 0.3e 4.0t Sarti et al., 1992, 199428,27
Mexico Xoxocotla 1005 4.9 0.2e 6.5t Sarti et al., 199229
Guatemala Quesada 862 11.0 1.0c,e 4.0t Allan et al.,199630,
Garcia Noval et al., 200131
Guatemala El Jocote 955 20.0 2.8c,e 14.0t Allan et al.,199630,
Garcia-Noval et al., 200131
Notes:
1. EITB: enzyme-linked immunoelectrotransfer blot.
2. Prevalence of antibodies to cysticercosis measured in humans by EITB assay (Reference 26).
3. Prevalence of taeniasis measured by examination of faecal specimens for eggs e or coproantigensc or
both.
4. Prevalence of cysticercosis in pigs measured by visual examination and palpation of tongue t or
detection of antibodies by EITB assay i.
5. n.d.: not done.
68 P.M. Schantz
the impact of the disease on the health of purposefully, e.g. ‘pig-sty privies’, thus also
these communities. leading to transmission of T. solium. Such
Using data on seroprevalence and seizure conditions may appear to be the endpoint of
disorder rates from multiple population- social neglect but usually represent an effec-
based community studies in Peru, Bern et al. tive adaptation to poverty and circumstance
estimated that there were from 23,512 to whereby the pig is nourished adequately at
39,186 symptomatic cases of NC in Peru virtually no cost to the owner and, simulta-
alone42. Extrapolating from limited serologi- neously, serves as a community scavenger or
cal surveys in other countries of Latin ‘sanitary police’. Through coprophagy, pigs
America, these authors calculated that 30–50 readily become infected, often at high rates
million persons may have been exposed to T. and very intense levels. Recent surveys in
solium in Latin America alone and that there disease-endemic communities of Latin
were an estimated 400,000 infected persons America have revealed that infection rates in
with symptomatic disease. In most countries pigs approach 5–50%27–31,35,36,39,44–46. In T.
where T. solium infection is endemic, com- solium-endemic areas, local populations,
munity-based prevalence data are not yet including pig owners, are often unaware of
available and there exist no realistic, data- the threat to public health that this infection
based estimates of the worldwide prevalence in pigs represents and do not relate the
of T. solium infection in humans, however, lesions in their animals to disease in humans.
the diagnostic technology now exists to Nevertheless, pig owners may routinely
begin to amass such data. There is a need for check their live pigs for cysticercosis by
provision of diagnostic and therapeutic direct examination of the tongue. This con-
resources at the community level to deter- cern is motivated by the knowledge that cys-
mine the prevalence of infection and rates of ticerci-infected meat may be rejected at
associated morbidity. slaughter (where visual meat inspection is
practised) or will bring a significantly
reduced price. Consequently, infected pigs
Patterns of Transmission may be slaughtered and sold clandestinely
or consumed by the pig-owner’s family. In
Endemic transmission villages of Central Peru, where infection
rates in pigs varied from 14% to 25%, virtu-
Throughout its worldwide distribution, T. ally none of the infected pigs were processed
solium is maintained by cyclic transmission at the local slaughterhouse. Rather, pig own-
in swine and human hosts. More than 40 ers and vendors purposefully bypassed for-
years ago, T. solium infection was called a mal slaughterhouses. The investigators
‘testimony to under-development’43; that estimated that 23% of the total pork con-
characterization remains true today. sumed in the community was derived from
Transmission of T. solium requires that pigs pigs infected with cysticerci46. Studies in
have access to human faeces and that Mexico, Guatemala and Peru have shown
humans ingest inadequately cooked meat of that the principal factors associated with the
pigs. Such conditions are common in rural likelihood of infection in pigs include
areas of many under-developed or unevenly increasing age and access to human faeces.
developed countries characterized by poor Confined pigs tend to be protected from
hygiene, deficient sanitary facilities and infection but only if confinement is habitual
primitive swine husbandry practices that and they are not deliberately fed faeces28,29,47.
allow pigs to run loose all or part of the time; Improved understanding of the epi-
such communities have not yet directly ben- demiology of T. solium transmission
efited from the achievements in sanitation requires a better understanding of the risk
and hygiene often referred to as the ‘first factors for intestinal-stage infection and the
public health revolution’. In certain situa- modes of dispersal of infective eggs by
tions where pigs are kept in enclosures or are human tapeworm carriers because taeniid
restrained, they may be fed human faeces eggs in faeces or contamination of the
hands of infected humans are the direct Imported and introduced disease
source of cysticercosis in both pigs and
humans. Surveys in disease-endemic com- Imported cases of T. solium taeniasis/cysticer-
munities in Mexico, Guatemala, Peru and cosis are those acquired in a foreign country.
Honduras have shown rates of T. solium Onset of illness in NC typically occurs a year
taeniasis varying from 0.3% to or more after initial acquisition of the infec-
6%27,29,30,35,38. Factors associated with taeni- tion; therefore, among internationally mobile
asis include age (rates of intestinal taeniid persons exposed to infection, it is not uncom-
infections tend to peak in middle adult- mon that development of the disease occurs in
hood; however, infections occur in all age a country different from that in which the
groups) and frequency of pork consump- infection was acquired (‘imported case’).
tion11,29,30,38. In some populations, taeniid Returning tourists or immigrants can also
infections are observed significantly more import intestinal-stage T. solium infections into
frequently in women than in men29,30. The the country; when the tapeworm carrier trav-
presence of a tapeworm-infected individual els home or emigrates to a foreign country and
within a household is an important risk fac- inadvertently transmits the infection to
tor for exposure to T. solium cysticercosis another person, or to a pig, the infection has
and this risk may be increased if the tape- been ‘introduced’ to the host country. More
worm carrier is an individual engaged in rarely, the infection can be introduced by inter-
food preparation and child care activities. national transport of infected pigs and subse-
In Peruvian mountain villages, food han- quent consumption of their infected meat.10,12
dlers engaged in preparing and selling a
traditional pork dish (‘chicharrones’) were
Imported disease
shown to harbour intestinal taeniid infec-
tions at a significantly higher rate than A unique historical epidemic of imported
other persons in the community39,40. NC was that which occurred in British
Serological screening of humans from these troops stationed in India. In at least 450 cases
villages documented levels of apparent soldiers or their family members developed
exposure to T. solium cysticercosis varying symptoms 1–30 years (average: 5 years) fol-
from 5% to 24% (Table 7.1). Significantly lowing their deployment in India48.
higher levels of seropositivity in humans Approximately a quarter of these patients
were associated with low levels of sanitary reported a history of taeniasis; however, little
infrastructure and personal hygiene, age other information was reported on their pos-
more than 20 years and personal histories sible sources of infection. More recently,
of taeniasis. Highest seropositivity rates imported cases of NC are diagnosed every
were found in persons with multiple fac- year in countries throughout the world in
tors39, suggesting that these apparent risk immigrants or tourists returning from coun-
factors and behaviours acted cumulatively. tries where T. solium infection is endemic.
In some communities, there was evidence This phenomenon is fed by the recent
of ‘clustering’ of seropositive persons in increase in international movement as a
households of persons with histories of or result of tourist and business travel and emi-
current taeniasis28,29,30,37. In Guatemala, for gration (the World Tourist Organization cur-
example, one-third of all seropositive per- rently estimates that at least 400 million
sons were clustered within the same house- international border crossings occur each
holds30. These observations suggest a year). In recent years, imported cases of NC
‘focal’ pattern of transmission associated have been reported from Australia49–51,
with the presence of a tapeworm carrier. Norway52, Spain23, Argentina53, Denmark54
There is a need for further studies in other and the USA55. By virtue of the number of
areas where T. solium is currently transmit- immigrants entering the USA every year
ted to be able to provide baseline epidemio- from countries where T. solium infection
logical data and suggest strategies for is endemic, more cases of imported NC
control. are diagnosed in that country every year
70 P.M. Schantz
to control the disease must consider costs new knowledge of the impact of the
and locally available resources. Never- zoonotic disease on local health and the
theless, the many recent advances in diag- economy, provide incentive and improved
nosis and treatment of the disease, and the means to undertake these tasks57–59.
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8
What Have We Learnt From
Epidemiological Studies of Taenia solium
Cysticercosis in Peru?
Churusapa) and five water samples (each of the Mother’s Club of the village, and
after concentrating 250–500 l of river water) obtained similar findings3. In order to
were obtained. The study determined that obtain a thorough assessment of the
the EITB-human seroprevalence was 8% geographical prevalences within Peru, the
and porcine seroprevalence, 45% (Table 8.1). CWG studied an endemic community
The coproparasitological survey detected (Monteredondo) in the Coastal zone (popu-
Taenia eggs in about 1% of the human popu- lation: 1200; altitude: 300 m)4. An inspection
lation. Most seropositive individuals were of this region noted that pigs were kept tied,
neurologically asymptomatic. Taenia ova and human faeces were disposed in the
were not found in any soil or water sample. fields, but usually in fixed places. A total of
Subsequently, the CWG focused upon a 489 individuals were sampled and human
different geographical environment, the seroprevalence was estimated at 16%.
Highlands. A survey was carried out in However, interestingly, seroprevalence in
Haparquilla (population: 371; altitude: 3400 pigs (13%) was considerably less than
m), a village in the southern Highlands, human seroprevalence as well as prevalence
close to Cusco, in 19903. The Highlands are figures in porcine populations in other geo-
different from the jungle in that the graphic locations (Table 8.1)4. The low
weather is much colder. Moreover, the sur- prevalence in pigs was somewhat unex-
vey found that pigs were mostly corralled pected. When the CWG attempted to
in the backyards. There were virtually no analyse the reasons behind the low rates of
latrines and villagers defecated in their porcine infection in this community, it found
backyards. Electricity supply existed, how- that the Monteredondo community began to
ever there was no facility of potable water. grow rice, 3 years before the survey. This led
Human seroprevalence in the Highland the villagers to tether pigs in order to protect
community was found to be 13% and was the rice crop. Therefore, at the time of the
comparatively higher than in the jungle survey, all pigs were less than 3 years of age
communities. Porcine seroprevalence was and were tethered; accordingly seropositvity
similarly high (Table 8.1)2. Two years later, rates were low. Serological status in humans
we performed a survey in Saylla, another remained high since it represented the
community in the Highlands, with the help cumulative effects of exposure over a
Table 8.1. Characteristics of human and porcine populations and EITB based seroprevalence of Taenia
solium cysticercosis in Peru.
Population
sampled 371 (88%)* 134 (48%)* 108 (30%)* 99 (20%)* 489
Type of sample General General General Mothers’ Club General
population population population and relatives population
Human
seroprevalence 8% 7% 13% 24% 16%
Males 7% 6% 10% 41% 13%
Females 9% 7% 15% 18% 20%
Stool disposal Open field Open field Backyard Backyard Defined
Porcine
seroprevalence 43% (57/133) 49% (43/87) 46% (51/110) 36% (19/53) 13%
Pig raising Free Free Free/corralled Free/corralled Tied
*Figures in parentheses represent the percentage of the total population of the village that was sampled.
much longer period of time. Other commu- location (Quilcas, Central Highlands), 398
nity surveys have similarly described high villagers were sampled in 1996; 140 were
seroprevalence rates in endemic communi- found to seropositive while 258 were
ties within Peru; 15 (13%) out of 112 indi- seronegative. Three years later, in 1999, 69
viduals attending a health centre in out of the 140 that were initially seropositive
Pomabamba, Ancash, and 72 (21%) out of (50%; 95%CI: 41–58%) were now seronegative.
334 in Vichaycocha, Central Highlands These data demonstrated that many newly
were seropositive. Two large-scale surveys infected (or exposed) individuals developed
in a population of 3000 in Quilcas only transient serologic antibody reactions.
(Huancayo, Central Highlands) and 4500 These individuals may have been exposed to
in Andahuaylas (Apurimac, southern T. solium, but did not eventually develop
Highlands) established seroprevalence rates viable infection, or they may have had cys-
of 12–15%. In addition, a recent survey in ticercosis that spontaneously resolved. This
Tumbes in the northern Coast, found 22% of could also explain the discrepant finding of
individuals sampled to be seropositive. The high background levels of putatively inac-
above findings are representative of the tive, calcified brain lesions in seronegative
prevalence in T. solium endemic regions of controls8–10; it may be surmised that these
Peru. In non-endemic areas, the seropreva- currently seronegative individuals had tran-
lence has been consistently found to be less sient seropositivity in association with active
than 1% (1% in unselected urban groups in or transitional cysticercosis that eventually
Lima5 and a specialized sheep-raising coop- resolved with calcification.
erative farm in the Highlands6 and no
seropositive cases among the low-Jungle
communities in Iquitos and La Merced). From initial evaluation to intervention
give blood samples were seropositive. seropositive cases were found among 16 indi-
There was however, discordance between viduals with history of seizures13. Eight of
clinical and serological diagnoses: over half them (four seropositive and four seronega-
of the patients clinically diagnosed as hav- tive) agreed to undergo complete neurologi-
ing cysticercosis were seronegative. On the cal and CT examination at a reference centre.
other hand, ten seropositive patients had All four seropositive individuals had evi-
diagnoses other than cysticercosis. One of dence of NC upon CT: single enhancing
them had intestinal Taenia infection and lesion (1), multiple live cysts and calcifica-
another previously had surgery for cerebral tions (1) and multiple calcifications (2). The
cysticercosis (antecedent was not recorded four seronegative individuals had normal
in the current clinical chart). Three seroposi- cerebral CT scans. Age of onset of seizures
tive subjects were diagnosed to have NC by was 17 or older in seven of the eight patients
computed tomography (CT) scan (showing (excepting one seropositive case).
multiple cysts) upon follow-up, one had a When results of consecutive EITB-based
lesion diagnosed on CT as ‘expansive tem- serological studies at a serological labora-
poral lesion’, and another patient had tory of a large hospital were evaluated, the
hydrocephalus5. overall proportion of positive cases was 18%
Another serological survey was per- in serum samples and 28% in CSF samples14.
formed upon patients visiting a private Factors potentially associated with seropos-
radiology centre for brain CT scan10. itivity were analysed using logistic regres-
Seroprevalence was 8% in this population. sion techniques. Four factors were
Again, there were discrepancies between significantly associated with a positive test:
radiological diagnoses and seropositive sta- to be born outside Lima, to have raised
tus. Moreover, when the scans were inter- pigs, age older than 20, and a history of tae-
preted by a second neuroradiologist niasis. We have also studied the time to dis-
(masked to the original interpretation), only appearance of antibodies in a series of 50
one of ten scans was confirmed as having patients with NC treated with albenda-
‘active’ NC, and five of 14 were not recog- zole15,16. Only three of the 14 cured patients
nized as having NC. At the Instituto de became seronegative at one year after suc-
Ciencias Neurológicas, Lima, 498 neurologi- cessful treatment. In most patients, who had
cal outpatients were examined by EITB11. strong baseline serology (displaying all
Of patients with seizures, 12% were seven reactive bands on EITB), the reactive
seropositive, compared with 3% of those bands persisted at the end of 1 year of fol-
with other neurological symptoms. low-up. Interestingly, an increase in the
Seroprevalence increased to 20% if patients number of bands was observed around the
had late-onset epilepsy or were born out- second week of therapy in patients with
side Lima, and to 29% if they had both risk viable cysts.
factors. A careful coproparasitological evaluation
The relationship between serological sta- of a prospective series of patients with NC
tus and seizures was also evaluated in the identified intestinal taeniasis in 15%. This
community setting during a survey in prevalence was higher than expected. A
Monteredondo12. Of 52 individuals who were direct correlation between the number of
evaluated, 49 had neurological symptoms. cysticerci and the presence of intestinal T.
Fourteen (34%) of 41 epileptic individuals solium was noted, suggesting that heavy
were found to be seropositive, in comparison infections were commonly the result of
to one (12.5%) of eight with headache and/or autoinfection17. Furthermore, we have con-
dizziness. Of the 14 seropositive epileptic firmed elsewhere that the frequency of adult
individuals, 13 agreed to undergo CT. Seven T. solium infection is high among patients
of these 13 scans revealed evidence of NC: with massive cysticercus infection18.
single cyst (2), multiple cysts (1), two calcifi- When imaging features in seropositive
cations (2), and multiple calcifications (2). In individuals were analysed it was found that
a different community in Huaraz, five (35%) individuals with transitional (enhancing)
lesions were younger in comparison to those sis28. The reader is referred to Chapter 15 for
with active (viable) cysts; at older ages both a comprehensive review of these studies.
active (viable) cysts and calcified lesions
were frequent. This suggested that some
infections (probably those with lesser num- Conclusions
bers of parasites) were controlled by the host
immune response resulting in early death of After more than a decade of studies by the
parasites, whereas others persisted for long CWG, several concepts have emerged while
periods. Patients with hydrocephalus were others have been clarified. The most signifi-
older than those with viable cysts, enhancing cant of these is that taeniasis/cysticercosis is
lesions, or calcifications alone (CWG, unpub- extremely common in Peru. The magnitude
lished data). of transmission may be as high as 25% of
humans infected at a given time in hyperen-
demic villages, and may easily be over 10%
Porcine Cysticercosis in many endemic zones. While seropreva-
lence rates are high, neurologically sympto-
Porcine cysticercosis has been reviewed by matic individuals constitute the tip of the
Gonzalez et al. (Chapter 15). Certain features iceberg. Also, a proportion of asymptomatic
that are specifically relevant to the under- individuals has imaging abnormalities sug-
standing of the epidemiology of T. solium cys- gestive of NC7–9; these are mainly seronega-
ticercosis in Peru are discussed here. Before tive individuals with residual, inactive
1990, the veterinary team of the CWG evalu- calcified brain lesions. On a converse note, it
ated the sensitivity and specificity of tongue is also common to encounter asymptomatic
palpation vis-à-vis EITB serology, in a con- seropositive individuals in community stud-
trolled design. When evaluated against ies. As for many other infectious diseases,
necropsy, tongue palpation was over 70% seropositivity in asymptomatic individuals is
sensitive and highly specific, whereas EITB generally interpreted as a marker of current
detected all necropsy-positive pigs19. The vet- subclinical or past infection.
erinary team also studied and identified the A common pitfall in the interpretation of
pig marketing circuits in Peru. They noted serological data is to compare different kinds
that official marketing and slaughtering facil- of populations. A 10% prevalence in neuro-
ities were completely circumvented by peas- logical patients at a large urban medical facil-
ants particularly in the Central Highlands. ity (where the overall seroprevalence is likely
Slaughtering was performed under clandes- to be below 10%) cannot be equated to a 10%
tine conditions; infested carcasses thus prevalence in the general population of an
obtained were later introduced into the for- endemic community (where surveying
mal market. A significant proportion of com- epileptic patients may reveal seroprevalence
mercialized pork was infected in the rates of 30–35%). Another pitfall is to assume
Highlands. Infected pork was sold at cheaper that, since the majority of seropositive indi-
prices and often mixed and disguised with viduals in endemic communities are asymp-
clean meat in order to facilitate its sale to tomatic, seropositivity has no relationship
public eating facilities20. Other major accom- with neurological symptoms. Some authors
plishments of the veterinary team of the have questioned the role of NC in the aetiol-
CWG include the establishment of the feasi- ogy of seizure disorders. However, studies by
bility of using sentinel pigs as an indicator of the CWG in Peru have demonstrated that
the burden of infection in a given area21, seroprevalence rates in neurological patients
demonstration of the passive transplacental are consistently much higher than in compa-
transfer of immunity and seropositivity22, the rable general populations. This increases fur-
use of drugs such as albendazole and ther when specific subgroups, for instance,
oxfendazole for treatment in control mea- those with late onset seizures are examined.
sures23–27 and of intramuscular inoculation in Another important outcome of the work done
an experimental model of porcine cysticerco- by the CWG is the realization of the intimate
relationship between domestic pig raising, The CWG is now in the concluding phase
taeniasis and human cysticercosis. Porcine of a randomized study designed to evaluate
seroprevalence reflects recent infection and the clinical benefits of anticysticercal therapy
porcine serosurveys are the fastest and least for NC, along with radiological (CT/MRI)
expensive method to document levels of and immunological (clinical significance of
ongoing transmission. Pigs are infected early individual antibodies, antigen detection30,31,
in life29 and are usually slaughtered by the cytokine pathways32) studies in the natural
age of 1 year. In a survey in an urban com- and post-treatment evolution of human NC.
mercial pig slaughterhouse, no animals had
cysticercosis. Usually porcine seroprevalence
is twice that of human seroprevalence. Acknowledgements
However, Monterendondo was an exception.
Thus human seroprevalence reflects cumula- Support from grants FD-R-001107 from the
tive effect of past exposure, while porcine Food and Drug Administration, and U19-
seroprevalence is an indicator of recent trends A145431 from NIAID/NIH (USA) is
in infection burden in a given community. acknowledged.
References
1. Diaz, F., García, H.H., Gilman, R.H., et al. (1992) Epidemiology of taeniasis and cysticercosis in a
Peruvian village. American Journal of Epidemiology 135, 875–882.
2. García, H.H., Araoz, R., Gilman, R.H., et al. (1998) Increased risk for cysticercosis and taeniasis
among professional fried pork vendors and the general population of a village in the Peruvian high-
lands. American Journal of Tropical Medicine and Hygiene 59, 902–905.
3. García, H.H., Gilman, R.H., Gonzalez, A.E., et al. (1999) Human and porcine T. solium infection in a
village in the Highlands of Cusco, Peru. Acta Tropica 73, 31–36.
4. Gilman, R.H., García, H.H., Gonzalez, A.E., et al. (1999) Shortcuts to development: methods to con-
trol the transmission of cysticercosis in developing countries. In: García, H.H., Martínez, S.M. (eds)
Taenia solium Taeniasis/Cysticercosis, 2nd edn. Editorial Universo SA, Lima, Peru, pp. 313–326.
5. García, H.H., Martinez, M., Gilman, R.H., et al. (1991) Diagnosis of cysticercosis in endemic regions.
Lancet 338, 549–551.
6. Moro, P.L., Guevara, A., Verastegui, M., et al. (1994) Distribution of hydatidosis and cysticercosis in
different Peruvian populations as demonstrated by an enzyme-linked immunoelectrotransfer blot
(EITB) assay. American Journal of Tropical Medicine and Hygiene 51, 851–855.
7. García, H.H., Gonzalez, A.E., Gilman, R.H., et al. (2001) Transient antibody response in Taenia solium
infection in field conditions: a major contributor to high seroprevalence. American Journal of Tropical
Medicine and Hygiene (in press).
8. Cruz, M.E., Schantz, P.M., Cruz, I., et al. (1999) Epilepsy and neurocysticercosis in an Andean com-
munity. International Journal of Epidemiology 28, 799–803.
9. Sanchez, A.L., Lindback, J., Schantz, P.M., et al. (1999) A population-based, case-control study of
Taenia solium taeniasis and cysticercosis. Annals of Tropical Medicine and Parasitology 93, 247–258.
10. García, H.H., Herrera, G., Gilman, R.H., et al. (1994) Discrepancies between cerebral computed
tomography and western blot in the diagnosis of neurocysticercosis. American Journal of Tropical
Medicine and Hygiene 50, 152–157.
11. García, H.H., Gilman, R., Martinez, M., et al. (1993) Cysticercosis as a major cause of epilepsy in
Peru. Lancet 341, 197–200.
12. García, H.H., Gilman, R.H., Tsang, V.C.W., et al. (1997) Clinical significance of neurocysticercosis in
endemic villages. Transactions of the Royal Society of Tropical Medicine and Hygiene 91, 176–178.
13. García, H.H., Talley, A., Gilman, R.H., et al. (1999) Epilepsy and neurocysticercosis in a village in
Huaraz, Perú. Clinical Neurology and Neurosurgery 101, 225–228.
14. García, H.H., Gilman, R.H., Tovar, M., et al. (1995) Factors associated with T. solium cysticercosis.
Analysis on 946 Peruvian neurologic patients. American Journal of Tropical Medicine and Hygiene 52,
147–150.
15. García, H.H., Gilman, R.H., Horton, J., et al. (1997) Albendazole therapy for neurocysticercosis: a
prospective double blind trial comparing 7 vs. 14 days of treatment. Neurology 48, 1421–1427.
16. García, H.H., Gilman, R.H., Catacora, M., et al. (1997) Serological evolution of neurocysticercosis
patients after antiparasitic therapy. Journal of Infectious Diseases 175, 486–489.
17. Gilman, R.H., Del Brutto, O.H., García, H.H., et al. (2000) Prevalence of taeniasis among neurocys-
ticercosis patients is related to the severity of cerebral infection. Neurology 55, 1062.
18. García, H.H., Del Brutto, O.H. and The Cysticercosis Working Group in Perú (1999) Heavy non-
encephalitic cerebral cysticercosis in tapeworm carriers. Neurology 53, 1582–1584.
19. Gonzalez, A.E., Cama, V., Gilman, R.H., et al. (1990) Prevalence and comparison of serologic assays,
necropsy, and tongue examination for the diagnosis of porcine cysticercosis in Peru. American
Journal of Tropical Medicine and Hygiene 43, 194–199.
20. Cysticercosis Working Group in Peru (1993) The marketing of cysticercotic pigs in the sierra of Peru.
Bulletin of the World Health Organization 71, 223–228.
21. Gonzalez, A.E., Gilman, R.H., García, H.H., et al. (1994) Use of sentinel pigs to monitor environmen-
tal Taenia solium contamination. American Journal of Tropical Medicine and Hygiene 51, 847–850.
22. Gonzalez, A.E., Verastegui, M., Noh, J.C., et al. (1999) Persistence of passively transferred antibodies
in porcine Taenia solium cysticercosis. Veterinary Parasitology 86, 113–118.
23. Gonzalez, A.E., García, H.H., Gilman, R.H., et al. (1995) Treatment of porcine cysticercosis with
albendazole. American Journal of Tropical Medicine and Hygiene 53, 571–574.
24. Gonzalez, A.E., García, H.H., Gilman, R.H., et al. (1996) Effective, single dose treatment of porcine
cysticercosis with oxfendazole. American Journal of Tropical Medicine and Hygiene 54, 391–394.
25. Gonzalez, A.E., Falcon, N., Gavidia, C., et al. (1997) Treatment of swine cysticercosis with oxfenda-
zole: a dose-response trial. Veterinary Record 141, 420–422.
26. Gonzalez, A.E., Falcon, N., Gavidia, C., et al. (1998) Time–response curve of oxfendazole in the treat-
ment of swine cysticercosis. American Journal of Tropical Medicine and Hygiene 59, 832–836.
27. Verastegui, M., Gonzalez, A.E., Gilman, R.H., et al. (2000) Experimental infection model for Taenia
solium cysticercosis in swine. Veterinary Parasitology 94, 33–44.
28. Gonzalez, A.E., Gavidia, C., Falcon, N., et al. (2001) Cysticercotic pigs treated with oxfendazole are
protected from further infection. American Journal of Tropical Medicine and Hygiene 65, 15–18.
29. Diaz, F., Verastegui, M., Gilman, R.H., et al. (1992) Immunodiagnosis of human cysticercosis (Taenia
solium): a field comparison of an antibody-enzyme-linked immunosorbent assay (ELISA) an anti-
gen-ELISA and an enzyme-linked immunoelectrotransfer blot (EITB) assay in Peru. American Journal
of Tropical Medicine and Hygiene 46, 610–615.
30. García, H.H., Harrison, L.J.S., Parkhouse, R.M.E., et al. (1998) Application of a specific antigen detec-
tion ELISA to the diagnosis of human neurocysticercosis. Transactions of the Royal Society of Tropical
Medicine and Hygiene 92, 411–414.
31. García, H.H., Parkhouse, R.M.E., Gilman, R.H., et al. (2000) Serum antigen detection in the diagno-
sis, treatment, and follow-up of neurocysticercotic patients. Transactions of the Royal Society of Tropical
Medicine and Hygiene 94, 673–676.
32. Evans, C.A.W., García, H.H., Hartnell, A., et al. (1998) Elevated concentrations of eotaxin and inter-
leukin-5 in human neurocysticercosis. Infection and Immunity 66, 4522–4525.
Elsa Sarti
0
Less than 1 year old
1–4
5–14
15–24
25–44
*Incidence rate by 100,000 inhabitants
45–64 in Mexico (average 3.0)
Older than 65 years 0.19 –2.87 (15 states)
Fig. 9.1. State-wise and age-wise incidence of Taenia sp. infection in México, 1994–2000 (Source: National epidemiological surveillance system)10.
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E. Sarti
12
6
0
Less than 1 year old *Incidence rate by 100,000 inhabitants
1–4 in Mexico (average 0.5)
5–14 0 –0.19 (4 states)
15–24 0.20– 0.63 (14 states)
25–44
0.64– 2.52 (9 states)
45–64
Older than 65 years 2.53– 3.94 (5 states)
Fig. 9.2. State-wise and age-wise incidence of neurocysticercosis in México, 1994–2000 (Source: National epidemiological surveillance system)10.
Subject to the CABI Digital Library Terms & Conditions, available at https://cabidigitallibrary.org/terms-and-conditions
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Singh - Chap 09 4/9/02 4:39 pm Page 87
88 E. Sarti
nated by Taenia eggs32. These modalities of asis were measured by the frequency of
transmission have not been confirmed by Taenia coproantigens and Taenia eggs in fae-
studies in Mexico6,17,33. ces. Swine cysticercosis was measured by
palpating tongue and the presence of serum
antibodies. Changes in knowledge, attitudes
Step 3 (Developing interventions for and practices in the communities were eval-
control) uated by questionnaires prepared ex professo
as well as by direct observation by inter-
viewers. Praziquantel treatment reduced
An evaluation of the efficacy of mass tae-
rates of taeniasis by 66%. However, treat-
niacidal treatment was carried out during
ment alone, had no impact on swine cysticer-
1990, in a community in Sinaloa26.
cosis. A 66–77% decrease in swine
Praziquantel treatment was administered to
cysticercosis was observed in communities
the population of approximately 2000 inhabi-
where health education was provided (‘B’
tants. Before treatment, 1.3% of the individu- and ‘C’). Evaluation of long-term outcome
als had taeniasis and only one out of the 72 (42 months after the intervention) revealed a
pigs examined had cysticercosis. Treatment reduction of 48% of taeniasis in community
lead to complete eradication of intestinal tae- ‘B’. This underscored the importance of
niasis but data on porcine cysticercosis was health education in the effective control of
inadequate. By comparison, another study in taeniasis–cysticercosis. Health education
1987 provided insights into the role of health had a twofold effect. Improved sanitary
education, and demonstrated that health practices and curtailing free-ranging pigs
promotion could be a short-term alterna- led to a decrease in the frequency of
tive26,27. A promotional campaign emphasiz- porcine cysticercosis and ultimately human
ing upon the need to construct latrines in taeniasis. Secondly, awareness of the utility
every home and the hazards of open-air of taeniacidal treatment and its use pre-
defecation was conducted in schools. The vented human and porcine cysticercosis.
study demonstrated that the campaign cre- Results of our studies suggested that health
ated awareness about the parasite; unfortu- educational programmes are effective for T.
nately, mass taeniacidal treatment of solium control.
members of this community was not success-
ful as the prevalence of porcine cysticercosis
had doubled 1 year after intervention. It Mexican Surveillance to Monitor and
must be mentioned that this study was not Control Taeniasis–Cysticercosis
oriented to community intervention, but to
the identification of the risk factors. Mexico has a Unique Information System for
We have evaluated two alternative strate- Epidemiological Surveillance (SUIVE) gener-
gies for control of T. solium in the last decade: ating information on community health-
(i) mass taeniacidal drug administration; and related risk factors, treatment and control at
(ii) health education28,29,34. Both measures all operative levels. Information on several
were applied to three rural communities of diseases subject to epidemiological surveil-
Mexico with similar social, economical and lance, including taeniasis and cysticercosis is
cultural characteristics. Community ‘A’ collected in a specifically prepared format by
received mass praziquantel treatment (5 mg some 17,000 primary health care units and is
kg1), community ‘B’ received health educa- transmitted to State and Federal health
tion and community ‘C’ received both mass authorities for analysis at a national level.
praziquantel treatment and health education. Health care personnel manning the primary
Demographic, epidemiological, clinical, sani- health care units are imparted continuing
tary and sociological data from 98% of the education regarding simple and effective
inhabitants were obtained. Evaluations were screening and treatment of taeniasis and cys-
performed 6 and 42 months after interven- ticercosis. It is recommended that all individ-
tion. Prevalence and incidence rates of taeni- uals presenting to these centres for health
check-ups and treatment for any ailment swine cysticercosis may be as high as 23.8%.
should be screened for taeniasis–cysticerco- Risk behaviours for taeniasis include free-
sis. As mentioned earlier, a simple inquiry ranging pigs with access to human faeces
about the passage of proglottides suffices as and poor personal hygiene. Human cysticer-
a screening tool. Both cases that are identi- cosis, on the other hand, is clustered around
fied as positive by screening and their fami- intestinal adult T. solium carriers. Currently
lies should be offered taeniacidal treatment. intervention trials focusing on the modifica-
tion of these risks are underway. The impact
of health education and improving sanitary
Conclusions infrastructure is considered important.
Finally strategies employing the above inter-
The prevalence of human taeniasis in Mexico ventions both individually as well as in com-
varies between 0.2% and 0.4%, while that of bination, must be evaluated in order to
human cysticercosis is 4.9–10.9% and that of develop a unified national control policy.
REFERENCES
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Púbica de México 28, 556–563.
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and cysticercosis in humans and pigs in a village in Morelos, Mexico. American Journal of Tropical
Medicine and Hygiene 46, 677–684.
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Enfermedades Tropicales. Secretaría de Salud, México, DF, Mexico, pp. 335–345.
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tions in a rural community in Mexico. Transactions of the Royal Society of Tropical Medicine and Hygiene
84, 563–566.
9. Sarti, E., Schantz, P., Plancarte, A., et al. (1994) Epidemiological investigation of Taenia solium taenio-
sis and cysticercosis in a rural village of Michoacan State, Mexico. Transactions of the Royal Society of
Tropical Medicine and Hygiene 68, 49–52.
10. Secretaría de Salud (2000) Boletín Semanal de Epidemiología, 1994–2000. Dirección General de
Epidemiología, México DF, Mexico.
11. Schantz, P., Sarti, E. (1989) Diagnostic methods and epidemiologic surveillance of Taenia solium
infection. Acta Leidensia 57, 153–163.
12. Medina, M.T., Rosas, E., Rubio-Donnadieu, F., et al. (1990) Neurocysticercosis as the main cause of
late onset epilepsy in Mexico. Archives of Internal Medicine 150, 325–327.
13. Rabiela, M.T., Rivas, A., Rodriguez, I.J. (1979) Consideraciones anatomopatológicas de la cisticerco-
sis cerebral como causa de muerte. Patología (México) 17, 119–124.
14. Schantz, P., Sarti, E., Plancarte, A., et al. (1994) Community based epidemiological investigations of
cysticercosis due to Taenia solium. Comparison of serological screening tests and clinical findings in
two populations in Mexico. Clinical Infectious Diseases 18, 879–885.
15. Flisser, A., Correa, D., Plancarte, A., et al. (1990) New approaches for the diagnosis of Taenia solium
taeniasis/cysticercosis. Annals of Human and Comparative Parasitology 65, 95–98.
16. Aluja, A.S. (1982) Frequency of porcine cysticercosis in Mexico. In: Flisser, A., Willms, K., Laclette, J.,
et al. (eds) Cysticercosis: Present State of Knowledge and Perspectives. Academic Press, New York,
pp. 47–50.
90 E. Sarti
17. Sarti, E., Schantz, P., Aguilera, J., et al. (1992) Epidemiologic observations in a rural community of
Michoacan State, Mexico. Veterinary Parasitology 41, 195–201.
18. Aluja, A., Villalobos, N., Plancarte, A., et al. (1996) Experimental Taenia solium cysticercosis in pigs.
Characteristics of the infection and antibody response. Veterinary Parasitology 61, 49–58.
19. Woodhouse, E., Flisser, A., Larralde, C. (1982) Seroepidemiology of human cysticercosis in Mexico.
In: Flisser, A., Willms, K., Laclette, J., et al. (eds) Cysticercosis: Present State of Knowledge and
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20. Goldsmith, R.S., Kagan, I.G., Reyes-González, M.A., et al. (1971) Estudios serepidemiológicos real-
izados en Oaxaca, Mexico. I. – Encuesta de anticuerpos parasitarios mediante la prueba de
hemaglutinación indirecta. Boletin de la Oficina Sanitaria Panamericana (Washington DC) 71, 500.
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Medicine (México) 7, 107–113.
22. Larralde, C., Padilla, A., Hernández, M., et al. (1992) Seroepidemiology of cysticercosis in Mexico.
Salud Pública de México 34, 197–210.
23. Schantz, P., Sarti, E., Plancarte, A., et al. (1991) Clinical, radiological and epidemiological correlation
of ELISA and immunoblot assays for Taenia solium cysticercosis in 2 populations. Mexico. American
Journal of Tropical Medicine and Hygiene 45, 130–131.
24. Alan, J.C., Avila, G., Garcia-Noval, J., et al. (1990) Immunodiagnosis of taeniasis by coproantigen
detection. Parasitology 101, 473–477.
25. Díaz, S., Candil, R., Suate, P., et al. (1991) Epidemiologic study and control of Taenia solium infections
with praziquantel in a rural village of Mexico. American Journal of Tropical Medicine and Hygiene 45,
522–531.
26. Keilbach, N., Aluja, S., Sarti, E. (1989) A program to control taeniosis and cysticercosis (Taenia
solium). Experiences in a Mexican village. Acta Leidensia 57, 181–189.
27. Rodriguez Canul, R., Fraser, A., Allan, J.C., et al. (2000) Epidemiological study of Taenia solium taeni-
asis/cysticercosis in a rural village in Yucatan state, Mexico. Annals of Tropical Medicine and
Parasitology 93, 57–67.
28. Sarti, E., Flisser, A., Schantz, P.M., et al. (1997) Development and evaluation of health education
intervention against Taenia solium in a rural community in Mexico. American Journal of Tropical
Medicine and Hygiene 56, 127–132.
29. Sarti, E., Schantz, P., Avila, G., et al. (2000) Mass treatment against human taeniosis for the control of
cysticercosis. A population based intervention study. Transactions of the Royal Society of Tropical
Medicine and Hygiene 94, 85–89.
30. García, H.H., Gilman, R., Tovar, M., et al. (1995) Factors associated with Taenia solium cysticercosis:
analysis of nine hundred forty-six Peruvian neurologic patients. American Journal of Tropical Medicine
and Hygiene 52, 145–148.
31. Lawson, J.R., Gemmel, M.A. (1983) Hydatidosis and cysticercosis: the dynamics of transmission.
Advances in Parasitology 22, 261–308.
32. Spindola Feliz, N., Rojas Wastanino, G., de Haro, Arteaga, L., et al. (1996) Parasite search in straw-
berries from Irapuato, Guanajuato and Zamora, Michoacán (México). Archives of Medical Research 27,
229–231.
33. Sarti, E., Bronfman, M., Schantz, P., et al. (1993) Estructuración de un proyecto epidemiológico para el con-
trol de la Taenia solium. Comparación del uso de quimioterapia masiva contra la teniasis y de la impartición
de educación para la salud, como método de intervención de mayor utilidad. Conmemoración Jubileo.
Instituto de Investigaciones Biomédicas. UNAM. México DF, México 2, pp. 413–415.
34. Sarti, E. (1989) Epidemiología de la teniasis y cisticercosis. In: Flisser, A., Malagón, F. (eds)
Cisticercosis Humana y Porcina, su Conocimiento e Investigación en México. Limus Noriega, México DF,
México, pp. 233–242.
92 J. Garcia-Noval et al.
Belmopan
Belize
Managua
200 km Panama
Fig. 10.1. Map of Central America showing countries and capital cities.
from health centres in Honduras indicated a Carolina but none in migrants from Mexico
mean prevalence of 0.47% of intestinal taeni- or Haiti34. Data from field studies in rural
asis in 365,400 faecal samples22. The areas of Honduras and Guatemala have indi-
Honduran data also brought out significant cated that T. solium is responsible for
regional variation in prevalence with rates 75–100% of all Taenia species worms identi-
between 0.06% and 1%. From 1978 to 1987, a fied to the species level22,24–26. This contrasts
survey by the Ministry of Health, Costa Rica with hospital data from large urban centres
recorded a relatively low rate of intestinal where typically no diagnosis to the species
taeniasis, with a mean prevalence of 0.05% in level is carried out10,22.
1,176,332 faecal samples examined23. Recent There are clear patterns in the distribution
data on rates of taeniasis from rural Central of cases of taeniasis within the population of
America are available from Honduras and the region. Rates have been demonstrated to
Guatemala13,22,24–26. Rates of up to 6.2%, with vary considerably between, closely situated,
an average prevalence of 2% of intestinal tae- communities. For instance, in one study of
niasis have been recorded by microscopy in four similarly sized rural communities, all
Honduran communities22,25,26. Rates of within 5 km of each other, prevalence rates
approximately 1% have been detected by of taeniasis varied between 1% and 5.7%,
microscopy in Guatemala13,24,27. These data with statistically significant differences in
appear to indicate that, in comparison to prevalence between the communities13. The
countries in Latin America, rates in these two variations may be linked to socio-economic
countries are high. For instance, average factors such as sanitation, pig husbandry
prevalence in Mexico is typically below techniques and rates of pork consumption.
0.5%28–33. Interestingly, a study carried out in Furthermore, within individual communities
the United States indicated a prevalence of the inter-household distribution of intestinal
4.4% of intestinal taeniasis in Central taeniasis has been shown to be clus-
American migrant workers to North tered13,24,25. In the same Guatemalan study,
rates of taeniasis in household members of study of 10,600 Costa Rican autopsy reports
indicator cases of the taeniasis were shown showed 24 cases of NC (0.23%)37. All the cases
to be nearly double that of the general rate of were aged above 7 years and the number of
taeniasis in the population (4.7% vs. 2.7%)13. the cysts was overdispersed, with 11 of the 24
This is consistent with the clustered pattern autopsies (41.6%) disclosing only one cyst, a
of intestinal taeniasis reported elsewhere in median of two cysts per person and a maxi-
Latin America28,30,31. Data from both hospi- mum of 17 cysts (Fig. 10.3)37. Retrospective
tals and rural communities within the region review indicated that 11 cases (45.8%) had
suggest that the highest rates of intestinal apparently been neurologically asymptomatic,
taeniasis are in individuals in their late teens intracranial hypertension had been diagnosed
to early forties (Fig. 10.2)10,13. Some data sug- in 7 cases (29.1%), convulsive crisis in three
gest that females may be at higher risk than cases (12.5%) and motor deficit in two cases
males13,22. Similar sex-biased distributions of (8.3%). One case was not classified37. More
intestinal taeniasis have been reported in recent hospital data from Costa Rica demon-
Ecuador and in Latin American immigrants strates the continued presence of low levels of
to the United States35,36. Once again the rea- human cysticercosis in that country23.
sons for this are unknown. When computed tomography (CT) scan-
ning was introduced to Guatemala in 1980,
the number of cases of NC diagnosed
Human Cysticercosis, increased greatly, resulting in the finding
Neurocysticercosis and Seizures that NC accounted for at least 8% of all
admissions to neurological wards in
From 1952 to 1961, in a study of hospital Guatemala City38. Similarly, the introduction
records from El Salvador and Guatemala, 118 of CT and ELISA to Honduras in the middle
cases of cysticercosis were detected by of the 1980s led to a fivefold increase in the
autopsy, of which 71 were shown to involve number of diagnoses of NC made in
cysts in the brain10. In 1967, a retrospective University Hospital, Tegucigalpa22.
5.0
4.5
4.0
Percentage prevalence
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
0–4 5–9 10–19 20 – 29 30 – 39 40 – 49 50 – 59 60 – 80
Age cohort (years)
Fig. 10.2. Age prevalence of intestinal taeniasis from a study of four rural communities in Guatemala13.
A total of 92 cases were diagnosed from a sample size of 3399 individuals (2.7% prevalence). Of the
cases 56 were Taenia solium, one case was T. saginata and in 35 cases it was not possible to determine
the species present.
94 J. Garcia-Noval et al.
12
10
Number of individuals
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Number of cysticerci
Fig. 10.3. Distribution of intracerebral Taenia solium cysticerci detected in a retrospective study of
autopsy results carried out in Costa Rica37.
indicated a prevalence of 5.8 cases of active neuroimaging studies than apparently neu-
epilepsy per 100048. Combined rates of active rologically normal controls (47% vs. 24%, P
and inactive epilepsy in rural Honduras have 0.007) (Fig. 10.4)24. In Honduras, one
been recorded at 22.7 per 100049. High rates study in a rural community found 41% of 90
of active epilepsy have been detected in other epileptics having lesions compatible with
studies. For instance, prevalence rates of 29 NC40. A second Honduran community study
per 1000 in rural Honduras26 and 18 per 1000 found a 17.6% rate of intracranial lesions
in rural Guatemala50 have been detected. suggestive of NC in persons with a normal
Furthermore, the estimated prevalence in a neurological examination26. Finally, an eval-
rural population of Guaymi Indians, living uation of family contacts of an indicator case
on the Caribbean coast near Costa Rica, was of cerebral cysticercosis at an urban
up to 57 per 1000, much higher than the rate Panamanian hospital resulted in the detec-
of active epilepsy in the lower social class tion of three of six other family members as
population of Panama City (22 per 1000)51. EITB positive and two of six (including one
of the three seropositives) as having calcified
lesions indicative of NC by CT (Fig. 10.4)52.
Neurocysticercosis and seizure disorder: In the clinical setting, a study in
imaging studies Honduran neurological patients indicated
that 84% of individuals with seizures and
Central American studies carried out in 69% of those with neurological problems
urban centres, rural populations and among other than seizures had lesions suggestive of
neurological patients have all established NC (Fig. 10.4)53. Furthermore, recent data
that cysticercosis is a major cause of morbid- from Honduras indicate that the two major
ity due to seizure disorders throughout the causes of seizures in that country were
region24–26,40,50,51. Data from two rural neonatal hypoxia, as a result of lack of med-
Guatemalan communities revealed that indi- ical attention during delivery, and NC (Ada
viduals with history of seizures had a signifi- Zelaya, National University of Honduras,
cantly greater chance of exhibiting abnormal personal communication). Finally, there is
intracranial lesions suggestive of NC upon evidence from a Honduran study to suggest
Seizures 1 1 (100%)
Trace back to family
(Panama)
No seizures 6 2 (33%)
Fig. 10.4. Correlation between history of seizures and neuroimaging abnormalities detected by CT scan
in different populations in Central America: rural village population24; neurological patients52 and trace
back to family members of an individual in whom NC was diagnosed51.
96 J. Garcia-Noval et al.
that headache may also be linked to NC53. location of cystic infections. For instance in
This link has previously been reported from Central America there appears to be a rela-
a rural population in Ecuador and may bear tively high frequency of single active lesions
further investigation54. and calcified lesions detected by CT scan in
In both field epidemiological studies and rural populations (see Figs 10.3 and 10.4). It
studies of neurological patients the most com- is known that the EITB, though essentially
mon type of abnormal intracerebral lesions 100% specific for T. solium, is less sensitive in
seen by CT scanning have been punctate cal- infections involving single cysts and in indi-
cifications (Fig. 10.4)24,26,50,53. Furthermore, viduals with calcified lesions56. Furthermore,
studies from the region have indicated that, the high rates of NC in apparently asympto-
besides imposing a burden of neurological matic individuals in Central America and the
disease, that, conversely, significant numbers frequency of extraneural infection may fur-
of apparently neurologically normal individu- ther explain the apparent lack of association
als have abnormal intracranial lesion sugges- between serological status and epilepsy in
tive of NC14,24–26,50,52. This has led to the rural Central America. Some studies carried
suggestion that the majority of cases may, in out within the region have, however, demon-
fact, be asymptomatic as has been suggested strated association between epilepsy and
in other endemic regions24,26,54,55. serological status in rural populations.
Indeed Panamanian data, collected before the
introduction of the glycoprotein-based EITB
using an ELISA, demonstrated that signifi-
Human cysticercosis and seizure
cantly more active epileptics were seroposi-
disorder: serological observations
tive for cysticercosis than age- and sex-
matched controls in a population of Guaymi
Serological testing, particularly using the EITB Indians (44% vs. 6%, relative risk = 14)51.
has been useful in detecting areas of transmis-
sion, identifying risk factors associated with
infection and producing data that allow com- Porcine Cysticercosis
parison both within the region and between
Central America and other endemic areas39. In For many years there has been an under-
the hospital-based setting, clear associations standing that porcine cysticercosis imposes a
have been shown between T. solium specific significant economic burden on Central
serological status and seizure disorder. This American pork producers10,57,58. In a study
sometimes represents the only recently avail- carried out across the whole region, except
able data from some countries. For instance, in Belize, from 1959 to 1961, it was reported that
an ongoing study in Nicaragua, 14.7% of 88 68% of all the hogs condemned for any reason
epileptic patients and 2.94% of 102 controls in the six main abattoirs serving the capital
from Leon had antibodies detected by EITB cities of Guatemala City, San Salvador,
(P0.05, odds ratio = 4.25) (Felix Espinoza, Tegucigalpa, Managua, San José and Panama
National Autonomous University of City, were condemned because of cysticerco-
Nicaragua, personal communication). sis10. This represented 2.13% of all the pigs
Epidemiological studies in the region, and slaughtered over this period in these abat-
particularly those carried out in endemic toirs. This situation does not appear to have
communities, have, however, not generally improved: Honduran figures indicate that,
shown an association between either epilepsy from 1981 to 1986, an average of 4.8% of all
or abnormal CT images suggestive of cys- pigs slaughtered at the main abattoir serving
ticercosis and serological status in this Tegucigalpa were condemned due to cysticer-
test14,24–26. This contrasts with studies in other cosis22. Furthermore, in 1994 and 1995 respec-
areas41,42,46. These interregional variations tively, in the same abattoir, 2.8% and 3% of
may be related to the study design. There pigs slaughtered were condemned due to cys-
may, however, be some differences caused by ticercosis (Alexis Mendoza, PROMDECA,
the underlying prevalence and intensity and personal communication).
The failure of the meat inspection process Conclusions: Prospects for Control
to control this parasite can be seen in data
from the mid 1960s, where 6% and 6.5% The prospects for control of T. solium within
respectively, of 99 pork sausages and 107 Central America remain poor. None of the
‘chorizo’ (Spanish type) sausages purchased countries has a formal comprehensive con-
from a range of randomly selected establish- trol system and abattoir meat inspection is
ments in Guatemala City were found to har- ineffective due to slaughter of significant
bour cysticerci57. More recent studies from numbers of pigs outside the formal, regu-
Guatemala revealed that 4% and 14%, respec- lated, system. Further to this, for much of the
tively, of pigs in two rural communities had region, there is a lack, or indeed complete
cysts present in their tongues ante mortem24. In absence of epidemiological data. Without
these respective communities, 22% and 55% such data to assess the magnitude of the
of families raised pigs and 77% and 83% of problem, control programmes cannot be
those families that raised pigs allowed them
either properly planned or implemented.
to roam freely in the village. At least 75% of
Within the region, one study, carried out in
families stated that their main source of pork
Guatemala, has indicated that mass
was pigs killed either at home or in the village
chemotherapy with niclosamide significantly
with no official meat inspection. In one village
reduced prevalence of intestinal taeniasis and
27% of families were aware of having pur-
chased pork containing cysts while in the seroprevalence of cysticercosis in pigs 10
other community, 6% were aware of this24. months later60. Whether such an approach is
Further studies in Guatemala have indicated economically or logistically feasible is, in the
seroprevalences of antibodies to T. solium anti- current economic climate of much of the
gens using the glycoprotein-based EITB59 of region, questionable. If regional governments
40% and 64% in pigs from two communities60. were to identify T. solium as a problem that
Data from Honduras indicate that 27.1% of needed attention, this might improve the situ-
pigs in one community were seropositive in ation. The authors are unaware of any initia-
this test and that pigs may be infected soon tives on this parasite backed by any of the
after birth, although recent data on the pas- regional governments. Similarly, there
sive transfer of antibodies from infected sows appears to have been relatively little work
to piglets complicates the interpretation of the undertaken on this parasite by the local scien-
serological data61,62. tific, veterinary or public health communities.
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11 Neurocysticercosis in Brazil:
Epidemiological Aspects
Svetlana Agapejev
102 S. Agapejev
Fig. 11.1. Some endemic factors for the maintenance of taeniasis/cysticercosis complex: (a) Rubbish
near a sign (arrow) saying ‘No rubbish disposal ’. (b) Lake water used for drinking and hygiene for
humans (arrows) and swine (foreground). (c) Vegetable garden irrigated with contaminated water from
the river (arrow). (d) Contaminated pork at a clandestine slaughterhouse.
in the hot sun. In South and Southeast Brazil, Geographic prevalence of NC within
pork is roasted or fried. Brazil is a rapidly Brazil
developing country, making great strides in
industrialization. Piped water supply exists While NC is endemic throughout most of
in three-quarters and sewer or septic Brazil, definite information about the
cesspool facilities in one-half of the homes. endemic nature of the disease is available
The Brazilian Association of Pig Producers from several states (shown in Fig. 11.2). Other
has 12 million pigs registered in South Brazil, states have non-confirmed occurrence of NC.
9 million in Northeast Brazil, 7 million in These projections are mostly derived from
Southeast Brazil and 6 million in Central- hospital-based reports and these may not
West Brazil. This, however, is not a true esti- reflect the true prevalence of disease. For
mate of the porcine population, since a large instance, Northeast Brazil is an economically
number of pigs are raised in backyards or are underprivileged area and one would expect
free ranging. Official data from government large number of cases to be reported from
sources revealed that the prevalence of swine this region. However, this might not be the
cysticercosis for the period 1952–91 was case as a large proportion of cases may be
0.03–6.9%, through several regions in Brazil. undiagnosed on account of the lack of inves-
However, epidemiological surveys estimate tigative facilities like computed tomography
that the actual prevalence may be as high as (CT). Similarly, it appears from the review of
13–28% in certain regions within Brazil. literature that more severe cases like intracra-
nial hypertension and racemose cysticercosis hospitals in Brazil indicate that NC was
are frequently seen in hospital services in responsible for about two admissions every
Southern and Southeast Brazil in comparison month there. These data are at best an underes-
to North and Northeast Brazil, where most of timate especially since the reporting of
the hospital-based reports are those of milder taeniasis–cysticercosis is not obligatory in
varieties of NC. These differences may Brazil.
merely reflect different referral patterns,
access to medical care and of expertise in the
treatment of more difficult cases in South and Epidemiological Characteristics
Southeast Brazil. Therefore geographical dif- Inferred from Autopsy
ferences in clinical presentations may be
more apparent than real (Figs 11.2 and 11.3). Autopsy is an important tool to confirm clin-
From a review of published autopsy and ical diagnosis and estimate disease fre-
clinical service-based data from 1907 to 2000 quency. Unfortunately, however, resort to
and 1915 to 2000, respectively, an average of autopsy is infrequent in Brazil, primarily
600 autopsy diagnoses of NC and 500 clinico- owing to factors such as excessive trust in
radiological diagnoses of NC were made every laboratory diagnoses, difficulty in obtaining
year60. Similarly, data available from general family authorization, lack of systematic
104 S. Agapejev
(a)
12.9% North-Northeast
Central-West
South-Southeast
Viable cysts
26% 5.2%
67% 4.6%
4.0%
2.0% 1.8%
1.6% 1.5%
0.4%
(b) North-Northeast
77% South-Southeast
57%
50% 48%
47%
28%
10%
5%
requirement of obligatory autopsy even in tion may provide a more realistic estimate of
university hospitals, and a high frequency of the prevalence of NC since ocular globes,
domiciliary deaths. Since autopsy is difficult skeletal muscles and spinal cord with the
to perform in many areas, many cases of dis- nerve roots are analysed in addition to the
ease go unnoticed. There is a lack of uniform brain. Nevertheless, NC ranked 19 among
protocol for organ examination at autopsy pathological diagnoses at autopsy in a gen-
services. Furthermore, slices are usually eral hospital in the city of São Paulo15.
made at more than 1 cm at autopsy; and as a The frequency of detection of NC at
result, a small pathological lesion may escape autopsy in different series in Brazil from
detection leading to an underestimation of 1915 onwards is shown in Table 11.1. A range
disease frequency. Survey of necropsy at of frequency from 0.12% to 9.0%, giving an
Legal Medicine institutes and in the popula- average of 1.5% has been reported1–22,60.
Note: The data refer to frequency of neurocysticercosis and not to cysticercosis in general.
*Federal State of Brazil in which the study was conducted (see Fig. 11.2).
†Number of studied cases from which those with neurocysticercosis were selected.
‡Studies in general hospitals.
§Studies conducted on psychiatric patients.
Numbers reported depend primarily upon Autopsy data from Brazil also indicate
the autopsy protocol adopted, the repute of that NC is the primary cause of death in
the medical facility in treatment of disease 16–34% of those cases in which it was
and possibly on the geographical location detected1–22,60. The final cause of death was
within Brazil. For instance, high rates of found to be intracranial hypertension in
detection of NC have been noted in autopsy 47–69% of these cases18,20. Even in autopsies
series reported from Southeast Brazil performed in those who had neurological
(0.1–9.0%) in comparison with Northeast symptoms during life, NC may be an inci-
Brazil (0.30–0.45%). Dichotomy also exists in dental finding in about 26%18. While
the relative proportions of viable, asympto- parenchymal calcifications and viable cysts
matic and symptomatic cysticercosis. In a are the most common incidental findings,
large series from the state of Bahia in North autopsy could occasionally reveal asympto-
Brazil, 67% of examined parasites were matic intraventricular or cisternal cysticerco-
viable and there was a high proportion of sis. NC may also be diagnosed at autopsy in
asymptomatic NC11. The latter refers to those those patients who die as a result of other
autopsies in which the individuals had no infectious and parasitic diseases such as pul-
symptoms related to NC during life and monary tuberculosis, paracoccidiomycosis,
autopsy revealed incidental cysts. In com- Chagas’ disease and AIDS18,20. Co-infection
parison, data from our centre in Southeast probably reflects poor socio-economic and
Brazil revealed viable cysticerci in 26% of the health-related conditions that predispose to
autopsies18. both infections.
106 S. Agapejev
Note: The data refer to frequency of neurocysticercosis and not to cysticercosis in general.
*Federal State of Brazil in which the study was conducted (see Fig. 11.2).
†Number of studied cases from which those with neurocysticercosis were selected.
‡Studies in general hospitals.
§Studies limited to paediatric cases.
in the capital city and two outside the capi- quency of 2–6% in radiological investiga-
tal, NC was responsible for 0.1–0.2% and tions20,22,45,60. Several studies have addressed
0.3–2.5% of hospital admissions, respec- the frequency of diagnosis of NC among
tively60. In comparison, this disorder was patients referred to CT scan units38,41,43,48,52,61.
responsible for up to 13% of admissions to While these numbers give us an idea of the fre-
neurology and neurosurgery services. quency of NC in comparison to other neurolog-
Headaches and seizures are the most ical disorders, they cannot be extrapolated to
commonly reported symptoms; headaches establish prevalence of the disease in the com-
are more frequent in women, while seizures munity. In addition, the frequency may depend
are more common in men. Seizures occur upon whether the CT unit is that of a general
more frequently in series collected from out- hospital or a specialized neurological facility. In
patient departments in Brazil. most of such published series from Brazil, a
In available hospital-based reports of diagnosis of NC was made in 1–2% of the CT
series of patients with NC from Brazil, examinations38,41,43,48,52,61. More meaningful is
patients are mostly of rural origin (30–79%). the fact that the commonest CT abnormality in
However, urban origin becomes more fre- these reports has been either single or multiple
quent when more severe clinical presenta- parenchymal calcifications38,41,43,48,52,61.
tions of NC in children and adults are
considered60–62. Skin colour does not seem to
be a selection factor since its frequency was Compulsory Notification
proportional to the studied populations, with
no significant statistical difference18,46. In the The study of frequency and manifestations of
majority of published studies, the most NC seen in a single hospital does not reflect
affected age group is 11–60 years, with a fre- actual disease prevalence and patterns, since
quency of 22–67% between 21 and 40 years60. they are largely dependent on the pattern of
In general, there is a predominance of males referral to that hospital. Compulsory notifica-
(51–80%) in most series20,22,46,51,60,61. However, tion is a more accurate estimate of disease
severe manifestations are more commonly frequency and patterns45. Compulsory notifi-
reported among females47,48,50,60,63. cation in Ribeirão Preto, São Paulo, established
The period of hospitalization for patients a prevalence of 54/100,000 inhabitants45. While
with NC ranges from 1 to 254 days. Most compulsory notification is useful in estimating
patients require hospitalization for about a the prevalence of clinically overt NC, it would
week18,34. Nearly one half of the patients not be able to detect the large number of
require multiple admissions (up to nine, in asymptomatic cases known to exist.
Brazilian literature)18,34,35. The mortality rate in
several of the general hospital based series in
Brazil is low (approximately 0.3%). However, Community-based Serological
among patients with NC, the mortality rate is Studies
4.8–25.9%18,25,26,33,34,37. NC is responsible for
0.6–3.6% of hospital deaths due to neurologi- The seroepidemiology of human cysticerco-
cal disorders in Brazil. When studies from sis has not been systematically studied with
neurosurgical departments are evaluated, the the help of contemporary methods of evalua-
mortality may be as high as 60%64. tion. Some of the earlier studies have been
based upon indirect haemagglutination and
ELISA (reviewed in Table 11.3)52–59.
Epidemiological Data Inferred from
Imaging Facilities
Conclusions
While asymptomatic forms of NC (cases with
no neurological manifestations during life) are A plethora of clinical, hospital-based and
often diagnosed at autopsy, they can also be autopsy reports of human cysticercosis are
detected as an incidental finding with a fre- available from Brazil. These reports suggest
108 S. Agapejev
Note: The data refer to incidence of positive reactions for cysticercosis in serum.
* Federal State of Brazil in which the study was conducted (see Fig. 11.2).
†Number of studied cases from which those with cysticercosis were selected.
‡Biondi, G.F., Nunes, C.M., Cruz, J.M.C., et al., 1998 – unpublished observations.
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Introduction Indonesia
Taenia solium infections remain widely Geography, people, customs and food
prevalent throughout Asia, Africa and habits
South and Central America. A large num-
ber of community-based, epidemiological Indonesia comprises 17,000 islands, of which
surveys carried out in several Latin 6000 are inhabited2. The islands are situated
American countries, provide accurate infor- on the archipelago between the Indian and
mation on the burden of T. solium taeniasis Pacific Oceans, straddling the equator.
and cysticercosis in these countries (see Important islands include Java, Sumatra,
Chapters 8–10). In this regard, a series of Borneo, Bali and Irian Jaya (now called West
investigations in Peru stands apart in terms Papua Guinea). The last mentioned comprises
of their completeness and accuracy of por- the western half of New Guinea, the other
trayal of the status of disease there (see eastern half of which is a separate country,
Chapter 8). In contrast, precise epidemio- namely Papua New Guinea (formerly East
logical proportions of T. solium infection Irian Jaya) (Fig. 12.1). Indonesia has a landed
have not been defined adequately in most area of 1.8 million km2 and a population of 21
Asian countries. All we know is that the million. About 88% of the population is
disease does exist in several countries like Moslem, the remaining 12% consists of
Indonesia, China, India and Nepal. More Christians, Hindus and Buddhists2. Certain
accurate data are, however, lacking. islands have a majority of non-Moslem com-
Information regarding taeniasis–cysticerco- munities, for instance of Christians in Irian
sis is now available from Indonesia1. In the Jaya and Hindus in Bali. Some 80% of the
present review, several researchers review people live in the countryside.
available knowledge about the situation of Reliance upon traditional sanitary prac-
T. solium cysticercosis in their countries, tices and inadequate cooking of infested
with particular emphasis upon Indonesia, pork are principal reasons for the high
India, Korea, China and Japan. prevalence of T. solium taeniasis and cys-
Philippines
Pacific Ocean
Malaysia Irian Jaya
Australia
Wandra et al. reported 120 burn casualties Singapore is a developed country, it is ‘at-risk’
and new onset seizures in 293 individuals for T. solium cysticercosis, given the high vol-
among a community of 15,000 in Jayawijaya ume of travel to and from this country.
district in East Irian Jaya33. Histo-
pathological examination of subcutaneous
cysts removed from a number of affected Vietnam, Cambodia and Laos
individuals confirmed the diagnosis of cys-
ticercosis. Over the years, cross-border Studies in the post-Vietnam war period
migration between Indonesian Irian Jaya focused on morbidity patterns among war
and Papua New Guinea has given rise to veterans and refugees. Among various ill-
concerns about the disease getting estab- nesses, a high rate of helminthiasis was
lished in Papua New Guinea34. In fact, in described in war veterans and refugees by
1990, Fritzsche et al. detected a serologically several authors44–47. Several case reports
confirmed cases of cysticercosis among from medical facilities affirmed the occur-
Irianese refugees in Papua New Guinea35. rence of T. solium cysticercosis in good num-
More recently, however, a survey found 3% bers in Vietnam48–50. In 36 children
of the population of Papua New Guinea to convalescing from a flu-like illness in
be seropositive and among them, local Vietnam, 3% of the serum samples were
inhabitants were also positive18. positive for anticysticercus antibodies,
when tested in an ELISA in 1972–197324.
Contemporary data is now available;
Philippines Brandt et al. reported reported a seropositiv-
ity of 5.7% among inhabitants of North
The estimated prevalence of T. solium taenia- Vietnam51, while reliable estimates of
sis in Philippines is about 2%36. In one sur- seropositivity are around 8% in Hanoi and
vey of over 200,000 stool examinations in 10% in Cambodia and Laos (Carlo Urbani,
Manila and elsewhere within the country, the Hanoi, Vietnam, personal communication).
prevalence of T. solium infection was 0.02%37.
The estimated prevalence of porcine cysticer-
cosis is 0.16%38. A Medline search indicated Thailand
several reports of isolated cases and series of
NC originating from Philippines39,40. According to Vejjajiva, T. solium infestation
is uncommon in Thailand52. However,
reports of sporadic case and series have
Hong Kong and Singapore been made from several hospitals located
throughout Thailand53–57. These indicate
Published reports indicate the occurrence of that low levels of infection do exist in this
both indigenous and imported cases in Hong country. A recent report from a provincial
Kong, now part of China41,42. Local or indige- general hospital in Surin, in Northeast
nous cases result from consumption of pork Thailand, alluded to the frequent occurrence
imported from the Chinese mainland42. With of solitary cysticercus granulomas57. There, a
specific reference to exotic cases, Heap solitary cysticercus granuloma was identi-
reported that a diagnosis of cysticercosis was fied in 110 (11%) of 972 patients with a
quite common in Nepalese Gurkha recruits in seizure disorder over a 3-year period.
the Territorial Army43. The Gurkhas presum-
ably acquired infection while in Nepal. Coker-
Vann et al. surveyed three different ethnic Myanmar
communities using an anticysticercus ELISA
and determined an overall prevalence of 8%24. One of the earliest Asian reports of cys-
Rates were highest among individuals of ticercosis was made from Myanmar
Chinese origin (13%) in comparison to those of (Burma) (1912)58. However, a review of lit-
Indian (5%) or Malay (3%) origin24. While erature, including a Medline search did not
Uttar Pradesh
Bihar
Assam
Calcutta
Kerala
Fig. 12.2. Geographical representation of regions within India, from where Taenia solium taeniasis and
cysticercosis have been reported in considerable numbers.
facility in Banglore, South India, in the period tals77,78. Amatya and Kimula collected 62
when CT and magnetic resonance imaging cases of cysticercus skin mucosal and breast
(MRI) were not accessible, revealed a diagno- nodules out of a total of 23,402 biopsies over
sis of cerebral cysticercosis in 2%73. With the a 5-year period at the Patan Hospital in the
availability of CT and MRI, the proportion of capital city of Kathmandu77. Cases were
seizures due to cerebral cysticercosis rose. drawn from all over the country, though the
Thus Murthy and Ravi, from Hyderabad in majority were from the capital city itself.
South India, diagnosed cerebral cysticercosis Most patients were less than 30 years of age.
in 220 (8.7%) of an unselected group of 2537 Data from neurological facilities indicate
consecutive patients with seizure disorder74. that NC is the commonest cause of sympto-
Similarly, Sawhney et al. noted cerebral cys- matic seizures in Nepal79. Both solitary and
ticercosis in 49 (31%) of 158 patients among a multiple forms of cerebral cysticercosis are
series of 407 patients with seizure disorder in seen, though the former predominates.
whom a CT scan was done75. In both series,
solitary cerebral cysticercus granulomas pre-
dominated. Sri Lanka
Within the country, NC appears to be
more prevalent in the northern region According to Senanayake (Peradinya, Sri
including the states of Bihar, Uttar Pradesh Lanka, personal communication), NC,
through Punjab. Other states also have a fair including the solitary cysticercus granuloma,
proportion of disease with the possible which occurs very commonly in several
exception of Kerala, where low levels of dis- neighbouring countries, does not occur
ease reflect efficient sanitation, pig hus- locally in Sri Lanka.
bandry and a superior socio-economic and
educational status and in Kashmir with its
predominant Moslem population, where the China
consumption of pork is forbidden.
Experience with contemporary tools of China has an area of 9.5 million km2 and a
epidemiogical evaluation such as the population of 1.2 billion. The country is
enzyme-linked immunoelectrotransfer blot divided by the river Yangtze into two: the
(EITB) is limited76. An EITB-based sero-sur-
warm tropical south and the cold and dry
vey of household family contacts of children
north. About 70% of the population is rural.
with solitary cysticercus granulomas found
There is a substantial portion of the popula-
anticysticercus antibodies in 27% of the fam-
tion that is Buddhist, Taoist or Moslem,
ily contacts. These figures are high because
important because these communities do not
they are from a population that is at risk of
consume pork. China also has the largest pig
exposure, possibly due to consumption of
population in the world. The Food and
common food items and similar socio-eco-
nomic and sanitary conditions as with index Agricultural Organization estimated in 1997
cases with solitary cysticercus granuloma. that there were 4.6 billion pigs in China59.
Despite this, levels of pork consumption do
not approach those noted in the Western
Nepal Hemisphere. Nevertheless, the conditions do
exist in China that may perpetuate the
A systematic evaluation of the dimensions of pig–human–environment cycle. Surveys in
the problems related to T. solium cysticercosis Yunnan Province indicated that significant
has not been undertaken in this Himalyan numbers of the Pumi and Bai minorities ate
nation with an area of 140,000 km2 and a raw meat80,81. Surveys in rural portions of the
population of 24 million. The disorder has Shandong Province revealed that pigs were
been recognized as a major health hazard in rarely corralled, human defecation was indis-
the country only lately as is evident from criminate and awareness of the means to rec-
few recent reports from major referral hospi- ognize infected pork was lacking82,83.
Neurocysticercosis has been reported Neimeng and Shanxi), (iii) Northwest China
from hospitals all over China. Yingkun et al. (including Ganxu, Ningxia and Qinghai); (iv)
collected a series of 158 cases between 1956 a fourth zone comprising of Shandong,
and 1974 at a large hospital in Beijing84. Most Henan, Anhui and Hubei; and (v) finally, a
clinic-based data is however not published fifth zone comprising of Guangdong, Guangxi,
or is published in Chinese scientific litera- Hainan, Yunnan and Sichuan (Fig. 12.3).
ture, to which the rest of the world’s scien- Sporadic cases have also been reported from
tific community has poor access. the provinces of Jiangshu, Shanghai, Zhejiang,
Fujian, Taiwan, Guizhou, Xinjiang and Tibet.
Most epidemiological studies have
Intestinal taeniasis focused on the prevailing situation in
Shandong Province82,83,89. Here, 38 clinical
Adult T. solium infection is distributed broadly cases were detected among 35,512 patients
throughout China. Confirmed cases have been examined in 2000, giving a frequency of
noted in at least 28 provinces. Neimeng, 0.2%89. In this province, a seroprevalence
Henan, Shandong, Hebei and Anhui are con- (with a specific IgG4 antibody) of 2.2% was
sidered hyperendemic, while other provinces noted89. In another study using the indirect
like Guangxi, Guizhou, Yunnan, Sichuan and fluorescent antibody assay, a seroprevalence
Tibet have moderate prevalence of intestinal of 3.2% was found83. Seropositivity rates
infection85. The National Investigation of increased with age and were highest in per-
Human Parasitic Diseases estimated an aver- sons over 60 years of age. Other factors that
age prevalence of 0.112%; however, in certain were significantly associated with seroposi-
regions, local prevalence rates were as high as tivity were indiscriminate defecation, inabil-
0.66–6.0%86. The investigation estimated that ity to identify diseased pork and raising pigs.
there were approximately 1.26 million persons Outside the Shandong Province seropositiv-
with adult T. solium in the entire country. ity rates are reportedly low94: Haerbin city of
Several regional surveys have indicated vary- Helongjiang Province – 4.3%95; Liaoning
ing levels of infection in different provinces Province – 0.02%96; Henan Province –
within China. For instance, between 1975 and 0.1–1.2%97,98 and Sichuan – 0.8%97. Higher
1987, a coproparasitological evaluation of over seroprevalence rates have however been
34,000,000 individuals in Henan Province noted in the Pumi nation area of Yunnan
revealed T. solium taeniasis in 0.55%87. Province (11.2%)81 and Guangxi (9.5%)99.
Investigations in other regions have yielded
similar results: Shandong – 0.8%88; Jinan,
Taian and Laiwu City – 0.1%89; Yunnan – Korea
6.93%; Dali City (Louyi village of Eryuan
county) – 19.5%; Jilin (Yanji City) – 0.11%; Intestinal taeniasis
Liaoning (Shengyang and Dalian cities) –
0.005%80; Sichuan (Xide county) – 4.0%90 and During the past three decades, Taenia infec-
Fujian (Xianyou county) – 0.13%91. tion has decreased steadily in Korea. In a
series of national surveys for intestinal
helminth infections, undertaken every 5
Human cysticercosis years, the egg positive rates of Taenia species
were 1.9% in 1971, 0.7% in 1976, 1.1% in
The earliest report of confirmed human cys- 1981, 0.3% in 1986, 0.06% in 1992 and 0.002%
ticercosis from China was made in 193092. The in 1997, respectively, when one random
National Investigation of Human Parasitic sample of 1000 people was examined by
Diseases revealed that T. solium cysticercosis stool microscopy100. In interpreting these
was reported from 671 counties in 29 data, low sensitivity of stool microscopy for
provinces within China93. Five zones of high detecting Taenia infection should be consid-
endemicity have been described: (i) Northeast ered. However, the decreasing trend has well
provinces; (ii) North China (including Hebei, been depicted in the consecutive surveys.
Miles
600
300
0
300
By examining morphology of Taenia ally before the 1990s. The egg positive rate
expelled after chemotherapy, the proportion has always been the highest in Cheju
of T. solium was found in the wide range of Province, although the infections were
4.1–36.7%101 among the Taenia egg passers. found throughout the country (Fig. 12.4).
As of 1997, the least number of infected peo- Except for a few academic surveys, mass
ple with two species of Taenia was about chemotherapeutic control has not been
9000, which were mostly aged people older undertaken in Korea against intestinal Taenia
than 60 years, living in rural Korea. From infections. Instead, taeniafuges such as
them, nationwide number of T. solium infec- bithionol (marketed since 1964), niclosamide
tion could be estimated as being in the range (since 1976) and praziquantel (since 1981)
of 400–3200 out of 46 million people in were allowed to be available to the public,
Korea. The present intestinal infections are and infected individuals can purchase the
regarded as persisting ones contracted actu- drug without prescription.
Pyongyang
Seoul
Not surveyed
< 2.5%
2.5–4.9% Pusan
5.0–7.4%
> 7.5%
Cheju
Fig. 12.4. Geographic map of Korea depicting major geographical foci of Taenia solium taeniasis and cysticercosis.
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an important loss of productivity. This forms sis is limited. The clinical presentation of neu-
a vicious cycle that is very difficult to break. rocysticercosis (NC) is extremely variable and
In most rural areas, meat inspection is the diagnosis is easy to miss. It is interesting
improper or absent. Even in localities where that diagnosis of the first case of NC in a
slaughterhouses exist, illegal channels of meat country often follows the completion of train-
marketing exist. Moreover, slaughterhouses ing of the first neurologist in that country.
do not exist in villages and people butcher The first autopsy report of human cys-
their own animals, offering the meat for sale. ticercosis in Africa was made from
Free-ranging pigs with access to human fae- Madagascar in 1910 by Andrianjafy3.
ces abound. Too many inhabitants in remote Bettencourt in 1911, reported cysticerci in an
areas of the continent ignore the danger of Angolan individual who died of trypanoso-
eating meat infected with cysticerci. Different miasis. In 1938, Gallais reported NC in an
gastronomic customs and beliefs concerning epileptic individual from Benin4.
meat consumption also play an important Review of international literature indicates
role in transmission of T. solium cysticercosis. that T. solium cysticercosis has been reported
In a few ethnic groups, pork infested with from many African countries. Cases have been
cysticercosis is believed to have a better taste reported from Senegal5–7, Benin8, Ivory
than healthy meat. Raw or insufficiently Coast9–11, Togo12, Ghana13, Burkina Faso1 and
cooked pork meat is consumed to ensure Nigeria14 in West Africa, Democratic Republic
virility in certain other communities. In some of Congo (ex-Zaire)15–17, Cameroon18, Burundi19,
tribes of South Africa, tapeworm proglot- Kenya20, Rwanda21–23, Tanzania1 and Uganda1
tides are a component of the ‘muti’ adminis- in Central and East Africa, and Zimbabwe24–26,
tered by native herbalists to expel intestinal South Africa27–35 and Madagascar36 in southern
worms2. Africa.
In Africa, maybe more than anywhere Human cysticercosis was found in 7% of
else, environment and disease are closely 300 autopsies carried out at Butare,
related. As with other communicable dis- Rwanda23. Gelfand reported cysticercosis in
eases, the geographic, demographic and cul- 0.45% of 2148 autopsies conducted in
tural characteristics of the region influence Zimbabwe24. Proctor, identified 71 cases of
the epidemiology of cysticercosis. For taeniasis in an autopsy survey of 7597 cases,
instance, T. solium egg survival in the exter- most of them also had cysticercosis25.
nal environment is influenced by tempera- In Togo, 38 (1.45%) of 2604 consecutive
ture and humidity. The tropical climate of patients presenting for neurological consulta-
Africa favours egg survival. In addition, ova tion to the outpatient department of a teaching
can be transported over many kilometres by hospital, were found to have cysticercosis12.
streams and rivers, and mechanically over Mason et al. observed that 12% of 630 hospital-
long distances by birds. Some insects may ized patients were seropositive for anticys-
also transmit the disease. The use of irriga- ticercus antibodies with an ELISA26. Sacks and
tion water contaminated by animal wastes Berkowitz noted a seropositivity rate of 7.4%
contributes to transmission of cysticercosis. among hospitalized adult patients in
Finally, a high rate of transmission is noted Johannesburg with an ELISA test35. In
in specific familial environments. Madagascar, Michel et al., using ELISA and
enzyme-linked immunoelectrotransfer blot
(EITB) reported a seroprevalence rate of 36%
Human Cysticercosis among 1132 neurologic patients36.
Powell et al. noted seizures in 58% of 48 Several studies from South and Central
patients with proven cysticercosis from America indicate that NC is the most com-
Zimbabwe37. In Madagascar, seizures were mon cause of adult-onset seizures40–42.
the presenting symptom in 57% of 241 Studies from Africa have produced conflict-
patients with NC38. A total of 33 (87%) of 38 ing viewpoints on the association between
patients with NC presented with seizures in NC and seizures (Tables 13.1 and
Togo12. Shasha et al. analysed 141 cases of 13.2)2,12,34,37,43–50. Dumas et al. demonstrated
cysticercosis from South Africa and reported evidence of cysticercosis in 26 of 88 individ-
seizures with or without other neurological uals with seizure disorder identified during
syndromes in 95 (67.4%) of them39. In a pae- a population-based survey in Togo48. The
diatric cohort of 61 cases of cerebral cysticer- diagnosis of cysticercosis was based upon
cosis from South Africa, seizures were presence of one of the following findings:
recorded in 43%30. positive serology by ELISA; presence of
Table 13.2. Seroprevalence of cysticercosis in case–control and transversal studies in sub-Saharan Africa.
established a prevalence of taeniasis (both T. Besides, cysticercosis has also been recog-
solium and T. saginata) of 0.16% in 1992, nized in West Africa and southern Africa.
0.25% in 1993 and 0.25% in 1994 among Studies from Benin and Togo have succeeded
school children in Rumonge, Burundi44. The in increasing the awareness of local political,
highest reported prevalence was reported administrative and public health authorities
from South Africa, where a survey found concerning cysticercosis and NC. In Benin,
10% prevalence of adult Taenia infection. information on sanitation has been dissemi-
nated through a published handbook. More
work of this nature on a collaborative basis
Conclusions involving countries within Africa and
beyond are clearly required to assess and
While human and porcine cysticercosis have contain the situation in Africa.
been recognized as major health and eco-
nomic problems in Latin America and also in
few developed countries, their impact upon Acknowledgements
health and economy in Africa has not been
adequately appreciated. Preliminary epi- We would like to thank the Conseil Régional
demiological data indicate that sub-Saharan du Limousin for their financial help and Dr
Africa may be a major focus of disease. Bernard Bouteille for technical assistance.
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Another American series of cysticercosis revealed 447 cases diagnosed with NC11. The
cases diagnosed in the USA involved two number of cases, however, only began to
intraventricular cases and one parenchymal increase during the last few years of the
case6. The three patients were from Portugal, 1970s. There was a fourfold increase in the
Guatemala (the intraventricular cases) and number of cases diagnosed between l977 and
Angola (the parenchymal case). Subsequent l981, which was far greater than the increase
articles broadened the clinical spectrum of in the number of immigrants. The major fac-
disease, and showed that surgical interven- tor associated with the increased number of
tion improved the outcome of selected cases was the introduction and widespread
cases7–9. Thus, the number of cases described utilization of CT scans. This technology so
before the 1970s was limited, perhaps due to enhanced the clinician’s ability to identify
limitations of diagnostic tests. In addition, the and define the nature of intracerebral lesions
spectrum of disease was skewed towards that its introduction overshadowed any other
cases that were obvious (e.g. patients with factors. The vast majority of the patients
parasites visible in the eye) or more severe reported during this period were Hispanic.
(e.g. intraventricular disease). Most were presumably from Mexico. Even in
this early report, however, 12 of the cases
(3%) had no history of travel to disease-
T. solium Infections: 1970 Onwards endemic areas outside of the USA11. Thus, their
infections were presumably acquired locally.
The spurt in T. solium cases in the 1970s As the number of immigrants increased
and the geographic range of Hispanic immi-
In the late 1970s, computed tomography (CT) gration broadened, so did the extent of NC.
scanning became widely available in the USA. By the 1990s, we estimated that 1000 NC cases
The result was that parasites in the central ner- were diagnosed in the USA each year12. With
vous system could be identified without inva- the continued increase in immigration from,
sive testing. At about the same time, the and travel to endemic areas, the number of
number of immigrants from endemic areas cases is probably higher now. In support of
began to increase. Between 1960 and the 1990s, this is the continuing increase in the number
the proportion of the US population born in of cases in Los Angeles13. While cases were
foreign countries doubled. Furthermore, there initially noted in southern California, large
was a shift in the country of origin for US cases series have subsequently been reported
immigrants. Prior to the 1970s, most immi- from Colorado, Texas, Chicago and New
grants to the USA were of Canadian or York12,14–17. Interestingly, these case series are
European origin. Changes in immigration pol- reported from cities with large immigrant
icy led to the influx of large numbers of immi- populations, especially those from Mexico
grants from Latin America and Asia. The and Central America. However, up to 42% of
recently completed 2000 US Census recorded the patients were persons born in the
35.3 million persons of Hispanic origin living USA15,16. Reported sources of possible expo-
in the USA, representing an increase of 12.9 sure in these persons included travel to
million in the past decade10. US immigrants of Mexico or Central America (50%) or visitors
Mexican origin now number over 20 million. in the home from Latin America (20%).
There was also increased travel to endemic To document the extent of disease, an
areas with an estimated 200 million persons ongoing multi-state surveillance project of 11
crossing the US–Mexico border every year. university-affiliated hospital emergency
Increased immigration plus widespread departments was begun in the late 1990s18.
availability of non-invasive neuroimaging NC was documented as the apparent cause
tests resulted in a dramatic increase in recog- of approximately 2% of cases of seizures.
nition of NC. This was initially noted in Most cases were seen in the southwestern
California. For example, review of hospital states. Patients with no travel history and in
records from four large medical centres in whom infections may have been locally
Los Angeles for the period 1973–1983 acquired represented 8% of identified cases.
Risk factors for T. solium infection in USA may have been due to ascertainment bias,
with only more severe or obvious cases
To further characterize the epidemiology of being diagnosed.
NC, we interviewed NC cases diagnosed in
Houston19. Of 35 immigrants questioned,
83% were from families that raised pigs, 43% Locally acquired infections
had a history of taeniasis, and 54% had a
family history of taeniasis. The median Locally acquired infections have also occa-
period from immigration to diagnosis was 28 sionally been noted. Pigs sold and consumed
months for the 13 patients who had not left in the USA however, are infrequently infected
the USA after immigration. Thus, NC cases with cysticercosis and among over 80 million
were concentrated in immigrants from vil- swine slaughtered annually, fewer than 10
lages in known endemic regions. Travel pigs show evidence of infection1. Thus, local
between the endemic villages and cities in acquisition of T. solium adult tapeworms (tae-
the USA was surprisingly frequent19,20. niasis) is unlikely to be a significant problem.
In the late 1980s, NC was made a By contrast, local acquisition of NC has been
reportable disease in southern California. noted. Twelve US-born patients with NC
Surveillance was started in 1988 and within 3 who had not left the USA were identified in
years the county health system in Los the hospital-based survey from Los
Angeles was notified of 138 cases21. The Angeles21. Similarly, locally acquired cases
number of cases was significantly fewer than were also identified in patients from
would be predicted from hospital surveys, Massachusetts and North Carolina24. A small
suggesting significant underreporting. As series of patients with no travel outside of the
might be expected the case rates were over USA was also reported from Chicago16.
2.5 times higher in the Hispanic than in the Direct or circumstantial evidence commonly
non-Hispanic communities. In addition, links these cases to direct or indirect exposure
many of the non-Hispanic patients were to immigrants from Latin America, who pre-
Asian immigrants. sumably are (or were previously) carriers of
With the increase in numbers of cases, adult-stage T. solium. This was most dramati-
there was also a shift in the spectrum of dis- cally shown in a cluster of cases in four unre-
ease. Most cases diagnosed after the wide- lated families of an Orthodox Jewish
spread use of neuroimaging studies were community in New York City25. The clue to
due to parenchymal cysticerci. Previously, it the epidemiological puzzle in these cases was
was widely assumed that NC carried a grave the employment of ‘live-in’ housekeepers in
prognosis and that patients would do poorly all of the exposed households. These female
unless treated with anticysticercal drugs. employees had recently emigrated from Latin
Based on uncontrolled studies, praziquantel American countries where T. solium is
and subsequently albendazole became endemic and were considered the most likely
widely used. During the early 1980s, neither sources of infection for the infected members
of these drugs was widely available in the of these households. Examination of six
USA. Several investigators in California fol- housekeepers currently or previously
lowed the natural history of patients treated employed in the four case households
with only symptomatic therapy22,23. US revealed an active Taenia sp. infection in one
investigators reported that most patients and a positive serological test result in
with NC presented with seizures and usually another. Employment of immigrants as
a single enhancing lesion on CT scans. These domestic workers was very common in this
patients did very well with only sympto- community; a random telephone survey
matic therapy. By contrast, ocular, ventricu- determined that 94% of the approximately
lar and meningeal disease (which comprised 7000 households in the community employed
most of the reported cases before the CT era) housekeepers, almost all of whom had
were only a small minority of cases. Thus, recently emigrated from rural areas of
the poor prognosis reported in older series Mexico or countries of Central America.
Each household employed an average of (4.4%), but none in those from Haiti or
three such women per year. Mexico27. Thus, widespread employment of
To further evaluate the extent of this domestic workers from disease-endemic
problem, a serosurvey was conducted in the regions and high employee turnover may
same community which sought to identify contribute to exposure risk. It is unclear,
exposures and practices associated with however, whether local transmission is in
acquisition of infection. Anticysticercus anti- fact rare or merely under-recognized. In
bodies were detected by enyme-linked Los Angeles, Sorvillo et al. attempted to
immunoelectrotransfer blot (EITB) in 23 identify tapeworms among contacts of NC
(1.3%) of 1789 persons from 612 families26. patients21. They identified carriers in 1.1%
All 23 seropositive persons were asympto- of the household contacts of their patients.
matic, and no intracerebral lesions were Among the subgroup of NC patients that
found in the 21 seropositive persons who were not from and had not travelled to
underwent brain imaging. Seropositivity endemic areas, 22% had tapeworm carriers
was significantly associated (P 0.05) with among household contacts.
female sex, employment of domestic work-
ers for child care duties, and with employ-
ment of persons from Central America. This Conclusions
cluster of patients within a community in
New York that never ate pork and enjoyed Overall, NC is a growing public health prob-
modern hygienic facilities underscored the lem in the USA. Initial recognition resulted
importance of faecal–oral hygiene in the from improved imaging studies and has
transmission cycle. The prevalence of these included more cases of mild disease (e.g. sin-
risk factors among the US population in gen- gle parenchymal cysticerci) than in most
eral is unknown. series from developing countries. NC in the
The prevalence of taeniasis among USA is primarily a disease of immigrants
immigrant employees in surveyed house- infected abroad. Thus, as immigration and
holds is unknown and may be difficult to travel from Latin America and Asia increase,
determine. Most employees live in the so the number of cases. In addition, small
households; many are undocumented numbers of cases of locally acquired infec-
aliens; access to the population is limited, tions are recognized. While the number of
and confidentiality of test results is difficult such cases is small, the risk factors associated
to ensure. A stool examination survey of with locally acquired infection need better
migrant workers in North Carolina found definition and the magnitude of this problem
taeniasis in Central American workers requires further study.
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9. Carmalt, J.E., Theis, J., Goldstein, E. (1975) Spinal cysticercosis. Western Journal of Medicine 123,
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of American Medical Association 254, 3444–3448.
12. Shandera, W.X., White, A.C. Jr, Chen, J., et al. (1994) Cysticercosis in Houston, Texas: a report of 112
cases. Medicine 73, 37–52.
13. Zee, C.S., Go, J.L., Kim, P.E., et al. (2000) Imaging of neurocysticercosis. Neuroimaging Clinics of North
America 10, 391–407.
14. Earnest, M.P., Reller, L.B., Filley, C.M., et al. (1987) Neurocysticercosis in the United States: 35 cases
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Clinical Infectious Diseases 23, 262–268.
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cases. Pediatrics 98, 974–977.
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Houston, Texas. International Conference on Emerging Infectious Diseases, Atlanta, Georgia (abstract).
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in four, rural, Guatemalan communities. Annals of Tropical Medicine and Parasitology 90, 157–165.
21. Sorvillo, F.J., Waterman, S.H., Richards, F.O., et al. (1992) Cysticercosis surveillance: locally acquired
and travel-related infection and detection of intestinal tapeworm carriers in Los Angeles. American
Journal of Tropical Medicine and Hygiene 47, 365–371.
22. Mitchell, W.G., Crawford, T.O. (1988) Intraparenchymal cerebral cysticercosis in children: diagnosis
and treatment. Pediatrics 82, 76–82.
23. Kramer, L.D., Locke, G.E., Byrd, S.E. (1989) Cerebral cysticercosis: documentation of natural history
with CT. Radiology 171, 459–462.
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Carolina, Massachusetts, and South Carolina, 1989–1991. Morbidity and Mortality Weekly Report 41,
1–4.
25. Schantz, P.M., Moore, A.C., Muñoz, J.L., et al. (1992) Neurocysticercosis in an Orthodox Jewish com-
munity in New York City. New England Journal of Medicine 327, 692–695.
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Jewish community. American Journal of Tropical Medicine and Hygiene 53, 439–442.
27. Ciesielski, S.D., Seed, J.R., Ortiz, J.C., et al. (1992) Intestinal parasites among North Carolina migrant
farmworkers. American Journal of Public Health 82, 1258–1262.
15 Porcine Cysticercosis
serological results are obtained and subse- others, suggesting that maternally trans-
quent necropsy results are negative. D’Souza ferred antibodies may confound results
and Hafeez described that 33.33% of free- obtained by using serological methods15,16.
ranging pigs, in which parasites could not be Subsequently, it was demonstrated that pas-
detected at meat inspection, were positive sive humoral immunity persists in piglets
using ELISA11. This problem affects any anti- born to seropositive sows up to 35 weeks
body-based diagnostic test, including the postpartum4. Infection-specific antibody pat-
highly sensitive and specific EITB assay. terns in the piglets are indistinguishable from
Sciutto et al. reported that antigen and anti- maternally transferred antibody reactions. In
body detection assays showed lower sensi- contrast, new reaction bands produced by the
tivity and specificity when used in pigs that piglet alone most certainly represent a new
were reared in rural environments versus antigenic stimulus, and therefore are pre-
those raised on commercial farms12. These sumed to be the result of new infection14.
data demonstrate that it is not uncommon to Although the presence of antibodies in
detect specific antibody responses in pigs necropsy-negative pigs may, in some ways,
from endemic areas, especially if pigs are limit the use of EITB, the number of bands in
free ranging. A positive serological result in the infected animals suggests that diagnostic
the face of a negative necropsy could occur patterns do not happen at random and that
from either prior effective treatment, past these results may be related to the final infec-
infection that has cleared, or exposure to T. tion outcome (A.E. Gonzalez, unpublished
solium, among other explanations. data).
In the past, when investigators used the A study was designed to answer some of
EITB to diagnose porcine cysticercosis, the these questions to enable a better understand-
problem of passively transferred maternal ing of the EITB results. A total of 482 pigs were
antibodies was recognized as a potential sampled from an endemic area in Huancayo,
source of bias13. The presence of passive anti- in the Peruvian Central Highlands. A total of
bodies hampers the use of cohort studies for 279 pigs were found to be EITB positive. The
porcine cysticercosis because in highly prevalence of seropositive pigs in the area was
endemic villages most piglets must be therefore calculated to be 53.59–62.41%
excluded due to the presence of maternal (95%CI). A subset of 84 from the 279 EITB-posi-
antibodies, which cannot be differentiated tive pigs were bought and necropsied. The
from acquired antibodies. Investigators number of EITB bands and necropsy results
addressed this issue by sampling only pigs were registered by age and have been tabu-
that were older than 3 months. Later, the lated (Table 15.1). The information (Table 15.1)
presence of maternal anticysticercal antibod- was used to develop a stochastic model in a
ies was noted in sentinel pigs that were older spreadsheet (Excel 2000) format using simula-
than 3 months14. Seropositive results that did tion software @risk (Palisade). The probability
not correlate with age were also reported by function of having a necropsy-positive result
Age
Number of 8 months 8 months
EITB bands
diagnosed Positive Negative Positive Negative
1–2 7 13 3 15
3 5 7 20 7
4+ 2 1 3 1
Total 14 21 26 23
given a band and age combination was simu- to another, the minimum number of living
lated using distributions. The original 279 cysticerci that could be detected was 88.
positive pigs were also organized by age and Animals harbouring only dead cysticerci
number of bands (Table 15.2). The confidence gave negative reactions and cross-reactions
limits for the number of expected positive pigs were observed with sera infected by other
for each group were simulated using binomial taeniids. The test was also able to detect cir-
distributions that considered the number of culating antigen in sheep and pigs, infected
positive pigs observed in each group and the with T. ovis and T. solium respectively, and in
probability previously calculated. The distri- serum samples of confirmed cases of human
butions above described were then used to cysticercosis18. Another MAb, the HP10, gen-
simulate the number of necropsy-positive pigs erated against a repetitive epitope present on
in each stratum in 500 interactions. The simu- the surface and in excretory–secretory anti-
lation results showed that the mean preva- gens of T. saginata cysticerci was selected for
lence of EITB seropositivity was 28% (90%CI: its ability to detect circulating antigen in a
22–33%) (Fig. 15.1). double antibody sandwich ELISA19. The
Antigen detection assays (reviewed in assay was evaluated in a randomized study
Chapter 34) have also been evaluated in pigs. using control, positive, negative and heterol-
Monoclonal antibodies (MAbs) produced ogous infection sera (A.E. Gonzalez, unpub-
against T. saginata excretory–secretory prod- lished data). Sensitivity and specificity
ucts were unable to detect lightly infected values were calculated using sera (that
animals17. Brandt et al. developed an assay served as control) from 40 necropsy-positive
using two MAbs that recognized antigenic pigs with varying infection burdens and 40
components of T. saginata18. Although the necropsy-negative pigs from non-endemic
sensitivity of the test varied from one animal areas. Cross-reactions were evaluated using
sera from pigs infected with Cysticercus
tenuicollis, hydatid cysts and liver flukes.
Sensitivity was 83% (95%CI: 71–94%) with a
Table 15.2. Frequency of positive pigs by age.
specificity of 88% (95%CI: 77–98%). After
Bands 8 months 8 months grouping positive sera according to infection
burden, it was found that 10 of 15 (67%) sera
1–2 78 47
from mild infections, 10 of 12 from moderate
3 39 75
4+ 15 25
infections (83%) and 13 of 13 from heavy
infections gave positive results. Also, 24 of 27
16
Mean = 0.2790083
Distribution for prevalence/H27
14
12
10
0
0.18 0.23 0.28 0.33 0.38
5% 90% 5%
0.23 0.33
Fig. 15.1. Simulated prevalence of Taenia solium cysticercosis in swine.
The feasibility of using sentinel pigs as a willing either to pay for the service, or
surveillance tool in intervention pro- expose their animals to the risk of confisca-
grammes, as well as an alternative to experi- tion2. Evaluation of environmental contami-
mental infection, was further assessed in two nation by direct detection of T. solium eggs in
trials32. In the first, 51 sentinel pigs were the soil has proved inefficient every time it
exposed to T. solium eggs from February to has been tried. Taenia sp. eggs are rarely
April 1996 (Casacancha) and April to June found in soil or water, or even in sewage-irri-
1996 (Rangra). In the second trial, a total of gated vegetables13,29,30. Tongue examination
38 sentinel pigs were relocated and exposed of pigs will only detect a subset of heavily
in Casacancha during April to June 1997. infected animals, and miss out on infections
Basically, the sentinel pig model consists of outside the tongue3. More importantly,
relocating a group of susceptible pigs from a tongue examination is familiar to villagers,
cysticercosis-free area into an endemic and the decision to bring their pigs for
region. After 3 months of exposure, pigs are inspection may be biased towards bringing
transported to a cysticercosis free area, kept only healthy pigs if they have fear of confis-
for an additional 3-month period to allow for cation, or only those pigs more at risk if they
cysts to achieve full growth, and then killed. feel they can use the service to ‘screen’ their
The infection status is determined by sero- animals2. Serological determination of
logical examination and detailed necropsy32. porcine prevalence is somewhat similar to
The experiments were successful in the sentinel pig model, but has the disadvan-
Casacancha, where over two-thirds of sen- tage of dealing with a population with a fast
tinel pigs were recovered at both opportuni- turn-over and long-lived passive anticys-
ties, but not in Rangra, where only one-third ticercal antibodies4.
of animals were recovered. The low recovery
percentage in Rangra prompted the cancella-
tion of this village in the second experiment. Socio-economic aspects
The overall attack rate for the first trial was
50% (12/24). Ten out of the 12 EITB-positive Economic losses resulting from food-borne
pigs had cysts or cyst scars at necropsy. parasitic zoonoses are difficult to assess.
Apparently, the infection rate was higher in Estimation of the global economic impact of
Rangra (7 of 10) than in Casacancha (5 of 14) these diseases is handicapped by inadequate
in the first trial, but the numbers involved information on the prevalence and public
were small and hence not statistically signifi- health importance of parasitic zoonoses for
cant. The overall attack rate in the second most countries. However, the economic
trial was 55% (16 of 29). Again, almost all the losses due to porcine cysticercosis have been
EITB-positive pigs yielded necropsy-positive estimated for some countries; in these
results (15 of 16). The application of the sen- instances the costs are significant33. In
tinel pig model demonstrated a high level of Mexico, for example, porcine cysticercosis is
environmental contamination in the study responsible for a loss of more than one-half
area in both trials. Currently used monitor- of the national investment in swine produc-
ing tools (slaughterhouse inspection, search tion whereas for all Latin America, porcine
for Taenia eggs in the environment, estima- cysticercosis accounts for an economic loss
tion of porcine cysticercosis by tongue exam- of US$164 million34. Besides, T. solium not
ination or serology, estimation of the only causes severe economic losses to the
prevalence of human taeniasis by stool pig industry but also causes a severe
examination, of human neurocysticercosis zoonotic disease35.
(NC) by clinical screening, or of human cys- Peasants practise pig rearing for short-
ticercosis by serology) would not have per- term savings. Furthermore, they optimize
mitted this demonstration. In Peru, as in the profit of rearing pigs by keeping invest-
other developing countries, pigs do not ment to a minimum. This attitude towards
always go through slaughterhouse inspec- pig rearing explains why pigs range freely to
tion. Even if available, villagers would not be obtain a variety of foods, including human
faeces36. The driving force behind peasants’ and consequent risk assessment in other
practices and attitudes to T. solium is the eco- tropical disorders such as malaria, onchocer-
nomic benefit in the short- and mid-term ciasis and schistosomiasis40–42. Global posi-
periods. People will require an economic tioning satellite technology was used to
incentive for changing their pig-rearing prac- determine the exact position of every house-
tices. Control strategies that fail to recognize hold in a village with sub-metre accuracy40.
the economic significance of pig keeping are After processing, global positioning satellite
unlikely to be successful in controlling T. files were directly exported to a GIS data-
solium. An interesting observation in a rural base for analysis, showing that clusters of
community in coastal Peru illustrates this incident cases are related to tapeworm carri-
point36. Factors responsible for the reduction ers (Fig. 15.2). Although T. solium cysticerco-
in the prevalence of porcine cysticercosis in sis clusters have been previously
this community over a 2-year period were demonstrated using prevalence data, the
studied. The decrease was found to be linked clusters were not as clearly defined as when
to the practice of corralling or tethering of incident cases were studied using the GIS
pigs, which was enforced to protect the technique. Furthermore, the map made evi-
recently introduced rice crop from being dent that not all tapeworms contaminate the
ruined by free-ranging pigs (see Chapter 8). environment. It became clear that careful
Rice cropping was not only more profitable, observation of infection within longitudinal
but also provided by-products to feed the studies provided the most useful informa-
corralled pigs. Therefore, the community tion on transmission dynamics.
agreed to corral their animals. Porcine cys-
ticercosis then decreased because tethering
and corralling indirectly prevented the ani- The marketing of cysticercotic pigs in the
mals from accessing human faeces. Sierra of Peru
Incident pigs
one
two
Taenia
one
two
House
Road
River
Main square
Other buildings
Ruins
Llacta
100 0 100 200 300 400 500 600 700 800 900
Fig. 15.2. GIS map of a village endemic for Taenia solium cysticercosis depicting location of tapeworms
and incident pigs.
quality and inspected for cysticercosis. No Infected pigs were often bought by buyers
restrictions were placed on the sale of the because of their low price. Buyers men-
meat, based on where or how the carcass tioned that they also examined the pigs’
was obtained. Infected meat was not sold in tongues for scars; sellers would apparently
the official market. At four visits to the mar- excise cysts from the tongue in order to
ket for the purpose of direct observation, increase the market value of the pigs. Based
220 pig carcasses were inspected and only on findings of the tongue examinations per-
two were found to be infected. These car- formed by buyers, approximately 15% of the
casses were then returned to their owner. pigs sold in the live market were considered
Observations were then carried out at two to be infected.
local live pig markets in the area surround- A total of 52 pigs were inspected at six
ing Huancayo. Official pig inspections were informal slaughterhouses. Examination of the
never observed in over ten separate visits to heads and carcasses of these pigs indicated
each fair. Instead, tongue examinations were that seven (14%) had cysticercotic cysts in the
routinely performed by local peasants in an muscles or brain. Interviews with the infor-
attempt to establish the value of the pigs. mal butcher revealed that infected meat was
sold either to another city or for use in fried A novel method for infecting pigs with T.
pork (chicharrones). Infected meat was sold solium using an intramuscular inoculum of
only to selected individuals known to the oncospheres was investigated in a series of
seller. Two processed meat sellers were inter- five experiments in 18 animals49. The first
viewed, both admitted to selling infected experiment evaluated three routes of infec-
meat; small quantities of infected meat were tion: intraperitoneal (IP; n=4), intravenous
mixed with non-infected meat, and the mix- (IV; n=2) and intraduodenal infection (n=1)
ture was then roasted or fried in fat. with either 6000 or 15,000 oncospheres.
Successful infections were obtained follow-
ing IP and IV inoculation. All cysts in IP
Intramuscular Oncosphere Assay inoculated pigs were viable, whilst cysts
(IMOA): a Novel Experimental were either viable or degenerated in IV inoc-
Infection Model to Evaluate ulated pigs. After one IP inoculation, a well-
Chemotherapeutic Agents defined cluster of 35 cysts was found in the
abdominal muscle. It became apparent that
Previously, experimental models for taeniid the injection of oncospheres was accidentally
tapeworms have employed oral challenge of made into the muscle rather than into the
hosts, other than the natural intermediate peritoneal cavity. The results prompted four
hosts (e.g. sheep for T. saginata, SCID mice for consecutive experiments devoted to stan-
Asian Taenia and T. solium, and rodents for T. dardize inoculation site, time to necropsy,
solium) (reviewed in Chapter 4)43–46. Methods and inoculation dose via the intramuscular
other than oral egg challenge, for instance, route and to evaluate the feasibility of oncos-
intramuscular injection of T. saginata oncos- phere activation in the intramuscular model.
pheres and subcutaneous T. solium and Asian Histopathologically, the cysts that developed
Taenia oncosphere injection in SCID mice in the IMOA were no different from those
have also been tried. Currently, the evalua- seen with natural infection.
tion of porcine cysticercosis model vaccines is The IMOA model is simple to perform,
requires a minimal number of oncospheres,
limited to pigs infected through the oral route
permits multiple infections per animal, and
because no other experimental model exists.
decreases the variability in the numbers of
However, infecting pigs with eggs or proglot-
cysts recovered, inherent to oral infection
tides requires very large numbers of infective
models. The direct injection technique is sim-
eggs and results in unpredictable numbers of
ple and reproducible. It produces relatively
cysts. No more than 21 cysts were found in
constant levels of infection with the same
any of the pigs when infected with three
inoculum in different pigs. Also the number
gravid proglottides in one experiment47. In
of cysts produced is relatively large so that
another Mexican study, oral challenge with
differential effects can be easily observed. In
105 eggs eventually produced from four to
contrast, an intestinal model permits only
212 cysts per pig48. The poor yield may be one inoculum per test pig and produces
due to variations in intestinal transit times, marked variation in the number of animals
which might affect the dissolution of the infected and in cyst numbers. Thus, the
eggshell. Furthermore, obtaining T. solium IMOA may be a valuable tool to evaluate
with gravid proglottides is not easy since therapeutic agents or potential vaccines for
standard therapy with niclosamide or prazi- porcine cysticercosis.
quantel often destroys the proglottid. In addi- Immunity to T. solium was investigated
tion, each experiment requires the use of using the IMOA model in a series of experi-
25,000–100,000 eggs to obtain reasonable ments (M. Verastegui, A.E. Gonzalez, R.H.
infection. The large number of eggs required Gilman et al., unpublished observations).
for each animal restricts studies to a small Three naturally infected pigs were treated
number of animals. These limitations of the with oxfendazole and then inoculated with
oral model have prevented its widespread oncospheres using the intramuscular route
use in vaccine and therapeutic trials. 3 months after treatment. None of the
treated pigs developed cysts after intramus- cysticercosis in pigs: tongue inspection and
cular inoculation, while the three unin- palpation, meat inspection in abattoirs and
fected, untreated, control pigs developed serum EITB. The last of these has been found
intramuscular cysts following inoculation, to be most sensitive, specific, safe and eco-
confirming that successful treatment with nomical. The prevalence of porcine cysticer-
oxfendazole provided immunity against cosis in a population at any given time has
further challenge. In a second experiment, been shown to be a sensitive indicator of the
two pigs were injected with oncospheres current levels of T. solium in that population.
once a week, at different sites. No new cysts The sentinel pig model has been found to be
developed after the second injection in particularly useful in this regard. Briefly, it
these pigs. In a third study, two groups of involves translocation of pigs from a cys-
three pigs each were immunized with crude ticercosis-free zone to an endemic zone for 3
T. solium oncosphere and metacestode anti- months and then back to the former for
gens, respectively, and subsequently inocu- another 3 months. Porcine infection rates are
lated intramuscularly with oncospheres. determined at the end of 6 months; they
Immunization with crude oncosphere anti- indicate levels of T. solium infection in the
gens induced 100% protection, whilst endemic community.
metacestode antigens provided partial pro- Porcine cysticercosis not only poses
tection to oncosphere challenge since ani- health hazards to humans but is a major
mals immunized with this antigen produced cause for economic loss to pork-producing
some, albeit degenerated, cysts. These farmers since the price of infested pork is
results are similar to other studies where considerably less than that of healthy pork.
immunization with metacestode extracts did Therefore, control of porcine cysticercosis
not appear to provide complete protection accrues not only health-related but also
against cysticercosis (see Chapter 3). financial benefits. The viewpoint that only
those control measures that provide eco-
nomic benefits are likely to be successfully
Conclusions implemented is presented. However, for the
present, most cysticercotic pigs bypass offi-
The study of the epidemiology of porcine cial meat inspection channels in developing
cysticercosis has now provided important countries; this is a major cause for concern
insights in to the burden and control of T. to all involved in initiatives to control T.
solium infection. Three methods are available solium infection through strategies targeting
for the determination of the prevalence of the pig.
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28. Sarti, E., Schantz, P., Lara, R., et al. (1988) Taenia solium taeniasis and cysticercosis in a Mexican vil-
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31. Fernandez, M., Gutierrez, A. (1986) Como son las Comunidades de la Zona Intermedia del Valle del
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44. Froyd, G., Round, M.C. (1960) The artificial infection of adult cattle with Cysticercus bovis. Research in
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45. Ito, A., Ito, M., Eom, K.S., et al. (1997) In vitro hatched oncospheres of Asian Taenia from Korea and
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47. Pathak, K.M., Gaur, S.N. (1990) Immunization of pigs with culture antigens of Taenia solium.
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48. Nascimento, E., Costa, J.O., Guimaraes, M.P., et al. (1995) Effective immune protection of pigs
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solium cysticercosis in swine. Veterinary Parasitology 20, 33–44.
The farther backwards you look, the farther forwards you can see.
Winston Churchill
constituted a herbal remedy for intestinal For a detailed account of the developments
taeniasis. References to intestinal parasitism in classification and nomenclature of tape-
also appear in the Chinese Yellow worms, the reader is referred to Mönnig
Emperor’s Canon of Medicine written in 200 (1950)7. The unravelling of the structure of
BC5. More specifically, Chao alluded to Taenia the tapeworms is credited to several workers
in his Etiology and Symptoms of Diseases in AD including Edward Tyson (AD 1650–1708),
6106. The ancient Indian treatise on medi- Karl Asmund Rudolphi (AD 1771–1832) (Fig.
cine, the Charaka Samhita also mentions 16.1a) and P.J. van Beneden. Carl Linnaeus
worms and specifically flatworms, which (AD 1707–1778) (Fig. 16.1b) described the
are broad, white and tape-like. At one place, taxonomy of tapeworms, assigning the
it states that worms (in general) can cause genus Taenia for all types of tapeworms in
maladies of the head, where they may be his work Systema Naturae8–10. In 1782, Goeze
observed. However, seizures are not men- published Versuch einer Naturgeschichte de
tioned as a symptom of this malady and Eingeweidewurmer hierischer Korper and clas-
there is no reference to pork or meat as a sified tapeworms on the basis of Linnaeus’s
causative agent in the chapter on epilepsy. It nomenclature11. He also put forward the
is thus conjectural if cysticercosis existed in theory that tapeworms could be inherited.
ancient India. Rudolph Leuckart (AD 1822–1898) (Fig. 16.1c)
made notable contributions to the study of
science of tapeworms. Significant among
Beginnings of the Modern them were the recognition of facts that T. sag-
Understanding of the Biology of inata occurred only in cattle and T. solium in
T. solium the pig12. He and Rudolph Virchow were
instrumental in the realization of meat
The classification of tapeworms inspection laws in Germany in the latter part
of the 18th century. He also published a
Records of modern attempts at understand- series of ‘Wandtafeln’ (wall charts) depicting
ing the biology, life cycle, morphology and the morphology of tapeworms among sev-
nomenclature of tapeworms date to AD 1600. eral other animal species (Fig. 16.2).
Fig. 16.2. Wall chart (Wandtafeln) of Rudolph Leuckart, depicting flatworms. (Source: Marine Biological
laboratories. Reproduced with permission.)
The link between adult and larval forms of 158814. None of the early workers recognized
tapeworms the link between adult tapeworms and cys-
ticercosis. In fact, Goeze segregated tape-
The earliest description of cysticercosis was worms into two different classes, T. visceralis
by Paranolus in 1550, who described vesicles (cystic forms) and T. intestinalis (worm-like
in the corpus callosum13. Rumler detected forms) based upon whether they were cystic
cysts in the dura mater of an epileptic in or worm-like in morphology11. Thus, while
Fig. 16.3. (a) Cover of the journal that contains Rudolph Virchow’s landmark article ‘Traubenhydatiden der weichen Hirnaut’, believed to be the first description of racemose
cysticercosis. (Source: Clendening Library of the History of Medicine, Kansas University Medical Center, USA. Reproduced with permission.) (b) Diagrammatic description of the
161
pathology of racemose cysticercosis by Virchow. (Source: Clendening Library of the History of Medicine, Kansas University Medical Center, USA. Reproduced with permission.)
Subject to the CABI Digital Library Terms & Conditions, available at https://cabidigitallibrary.org/terms-and-conditions
Downloaded from https://cabidigitallibrary.org by 223.255.231.132, on 03/21/24.
Singh Chapter 16 17/9/02 12:01 pm Page 162
cant finding because in several of the subse- resonance imaging (MRI) in the present
quent series of cysticercosis that followed day era, would have been missed. We
these initial studies and were published from now know that solitary or few cysts36 are
endemic areas of Brazil and Mexico, it was far more common than multilesional-
not possible to determine the incubation disseminated cysticercosis37; the former
period, because in endemic regions exposure carry a good prognosis in comparison to
could have occurred at any time33,34. Finally, heavy, multiple cysticercosis.
the fact that symptoms of cerebral cysticerco-
sis were related to degeneration of larvae
was also appreciated: Serodiagnosis of T. solium cysticercosis
These parasites cause little disturbance in the
early stages, and the patient may live for years Weinberg in 1909 was the first to use the
with numerous cysts in both cerebral complement fixation test on the serum of
hemispheres. After their death, however, the cysticercotic pigs38. In 1910, Robin and
parasites may cause symptoms partly by their Fiessenger first performed the test upon
toxic effects and partly by their increase in size. humans. Other notable contributions so far
(Dixon and Smithers, 193430) to the serological diagnosis of cysticercosis
Early studies, particularly by MacArthur, have been those of Rothfeld39, Biagi and
pictured a uniformly dismal prognosis of the Tay40, and Neito41. Studies at this stage were
disorder, with virtually every case ending up not optimistic about the role of serological
in lunacy and leading to death24–26. Dixon studies in the clinical context, though Neito
and Hargreaves disagreed with MacArthur’s reported excellent results of his lengthy and
view and remarked31: remarkable set-up with the complement fixa-
tion tests in the spinal fluid41.
Our observations have not borne out the view Serological confusion compounded clini-
of MacArthur, who believed that the general
cal confusion with neurosyphilis, an impor-
tendency was one of retrogression, as
tant disorder in the early part of the 19th
evidenced by signs of mental deterioration
which might be so marked so as to necessitate century. In an account of one such confusion,
institutional segregation. Castellani described the occurrence of subcu-
taneous nodules, a positive Wasserman’s
When MacArthur reviewed Dixon and reaction in the serum and response to anti-
Hargreaves’s paper in the Tropical Diseases syphilitic treatment in three persons under
Bulletin he countered35: the name, ‘luetic pseudo-cysticercosis’41,42.
In my experience, relapse has followed
symptom free intervals which had lasted for
10, 13, and 20 years. I believe that when a long Radiology
remission occurs, one can but wait and hope
for the best, while cautiously remembering the According to Grove, the earliest roentgeno-
scriptural injunction, ‘Judge none blessed logical description of dead cysticerci was by
before his death.’
Roth in 192620,43. Broughton-Alcock and
The reason why early workers inferred a Weinbren described muscle calcification
discouraging outcome can now be related to picked up incidentally on a radiograph of a
the lack of availability of contemporary meth- gunshot wound44. They compared radiologi-
ods of diagnosis. The diagnosis of cysticerco- cal appearances of calcification due to dead
sis was based upon histology from excised cysticerci with those of Trichenella spiralis in a
subcutaneous cysts or radiology depicting radiograph of a post-mortem specimen of
soft tissue calcification/s. Obviously, only the muscle obtained from Sir Arthur Keith. They
most severe forms were diagnosed by these found that calcifications of Taenia solium were
archaic tools. On the other hand, benign larger than those of Trichenella spiralis. Major
oligolesional forms like those due to a solitary contributions on the radiology also came
or few cysts that would be easily picked up from Morrison45 and Brailsford46,47. It was
on computed tomography (CT) or magnetic recognized that cerebral calcification was
less common and appeared later than muscle aracae)6,52. Other remedies used in the early
calcification and if the soft tissue radi- part of the last century included ‘betel nut’
ographs did not reveal calcifications, skull boiled in water, tetrachloroethylene, thymol,
roentgenograms rarely contributed to the carbon tetrachloride and hexylresorcinol51–57.
diagnosis. Brailsford was eloquent in his Thus Allan in 191255 and Carman in 193156
opinion on the role and limitations of reported the use of thymol and carbon tetra-
roentgenography47: chloride respectively. In the 1930s through
Radiography permits of the diagnosis of 1950s, filix mas and carbon tetrachloride were
cysticercosis when the parasites have most often used for the treatment of tape-
degenerated and calcified but affords no help worms. With both remedies, prior starvation
in the earlier years of infestation. … Actually it and subsequent purgation was advocated.
is rare to obtain radiographic evidence of For 2 days before the administration of filicis
cysticerci in the brain in patients with liquidum, the individual was fed upon a liq-
symptoms of central nervous system disease. uid diet consisting of orange juice and dex-
… In the later years, when symptoms have as a
trose. Following the active drug, a saline
rule ceased, radiography for other reasons may
reveal the calcified parasites.
purgative was administered. Castor oil was
specifically contraindicated as it dissolved the
In 1945, Arana and Asenjo published a filix mas and led to intoxication. The stools
landmark paper on the ventriculographic obtained following the purge were sieved and
diagnosis of posterior fossa cysticercosis examined against a black background to iden-
from Santiago, Chile48. Incidentally, tify the head of the tapeworm. The identifica-
MacArthur expressed surprise over the tion of the head of the tapeworm was taken to
authors’ observations and commented49: be an indicator of successful taeniacidal ther-
It looks, therefore, as if the commoner types apy. If the head was not passed, treatment
which would bring the above more into their was repeated and, if still unsuccessful, a duo-
proper proportions may not be coming to denal tube was passed and the drugs were
light. Perhaps the explanation is that only infused directly through the tube. However, it
patients supposed to be suffering from a was soon recognized that these chemicals
cerebral tumour were sent to the institute
were associated with severe toxicity, primarily
for investigation.
renal and hepatic.
In the 1940s and 1950s, attention focused
on the use of atarabine as a taeniacidal
The Search for an Effective Treatment agent57–59. Though anecdotally this drug
proved to be effective, its major limitations
The history of the search for effective treat- were the side effects of severe vomiting and
ment for taeniasis and cysticercosis is as old encephalopathy. Vomiting was prevented by
as the recognition of tapeworms and cys- the concomitant administration of largactil
ticerci. The oldest remedies were the herbal or by intraduodenal administration of atara-
remedies used, for instance, by the ancient bine. Delirium was treated by the concomi-
Egyptians and Chinese. One can find men- tant administration of phenobarbitone
tion of the use of herbs such as Acacia nilotica (phenobarbital).
and Aloe vera for treatment of worms in the While in the early part of the 19th century
Egyptian papyri1. Similarly, a fungus, several efforts were made to develop an
‘Raigan’ (Omphalia lapidescens), that grows on effective taeniafuge, similar drives for the
bamboo, has been used by the Chinese as an development of anticysticercal agents were
anthelminthic for nearly 2000 years50. not evident. In fact, in a discussion on
One of the early remedies for the tape- MacArthur’s paper25, Sir Hamilton Fairley
worm was an extract of the male fern, pointed out that according to Colonel
Dryopteris filix-mas, the active medicament of MacArthur’s description, the cysticerci
which was filix mas51. Other important reme- should be kept alive as long as possible; spe-
dies included the ground seeds of Cucurbita cific drug therapy was contraindicated27.
moschata (pumpkin) and Areca catecho (semen Similarly Dixon and Smithers stated29:
There is no known treatment for the established to us that the only surgical operation justi-
disease, in fact the administration of such fied is decompression in order to save sight.’
substances as Tartar emetic have in some cases
produced an exacerbation of symptoms or a
fresh crop of palpable nodules, presumably by
Conclusions
causing the death of more parasites.
Thus the fact that specific chemotherapy In about 1969, a United States General
of larvae could cause exacerbation of symp- remarked that it was time to close the book
toms and the mechanisms thereof were rec- on infectious diseases. His remark was at
ognized very early. Other agents such as best a gross underestimate. Taenia solium
neoarsphenamine and bismuth (both anti- cysticercosis is a classical example of a re-
syphilitic treatments), atarabine, quinine, emerging disease that the United States has
antimony tartrate, chloroquine, sulfasalazine to cope with, as a result of increasing immi-
and streptomycin were tried with no good gration, travel and general globalization.
results. Radiation therapy was also tried but This is one aspect of the global epidemiol-
results were not satisfactory5. Henneberg ogy of T. solium. The other, which is per-
advocated repeated lumbar punctures in haps less well appreciated, is the presumed
selected patients with intracranial hyperten- but precisely unknown large number of
sion as a palliative measure60. Another pal- people affected by the disorder in several
liative measure comprised of the use of developing countries. For these countries,
bromides and luminal for control of seizures. their governments and authorities, history
The earliest attempt at surgical treatment professes that T. solium, which was once
was by Krausse in 190161. MacArthur clearly widely prevalent in Europe, was eradicated
advocated against resorting to surgery in solely by developing sanitary infrastructure
view of the widespread distribution of lar- and enforcing meat hygiene. Perhaps, the
vae24–26. In a series of 99 patients reported best thing that they can learn from history
by Dixon and Hargreaves, 14 were is that the only way to surely eradicate
operated31. Indications for surgery included, cysticercosis is by improving sanitation,
the lack of diagnosis, as a relief measure for meat inspection, human behaviours and
control of intracranial hypertension and con- attitudes and most importantly by socio-
trol of seizures. They concluded: ‘It appears economic development.
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17 Neurocysticercosis: an Overview of
Clinical Presentations
Box 17.1. Diagnostic criteria for neurocysticercosis (NC). (Adapted from references 9 and 10.)
Absolute criteria
1. Histological demonstration of cysticerci from either a central or peripheral source.
2. Direct visualization of ophthalmologic cysticerci.
3. Demonstration of a cyst containing a scolex upon neuroimaging study.
Major criteria
1. Evidence of lesions suggestive of NC on neuroimaging studies without demonstration of a
scolex (MRI or CT showing cystic lesions, ring-enhancing lesions, parenchymal brain
calcifications, hydrocephalus, and abnormal enhancement of the leptomeninges. Myelograms
showing multiple filling defects in the column of contrast material).
2. Serum anti-cysticercal antibodies demonstrated by immunoblot, or spinal fluid
anticysticercal antibodies demonstrated by immunoblot or ELISA.
3. Characteristic cigar-shaped calcifications demonstrated by soft-tissue radiographs of the
thigh and calf.
Minor criteria
1. Subcutaneous nodules suggestive of cysticerci (without histological confirmation).
2. Punctate intracerebral or soft-tissue calcifications on plain radiographs.
3. Clinical manifestations suggestive of NC (seizures, focal neurological deficits, symptoms of
increased intracranial pressure, dementia).
4. Disappearance of intracranial lesions after treatment with anticysticercal drugs.
Epidemiologic criteria
1. Residence in a cysticercosis endemic area.
2. Frequent travel to cysticercosis endemic areas.
3. Household contact with an individual infected with Taenia solium.
Based on the above diagnostic criteria, the following diagnostic categories were proposed:
A. Definite NC (one of the following)
One absolute criterion
Two major criteria
One major, two minor and one epidemiologic criterion
B. Probable NC (one of the following)
One major and two minor criteria
One major, one minor and one epidemiologic criterion
Three minor and one epidemiologic criterion
C. Possible NC (one of the following)
One major criteria
Two minor criteria
One minor and one epidemiologic criterion
Overview of Disease Staging and tions11. This was one of the earliest versions
Classification of more contemporary classifications. A
major objective of classification is to guide
The lack of pathognomic clinical features management approaches and obtain prog-
despite the large number of clinical presenta- nostic information. Since in the early part of
tions of human T. solium cysticercosis was the 20th century, surgery was the only estab-
recognized very early by medical scientists. lished method of treatment, initial classifica-
This led to attempts at systematic classifica- tion systems were made in order to
tion of disease. Thus, Küchenmeister recog- determine the need and nature of surgical
nized the presence of cysticercosis in approach. Several orderly classifications
meningeal, cortical and ventricular loca- were given and perhaps that of Stepien and
Chorobski is most well known (Table 17.1)12. included in active disease presentations.
The classification worked well in those Parenchymal calcifications and hydrocephalus
times, effectively dictating the surgical secondary to meningeal fibrosis were classified
approach in the absence of modern tools of into inactive forms. Thus, symptoms of active
diagnosis like CT, MRI and enzyme- forms of NC included seizures (most com-
linked immunoelectrotransfer blot (EITB). monly), acute or subacute hydrocephalus (less
Understandably, it has been replaced by clas-
sification/s that incorporate contemporary
diagnostic and therapeutic options13,14.
Table 17.2. Anatomical classification of neuro-
Classifying NC according to the anatomic cysticercosis (NC).
compartment of involvement is advantageous
to clinicians, radiologists and pathologists 1 Parenchymal NC
(Table 17.2). It separates clinical concomitants 2 Extraparenchymal NC
into those of parenchymal NC (presenting with Venticular
seizures, space-occupying effects and intracra- Subarachnoid
3 Mixed
nial hypertension), subarachnoid NC (present-
ing with meningitis, space-occupying effects
and hydrocephalus) and ventricular NC (man-
ifesting as acute hydrocephalus, meningitis or
Table 17.3. Classification of neurocysticercosis
rarely space-occupying lesions). A classifica-
into active and inactive forms. (Reproduced with
tion system that is oriented purely anatomi- permission from reference 15.)
cally however, does not take into account the
evolutionary stage of NC, which also influ- Active forms of NC
ences clinical presentation. In 1985, Sotelo et al. Arachnoiditis
proposed the classification of NC into active Hydrocephalus secondary to meningeal
inflammation
and inactive disease (Table 17.3)15. The classifi-
Parenchymal cysts
cation derives from pathological-radiological
Brain infarction secondary to vasculitis
staging of NC, which have been described else- Mass effect due to large cyst or cyst clumps
where in the book (Chapters 30 and 32) in 753 Intraventricular cysts
cases. Both viable, live (non-inflamed) Spinal cysts
parenchymal cysts and degenerating
Inactive forms of NC
parenchymal cysts represented the active form.
Parenchymal calcifications
Extraparenchymal presentations of active Hydrocephalus secondary to meningeal fibrosis
meningitis or arachnoiditis were likewise
common) due to meningeal inflammation, involuting. Thus this patient may pass
arachnoiditis, obstruction by intraventricular through several stages of NC: active (asymp-
cysts, meningitis and stroke (not uncommon) tomatic) initially, transitional, inactive and
and mass effect due to space-occupying lesions then again, transitional.
(rare) and myelopathy (rare). Clinical presenta- The usual course of illness in most
tions of inactive NC included seizures due to patients, particularly those with one or few
parenchymal calcified NC and chronic hydro- parenchymal cysts, is benign and self-limit-
cephalus. The purpose of this classification was ing. These patients have few seizures, often
to differentiate between those cases that clustered, that remit rapidly. It is not uncom-
required definitive medical (anticysticercal mon to find some parenchymal cysts under-
treatment and/or steroids) or surgical manage- going involution/degeneration at about the
ment versus those that required only sympto- same time rather than one after another
matic medical (antiseizure medications) or upon CT. The simultaneous involution is
surgical (ventriculoperitoneal shunt) manage- surmised to result from an antigenic stimula-
ment. This classification is perhaps the most tion following degeneration of one cyst that
widely used in the present day. Carpio et al. induces an immune response against the
classified NC into active, transitional and inac- other cysts as well. This often is the reason
tive forms16. This classification is an appropri- for the short, self-limiting course of NC
ate staging system based upon clinical and rather than a protracted course. In contrast,
imaging characteristics and has therapeutic clinical syndromes associated with multiple
implications as well. Active NC forms, which inflamed parenchymal cysticercosis, often
refer to live, viable parenchymal or extra- synonymously called cysticercotic encephali-
parenchymal cysts, rarely produce symptoms tis and profuse, non-inflamed cysticercosis,
apart from the rare instance of mass effect. also called ‘disseminated cysticercosis’
Symptomatic NC is incident upon the transi- (reviewed in Chapter 19), or even few cysts
tional forms, where degenerating parenchymal in the intraventricular (discussed in Chapter
cysts produce acute symptomatic seizures. 20) or subarachnoid (discussed in Chapter
Likewise degenerating subarachnoid cysts pro- 18) locations, often have a foreboding course.
duce meningitis, arachnoiditis and hydro-
cephalus and ventricular cysts lead to acute
hydrocephalus. Inactive disease again is exem- Temporal and Geographical Trends in
plified by single or multiple parenchymal calci- Clinical Presentation
fication/s and/or hydrocephalus secondary to
meningeal fibrosis. Temporal trends
8.2 years with a range of 1–52 years before be resolved by careful prospective collec-
19626. This time period has been reduced to tion of data from similar facilities that are
days or months in most developing coun- matched for therapeutic expertise and rep-
tries and most certainly to hours or days in utation, referral pattern and patient vol-
developed countries. In another example, ume. Some of the important published
the traditional viewpoint prevailed in India series of NC in persons of Latin American
that regarded NC as a disorder with multi- origin are summarized in Table 17.4. These
ple parenchymal cysts. With the advent of have been compared with a series collected
CT in the early 1980s, a solitary ring-enhanc- in a large tertiary care public hospital facil-
ing lesion that resolved spontaneously in ity in India. The presence of NC was estab-
3–6 months was noted upon CT. It took clin- lished by imaging, surgical pathology and
ical neurologists nearly a decade to under- autopsy in this series. Indeed, comparison
stand and accept that these single of these series does not reveal differences in
self-limiting forms were of cysticercal aetiol- clinical presentation.
ogy. In this regard, therefore, CT and later
MRI have made the most dramatic impact
on our understanding of the disorder. Conclusions
Table 17.4. Clinical syndromes (not necessarily the presenting ones) of neurocysticercosis in various
published series in the 1980s, about the time when computed tomography was becoming available.
Reference 23 15* 24 25 26
References
1. Miyake, H., Takahashi, K., Tsuji, M., et al. (1993) A surgical case of solitary cerebral cysticercosis. No
Shinkei Geka 21, 561–565.
2. Matson, D.O., Rouah, E., Lee, R.T., et al. (1988) Acanthamoeba meningoencephalitis masquerading
as neurocysticercosis. Pediatric Infectious Diseases Journal 7, 121–124.
3. Walus, M.A., Young, E.J. (1990) Concomitant neurocysticercosis and brucellosis. American Journal of
Clinical Pathology 94, 790–792.
4. Bandres, J.C., White, A.C., Jr, Samo, T., et al. (1992) Extraparenchymal NC: report of five cases and
review of management. Clinical Infectious Diseases 15, 799–811.
5. Lobato, R.D., Lamas, E., Portillo, J.M., et al. (1981) Hydrocephalus in cerebral cysticercosis.
Pathogenic and therapeutic considerations. Journal of Neurosurgery 55, 786–793.
6. Dixon, H.B.F., Lipscomb, F.M. (1961) Cysticercosis: an analysis and follow up of 450 cases. Medical
Research Council Special Report. Series No. 299. Her Majesty’s Stationery Office, London, pp. 1–58.
7. Wadia, N.H., Desai, S.B., Bhatt, M.B. (1988) Disseminated cysticercosis – new observations including
CT scan findings and experience with treatment by praziquantel. Brain 11, 597–614.
8. Garcia, H.H., Del Brutto, O.H. (1999) Heavy nonencephalitic cerebral cysticercosis in tapeworm car-
riers. Neurology 53, 1582–1584.
9. Del Brutto, O.H., Wadia, N.H., Dumas, M., et al. (1996) Proposal of diagnostic criteria for human
cysticercosis and NC. Journal of the Neurological Sciences 142, 1–6.
10. Del Brutto, O.H., Rajshekhar, V., White, A.C., Jr, et al. (2001) Proposed diagnostic criteria for neuro-
cysticerosis. Neurology 57, 177–183.
11. Küchenmeister, F. (1855) Die in und an dem Körper des lebenden Menschen vorkommenden
Parasiten. Ein Lehr- und Handbuch der Diagnose and Behandlung der thierischen und pflanzichen Parasiten
des Menschen. BG Teubner, Leipzig, pp. 486. Translated by E. Lankester (1857). In: On Animal and
Vegetable Parasites of the Human Body. Vol. 1. Animal Parasites Belonging to the Group Entozoa. The
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12. Stepieñ, L., Choróbski, J. (1949) Cysticercosis cerebri and its operative treatment. Archives of
Neurology and Psychiatry (Chicago) 61, 499–527.
13. Colli, B.O., Martelli, N., Assirati, J.A., et al. (1994) Cysticercosis of the central nervous system. I.
Surgical treatment of cerebral cysticercosis. Arquivos de Neuropsiquiatria 52, 166–186.
14. Colli, B.O., Martelli, N., Assirati, J.A., et al. (1995) Surgical treatment of cysticercosis of the central
nervous system. Neurosurgery Quarterly 5, 34–54.
15. Sotelo, J., Guerrero, V., Rubio, F. (1985) Neurocysticercosis: a new classification based on active and
inactive forms. A study of 753 cases. Archives of Internal Medicine 145, 442–445.
16. Carpio, A., Placencia, M., Santillán, F., et al. (1994) A proposal for classification of neurocysticercosis.
Canadian Journal of Neurological Sciences 21, 43–47.
17. MacArthur, W.P. (1933) Cysticercosis as a cause of epilepsy in man. Transactions of the Royal Society of
Tropical Medicine and Hygiene 26, 525–528.
18. MacArthur, W.P. (1934) Cysticercosis as seen in the British army, with special reference to the pro-
duction of epilepsy. Transactions of the Royal Society of Tropical Medicine and Hygiene 27, 343–357.
19. Dixon, H.B.F., Smithers, D.W. (1934) Epilepsy in cysticercosis (Taenia solium). A study of seventy-one
cases. Quarterly Journal of Medicine 3, 603–616.
20. Dixon, H.B.F., Hargreaves, W.H. (1944) Cysticercosis (Taenia solium). A further ten years clinical
study covering 284 cases. Quarterly Journal of Medicine 13, 107–121.
21. MacArthur, W.P. (1945) Tropical Diseases Bulletin 42, 908–909.
22. Arana, R., Asenjo, A. (1945) Ventriculographic diagnosis of cysticercosis of the posterior fossa.
Journal of Neurosurgery 2, 181–190.
23. McCormick, G.F., Zee, C.S., Heiden, J. (1982) Cysticercosis cerebri: review of 127 cases. Archives of
Neurology 39, 534–539.
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25. Scharff, D. (1988) Neurocysticercosis. Two hundred thirty-eight cases from a California hospital.
Archives of Neurology 45, 777–780.
26. Veerendra Kumar, M. (1986) Clinico-pathological Study of Neurocysticercosis. Thesis. University of
Bangalore, Bangalore, India.
18 Meningeal Cysticercosis
head armed with suckers and hooks, an their location. Cysticerci located at the corti-
elongated neck, and a rudimentary body. A cal surface of the brain usually have a scolex
scolex may not be identified in all cysticer- and are of the cellulose form (Fig. 18.1). This
cus vesicles. These latter forms consist of is the most common location of intracranial
several membranes attached to each other, cysticerci in pathological series15,17. The
usually located within basal cisterns17,18. cysts rarely measure greater than 10 mm
Histological studies have shown that these because pressure of the brain parenchyma
structures represent proliferation of para- prevents further growth of vesicles. In con-
sitic membranes after degeneration of the trast, cysticerci located within basal cisterns
scolex. Their histochemical composition is often attain sizes of about 50 mm since their
unique, because of the presence of acid growth is not limited by brain parenchyma.
mucosubstances and hydrophilic lipids in Giant cysts usually lack a scolex. They are
large amounts19. commonly located within the Sylvian fis-
Rabiela et al. described the morphologi- sures, cerebellopontine angles, perimesen-
cal characteristics of cellulose and racemose cephalic and prepontine cisterns, and
forms of the cysticercus, providing evi- optochiasmatic region.
dence that they arise from a single Taenia Upon involution, meningeal cysticerci
sp.20,21. The authors also described another elicit severe inflammatory reaction in the
form of cysticercus that conserves the subarachnoid space with formation of
scolex but has two or more small bladders dense exudates composed of collagen fibres,
sprouting from the main vesicle. This is an lymphocytes, multinucleated giant cells,
‘intermediate form of cysticercus’, repre- eosinophils and hyalinized parasitic
senting an initial stage in the transforma- membranes, leading to thickening of
tion from cellulose to racemose form. leptomeninges (Fig. 18.2). Meningeal
Mechanisms responsible for this transfor- inflammation may be disseminated, induc-
mation are incompletely understood. It is ing neural and vascular damage distant
believed that vesicles grow and their scol- from the sites where parasites lodge.
ices disappear as the result of hydropic Indeed, leptomeningitis may extend from
degeneration, caused by the continuous the optochiasmatic region to the foramen
adsorption of cerebrospinal fluid (CSF)18. magnum15,18. The optic chiasm is frequently
Macroscopic appearances of meningeal trapped by this dense exudate, leading to
(subarachnoid) cysticerci vary according to visual field defects22. Cranial nerves arising
Fig. 18.1. Small subarachnoid cysticercus located in the depths of cortical sulci. (Reproduced with
permission from reference 34.)
Fig. 18.2. Cysticercotic arachnoiditis causing abnormal thickening of leptomeninges around the brainstem.
from the ventral aspect of the brainstem ticerci enter the spinal subarachnoid space
may also be encased, giving rise to cranial by retrograde flow through epidural verte-
nerve palsies23. The foramina of Luschka bral veins32. Cysticerci located in the spinal
and Magendie may also be occluded by subarachnoid space cause spinal lepto-
thickened leptomeninges and parasitic meningitis with resulting inflammatory or
membranes with subsequent development demyelinating changes in ventral and dor-
of obstructive hydrocephalus24. The sub- sal roots or peripheral nerves.
arachnoid inflammatory reaction elicited by
meningeal cysticerci may also involve
intracranial vessels. Walls of small penetrat- Clinical Manifestations
ing arteries arising from the circle of Willis
are invaded by inflammatory cells, leading The clinical pleomorphism of meningeal cys-
to endarteritis, adventitial thickening, ticercosis is related to individual variations
medial fibrosis and endothelial hyperplasia in number, size and location of parasites, as
(Fig. 18.3). The hyperplasia reduces or well as the severity of the subarachnoid
occludes the lumen of the vessels, leading inflammatory reaction33,34. While a typical
on to cerebral infarction25. Major intracra- syndrome of meningeal cysticercosis cannot
nial arteries may also be occluded by be defined, focal neurological deficits,
atheroma-like luminal deposits resulting meningitis and intracranial hypertension in
from disruption of the endothelium; this varying combinations are the most common
vascular involvement may cause large cere- presenting features33–35.
bral infarcts in the territory of the anterior
or middle cerebral arteries26–28. Adherence
of the cysticercus to a subarachnoid blood Focal neurological deficits
vessel may weaken the vessel wall, result-
ing in the formation of a mycotic As previously noted, cysticercotic arach-
aneurysm29. Finally, meningeal cysticerci noiditis causes entrapment of cranial
may also be located at the spinal subarach- nerves arising from brainstem. The oculo-
noid space30,31. These are the result of motor nerves, which run a long course
migration of cysts from the intracranial sub- along the basal meninges from their origin
arachnoid space. It is also possible that cys- until their entrance into the cavernous
Fig. 18.3. Microscopic section of an occluded leptomeningeal blood vessel affected by cysticercotic
endarteritis. A dense collagen capsule and parasitic membranes surround the vessel. (Reproduced with
permission from reference 34.)
sinuses, are particularly susceptible in this noiditis associated with subarachnoid cysts
regard. Clinical manifestations include in the suprasellar cisterns. These infarcts
diplopia due to extraocular muscle paraly- are located in the posterior limb of the
sis, and blurred vision due to pupillary internal capsule or corona radiata, and pro-
abnormalities36. Encasement of the optic duce syndromes such as pure motor hemi-
nerves and/or optic chiasm by suprasellar paresis and ataxic hemiparesis, that are
exudates leads to decreased visual acuity clinically indistinguishable from those
and visual field defects37,38. Large cyst/s in caused by hypertension43,44. Lacunar
the cerebellopontine angle cistern present infarcts may also be located in the midbrain
with a syndrome characterized by various and thalamus, particularly when the para-
combinations of sensorineural hearing loss, median thalamopeduncular branches of the
vertigo, facial palsy, facial numbness and mesencephalic artery are involved by the
pain, that may be accompanied by signs of process of angiitis; in these cases, clinical
long-tract dysfunction, motor weakness manifestations include impaired vertical
and cerebellar ataxia39. Likewise, clumps of gaze, pupillary abnormalities, somnolence,
cysts inside the Sylvian fissure may cause paraparesis, and urinary incontinence25.
contralateral motor weakness and sensory Large cerebral infarcts are caused by
deficits and language disturbances40. Most occlusion of the internal carotid artery, or
manifestations described above have a the anterior or middle cerebral arter-
subacute onset and progressive course, ies26–28,45–47. Patients present with severe
often mimicking brain tumours33–40. Stroke- focal neurological deficits secondary to an
like presentations occur in 3% of the infarct involving the basal ganglia and/or
patients with subarachnoid cysticercosis41. cerebral cortex. Finally, there are anecdotal
Ischaemic cerebrovascular complications reports of patients with subarachnoid
include lacunar as well as large cerebral haemorrhage due to rupture of mycotic
infarcts5,42. Lacunar infarcts occur as the aneurysms of the basilar artery related to
result of inflammatory occlusion of small large subarachnoid cysticerci attached to
perforating arteries secondary to arach- the artery29.
be noted, a finding that facilitates the diagno- However, other conditions with similar pre-
sis of neurocysticercosis (NC). Small sub- sentation, including fungal, tuberculous and
arachnoid cysts over the convexity of the carcinomatous meningitis should be consid-
cerebral hemispheres were considered rare in ered in the differential diagnosis. Angio-
initial CT studies of NC56,57. However, the graphic findings in cysticercotic angiitis
development of new generation CT equip- include segmental narrowing of the middle
ment and MRI led to the recognition of such cerebral artery, occlusion of the anterior or
lesions58,59. It is unusual for large cysts to middle cerebral arteries or even the internal
develop over the convexity of cerebral hemi- carotid artery, and mycotic aneurysms26–29,44,46.
spheres, although isolated cases have been The exact prevalence of angiographic abnor-
reported40. These cysts are spherical rather malities in NC is unknown. However, a recent
than multilobulated and in some cases, a report suggests that angiographically docu-
large hyperdense nodule corresponding to the mented arteritis is relatively common in
scolex may be seen. Large cysts usually have meningeal cysticercosis, including cases
a multilobulated appearance, displace neigh- without clinical or neuroimaging evidence of
bouring structures, and behave as space-occu- cerebral infarction61.
pying lesions in the Sylvian fissure, CT and MRI are often non-contributory in
cerebellopontine angle and the ambiens and the diagnosis of spinal meningeal cysticerco-
prepontine cisterns (Fig. 18.5)39,60. sis. Myelography may be useful in such situa-
Ischaemic cerebrovascular complications tions and may demonstrate multiple filling
are well visualized with CT and MRI42. defects in the column of contrast material cor-
Findings are, however, non-specific since the responding to the cysts. These cysts may be
appearance of NC-related cerebral infarcts is freely mobile within the spinal subarachnoid
similar to those due to other causes. The space and may change their position during
accompanying presence of subarachnoid cys- myelographic examination according to
tic lesions or abnormal enhancement of basal movements of the patient on the exploration
leptomeninges may establish a diagnosis of table. This finding is of diagnostic
meningeal cysticercosis in some instances43,44. significance30,54,62.
Fig. 18.4. Contrast-enhanced MRI of a patient Fig. 18.5. MRI showing a giant cysticercus in the
with severe cysticercotic arachnoiditis showing Sylvian fissure. Note the multilobulate appearance
abnormal enhancement of basal leptomeninges. of the lesion and the displacement of the midline.
Table 18.1. Differences between larval cellulose and racemose forms of Taenia solium.
Fig. 18.6. CT before (a) and 3 months after (b) albendazole therapy of a patient with a subarachnoid
cysticercus in the interhemispheric fissure. Note resolution of lesion as the result of therapy.
important to avoid further neurological shunt. A drawback of the new shunt device
damage. The continued administration of was insufficient drainage of CSF, a problem
prednisone in doses of 50 mg three times a that may be resolved by increasing the
week for up to 2 years can reduce the risk cross-sectional internal area of the peri-
of shunt dysfunction from 60% to 13%77. toneal end of the catheter.
Sotelo recently designed a new shunt
device that functions at a constant flow
without a valvular mechanism78. This pre- Conclusions
vents the entry of spinal CSF into the ven-
tricular system towards the inlet of the Meningeal cysticercosis involves the basal
shunt device. The inversion of CSF transit CSF cisterns or the convexity CSF spaces.
is one of the most common causes of shunt The pathological appearance is one of
dysfunction as it allows the entry of sub- grape-like multilobulated vesicles, without
arachnoid inflammatory cells and parasitic a scolex, occupying much of the volume of
debris into the ventricular system79. A the basal cistern or of small cystic struc-
recent study reported good shunt function tures with a scolex over the cerebral con-
at a mean of 9 months in 96% of patients vexity. Focal neurological deficits,
with hydrocephalus due to cysticercotic meningitis and intracranial hypertension
arachnoiditis80. Another study compared are the most common presenting clinical
the effectiveness of this new shunt with features. In addition, convexity meningeal
that of a conventional Pudenz-type shunt81. cysticerci may present with seizures.
One year after follow-up, the Pudenz-type Imaging studies reveal a constellation of
shunt had to be withdrawn or surgically findings in varying combination: cysts,
revised in 45% of the patients. This com- infarcts and hydrocephalus. Treatment
pared with the requirement of shunt revi- includes surgical and medical options. A
sion in 30% of those with the new shunt judicious choice between the use of the
implant. The main cause of shunt dysfunc- anticysticercal drug, albendazole for small
tion in Pudenz-type shunt is shunt occlu- cysts, and surgery for large cysts and
sion. This complication is rare with the new hydrocephalus needs to be made.
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Imaging features
Therapy
Clinical manifestations
individualized decision on the use of anti- result from either a massive load of T. solium
cysticercal drugs; adequate supportive mea- eggs, or a continued source of infection, and
sures when using them; maintenance of the degree of inflammation, closely correlated
imaging surveillance; and long-term corti- to the clinical expression, is probably depen-
costeroid therapy if anticysticercal agents are dent on the previous exposure of the host
not prescribed, are all important aspects of immune system to T. solium antigens41,42.
the treatment plan. Subcutaneous and mus-
cular cysticercosis do not require specific
therapy unless mass effects due to cyst Conclusions
clumps occur. In these cases, either surgical
excision or anticysticercal therapy is effective Three major clinical syndromes with heavy,
(again, after first ruling out the possibility of multilesional cysticercosis have been
ocular or cerebral cysticercosis). described. The first, cysticercotic encephalitis,
is characterized by a profuse inflammatory
response to several degenerating cysticerci in
Comment the cerebral parenchyma, giving rise to cere-
bral oedema and intracranial hypertension.
Evidence from animal studies (Gonzalez et In the second condition, known as ‘heavy non-
al., unpublished data, 2001) and data on soft- encephalitic NC’, there are hundreds of live,
tissue roentgenograms from older series of active and viable cysts throughout the brain
cysticercosis suggest that almost all human parenchyma with no surrounding oedema.
cases of NC are disseminated to an extent. The condition, which is not catastrophic like
This dissemination, however, does not cause cysticercotic encephalitis, manifests with
discernible manifestations because infection intracranial hypertension and neuropsychi-
is controlled by the host immunity in sites atric features. The third form, i.e. ‘dissemi-
other than the brain39. If this is the case, the nated cysticercosis’, implies the existence of
heavy infections described hitherto imply cysticerci, again live, in still larger numbers,
that either the host’s immune system is ill- probably thousands, throughout the brain,
prepared to counteract tissue infection, or muscles, skin and eyes. The latter presents
that the infecting parasite load was large with muscular pseudohypertrophy in addi-
enough to overcome the host’s ability to tion to dementia and other neuropsychiatric
destroy cysts. Although the diagnosis of cys- disturbances. The clinical behaviour and
ticercosis in these cases will easily fulfil the imaging characteristics of the three syn-
recommended criteria for NC40, identification dromes differ; however, a uniting feature is
of specific syndromes is necessary for sound the proclivity of anticysticercal therapy to
and appropriate therapy. Since only a few cause serious, often life-threatening adverse
reports of each syndrome are available, some effects due to massive inflammatory oedema
degree of overlap between them does occur. and intracranial hypertension that may fol-
In any case, one or more of these syndromes low death of the cysticerci. Therefore,
can be clearly identified when a patient pre- extreme caution is to be exercised if resort to
sents with massive infection. All these forms anticysticercal therapy is sought.
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20 Intraventricular Neurocysticercosis
tricular cysts with or without hydrocephalus. vation of arterial blood pressure, seizures,
Thus, there are patients presenting with and alteration of consciousness. Abrupt
seizures due to parenchymal involutional intermittent obstruction of the intraventricu-
cysts who also have asymptomatic intraven- lar CSF flow by the cyst produces abnormali-
tricular cysts (Fig. 20.1). ties lasting hours to days. Sudden changes of
head position may change the location of the
cyst and trigger or alleviate the headaches4,9.
Symptoms mainly due to obstruction of Also, sudden change of head position may
the CSF flow produce fleeting loss of strength or muscle
tone9. These drop attacks may be due to
Intraventricular cysts may totally obstruct associated sudden bilateral ischaemic
the CSF flow. This obstruction can be abrupt changes in brainstem. Abrupt permanent
or gradual. Cysts moving freely within the obstruction leads to acute hydrocephalus
ventricular system may lodge in one of the with stupor, coma, and death from brain her-
vital communication passages of the ventric- niation4,9–12. Obstruction may occur in the
ular system with intermittent or permanent foramen of Monro, third ventricle, aqueduct
blockade of CSF flow4. of Sylvius, or fourth ventricle11. Any
obstructing cyst located in the ventricles
results in a non-communicating hydro-
Abrupt obstruction
cephalus that requires prompt therapeutic
Abrupt obstruction of the ventricular system intervention to prevent brain herniation.
results in acute hydrocephalus with symp- In the fourth ventricle, direct compression
toms and signs such as headache, diplopia, of the brainstem and midcerebellar structures
dizziness, vomiting, restlessness, drowsi- produces, in addition to symptoms of
ness, respiratory changes, bradycardia, ele- increased ICP, focal deficits due to local mass
Fig. 20.1. Axial T1-weighted post-contrast MRI shows multiple parenchymal cysts and an intraventricular
cyst in the occipital horn of the right lateral ventricle. This 32-year-old man presented with seizures. The
hydrocephalus had not yet produced symptoms.
effects, such as gait ataxia, dysmetria and medical and surgical treatment1,16. Fixed cysts
diplopia13,14. In children, this clinical presen- are not susceptible to surgical removal with-
tation may suggest the presence of a midline out damage to brain tissue1,7.
cerebellar tumour. A superior aqueductal Patients present with a picture of
syndrome is seen in patients with blockade of increased ICP, meningoencephalitis (fever,
the aqueduct of Sylvius. These patients have alteration of consciousness and nuchal rigid-
paralysis of vertical gaze as well as other ity), focal neurological deficit and inflamma-
symptoms and signs of increased ICP15. tory reaction in the CSF7,17. A final clinical
stage includes mental deterioration, blind-
Chronic obstruction ness, quadriparesis, and ataxia, despite
appropriate treatment17. There are many
Most cases present with insidious, gradual complications contributing to clinical deteri-
onset of increased ICP4. The obstruction of oration, including cerebral and brainstem
the CSF circulation may be due to the pres- infarcts due to angiitis, hypothalamic dys-
ence of a large cyst in the ventricular cavi- function, infections, repeated shunt failure,
ties, particularly in the fourth ventricle. and progression of the disease with arach-
Symptoms include headaches, nausea, vom- noiditis, ependymitis, ventriculitis and irre-
iting, somnolence, memory and behavioral versible tissue damage.
changes, and gait disturbance for several Inflammatory cysts in the fourth ventricle
months before presentation4,5,9,12. The neuro- pose a difficult problem because there is
logical examination may reveal decreased associated widespread granular ependymitis
alertness, papilloedema, and focal motor and ventriculitis. This leads to ventricular
neurological deficits, including corticospinal enlargement that may persist even after a
tract signs and frontal lobe motor apraxia. ventriculoperitoneal shunt (VPS) is placed
The latter is due to extensive bilateral lesions for the relief of the hydrocephalus7.
of long motor tracts originating from the Although there may be single or multiple
frontal lobes by the enlarging lateral ventri- involutional cysts in the fourth ventricle, in
cles. Also, ventricular expansion is maximal many cases there are no cysts detected by
in the frontal horns with consequent impair- neuroimaging or found during surgery.
ment of frontal lobe functions. If not treated,
these patients can decompensate and deteri-
orate abruptly9.
Communicating hydrocephalus from
basilar arachnoiditis and leptomeningeal
scarring
Symptoms due to both obstruction of
CSF flow and inflammation
This type of basilar meningeal cysticercosis
Most people who die from chronic complica- is discussed in Chapter 18.
tions belong to this category. When the larva
in the cyst dies, the involutional process and
inflammation turn an asymptomatic intraven- Radiological and Laboratory Diagnosis
tricular cyst into a symptomatic one. The invo-
lutional cyst liberates antigenic substances that The criteria for the diagnosis of IVNC are
generate an inflammatory reaction throughout based on clinical presentation, magnetic res-
the ventricular system, and a severe localized onance imaging (MRI) evidence of cystic
reaction of granular ependymitis that fixes the lesions containing the scolex, and histologi-
cyst capsule to the ventricular wall with cal demonstration of the parasite from the
strong adhesions and fibrosis that may pro- brain lesions or from the CSF. Since the clini-
duce irreversible blockade of the CSF circula- cal presentation of IVNC is by no means spe-
tion. The fourth ventricle is frequently cific, it is important to review the clinical
affected. The result is progressive hydro- history, laboratory findings and imaging
cephalus, increased ICP, and poor response to studies to arrive at a correct diagnosis.
(a)
(b) (c)
Fig. 20.2. (a) Sagittal T1-weighted MRI shows a large inflammatory (involutional, transitional) cyst in the
fourth ventricle. The mural nodule is visible. There is oedema of adjacent brain tissue. (b) Axial T1-weighted
post-contrast MRI shows an inflammatory cyst in the fourth ventricle with a ring-like enhancement. There is
oedema of adjacent brain tissue. (c) An axial fluid attenuation inversion recovery (FLAIR) MRI shows an
inflammatory cyst in the fourth ventricle, oedema in the surrounding brain tissue, and the mural nodule.
Anticysticercal drugs
Chronic hydrocephalus; viable cysts
Some investigators have advocated the use
Patients with chronic hydrocephalus and of anticysticercal drugs in conjunction with
increased ICP usually require a permanent VPS5,12 to decrease shunt failures and
VPS35. Open surgical or endoscopic removal destroy viable cysts. The use of praziquantel,
of the viable cysts should be done if they are an isoquinoline with broad anthelmintic
large, if they obstruct the CSF flow, if they activity, in IVNC is controversial, since ear-
complicate shunting, if they cause a mass lier studies have associated such therapy
effect despite shunting, and if the diagnosis with a poor outcome38. Both failures2,17,38–40,
is uncertain35. Viable cysts in the fourth ven- and successes5,41,42, with praziquantel have
tricle should be extirpated because by their been observed in the treatment of intraven-
mass effect, these cysts may cause herniation tricular cysts. The recommended dose is 50
even after VPS9. A transcortical approach is mg kg−1 day−1 for 14 days with concomitant
used for removal of cysts from lateral ventri- use of dexamethasone.
cles; a transcallosal approach for cysts in the There are several reports describing the
third ventricle; and a midline suboccipital successful treatment of intraventricular cysts
direct approach for cysts in the fourth ventri- with albendazole (Fig. 20.3a,b)2,43–45. In some
cle1,11,32. Bergsneider and Nieto (see Chapter series, intraventricular cysts disappeared
40) discuss the option of direct endoscopic within 3 months after this approach2,43–45.
removal of cyst/s without resort to VPS. Albendazole is used at a dose of 15 mg kg−1
The surgeon must consider the possibility of day−1 for 15 days. The daily dose is divided
cyst migration between the time of diagnosis and into three administrations, and dexametha-
craniotomy36. Migration of the targeted cyst must sone is given concomitantly. Two courses of
be ruled out by a neuroimaging procedure done medication are given 1 month apart.
immediately before surgery19,33. In cases of multi- Intermittent long-term steroid therapy may
ple cysts and multiple obstructions with locu- reduce shunt malfunction46.
lated hydrocephalus, there may be a need for The favourable response to treatment of
multiple shunt procedures, each draining a sepa- IVNC with either praziquantel or albenda-
rate compartment31. Patients with intraventricu- zole is by no means definite and may be a
lar cysts without hydrocephalus, or with only reflection of the natural history of the condi-
slight dilatation of the ventricles, require close tion. When the larva in the cyst dies as a
supervision in case shunting becomes necessary. result of anticysticercal therapy, there is an
inflammatory reaction similar to the one seen
with the natural death of the larva47,48. The
Chronic hydrocephalus; inflamed cyst local reaction with scarring and granuloma-
tous ependymitis may lead to an irreversible
VPS remains the mainstay of therapy of blockade of CSF flow due to a permanent tis-
inflamed IVNC. However, shunts are prone to sue damage. In addition, resolution with
complications in these patients. The most anticysticercal drugs may take a long period
common cause of dysfunction of VPS is of time, usually in months. During this
obstruction either by gelatinous material from period, the patient is at risk of developing
(a)
(b)
Fig. 20.3. (a) T1-weighted MRI shows an intraventricular cyst in the frontal horn of the right lateral
ventricle. (b) Same patient as in (a), 12 months later. There was a resolution of the cyst.
complications such as ependymitis and acute long-term sequelae49. Therefore, the use of
ventricular obstruction. For this reason, some anticysticercal therapy in IVNC continues to
authors question the effectiveness of anticys- be debated50. Collaborative clinical trials are
ticercal therapy in IVNC, even suggesting needed to evaluate specific medical treatment
that the treatment with anticysticercal agents of IVNC and to develop a better understand-
is associated with an increase in frequency of ing of the clinical course49.
(a)
(b) (c)
Fig. 20.4. (a) CT scan of a 46-year-old man shows intraventricular and parenchymal active cysts. (b) CT
scan, 11 months later shows resolution of the cyst. (c) One year later the patient presented with
increased intracranial pressure. CT scan showed non-communicating hydrocephalus.
some cases, the most likely reason is the increased ICP and meningoencephalitis.
obstruction of the CSF pathways by chronic Neuroimaging is the most important tool for
adhesions and thickening left by involu- the diagnosis of IVNC. The finding of cysts in
tional cysts. This emphasizes the need for different stages of evolution helps in the diag-
aggressive initial treatment in these patients. nosis. The treatment of IVNC is symptom
specific. Surgical treatment of acute hydro-
cephalus consists of ventriculostomy followed
Conclusions by permanent VPS. Dexamethasone alleviates
the increased ICP, cerebral oedema and
IVNC is a serious and disabling condition inflammation. In chronic hydrocephalus and
with obscure peculiarities in its natural his- intraventricular cysts, the selection of treat-
tory, grave complications, and a high rate of ment modalities such as VPS, surgical removal
poor outcomes. Active, viable intraventricular of the cysts, and anticysticercal therapy is a
cysts produce no reaction from the host, but subject that challenges the common sense,
can mechanically interfere with CSF flow, experience, and judgement of the treating
leading to complex clinical syndromes mainly physician. There are reports of successes and
because of obstructive hydrocephalus. These failures with the use of anticysticercal medica-
cysts can migrate freely in the ventricular sys- tion. The use of anticysticercal medications to
tem, giving rise to acute intermittent or per- hasten the involution of intraventricular viable
manent symptoms from hydrocephalus and cysts may trigger an inflammatory response
increased ICP. When the larva dies, there similar to the one seen with the natural death
occurs a local granulomatous ependymitis and of the parasite, with consequent increased fre-
generalized ventriculitis with hydrocephalus, quency of long-term sequelae.
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47. Spina-Franca, A., Nobrega, J.P.S. (1980) Neurocysticercose e praziquantel. Revista Paulista de
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48. Garcia, H.H., Gilman, R.H., Horton, J., et al. (1997) Albendazole therapy for neurocysticercosis: a
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49. Carpio, A., Santillan, F., Leon, P., et al. (1995) Is the course of neurocysticercosis modified by treat-
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50. Salinas, R., Counsell, C., Prasad, K., et al. (1999) Treating neurocysticercosis medically: a systematic
review of randomized, controlled trials. Tropical Medicine and International Health 4, 713–718.
9.60%
3.50% Cysticercosis
0.90% Others
Tumours
5.70%
Stroke
5.20% Infections
61.70%
Head trauma
3.90%
Perinatal insult
9.60%
Idiopathic
mon diseases in most developing countries. EEG findings have poor correlation with
Because of their high prevalence, a causal as symptoms and CT lesions in patients with
well as fortuitous relationship between the NC5,41–43. A positive correlation between CT
two conditions might exist3,34–36. lesions and localizing or lateralizing EEG
Seizures may occur at any evolutionary abnormalities has been reported for only
stage of the parasite. Acute seizures are more 15–30% of patients. Similarly, the correlation
frequent with the transitional form owing to between seizure type and EEG abnormalities
the inflammatory reaction in the vicinity of ranges from around 7% to 20%43.
cortically or subcortically located cysts. In Discrepancies between clinical localization
the active form, seizures have been attrib- based on seizure semiology and location of
uted to mechanical compression by cysticer- the lesion on neuroimaging is not uncom-
cal cysts2,27. We can theorize that risk of mon in patients with NC. Nevertheless,
seizure recurrence (i.e. epilepsy) probably some authors suggest that this reflects the
occurs in the inactive or calcified form of spread of seizure discharges37,42. In patients
NC37. This possibility has been attributed to with occipital-lobe epilepsy, an occipitotem-
residual perilesional gliosis that results in poral spread was demonstrated in those
chronic epileptogenic foci38. This theory, patients who had automatisms typical of
however, requires further confirmatory stud- temporal-lobe seizures, and suprasylvian
ies. Some authors have suggested that mild spread was demonstrated in those patients
inflammation, visible on contrast-enhanced who presented tonic or clonic motor mani-
MRI or CT, may persist in the calcified stage festations44. A non-causal relationship
of NC, and may be associated with an between epilepsy and cysticercosis in some
increased risk of recurrent seizures39,40. cases might explain these apparent discrep-
These authors theorize that the perilesional ancies37. Studies correlating epileptic foci
oedema surrounding calcified lesions due to and intracranial calcifications suggest that
NC is a persistent host-inflammatory calcifications themselves were not the origin
response provoked by antigens released of the epileptogenic lesion in at least 50% of
from the calcified lesions. However, in the cases36. Some authors tried to correlate
patients with multiple calcifications, it is not EEG with the cyst viability41. They found
clear why only some of the calcified lesions interictal EEG abnormalities in 28% of
would induce inflammation. patients with any form of NC, but no EEG
Electroencephalography (EEG) has been abnormalities in patients with inactive NC.
found to be abnormal in 30–50% of patients These authors suggested that perilesional
with seizures due to NC. It is assumed that gliosis might be insufficient to cause scalp
EEG abnormality in the inactive form of NC. are no controlled clinical trials to establish
Further prospective cohort studies, properly specific indications, definitive doses, and
designed to study ictal and interictal EEG duration of treatment2. A critical review of
abnormalities in patients with seizures, cor- the literature suggests that the studies upon
related with the different evolutionary stages which these assumptions are based are
of the parasite, may clarify the relationship flawed in terms of patient selection, assign-
between NC and epilepsy. ment to treatment, and selection and mea-
The coexistence of hippocampal atrophy surement of outcome variables. Many
and extrahippocampal pathological abnor- authors have appropriately criticized publi-
malities, such as cortical dysgenesis and glio- cations on this topic and have concluded that
sis, referred as ‘dual pathology’, has been no adequate studies of efficacy have been
reported in 5–30% of patients with medically reported (see Chapter 38)5,17,46,47. Other
refractory partial seizures33,45. Dual pathol- authors have warned that this therapy might
ogy implies that both lesions somehow inter- be harmful in some patients, particularly
act with each other and contribute to when cysts are in the subarachnoidal loca-
epileptogenesis through mechanisms still tion, because these drugs might lead to the
poorly understood. Some authors have also development of arachnoiditis, arteritis and
attributed hippocampal sclerosis to NC3,35. hydrocephalus48,49.
Patients with calcifications due to NC and A randomized clinical trial of treatment of
mesial temporal lobe epilepsy (hippocampal patients with newly identified active NC
sclerosis) became seizure-free after used oral prednisolone alone, praziquantel
anteromesial temporal lobectomy, without with prednisolone, or albendazole with
resection of the cysticercotic lesion, suggest- prednisolone49. At 6 months and at 1 year
ing the two phenomena are independent34. after treatment there were no differences in
The possibility of dual pathology related to the three treatment groups in terms of the
NC needs further clarification in prospective proportion of cases free of cysts, or the rela-
cohort studies. tive reduction in number of cysts. At 2 years,
Considering that epileptogenicity of cys- there was no difference in the proportion of
ticercotic lesions is probably low for residual cases free of seizures over the entire follow-
calcifications, one should consider the up period. Based on these results, it appears
chance association between the two condi- that treatment with anticysticercal drugs
tions34,35. Unequivocal evidence of causal does not modify the prognosis of seizures in
relationship between NC and epilepsy could patients with NC. This study addressed
be deduced from correlation between clini- questions about to what extent and in which
cal, EEG, and imaging data. This evidence patients, treatment with either praziquantel
should be demonstrated in patients with sin- or albendazole is indicated. The improve-
gle or multiple NC lesions shown by imag- ment attributed to anticysticercal drugs in
ing studies, in whom video-EEG monitoring previous studies may be related to the lack
displays ictal and interictal abnormalities of appropriate controls and is likely to be a
correlated with type of seizures. The associa- reflection of the natural history of the condi-
tion could be confirmed and the level of risk tion. Placebo-controlled trials for NC treat-
determined through appropriate epidemio- ment that are under way should clarify these
logical studies. uncertainties. It has been suggested that
seizure control in patients with NC is
improved and that the chance of remaining
Effect of Anticysticercal Treatment on seizure-free after the withdrawal of
Epilepsy antiepileptic drug (AED) is greater after a
course of anticysticercal drugs when com-
Despite the first reports regarding treatment pared with seizure control in those in whom
for NC with anticysticercal drugs such as the disease is left untreated10,11. However,
praziquantel and albendazole being pub- these studies do not distinguish between
lished more than 15 years ago2, to date there acute symptomatic seizures, chronic recur-
rent seizures that antedate the infection and ment plus the anticysticercal drug, albenda-
patients with newly diagnosed recurrent zole, 15 mg kg1 day1, for 8 days (44
unprovoked seizures. These distinctions are patients). Thirty patients (39%) experienced
crucial in order to interpret results of such seizure recurrence; however, when using
interventions. Kaplan–Meier survival analysis, 60% of cases
experienced a seizure recurrence in the 5-year
period following a first acute symptomatic
Prognosis of First Seizure due to NC seizure. Half of these recurrences occurred in
the first year. The estimated recurrence was
There are inconsistent data on the risk of fur- 20% at 6 months, 29% at 12 months, 35% at 24
ther seizures in patients with first seizure due months, and 60% at 48 months. This high
to NC. In most studies, the sample size has recurrence is in part related to recurrence of
been small, assessment has been carried out acute symptomatic seizures. Among a large
retrospectively, and optimal analytical meth- array of variables that were assessed as poten-
ods have not been used. Some authors report tial risk factors for recurrence, only persistence
that NC patients with acute symptomatic of abnormalities on follow-up CT scan was
seizures have a good prognosis in terms of predictive of seizure recurrence. Recurrence
remission of seizures3,7,12,13; others report that risk ranged from 22% in patients in whom
most patients have a high risk of seizure cysts disappeared, to 78% in patients showing
recurrence, and suggest that prognosis no change in number of cysts. There were no
improves after anticysticercal treatment10,11. significant differences in the Kaplan–Meier
In a prospective cohort study, patients with curves of recurrence when treatment groups
a first seizure and evidence of an active or were compared (Fig. 21.2). It appears that anti-
transitional form of NC were enrolled and fol- cysticercal treatment did not modify the risk
lowed up for up to 5 years to identify the risk of seizure recurrence. A similar seizure recur-
of subsequent seizures49,50. Additional analysis rence risk (37%) has been reported in patients
was performed after stratification by treat- with single enhancing CT lesions42. This
ment of the acute condition: symptomatic relapse rate is similar to that reported in other
treatment alone using AED(s) and pred- studies of seizure recurrence in cases with a
nisolone (33 patients), or symptomatic treat- first acute symptomatic seizure35,51,52.
1.1
1.0
Cumulative probability
0.9
0.8
0.7 Anticysticercal
treatment
0.6
Yes
0.5 Yes-censored
0.4 No
0 10 20 30 40 50 60 No-censored
Follow-up in months
Fig. 21.2. Probability of seizure recurrence after a first seizure in 77 patients with neurocysticercosis as
a function of anticysticercal treatment. (Source: reference 32.)
There are no guidelines regarding the even if they occur many months after pre-
duration for which AEDs should be contin- sentation. It is appropriate to monitor cyst
ued following an acute NC episode. Some activity with CT scanning and to continue
clinicians routinely continue AEDs for 1 year AEDs until resolution of the acute lesion.
but shorter and longer intervals have been After this time, AEDs may be discontinued.
recommended12. The antiseizure medications Seizures occurring in individuals after reso-
currently used have no antiepileptogenic lution of oedema and resorption or calcifica-
effect but do effectively prevent acute symp- tion of the degenerating cyst should be
tomatic seizure recurrence53. One assumes considered unprovoked and, in this situa-
that the risk of seizures is substantial as long tion, long-term AEDs are warranted (Fig.
as there is an active ongoing process as char- 21.3). These are individuals who truly have
acterized by persistence of oedema around epilepsy42. Seizure recurrence among those
the degenerating lesion. Because of this, we with cyst resolution was about 20%, a figure
feel CT scan is a useful tool for these treat- in accord with studies evaluating unpro-
ment decisions. Seizures in the context of voked seizure risk among individuals with
oedema and a degenerative lesion should be structural brain abnormalities and acute
considered to be acute symptomatic seizures, symptomatic seizures25,51,52.
Degenerative (transitional)
and/or active cysts Only calcification
Initiate AED
Initiate AED
Seizure
No seizure
recurrence
Cyst(s) resolved recurrence
Cyst(s) not
but seizure for 1 year
resolved with or
recurrence
without seizure
recurrence
Fig. 21.3. Suggested protocol for antiepileptic drugs for patients with first seizure due to
neurocysticercosis.
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22 Cerebrovascular Manifestations of
Neurocysticercosis
Clinical Features
Large territorial infarction
In common with other non-atherosclerotic
vasculopathies, cysticercotic arteritis is com- Occlusion of large blood vessels including the
monly encountered in young individuals. The middle and anterior cerebral arteries and
mean age at diagnosis was 36 years in a series even the internal carotid artery may occur in
of 65 patients described by Cantú and NC13,15,16,25. Large infarctions are infrequent in
Barinagarrementeria7. Generally, individuals comparison to deep small infarcts. Large ves-
with stroke due to NC have no underlying sel arteritis results from inflammatory degen-
vascular risk factors. Cysticercotic arteritis can eration of closely located cysticerci. On
involve the small, medium and large sized occasion, large vessel arteritis and consequent
vessels. Small vessel occlusion with conse- infarction is precipitated by an inflammatory
quent lacunar infarction is most frequent. response to the administration of anticysticer-
cal drugs9,15. The latter should, therefore, be
administered with caution in those patients
Lacunar syndromes with extensive cyst load, located particularly
in relation to major arteries.
The term ‘lacunar syndromes’ originally
referred to clinical features associated with
small infarcts resulting from atheromatous or Haemorrhagic stroke
embolic occlusion of penetrating branches of
large arteries. It was later realized that these Subarachnoid, parenchymal and intracystic
syndromes might also result from inflamma- haemorrhage may occur in the setting of
tory arteriopathies. In the particular context NC3,25,26. These complications are extremely
of NC, Barinagarrementeria and Del Brutto rare. Subarachnoid haemorrhage may result
described seven patients with lacunar syn- from the rupture of a mycotic aneurysm that
dromes due to NC10. The patients presented develops in relation to a racemose cyst
with typical lacunar syndromes including adherent to an artery (Fig. 22.2)25,26.
pure motor hemiparesis, ataxic hemiparesis
and sensorimotor paralysis10,24. Lacunar
infarctions were located in the posterior limb Clinicopathological Correlations
of internal capsule or corona radiata on com-
puted tomography or magnetic resonance Occlusive stroke characteristically occurs in
imaging (CT/MRI) (Fig. 22.1a–c). Four of the setting of meningeal racemose cysticerco-
these patients had evidence of a racemose sis25. Among various locations and stages,
cyst in the ipsilateral suprasellar cistern. It stroke is more commonly seen with involve-
was surmised that the cyst and the surround- ment of the basal cisterns and during the
ing meningeal inflammatory reaction and inflammatory stages as recognized by pleocy-
subsequent arachnoiditis led to occlusion of a tosis and/or increased protein upon cere-
penetrating branch of the proximal segment brospinal fluid (CSF) examination. Very
of the middle cerebral artery (Fig. 22.1a–c). rarely, arterial occlusion may occur in the set-
Fig. 22.1. (a) Axial T2-weighted MRI scan shows a cystic lesion in the left suprachiasmatic cistern,
adjacent to the middle cerebral artery. (b) Axial T2-weighted MRI scan reveals cerebral infarction in the
left middle cerebral artery territory secondary to vasculitis associated with a suprachiasmatic cyst. (c)
Coronal T1-weighted Gd-MRI scan, taken several months after stroke onset, shows a persistent focal
enhancement of the cyst and the old cerebral infarction in the ipsilateral corona radiata.
ting of parenchymal NC16. Besides, the occur- In the latter group, epilepsy and intracranial
rence of stroke is also determined by the hypertension were the most frequent present-
extent of arachnoiditis. In a study of 65 ing manifestations. Headache in association
patients with cerebrovascular complications with cerebral infarction occurred in about
of NC, Cantú and Barrinagarrementeria one-third of patients with focal arachnoiditis.
found that those with focal arachnoiditis had It is possible to predict the occurrence,
a sudden onset of the disease, implying the nature and severity of cerebrovascular involve-
occurrence of a symptomatic cerebral infarc- ment by studying the distribution of cysticercal
tion7. In comparison, only 20% of those with disease and the severity of concomitant chronic
diffuse arachnoiditis had an apoplectic onset. arachnoiditis7. When cysts are confined to a
Fig. 22.2. Mycotic aneurysm of the middle cerebral artery formed in relation to a degenerating cysticercus after
surgical removal of both. (Source: Svetlana Agapejev, São Paulo, Brazil.)
Fig. 22.3. (a) Coronal T1-weighted Gd-MRI scan demonstrates diffuse enhancement of the basal cisterns,
extending to the proximal portion of the Sylvian fissures; small cysticerci are evident. (b) Lateral left angiogram
discloses the common carotid artery with segmental stenosis of the middle cerebral artery (arrow and arrowhead).
Fig 22.4. (a) Coronal T1-weighted Gd-MRI scan shows numerous cysticerci in the basal cisterns and both
Sylvian fissures, with only a mild meningeal enhancement. (b) Corresponding left anteroposterior carotid artery
angiogram reveals a segmental narrowing of the trunk of the middle cerebral artery (arrow).
22.3b and 22.4b) and posterior cerebral arter- 56 (86%). The intensity of inflammation
ies. The latter were involved in more than depicted by the CSF study correlated with
half of the patients. Single artery involvement the severity and extent of arteritis and the
was noted in eight patients. However, angio- degree of meningeal enhancement upon Gd-
graphic abnormalities were noted in two MRI, so that patients with diffuse basal
arteries in four patients and three or more involvement upon Gd-MRI exhibited severe
arteries in three patients, respectively. A dif- and persistent CSF abnormalities.
fuse meningeal enhancement was observed
by gadolinium (Gd)-MRI in five out of
seven patients with involvement of more MRI (including Gd-MRI)
than one artery upon angiography.
Interestingly, we observed asymptomatic Gd-MRI outlines the presence and distribu-
cerebral arteritis in 20% of the patients with tion of cysts, character and extent of arach-
subarachnoid cysticercosis. noiditis and the number and location of
cerebral infarctions. In our series of 65
patients with cerebrovascular complications,
CSF examination MRI detected one or more cyst(s) in the sub-
arachnoid space, commonly in the basal or
CSF abnormalities correlate with the location Sylvian cisterns (Fig. 22.3a) in the neighbour-
of cysticercus and are more commonly seen hood of the ischaemic area in 54 (83%)7.
in the setting of meningeal-racemose cys- Uncommonly, Gd-MRI may not visualize
ticercosis. Therefore, as a rule the CSF study cysts but reveal only intense enhancement of
is abnormal in individuals with cysticercotic the meninges. Based on the degree and
arteritis. We noted CSF abnormalities in 58 extent of meningeal enhancement upon Gd-
(89%) of 65 patients with documented cys- MRI, chronic arachnoiditis associated with
ticercotic arteritis7. The abnormalities cysticercotic arteritis can be categorized as
included lymphocytic pleocytosis (57; 88%), focal or diffuse28. Focal arachnoiditis is iden-
increased protein levels (44; 68%) and hypo- tified by contrast enhancement restricted to a
glycorrhagia (24; 37%). CSF eosinophilia was single cerebral cistern, whereas diffuse
noted in 33 (51%) patients, while immuno- arachnoiditis is characterized by enhance-
logical tests for cysticercosis were positive in ment involving several cerebral cisterns.
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Fig. 23.1. Extradural spinal cysticercosis. CT myelographic (a) and histological (b) appearances.
(Reproduced with permission from reference 11.)
Fig. 23.2. Intradural extramedullary spinal cysticercosis. T1 sagittal (a) and T2 axial (b) and sagittal (c)
MRI sections demonstrating that intradural extramedullary cysticercosis represents an extension of
cranial subarachnoid cysticercosis into the spinal canal. (Reproduced with permission from reference
27.) (Source: E. Citfci and A. Hayman, Baylor, Texas, USA.)
Fig. 23.3. T2 (a) and T1 (b) and post-gadolinium (c) sagittal MRI showing the subarachnoid space filled
with serpentine material giving a high signal on T2 and low signal on T1 images. (Reproduced with
permission from reference 23.)
between the two conditions. Hydromelia tions, while the inner surface has a smooth
appears hypointense on T2 glistening texture30. A scolex may or may not
sections because of mobility of fluid in the be discernable. Calcific knobs may be seen39.
cavity. Other cystic lesions that may be Microscopically, there is surrounding gliosis
considered in the differential diagnosis and granulation tissue consisting of plasma
of intramedullary cysticercosis include pri- cells and foamy macrophages29,30,40.
mary and secondary neoplastic cysts,
syringomyelia and hydatid cysts. Corral et al.
reported MRI appearance of IMSC in a Management and outcome
patient with multiple cerebral cysticercosis
who was administered albendazole for treat- Until recently, surgery was advocated as stan-
ment of cerebral cysts34. Spinal MRI revealed dard treatment for IMSC. It was often diag-
focal spinal cord enlargement, oedema and nosed at surgery30,31 or rarely at necropsy5
irregular enhancement with no definite cystic because myelographic appearances of this con-
lesion. The authors surmised that these dition were non-specific. Postoperative neuro-
appearances were of an inflammatory logical outcome varied. As a general rule, there
parenchymal reaction to a dead cyst. It may was partial recovery over few months with
be interesting to speculate a cysticercal aetiol- some residual permanent neurological deficit.
ogy in some of the cases of myelopathies The availability of MRI offered the unique
with clinical and MRI features of non-specific opportunity of identifying intramedullary
myelitis in cysticercus endemic areas. cysts before surgery and opened prospects for
non-surgical management. To our knowledge,
there are at least three reports of IMSC treated
Ancillary investigations with albendazole for about a month34,37. The
outcome has been extremely favourable in
In contradistinction to IDEMSC, which is terms of neurological recovery in all three
usually accompanied by intracranial involve- cases. It may be necessary to co-administer cor-
ment, it is not uncommon for IMSC to occur ticosteroids in order to manage inflammatory
as an isolated lesion with no clinical or radio- myelopathic exacerbations related to anticys-
logical evidence of cerebral involvement. ticercal treatment. In view of the rarity of the
However, the presence of cerebral cysticerco- condition, an accurate assessment of the role of
sis is a supportive feature in the preoperative non-operative management of IMSC will per-
diagnosis of IMSC. Since IMSC is an oligo- haps take time.
cystic form of disease, stool evaluations for
Taenia solium, blood eosinophilia, soft tissue
calcifications and CSF examination are rarely Sellar Cysticercosis
contributory to the diagnosis5,22,32,39,40.
The pituitary fossa and its neighbourhood
are an infrequent site for cysticercosis.
Pathology Besides a series of eight pathologically veri-
fied cases reported by Del Brutto and col-
Morphological aspects of IMSC have leagues41, there have been isolated case
been studied at necropsy and surgery. The reports of the condition in literature42–45.
cyst causes focal, smooth enlargement of the
spinal cord. There may occur thickening
and adhesions of the overlying lep- Clinical features
tomeninges5,29,31. The glistening white cap-
sule of the cyst can be seen after a vertical
Asymptomatic sellar cysts
myelotomy. The cyst is usually non-adherent
and can be dissected from the cord without On occasion, sellar cysts may be asympto-
difficulty29,30,40. The fluid contained in the matic and present with sellar enlargement on
cyst may be turbid or xanthochromic29,30. The skull radiographs2. Incidental sellar cysts
outer surface contains fine hair-like projec- have been reported at necropsy2,46.
Table 23.1. Differentiating features between sellar cysticercosis and pituitary adenoma.
trast. Multiplanar MRI is useful in demon- boy with CT features of cerebral cysticerco-
strating the anatomical extent of the cystic sis48. The myoclonus resolved, as did the CT
lesion. Sagittal and coronal sections clarify abnormalities after two courses of praziquan-
its relationship to the optic chiasma and may tel, in addition to sodium valproate. Otero et
demonstrate arachnoiditis. al. reported the development of complex par-
tial seizures and an acquired language disor-
der in a previously normal child at age 649.
Laboratory diagnosis The child had comprehension deficits, literal
and verbal paraphasias and telegraphic spon-
CSF examination was normal in five of eight taneous speech. Electroencephalography
patients studied by Del Brutto et al. All five revealed sharp and slow waves arising from
patients had isolated sellar cysticercosis. the left centrotemporal region. MRI revealed a
Serological studies were also non-contribu- small subarachnoid cysticercus cyst situated
tory in these patients41. deep in the left Sylvian fissure. The authors
postulated that the unique location of the cyst
and the age of the patient were responsible
Management for the Landau–Kleffner-like presentation.
The patient’s condition, including seizures
Surgical resection of the cyst is the standard and the language dysfunction, improved after
management of sellar cysticercosis. A trans- a course of albendazole. Chung et al. gave an
frontal approach is usually advocated in account of chronic intractable left mesial tem-
view of suprasellar growth of the cysts and poral lobe epilepsy of 20 years’ duration, in a
the frequent association with optochiasmatic middle-aged man50. Imaging studies revealed
arachnoiditis41. However, if MRI studies rule a calcified cysticercal cyst in the left medial
out suprasellar growth and arachnoiditis, a temporal region in addition to ipsilateral hip-
transsphenoidal approach may be under- pocampal atrophy. The patient was seizure-
taken42. The prognosis for recovery of visual free after standard left temporal lobectomy.
and endocrine function is dismal. None of the Histological sections revealed degenerated
patients in the series reported by Del Brutto et cysticercus and scolex embedded in the hip-
al. showed good postoperative recovery in pocampus in addition to neuronal loss. The
visual function41. This is in contrast to the authors postulated that the calcified cysticer-
good prognosis for recovery of visual function cus cyst was responsible for the peculiar
after surgery for pituitary adenomas, where epileptological condition. Finally, there is doc-
complete recovery of vision may be noted in umentation of periodic lateralized epilepti-
up to 20% and partial recovery in 80% of form discharges in massive parenchymal
patients47. It may be surmised that optochias- cysticercosis51,52. These rare electroencephalo-
matic arachnoiditis, which often accompanies graphic abnormalities are attributed to the
sellar and suprasellar cysticercosis, is responsi- inflammatory reaction in the brain to cystic
ble for poor postoperative outcome of visual degeneration either spontaneously or as a
function. There is no evidence so far that result of anticysticercal treatment.
either praziquantel or albendazole help in res-
olution of sellar cysticercosis.
Extrapyramidal Disorders
Uncommon Epileptic Syndromes
Few of the earliest descriptions of NC in lit-
Partial or generalized tonic clonic seizures erature alluded to extrapyramidal manifesta-
are commonly seen in a majority of the cases tions. Bickerstaff recounted the case of a
with parenchymal cysticercosis. Uncommon 51-year-old housewife of an Indian soldier,
epileptic syndromes have been reported in who developed progressive choreoathetosis
few cases. Puri et al. described stimulus- along with mental impairment, a clinical pic-
sensitive generalized myoclonus in a young ture resembling Huntington’s chorea53.
Necropsy revealed cysticerci in both caudate one report of such a case, trauma from a
and lentiform nuclei. There is a paucity of vehicular accident led to rupture of cysts
reports of extrapyramidal disorders in recent and sudden death61.
literature. Nevertheless, parkinsonism, uni-
lateral tremors, chorea, facial myokymia and
blepharospasm have been described in Conclusions
NC6,53–56. Racemose cysticercosis of the pos-
terior fossa may present with ataxia57. The presenting manifestations of T. solium
Bickerstaff described the occurrence of pro- cysticercosis are primarily related to the loca-
gressive ataxia in a 50-year-old woman58. He tion of cysticerci. Therefore, when cysticerci
reported operative findings of ‘a delicate lodge in remote areas within the central ner-
elongated structure resembling a bunch of vous system, they produce uncommon mani-
grapes lying over and around the lower festations. Among the protean manifestations,
brainstem and hanging on to the upper cer- spinal cysticercosis, sellar cysticercosis and
vical region’. Ataxia may be intermittent as uncommon epileptic and extrapyramidal syn-
with cysts of the fourth ventricle, where dromes are reviewed.
intermittent obstruction (Bruns’ syndrome) Spinal cysticercosis is classified in to
is the cause of isochronal symptoms57. It may extradural spinal cysticercosis, intradural
be asymmetric, when it results from race- extramedullary (IDEMSC) (most common),
mose cysts of the cerebellopontine angle58. intramedullary (IMSC) and mixed forms.
IDEMSC is commonly accompanied by
intracranial cysticercosis; it is believed to
Lingual Cysticercosis result from the downward migration of
intracranial subarachnoid-racemose cys-
Lingual cysts are usually observed in the ticerci. When the spinal cysts degenerate,
context of disseminated cysticercosis59. they lead to the clinical syndrome of a
Rarely, cysticercosis may occur as an iso- myeloradiculopathy involving the cervical
lated tongue mass59. The differential diagno- spinal cord most commonly. Intramedullary
sis in such instances includes lingual cysticerci occur in isolation with preference
carcinoma, haemangioma, mucocoele, papil- for the thoracic spinal cord. MRI is the imag-
loma and lingual thyroid. ing modality of choice for spinal cysticerco-
sis. The treatment of IDEMSC is surgical.
Surgery is also advocated for IMSC, though
Sudden Death reports of successful medical treatment are
now accumulating.
Sudden death in otherwise asymptomatic Sellar cysticercosis of the racemose vari-
persons may occur due to massive antigenic ety presents with visual and endocrine dis-
release from ruptured cysts in the brain turbances. The diagnosis is established by
parenchyma and surrounding meninges60,61. MRI and the treatment is surgical. Several
The massive antigenic release may result in other uncommon manifestations reviewed
a severe inflammatory response in the brain here often present a diagnostic and thera-
as well as systemic anaphylactic reaction peutic challenge to the treating physician
with pulmonary and visceral oedema. In both in endemic and non-endemic regions.
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Vedantam Rajshekhar
242 V. Rajshekhar
244 V. Rajshekhar
of the lesion was sampled in the stereotactic the histological diagnoses in both groups were
biopsy and rest of the lesion was left in situ. identical, revealing a cysticercus or parasitic
These 15 patients constituted Group A and granuloma in both. There were no tuberculo-
their lesions were monitored and followed mas or neoplasia in either group. Thus it was
up upon CT. Finally, 15 consecutive patients abundantly clear that the reason for persis-
with similar clinical and imaging characteris- tence was not a difference in aetiology but a
tics (Group B) had their lesions excised. variable natural history of the SCG in different
Follow-up CT monitoring in 12 of 15 patients individuals. Thus we argued that persistent
in Group A (three were lost to follow-up) SSECTLs need not be treated any differently
revealed disappearance in six, calcific residue from those that resolved early, i.e. with AEDs,
in five and reduced size in one. This observa- provided that patients did not have new
tion confirmed the fact that the lesions in this symptoms or signs of progressive neurological
larger homogeneous group of 30 patients deficit or raised intracranial pressure.
were disappearing SSECTLs. The histology of
the 15 lesions in Group B would therefore
indicate the pathology of the disappearing SSECTLs within the Perspective
SSECTLs. The pathology of the lesions in of Neurocysticercosis
Group B has been presented above, i.e. 12 of
the 15 biopsies revealed a cysticercus or a Ideally, the cysticercus granuloma should
parasitic granuloma and the rest, residue of have been an active aetiological considera-
an inflammatory lesion. Therefore, we tion in the case of SSECTLs that resolve
believe that this provided adequate proof spontaneously. The appearance of the cys-
that the ‘disappearing’ SSECTL is an SCG. ticercus granuloma on CT was known to be
identical to that of the SSECTL. Some of the
authors who had labelled SSECTL as ‘micro-
Problem of Persistent Lesions tuberculomas’ also commented upon this
similarity1,2,19. Furthermore, spontaneous
Sethi et al. noted resolution of the CT lesion in resolution of cysticercus granulomas has
all of their patients after an interval of 6–24 been adequately documented20–22. Punctuate
weeks (with AEDs alone)11. Adopting this calcifications that are sequelae of SSECTL
time frame, several physicians managing these were known to occur in NC well before spe-
patients with AEDs alone noted that SSECTLs cific therapy for cysticercosis was intro-
often persisted upon follow-up CT, performed duced. Finally, seizures are the commonest
3 months later. Moreover, several individuals manifestation of NC23. All the above features
with persistent lesions continued to have suggest that a cysticercus granuloma is a
symptoms. The management of these persis- likely aetiology for the SSECTL. Several
tent lesions posed a challenge because it was authors, however, dismissed cysticercosis as
commonly believed that disappearing a cause for SSECTL for one or more rea-
SSECTLs that resolved within about 3 months sons2,11,14,19. The three commonly mentioned
were different in aetiology from SSECTLs that reasons included: (i) cysticercosis is uncom-
were persistent beyond this time frame. It was mon among Indians; (ii) it is rare for NC to
not uncommon for physicians to resort to ATT present as a solitary lesion; and (iii) a cys-
in individuals with persistent lesions because ticercus granuloma would not be expected to
of their belief that persistent lesions were resolve spontaneously. Counter-arguments
likely to be tuberculomas. We looked at the to these are: (i) cysticercosis is endemic in all
histology of ‘persistent’ and ‘fresh’ lesions in parts of India; (ii) the myth that solitary cys-
25 consecutive patients with SSECTL18. The ticercal lesions were rare was derived from
duration of symptoms was less than 12 weeks data from the Western hemisphere; and (iii)
(3–12 weeks) in six patients and ranged from 4 finally, cysticercosis can resolve sponta-
months to 5 years in 19 patients. Both groups neously. Several authorities exclude a cys-
were found to be essentially similar in their ticercal aetiology for the SSECTL on the
clinical and imaging attributes. Importantly, premise of a negative serological test.
However, it is worth mentioning that sero- form’ and noted that they carried a better
logical tests for cysticercosis including both prognosis than other forms of NC31.
the ELISA and enzyme-linked immunoelec-
trotransfer blot (EITB) have poor sensitivity
in patients with SCG (see Chapter 33)24,25. Diagnostic criteria for SCG
Therefore, a negative serological test has no
relevance in the diagnostic scheme of We evolved a set of diagnostic criteria for an
SSECTL. initial presumptive diagnosis of SCG upon
presentation (Table 24.1)32,33. These criteria
were derived from clinical and CT observa-
Reports of SSECTL in NC literature tions in patients with histologically proven
SCGs and solitary small tuberculomas. The
Early reports of the CT appearance of cere- criteria were evaluated and validated
bral cysticercosis did not mention solitary prospectively and proved to be extremely
granulomas26. Zee et al. first drew attention reliable in predicting the diagnosis of SCG in
to this form of NC in 198027. Byrd et al. in Indian patients with seizures. We studied
their report on CT appearances of cerebral 401 patients presenting with seizures and an
cysticercosis, described a group of lesions, SSECTL. Of these, 215 fulfilled all the criteria
which were mostly solitary and enhanced for the diagnosis of a SCG. A final diagnosis
uniformly (the so-called disc lesions)28. was considered to have been confirmed in
These lesions measured between 10 mm and 197; 16 patients were excluded due to inade-
20 mm in size and did not produce any mass quate follow-up. A false-positive diagnosis
effect. Most of patients harbouring these of SCG was made in only two patients; one
solitary lesions presented with seizures. had metastatic disease and the other had
Also, in 1983, Minguetti and Ferriera pyogenic abscess. A false-negative diagnosis
alluded to an entity of ‘single acute lesions’ was made in one patient with SCG who had
measuring less than 20 mm in size, in severe oedema causing a midline shift and
patients presenting with seizures29. In 1988, therefore underwent excision of the lesion.
Mitchell and Crawford described lesions All eight solitary tuberculomas in our study
which were obviously similar to SSECTL, in could be clearly distinguished from SCG on
children and suggested that these were a the basis of the diagnostic criteria. Overall
distinctly benign form of NC30. They the diagnostic criteria had a sensitivity of
labelled these lesions as ‘acute lesions’. 99.5%, specificity of 98.9%, positive predic-
More recently, in 1995, Del Brutto referred to tive value of 99% and negative predictive
these lesions as ‘single acute encephalitic value of 99.5%.
Table 24.1. Clinical and computed tomography (CT) criteria for diagnosis of solitary cysticercus
granuloma (SCG).*
A. Clinical criteria
1. Clinical presentation with seizures
2. Absence of any evidence of a progressive neurological deficit
3. Absence of any features of persistent raised intracranial pressure
4. No clinical evidence of any systemic disease.
B. CT criteria
1. Solitary lesion
2. The lesion should measure less than 20 mm in maximal dimension
3. The lesion should enhance after contrast injection
4. There may or may not be oedema associated with the lesion but it should not be severe enough to
produce a shift of the midline structures.
246 V. Rajshekhar
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Antiepileptic drug(s)
(AED(s))
Clinical monitoring
Serological assay for
cysticercus antibodies
(ELISA/EITB)
Repeat CT scan after 6 months
Continue AEDs
Clinical monitoring
Repeat CT scan
after 6 months
Continue AED(s)
Taper AED(s) Clinical and CT
monitoring
Fig. 24.3. Management algorithm for patients presenting with single, small enhancing CT lesion
(SSECTL).
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tion of a distinct form of neurocysticercosis with a benign prognosis. Journal of Neurology,
Neurosurgery and Psychiatry 58, 247–249.
32. Rajshekhar, V., Haran, R.P., Prakash, S., et al. (1993) Differentiating solitary small cysticercus granu-
lomas and tuberculomas in patients presenting with epilepsy: clinical and computerized tomo-
graphic criteria. Journal of Neurosurgery 78, 402–407.
33. Rajshekhar, V., Chandy, M.J. (1997) Validation of diagnostic criteria for solitary cerebral cysticercus
granuloma in patients presenting with seizures. Acta Neurologica Scandinavia 96, 76–81.
250 V. Rajshekhar
34. Rajshekhar, V., Chandy, M.J. (2000) Solitary Cysticercus Granuloma: the Disappearing Lesion. Orient
Longman, Chennai, India.
35. Rajshekhar, V., Chandy, M.J. (1996) A comparative study of contrast computerized tomography and
magnetic resonance imaging in patients with solitary cysticercus granulomas and seizures.
Neuroradiology 38, 542–546.
36. Rajshekhar, V., Chandy, M.J. (1994) Enlarging solitary cysticercus granulomas. Journal of
Neurosurgery 80, 840–843.
37. Rajshekhar, V. (1993) Albendazole therapy for persistent, solitary cysticercus granulomas in patients
with seizures. Neurology 43, 1238–1240.
38. Rajshekhar, V. (1998) Incidence and significance of adverse effects of albendazole therapy in patients
with a persistent solitary cysticercus granuloma. Acta Neurologica Scandinavia 98, 121–123.
39. Rajshekhar, V. (2000) Severe episodic headache as the sole ictal presentation of solitary cysticercus
granuloma. Acta Neurologica Scandinavia 102, 44–46.
40. Garg, R.K., Kar, A.M. (1997) Episodic headache in a non-epileptic patients having disappearing sin-
gle (ring enhancing) CT lesion. Neurology India 45, 110–111.
J.M.K. Murthy
upon the inflammatory response of the where SCG is prevalent, the diagnostic predic-
brain. The slow degeneration of the cyst tive value of seizure clusters seems to be very
probably acts as a constant source of antigen high. In our study, the probability of a patient
to induce the host immune response and with seizure clusters at the initial presentation
may be an important factor responsible for or during the course, harbouring this lesion
recurrence of seizures5. was 88% (J.M.K. Murthy, Hyderabad, unpub-
lished data). Clinical and radiological criteria
for SCG have been reviewed by Rajshekhar in
Solitary Cysticercus Granuloma and Chapter 24. These criteria are specific and sen-
Seizures sitive. They have been validated in a prospec-
tive study involving 401 patients presenting
Seizures may be isolated or recurrent and with seizures and a solitary mass lesion on CT;
may occur in clusters. The reported fre- of these 215 had SCG. The criteria had a sensi-
quency of isolated seizures varies from tivity of 99.5%, specificity of 98.9%, and posi-
17.6% and 65%5,12,13 and that of a seizure tive predictive value of 99% and a negative
cluster varies between 20% and 80%5,14,15. predictive value of 99.5%.
After the initial seizure, patients may not
experience more attacks for several weeks to
months, and at times for several years, only Factors that Influence Seizure
to have a recurrence later. Breakthrough Outcome
seizures, i.e. seizures that occur after
antiepileptic drug (AED) treatment has Natural course
begun but before achieving remission, are
common in patients with SCG13,16. In the The natural history of the SCG can take one
author’s series, 37% of patients had break- of two courses: (i) it resolves entirely or (ii) it
through seizures5. Rarely, status epilepticus leaves a punctate calcification as residue. The
can be the presenting feature; its reported duration or time of resolution of the lesion is
incidence in different series varied between quite variable, from a few weeks to more
0.07% and 13%5,17,18. Seizures can be of any than a year20,21. A recent long-term follow-up
type. Simple or complex partial seizures with study of the natural history of the CT lesion
or without secondary generalization are in patients with SCG suggests that within 6
most common and have been reported in months of initial presentation over 70% of
70–88% of patients5,14,16,19. Often these lesions would show some degree of resolu-
patients present with partial onset or gener- tion and 54% of lesions would resolve com-
alized tonic–clonic motor seizures with no pletely22. The author’s experience, based on
localization. Seizure semiology depends on the interval between initial presentation and
the anatomical location of the lesion. resolution of the CT lesion, suggests that
Discordance between clinical localization these lesions can be divided into two types:
based on seizure semiology and location of (i) ‘rapid resolvers’, lesions that resolve
the lesion on neuroimaging is not uncom- within few weeks to months, and (ii) ‘persis-
mon. Patients with SCG may exhibit some ters’, lesions that resolve over several
postictal neurological deficit lasting for few months to years. Symptoms in patients with
minutes or even weeks. persistent lesions are often phasic. Seizures
may cease for several months or years, but
recur later. No characteristic CT or magnetic
When to suspect a diagnosis of SCG resonance imaging (MRI) morphological fea-
tures distinguish between the two types of
Patients with SCG present with partial or lesions. In the author’s study, a demonstra-
unlocalized tonic–clonic seizures with no ble mural nodule on CT was associated with
obvious cause. Seizure clusters at presentation high rates of seizure recurrence and longer
or during the course of illness occur in a sig- disease duration23. Histological studies cor-
nificant proportion of patients. In the regions roborate that the mural nodule on CT or MRI
corresponds to the scolex and is a pathog- those for any other remote symptomatic
nomic sign of active cysticercosis24,25. It is epilepsy. Of the 97 patients followed by
possible that some of the lesions with this CT Murthy and Reddy23, for 7 years, 71.5%
morphology may take several months to (95%CI 53.7–85.4%) of patients achieved a 3-
degenerate. The presence of a slowly degen- year seizure remission and 66% (95%CI
erating cyst presumably acts as a constant 32.4–88.2%) achieved a 5-year remission.
source of antigen to induce host inflamma- Patients had a high rate of breakthrough
tory reaction and may be responsible for the seizures before remission and a high rate of
phasic nature of the symptoms. relapse following the withdrawal of AEDs.
Seizure relapse can be immediate or after sev-
eral months to years. It appears these patients
Single small cerebral calcific CT lesion require AEDs for long periods of time.
tomatically with AED(s) alone, the lesion use of anticysticercal drugs. However, the
persisted for 73 months5. Most clinicians results of the two double-blind randomized,
treat seizures associated with SCG – for a placebo-controlled studies using albendazole
2–3 year seizure-free period – just as they are contradictory. One study involving 75
would treat any other type of epilepsy27. adult patients did not show any benefit32,
Our long-term follow-up study has shown whereas another study involving 63 children
that seizures associated with SCG have a revealed that anticysticercal therapy has-
good prognosis and AED can safely be with- tened resolution of the SCG33. In the author’s
drawn after resolution of the CT lesion5. The opinion, some parasites may involute
mean period of follow-up was 45 months rapidly over a period of weeks to few
(range 19–101 months) and only one patient months (‘rapid resolvers’), while others invo-
who had CT-demonstrable scar had recur- lute over a period of several months to years
rence of seizures. However, a recent study (‘persisters’). Anticysticercal drug trials will
suggested that gliosis visible on magnetiza- be negative if the study mostly involves
tion-transfer spin-echo MRI, 2 years after ‘rapid resolvers’. The real efficacy of anticys-
initial presentation, was positively corre- ticercal therapy can only be tested in patients
lated with the risk of seizure recurrence. The with lesions that persist for several months
authors argued that such patients should be to years (‘persisters’). In an open-label study
treated with AEDs for long periods28. Our of 43 patients with lesions that persisted
present policy is to treat patients with SCG beyond 3 months, a response to albendazole
with AEDs until such time their CT lesions was seen in 20 (46.5%) patients27. We did a
resolve. Patients in whom follow-up CT retrospective analysis of efficacy of albenda-
scan shows calcification or gliotic scars zole on the seizure-control profile. The base-
should be treated as for any remote sympto- line demographic characteristics of patients
matic epilepsy. In our series, recurrence of who did not receive albendazole and who
seizures occurred following AED with- did receive albendazole were similar. Clearly,
drawal in two patients who had a gliotic albendazole produced benefits in terms of
scar demonstrable on CT. seizure-control profile in patients with per-
sistent lesions even after 6 months of symp-
tomatic treatment with AEDs (J.M.K.
Anticysticercal drug therapy Murthy, Hyderabad, unpublished data). Our
data also suggest that there is probably a role
The role of anticysticercal drug therapy in for anticysticercal therapy in patients with
patients with SCG is not clear. The argu- SCG with a visible scolex. Lesions with this
ment against anticysticercal therapy is that CT morphology are likely to take longer to
seizures associated with this lesion are resolve and are associated with high seizure
because of the inflammatory response of the frequency5. The reader is referred to Chapter
brain and the lesions are known to resolve 38 for a detailed discussion on the role of
spontaneously1. However, earlier reports anticysticercal therapy in NC.
suggested that anticysticercal therapy influ-
enced the management of patients with
SCG in several ways. In a few studies, anti- Seizure Outcome and Prognosis
cysticercal therapy was shown to benefit
most patients with persistent seizures by Seizure outcome is good in patients with
hastening resolution of the lesion5,27,29. SCG. Breakthrough seizures before remission
Anticysticercal therapy given with AEDs has are common. Breakthrough seizures were
been shown to provide better control of seen in 37% of patients in the author’s series5
seizures29,30. The chance of remaining and in 14.5% in the series of patients studied
seizure-free after the withdrawal of AEDs by Rajashekhar and Chandy22. A recent long-
seems to be higher in patients with NC who term follow-up study suggests that epileptic
were previously treated with albendazole31. seizures associated with SCG recur as long
These findings provide a rationale for the as the lesion persists; and AEDs can safely be
withdrawn once the follow-up CT scan Seizures are the most common manifestation
shows resolution of the lesion5. However, of SCG. Patients with this lesion develop
patients with calcific lesions should be seizures because of the inflammatory
treated as for any type of remote sympto- response of the brain and their seizures may
matic epilepsy. It appears that patients with be categorized as acute symptomatic
calcific lesions need AEDs for a long time seizures. The natural history of SCG can
and seizure relapse rates after drug with- usually take one of two forms: (i) it resolves
drawal are very high. entirely or (ii) a punctate calcification may
be left as a residue. Seizure outcome is good
even when patients are treated with AEDs
Conclusions alone. Long-term follow-up studies suggest
that epileptic seizures associated with SCG
A single enhancing CT lesion measuring less can recur as long as the lesion persists; and
than 20 mm is a common CT finding in AEDs can safely be withdrawn once the fol-
patients with seizures in countries where low-up CT scan demonstrates resolution of
NC is endemic. Pathological studies suggest the lesion. The role of anticysticercal therapy
that most of these lesions represent SCG. is not clear.
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tion of a distinct form of neurocysticercosis with a benign prognosis. Journal of Neurology,
Neurosurgery and Psychiatry 58, 267–269.
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5. Murthy, J.M.K., Reddy, Y.V.S. (1998) Prognosis of epilepsy associated with single CT enhancing
lesion: a long-term follow-up study. Journal of the Neurological Sciences 169,151–155.
6. Rajashekhar, V. (1991) Etiology and management of single small CT lesions in patients with
seizures: understanding a controversy. Acta Neurologica Scandinavia 144, 819–823.
7. Murthy, J.M.K., Yangala, R. (1998) Etiological spectrum of symptomatic localization related epilep-
sies: a study from South India. Journal of the Neurological Sciences 158, 65–70.
8. Murthy, J.M.K., Yangala, R., Mantha, S. (1998) The syndromic classification of the International
League Against Epilepsy: a hospital based study from south India. Epilepsia 40, 48–54.
9. Murthy, J.M.K., Yangala, R. (1999) Acute symptomatic seizures – incidence and etiological spectrum:
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11. Chacko, G., Rajashekhar, V., Chandy, M.J., et al. (2000) The calcified intracorporeal vacuole: an aid to
the pathological diagnosis of solitary cerebral cysticercus granuloma. Journal of Neurology,
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Neurology India 36, 139–150.
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31. Del Brutto, O.H. (1993) The use of albendazole in patients with single lesions enhanced on contrast
CT. New England Journal of Medicine 328, 356–357.
32. Padma, M.V., Behari, M., Misra, N.K., et al. (1994) Albendazole in single CT ring lesions in epilepsy.
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33. Baranwal, A.K., Singhi, P.D., Khandelwal, N., et al. (1998) Albendazole therapy in children with
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26 Paediatric Neurocysticercosis
ment of children below 5 years. One study, occurred very early in life, cysticercosis
however, from Honduras found a higher would not manifest clinically until after 6
seropositivity rate in the 0–9 years age group years of age. In most series of paediatric NC,
(18%) in comparison to average seropositvity the average age of presentation was around
(16.6%)10. Here, children accounted for 28.75% 8 years17–31. However, NC has been reported
of the seropositives in the community. to manifest as early as 14 months of age32.
Differences in age-specific seroprevalence rates Those cases that occur during later child-
were however, not statistically significant. hood probably represent acquisition of T.
Interestingly, when computed tomography solium through food. Cases of cysticercosis
(CT) scans were performed on the subjects, during early childhood probably represent
two of 21 (9.5%) in the age group 0–9 years as infections acquired through caregivers,
opposed to five of 14 (35.7%) in the age group including those within the family as well as
40–49 years were found to have lesions com- housekeepers and food handlers that are
patible with NC (Ana L. Sanchez, Ontario, employed within the household33. The possi-
Canada, personal communication). These data bility of transplacental transmission has been
indicate that, while NC was less common in considered but never proven.
the paediatric population, exposure to T. solium Since children are often restricted to the
began at a very early age in the study village. confines of a well-protected home environ-
ment, their chances of exposure to T. solium
are less in comparison to adults, who may
Hospital-based data also be exposed through food and water out-
side their homes. It becomes all the more
Seropositive cases merely indicate exposure important, therefore, to screen household
to T. solium and do not necessarily imply clini- family, caregivers and food handlers, in con-
cal NC and, therefore, do not provide an esti- tact with children with NC, for adult and lar-
mate of the neurological morbidity due to val T. solium infection. Indeed, a survey of 51
paediatric cysticercosis. The results of a study household family contacts of 20 children with
of neurological outpatients with seizures in a solitary cysticercus granuloma showed that
Lima are of interest in this regard11. In this 14 (27%) had serological evidence of expo-
clinic-based population, 8% of patients with sure to T. solium34. Among the seropositive
seizures, who were above 20 years, were contacts, a history of seizures was obtained in
seropositive in comparison to 2% seroposi- five. Imaging revealed evidence of active or
tives among those below 20 years. These data, inactive NC in four. These data underscore
in common with population data indicate that the importance of screening household fam-
both exposure to T. solium and clinical NC are ily contacts of children with NC.
uncommon below the age of 20 years.
A number of published, hospital-based,
large series of NC have either not included Clinical Manifestations
paediatric cases or not described the age
structure of their cohorts12–14. For those A few of the earlier studies of cysticercosis in
series, where breakdown according to age is children suggested that whilst cysticercosis
available, data indicate that the frequency of was rare among children, its manifestations
NC below the age of 15 years is about one- were more severe. In one of the earliest
tenth as its frequency above that age15,16. reports of paediatric NC, Robles (1945) por-
trayed that the outcome in paediatric NC
was far more serious than adults35. Some 16
Modalities of Transmission Among years later, however, Dixon and Lipscomb
Children disagreed36: ‘In the present series then there
were no deaths among patients certainly or
Taenia solium cysticercosis has a long incuba- probably infected in childhood, and only one
tion period; it may be as long as 5 years. case of severe disablement… The findings
Therefore, even if exposure to T. solium suggest a prognosis far less gloomy…’.
Some authors consider that more severe tion, hyperkinetic behaviour and cerebral
forms of NC, including cysticercotic palsy in children with definite NC31,39.
encephalitis, are common in children37–39. It is However, to date, there has been no system-
not clear whether the latter condition repre- atic study using contemporary tools of assess-
sents a true age-dependent predisposition or ment of these neurological abnormalities in
a bias in case collection. A geographical bias children with either active or inactive NC.
however does exist in the pattern of clinical There is however, anecdotal mention of age-
presentations of paediatric NC. Thus, reports specific neurological syndromes in children
of paediatric NC from developed countries with NC. Otero et al. described the occurrence
like United States emphasize benign, self-lim- of Landau–Kleffner’s syndrome in a patient
iting single lesions17–20. These lesions disap- with NC in the left Sylvian fissure40. Similarly,
pear in 6–12 months, and do not require any Morales et al. described the occurrence of
specific therapy apart from antiepileptic Lennox–Gastaut syndrome in a patient with
drugs for about 1–2 years. Patients with these NC with hydrocephalus31. Both cases, though
lesions present to the emergency department extremely rare, could represent age-related
with acute non-febrile seizures and have expressions of a severe non-specific neurolog-
been reported in several states of the United ical insult, in these cases, NC.
States21. In comparison, reports of paediatric
NC from endemic regions such as Latin
America have emphasized the occurrence of Investigations
features of intracranial hypertension in addi-
tion to seizures22–25. These are patients who Radiology, including CT and magnetic reso-
have either multiple parenchymal cysts or nance imaging (MRI), is most often
intraventricular or subarachnoid NC. employed for establishing a diagnosis of NC.
Intracranial hypertension has been reported The diagnosis is further supported by ancil-
consistently as the second most common lary tests such as eosinophil counts, stool
manifestation of NC in reports from Latin examinations for Taenia sp. ova, soft tissue
America22–25. It may be conjectured that the roentgenograms, cerebrospinal fluid (CSF)
former benign presentations arise out of studies and serological studies (both, EITB in
brief, limited exposure to T. solium, while the serum and ELISA in CSF).
later, more grave presentations in endemic There is no evidence to suggest that the
regions are the result of more severe or pattern or intensity of antibody responses in
repeated exposure to T. solium. Even in India, paediatric cases with NC are any different
several of the earlier reports emphasized the from those seen in adults. One confounding
occurrence of more severe presentations of issue in clinical as well as community-based
intracranial hypertension and meningoen- settings could be the presence of maternally
cephalitis26–28. More recent reports however, transferred antibodies in children, for it has
have described the common single, benign been demonstrated that children born to
self-limiting colloidal-granular NC very com- EITB-positive mothers are seropositive
monly in childhood29,30. (Hector H. García, Lima, Peru, personal
In general, the common manifestations of communication). However, given the low
childhood NC include seizures, headaches reproductive rate in humans it is unlikely
and focal neurological deficits. There is how- that this could be a major source of error in
ever no consensus of opinion regarding the population studies.
role of NC as an aetiology in developmental A serological study based on ELISA indi-
delay, cerebral palsy, learning disability, cated that serological responses were weaker
developmental regression and behavioural in children with malnutrition in comparison to
disorders in children in areas where T. solium nutritionally healthy children41. This has not
is endemic. Understandably, these disorders been observed in several of the recent EITB-
would be expected to occur only in the more based studies from Latin America. However,
severe cysticercotic syndromes such as cys- the effect of nutrition on the antibody status
ticercotic hydrocephalus. A few authors have may be an issue in many developing countries
described the occurrence of mental retarda- where malnutrition is common.
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27 Psychiatric Manifestations of
Neurocysticercosis
Orestes V. Forlenza
Table 27.1. Prevalence of psychiatric manifestations according to several different studies drawn from
neurological and psychiatric samples. The far right column indicates (whenever available) an estimate of
the frequency of pure psychiatric forms*.
Prevalence of Pure
Author/s and Source of Number of psychiatric psychiatric
year of publication Country patients patients manifestations (%) forms* (%)
*There is some controversy in the literature regarding the implications of ‘pure psychiatric presentations’.
Brinck and Beca described psychiatric syndromes in 12 of their 16 patients; two of them had no other
symptoms attributable to cysticercosis7. Lima emphasized that ‘pure psychiatric forms’ were cases
without epilepsy, intracranial hypertension and meningitis, thus allowing the presence of minor
neurological symptoms34. Takayanagui and Jardim noted that psychiatric forms were usually associated
with other neurological manifestations although two ‘pure’ psychiatric cases were reported40.
†Data not available.
drawn from neurological facilities, and case dichotomy of parenchymal and ventriculo-
reports of particularly interesting or intense subarachnoid cysticercosis, there is no possi-
psychiatric syndromes14–16,18. There is a ble classification of the disease according to
paucity of reports of mild psychiatric symp- affected brain areas. Parenchymal cysts may
toms such as anxiety and dysthymia, possi- develop at any locus within the brain,
bly because such minor abnormalities of the although there is a strong propensity for
mental state may be overlooked in the gen- their location at the grey-white matter transi-
eral-hospital setting if assessment is carried tion zone tissue23. As a result of such
out without the aid of standardized psychi- anatomical heterogeneity, one would need
atric instruments16,19. In view of that, it has very large patient samples in order to corre-
not been so far possible to ascertain the late psychiatric findings and lesion location.
prevalence of psychiatric morbidity among In addition, there is also important variation
patients with NC. Estimates vary from 3.4 to in the ability of each individual cyst to
75% (Table 27.1), as a result of the varying become pathogenic, bearing in mind the long
sensitivity of diagnostic methods, sampling and unpredictable time lag between the
bias, and other methodological limitations, appearance of cysts in the brain and their
which are perhaps understandable in view degeneration and calcification17. Most prob-
of the clinical and pathological heterogeneity ably, degenerating cysts and the reactive
of the disease. inflammation within the adjacent nervous
tissue, which are strong determinants of NC-
induced epilepsy, may as well be the trigger
Brain pathology and mental symptoms of psychiatric symptoms, particularly among
predisposed individuals.
Attempts to classify the different psychiatric
syndromes and relate them to the respective
neurological conditions in which they are Prevalence of psychiatric disorders
likely to be found have also been made,
although never reaching consensus11. As a In a cross-sectional study of 38 cases at a neu-
general rule, ventricular cysticercosis and rology outpatient clinic in Brazil, depression
subarachnoid cysticercosis, which are usually syndromes were the commonest psychiatric
associated with meningitis and/or intracra- manifestation, as shown by the Present State
nial hypertension, may result in more cogni- Examination and the Schedule for Affective
tive dysfunction, with attention deficits, Disorders and Schizophrenia – Lifetime
impaired consciousness and delirium20. On Version semi-structured interviews24–26. Signs
the other hand, patients with parenchymal of psychotic disorder were observed in five
cysts and calcifications are prone to experi- patients although none had a clear-cut schiz-
ence the neuropsychiatric complications of ophrenic or manic-depressive presentation.
epilepsy, intracranial hypertension and Only 13 patients (34.2%) were presumed
space-occupying lesions. In view of that, ven- mentally healthy by the aforementioned psy-
triculosubarachnoid forms are prone to pre- chometric methods. Thirty-two patients were
sent with psychomotor agitation, sleep–wake assessed by the Mini-Mental State
cycle disturbances and other behavioural Examination and the Strub and Black’s
symptoms suggestive of acute cognitive dys- Mental Status Examination27,28. Neuro-
function. Dementia has been associated with psychological dysfunction was identified in a
massive and scattered infections of the brain majority of the cases (87.5%), although severe
parenchyma and subacute forms of intraven- cognitive abnormalities were less frequent
tricular cysticercosis21,22. (15.6%)26. Attention deficits were detected in
On the one hand, it may be acceptable all the patients assessed, being probably
that lesion location correlates with specific influenced by the effect of antiepileptic drugs
neuropsychological deficits, on the other, the (carbamazepine and barbiturates). Anyhow,
same assumption cannot be made towards 59.4% had mild to moderate and 40.6%
psychopathology. Except for the gross severe attention disturbance. Memory and
language were altered in 78% of the patients and cysticercosis were candidates for long-
and higher cognitive functions in 87.5%. term inpatient care, suggesting refractory
Other deficits included disorders of praxis disease. In the present-day context, most
and motor functions (50%). Reading and patients with NC have chronic depression
writing skills were less frequently affected and mild or moderately severe brain pathol-
(28% and 0.6% of patients, respectively). ogy (few cysts and/or calcifications). In
However, there was no clear pattern of local- such cases, psychiatric treatment is very
ization for the neuropsychological dysfunc- helpful and should follow the guidelines for
tion in the patients. the treatment of other organic mental ill-
In spite of the clinical heterogeneity of the nesses. Regarding severe forms of NC, such
test group, there was a mild correlation as massive infections with intracranial
between the occurrence of depression and lab- hypertension, space-occupying parenchymal
oratory signs of active disease (defined by the lesions, and intraventricular cysts, psychi-
presence of parenchymal cysts, not calcifica- atric treatment should follow neurological
tions only, as shown by computed tomogra- and neurosurgical procedures. Psycho-
phy (CT) and magnetic resonance imaging pharmacological treatment should be com-
(MRI) scans, and/or inflammatory cere- plementary to neurological care.
brospinal fluid (CSF)) (P = 0.04), and modest
correlation with the occurrence of intracranial
hypertension (P = 0.1). Psychosis also possibly Conclusions
correlated with intracranial hypertension (P =
0.06) but not with disease activity (P = 0.5). No The finding of mental abnormalities and
association was found between the psychiatric cognitive dysfunction in 65.8% and 87.5%,
manifestations and the occurrence of epilepsy respectively, of a cross-section of neurologi-
(P = 0.63), even when the epidemiological cal outpatients with NC is an estimate of
group of active epilepsy29 was considered (P = the high prevalence of psychiatric morbid-
0.72), nor with the current use of steroids (P = ity in such setting. Samples of psychiatric
1). Previous history of depressive disorders inpatients might provide a different profile
was strongly associated with current depres- of psychiatric findings, with more severe or
sion (P = 0.006) and psychosis (P = 0.04)26. even specific forms of mental disease, since
These findings parallel several other studies psychiatric surveys based on patients from
that have addressed the aetiology of organic mental institutions in the first half of the
mood disorders. Family history of depression 20th century reported up to 75% of severe
and history of depression before the onset of mental disease in association with cysticer-
the organic disease are regarded as risk factors cosis. Such a high rate might be explained
for developing depression in cerebrovascular by a long duration of the untreated organic
disease and multiple sclerosis, through greater disease, since many of the aforementioned
biological vulnerability30,31. Disease activity patients had previous evidence of neuro-
(which implies diffuse or localized central ner- logical syndromes before psychiatric
vous system inflammation) is temporally admission, according to their medical
related to organic mood disorders, as shown records. Thus, it is possible that mental dis-
in other medical and neurological conditions, ease represented one of the consequences
such as systemic lupus erythematosus and of the deteriorating organic illness, in the
multiple sclerosis32,33. absence of effective therapeutic strategies
for the parasitic infection at that time.
Although there is consensus that NC may
Treatment be responsible for most of the major psychi-
atric syndromes and dementia, a particu-
There is a paucity of data regarding psychi- larly interesting finding from the study of
atric treatment and outcome in NC. From outpatients is the non-specific pattern of
the earlier classical papers it was made clear psychiatric morbidity, as well as the greater
that patients with psychiatric syndromes incidence of minor psychiatric and neu-
ropsychological abnormalities. Such mani- ties were usually included. Attention and
festations were possibly underestimated by memory are also affected in a high propor-
most of the studies that did not use instru- tion of patients, which is consistent with
ments sensitive enough for an appropriate the findings of other authors in the past
assessment, so that only the most dramatic and reinforces the role played by NC as an
cases of mental or behavioural abnormali- aetiology of dementia.
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Fig. 28.2. Intravitreal cysticercus with retinal detachement (a) and overlying vitreal reaction (b).
Fig. 28.4. Communicating cysticercus. A large (15 disc diameters) spheroid translucent cyst can be seen
in the superotemporal quadrant, attached to, and obscuring the visibilty of the retina (a, b). The dense
white structure within represents the scolex (a). This particular cyst was alive and made undulating
movements, especially on exposure to the strong illumination of the ophthalmoscope. (c) Upon B-mode
ultrasound scan, the posterior wall of the cyst was not distinguishable from the retinoscleral echo, raising
suspicion that the cyst was communicating.
diagnosis. Ocular cysticercosis should be sponding to the anterior and posterior walls
suspected in an individual who has lived in of the cyst. Low amplitude spikes that are
an endemic area and who develops uveitis, representative of the cavity of the cyst sepa-
leukocoria and/or neurological symptoms. rate the high echospikes. An additional
This diagnosis should also be suspected in 100% high spike may be observed within the
individuals with subconjunctival cysts or cyst when the beam passes through the
lid nodules. scolex, which is usually located eccentrically.
B-scan also demonstrates the complete cyst
with an eccentric high-reflective opacity
Differential diagnosis (scolex) and low-reflective, mobile opacities
filling the cyst cavity (Fig. 28.5). Upon B-
Hydatid cyst infestation may rarely occur in scan ultrasonography, the subretinal cys-
the extraocular muscles. The cysts are quite ticercus appears as a round density
large in size, the average size being 3–5 mm, connected to a curvilinear echo correspond-
and can reach up to 10 cm. In children, the ing to the scolex and the cyst wall, respec-
inflammatory response to a dying cysticer- tively. Intravitreal cysticercus gives an
cus should be differentiated from other appearance of a curvilinear cystic structure
causes of leukocoria, especially retinoblas- floating freely in the vitreous cavity.
toma and parasitic infections such as toxo- Intravitreal inflammatory reaction around
cariasis32. In the anterior chamber, the the cyst, when present, is characterized by
inflammation may be so severe that it is diffi- low-medium amplitude echoes in the vitre-
cult to differentiate a cyst from a lens dislo- ous cavity. Echography permits real-time,
cated into the anterior chamber16. dynamic evaluation with direct visualiza-
tion of the undulating movements of the
parasite. In cases of communicating cysts,
Diagnosis where the intravitreal cysticercus communi-
cates subretinally, both A- and B-scan reveal
Laboratory and immunologic tests the presence of a well defined anterior wall
of the cyst, whereas the posterior wall of the
Laboratory tests are of limited value in diag- cyst is not discernible separately from the
nosing intraocular cysticercosis. Complete retinal scleral echo (Fig. 28.4c)43. A careful
blood count, serum chemistries and erythro- ultrasonography is warranted in such cases,
cyte sedimentation rate may all be normal; since demonstration of any subretinal exten-
eosinophilia is uncommon. Repeated stool sion may alter the surgical approach and
samples may not show any proglottides or possibly the surgical outcome43.
eggs of T. solium. An anterior chamber tap Computed tomography (CT) of extraocu-
showing a high eosinophil count supports a lar myocysticercosis may reveal the presence
diagnosis of intraocular cysticercosis44. of cystic lesions in the extraocular muscle or
diffuse myositis. A cystic lesion with a scolex
on either CT scan or echography confirms a
Radiological examination diagnosis of myocysticercosis. CT evidence
of a cystic lesion without a scolex or diffuse
Orbital echography is often used to delin- myositis in the presence of a positive
eate the cystic lesions with a scolex in an immunoserological test, preferably enzyme-
enlarged extraocular muscle. Intraocular linked immunotransfer blot (EITB) for anti-
cysticercosis has characteristic echographic cysticercal antibodies, is also considered
features30,44–46. The cyst may be seen under- diagnostic47. Magnetic resonance imaging
neath the retina, in the vitreous cavity, sur- (MRI) findings of neurocysticercosis have
rounded by inflammatory membranes, or, been extensively described (see Chapter 32).
more rarely, in the anterior chamber. MRI appearances are characteristic; cysts in
Standard A-scan ultrasonography reveals the extraocular muscle with a scolex within
two equally high reflective echospikes corre- the cyst can be seen.
Fig. 28.5. B-mode ultrasound scan demonstrating the cystic nature of the lesion with an eccentric high
reflective opacity representing the scolex.
cus, the coagulated parasite produces only tis. Open sky and pars plana vitrectomies
localized inflammatory reaction and does have been employed to remove subretinal
not induce severe endophthalmitis. cysticerci and have several advantages over
Following photocoagulation, the patient is classic sclerotomy1,15,17,26,28,31,34,52. The visi-
given periorbital and systemic corticos- bility of the parasite during surgery is excel-
teroids for 3–6 weeks. The exudative reac- lent and the risk of subtotal cyst removal
tion clears in 1 month, usually leaving an and choroidal bleeding, as with the external
atrophic scar, with a white calcified scolex in approach, is minimal. The risks of retino-
the centre. Complications of photocoagula- tomy can be further minimized by preoper-
tion include retinal rupture, survival of the ative application of delimiting laser
parasite, macular scarring and severe photocoagulation. This also prevents preop-
uveitis3. Retinal rupture occurs when high- erative or perioperative cyst migration
energy shots are applied to the edge of the within the subretinal space. Following
parasite close to the normal retina or when three-port pars plana vitrectomy incisions,
the retina is thinned because of impending the posterior vitreous overlying the cys-
migration of the cyst into the vitreous. ticercus is exposed. Endodiathermy is used
Rupture can hasten passage into vitreous. to create a retinotomy and enter the subreti-
Survival of the parasite with return of con- nal space over the cyst. The suction catheter
tractile movements is due to insufficient is used as a cutter and is inserted through
treatment and requires further photocoagu- the retinotomy. The cyst is then removed
lation. Macular scarring is unavoidable from within the subretinal space. The scolex
when the parasite is in the macular location. is brought into the midvitreous where it is
Subretinal cysticercosis has also been examined, cut and aspirated. Internal
managed by subretinal release of the cyst. drainage of subretinal fluid is followed by
The cyst must be precisely localized by endolaser photocoagulation to surround the
indirect ophthalmoscopy and scleral retinotomy. Internal tamponade is achieved
depression. A deep, lamellar, L-shaped scle- either with silicone oil or a gas–fluid
ral dissection is made over the cyst13,29,48. exchange performed using 12% perfluoro-
Transillumination of the dissected scleral propane. After retinopexy, the cyst can also
bed delineates large choroidal vessels and be pulled into the vitreous and extracted
helps in avoiding them. The choroid is then from the eye in one piece, after enlargement
exposed through a small incision in the of the pars plana incision. The risk of
scleral bed and, after adequate diathermy spilling of cyst contents is minimal with this
to avoid bleeding, it is perforated carefully procedure as the cutting or aspiration of the
to avoid rupture of the cyst. The cyst is cyst is avoided.
then delivered through the choroidoscleral
incision. Gentle pressure on the globe can
help to release the cyst. Complications of Conclusions
the procedure include failure to remove the
parasite, retinal detachment, retinal tear, Modern imaging techniques have made the
vitreous loss and haemorrhage48. diagnosis of ophthalmic cysticercosis easy.
Removal of subretinal parasites via scle- Nevertheless, clinical suspicion of the con-
rotomy, however, carries risks. Extensive dition should be high and the diagnostic
periocular surgery may be required to gain consideration may be invoked in any
adequate exposure28,29,53,55–57. Inadequate patient in endemic areas with a cystic
localization may lead to non-removal of the lesion or uveitis, retinitis and endoph-
parasite, perioperative migration of the cyst thalmitis. This is particularly important
within the subretinal space and migration because prognosis in untreated cases of
into the vitreous cavity. Other possible com- intraocular cysticercosis is uniformly poor.
plications include retinal detachment, reti- Successful treatment lies in early and com-
nal tear with vitreous loss, vitreous plete surgical removal of ocular cysticerci.
haemorrhage and bacterial endophthalmi- When not treated, intravitreous or subreti-
nal cysticercus usually leads to blindness the eyelid and/or conjunctiva are more
within 3–5 years. Without treatment, the benign, and spontaneous extrusion of the
cysticercus increases in size and begins to subconjunctival cyst may occur. Once the
release toxins, leading to a profound infection is diagnosed, however, it is of the
inflammatory reaction with eventual utmost importance to rule out central ner-
destruction of the eye. Cysticerci located in vous system involvement.
References
27. Sen, D.K. (1982) Acute suppurative dacryoadenitis caused by a cysticercus cellulosa. Journal of
Pediatric Ophthalmology and Strabismus (Thorofare) 19, 100–102.
28. Fishman, M., Kerman, B., Foxman, S. (1987) Intraocular cysticercosis: migratory. In: Ossoing, K.C.
(ed.) Ophthalmic Echography. Proceedings of the 10th SIDUO Congress. Martinus Nijhoff, Dordrecht.
29. Aracena, T., Perez-Roca, F. (1981) Macular and peripheral subretinal cysticercosis. Annals of
Ophthalmology 13, 1265–1267.
30. Kruger-Leite, E., Jalkh, A.E., Quiroz, H., et al. (1985) Intraocular cysticercosis. American Journal of
Ophthalmology 99, 252–257.
31. Giovannini, A., Chillemi, P., Coccia, L., et al. (1985) Ocular cysticercosis. Apropos of a clinical case of
presumed ocular cysticercosis. Journal Francais d’ Ophthalmologie 8, 789–795.
32. Zinn, K.M., Guillory, S.L., Friedman, A.H. (1980) Removal of intravitreous cysticerci from the sur-
face of the optic nerve head: a pars plana approach. Archives of Ophthalmology 98, 714–716.
33. Sen, D.K., Mathur, R.N., Thomas, A. (1967) Ocular cysticercosis in India. British Jounal of
Opthalmology 51, 630–632.
34. Kapoor, S. (1978) Ocular cysticercosis in India. Tropical and Geographical Medicine 30, 253–256.
35. Krishna, D., Mohan, H. (1978) Ocular cysticercosis in India. Journal of Pediatric Ophthalmology and
Strabismus (Thorofare) 15, 96–102.
36. Reddy, P.S., Satyendran, O.M. (1964) Ocular cysticercosis. American Journal of Ophthalmology 57, 664–666.
37. Rao, A.V.M., Satayandran, O.M., Shiva Reddy (1967) Cysticercosis of the eye. Oriental Archives of
Ophthalmology 6, 249–255.
38. Shekhar, G.C., Lemke, B.N. (1997) Orbital cysticercosis. Ophthalmology 104, 1599–1604.
39. Menon, V., Kumar, G., Prakash, P. (1994) Cysticercosis of extraocular muscle. Journal of Pediatric
Ophthalmology and Strabismus (Thorofare) 31, 126–129.
40. Madan, N., Chopra, K., Popli, V. (1995) Proptosis as a manifestation of cysticercosis. Indian Pediatrics
32, 914–918.
41. Schmidt, U., Klauss, V., Stefani, F.H. (1990) Unilateral iritis by cysticercal larva in the anterior cham-
ber. Ophthalmologica (Basil) 200, 210–215.
42. Segal, P., Mrzygold, S., Smolarz Dudarewicz, J. (1964) Subretinal cysticersosis in the macular region.
American Journal of Ophthalmology 57, 655–664.
43. Kumar, A., Verma, L., Khosla, P.K., et al. (1989) Communicating intravitreal cysticercosis. Ophthalmic
Surgery 20, 424.
44. Manschot, W.A. (1968) Intraocular cysticercus. Archives of Ophthalmology 80, 772–774.
45. Murthy, H., Kumar, A., Verma, L. (1990) Orbital cysticercosis – an ultrasonic diagnosis. Acta
Ophthalmologica 68, 612–614.
46. Meyerson, L., Pienaar, B.T. (1961) Intra-ocular cysticercus. British Journal of Ophthalmology 45, 148–149.
47. Stewart, C.R., Salman, J.F., Murry, A.D., et al. (1993) Cysticercosis as a cause of severe medial rectus
myositis. American Journal of Ophthalmology 116, 510–516.
48. Santos, R., Chavarria, M., Aguirre, A.E. (1984) Failure of medical treatment in two cases of intraocu-
lar cysticercosis. American Journal of Ophthalmology 97, 249–250.
49. Kestelyn, P., Taelman, H. (1985) Effect of praziquantel on intraocular cysticercosis: a case report.
British Journal of Ophthalmology 669, 788–790.
50. Sihota, R., Honavar, S.G. (1994) Oral albendazole in the management of extraocular cysticercosis.
British Journal of Ophthalmology 78, 621–623.
51. Raina, U.K., Taneja, S., Lamba, P.A., et al. (1996) Spontaneous extrusion of extraocular cysticercosis
cysts. American Journal of Ophthalmology 121, 438–441.
52. Barraquer, J. (1963) Lens Extraction and Extraction of Cysticercus. American Academy of
Ophthalmology and Otolaryngology Meeting, New York (Film presentation).
53. Hutton, W.L., Vaiser, A., Snyder, W.B. (1976) Pars plana vitrectomy for removal of intravitreal cys-
ticercus. American Journal of Ophthalmology 81, 571–573.
54. Patnaik, B., Kalsi, R. (1983) Intraocular cysticercosis and its surgical management. In: Henkind, P.
(ed.) Acta XXIV International Congress of Ophthalmology. JB Lippincott, Philadelphia, pp. 152–159.
55. Verdaguer, T.J., Lechuga, M., Ibanez, S. (1977) Tratamiento quirurgico da la cisticercosis intravitrea.
Archivos de Chilian del Ophthalmologia 34, 49–54.
56. Gemolotto, G. (1955) Contributo alla terapia chirurgica del cisticerco andocular. Archives of
Ophthalmology 59, 465–368.
57. Jain, I.S., Dhir, S.P., Chattopadhiya, P.R., et al. (1979) Ocular cysticercosis in North India. Indian
Journal of Ophthalmology 27, 54–58.
other immunocompromised states as well. and causes cysts in the subcutaneous tissue
The alterations in the immune system of the and viscera of rodents. It may, however, be
host described in patients with NC may be in added to the list of opportunistic infections
some cases a predisposition to, rather than a that occur in AIDS.
consequence of, HIV infection1. Second, the
therapeutic response to anticysticercal drugs
(praziquantel and albendazole) may differ in Differential diagnosis of NC in AIDS
HIV-infected patients since successful anti-
cysticercal treatment requires a simultaneous Intracranial mass lesions are frequent in
drug effect on both the parasite and host AIDS. The nature of these mass lesions can
immune system. Third, clinical and serologi- be broadly divided into three distinct
cal manifestations of NC might be modified groups: opportunistic infections, neoplasms
by HIV infection. and cerebrovascular disease7. Toxoplasmosis,
a common cause of intracranial mass lesions
in AIDS, can frequently be confused with NC
Taenia crassiceps cysticercosis in AIDS because of similar clinical and imaging pre-
sentations. A point of difference upon imag-
Klinker et al., in 1992, first reported the ing studies is that toxoplasma lesions
occurrence of subcutaneous cysticercosis due involve subcortical structures such as basal
to T. crassiceps in AIDS5. Subsequently, ganglia, thalamus and cerebellum in com-
Francois et al. described the development of parison to NC, which is characteristically
a fluctuant painful subcutaneous and intra- located at the cortical–subcortical interface.
muscular tumour of the forearm due to T. A reliable non-invasive diagnosis of toxo-
crassiceps cysticercosis in AIDS6. Taenia crassi- plasmosis is made with the help of positive
ceps is ordinarily non-pathogenic to humans antitoxoplasma serology and a good thera-
Fig. 29.1. Magnetic resonance image (fluid attenuation recovery sequence) showing solitary cysticercus
granuloma (a) with a scolex and surrounding oedema and thalamic and sub-thalamic lesions (b)
characteristic of Japanese B encephalitis.
diagnosis and treatment, it is important to mosis may produce clinical and imaging mani-
differentiate this condition from cysticer- festations similar to that of NC. Toxoplasmosis
cotic encephalitis19. Several authors have is rare in immunocompetent hosts, while NC
tried to explain this association on the basis occurs rarely in immunosuppressed hosts20. A
of anatomical derangements in the variety of investigative techniques including
blood–brain barrier during the inflamma- neuroimaging, thallium-201 single photon
tory phase of cerebral cysticercosis that emission computed tomography, polymerase
facilitate viral entry15–18. Furthermore, T. chain reaction analysis of CSF and special
solium larvae are also thought to sensitize histopathological methods may be required to
the brain to more severe injury by Japanese reliably differentiate acquired toxoplasmosis
B encephalitis. Indeed, it has been surmised from cerebral cysticercosis20.
that concomitant cerebral cysticercosis Wallus and Young reported the rapid
adversely determines the outcome of the development of a large cystic parenchymal
encephalitis16,18. In our view, the swine pop- lesion in a young woman, which was surgi-
ulation is an important reservoir for cally removed and found to contain pus
Japanese B encephalitis and also constitutes rather than clear fluid21. The pus was cul-
the intermediate host population for T. tured and grew Brucella melitensis. The case
solium. Therefore, there is a likelihood of a allegorizes bacterial superinfection of cere-
chance association to occur in areas where bral cysticercosis and as well as the point
free-ranging pigs are common. that clinicians should be aware of multiple
simultaneous infections.
pregnancy and the latter may occur in a milk and its effects on neonates and infants
woman with pre-existing NC22–24. Our are not yet known22.
experience on this association is largely
based on anecdotal case reports22–24. NC
can be responsible for new-onset seizures Neurocysticercosis and Malignancies
during pregnancy. However, seizures
have a different connotation in pregnancy Systemic malignancies
than otherwise. First, seizures are more
commonly a manifestation of eclampsia Herrera et al. investigated the possibility of
and NC must be differentiated from this an association between NC and systemic
condition24. Second, both mother and cancer26. The authors reviewed 1271
fetus are at risk of death during and after autopsy files and selected those with malig-
a major seizure. Hypoxia and acidosis nancy cases. Autopsies revealing any non-
caused by convulsions, though, well toler- malignant disease served as controls. NC
ated by the mother, can be fatal to the was significantly more frequent in haema-
fetus. Unsuspected NC may also pose tological malignancies in comparison to
diagnostic problems during pregnancy. controls. It was concluded that since
The investigation of choice for the diagno- human cancer arises from interaction of
sis of NC in pregnant women is magnetic several factors including xenobiotics and
resonance imaging (MRI); computed endogenous constituents, it is difficult to
tomography (CT) scanning should be establish NC as a causal agent of haemato-
avoided as far as possible, especially dur- logical malignancies; however, it should be
ing early part of pregnancy. considered as a potential risk factor for
Data is insufficient about safety of anti- haematological malignancies in endemic
cysticercal drugs during pregnancy. countries. Mutagenic abnormalities includ-
Praziquantel does not cause teratogenicity in ing chromosomal aberrations and HPRT-
mammalian assays or reproductive impair- locus mutations have been reported with
ment in rats, mice or rabbits. There are no increased frequency in individuals with
available data on human reproductive ill NC27,28. Although some authors relate these
effects from this agent25. Anecdotal use in abnormalities to the administration of prazi-
pregnant individuals who were not yet quantel, the prevailing view is that these
aware that they were pregnant, so were in abnormalities are caused by NC itself and
very early pregnancy (at the time of maximal that they revert back with praziquantel
teratogenic potential), have not revealed any administration27–29. Some authorities believe
congenital anomalies25. Use in later gestation that T. solium infestation causes depression
has not been associated with an increase in of cell-mediated immunity, in particular cer-
fetal or neonatal mortality or morbidity22. tain aspects of T-cell function30,31. Since the
Though human data are lacking, albendazole latter is involved in surveillance against can-
has been found to be embryotoxic and ter- cer, it may be surmised that the parasite-
atogenic to laboratory animals; therefore its induced immunosuppression underlies the
use during pregnancy, especially the first predisposition to malignancies.
trimester, is not recommended.
We recommend that if the patient is preg-
nant and seizures are in good control on Central nervous system malignancies
antiepileptic drugs (AEDs) then definitive
treatment with anticysticercal drugs can be In non-endemic regions where incidence of
delayed till after delivery. On the contrary, if NC is very low, it is not surprising that
the disease is progressive or seizures are not lesions of NC are mistaken as cerebral
well controlled, then anticysticercal treat- tumour. Silver et al. reported one such exam-
ment should be considered during preg- ple; a 9-year old girl presented with severe
nancy22. Finally, note should be made of the acute headache, vomiting and convulsions –
fact that praziquantel is secreted in breast imaging revealed a ring-enhancing CT
References
1. Thornton, C.A., Houston, S., Latif, A.S. (1992) Neurocysticercosis and human immunodeficiency
virus infection. A possible association. Archives of Neurology 49, 963–965.
2. White, A.C. Jr, Dakik, H., Diaz, P. (1995) Asymptomatic neurocysticercosis in a patient with AIDS
and cryptococcal meningitis. American Journal of Medicine 99, 101–102.
3. Soto Hernandez, J.L., Ostrosky Zeichner, L., Tavera, G., et al. (1996) Neurocysticercosis and HIV
infection: report of two cases and review. Surgical Neurology 45, 57–61.
4. Mosowitz, L.B., Hensley, G.T., Chan, J.C., et al. (1984) The neuropathology of acquired immune defi-
ciency syndrome. Archives of Pathology and Laboratory Medicine 108, 867–872.
5. Klinker, H., Tintelnot, K., Joeres, R., et al. (1992) Taenia crassiceps infection in AIDS. Deutsche
Medizinische Wochenschrift 117, 133–138.
6. Francois, A., Favennec, L., Cambon-Michot, C., et al. (1998) Taenia crassiceps invasive cysticercosis: a
new human pathogen in acquired immunodeficiency syndrome. American Journal of Surgical
Pathology 22, 488–492.
Fig. 30.1. Parenchymal cysticercosis. Coronal section of the brain with multiple cysts lodged in cortical
grey and subcortical white matter and leptomeningeal space. Some of the cysts display a characteristic
larva inside the vesicle. Notice also that the parasites in the right putamen, and at the tip of third frontal
and first temporal convolution in the left hemisphere, have lost their vesicular morphology and
transformed into homogenous colloidal/granular nodular structures. This is an example of cysticerci in
different stages of resolution at one time.
Fig. 30.2. (a) Vesicular stage of a cyst found in the fourth ventricle. The C-shaped larva protrudes from
the previously opened vesicular membrane. (b) Two meningeal cysticerci with hyaline change within their
vesicular membranes.
Fig. 30.3. Rostellum, suckers and crown of hooklets identify a cysticercus cellulosae. Fresh specimen
prepared according to the technique for rapid diagnosis, as described in the text (scale bar: 330 m).
Colloidal stage
Granular nodular stage
The colloidal stage is characterized by degen-
erative changes in the aging parasite conse- In the granular nodular stage, there occurs
quent upon host immunological response. The retractional involution of cyst/s. Its contents
transparent fluid within the cyst is replaced by are mineralized and tend to appear granular.
jelly-like whitish material. The larva is still The larva becomes fragmented, but careful
identifiable, but it exhibits hyaline degenera- histological examination still permits identifi-
tion and early mineralization. Due to the cation of the remaining parts of the festooned
microscopic resemblance to a colloid cyst, this membrane and scolex (Fig. 30.7). Both struc-
stage has been named the ‘colloidal stage of tures are difficult to identify; however, the use
the vesicular form’ of cysticercosis. In a more of Masson’s trichrome technique may permit
advanced stage, the cyst begins to decrease in identification. With this stain, the membrane
size, its walls become thicker, and its contents appears bright red, while the scolex has a red
undergo mineralization with calcium salts, and blue tint because of collagen tissue. The
and are transformed into coarse granules. If collagen capsule around the cysts is thick,
the cyst is located in the parenchyma, granula- stains heavily blue, and is infiltrated and sur-
tion tissue appears around the lesion (Fig. rounded by a decaying inflammatory reaction.
Fig. 30.4. (a) The vesicle of a live cysticercus cellulosae displays the characteristic three-layered
structure; notice the microtriches covering the festooned surface of the cuticle (haematoxylin and eosin;
scale bar: 35 m). (b) Advanced hyaline change and disappearance of the three layers in the vesicular
membrane of a dead meningeal cysticercus. Concomitant intense inflammatory infiltrate and
multinucleated giant cells cover the surface of the membrane (haematoxylin and eosin; scale bar: 90 m).
(c) Calcareous corpuscles in the reticular layer of the vesicular membrane of a viable cysticercus
(haematoxylin and eosin; scale bar: 90 m).
Fig. 30.5. Parenchymal cysticercosis. (a) Cysticercus in the vesicular stage. The histological section
displays the spiral canal, hooklets and the well preserved vesicular membrane. (b) Parenchymal
cysticercus showing a marked inflammatory infiltrate both inside the locus and outside it in the adjacent
parenchyma. (c) Dead parenchymal cysticercus with a hyalinized vesicular membrane is completely
surrounded by an intense inflammatory exudate both inside the locus and outside it into the adjacent
parenchyma. There are multiple foci of perivascular cuffing (haematoxylin and eosin; scale bar: 225 m).
Fig. 30.6. Parenchymal cysticercosis. A live vesicular stage cysticercus appears lodged in the right
dorsomedial thalamic nucleus. The larva can be seen through the translucent vesicle. Another parasite is
partially exposed in the dorsal portion of the internal capsule on the opposite side (scale bar: 5 mm).
Fig. 30.7. Meningeal cysticercus in an advanced colloidal to granular nodular stage. A thick collagen
membrane encases the parasite and its vesicular membrane; notice the total loss of the structure of the
strobila (Masson’s trichrome technique; scale bar: 2.5 mm).
Fig. 30.8. High power photomicrograph of the inflammatory parenchymal infiltrate and reactive
astrocytic gliosis in the acute encephalitic phase of parenchymal cysticercosis. The vesicular membrane
lies next to the parenchymal wall of the locus (haematoxylin and eosin; scale bar: 90 m).
Fig. 30.9. Basal cysticercotic meningitis. (a) Photomicrograph displaying hyalinized membranes of
cysticercus and an arterial branch with partial destruction of the lamina elastica. There is partial occlusion
of the lumen due to an atheromatoid plaque, a common finding in the vicinity of the parasites
(haematoxylin and eosin). (b) An arteriole with intense inflammatory periarteritis and endarteritis
associated with collagen proliferation (Masson’s trichrome stain; scale bar: 22 m). (c) Hyalinized
membranes of cysticercus and abundant debris adherent to the markedly fibrotic leptomeninges
(Masson’s trichrome stain). (d) Intense inflammatory infiltrate and multinucleated macrophages that
surround debris of the cysticercus membranes (Masson’s trichrome stain; scale bar: 90 m).
Fig. 30.10. Intraventricular cysticercosis. (a) Vesicular cysticercus in the temporal horn of the right lateral
ventricle. There is granular ependymitis on the walls of the ventricle (scale bar: 5 mm). (b) The fourth
ventricle is occluded by a cysticercus in the granular-nodular stage (scale bar: 5 mm). (c)
Photomicrograph of the aqueduct blocked by the membrane of a cysticercus partially hyalinized. Note
the marked fibrosis, inflammatory infiltrate and gliosis around the parasite (Masson’s trichrome
technique; scale bar: 300 m).
Fig. 30.11. Encapsulated cysticercus. (a) An ovoid structure wrongly interpreted as a brain tumour upon
magnetic resonance imaging. Gross examination of the specimen displayed coarse granular fragments
and amorphous homogenous structures. (b) Histological section of (a) shows hyaline membranes, debris
and the scolex and hooklets of the cysticercus inside a thick collagen capsule with the use of Masson’s
trichrome technique (scale bar: 30 mm).
Fig. 30.12. Basal subarachnoid-cisternal cysticercosis. (a) Racemose cysticercosis. A clump of vesicular
cysticerci lie under the base of the cerebellum at the cisterna magna. (Reproduced with permission from
reference 25.) (b) Basal cysticercotic meningitis: Close up view of the base of the brain showing marked
fibrosis of the leptomeninges over the ventral wall of the diencephalon and the brain stem, obscuring the
vascular structures and cranial nerves. It is possible to identify a few cysticerci partially buried within the
gummatous arachnoiditis. (c) Thickening of the basal leptomeninges in this coronal section at the level of
the optic chiasma extending into both sylvian fissures (white solid arrow) and a large empty vesicle on
the left. Notice also the increased thickness of the vessels trapped in the meningitis and the granular
ependymitis on the walls of the third ventricle.
racemose forms appear to be made up of foramina at the outlet of the fourth ventricle
multiple vesicles, some of them multilobu- or CSF cisternal pathways.
lated, of variable size and shapes giving the
peculiar aspect that led Virchow to name
them ‘Traubenhydatiden’5. A racemose cyst Intraventricular cysticercosis 19,26,27
does not contain a scolex. However, careful
examination of cystic contents sometimes The fourth ventricle is the most common
leads to the identification of hooklets; this location of intraventricular cysticercosis.
appears to indicate that a scolex was present More often than not, the cyst is single (Fig.
initially but underwent hydropic degenera- 30.10a). When the cysts lodge at the foramen
tion subsequently. On rare occasions a com- of Monro, the aqueduct of Sylvius or the
plete larva may be identified. fourth ventricle cavity (Fig. 30.10b and c), the
result is an obstructive symmetrical hydro-
cephalus19,26,27. Secondary syringomyelia and
Basal cysticercotic meningitis 9,14,15,19,22,25 syringobulbia28 may rarely develop as a com-
In endemic regions, the pathologist may on plication of the chronic obstructive hydro-
occasion be confronted by a specimen dis- cephalus due to fourth ventricular
playing marked thickening of the lep- cysticercosis. This is incidental to sustained
tomeninges. The appearance is one of a thick increased intraventricular pressure and to the
layer of fibrous granulomatous tissue cover- disruption of the ependymal lining with
ing the entire basal surface of the brain from marked subependymal glial proliferation.
the optochiasmatic region to the caudal por-
tion of the medulla and extending over the
sides to the dorsal mesencephalon and cere- Parenchymal cysticercosis
bellopontine angle (Fig. 30.13a and b, Fig.
30.12b and c). When examined with the Cysticerci are usually located in the grey
naked eye, no cystic parasites are seen and, matter owing to its rich blood supply.
in their absence, pathological appearances Parasites are mostly located in the cortex,
are indistinguishable from tubercular menin- though a few may be found in deep grey
gitis. Examination of multiple sections structures. It is also possible to find cysts in
through the leptomeningeal thickening may the subcortical white matter. The number of
discern cysts. Often a diagnosis of cysticercal parasites may reach several hundred, but
basal meningitis is based upon the histologi- commonly one finds only a scattered few.
cal demonstration of cysts or cystic remnants Parenchymal cysts are mostly homogenous
(Fig. 30.14a and b). A good example of the and less than 10 mm in size. They are round
latter situation is the identification of degen- or ovoid (Figs 30.1 and 30.6). The inflamma-
erative festooned membranes surrounded by tory reaction around parenchymal cysts is
granulomatous reaction with the aid of well circumscribed and less intense in com-
Masson’s trichrome technique (Fig. 30.9c and parison to leptomeningeal cysticerci.
d). Vascular reactions of angiitis including However, in the acute encephalitic type of
endarteritis and periarteritis, endothelial NC, the host immune response is intense,
proliferation, and hyaline and fibrinoid leading to diffuse inflammatory reaction and
necrosis are usually conspicuous in cysticer- oedema16,24,29.
cotic basal meningitis (Fig. 30.9a and b).
Cranial nerves also become encased in the
leptomeningeal fibrosis and display intersti- Mixed forms
tial and perineural inflammation. The under-
lying parenchyma shows marginal gliosis, Most often, there occurs a combination of the
inflammatory infiltrates, perivascular cuffing different types of cysticerci. In our pathologi-
and multiple ischaemic infarcts. Finally, cal material, we commonly encounter a com-
basal cysticercotic meningitis may lead to bination of meningeal and ventricular forms.
ventricular dilation due to obstruction of the However, any combination is possible.
Fig. 30.13. Basal cysticercotic meningitis. (a) Axial section of lower brain stem showing intense thickening
of the leptomeninges over the ventral surface of the upper medulla. The fourth ventricle appears enlarged
due to blockage of the draining foramina and there is granular ependymitis. (b) Two axial sections of the
midbrain. There are fibrotic leptomeninges and occlusion of the aqueduct. The latter was due to a
cysticercus identified on histological examination (see Fig. 30.10). The substantia nigra appears pale.
Fig. 30.14. Basal cysticercotic meningitis. Macrophotographs of histological slides of sections (a)
through the middle pons, and (b) upper medullary level. The hyalinized membranes of cysticerci are
encased by the fibrotic leptomeninges. There is also granular ependymitis (Masson’s trichrome
technique; scale bar: 2 mm).
References
1. Aluja, A., Escobar, A., Escobedo, F., et al. (1987) Cisticercosis. Una recopilación actualizada de los
conocimientos básicos para el manejo y control de la cisticercosis causada por Taenia solium. Fondo de
Cultura Económica, México DF, México, pp. 115.
2. Richards, F.O., Schantz, P.M., Ruiz-Tiben, E., et al. (1985) Cysticercosis in Los Angeles County.
Journal of the American Medical Association 254, 3444–3448.
3. MacArthur, W.P. (1934) Cysticercosis as seen in the British army, with special reference to the pro-
duction of epilepsy. Transactions of the Royal Society of Tropical Medicine and Hygiene 27, 343–363.
4. Henneberg, R. (1936) Die tierischen Parasiten des Zentralnervensystems. In: Bumke, O., Foerster, O.
(eds) Handbuch der Neurologie, Vol. 14. Springer Bd, Berlin, pp. 286–322.
5. Virchow, R. (1860) Traubenhydatiden der weichen Hirnhaut. Archiv für pathologische Anatomie und
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Archives of Internal Medicine 157, 1991–1997.
Geeta Chacko
308 G. Chacko
Fig. 31.1. Degenerated cysticercus outlined by calcified intracorporeal vacuoles (haematoxylin and
eosin; 200).
Fig. 31.2. Calcified bodies in amorphous debris without any typical cysticercus parts (haematoxylin
and eosin; 200).
Fungal granuloma
Conclusions
A granuloma containing multinucleated
In conclusion, an SSECTL may be seen at
giant cells, lymphocytes and plasma cells is
any stage in the natural evolution of
visible. Fungal elements can be demon-
Cysticercus cellulosae. At one end of the
strated with special stains.
spectrum the entire parasite might be identi-
fied while at the other end calcareous
Microabscess residues might be the only evidence of a cys-
ticercal aetiology of the granuloma. The vast
This is a non-granulomatous cavitary lesion majority are seen as cavitary lesions while a
with inflammatory exudate in the cavity minority shows a fibrous cicatrix.
References
1. Rajshekhar, V. (1991) Etiology and management of single small enhancing CT lesions in patients
with seizures: understanding a controversy. Acta Neurologica Scandinavica 84, 465–470.
2. Chandy, M.J., Rajshekhar, V., Ghosh, S., et al. (1991) Single, small, enhancing CT lesions in Indian
patients with epilepsy: clinical, radiological and pathological considerations. Journal of Neurology,
Neurosurgery and Psychiatry 54, 702–705.
310 G. Chacko
3. Rajshekhar, V., Haran, R.P., Prakash, S.G., et al. (1993) Differentiating solitary small cysticercus gran-
ulomas and tuberculomas in patients with epilepsy: clinical and computerized tomographic criteria.
Journal of Neurosurgery 78, 402–407.
4. Rajshekhar, V., Chacko, G., Haran, R.P., et al. (1995) Clinicoradiological and pathological correlations
in patients with solitary cysticercus granuloma and epilepsy: focus on presence of parasite and
edema formation. Journal of Neurology, Neurosurgery and Psychiatry 59, 284–286.
5. Chacko, G., Rajshekhar, V., Chandy, M.J., et al. (2000) The calcified intracorporeal vacuole: an aid to
the pathological diagnosis of solitary cerebral cysticercus granulomas. Journal of Neurology,
Neurosurgery and Psychiatry 69, 525–527.
6. Chacko, G. (2000) Pathogenesis and pathology of neurocysticercosis. In: Rajshekhar, V., Chandy, M.J.
(eds) Solitary Cysticercus Granuloma – the Disappearing Lesion. Orient Longman, Chennai, India,
pp. 96–111.
may be seen in some instances. The fibrous views7. The small (2–3 mm) rounded shape
nodule frequently calcifies, as seen in of cerebral cysticercosis is distinguishable
57–64% of cases on computed tomography from the larger oat-shaped calcification in
(CT)3,6. Calcification as noted upon CT may muscle (Fig. 32.1b). Cyst calcification is less
represent partial dystrophic calcification of a frequent in the neuraxis than in muscle.
necrotic larva or the calcareous corpuscles1,2. Also, NC frequently coexists with muscle
Dystrophic calcification is a long process cysticercosis. Therefore, in the past, soft-tis-
and may take from 2 to 10 years to be sue radiography would often establish a
detected on roentgenographs. diagnosis of cysticercosis when skull
roentgenograms were normal8.
When multiple, lesions are often at differ-
ent stages of their development, a phenome-
non that could reflect different infectious
Cranial Conventional Angiography
episodes. The sequence of events for any sin-
gle lesion is from an innocuous cyst to gran-
In the pre-cross-sectional imaging era, con-
uloma and then to a calcified nodule.
ventional angiography was used to demon-
However, a cysticercus may move from one
strate mass effect. Displacement of the
stage to another stage by skipping the regu-
vessels and early venous drainage due to
lar sequences of stages or may disappear
soft-tissue masses produced by live
completely with or without undergoing any parenchymal larvae have been described
sequence of degeneration. This may take (Fig. 32.2)9. Angiography is also useful in
several years in untreated lesions and several demonstrating vasculitis in association with
months for treated lesions. meningeal racemose cysticercosis. Findings
range from mild arterial narrowing to com-
plete occlusion along with distortion of
Plain Skull Roentgenograms carotid and/or vertebral arteries (see
Chapter 22)10. Abnormalities are most severe
Parenchymal lesions are characterized by in the immediate vicinity of racemose cysts.
either mass effect or intracranial calcifica- On occasion, an angiogram may reveal an
tion. Signs of raised intracranial tension inflammatory aneurysm in the vicinity of a
such as sutural diastasis, enlargement of racemose cyst11. In the present-day context,
sella turcica and erosion of anterior and however, conventional angiography is rarely
posterior clinoid processes may be seen required and has been replaced by CT and
upon skull roentgenograms. Calcification is magnetic resonance imaging (MRI).
representative of dead larva(e). However,
the presence of calcification does not
exclude the presence of live larvae; active Negative and Positive Contrast
cysts have been demonstrated concomi- Ventriculography
tantly with calcified lesions. Typically, the
calcified cysticercus gives the appearance of Negative contrast (air) studies are haz-
slightly off-centre spherical calcification of ardous and of historical importance only.
1–2 mm in diameter representing the dead One finds ample illustrations of hydro-
scolex. It may be surrounded by a 7–12 mm, cephalus, asymmetry of the lateral ventri-
partially or totally calcified sphere repre- cles and atrophy of the brain parenchyma
senting the body of the cystic larva (Fig. as well as large ventricular cysts in older
32.1a)7. Old shrunken (5–7 mm) cysts may literature (Fig. 32.3a)7,12. Positive contrast
lose their spherical shape, yet maintain a cisternography and ventriculography with
recognizable morphology. One often finds the aid of intraventricular metrizamide out-
that innumerable calcified cysts are distrib- lines cisternal and ventricular cysts (Fig.
uted in the brain in a pattern perfectly com- 32.3b). Ependymitis and ventricular
patible with the proportion of blood supply synechiae may be visualized as septate
as judged on stereoscopic frontal and lateral ventricular loculations7.
(a) (b)
Fig. 32.2. Conventional cranial angiogram (lateral view). The mass effect on the distal branches of the
middle cerebral artery secondary to the cluster of intraparenchymal cysts in the left parietal region is noted.
Fig. 32.3. (a) Air-contrast study demonstrating dilatation of the right lateral ventricle owing to obstruction
of the right foramen of Monro. The obstructing cyst is not clearly made out. (b) Metrizamide
ventriculogram followed by introduction of air through lumbar puncture demonstrating the dilated lateral
ventricles and the outline of a cyst within.
cysts and cystic astrocytoma14. Vesicular multiple cysticercosis, other lesions at dif-
cysticercus does not produce symptoms; ferent stages of evolution may be seen; the
when single it is detected as an incidental latter are responsible for bringing the
finding upon imaging studies. In the case of patient to attendance.
Fig. 32.4. Vesicular (a) and calcified (b) stage of neurocysticercosis. Non-contrast computed tomography
scan at supraventricular level showing multiple cysts each with an eccentrically placed nodule
representing the scolex (a). The cysticerci are not surrounded by oedema. Calcified cysticerci can be
made out in addition to the vesicular cysticerci (b).
Nodular-calcified stage
Granular–nodular stage
Non-contrast CT reveals an isodense cyst This stage is represented by a small
with a hyperdense-calcified scolex and sur- (7–11 mm), round, punctate or oval, high-
rounding oedema. The walls of the granu- attenuation areas (80–360 HU)14–16. Rarely cal-
loma may be hyperdense because of calcium cifications may be reasonably large. Calcified
deposition16. Granulomas are of variable granulomas are not associated with mass
sizes, but even if quite small, they usually effect and do not enhance after contrast
have a definite ring or disc pattern of con- administration. However, perifocal oedema
trast enhancement around a low-density cen- may be present, particularly if CT is under-
tre (Fig. 32.5a and b). The ring is of variable taken within 24–72 hours of a seizure (Fig.
thickness, but usually thicker than that in 32.6a–c)14. Calcified cysticerci may be single or
pyogenic abscess17. The evolutionary stages multiple. They are usually located within the
form a continuous spectrum. Hence, the cyst grey matter or at grey–white matter junctions.
wall and scolex may be identifiable even Rarely, they may be seen in basal ganglia and
during the granular–nodular stage. Multiple deep white matter. The differential diagnosis
homogeneously hypodense nodules with of multiple, dispersed calcifications includes
surrounding oedema and contrast enhance- toxoplasmosis and tuberous sclerosis14.
Intraventricular cysticercosis
Subarachnoid-racemose cysticercosis
Intraventricular cysticercosis may not be
identified upon CT because of a thin wall, Visualization of subarachnoid-racemose
approximate CSF-equivalent content and cysts on CT scan depends upon their size
lack of contrast enhancement. Therefore, and location. Cysts have a density identi-
evidence for intraventricular cysticercosis is cal to the CSF. Furthermore, cyst walls are
often indirect. For instance, an expanding too thin to be identified. Therefore, their
cyst or obstruction of the foramen of recognition depends upon deformity of
Fig. 32.6. Calcified stage of neurocysticercosis. Non-contrast computed tomography (a) and T2-
weighted axial magnetic resonance imaging (b) showing a calcified lesion. One year later, after the
patient had a seizure, a post-gadolinium T1-weighted image revealed a ring-like enhancement and
surrounding oedema (c).
the normal configuration of cisterns. and conform to the shape of the cisterns in
Relatively large cysts are required to which they lie. Despite this, chronic pres-
deform the quadrigeminal, cerebellopon- sure effects with bone remodelling may be
tine and suprasellar cisterns. Smaller cysts noted. CECT scan may show lep-
are readily detected in the Sylvian fissure tomeningial enhancement in the basal cis-
and cortical sulci. Cysts are usually pliable terns around cysts or more diffusely. The
(a) (b)
Fig. 32.7. Intraventricular neurocysticercosis. T1-weighted magnetic resonance imaging (a) showing
asymmetric dilatation of the lateral ventricles with no discernable intraventricular lesion. Metrizamide
computed tomography ventriculography (b) clearly depicting two intraventricular cysticerci. (Source:
Svetlana Agapejev, São Paulo, Brazil.)
Fig. 32.9. Vesicular neurocysticercosis. T1-weighted axial (a) and post-gadolinium T1-weighted coronal
magnetic resonance imaging (b) showing the clear cystic contents, the eccentric scolex and the lack of
enhancement or surrounding oedema. (Source: Eric Kossof, Baltimore, USA.)
Fig. 32.10. T2-weighted axial image (a) at the level of midbrain shows multiple hyperintense areas
bilaterally with perifocal oedema in some. T1-weighted image (b) shows hypointense nature of these
lesions. On magnetization transfer-T1-weighted image (c), peripheral hyperintensity is seen in some of
the lesions. Post-contrast T1-weighted image (d) shows ring-enhancement of the lesions in the left frontal
and right occipital region.
MRI
Prevesicular Initially solid, Normal Normal / ? Isointense / Isointense – May Not seen No
later cystic hyperdense hypointense enhance
developing specs very early
larva
4:45 pm
Vesicular Cystic with Isodense / ? Usually no Hypointense Hyperintense Hypointense Non-enhancing Present Usually not,
fluid-filled hypodense contrast except in
thin enhancement early
membrane, except in degenerating
single scolex, early stages stage
no inflammatory of degeneration
Page 323
response ( 3 months)
Colloidal Cystic with Hypodense, Ring or disc Intensity Hyperintense Intensity Enhances after May be Always
hyaline surrounding shaped CSF CSF contrast present (T1 present
degeneration, oedema contrast isointense,
cyst fluid thicker may be enhancement T2 iso-/
and protein- present hypointense)
aceous, breach
in blood–brain
barrier and
surrounding
inflammation
Granular- Retracted- Hypodense Ring- or disc- Isointense Iso-/hypointense – Ring-/nodule- Occasion- Usually
nodular involuted larva with shaped contrast with central like enhancement ally present present
Imaging and Spectroscopy of Neurocysticercosis
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Fig. 32.12. T2-weighted image (a) through the supraventricular region shows a hyperintense mass with
hypointense rim and associated perifocal oedema. The lesion appears hypointense on T1-weighted
image (b). In vivo proton-MRS done using spin echo shows a prominent resonance at 2.4 ppm consistent
with succinate (S) and a small resonance of lactate at 1.33 ppm (L). The resonances at 2.02, 3.02 and
3.22 ppm are seen as contaminant from the parenchyma around the cyst assigned to N-acetylaspartate
(NAA; 1), creatine (Cr; 2), and choline (Cho; 3) respectively (c). Ex vivo proton-MRS confirmed the
assignments seen in vivo (d).
References
26. Jena, A., Sanchetee, P.C., Gupta, R.K., et al. (1988) Cysticercosis of brain shown by magnetic reso-
nance imaging. Clinical Radiology 39, 542–546.
27. Creasy, J., Alacron, J. (1994) Magnetic resonance imaging of neurocysticercosis. Topics in Magnetic
Resonance Imaging 6, 59–68.
28. Chang, K.H., Cho, S.Y., Hesselink, J.R., et al. (1991) Parasitic diseases of the central nervous system.
Neuroimaging Clinics of North America 1, 159–178.
29. Chang, K.H., Lee, J.H., Han, M.H., et al. (1991) The role of contrast enhanced MR imaging in the
diagnosis of neurocysticercosis. American Journal of Neuroradiology 12, 501–513.
30. Rajshekhar, V., Chandy, M.J. (1996) Comparative study of CT and MRI in patients with seizures and
a solitary cerebral cysticercus granuloma. Neuroradiology 38, 542–546.
31. Spickler, E.M., Lufkin, R.B., Teresi, L., et al. (1989) High-signal intraventricular cysticercosis on T1-
weighted MR imaging. American Journal of Neuroradiology 10, S64 (Case Report).
32. Suh, D.C., Chang, K.H., Han, M.H., et al. (1989) Unusual MR manifestations of neurocysticercosis.
Neuroradiology 31, 396–402.
33. Jena, A., Sanchetee, P., Tripathi, R., et al. (1992) MR observations on the effects of praziquantel in
neurocysticercosis. Magnetic Resonance Imaging 10, 77–80.
34. Rhee, R.S., Kumasaki, D.Y., Sarwar, M., et al. (1988) MR imaging of intraventricular cysticercosis.
Journal of Computer Assisted Tomography 11, 598–601.
35. Gupta, R.K., Jain, V.K., Kumar, S., et al. (1993) Unusual MRI appearance of cysticercus within the
fourth ventricle. Neuroradiology 35, 457–458.
36. Del Brutto, O.H. (1992) Cysticercosis and cerebrovascular disease: a review. Journal of Neurology,
Neurosurgery and Psychiatry 55, 252–254.
37. Gupta, R.K., Kathuria, M.K., Pradhan, S. (1999) Magnetization transfer MR imaging in central ner-
vous system tuberculosis. American Journal of Neuroradiology 20, 867–875.
38. Gupta, R.K., Kathuria, M.K., Pradhan, S. (1999) Magnetization transfer MR imaging demonstration
of perilesional gliosis: its relationship with epilepsy in treated or healed neurocysticercosis. Lancet
354, 41–42.
39. Pradhan, S., Kathuria, M.K., Gupta, R.K. (2000) Perilesional gliosis and seizure outcome: a study
based on magnetization transfer magnetic resonance imaging in patients with neurocysticercosis.
Annals of Neurology 48, 181–187.
40. Del Brutto, O.H., Santibanez, R., Noboa, C.A., et al. (1992) Epilepsy due to neurocysticercosis: analy-
sis of 203 patients. Neurology 42, 389–392.
41. Yamada, N., Imakita, S., Sakuma, R.T., et al. (1996) Intracranial calcification on gradient-echo phase
image depiction of diamagnetic susceptibility. Radiology 198, 171–178.
42. Yang, D., Korogi, Y., Ushio, Y., et al. (2000) Increased conspicuity of intraventricular lesions revealed
by three-dimensional constructive interference in steady state sequences. American Journal of
Neuroradiology 21, 1070–1072.
43. Govindappa, S.S., Narayanan, J.P., Krishnamoorthy, V.M., et al. (2000) Improved detection of intra-
ventricular cysticercal cysts with the use of three-dimensional constructive interface interference in
steady state MR sequences. American Journal of Neuroradiology 21, 679–684.
44. Chang, K.H., Song, I.C., Kim, S.H., et al. (1998) In vivo single voxel proton MR spectroscopy in
intracranial cystic masses. American Journal of Neuroradiology 19, 401–405.
45. Jayasundar, R., Singh, V.P., Raghunathan, P., et al. (1999) Inflammatory granulomas: evaluation with
proton MRS. Nuclear Magnetic Resonance in Biomedicine 12, 139–144.
46. Garg, M., Chawla, S., Prasad, K.N., et al. (2002) Differentiation of hydatid cyst from cysticercus cyst
by proton MR spectroscopy. NMR in Biomedicine (in press).
47. Nagayama, M., Sbinohara, Y., Nagakura, K., et al. (1996) Distinctive serial magnetic resonance
changes in a young woman with rapidly evolved neurocysticercosis, with positron emission tomog-
raphy results. Neuroimaging 6, 198–201
33
Taenia solium Cysticercosis:
Immunodiagnosis of Neurocysticercosis
and Taeniasis
*In this text and elsewhere in the book, EITB will refer specifically to the enzyme-linked immuno-
electrotransfer blot, developed at the CDC5; immunoblot refers to other blot assays, in general.
© CAB International 2002. Taenia solium Cysticercosis
(eds G. Singh and S. Prabhakar) 329
included in a proposed algorithm for the and GP13, based on relative molecular
diagnosis of NC8. Of the antibody-detection weight determinations using SDS-PAGE. In
tests available today, it performs best, with cases where two or more cysts are present,
exquisite specificity and excellent sensitivity. this assay is very sensitive, 100% and 95%,
Briefly, cysts, collected from naturally using serum or cerebrospinal fluid (CSF),
infected pigs, are homogenized and proteins respectively, and is 99% specific for either
are solubilized in urea. The resultant extract sample6. Mainly because of its ease of collec-
is eventually purified using lentil lectin affin- tion for epidemiological studies, saliva was
ity chromatography. The lentil lectin-bound also evaluated as a source of anticysticercal
glycoproteins (LLGP) are separated using antibodies using EITB. However, saliva was
sodium dodecyl sulphate polyacrylamide gel inferior to serum as an antibody source; of
electrophoresis (SDS-PAGE) and then elec- the cases that were detected using serum,
trophoretically transferred to nitrocellulose only 70% were positive using saliva9.
membranes. The EITB detects antibodies to EITB is highly sensitive in patients
any one of seven cyst-derived glycoproteins with multiple, enhancing intracranial
(Fig. 33.1). These proteins are designated as lesions1,2,10,11. The original description and
GP50, GP39–42, GP24, GP21, GP18, GP14 evaluation of the EITB was performed using
sera from biopsy proven cases of NC, typi-
cally with multiple lesions as detected by
skeletal radiographs6. Continued monitoring
of the test performance, compared with clini-
cal findings using newer imaging tech-
niques, such as CT and MRI, suggested that
the sensitivity of the assay was lower in
cases with single lesions or calcified cysts
(see Chapter 36)12. Several studies demon-
strated that the test is less sensitive, between
60% and 80%, using sera from patients with
a single parenchymal cyst or only calcified
lesions11–13, perhaps because of insufficient
gp 50 immune stimulation11,14. In these situations,
the test sensitivity using CSF also drops con-
gp 42
siderably, to approximately 35%13.
Intraventricular cysticercosis occurs much
gp 24 less frequently than parenchymal NC10.
While MRI is very efficient in revealing the
gp 21
presence of intraventricular cysts, CT is not,
gp 18
yet access to MRI is generally not available
gp 14 in developing countries. Consequently, there
gp 13 is very little published data on the usefulness
of the EITB in intraventricular cysticercosis.
A study of four patients with intraventricu-
Fig. 33.1. Enzyme-linked immunoelectrotransfer lar cysts from Texas found that all four were
blot (EITB) for immunodiagnosis of cysticercosis. EITB positive15. It is our experience, using
Individual sera from persons with possible
results that have been accumulated over
cysticercosis were analysed by the EITB assay;
more than a decade in the Parasitic Diseases
lane 1: negative control sera; lane 2: positive control
sera; lanes 3–11 patient specimens. Sera in lanes Reference Diagnostic Laboratory at CDC
3–6 and 8–9 demonstrate positive antibody from patients with intraventricular cysticer-
reactivities to Taenia solium cyst lentil lectin-purified cosis, that the great majority of these patients
antigens, lane 8 is a weak positive; sera in lanes 7, are EITB positive (Table 33.1). In patients
10 and 11 are negative. Positions of the defined with intraventricular cysts, as opposed to
LLGPs are marked on the left side of the blot. those with parenchymal cysts, it appears that
*Patients had two or more intraventricular cysts, or had both one or more
intraventricular cysts and one or more parenchymal cysts.
†Thirteen of the 34 patients with intraventricular cysts had paired serum and CSF
samples; 10 of 13 pairs were EITB positive, one of 13 pairs was serum positive
but CSF negative, and two pairs were EITB negative (one pair from a patient with
a single active cyst, one pair from a patient with two active cysts).
the antibody response is influenced more by and 12% showed a decrease in the number of
the location of cysts than by the number of proteins recognized in the EITB 1 year after
cysts. Intraventricular cysts are constantly treatment. These data suggest that antibody
bathed in CSF allowing easy access of persistence is proportional to the intensity of
immune cells and mediators, which may be the initial immune response.
involved in initiating the humoral response. The diagnostic utility of EITB vis-à-vis CT
The presence of antibodies to any of was evaluated in a cohort of 383 individuals
seven glycoprotein antigens is considered undergoing CT16. When non-specific CT
diagnostic for NC using the EITB. Over 98% abnormalities such as single lesions and iso-
of the time, sera from infected individuals lated hydrocephalus were excluded, CT
contain antibodies that react with one or scans revealed abnormalities diagnostic of
more of the seven immunodiagnostic pro- NC in 44% of the EITB-positive individuals.
teins6. In a recent hospital-based study in Several explanations may be offered for posi-
Peru, about half of NC patients had serum tive EITB results in individuals with normal
antibodies that reacted to all seven diagnos- CT, such as the presence of extra-neural cys-
tic proteins16. The proteins most frequently ticercosis, or past resolved cerebral cysticer-
recognized are the GP39–42 complex (95%) cosis with persisting antibodies. It is
and GP24 (94%); the lower molecular important to note that serological results
weight proteins, GP14 and GP13, are recog- should be used in conjunction with neu-
nized the least6. roimaging studies, clinical manifestations
A recent study examined the presence of and exposure history for consistent, accurate
anticysticercal antibodies in serum of NC diagnosis of NC8,13.
patients before and after anticysticercal treat-
ment11. At admission, approximately half of
the patients had antibodies that recognized ELISA for Diagnosis of NC
all seven diagnostic proteins. Of these per-
sons, those who were successfully treated Although EITB is accepted as the best diag-
still had antibodies that reacted to all seven nostic test available today, ELISA continues
proteins 1 year after treatment. Of the to be used extensively for both epidemiologi-
patients with antibodies to fewer than seven cal surveys17 and for clinical diagnosis,
proteins, 7% were seronegative after 1 year mainly because of its technical simplicity as
compared to EITB. There is extensive litera- control sera. In contrast, ELISA gave presum-
ture describing the usefulness of ELISA as a ably false positive results with sera from
method for diagnosing NC; much of that patients with several other cestode infec-
work has been reviewed elsewhere18. ELISA tions, including those caused by Taenia sagi-
has been shown to be a useful adjunct for nata, H. nana and Echinococcus granulosus.
diagnosing NC if CSF, not serum, is tested. However, the heterologous infection sera
In one study, an ELISA, which detected anti- used in this study were collected in a region
gen-specific immunoglobulin M (IgM), in Peru known to be endemic for diseases
demonstrated a sensitivity of 87% and speci- caused by all of these parasites; therefore, it
ficity of 95% in CSF specimens from patients is possible that these samples were collected
with active or inactive NC19. However, many from persons with subclinical cysticercosis or
ELISA tests have high false positive and false prior exposure to T. solium. A similar study
negative rates, so results should be inter- compared the ability of both ELISA and EITB
preted with caution3. Most ELISAs detect to detect anticysticercal antibodies in paired
antibodies to antigens that are present in serum and saliva samples from clinically
crude cyst extracts or cyst vesicular fluid. defined NC patients9. In this study, the sensi-
Because the parasite antigens used in these tivity using serum samples was 100% with
assays are not typically purified, ELISA has EITB and 74% with ELISA. However, in
historically demonstrated a lower specificity saliva samples, the sensitivity was 70% using
and sensitivity than EITB. For this review, EITB and 82% with ELISA. These data sug-
we have elected to discuss the ELISA in the gest that ELISA with saliva may be a useful
context of the EITB and examine studies screening test for cysticercosis in the epi-
where the two tests were compared directly; demiological setting. However, its sensitivity
when the ELISA was directly compared with does not equal that of EITB in serum and
the EITB, the EITB has always outperformed specificity remains an issue. In yet another
the ELISA (Table 33.2). study, comparing a commercially available
In one study, sera and CSF from patients ELISA (LMD Laboratories, Carlsbad, CA,
with parasite-confirmed NC were tested USA) with EITB, the latter performed with
using both ELISA and EITB20. Using EITB, higher sensitivity and specificity than
94% and 86% of all confirmed cases were ELISA21. Although there was a good level of
detected using serum and CSF, respectively. concordance between the two tests (85%),
ELISA detected 65% and 62% of cases, this study demonstrated the lack of speci-
respectively, using the same samples. In this ficity often seen with ELISA; 9% of sera were
particular study EITB proved to be 99% positive that were collected from persons
(1/83) specific, possibly falsely detecting one with no clinical or epidemiological evidence
case of Hymenolepis nana infection among 59 of cysticercosis.
Table 33.2. Studies comparing the ELISA and enzyme-linked immunoelectrotransfer blot (EITB) for
diagnosis of neurocysticercosis (NC).
Reference Sample EITB+ (%) ELISA+ (%) EITB+ (%) ELISA+ (%)
The sensitivity of ELISA for detecting of the EITB, but also utilize a simpler assay
cases of NC characterized by single lesions format, such as that of the ELISA. Some
has not been discussed in the literature. investigators have focused on less complex
Consequently, using data accumulated in the sources of parasite material, such as T. solium
Parasitic Diseases Reference Diagnostic cyst fluid22,23. Other scientists have focused
Laboratory at the CDC, we compared the on purification and characterization of the
sensitivity of EITB with that of LMD ELISA seven individual glycoprotein antigens that
by testing 31 samples from persons with are components of the LLGP fraction used in
either pathologically proven or clinically EITB24–26. Still others have opted for using a
documented cases of NC with single lesions more available source of parasite material
(Table 33.3). EITB was positive in 55% of the present in heterologous rodent Taenia
cases, while ELISA was positive in 29%. species, T. crassiceps, as an antigen source27.
These data indicate that the ELISA is less Virtually simultaneously, several labora-
effective than EITB for detecting NC cases tories reported purification of individual
with single lesions. antigens, cloning of complementary DNA
EITB and ELISA were compared in one (cDNAs) and incorporation of corresponding
community-based study in Mexico to identify recombinant or synthetic antigens in new
NC cases and risk factors associated with the immunodiagnostic assays for NC28–30. Many,
disease17. Positive results in each test were but not all, of the recombinant antigens
correlated with epidemiological and clinical reported are components of the LLGP frac-
data. Twelve of 42 persons, reporting a history tion28 and others, although not directly puri-
of seizures, were identified using EITB, but fied from the LLGP fraction29,30, appear to be
none were detected using ELISA. These data closely related to the protein antigens found
demonstrate the superiority of EITB, even in in the LLGP fraction. One of the primary
the community setting, as an important epi- research goals in this field is development of
demiological tool for identifying NC. simpler assays for immunodiagnosis of NC;
therefore, these findings merit a more exten-
sive discussion, presented below.
Recent Advances in Utilizing the LLGP fraction employed in
Immunodiagnosis of EITB, several investigators identified native
Neurocysticercosis 10-, 14- and 18-kDa antigens that are similar
(Fig. 33.2a)25,26. Using amino-terminal amino
Because of the technical difficulties associ- acid sequencing, these three native proteins
ated with EITB procedures, researchers are share identity in 13 of 19 amino acid cycles for
attempting to develop novel tests that would which meaningful sequence was obtained,
not only retain the sensitivity and specificity and similarity at remaining positions. Both
Fig. 33.2. Alignment of cloned diagnostic antigens of neurocysticercosis (NC). CLUSTAL_ alignment
of the deduced amino acid sequences of some recombinant polypeptides reported to have value as
diagnostic antigens for detection of NC65. (a) Sequences 1–4, 6 and 8 represent deduced polypeptides
reported by Greene et al.28; sequences 5, 7 and 9–10 are reported in Sako et al.30; (b) sequence 11 was
reported in Chung et al.29.
groups used native purified proteins in EITB of both the 24- and 39–42-kDa components of
assays and showed these proteins to be sensi- the LLGP fraction and, upon reduction,
tive and highly specific for detecting anticys- yielded two similar, but not identical, 10-kDa
ticercal antibodies, although the 10- and proteins25. The 14- and 18-kDa antigens were
14-kDa antigens appeared more sensitive than purified following reduction of larger LLGPs,
the 18-kDa antigen26. These three antigens, the which ranged in size from 25 kDa to 45 kDa26.
10-, 14- and 18-kDa proteins were all shown to Polyclonal antibodies were generated by both
be components of the larger diagnostic anti- groups that further indicated that these anti-
gens present in the LLGP fraction. The 10-kDa gens are components of larger protein anti-
antigen was identified by separate purification gens. Plancarte et al. generated polyclonal
antibodies against purified GP24 or GP39–42 related cDNAs were cloned that predicted
that reacted with the 10-kDa antigen25. polypeptides ranging in size from 9.6 kDa to
Conversely, Greene et al. produced polyclonal 13 kDa. Escherichia coli-expressed, thiore-
antibodies to the 14-kDa protein that reacted doxin-fusion proteins were evaluated for
with six distinct moieties, co-migrating with specificity and sensitivity. A chimeric con-
GP14, GP18, GP21, GP24, and GP42 antigens struct was created using the cDNA
in the LLGP fraction28. sequences from the two most promising
The cDNAs for the 14- and 18-kDa anti- recombinants, expressed in E. coli, and the
gens were subsequently cloned and resultant recombinant chimeric protein was
sequenced. During the process of cloning, a evaluated in an ELISA. Although a limited
total of five distinct cDNA clones were iden- number of sera (53 NC sera) were evaluated,
tified and all were closely related at both the the chimeric protein demonstrated remark-
nucleic acid and predicted amino acid levels. able sensitivity (100%) and specificity (90%).
Polypeptides that represent the mature pro- Another 10-kDa antigen has been isolated
teins were chemically synthesized (synthetic from cyst fluid that has been evaluated for its
Taenia solium, sTS) 14 and sTS18), and evalu- utility as a diagnostic antigen for detection of
ated as diagnostic antigens using an ELISA. NC cases. This antigen is a subunit compo-
sTS14 demonstrated greater utility than nent of a 150-kDa complex. When the native
sTS18 and was recognized in a disease-spe- 10-kDa antigen was evaluated in the
cific manner using defined sera from persons immunoblot format, the assay had a sensitiv-
with cysticercosis or other helminthic infec- ity of 85%; and only sera from persons with
tions. However, only 53% of sera from per- echinococcosis showed low-level cross-reac-
sons with cysticercosis reacted with this tivity (~10% of these particular sera reacted)22.
synthetic version of TS1428 although 76% of A full-length cDNA encoding this 10-kDa
sera reacted with the native 14-kDa molecule antigen has been cloned and a glutathione-S-
in an immunoblot format26. transferase (GST)-fusion protein was
When all of the data pertaining to the expressed and evaluated in an ELISA. The
purified LLGP antigens are evaluated, sev- overall sensitivity, using 200 sera from per-
eral things become apparent. One, all of the sons with NC, was 88% and was 97% in
proteins in the 10–42-kDa range appear to be detecting active cases of NC. Using approxi-
antigenically and structurally related. And mately 200 sera from persons with other
two, the 24-kDa and larger antigens appear helminthic infections, this assay demon-
to be comprised of subunits of at least two strated a specificity of 98%. The cDNA
smaller (10–14-kDa) proteins28. The precise sequence of this protein revealed that it, too,
manner in which these subunits are assem- is related to the other cDNAs and proteins
bled to form larger proteins remains a sub- encoding cyst fluid antigens, described
ject of intense investigation. above29,30. However, this cDNA and amino
Other significant advances towards devel- acid sequence appears to be the most distinct
oping simplified immunodiagnostic meth- of the sequences described to date (Fig. 33.2b).
ods for NC have been made using purified T. The five cDNA clones encoding the anti-
solium cyst fluid. The soluble antigens pre- gens in cyst fluid are not only all related to
sent in cyst fluid were further purified using one another, but are also related to the cDNA
isoelectric focusing (pH 9.2–9.6) for use in clones, which encode the LLGP antigens
ELISA or immunoblot formats. Three cys- (Fig. 33.2b). All polypeptides encoded by
ticercosis-specific antigens were identified by these cDNAs have similar structural charac-
immunoblotting: a 10-kDa and a 26-kDa teristics: N-terminal hydrophobic regions,
antigen, and a third antigen between 10 kDa which are predicted to be signal sequences
and 26 kDa23. The high level of specificity with signal sequence cleavage sites; all
and sensitivity seen in both the ELISA and encode polypeptides with predicted sizes of
immunoblot led to cDNA cloning and 7.6 kDa to 12.9 kDa; all have similar amino
expression of the recombinant proteins rep- acid compositions with isoelectric points
resenting the native cyst antigens30. Four between 8.0 and 9.6; and 10 of the 11 cloned
antigens contain a conserved IAQLAK pling pots between family members in field
amino acid sequence near the middle of the studies has occurred in the past (James C.
polypeptide. Clearly these proteins are mem- Allan, Sandwich, UK, personal observation).
bers of a larger family of antigenic Taenia
proteins that are expressed in the metaces-
tode stage of the parasite. Detection of coproantigens
positive in assays using antibodies against improvements to these assays, especially the
one species or the other38. Levels of speci- capability to differentiate T. solium and T.
ficity with faeces from infections other than saginata, would broaden their applicability.
Taenia sp. have been demonstrated to be
greater than 99%39–41, resulting in a high
positive predictive value in most T. solium Immunodiagnosis of intestinal Taenia
endemic areas. No cross-reactions have infection
been shown with faeces from other
helminth infections, including H. nana, H. A number of immunodiagnostic techniques
diminuta, Ascaris lumbricoides, Trichuris and have been applied to the diagnosis of human
hookworm39–41. In a field study where all of T. solium and T. saginata taeniasis. Early stud-
the Taenia tapeworms identified to the ies involved the application of intradermal
species level were shown to be T. solium, a tests but these were shown to have high
microtitre plate-based coproantigen assay false-positive and false-negative rates50–54. In
detected 2.6 times more tapeworm carriers particular, the tests were shown to remain
than microscopic detection of Taenia eggs in positive for long periods following treatment
faeces (55 cases diagnosed versus 21)41. The of the infection53. In some cases, reactions
coproantigen test diagnosed 98% of all cases were detected only after treatment or became
detected in the study while microscopy stronger after treatment53. Intradermal test-
diagnosed 38% (55/56 cases and 21/56 ing for T. solium gave false-positive rates of
cases, respectively). Coproantigen tests for 3–7% and a sensitivity of approximately
human taeniasis become negative within 76%54, however, 12% of individuals treated
approximately 1 week after successful for this parasite continued to give positive
treatment of intestinal infection38,43. In results for long periods after treatment, some
canine Taenia infections they are positive patients remaining positive for up to 18
several weeks before patency and give months. These techniques have never been
results independently of egg output39,42. applied on a large scale.
Indeed, the possible detection of at least Serum antibody detection in T. saginata
one pre-patent case of human intestinal T. infection by use of the indirect haemagglutina-
solium has been reported in a field study32. tion technique was also demonstrated55.
A visually interpreted dipstick assay has Prolonged persistence of antibodies after treat-
been used for detection of Taenia coproanti- ment, between 5 and 19 months in some
gens in faeces directly after collection in patients, was reported. Another study reported
rural communities in both Guatemala and that test sensitivity was 56%, with a false-
Mexico40. In a total of 41 cases of taeniasis, positive rate of 1.35%, leading to the conclusion
diagnosed by either coproantigen testing, that this approach was of limited applicability56.
microscopy, or questioning, the dipstick In contrast to the situation with human tae-
test detected 31 (76%) of all cases. This niasis, serum antibody detection has been
compared to 23 cases diagnosed by more thoroughly investigated in canine taeni-
microscopy (56%) and five by questioning asis. Studies in this area indicated both the
(12%). The dipstick format is known to be presence and diagnostic applicability of serum
less sensitive than the microtitre-based antibodies for the diagnosis of a number of
ELISA, but can be performed with minimal different taeniid species in dogs. A variety of
facilities, making it an extremely attractive antigenic preparations have been used includ-
option for epidemiological studies. ing adult worm somatic and ES products and
The results from studies that employed oncosphere antigens57–60. These studies
coproantigen detection assays for the identi- demonstrated that antibody could be detected
fication of Taenia carriers have indicated that before patency and with high levels of speci-
these assays are considerably more sensitive ficity, although cross-reactions occurred
than microscopy and have working charac- between sera from dogs infected with different
teristics suitable for practical application in taeniid species. Tests for antibodies took some
the field in T. solium endemic areas. Further time to become negative after treatment; those
for antibodies to oncosphere products becom- This serological assay for T. solium taeniasis
ing negative within a few weeks after treat- is a valuable method for identifying T. solium
ment. The ability to test for antibody in saliva tapeworm carriers which overcomes many
was also demonstrated61. of the obstacles associated with ova and par-
asite examination or coproantigen detection.
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with neurocysticercosis is related to severity of infection. Neurology 55, 1062.
65. Thompson, J.D., Gibson, T.J., Plewniak, F., et al. (1997) The CLUSTAL_X windows interface: flexible
strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Research 25,
4876–4882.
Antibody Antigens:
(capture molecular No. of No. of Sensitivity Specificity
Method Sample system) weight (kDa) patients controls (%) (%) Reference
Agglutination CSF Anti-CE ND 215 31 77 97 7
4/9/02
PoAb
ELISA/direct CSF Anti-CE ND 17 48 77 100 8,9
PoAb
HP10 200 – – 72 100 13
MoAb
ELISA/homologous capture CSF HP12 12,14
MoAb ND – – 72 100
Porcine anti-CE
Page 344
Serum ND 44
D. Correa et al.
Fraction – – 56 100
33–240
ELISA/heterologous capture CSF 212 13
Anti-CE
PoAb/ 150 ND ND 17
(subcutaneous
cysticercosis)
Subject to the CABI Digital Library Terms & Conditions, available at https://cabidigitallibrary.org/terms-and-conditions
Downloaded from https://cabidigitallibrary.org by 223.255.231.132, on 03/21/24.
Singh - Chap 34 4/9/02 4:45 pm Page 345
molecular weight 230 kDa and 190 kDa, in 14 blot (EITB)20,23,24. In contrast, antigens are
of 18 CSF samples using an immunoblot uncommonly detected. One reason for this
assay10. Similarly, a sensitivity of 75–86% observation could be the rapid sequestration
was obtained when CSF of patients with NC of antigens. Several findings support this
were evaluated with the HP10 MoAb11–13. notion. We detected antigen B, a component
The latter is specific for a 200-kDa glycopro- of the excretory–secretory products of cys-
tein. A molecule of similar molecular weight ticercus, in only 14% of the CSF samples of
was also detected by another MoAb (H7) in patients with NC12,25,26. This particular anti-
more than 50% of cases in CSF and serum of gen is immunodominant, i.e. it elicits a
patients with NC14. We have found five dif- strong antibody response23,27. It binds to col-
ferent antigens using an immunoblot assay lagen with high affinity, as well as to the C1q
in multilesional cysticercosis. A 200-kDa component of the complement cascade28,29.
band was most frequent among the five anti- We surmise that soon after secretion by the
gens, both in CSF and serum14,15. parasite, the antigen is sequestered in the
The 200-kDa antigen that has been identi- host tissues or serum. In a similar manner,
fied in most studies is best recognized by a other antigens that elicit antibody responses
capture assay using the HP10 MoAb in a can either be sequestered in host tissues adja-
homologous system12,13. It is a glycoprotein, cent to the parasite, ingested by phagocytes
having a repetitive epitope11. However, it is or transported to lymphoid tissues, where
not species-specific and this might interfere they may thus escape detection.
with its diagnostic role in extracerebral cys-
ticercosis in areas where other cestode infec-
tions are also prevalent. Among other Evidence of immune complexes in
molecules that have been found in CSF or neurocysticercosis
serum of patients with NC, a fraction larger
than 400 kDa was detected in 29% of patients’ Immune complex formation may be one of
CSF16. Studies by our group and Cho et al., the mechanisms by which antigens disap-
using PoAb and MoAb respectively, have pear and evade detection. There is evidence
revealed the presence of a 150-kDa molecule for the presence of immune complexes in
in 13% of CSF samples from NC cases6,15,17. cysticercosis. Community-based epidemio-
Besides, bands of 183 kDa and 50 kDa have logical studies have attempted to detect both
been found in the serum and the CSF respec- antibodies and antigens in sera of individu-
tively of NC patients in very few instances15. als21,22,30. However, it is extremely rare to
Two MoAb-based methods reported high sen- find antigens and antibodies concurrently in
sitivities (77–97%), but the antigens recognized a given serum sample. In two different stud-
were not identified18,19. An interesting finding ies of epileptics in rural communities of
from one of these studies was that individuals Mexico21 and Brazil (I. Gomes, A. Meza-
with subcutaneous cysticercosis presented Lucas, M. Veiga, et al., Universidade Federal
with antigens in CSF more frequently than da Bahia, Brazil, unpublished observations)
those with intracranial involvement alone19. respectively, the relation between age and
prevalence of antibodies was found to be
inverse to that between age and antigens.
Limitations of Antigen Detection The inability to detect antigens and antibod-
ies in concurrent samples is likely to be
Lack of antigens or sequestration? related to the formation of immune com-
plexes. Indirect evidence for the existence of
A variety of antibody responses in sera and immune complexes also came from a report
CSF of patients with NC have been demon- of nephrotic syndrome complicating cys-
strated with low-resolution procedures like ticercosis31. Renal biopsy revealed membra-
immunoelectrophoresis as well as by more nous glomerulonephritis, implicating the
contemporary and highly sensitive tests such production of immune complexes, surmised
as enzyme-linked immunoelectrotransfer to occur in response to cysticercal infection.
Swine antibodies against a crude cysticer- mising the sensitivity of the assay.
cus extract detected antigens in 48% of Accordingly, a balanced dilution needs to
human CSF samples, but gave negative be determined in order to optimize perfor-
results with sera of cysticercotic pigs12,32. mance of the assay.
The observed discrepancy between human
CSF and pig sera could be explained by the
similarity between native antibodies in Potential Applications of Antigen
infected pigs and the experimentally gener- Detection in the Study of T. solium
ated antibodies. Antigen epitopes may be Infection
blocked by native antibodies leading to
immune complex formation; the failure of Species specific antigens
experimentally generated antibodies to
detect antigens in pig sera may be related to PoAbs against crude preparations of
this immune complex formation. metacestodes cross-react with antigens of
other cestodes as well. This holds true for
MoAbs that have been developed for T.
Absence of antigens or technical solium antigen detection. Indeed, certain
problems? MoAbs that detect T. solium antigens were
raised against T. saginata antigens12,13,32.
The low yield of antigen detection assays Antigen detection assays are therefore only
could be related to several of the technical genus-specific, and their use is limited in
problems described below. In the capture areas where hydatidosis and cysticercosis
assays, PoAbs produce high backgrounds, are co-endemic. Recently, we developed a
confounding discrimination between posi- MoAb against the adult T. solium which
tive and negative samples. On the other reacts much less strongly or not at all with
hand, when MoAbs are used, small quanti- T. saginata and other parasitic antigens (Y.
ties of antigen may escape detection. Medina-Flores, R. García-Rodea, D. Correa,
Furthermore, in homologous-antibody cap- Instituto de Diagnóstico y Referencia
ture systems, it is necessary to have anti- Epidemiológicos & Instituto Nacional de
bodies that react with repetitive epitopes of Pediatría, Ministry of Health, México City,
the antigenic molecule. The latter problem México, unpublished observations). Its use
is overcome in direct capture assays since for antigen detection in cysticercosis
the sample is directly adsorbed. Estrada deserves further investigation.
and Khun developed an ELISA where CSF
antigens were directly bound to polystyrene
wells8. All four confirmed cases and one out Stage specific antigens
of seven patients with a strong clinical sus-
picion of NC were positive by this assay. Positive antigen seroassays do not neces-
Likewise, the sensitivity of a similar assay sarily imply a diagnosis of T. solium cys-
in a larger group of patients was 75%9. ticercosis because of sharing of antigens
While direct capture systems preclude the between the metacestode and adult stages
need for repetitive epitopes, they require of T. solium. We found circulating antigens
large antigen concentrations and therefore in sera of almost 20% of cases with taenia-
give positive results only in those individu- sis in an endemic community of Mexico21.
als with a large cyst load. Another technical In the hamster model of taeniasis, adult
point that has bearing on the positive yield antigens have been demonstrated to cross
is that concentrated serum samples inhibit the intestinal epithelium and enter the cir-
the signal obtained due to antigen. Dilution culation (G. Avila, M. Benitez,
improves this signal but may reduce anti- L. Aguilar, et al., Universidad Nacional
gen concentration as well, thereby compro- Autónoma de México, México DF, México,
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35
Polymerase Chain Reaction in the
Diagnosis of Taenia solium Cysticercosis
specific manner. PCR-based amplification should be specific for the target organism.
assays specific for e.g., Wuchereria bancrofti, The process consists of three steps. The first
Loa loa, Onchocerca volvulus, Setaria digitata and involves heating of the double-stranded
Dirofilaria sp., have been developed for use in sample DNA to denature it into two single-
research and diagnostics4–8. New PCR-based stranded DNA templates. In the second step,
methods for the diagnoses of multicellular the sample is cooled down for primers to
parasites are now being developed. anneal to the single-stranded DNA targets.
The annealing temperature is important for
the specificity and function of the PCR. The
Overview of PCR Technique final step entails amplification, during
which a thermostable DNA-polymerase syn-
Polymerase chain reaction is based on thesizes new DNA strands to the unfinished
amplification of a known sequence from the single strands from the nucleotides pro-
target DNA with two oligonucleotide vided in the mixture so that both strands are
primers. The sequence to be amplified fully built (Fig. 35.1). These amplification
5 3
Target double-stranded DNA
3 5
Heating of the reaction mixture →
Double strand is denatured,
Primers anneal to target binding sites
5 3
Primer A
Cycle 1
Primer B
3 5
Elongation of target DNA leading to
formation of two double-stranded
DNA with strands of variable lengths
Cycle 2
Cycle 3
Fig. 35.1. Polymerase chain reaction. The template DNA, primers, nucleotides and DNA polymerase are
mixed in the presence of a suitable salt concentration. One reaction cycle consists of three steps:
denaturation, annealing and elongation. During each cycle, the amount of DNA is duplicated.
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MgCl2, and 10 mM Tris-HCl. Make up the 72°C for 1 min (extension) and 72°C for 10
volume with dH2O. min (final extension).
2. The PCR master mix is prepared for all 4. Electrophoretic analysis of reaction products:
samples and controls. Add the sample DNA (i) Prepare an agarose gel into 1 TBE
(approximately 500 ng per reaction), buffer (the percentage of the gel depends on
taking care to prevent contamination. the size of the target product; 3% for the tar-
Subsequently, prepare the Taq polymerase (2 get DNA 500 bp, 2% for the target DNA
U per reaction). sized 500–1000 bp and 1.5% for 1000–2000
3. The amplification is performed in a pro- bp). Add ethidium bromide stock solution
grammable thermal cycler. This is a sug- to the gel (3 l per 100 ml);
gested protocol if primers from reference 17 (ii) Add 3 l of 10 loading dye to each
are used, otherwise the amplification proto- sample, remember to have the PCR marker
col is chosen according to the primers in one lane;
selected; 94°C, 10 min (initial denaturation) (iii) Electrophorese the gels;
followed by 35 cycles of 94°C for 1 min (iv) Analyse the results of PCR under
(denaturation), 58oC for 1 min (annealing), ultraviolet light.
36 Immunodiagnosis in Solitary
Cysticercus Granulomas
Anna Oommen
360 A. Oommen
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small enhancing lesions and multilesional cysticercosis. Journal of the Association of Physicians of India
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37 Pharmacology of Anticysticercal
Therapy
Pharmacokinetics: absorption,
distribution, metabolism, elimination and
bioavailability
1500
Plasma concentration (ng ml–1)
Fasting
Lipid diet
Carbohydrate diet
1000
500
0 2 4 6 8
Time (h)
Fig. 37.2. Mean plasma concentration (± SEM) of praziquantel in healthy volunteers administered a
single oral dose of 1800 mg (three tablets of 600 mg) during fasting () or immediately after high fat ()
or high-carbohydrate () meal. (Reproduced with permission from reference 26.)
6
Plasma concentration (g ml–1)
5
PZQ
PZQ + Dexamethasor
4
0
0 2 4 6 8
Time (h)
Fig. 37.3. Plasma levels of praziquantel when administered alone () and during dexamethasone
therapy () (n = 8). (Reproduced with permission from reference 27.)
PZQ + Cimetidine
PZQ
4
Plasma concentration (g ml–1)
0
0 2 4 6 8 10 12
Time (h)
Fig. 37.4. Mean plasma levels of praziquantel in eight healthy volunteers after three oral doses of 25 mg
kg1 administered every 2 hours when given alone () and with cimetidine (). (Reproduced with
permission from reference 29.)
S N
CH3 — CH2 — CH2
NH — CO — OCH3
N
H
Albendazole
S N
CH3 — CH2 — CH2
NH — CO — OCH3
N
H
Albendazole sulphoxide
S
CH3 — CH2 — CH2 N
NH — CO — OCH3
O
N
H
Albendazole sulphone
Fig. 37.5. Chemical structure of albendazole, albendazole sulphoxide, the main active metabolite, and of
albendazole sulphone.
effective against the larval form of T. bioavailability. They cause selective degen-
solium30,38,39. It is widely used in human and eration of parasitic cytoplasmic micro-
veterinary medicine. Albendazole is a tubules. This eventually leads to a decrease
colourless powder, insoluble in water, solu- in adenosine triphosphate levels and
ble in strongly acid solutions and slightly energy depletion. The antimitotic activity
soluble in some organic solvents. The solu- of albendazole is the result of binding to -
bility of its metabolite, albendazole sulphox- tubulin molecules, which causes inhibition
ide (ALBSO) is comparatively less40,41. of the formation of microtubules resulting
in disruption of cell division37. In addition,
there occurs loss of transport of secretory
Mechanism of action vesicles and failure of intestinal cells to
take up glucose, leading to starvation of the
All benzimidazoles are thought to have a parasite. Considering these mechanisms of
similar mode of action, and differences in action, the onset of anthelmintic action is
efficacy of the drugs against different para- slower than that of drugs that act directly
sites probably reflect variations in their on ion channels42,43.
1.6
Age
1.4 < 2 years
6 –15 years
1.2 33 – 68 years
1.0
Cp (g ml–1)
0.8
0.6
0.4
0.2
0
0 2 4 6 8 12 24 48
Time (h)
Fig. 37.6. Comparison of mean plasma levels of albendazole sulphoxide in patients of different ages
after single oral dose of 15 mg albendazole per kg body weight. (Reproduced with permission from
reference 52.)
one subject when administered albendazole sone (8 mg day1) for 8 days54. The plasma
with olive oil in milk (20 ml per 100 ml); levels of ALBSO increased by 50%, an effect
however, in three other subjects, there was that was attributed to impaired elimina-
little change in plasma levels45. In another tion. This finding has been exploited to
study, co-administration with a fatty meal the advantage of albendazole since simul-
(fat content: 40 g) increased ALBSO concen- taneous corticosteroid therapy is often
trations fivefold; Cmax values increased from required during anticysticercal treatment55.
0.45 mol l1 to 1.60 mol l1 during fasting Homeida et al. evaluated pharmacokinetic
state to 2.0–9.0 mol l1 after food, while interactions between praziquantel (40 mg
AUC increased from 2.0–9.0 mol l1 h1 to kg1) and albendazole (400 mg) in healthy
9.6–29.5 mol l1 h1, respectively53. The volunteers56. The authors found that the
facilitation of albendazole absorption by AUC of ALBSO increased 4.5-fold and Cmax
fatty meal presumably results from an values increased from 126 ±15 to 350 ±51
increased bile acid flow in response to neu- ng ml1. Despite high plasma concentration
tral fat in the duodenum. of ALBSO, no adverse systemic, haemato-
Several drug interactions can be logical or hepatic effect was noted.
expected as albendazole and ALBSO share Although the mechanism of this interaction
common hepatic metabolic pathways with is not clear, the finding is significant con-
several pharmacological agents. Their sidering that trials of combination
interaction with dexamethasone is of inter- chemotherapy are in consideration in the
est, primarily on account of the necessity of future. In human cystic echinococcosis,
co-administering the two to forestall or cimetidine was found to increase mean
manage inflammatory reactions to albenda- ALBSO concentrations in samples of bile
zole’s parasiticidal action. Jung et al. inves- and hydatid cyst fluid by about two-
tigated the nature of this interaction in times57. Combined administration of the
eight patients who were treated with alben- two drugs was recommended with a view to
dazole (15 mg kg1 day1) and dexametha- improve therapeutic efficacy of albendazole.
Therapeutic dosage regimens lar, hepatoxicity can occur at any time dur-
ing the course of treatment and does not
Albendazole was initially administered at appear to be related to ALBSO levels47. Liver
doses of 15 mg kg1 day1 for 1 month, based function tests and white blood cell counts
upon previous regimens used for treatment should be performed at baseline and every 2
of human hydatidosis7, 58. Subsequent clinical weeks during therapy. Albendazole has not
experience showed that the length of therapy been studied in pregnant women. However,
could be shortened from 30 to 8 days without studies in animals have shown that it is
compromising drug efficacy55,59–61. Dosage embryotoxic and teratogenic37,62.
intervals for albendazole have been estab-
lished on empirical grounds. Considering
that the average half-life of ALBSO is 11 h in Dosage forms
patients with NC, a twice-daily regimen is
recommended59. In order to compare the reg- Albendazole is approved in several
imen currently used for albendazole (5 mg European and most Third World countries.
kg1, three times a day) versus a regimen of In 1996, albendazole received marketing
7.5 mg kg1 twice a day, a randomized approval from Food and Drug
crossover pharmacokinetic study was per- Administration, USA for use against
formed in ten patients with parenchymal NC. parenchymal NC. The drug is available in
Results showed that in spite of an inter- oral suspension and in tablets containing
individual variability observed, no statistically 200 and 400 mg, each. Some commonly
significant differences were found in several used brand names are Zentel, Eskazole and
pharmacokinetic parameters between both reg- Albenza.
imens59. This suggested that a dosage regimen
of 7.5 mg kg1 every 12 h could favourably
replace the regimen of 5 mg every 8 h. Conclusions
Albendazole appears to be as effective in
paediatric and geriatric populations as in Praziquantel is a heterocyclic pyrazino-iso-
others and no drug-related problems have quinoline derivative. It causes an influx of
been observed in patients as young as 1 year calcium ions leading to muscle contraction
or older than 65 years. However, there is no
and paralysis. The drug is well absorbed
specific information comparing use of alben-
after oral administration, has an extensive
dazole in the elderly with other age groups.
first-pass metabolism, is 80% protein bound
and has an elimination half-life of 1.7–2.7 h.
It crosses the blood–brain barrier. Food
Adverse reactions
increases and antiepileptic drugs decrease its
Albendazole has a high therapeutic index. Its bioavailability. Plasma levels of praziquantel
low solubility may prevent absorption of are reduced to one-half upon dexametha-
quantities necessary to produce toxicity and sone co-administration. The recommended
hence account for the low toxicity profile. dosage regimen is 50 mg kg1 day1 for 2
Clinical experience indicates that albenda- weeks.
zole is well tolerated. Headache, nausea and Albendazole, a benzimidazole com-
vomiting occur in 6–11% of patients and are pound, causes selective degeneration of par-
the most common adverse effects. These are asitic microtubules. It is metabolized in the
related to acute inflammation secondary to liver to an active compound, ALBSO. High
sudden destruction of cysticerci30,39. When levels of both albendazole and ALBSO have
administered in high doses (600–800 mg been demonstrated in the CSF. Of interest, is
day1) over longer periods of time (1 their interaction with dexamethasone; the
month), elevated liver enzymes, headache, latter increases ALBSO levels by 50%.
hair loss, neutropenia, fever, rash and acute Recommended dosage regimens of albenda-
renal failure have been reported62. In particu- zole are 15 mg kg1 day1 for 8–15 weeks.
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In this variety the brain, subcutaneous tissue Patients with cysticercotic encephalitis (usu-
and muscles are riddled with innumerable ally children and adolescents) will require
cysticerci. Patients may present with high-dose corticosteroids with or without
seizures, features of raised intracranial pres- osmotic diuretics or rarely decompressive
sure, focal deficits or dementia. Wadia et al. surgery, depending on their clinical sta-
have cautioned against the use of anticys- tus20,21. In the series of patients reported by
ticercal drugs in this disseminated variety of Rangel et al. only one patient was adminis-
tered praziquantel; others were treated only There are however, other workers who
symptomatically for intracranial hyperten- advocate the use of anticysticercal agents. In
sion21. The prognosis in terms of outcome a recent double blind, placebo-controlled
was uniformly dismal in this series. Some study, Baranwal et al. observed significant
workers have treated severe forms of NC benefit in terms of disappearance of lesions
with albendazole and demonstrated in children who received albendazole ther-
favourable outcome in such patients22,23. apy9. In this study, 65 paediatric patients
Nevertheless, we recommend that the use of with SCG on CT scan were randomly
anticysticercal drugs is best avoided. If used, assigned to receive either albendazole (15
they should be given with caution and in mg kg1 day1) or placebo for 4 weeks.
conjunction with corticosteroids. Follow-up CT scans were performed, 1 and 3
months after beginning of albendazole ther-
apy. After 3 months, 23 of 31 patients who
Solitary cysticercus granuloma received albendazole and only 15 of 32 of
placebo-treated patients showed complete
Solitary cysticercus granuloma (SCG) is a resolution of CT lesions. We have to con-
common form of parenchymal NC24,25. sider, however, that 12.5% of the patients
Controversy regarding the use of anticys- were lost to follow-up in this trial, and that
ticercal drugs in this form of the disease when the results of this study were pooled,
stems from the fact that during the follow- in a meta-analysis, with those obtained by
up, many of these lesions resolve sponta- Padma et al.26 they are not statistically signif-
neously (see Chapter 24). Padma et al. icant any more.
performed a double blind, randomized con- It has been suggested that the empirical
trolled trial of albendazole in 75 patients use of anticysticercal drugs facilitates the
with seizures and SCG26. Albendazole (15 diagnosis of SCG in doubtful cases by hasten-
mg kg1 day1) or placebo was adminis- ing the resolution of these lesions28. Del
tered for 7 days and serial CT scans Brutto administered albendazole (15 mg kg1
obtained at the end of 1 week, 1 month and day1) for 8 days to 20 patients with SCG29.
3 months after beginning of treatment. A CT undertaken after 2 weeks showed disap-
group of 40 patients received albendazole pearance of lesion in 11 patients, partial reso-
and 35 patients received placebo. A total of lution in five and no change in four patients.
35 patients given albendazole and 33 The favourable response to albendazole in 16
patients given placebo demonstrated reso- of 20 patients was construed as supportive of
lution of the CT abnormality at 3 months. a diagnosis of NC. In three out of the four
The difference between the two groups was who had not responded to albendazole, the
not statistically significant. In an open study diagnoses were ultimately revised upon fol-
reported by Singhal and Ladiwala, clinical low-up; two were ultimately diagnosed to
and radiological follow-up of patients with have gliomas and another one, tuberculoma.
SCG showed no significant difference in In a later study, albendazole was used in 39
seizure control and resolution of the lesion patients with seizures and a single lesion
in patients treated with AEDs alone and upon CT30. Overall 32 (82%) patients
those treated with AEDs and anticysticercal responded to the drug and showed reduction
drugs24. Chopra et al. reported that of the 78 in the size of the lesion after 2–4 weeks of
patients with SCG (treated with AEDs therapy. Further investigations in the non-
alone), there was complete disappearance of responders revealed tuberculomas (two),
CT lesions in 47 patients and significant astrocytoma (one), metastatic tumour (one),
reduction in the size of the lesion and sur- granulomatous lesion of unknown aetiology
rounding oedema in another 24 patients (one) and cysticercus (one). The author rec-
upon follow-up CT in 6–12 weeks27. These ommended the use of albendazole not only
and other workers found no advantage in for clearance of cysts but also as a diagnostic
giving anticysticercal drugs in patients with tool to support the diagnosis of NC as the
SCG. cause of the lesion. Rajshekar suggested that
NC4. Cruz et al. noted similar effectiveness mation and oedema (responsible for symp-
when 800 mg of albendazole was given to toms) around dying cyst(s)60. However, the
patients with parenchymal NC for a vari- dose, duration, form, mode and, most sig-
able period (8 days for 19 patients, 15 days nificantly, timing of administration of corti-
for 23 patients and 30 days for 11 costeroids are not clear. In most cases the
patients)55. Garcia et al. compared the effi- clinicians use their own judgement to
cacy of 1 week versus 2 weeks of albenda- decide whether or not to use corticos-
zole therapy and noted no significant teroids. Corticosteroids are recommended
difference56. Current opinion favours a 1- as an important part of therapy for cysticer-
week course of albendazole therapy57. cotic encephalitis in children and dissemi-
Finally, Del Brutto et al. compared a single- nated NC. They are also recommended for
day praziquantel therapy with 1 week of treatment of acute neurological deficit
albendazole for NC and found similar resulting from oedema, vasculitis and large
favourable results58. Clearly, more double subarachnoid cysts. The use of corticos-
blind controlled studies are needed to teroids may modify the plasma levels of
assess the efficacy of praziquantel and anticysticercal drugs and affect the efficacy
albendazole using different dosage and of these drugs. Concomitant administration
duration schedules. of corticosteroids reduces the plasma level of
praziquantel (see Chapter 37). Shandera
et al. observed that patients treated with
Should patients with non-responding or praziquantel and corticosteroids were more
partially responding lesions receive a likely to require a second course of prazi-
second course of anticysticercal agents? quantel than those treated with praziquan-
tel alone61. It has been suggested that as the
It is well known that not all patients will half-life of praziquantel is 2–3 h, corticos-
show complete resolution of cysts with anti- teroids should be given 4 hours after the
dose of praziquantel to have optimal anti-
cysticercal drugs. Chong et al. reported a
cysticercal and anti-inflammatory effects.
patient with multiple parenchymal NC, in
Plasma levels of albendazole increase when
whom cysts persisted even after repeated
given concurrently with dexamethasone
courses of albendazole and praziquantel59.
and therefore many recommend the use of
In clinical experience, it is not uncommon to
albendazole in preference to praziquantel
see patients with a partial response upon
as an anticysticercal agent. The administra-
brain imaging in terms of the number and tion of intermittent long-term treatment
size of cysts that have resolved after anti- with corticosteroids has been demonstrated
cysticercal treatment. It is not clear whether to improve chances of ventriculoperitoneal
such individuals should be offered a second shunt patency in patients with hydro-
course of anticysticercal treatment. It is also cephalus due to NC. An open controlled
not clear as to what would be the appropri- study evaluated clinical status, incidence of
ate time to repeat the anticysticercal drug shunt malfunction and CSF abnormalities
and if a different drug or the same drug for up to 2 years in patients in whom a ven-
should be used for the repeat course of anti- triculoperitoneal shunt had been inserted
cysticercal therapy. for cysticercotic hydrocephalus62. Two of
the 13 patients given prednisolone (50 mg,
three times a week) required shunt revi-
Symptomatic Therapy of sion, while 18 of 30 patients in the control
Neurocysticercosis group required shunt revision when fol-
lowed up for 2 years. The difference was
Corticosteroids statistically significant; better shunt func-
tion in the prednisolone-treated group was
Corticosteroids are often administered in related to improvement in cerebrospinal
NC on the premise that they reduce inflam- fluid abnormalities.
steroids and AEDs) or to symptomatic treat- will include the persistence of seizures and
ment with albendazole. Patients with both the late development of hydrocephalus
intraparenchymal and extraparenchymal (Arturo R. Carpio, Cuenca, Ecuador, per-
cysts will be included but randomized inde- sonal communication). The results of these
pendently. The primary outcome measure two randomized, double blind placebo-con-
will be reduction of cysts at 1 year after trolled trials of anticysticercal therapy in
treatment. Secondary outcome measures NC are keenly awaited.
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39 Neurocysticercosis: Neurosurgical
Perspective
Fig. 39.2. Illustration of an unassembled ventriculoperitoneal shunt designed by Sotelo et al. (see text
for explanation). The ventricular catheter (above) and the peritoneal catheter (below) are shown. Scale
shows centimetres. (Reproduced with permission from reference 16.)
0 0
–100 –100
0 200 400 600 800 0 10,000 20,000 30,000
duncular and perimesencephalic cisterns. A ricle. However, the fourth ventricle dilates and
major limitation is that it will fail if the sub- balloons out, often leading to the complica-
arachnoid spaces in the CSF pathway distal tion of posterior fossa mass with transforam-
to the interpeduncular cistern are occluded inal or reverse herniation. It is important to
because of cysticercotic arachnoiditis. distinguish this condition from a fourth ven-
Torlkidsen’s operation involves the creation tricle cyst because the surgical approaches to
of a communication between the third ven- the two conditions are different. A trapped
tricle and the cisterna magna20. This proce- fourth ventricle may require the insertion of
dure is useful in cases of third or fourth a separate shunt in the fourth ventricle21.
ventricle obstruction. In the case of a unilat-
eral hydrocephalus due to obstruction at the
foramen of Monro, a septum pellucidotomy Hydrocephalus in association with viable,
may be undertaken either after open cran- free intraventricular or cisternal cysts
iotomy, stereotactic localization or endoscop-
ically (see Chapter 40)10. In the absence of evidence of inflammation
An uncommon situation is the occurrence associated with intraventricular and cisternal
of a trapped fourth ventricle21,22. This occurs cysts, in the form of ependymitis and menin-
in the event of dual obstruction; aqueductal gitis/arachnoiditis respectively, a primary
stenosis due to perimesencephalic arach- removal of the cyst can be recommended
noiditis or ependymitis causes hydrocephalus (Figs 39.1 and 39.4)23,24. This often obviates
and fourth ventricle outlet obstruction the need for VPS. Surgical excision of the cyst
because of intraventricular cysticercosis or needs to be accomplished for several reasons.
arachnoiditis obliterates the foramina of First, the role of medical treatment in intra-
Luschka and Magendie. In such an event, the ventricular and cisternal NC is controversial.
lateral ventricles and the third ventricles are There is a theoretical risk of inflammatory
decompressed by a VPS in the lateral vent- exacerbation of symptoms with anticysticer-
Neurocysticercosis
Trial with
anticysticercal
drugs/
Anticysticercal Asymptomatic Focal corticosteroids
therapy compression
Follow-up
Ventriculoperitoneal
shunt + partial
excision
Increase in
size
Excision
cal drugs. Second, free-floating intraventricu- ratory arrest. Finally, free and viable intra-
lar cysts are at risk of obstructing the CSF ventricular as well as viable cisternal cysts
flow across several points, including the fora- are at risk of inflammatory degeneration dur-
men of Monro, aqueduct and the fourth vet- ing the natural course of their evolution. This
ricular outlet, by a ball-valve phenomenon. elicits an inflammatory reaction in the ven-
This can lead to acute hydrocephalus with tricular walls leading on to ependymitis and
rise in ICP, manifesting clinically with altered meningitis in the case of intraventricular NC,
sensorium, leading to coma and cardiorespi- and meningitis and arachnoiditis in the case
of cisternal cysticercosis. Therefore intraven- defects. A cyst located within the fourth ven-
tricular and cisternal cysts should be ideally tricle is approached via posterior fossa cran-
removed in order to prevent the above men- iotomy. The free cyst may protrude
tioned complications. Cysts may be removed spontaneously through the foramen of
by open surgical intervention in the case of Magendie towards the cisterna magna or it
cisternal forms and by either open cran- may be gently pulled out of the fourth ven-
iotomy using microsurgical technique or tricle (Fig. 39.5a–c). When the cyst is adher-
endoscopically in the case of intraventricular ent to the wall of the ventricle or if the
NC. Stereotactic localization may be per- foramen of Magendie is stenosed or
formed before craniotomy in case of diffi- obstructed, it needs to be opened or widened
culty. Free cysts located in the lateral or third with section of the inferior portion of the
ventricle are operated using anterior inter- vermis to facilitate visualization of the inner
hemispheric transcallosal or transcortical part of the ventricle. Madrazo et al. proposed
approach through the middle frontal pipette suction technique for atraumatic
gyrus23,24. extraction24,25. They devised a special long
Intraventricular cysts are more commonly pipette, which attaches to the cyst by suction
located in the occipital horns of the lateral and permits removal without rupture. They
ventricles and these might be approached by considered intraoperative cyst rupture as a
an occipital incision with occipital lobec- dangerous event24. Others, however, do not
tomy. A complication that must be endured share this view15,23. However, in all cases of
in such event is the occurrence of visual field intraoperative rupture of cyst, intraventricu-
Fig. 39.5. Surgical exposure of fourth ventricle cysticercosis. An active cyst is seen protruding from the
foramen of Magendie (a, b). A degenerating cyst with thick opaque walls that was delivered by section of
the inferior portion of the vermis (c). (Source: B.O. Colli, São Paulo, Brazil.)
lar lavage with Ringer’s lactate solution at been tried but experience with this procedure
body temperature is advocated in addition is limited and not favourable31.
to the systemic administration of high
potency corticosteroids. Endoscopic excision
has been advocated both for supratentorial Diffuse cerebral oedema (encephalitic or
and infratentorial intraventricular cysts26–28. pseudotumoral form)
Endoscopic third ventricular cyst removal
may be carried out very effectively using a Miliary infestation with diffuse inflamma-
rigid rod lens endoscope through a frontal tory reaction and oedema in the brain
burr hole. The foramen of Monro may be parenchyma, constitutes the clinical syn-
identified upon entering the lateral ventricle drome of cysticercotic encephalitis. Intra-
by noting the presence of the choroid plexus cranial pressure is raised and a major
and the thalamostriate vein. It is not uncom- determinant of the poor outcome in this con-
mon in long-standing hydrocephalus, to dition. There is increase in parenchymal vol-
find multiple perforations within the sep- ume with corresponding reduction in
tum, hence it is important to identify the ventricular and cisternal volumes. The pri-
correct portal of entry into the third ventri- mary treatment of this form is with deconges-
cle. It is usually not possible to remove the tants and corticosteroids. The latter prevent
cyst in toto, and the cyst usually gets secondary inflammatory reaction triggered
ruptured during removal. Intraventricular by acute destruction of the parasites23. In
injection of corticosteroids to prevent ana- exceptional cases, where intracranial hyper-
phylactic reaction remains controversial27,28. tension is refractory to medical treatment and
Endoscopic removal is reviewed in detail in threatens life or vision, decompressive bitem-
Chapter 40. poral craniotomy, or unilateral temporal or
frontal craniotomy and lobectomy may be
considered (Fig. 39.6)29,30,32.
Tumour-like syndrome (space occupancy
or tumoral form)
Local compression
Cysticercal cyst(s) may grow in size in the
parenchyma, cistern(s) or ventricle(s) and may All forms of NC may produce symptoms
produce mass effect and intracranial hyperten- and signs of compression of neural tissue
sion. Such cases are best treated by direct sur- when cysts grow to large or giant propor-
gical excision. Active cysts adhere weakly to tions. The location of the pathology dictates
neural tissue and can easily be excised com- the surgical approach (Table 39.1; Figs 39.5
pletely (Fig. 39.4). In the degenerative phase, and 39.7a and b).
intense inflammatory reaction around the
cyst(s) makes them firmly adherent to nervous
tissue or blood vessels and their complete
excision carries a risk of producing neurologi-
cal deficit. Such cysts are treated by cyst
decompression or partial resection via a
direct/stereotactic/endoscopic approach.
Cyst puncture is a relatively simple proce-
dure for decompressing giant cysts. However,
it rarely produces lasting results because cysts
are often multiple and the possibility of cysts
refilling29,30. The establishment of a shunt
between the cyst and the subarachnoid space
is not recommended because of its proclivity
to cause cysticercotic meningitis and arach- Fig. 39.6. Surgical specimen of frontal lobectomy
noiditis10. Cystoperitoneal drainage has also for disseminated neurocysticercosis.
Fig. 39.7. (a and b) Exposure for cysts in the suprasellar region showing surgical anatomy of the
region. c, Cysticercus cyst; IC, internal carotid artery; ON, optic nerve. (Reproduced with permission
from reference 10.)
Surgical Outcome and Postoperative Sotelo et al. reported excellent results with
Management their new shunt device that has been
described in an earlier section of this chapter.
The high postoperative mortality and mor- Their shunt was reported to be functional for
bidity observed in the past has been reduced a mean period of 9 ±2 months in 25 patients;
to a minimum by the following. only one patient required shunt revision16.
However, while the new device took care of
1. Better identification of patients with free shunt occlusion, inadequate drainage became
intraventricular cysts with ventriculo-CT or a problem17. Clinicoradiological follow-up of
MRI. the patients revealed conversion of a hyper-
2. Use of microsurgical techniques. tensive hydrocephalus to normotensive
3. Satisfactory control of aseptic meningitis hydrocephalus17. Thus the clinical picture
with perioperative and postoperative corti- changed from one of intracranial hyperten-
costeroids. sion to that of a frontal lobe gait disorder,
4. Availability of better functioning shunt dementia and incontinence. Radiological
devices. studies revealed inadequate resolution of
ventricular size. In order to obviate this com-
plication, the authors increased the cross-sec-
tional area of the peritoneal catheter from
Hydrocephalus
0.126 mm2 to 0.146 mm2. Further experience
with the revised shunt device including long-
Cysticercotic hydrocephalus constituted
term follow-up is awaited.
group III of Stepien and Chorobski’s classifi-
cation of clinical presentations requiring neu-
rosurgical intervention11. Individuals with
Tumoral form
this presentation were treated with total or
partial cyst exeresis or, in cases where this
The prognosis is far better than other forms.
was not possible, by decompression.
Out of 55 patients with this presentation in
Understandably, results were poor and post-
Stepien’s series, 35% recovered, 40% showed
operative mortality was high. The use of VPS
improvement, 2% showed no improvement
improved outcome of cysticercotic hydro- and 24% died in the postoperative period12.
cephalus. However, as experience with VPS This led him to conclude: ‘It is tempting to con-
accumulated, it was realized that this proce- clude, therefore, that in every case in which a
dure was associated with a high rate of shunt diagnosis of localized cerebral cysticercosis is
malfunction particularly due to occlusion made, operation should be performed’.
within the first 2 years after its insertion. Thus Colli et al. operated on 12 patients with
Colli et al. noted that 54% of 144 patients who giant intracranial cysticercosis and observed
were submitted to shunting, required reoper- good postoperative outcome in all 1210.
ation, mostly in the first 2 years10. Others have
similarly reported high incidence of shunt
malfunction14. The frequency of shunt mal- Pseudotumoral form
function correlates with the degree of abnor-
mality in CSF cell count and protein. In Surgery is rarely required and advocated in
general, mortality in cysticercotic hydro- this form of cerebral cysticercosis. The out-
cephalus is as high as 50% within the first come after surgery is not good. Thus, in 34
year. Those who survive and do not develop patients who were operated on for pseudo-
complications in the initial 1 or 2 years gener- tumoral cerebral cysticercosis in Stepien’s
ally do well. Intermittent long-term pred- series, about half had partial improvement,
nisolone therapy after VPS reduces shunt 14% had no change in their clinical status
malfunction and improves functional status and 32% died after surgery12. Colli et al. per-
of the patient36. In these cases, prednisolone is formed bitemporal decompressive surgery in
started within the first postoperative week at five patients. Three patients improved, while
a dose of 50 mg three times a week. two died a few days later10.
References
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cysticercosis of fourth ventricle. Journal of Neurosurgery 87, 29–33.
2. Del Brutto, O.H., Quintero, L.A. (1995) Cysticercosis mimicking brain tumour: the role of albenda-
zole as a diagnostic tool. Clinical Neurology and Neurosurgery 97, 256–258.
3. Allcut, D.A., Coulthard, A. (1991) Neurocysticercosis: regression of a fourth ventricular cyst with
praziquantel. Journal of Neurology, Neurosurgery and Psychiatry 54, 461–462.
4. Sotelo, J. (1997) Treatment of brain cysticercosis. Surgical Neurology 48, 110–112.
5. Sotelo, J., Del Brutto, O.H., Penagoes, P., et al. (1990) Comparison of therapeutic regimen of anticys-
ticercal drugs for parenchymal brain cysticercosis. Journal of Neurology 237, 69–72.
6. Wadia, N.H., Desai, S., Bhatt, M. (1988) Disseminated cysticercosis. New observations including CT
scan findings and experience with treatment by praziquantel. Brain 11, 597–614.
7. Del Brutto, O.H., Santibanez, R., Nobla, C.A., et al. (1992) Epilepsy due to neurocysticercosis: analy-
sis of 203 patients. Neurology 42, 389–392.
8. Colli, B.O., Martelli, N., Assirati, J.A., et al. (1995) Surgical treatment of cysticercosis of the central
nervous system. Neurosurgery Quarterly 5, 34–54.
9. Sharma, B.S., Gupta, S.K., Khosla, V.K. (1998) Neurocysticercosis: surgical considerations. Neurology
India 46, 177–182.
10. Colli, B.O., Martelli, N., Assirati, J.A., et al. (1994) Cysticercosis of the central nervous system. I.
Surgical treatment of cerebral cysticercosis. Arquivos de Neuropsiquitria 52, 166–186.
11. Stepien, L., Chorobski, J. (1949) Cysticercosis cerebri and its operative treatment. Archives of
Neurology and Psychiatry (Chicago) 61, 499–527.
12. Stepien, L. (1962) Cerebral cysticercosis in Poland. Clinical symptoms and operative results in 132
cases. Journal of Neurosurgery 19, 505–513.
13. Salazar, A., Sotelo, J., Martinez, H., et al. (1983) Differential diagnosis between ventriculitis and a
fourth ventricle cyst in neurocysticercosis. Journal of Neurosurgery 59, 660–663.
14. Sotelo, J., Marin, C. (1987) Hydrocephalus secondary to cysticercotic arachnoiditis. A long-term fol-
low-up review of 92 cases. Journal of Neurosurgery 66, 686–689.
15. Lobato, R.D., Lamas, E., Portillo, J.M. (1981) Hydrocephalus in cerebral cysticercosis. Pathogenic
and therapeutic considerations. Journal of Neurosurgery 55, 786–793.
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extraction of intraventricular neurocysticercus cysts. Technical note. Journal of Neurosurgery 50,
531–532.
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27. Bergsneider, M., Hooloy, L.T., Lee, J.H., et al. (2000) Endoscopic management of cysticercal cysts
within the lateral and third ventricles. Journal of Neurosurgery 92, 14–23.
28. Bergsneider, M. (1999) Endoscopic removal of cysticercal cysts within the fourth ventricle. Technical
note. Journal of Neurosurgery 91, 340–345.
29. Couldwell, W.T., Zee, C.S., Apuzzo, M. (1991) Definition of the role of contemporary surgical man-
agement in cisternal and parenchymatous cysticercosis cerebri. Neurosurgery 28, 231–237.
30. Stern, W.E., (1981) Neurosurgical considerations in cysticercosis of the central nervous system.
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40 Endoscopic Management of
Intraventricular Cysticercosis
meets these goals. The other two options, Historically, the surgical removal of
anticysticercal drugs and CSF shunt diver- fourth ventricular cysts has generally been
sion, each have significant drawbacks that considered to require a standard suboccipital
have been considered in detail Chapters 20 craniectomy for direct visualization of the
and 39. fourth ventricle10,20,29–34. The endoscopic
The definitive removal of the cysticercal approach to the fourth ventricle is techni-
cyst from the ventricle requires a surgical pro- cally more difficult compared with that of
cedure. Primary removal of intraventricular the lateral and third ventricles especially
cysticercal cysts has been advocated by many when arachnoid adhesions are present. In
authors2,3,6,8,10–18. Classically, these lesions have appropriately selected patients, however, the
been approached as if they were neoplasms endoscopic approach to the fourth ventricle
that required a wide surgical exposure for (described below) is safe, effective and asso-
direct visualization and removed2,8,10,15,16,19,20. ciated with decreased operative time, less
For cysts located in the lateral or third ventri- blood loss and less postoperative pain com-
cles, the interhemispheric–transcallosal or pared with the suboccipital craniotomy35.
transcortical approaches via a craniotomy
have been the standard procedures21. The
potential morbidity associated with these Patient Selection and Preoperative
procedures, especially the third-ventricle Management
approach, is dependent upon surgical experi-
ence and can be devastating22–24. For cysts At our institution, every patient with docu-
within the lateral and third ventricles, a surgi- mented intraventricular cysticercal cysts is con-
cal approach using a flexible neuroendoscope sidered for endoscopic removal of the cysts. In
through a burr hole–transcortical approach is our experience, only a few of these cysts are
significantly easier, safer, and comparably incidental findings – testifying to the high pro-
effective compared with the classic open cran- clivity of intraventricular cysts to cause clinical
iotomy approach. In addition, an endoscopic problems. Whereas, magnetic resonance imag-
approach has several important advantages ing (MRI) including contrast, proton density
over craniotomy. One disadvantage of the and fluid attenuated inversion recovery
open craniotomy approach is that intraven- (FLAIR) imaging constitute the standard inves-
tricular cysts can migrate within the ventricu- tigative approach to intraventricular cysticer-
lar system25,26. This is especially true of lateral cosis, the most definitive neuroimaging study
ventricle cysts that frequently settle in the is the ventricular contrast computed tomogra-
occipital horn if the patient is in the supine phy (CT) scan (Fig. 40.1). This study, however,
position. In cases of cysts located in both lat- requires access to the CSF system (most often
eral ventricles, open craniotomy approaches via a ventriculostomy catheter placed for acute
become increasingly destructive in order to hydrocephalus) and a suitable anatomic situa-
gain access to both occipital horns. An easily tion. For example, a study showing only one
performed septum pellucidotomy with an compartment of a multiloculated hydro-
endoscope allows near complete access to the cephalus may fail to show cysts in other com-
entirety of both lateral ventricles and the third partments. When the diagnosis is suspected
ventricle. Compared with an open cran- and the MRI study is inconclusive or not
iotomy approach, access to the third ventricle obtainable, we instill 5 ml of CSF-compatible
with a flexible neuroendoscope is nearly non-ionic contrast via a ventriculostomy and
effortless. The posterior third ventricle can be obtain a CT scan approximately 20–30 min
explored without manipulating the fornices later. The results of this study can also be help-
or structures within the velum interpositum. ful in assessing the need for septum pellucido-
Lastly, compartmentalized hydrocephalus can tomy or third ventriculostomy.
be effectively and easily treated using the There are several relative contraindica-
endoscopic approach since it allows the sur- tions to endoscopic resection of intraventric-
geon to perform a third ventriculostomy ular cysts. First, the presence of ependymal
and/or a septum pellucidotomy27,28. enhancement immediately adjacent to an
Fig. 40.1. Coronal gadolinium-enhanced T1-weighted magnetic resonance imaging (left) demonstrating
mild hydrocephalus and ependymitis in the fourth ventricle (arrowhead). The study was suspicious but
not definitive for a fourth ventricular cyst. Axial computed tomography contrast ventriculogram (right)
showing a multilobulated filling defect confirming a fourth ventricle cysticercal cyst in this patient (see Fig.
40.4). The degree of hydrocephalus had increased between the two studies.
intraventricular cyst increases the chances tomy in order to have enough room to
that the cyst may be adherent to the ventric- remove the cyst and nodule.
ular wall (Fig. 40.2). We have found that Symptomatic patients who have acute
many of these cysts, which are degenerating hydrocephalus should be treated emergently
and causing inflammation, can be safely with a ventriculostomy catheter. It is impor-
removed using a judicious endoscopic tech- tant not to overdrain and collapse the ventri-
nique (see below). An endoscopic explo- cles since this will make endoscopy much
ration is not attempted in cases when there is more difficult or even impossible. All
extensive enhancement of the ependymal patients are given dexamethasone 4–10 mg
surfaces (Fig. 40.2) and subarachnoid spaces. intravenously just before surgery and every
In such cases, even open craniotomy 6 h thereafter for 24 h. Standard periopera-
approaches may not be effective9,36. Careful tive antibiotics are given as well.
attention must be paid to the fourth ventric-
ular outlet since an enhancement pattern in
this area may signify a technically difficult, if Endoscopic Technique
not impossible, endoscopic approach to the
Lateral and third ventricle cysts
fourth ventricle. A second relative con-
traindication to the neuroendoscopic
Instrumentation
approach is the lack of hydrocephalus. With
slit ventricles, the endoscopic retrieval of the Anecdotal reports of endoscopic approaches
cyst may be technically difficult and there- to the lateral and third ventricles for cysticer-
fore riskier. In our limited experience we cosis have used a variety of techniques and
have not come across such a situation since instruments2,3,25,30,33,37,38. To maximize surgi-
all of our patients have had some degree of cal possibilities and effectiveness, we prefer
ventricular enlargement. In rare cases, very a flexible endoscope such as the Codman 4-
large cysts containing solid components that mm steerable flexible neuroendoscope
are larger than the peel-away sheath may (Johnson & Johnson Professional, Inc.,
require an open craniotomy and corticec- Raynham, MA, USA). A rigid-lens endo-
Fig. 40.3. Video image-captures demonstrating the removal of a third ventricle cyst via a right precoronal
burr hole. (a) The free-floating cyst is identified in the posterior aspect of the third ventricle. (b) A
transendoscopic snare grasping instrument is used to capture the cyst. (c) The cyst is secured with the
instrument and maintained just distal to the tip of the endoscope. (d) Delivering the cyst through the
foramen of Monro into the right lateral ventricle.
Fig. 40.4. Video image-captures of an endoscopic removal of fourth ventricular cysts. (a) Extradural view
as the endoscope approaches the small dural opening. The dura is retracted with a suture on either side
of the opening. No bone has been removed as noted by the intact opisthion. (b) The endoscope has
entered the cisterna magna and is navigated cephalad. The cysticercal cysts are seen protruding from
the foramen of Magendie. An incidental choroid plexus cyst is present (possibly a migrating
transchoroidal cysticercal cyst). (c) The transendoscopic grasping is oriented so that the jaws open
horizontally, thereby decreasing the risk of injuring the brainstem. (d) The cysts are retrieved keeping the
tip of the grasping instrument just beyond the endoscope. (e) The cyst and the endoscope are withdrawn
simultaneously. (f, g) Inspection of the fourth ventricle reveals another large cyst that is retrieved in a
similar manner. (h) Note the ependymitis of the floor of the fourth ventricle. (i) Final inspection of the
ventricle showing the aqueduct of Sylvius. The subependymal haemorrhage present likely occurred when
the cyst passed from the third to the fourth ventricle before the surgical procedure.
Fig. 40.5. Intraoperative set-up for an endoscopic approach to the lateral and/or third ventricle. The
patient is positioned semi-recumbent with the head further flexed and resting on a horseshoe apparatus.
This enables the burr hole to be the most superior point of the head and therefore minimizes the amount
of postoperative intracranial air. The primary surgeon stands to the right looking directly at the video
monitor. The body of the flexible endoscope is suspended via a fixed Bookwalter mount.
away cannula. The cyst is retained just the interpeduncular cistern to confirm the
beyond the distal end of the endoscope and fenestration of the membrane of Liliequist.
delivered to the specimen cup. If the cyst
wall tears, the fragmented piece is delivered
and the capture and withdrawal technique Fourth ventricular approach
repeated until the entire cyst is removed. The
endoscope is navigated back into the ventri- Instrumentation
cle and additional cysts, if present, removed
The below-described approach requires a
using the aforementioned technique. Once
flexible neuroendoscope such as a Codman
all cysts are removed, irrigation is continued
4-mm flexible neuroendoscope (Johnson &
until cloudiness and particulate material
Johnson Professional, Inc., Raynham, MA,
within the ventricular fluid has cleared. For
USA). A rigid or semi-flexible endoscope
the wound closure, we prefer to leave a piece
cannot be used owing to the risk of injuring
of Gelfoam in the burr hole to prevent run-
the brainstem. A separate cannula (such as a
down bleeding into the ventricle and use a
peel-away sheath) is not used, nor required.
titanium (or equivalent) burr hole cover. The
A transendoscopic grasping instrument is
scalp is closed in a routine watertight fash-
needed. We use gravity-fed Plasma-Lyte or
ion. For patients who have a ventricu-
lostomy catheter placed preoperatively, this lactated-Ringer’s solution for irrigation. The
catheter is left in place for 24 h to monitor irrigation tubing is connected to the endo-
intracranial pressure (ICP) and discontinued scope using an irrigation adapter (Codman
if ICP is normal. Neuroglide, Johnson & Johnson Professional,
Inc., Raynham, MA, USA). The endoscope is
secured by a moveable holding system such
Septum pellucidotomy as a Bookwalter set-up28,35.
A septum pellucidotomy is performed if there
is need to inspect and remove other cysts in Operating room set-up and patient
the contralateral ventricle or if the ependymal positioning
irritation is marked and there is potential for
unilateral hydrocephalus. The perforation is The patient is placed prone in the so-called
made using a monopolar cautery wire ‘Concorde’ position with the head secured in a
(Codman ME2, Johnson & Johnson three-point rigid skull fixation device (Fig.
Professional, Inc., Raynham, MA, USA) or by 40.6). The neck is flexed to the same degree
using the neodymium:yttrium aluminium- that is used for a standard suboccipital craniec-
garnet (Nd:YAG) laser. The fenestration can tomy. The ventriculostomy catheter, if present
be mechanically enlarged by the endoscope. before surgery, is kept open to drainage during
induction of anaesthesia, but afterwards is
closed and used for monitoring of ICP only.
Third ventriculostomy The endoscope is set up and secured to
A third ventriculostomy can be performed the accompanying endoscope holder and
when hydrocephalus is associated with secured to a Bookwalter mount. The primary
aqueductal stenosis and the obstruction can- endoscopist stands at the patient’s left side
not be alleviated by removal of the cyst. We and the assistant stands at the right side. The
identify the standard anatomic landmarks television monitor is situated at the patient’s
and then puncture the tuber cinereum, just right side, next to the anaesthetist. A gravity-
posterior to the vascular discoloration fed irrigation solution similar in pH and
imparted by the infundibular recess, using osmolarity to CSF, such Plasma-Lyte (Baxter,
the straight end of a vascular guide wire Deerfield, IL, USA), is preferable to 0.9 M
(diameter: 0.81 mm/0.032 inch). A No. 3 saline because the low pH of the latter may
French Fogarty or Cook elliptical balloon interfere with the respiratory drive centres
catheter is used to expand the perforation adjacent to the fourth ventricle while the
and the flexible endoscope is navigated into patient recovers from anaesthesia.
Fig. 40.6. Intraoperative set-up for an endoscopic approach to the fourth ventricle. The patient is
positioned prone with the head further flexed and immobilized with a Mayfield three-point holder
(‘Concorde’ position). The primary surgeon stands to the patient’s left looking directly at the video
monitor. The body of the flexible endoscope is suspended via a fixed Bookwalter mount.
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Table 41.1. Synopsis of intervention strategies available for Taenia solium taeniasis–cysticercosis.
● Known contribution to elimination of parasite from ● Pigs in many endemic countries do not go to formal
carcasses (meat inspection) several developed countries slaughter
● Relatively easy to integrate with meat inspection for ● Infected pigs can be diagnosed ante mortem (tongue
several other important diseases inspection) and slaughtered outside regulated system to
avoid condemnation of carcasses
4:47 pm
Improved sanitation, hygiene and ● Known contribution to elimination of parasite from ● Economically difficult in many existing endemic areas
pig husbandry several developed countries
● Provides benefits beyond control of T. solium
Health education ● Provides benefits beyond control of T. solium ● Improved knowledge does not always result in change
of practices
Page 412
cysticercosis
Vaccination of swine ● Long-term protection ● Many existing producers in endemic areas do not
● Possible to integrate with existing veterinary and/or currently vaccinate against other diseases with high
pig husbandry practices economic impact on swine production
● Provides economic benefit to end user (avoidance of ● Vaccines not available now (other than at experimental
carcass condemnation) level)
● Compliance monitoring possible (serological testing)
Chemotherapy of infected swine ● Drugs available now ● Producers often do not treat for other economically
● Highly effective important parasites despite economic benefits
● Producers have economic motivation (avoidance of ● Existing systems of avoiding meat inspection reduce
carcass condemnation) economic advantages
● Other production benefits: can affect other economically
important parasites of swine
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Singh - Chap 41 4/9/02 4:47 pm Page 413
tively expensive if manageable at all. Work tered nature of these infections means that
of this nature has been undertaken in there is an increased likelihood of detecting
China, where T. solium taeniasis–cysticerco- another case of T. solium within the contact
sis is highly endemic throughout most of group. Such cases, particularly tapeworm
the country12. Several interventions that carriers, are clearly important to treat from a
have included mass targeted treatment have disease management and transmission
been undertaken there, but the results have standpoint. A number of studies have
not been formally published outside the demonstrated that the presence of a case of
local prefectural public health bureaus. For taeniasis within the household is a signifi-
example, a T. solium ‘elimination pro- cant risk factor for cysticercosis17,19–22.
gramme’ was undertaken by the Anti- Similarly cases of taeniasis are significantly
Epidemic Station of Wujiang County, more likely to have cysticercosis; data even
Zhangye Prefecture in north-central Gansu suggest that they will tend to have higher
Province in 1978 when the baseline rate of cyst loads22,33. There is, therefore, value in
human taeniasis was 1512 per 100,000 for determining whether a case of NC also has
the county. A total of 312 T. solium carriers taeniasis. Studies in populations with no
were identified after purgative treatment immediately apparent risk for T. solium have
using the traditional medicines of areca nut also indicated that trace-back of contacts of
and pumpkin seed extract. The porcine cys- NC cases can result in detection of taeniasis
ticercosis rate was 7.7%. Following bi- cases4,5. The long latency period from initial
annual targeted treatment of carriers infection with NC to the onset of symptoms
(including use of praziquantel from 1983) in may reduce the chances of detecting the case
conjunction with emphasis on confining or of taeniasis that caused the NC infection but,
restraining pigs by tying and health educa- given the clustered nature of NC, trace-back
tion propaganda in the media, the incidence may also allow diagnosis of other NC cases
of human taeniasis was officially reported that may benefit from case management34,35.
to have reduced to 21 per 100,000, and the For these reasons, from the standpoints of
porcine rate to 0.27%, by 1988 (X. Lie, preventive medicine and that of improved
Y. Zhang, Zhanyi, Gansu, China, and P.S. case management, there is value in following
Craig, unpublished observations). up contacts of T. solium cases diagnosed in
Since the above outlined approach the clinical setting.
requires a great deal of effort in the identifi-
cation of T. solium carriers, control through
mass untargeted treatment of entire high- Chemotherapeutic Agents
risk populations has been promoted and
undertaken on an experimental basis. Two anthelminthics, praziquantel and
These studies have used low-cost, yet niclosamide, are currently both indicated
highly efficacious drugs, where the cost of and widely available for treatment of human
population-based treatment is lower than intestinal taeniasis. Both are recommended
the cost of diagnosis and treatment follow- for treatment of intestinal T. solium infection
up of carriers. It should be noted that this as a single oral dose with efficacy greater
approach might also be applicable outside than 90%9,36.
endemic areas in relation to the treatment
of high-risk groups such as immigrant pop-
ulations moving from endemic areas to Praziquantel
non-endemic areas32.
From a public health standpoint, how- Praziquantel is an acylated isoquinoline-
ever, there is the opportunity to reduce trans- pyrazine discovered jointly by E. Merck and
mission of T. solium at a local level through Bayer AG in 19729. This molecule has a wide
trace-back of cases of taeniasis and neurocys- spectrum, being active in man against both
ticercosis (NC) diagnosed clinically to their trematodes and cestodes, including both larval
family and immediate contacts. The clus- and adult T. solium. The approved therapeutic
dose for intestinal T. solium is 5–10 mg kg1 Suitability of anthelminthic agents for
bodyweight. It should be noted that with the mass chemotherapy
available 150 mg tablets the given doses are
approximate mg kg1 values. The molecule Of the two main drugs dealt with here, prazi-
has a half-life of only a few hours in man and quantel may be cheaper than niclosamide (by
thus does not have any prophylactic effect. a factor of five times or more). The efficacy of
The molecule increases calcium permeability this molecule at its indicated dose also
in cestodes and flukes leading to muscle con- appears to be somewhat higher than that of
traction, paralysis and death. The drug is very niclosamide and it is becoming easier to
bitter and can cause gagging if bitten or obtain. An early report indicated that prazi-
chewed during administration. Praziquantel is quantel could be effective against Taenia sp.
very well tolerated in humans and cheap (as taeniasis in doses of 2.5 mg kg1 for purposes
little as US$0.20 per treatment)9. of control programmes where cost may be an
issue39. Indeed, earlier work on the therapeu-
tic efficacy of the molecule suggested that this
Niclosamide dose was highly effective against the parasite9.
Recently it has, however, been recommended
Niclosamide is a halogenated salicylanilide that the drug be used at a higher recom-
first patented by Bayer AG in 195936. This mended dose of 10 mg kg1 40. In addition
drug has activity against a variety of intesti- there is a possibility that praziquantel, even at
nal cestodes of man including T. solium. The the low dose used to treat taeniasis, may occa-
molecule is not absorbed after oral adminis- sionally cause complications, such as cerebral
tration. Its anthelminthic action is either inflammation in individuals with NC, through
through inhibition of oxidative phosphoryla- its anticysticercal properties. Such a possibility,
tion or by stimulating ATPase. The recom- which was not linked to praziquantel treat-
mended dose is 2 g in adults, 1 g in children ment with absolute certainty, has been
of 11–34 kg and 1.5 g in children over 34 kg. reported in a female, subsequently shown to
The tablet should be chewed36. As with any harbour numerous intracerebral cysticerci,
drug, the recommended storage conditions who developed severe headache within 24 h
and shelf-life should be carefully adhered to. of treatment with 5 mg kg1 praziquantel, a
It is known that polymerization occurring condition that lasted for approximately 10
through long-term storage can lower drug days41. Indeed the manufacturer’s label for
efficacy. This has been seen with some gener- praziquantel frequently includes warnings
ically produced niclosamide. with respect to the drug use in individuals
with T. solium cysticercosis, especially ocular
cysticercosis. Niclosamide does not act against
Benzimidazoles the cystic stage and thus would not cause such
potential complications. Safety of niclosamide
A number of other older drugs are known to has, however, not been tested during preg-
be efficacious against cestodes but, generally nancy and the drug is contraindicated with
because of poorer efficacy or adverse side alcohol. With both drugs, control intervention
effects, they are not now widely used36. programmes should consider the possibility of
Further to this, some of the benzimidazoles, adverse drug reactions occurring and have
including albendazole, are known to be effi- mechanisms in place for monitoring for their
cacious against cestodes but generally require occurrence and dealing with any that occur.
administration over 3 consecutive days and Therefore, there are a number of factors
appear to have lower efficacy against intesti- including cost, ease of administration, avail-
nal taeniids than either niclosamide or prazi- ability, efficacy, stability and possible con-
quantel37,38. The benzimidazoles are, traindications that should be considered when
however, also active against a broad spec- a decision is being made as to which molecule
trum of gastrointestinal helminths including is appropriate in the circumstances of particu-
hookworm, Trichuris and Ascaris. lar mass treatment programmes.
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far have been insufficiently effective to eradi- Crude vaccines against porcine
cate cysticercosis and protection against rein- cysticercosis
fection has not been studied.
In laboratory and field studies, a variety of
antigens have demonstrated effective partial
Protective Vaccination Against protection against T. solium challenge and
Porcine Cysticercosis these results are summarized in Fig. 42.1.
Molinari et al. showed that vaccination of
Vaccination of pigs to prevent porcine cys- healthy pigs with antigens derived from
ticercosis is an appealing strategy to improve whole T. solium cysticerci caused partial pro-
animal health, meat yield and to break the tection against the subsequent development
parasite life cycle, preventing taeniasis and of porcine cysticercosis10. A similar (65–75%)
consequently preventing human cysticerco- degree of protection was achieved in
sis. Considerable progress has been made in Yorkshire pigs immunized with antigens
this endeavour, which is reviewed below. extracted from the scolices of T. solium cys-
ticerci20. Greater than 99% protection was
achieved with chromatographically purified
Historical background antigens from T. solium scolices, with tenfold
greater protection from the first Sephadex
The complex host–parasite interaction in par- peak than the second21.
asitic infections has traditionally hampered There is considerable antigenic similarity
vaccine development, but great progress has between various Taenia species. A crude anti-
been made with immunization against experi- genic extract from murine T. crassiceps cysts
mental infection with metacestode parasites13. administered to pigs induced 50% protection
These studies have used a variety of antigens;
against subsequent T. solium egg chal-
and among crude parasitic antigens, those
lenge22,23. Approximately 96% protection was
derived from the infecting oncosphere stage
achieved with purified protein extracts from
have generally been the most effective14. The
T. crassiceps cyst fluid22. As discussed above,
best example of an effective metacestode vac-
many parasites exhibit stage-specific antigens
cine is that developed for the prevention of T.
ovis15. This recombinant antigen is produced and some studies have utilized T. solium
entirely in the laboratory without the need for oncosphere antigens to specifically induce an
parasite material and similar vaccines based immune response against the infecting stage.
on the 45W, 45WB/X, 16K and 18K antigens The only published study of immunization
have proved to be 90–100% effective16. with oncosphere extracts reported 83–89%
Vaccination against infection of cattle protective efficacy with oncosphere
with larvae of the beef tapeworm has been extracts19. Likewise, immunization of pigs
attempted with partial success using hatched with excretory–secretory products of T.
ova, but limited antigen supply has necessi- solium oncospheres caused a decrease in the
tated the use of recombinant DNA technol- number of cysticerci that developed from
ogy for sustainable vaccine production17. subsequent challenge infection24.
Unfortunately, the T. ovis vaccine was not
effective against bovine infection with T. sag-
inata, so genes were cloned from T. saginata Field studies of vaccines against porcine
that express proteins homologous to the cysticercosis
host-protective T. ovis antigens. This strategy
led to the development of a recombinant Immune response to vaccination in con-
vaccine (combined TSA-9 and TSA-18 anti- trolled laboratory experiments is likely to
gens) that induced up to 99.8% protection differ considerably from rural field use
against infection with T. saginata eggs18. A where malnutrition, simultaneous antigenic
similar recombinant T. ovis antigen vaccine challenges and co-infections are frequent.
has been used successfully to protect pigs The above experiments that demonstrated
from T. solium, as described below19. the efficacy of T. crassiceps antigen vaccine
10,000
Cyst extract (Molinari et al., 1983)10
1,000
Encystment rate (cysticerci per 100,000 eggs)
100
T. crassiceps cyst fluid extract (Manoutcharian et al., 1996)22
10
Scolex extract (Kumar et al., 1987)21
1
Oncosphere secretions (Pathak and Gaur,1990)24
0
Controls Vaccinated Recombinant T. ovis antigen (Plancarte et al., 1999)19
Fig. 42.1. Overview of Taenia solium vaccination trials involving experimental challenge infections. The
number of cysticerci per 100,000 T. solium eggs administered is shown for control and vaccinated pigs. Each
line represents a published experiment involving several pigs. Details of each experiment, including the dose
of parasites used for the challenge infection, are given in the text. The viability of cysticerci is not shown.
of the efficacy of vaccination. Where the nec- efficacy would reinforce the financial incen-
essary raw data have been published, this is tive for farmers to protect their livelihood
the approach used for calculating efficacy from this infection, which at least halves the
rates in this review and it yielded results sim- value of pigs in many endemic areas.
ilar to those presented by the original authors However, it is noteworthy that the least
(Fig. 42.1). Clearly, the wide range of vaccine effective study presented here observed no
efficacy and infection efficacy shown is likely effect on cyst numbers but did report a
to result from differences in the proportion of marked effect of vaccination on cyst
Taenia eggs obtained from gravid versus histopathology8. The actual viability of cys-
immature proglottides and differences in ticerci for causing human taeniasis is tradi-
autopsy procedures that may leave many tionally assessed by evagination assays, but
cysticerci undiscovered. Besides, variation in these are infrequently used12. No cysticerco-
the adjuvants used may also contribute to sis vaccines have yet been reported to be
discrepant results because the latter may 100% effective and it is desirable that future
cause cysticercal degeneration in control ani- studies should assess the ability of cysticerci
mals. For example, saponin adjuvant is much to evaginate, as well as their absolute num-
less likely to cause cysticercal degeneration bers19. It may be that the few parasites that
than incomplete Freund’s adjuvant or encyst despite previous vaccination are
Corynebacterium parvum8,20,22,23. Although immunologically damaged and unable to
these issues do not negate the clear effect of evaginate and cause human taeniasis.
some vaccines compared with controls
within individual, blinded experiments, they
do hamper comparison of results between Conclusions
different experiments. There has also been no
standardization of the size of the infection Vaccines derived from cysticercal extracts
challenge used to test cysticercosis vaccines. have already proved their utility in field tri-
The number of T. solium eggs administered als and recombinant vaccines are now suffi-
has varied from 8400 eggs in one experiment, ciently effective under controlled conditions
to 10,000 eggs, 15,000 eggs, 25,000 eggs, and to warrant widespread evaluation of this
as many as 100,000 eggs in the study with the sustainable intervention. Rapid recent
least effective results8,10,19–22,24. These progress with the sequencing and compari-
methodological differences are important son of antigens from T. solium and related
because the natural infecting dose in the field parasites makes it likely that more effective
is likely to vary over an even greater range. T. solium vaccines will be developed soon.
Only one group has formally tested the Although the effect of malnutrition, constant
effect of pig age on vaccine efficacy8. exposure to antigens, and the transfer of
Although their vaccine administered to mal- immunity from pregnant sows await investi-
nourished outbred pigs did not have any gation, this progress in the transfer of molec-
effect on cyst numbers, a significant effect on ular biology from the laboratory to the field
cyst viability was greater in older than has provided a powerful new tool for the
young pigs. Furthermore, there was no control of cysticercosis. Combined with treat-
detectable antibody response to vaccination ment of human tapeworm carriers, the immi-
in pigs inoculated at 40 (rather than 70) days nent expectation of an effective recombinant
of age. It is interesting to note that immu- vaccine against porcine cysticercosis makes
nization caused cysticerci to degenerate, eradication of cysticercosis a feasible goal.
compared with control animals, despite the
absence of a detectable antibody response,
implicating a cellular immune response to Acknowledgement
vaccination in this process8.
The goal of effective vaccination must be The author is funded by the Wellcome Trust
prevention of infection and absence of cys- as a Career Development Fellow in Clinical
ticerci from pig tissues at autopsy. Such total Tropical Medicine.
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24. Pathak, K.M.L., Gaur, S.N.S. (1990) Immunization of pigs with culture antigens of Taenia solium.
Veterinary Parasitology 34, 353–356.
25. Molinari, J.L., Rodriguez, D., Tato, P., et al. (1997) Field trial for reducing porcine Taenia solium cys-
ticercosis in Mexico by systematic vaccination of pigs. Veterinary Parasitology 69, 55–63.
26. Flisser, A., Lightowlers, M.W. (2001) Vaccination against Taenia solium cysticercosis. Memorias do
Instituto Oswaldo Cruz (Rio de Janeiro) 96, 353–356.
27. Lightowlers, M.W., Flisser, A., Gauci, C.G., et al. (2000) Vaccination against cysticercosis and hydatid
disease. Parasitology Today 16, 191–196.
28. Toledo, A., Fragoso, G., Rosas, G., et al. (2001) Two epitopes shared by Taenia crassiceps and Taenia
solium confer protection against murine T. crassiceps cysticercosis along with a prominent T1
response. Infections and Immunology 69, 1766–1773.
29. Toledo, A., Larralde, C., Fragoso, G., et al. (1999) Towards a Taenia solium cysticercosis vaccine: an
epitope shared by Taenia crassiceps and Taenia solium protects mice against experimental cysticerco-
sis. Infections and Immunology 67, 2522–2530.
30. Drew, D.R., Lightowlers, M.W., Strugnell, R.A. (2000) A comparison of DNA vaccine expressing the
45W, 18k and 16k host-protective antigens of Taenia ovis in mice and sheep. Veterinary Immunology
and Immunopathology 76, 171–181.
31. Rothel, J.S., Waterkeyn, J.G., Strugnell, R.A., et al. (1997) Nucleic acid vaccination of sheep: use in
combination with a conventional adjuvanted vaccine against Taenia ovis. Immunology and Cell Biology
75, 41–46.
32. Cano, A., Fragoso, G., Gevorkian, G., et al. (2001) Intraspleen DNA inoculation elicits protective cel-
lular immune responses. DNA Cell Biology 20, 215–221.
33. Manoutcharian, K., Terrazas, L.I., Gevorkian, G., et al. (1999) DNA pulsed macrophage-mediated
cDNA expression library immunization in vaccine development. Vaccine 18, 389–391.
34. Cruz-Revilla, C., Ross, G., Fragoso, G., et al. (2000) Taenia crassiceps cysticercosis: protective effect
and immune response elicited by DNA immunization. Journal of Parasitology 86, 67–74.
Armando E. Gonzalez
dead and degenerating cysts – leaving it dazole and may over-estimate the amount of
unsightly as a food product. drug needed for treatment of porcine cysticer-
cosis. Consequently, an experiment was
designed to establish the minimal effective
Oxfendazole single dose of oxfendazole that would kill all
cysticerci in pigs10. Three doses of oxfendazole
Oxfendazole (methyl [5-(phenylsulphinyl)-1H were tested: 10 mg kg1, 20 mg kg1 and 30
benzimidazole- 2-yl] carbamate; SynanthicTM) mg kg1. After treatment, more than 75% of
was first identified as having anthelminthic cysts in pigs from the control group (not
properties against larval and adult gastroin- treated) were viable, irrespective of their
testinal cestodes and nematodes in various anatomical location. Four animals among
animal species by Syntex Research, Palo Alto, those administered a dose of 10 mg kg1
California. Structurally, it comprises of a ben- exhibited viable cysts; the latter were present
zimidazole carbamate that is characteristic of in the muscle (three pigs), the tongue (two
this group of drugs (which includes albenda- pigs), and the brain (two pigs). Viable cysts
zole), with a phenylsulphinyl substituent in were also found in four animals in the 20 mg
position-58. The efficacy of single-dose kg1 group, although they were present only
oxfendazole alone, praziquantel alone, and in the muscle (one pig) and the brain (three
oxfendazole and praziquantel in combination, pigs). The number of viable cysts recovered
in the treatment of porcine cysticercosis were
from the treated animals was very low: 18 of
compared in a randomized, placebo-con-
216 (8%) animals that were administered the
trolled study. Oxfendazole, used in a single
10 mg kg1 dose, and 11 out of 198 (6%) given
dose of 30 mg kg1, was found to be highly
the 20 mg kg1 dose. No viable cysts were
effective for the treatment of porcine cysticer-
recovered from animals that were adminis-
cosis9. Both oxfendazole alone and in combi-
tered 30 mg kg1 oxfendazole. Carcasses of
nation with praziquantel killed all the
parasites, leaving behind only microcalcifica- pigs treated with 30 mg kg1 oxfendazole had
tions and minuscule scars in the meat, giving a normal appearance, and were considered
it a clean appearance. The appearance of the suitable for human consumption.
meat was suitable for marketing, and no
apparent differences in taste were found by
organoleptic experts from the pork sold in Time response of anticysticercal effect
markets of Lima. In contrast, a single dose of
praziquantel alone (50 mg kg1) showed no The time for cysts to die and disappear after
benefit when compared with the controls. oxfendazole administration is critical to the
Cysts appeared clearly visible in the carcasses determination of the specific timing of treat-
of the praziquantel and control groups. No ment of live infected pigs. A controlled
detectable side effects were seen in any of the study was designed to determine the time
groups. This study demonstrated the safety period between treatment and death of cys-
and efficacy of a single dose (30 mg kg1) of ticerci11. A clear decrease in viability and
oxfendazole in the treatment of porcine cys- number of cysts was noted after the first
ticercosis. All other regimens were either inef- week following treatment with oxfendazole,
fective, needed multiple dosing, had side though few live cysticerci were found in
effects or left the meat unsuitable for sale3–7,9. many tissues even at 4 weeks. Twelve weeks
after oxfendazole treatment, the meat exam-
ined was clear and only minuscule scars
Overview of Laboratory and Field were observed, except in one animal that
Trials with Oxfendazole had viable cysts in the brain. The predicted
time to total decay depended on the organ.
Dose considerations The time to zero viability in muscle and
heart were 4 and 3 weeks, respectively.
The dose of oxfendazole (30 mg kg1) was cal- Interestingly, the time to cyst disappearance
culated from previous experience with alben- in the tongue, a voluntary muscle was 5
weeks. This study demonstrated that imme- Protection of successful treatment with
diate pre-slaughter treatment of pigs with oxfendazole
oxfendazole does not result in death and
disappearance of cyticerci. Since treated pigs can theoretically acquire
new infections, the estimation of the duration
of protective effect conferred by oxfendazole
Field trial with oxfendazole treatment is critical to the understanding of
the development of pig chemotherapy-based
The availability and documented success of control interventions. Another controlled
oxfendazole led to its use in a field trial for study was designed to determine if cysticerco-
control of T. solium through porcine sis-infected pigs could acquire new infections
chemotherapy; such approaches were con- after having been treated with oxfendazole12.
sidered impractical primarily due to the A group of 20 cysticercotic pigs were treated
duration of treatment, and found expensive with oxfendazole and later matched with 41
before the use of oxfendazole. The naive (unexposed to T. solium eggs) pigs. Both
Cysticercosis Working Group in Peru carried groups were then exposed to a natural chal-
out an interventional study that evaluated lenge of T. solium eggs in a hyperendemic area.
the effect of combined mass therapy target- Seroprevalence of cysticercosis among native
ing both human and porcine populations in pigs at the field site at the time of the experi-
the Peruvian highlands (Hector H. García, ment was 75% (73/97 animals). From the orig-
Lima, Peru, unpublished data). Eight highly inal 61 pigs, 51 (84%) were recovered at the
endemic villages located in the Mantaro val- end of the study, 19/20 in the treatment group
ley were selected for the study. The selected (95%), and 32/41 (78%) in the control group.
population underwent a cysticercosis control New infections were demonstrated in 15/32
programme that included mass treatment of (47%) using EITB serology and in 12/32
human and porcine populations. All pigs (38%) by tongue palpation in the control
were treated twice with oxfendazole (single group. At necropsy, viable cysts were found
dose, 30 mg kg1) at the beginning of the in the carcasses of seven pigs (viable only:
experiment (month 0 and month 4). three; viable and degenerated: four) while
Following baseline sampling and 30 days degenerated cysts alone were noted in
after treating the pigs, the villagers in the another five animals. The numbers of cysts in
treatment branch of the study received prazi- these newly infected animals ranged between
quantel in taeniacidal doses. The strategy five and 30 per pig. Conversely, no viable
was shown to be successful in the short term. cysts were found in the carcasses of any of
Benefits of the intervention as measured by the 19 treated pigs.
incident cases of porcine cysticercosis In field conditions, most pigs live for
remained statistically significant up to 16 around 9 months (see Chapter 15). Cysts take
months (P = 0.04). However, within 2 years, about 2 months to develop, so it is reasonable
the prevalence of the porcine cysticercosis to assume that pigs will be infective only
rose to its original levels. Sentinel pig trials after 3–4 months of age. Therefore, if treated
corroborated that environmental contamina- at 3–4 months of age, cured pigs are unlikely
tion returned to baseline levels 18 months to be re-infected at least until 7 months of
after intervention. The biotic potential of age, and it is very probable that this protec-
T. solium ultimately recovered to steady-state tion will extend for longer periods and thus
baseline values. The study demonstrated cover the remaining lifetime of the pig. This
that information regarding variables affect- means that oxfendazole is potentially an
ing the biotic potential were important; these effective control agent because once treated,
were used to calculate the number of inter- pigs are refractory to re-infection even in the
ventions and the minimum treatment cover- event of ongoing exposure to the source of T.
age required for a strategy using either solium eggs. Obviously, other concomitant
common sense or mathematical approaches measures are still needed since seronegative
(reviewed in Chapter 44). pigs still remain susceptible to infection.
References
1. Keilbach, N.M., De Aluja, A.S., Sarti, E. (1989) A programme to control taeniasis–cysticercosis (Taenia
solium): experiences in a Mexican village. Acta Leiden 57, 181–189.
2. Cysticercosis Working Group in Peru (1993) The marketing of cysticercotic pigs in the Sierra of Peru.
Bulletin of World Health Organization 71, 223–228.
3. Tellez-Giron, E., Ramos, M., Montante, M. (1981) Effect of flubendazole on cysticercus cellulosae in
pigs. American Journal of Tropical Medicine and Hygiene 30, 135–138.
4. Flisser, A., Gonzalez, D., Shkurovich, M., et al. (1990) Praziquantel treatment of porcine brain and
muscle Taenia solium cysticercosis. 1. Radiological, physiological and histopathological studies.
Parasitology Research 76, 263–269.
5. Torres, A., Plancarte, A., Villabos, A., et al. (1992) Praziquantel treatment of porcine brain and muscle
cysticercosis. 3. Effect of 1-day treatment. Parasitology Research 25, 1443–1450.
6. Kaur, M., Joshi, K., Ganguly, N.K., et al. (1995) Evaluation of the efficacy of albendazole against the
larvae of Taenia solium in experimentally infected pigs, and kinetics of the immune response.
International Journal of Parasitology 25, 1443–1450.
7. Gonzalez, A.E., García, H.H., Gilman, R.H., et al. (1995) Treatment of porcine cysticercosis with
albendazole. American Journal of Tropical Medicine and Hygiene 53, 571–574.
8. Marriner, S.E., Bogan, J.A. (1981) Pharmacokinetics of oxfendazole in sheep. American Journal of
Veterinary Research 42, 1143–1145.
9. Gonzalez, A.E., García, H.H., Gilman, R.H., et al. (1996) Effective, single dose treatment of porcine
cysticercosis with oxfendazole. American Journal of Tropical Medicine and Hygiene 54, 391–394.
10. Gonzalez, A.E., Falcon, N., Gavidia, C., et al. (1997) Treatment of swine cysticercosis with oxfenda-
zole: a dose–response trial. Veterinary Record 141, 420–422.
11. Gonzalez, A.E., Falcon, N., Gavidia, C., et al. (1998) Time–response curve of oxfendazole in the treat-
ment of swine cysticercosis. American Journal of Tropical Medicine and Hygiene 59, 832–836.
12. Gonzalez, A.E., Gavidia, C., Falcon, N., et al. (2001) Cysticercosis pigs treated with oxfendazole are
protected from further infection. American Journal of Tropical Medicine and Hygiene 65, 15–18.
*A number of strategies evaluate the effect of disease in a population. When a disease outbreak is modelled
directly, an epidemic curve can be drawn which depicts changes in disease prevalence. If some economic
variables are considered, the economic changes during the epidemic curve can be assessed. Another strategy
is to model the population but not the disease. By running the model with and without disease parameters,
the cost of disease can be calculated. A third and more flexible approach is to combine population and
disease parameters in a single model and evaluate the effect of disease and control strategies from the final
output3. Development of a simulation model is the process of building a mathematical and/or logical model
of a system or a decision problem, and experimenting with the model to obtain insight into the system’s
behaviour or to assist in making decisions concerning the problem. Simulation models are designed so that
they mimic the system under study as closely as possible in order to achieve a substantial degree of
epidemiological realism. Thus, building the model is making use of information about a disease in the form of
algorithms and equations4,5. Continued on next page
© CAB International 2002. Taenia solium Cysticercosis
(eds G. Singh and S. Prabhakar) 437
individual in the population3. The model The latter in turn were organized in compo-
combined population and disease models into nents according to overall objectives. Calls to
an epidemiological model. specific components came from modules and
sub-modules. The program was structured in
three modules, namely: ‘input’, ‘simulation’
General Description of the and ‘output’. Obviously, the core of the pro-
Simulation Model gram lay in the simulation module, which
contained two sub-modules, ‘baseline’, and
Assumptions ‘intervention’. The former ran a simulation
without any disease control while the latter
It was assumed that the effective reproductive simulated the selected control strategy.
rate of the adult tapeworm (R) is equal to one6. The model was developed using Visual
This assumption considers that each adult Basic 4.0 (Fig. 44.1). The model considers
tapeworm produces one adult tapeworm as input, simulation and output forms. Three
an offspring. Therefore, the average number of forms were designed to set values to input
tapeworms remains constant through time. variables. Briefly, the first two consider input
Also, that the infection rates for humans were values for the simulation model itself; swine
the same for each individual in the popula- and human population, disease parameters,
tion. This assumption need not hold true in financial parameters and seasonality factors.
actual conditions; however, there are no data The third input form was designed to select
to support a more plausible assumption the choice of output presentation. Two out-
regarding T. solium egg contamination pat- put forms present results in either economic
terns. Regarding porcine cysticercosis, it was evaluations or disease evolution graphs.
assumed that the infection rate is the same for
all pigs, and that in highly endemic areas, if a
pig is exposed at birth to a contaminated envi- Main procedures
ronment, it will become infected during the
first 6 months of life. Assumptions were also Changes in tapeworm population
made for human infection. The number of
new cases of human and swine cysticercosis There are three disease states for a tapeworm
depends on the number of adult tapeworms carrier: infected with an immature tape-
present, the number of new cases of tapeworm worm, infected with a mature tapeworm,
infection depends on the number of infected and postinfection contamination. The latter
pigs consumed in that day and finally, that the is very important because, even though the
number of exposed humans remains constant human host no longer harbours the tape-
throughout the simulation. worm, a number of the produced eggs still
remain infective in the environment. The
routine deals with environmental contami-
Basic structure of the model nation and assigns a number of infective
days after the tapeworm is eliminated. This
The simulation of related events was pro- value varies from place to place, according to
grammed in routines and algorithms that climactic and hygiene conditions, and is
represent the basic units of the programme. required in the input form. The routine
Input frame
Set repetitions
Pre-simulation
SIMULATION
Output choice
assigns the infection status of the host disease status and counts the number of
according to the length of each period (also infective tapeworms for the simulated day.
required as input). The routine adds 1 day to Two infective forms are considered to calcu-
tapeworm age and modifies the host disease late the infection potential for the simulated
status according to age limits. This algorithm day: the number of adult tapeworms and the
does not include a random process to deter- number of hosts with residual environmen-
mine the daily outcome. It only changes the tal contamination.
Infection
Infected pig
Infection Blot negative
Immature cysts
15 days
Infected pig
Treatment Blot positive
Immature cysts
75 days
Treatment
Treated pig
28 days Blot positive
viable cysts
Fig. 44.2. Graphical description of the changes among disease status compartments.
the routine assigns a cost to the human or them. The objective of this particular vari-
porcine treatment. Costs and benefits are able is to coordinate human and porcine
added for every day of the simulation. At the strategies. Briefly, the component is run start-
end of the simulation period, a small routine ing from the date of the first intervention for
performs a net benefit analysis. the given number of human mass treat-
ments. The interval between interventions is
set to a default value, which can be modified.
Intervention component
The objective of the intervention component TAENIASIS CONTROL. The human control simu-
is to simulate mass taeniacidal treatment of lation component uses a Monte Carlo algo-
humans and/or anticysticercal treatment of rithm to simulate the outcome of the
pigs. This strategy is defined by the number intervention on an individual basis. Two key
of interventions and the interval between probability values can be identified in field
Table 44.1. Results of different intervention schedules in humans, considering a treatment coverage of 100%.
40 No No No No No No No No
50 No No No No No No No No
60 No No No No No No No Yes
70 No No No No Yes
80 No No No No Yes
90 No No No Yes
100 No No No Yes
Mass treatment of human and porcine porcine population. The latter strategy
population required nine interventions in humans to
eliminate the parasite from both human and
It was observed that treating the human
porcine populations.
population alone was insufficient; the strat-
Evaluating control programmes based on
egy required 800 days, and involved a large
human and porcine populations with less
number of interventions and considerable
than 90% coverage gave disappointing results
cost and effort. Therefore, the effect of
adding pig treatment to human mass in terms of eradication of the parasite. The
chemotherapy was evaluated systematically. success of the different schemes was attrib-
Briefly, the starting point considered was 11 uted to the high coverage rates in either or
consecutive interventions in the human pop- both populations. However, a target coverage
ulation with a 90-day interval and a 100% of 100% is unrealistic since not all humans
human coverage. Then, a number of inter- accept the treatment and it is very difficult to
ventions in pigs were added, also assuming treat all the pigs. Besides, it is dangerous and
100% coverage and an interval of 90 days. culturally unacceptable to handle and treat
The addition of one intervention in the sows in the later weeks of pregnancy.
porcine population did not decrease the
number of human interventions (Fig.
Financial analysis
44.3c). However, the addition of two inter-
ventions in the porcine population reduced A partial financial analysis was made for the
the number of human interventions to simulated strategies. This financial analysis
three (Fig. 44.3d). Further increase in the was made considering two variables, sale of
number of porcine interventions did not pigs and cost of intervention. The analysis
improve T. solium control. took no account of financial or economic
Evaluation of the strategies that consid- costs of human cases. The present value, at
ered 100% coverage in the porcine popula- the first day of intervention, of pig sales and
tion and 90% in the human population cost was calculated. Table 44.3 presents the
demonstrated that intervening in both discounted benefit for the control strategies
humans and pigs decreased the total number over the 2000 days of the simulation. Only
of interventions in the human population. the most successful strategy, with three inter-
Table 44.2 presents the results of evaluating a ventions in humans and two interventions in
range of strategies to control T. solium. It was pigs resulted in a discounted benefit greater
found that intervening twice in the porcine than no intervention. One of the arguments
population with an interval of 180 days used to promote cysticercosis control was
decreased the required number of interven- that it would result in economic benefits for
tions in humans from 18 to 12 mass treat- the peasants. The results of the simulation
ments. This effect could be further enhanced, experiment contradict this argument, limit-
if five interventions were considered in the ing its scope to those strategies that success-
(a) 61 0.5
49 0.4
37 0.3
24 0.2
12 0.1
49 0.4
37 0.3
24 0.2
12 0.1
49 0.4
37 0.3
24 0.2
12 0.1
49 0.4
37 0.3
Number of 24 0.2
tapeworms
Cysticercosis 12 0.1
prevalence
Table 44.2. Effect of control strategies that considered mass treatment of human and porcine populations.
14 90 2 90 No
10 90 2 180 No
11 90 2 180 No
12 90 2 180 Yes
9 90 3 180 Yes
9 90 5 90 Yes
100 15 60 0 0 0 9,147.00
100 12 70 0 0 0 28,422.00
100 12 80 0 0 0 28,965.00
100 11 90 0 0 0 35,885.00
100 11 100 0 0 0 35,381.00
90 18 90 0 0 0 –1,160.00
100 3 90 100 2 90 91,720.00
90 12 90 100 2 180 53,834.00
90 9 90 100 3 180 54,245.00
90 9 90 100 5 90 54,595.00
No intervention 83,090.00
fully eliminate the parasite in the short-term. considered. Table 44.4 presents the estimated
Results of the benefit analysis also call into number of new infections of human cysticer-
question control programmes that depend cosis with different control strategies.
on the sustainability of the strategy. Although human neurocysticercosis repre-
Apparently, there were no benefits in the sents a severe disease, the symptoms depend
short and mid term, unless the strategy erad- not only on the infection burden, but also on
icated the disease within 6 months. the location of the cysts in the brain.
Consequently, control programmes that are Therefore, it would be difficult to simulate
unlikely to produce financial gains may severity of illness and ultimately, the effect of
result in failure to retain the confidence of disease on other economic variables that
the producers. It is recognized that this would be relevant to the economic appraisal
analysis disregards the long-term benefits of different control strategies.
(after 2000 days) that would accrue from par-
asite elimination from the pig population.
However, it is argued that possible benefits Limitations
more than 5 years in the future would be of
little interest to the people concerned. The most important finding of the use of the
A major disadvantage of using financial simulation model was that treating both
analysis to determine economical feasibility human and porcine populations had a
is that, their impact upon public health is not greater impact upon control of the parasite
Table 44.4. Expected number of new cases of human cysticercosis during the simulation period (2000 days).
100 15 60 0 0 0 26.36
100 12 70 0 0 0 26.50
100 12 80 0 0 0 25.47
100 11 90 0 0 0 26.48
100 11 100 0 0 0 27.20
90 18 90 0 0 0 25.10
100 3 90 100 2 90 27.65
90 12 90 100 2 180 28.63
90 9 90 100 3 180 27.80
90 9 90 100 5 90 26.63
No intervention 27.60
than treating one population alone. The key age in order to treat effectively all infected
variables were treatment coverage and num- hosts. Another limitation of the simulation
ber of interventions. It was clear that lower model is that it does not consider additional
treatment coverage required more interven- measures that could have an impact on
tions and, therefore, demanded more time T. solium populations. Simulating the effect
and financial resources. A cut-off point of of additional measures against T. solium also
80% coverage for human and porcine popu- requires quantitative estimates of the impact
lations was therefore established. The omis- of such measures. The direct and indirect
sion of human and pig movements into the effect of other measures, such as education
population excluded the possibility of rein- or vaccination, is still in debate. Assuming a-
troduction of parasite during an eradication priori parameter values and event proce-
programme. However, in practice, it would dures to simulate the effect of any measure
be pointless to attempt the elimination of without previous knowledge could jeopar-
parasites from a single community that is dize the focus of the model. In addition, the
surrounded by more infected communities. simulation model was designed to provide
Therefore, the model is appropriate for the information of control strategies in the short
evaluation of parasite elimination strategies and medium term. Although measures such
at the community level, only in the context as health education and improvement of
of a wider programme of control involving sanitary infrastructure have an important
multiple communities. effect on T. solium, these measures are more
The presence of clusters of T. solium infec- likely to be implemented within a long-term
tions has been documented in the past14,15. integral development plan for rural com-
However, simulating the events that deter- munities rather than as specific actions
mine these clusters may obstruct rather than against T. solium.
assist the interpretation of the simulation
output. The main factors that determine the
presence and nature of infection clusters are Conclusions
human behaviour and the management of
pigs. The simulation of activities related to A description of the major factors that regu-
those factors is beyond the scope of this late T. solium and its relationship to porcine
model. Infection clusters represent the productions systems is crucial to an under-
worst-case scenario for control programmes, standing of the transmission dynamics and
because they require high treatment cover- thus to the planning of control programmes.
A simulation model that includes porcine, but also to define the benefits and costs for
human and tapeworm populations will the institution or community applying the
assist in this goal. An economic component control16. A number of schedules with vari-
in this model can produce estimates of the ous combinations and durations of human
financial impact of the disease, and help to and porcine treatment were evaluated in a
quantify the costs of control measures simulation model. Mass human chemother-
through cost–benefit analyses, considering apy alone proved insufficient to eradicate T.
not only effects on human and animal solium. Concurrent human and porcine treat-
health, but also economic optimization. ment was more effective in terms of control
When predicting the impact of any control of T. solium. None of the interventions was
intervention on cestode populations, there is economically more advantageous than no
a need not only to consider how effective the intervention, emphasizing that the core
measure will be in epidemiological terms, problem is economic.
References
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Journal of Tropical Medicine and Public Health 22, 377–381.
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necropsy, and tongue examination for the diagnosis of porcine cysticercosis in Peru. American
Journal of Tropical Medicine and Hygiene 43, 194–199.
3. McLeod, A. (1993) A model for infectious diseases of livestock. PhD thesis. University of Reading,
Reading, UK.
4. Vose, D. (2000) Risk Analysis. A Quantitative Guide, 2nd edn. John Wiley & Sons, New York, 417 pp.
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cysticercosis with oxfendazole. American Journal of Tropical Medicine and Hygiene 54, 391–394.
9. Allan, J.C. (1996) Detection of Taenia solium antigens in faeces. In: García, H.H., Martínez, M. (eds)
Taeniasis/Cisticercosis por T. solium. Editorial Universo, Lima, Peru, pp. 327–340.
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Index 457