Blood & Tissue Nematodes

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 Blood & tissue nematodes

W.bancrofti
lymphatics
B.Malayi

Loa loa
sucutaneous tissue
Onchocerca volvulus

Dracunculus medinensis
 Trichinella spiralis-striated muscles
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 Filariae
 are roundworms
 adult filaria live in
body cavities
 lymphatics
subcutaneous tissues
 microfilaria live in blood or dermis
 all require an insect or crustaean vector
 microfilaria (150-350 μ long)
 adults 2 cm – 120 cm (4 – 10 μ wide)
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 Lymphatic filariasis
• Wuchereria bancrofti
• Brugia malayi
• Brugia timori
lymphatic vessels and lymph nodes

Loiasis (Calabar swelling)

• Loa loa/ eye worm
• subcutaneous tissues
adult worms sometimes migrate across
the conjunctiva or eyelid
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  The microfilariae (1st stage larvae) can be

found in the blood

Show periodicity

 present in the peripheral blood in greater

numbers during certain hours which

correspond to the peak biting times of their

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insect vectors.
 Periodicity
 Nocturnal periodicity: Mf are present in greatest
numbers in the peripheral blood during night hours

 Diurnal periodicity: Mf are present in greatest

numbers in the peripheral blood during day hours

 Nocturnal subperiodicity/diurnal subperiodicity:

Mf can be found in the peripheral blood throughout
the 24 hours with only a slight increase in numbers
during day or night hours

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 Species identification

Distribution of nuclei with in the tail of microfilaria

Presence/absence of sheath
Species Sheath Arrangement of periodicity Vector
nuclei in tail

W.bancrofti Present free of nuclei nocturnal Aedes,Culex,Anopheles

B. malayi Present Two distinct nocturnal Aedes,
nuclei Anopheles,Mansonia

O. volvulus Absent Don’t extend to Non periodic Simulium (Black fly)

tail tip

Loa loa Present distinct Diurnal Chrysop(tabanid

continuous fly/mango fly)
extend to tail tip

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 W.bancrofti
Onchocerca volvulus

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B. malayi Loa loa
Lymphatic Filariasis
 The term “lymphatic filariasis” encompasses
infection with three closely related nematode
worms
Wuchereria bancrofti
Brugia malayi
 Brugia timori
 Although case fatality is low, millions suffer from
chronic ill health
 disfigurement & disability
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social rejection and psychological stress.
 Distribution

 one of the most prevalent tropical diseases

 120 million people infected

 >90 are caused by W. bancrofti

 About 40 million people have severe chronic

disease

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  W. bancrofti

endemic in tropical America, Caribbean,

tropical Africa, Egypt, the Middle East

India and South East Asia, southern and

eastern China, the Far East and New Guinea.

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  B. malayi and B. timori

endemic in South East Asia,south west India,

the Philippines, Vietnam, China, and South

Korea.
 B. timori
only in Timor Islands of Indonesia

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Transmission and life cycle
 W. bancrofti, B. malayi, B. timori are transmitted
by female mosquitoes
Culex
 Anopheles
 Aedes
Mansonia
 Infection- deposition of infective larvae on
human skin(blood meal)
 larvae penetrate the skin through the bite wound-
low infection rate
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 Low infection prevalence in mosquito-high fatality
rate in vectors
 High prevalence in humid areas-prevent desication

Vectors

 W.bancrofti-Culex,Anopheles & Aedes

 B. malayi- Anopheles and Mansonia.

monkeys are important reservoirs-zoonotic

 B. timori- Anopheles
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 The basic life cycle is the same for all of the

members of filariae

Two life cycle stages

 adult

 microfilaria(larvae)-L1-L4

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2 Hosts
 definitive host –human
 Intermediate hosts –
Mosquitoes-W. bancrofti,B. malayi
black flise –O. volvulus
 chrysops –loa loa
 Infection begins with the deposition of infective
stage larvae (L3) on the skin
 larvae then pass through the puncture wound and
reach the lymphatic system
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 L3 molting L4 molting adult

 adult worms take permanent residence in afferent

lymphatics or the cortical sinuses of lymph nodes

and generate microscopic live progeny called
“microfi lariae”.

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Pathogenesis & clinical manifestations

 Clinical features and pathology depend on:

 sites occupied by worms

number of worms

length of infection

immune responses of the host to dead worms

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 Symptoms develop with increasing numbers of
worms
 phases clinical course:
• Asymptomatic Microfilaremia
• Acute Adenolymphangitis (ADL)
• Chronic/Irreversible lymphedema
• Tropical pulmonary eosinophilia
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I. Subclinical (or asymptomatic) microfilaremia:
In endemic areas

significant numbers of microfilaria in blood

are carriers/reservoir of infection

• asymptomatic microfilaremics
o 10,000 microfilariae /ml of blood

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 Imaging techniques- may be presented with

marked dilatation of lymph vessels

collateral channelling

increased flow and abnormal patterns of lymph

flow
microscopic hematuria and/or proteinuria
(indicative of low-grade renal damage)
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 II. Acute manifestations
sudden onset of fever

 painful lymphadenopathy

lymphangitis

inflammation spreads distally away from lymph

nodes
 immune mediated response to dying worms
most common areas: inguinal nodes and lower
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extremities
 Mechanisms of acute attacks
acute filarial adenolymphangitis-immune-
mediated inflammatory response to dead or dying
adult worms.
• distinct well-circumscribed nodule along with
lymphadenitis and retrograde lymphangitis
• Fever is not usually present
• pain and tenderness at the affected site
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 acute dermatotolymphangitis- bacterial and
fungal superinfections of the affected limbs
• plaque-like lesion of cutaneous or
subcutaneous inflammation
• ascending lymphangitis and regional
lymphadenitis
• Edema of the limbs may/may not present

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  Bancroftian filariasis
lymph glands in the groin and lymphatics of
the male genitalia
Inflammation of the spermatic cord
blockage of the spermatic lymph vessels
 leading to accumulation of fluid in the
scrotal sac
o hydrocele
 Brugian filariasis
lymphnodes situated in the inguinal and
axillary regions
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III.Chronic Disease
 10 to 15 years after initial infection
 main clinical features
Hydrocele-Obstruction of spermatic cord &
testis lymphatcs
 lymphedema
elephantiasis
Entire lower limb_Scrotum_Entire
arm_Vulva_breast
chyluria
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  Elephantiasis is a complication of advanced
lymphatic filariasis
coarse thickening, hardening, and cracking of
the skin
 The legs are more commonly affected than the
arms
 thigh also is often involved
Grossly enlarged limbs make walking difficult
Secondary bacterial and fungal infections

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WHO staging of lymphedema
of the legs

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Stage I

 Swelling reverses at
night

 Skin folds-Absent

 Appearance of Skin-
Smooth, Normal
Stage II

 Swelling not
reversible at night

 Skin folds-Absent

 Appearance of skin-
Smooth, Normal
Stage III

 Swelling not reversible

at night

 Skin folds-Shallow

 Appearance of skin-
Smooth, Normal
Stage IV

 Swelling not reversible

at night
 Skin folds-Shallow
 Appearance of skin -
Irregular,
 * Knobs, Nodules
Stage V
 Swelling not reversible
at night

 Skin folds-Deep

 Appearance of skin –
Smooth or Irregular
Stage VI

 Swelling not reversible at

night

 Skin folds-Absent,
Shallow, Deep

 Appearance of skin *Wart-

like lesions on foot or top
of the toes
Stage VII
 Swelling not reversible at
night

 Skin folds-Deep

 Appearance of skin-Irregular

 Needs help for daily activities

- Walking, bathing…
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 IV. Tropical pulmonary eosinophilia
 Hypersensitive reaction to the destruction of
microfilariae in pulmonary capillaries.
 Males are more commonly affected than
females(4:1)
 can lead to chronic pulmonary fibrosis
 Symptoms are worse at night
 marked eosinophilia
 raised erythrocyte sedimentation rate
 high levels of filarial antibody including high
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titres of IgE.
  clinical features

• Nocturnal paroxysmal cough and wheezing

• weight loss

• low-grade fever

• adenopathy

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Other Manifestations
 a variety of renal abnormalities
Hematuria
proteinuria
nephrotic syndrome
 glomerulonephritis
circulating immune complexes
 Lymphatic filariasis may also present as arthritis
of the knee or ankle joint.

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Diagnosis
 detection of microfilariae in the peripheral blood
• thick blood film of capillary blood stained with
Giemsa stain
poor sensitivity
 concentration techniques
Knott’s concentration method
1 ml of whole blood is added to 9 ml of a 2%
formalin solution, centrifuged and the sediment
examined for microfilariae.
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 membrane filtration technique
1-5 ml of blood is passed through a 3 or 5
μM polycarbonate membrane which retains
the microfilariae

 Serology-poor specificity
IgG4 produced in large abundance in the
chronic stage
showed low cross reactivity

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 W.bancrofti
Onchocerca volvulus

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B. malayi Loa loa
Treatment
 Diethylcarbamazine (DEC)
reduces microfilariae concentrations
kills adult worms
 Albendazole
kills adult worms
 Ivermectin
kills the microfilariae produced by adult
worms
Treatme…..
 usually treated with single-dose regimens of a
combination of two drugs
 one targeting microfilariae
 one targeting adult worms
 (i.e.,either diethylcarbamazine and
albenadazole, or ivermectin and
albendazole
In some areas, DEC laced table salt is used
as a prophylactic
Hydroceles can be drained repeatedly or
managed surgically
Rx + hygiene, prevention of secondary bacterial infections
 Prevention and control

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 ONCHOCERCIASIS

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  Onchocerciasis/river blindness and, is a
parasitic disease caused by Onchocerca
volvulus
 is the world's second-leading infectious cause

of blindness
 obligatory endosymbiont,Wolbachia(Rickettial

bacteria) causes the severe inflammatory

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response
 Distribution
 > 17.7 million people live with onchocerciasis
 270,000 blind and 500,000 with severe visual
impairment
 99% occurr in tropical Africa
 O. volvulus occurs most widely along the
courses of fast running rivers and streams in
rain forests and savannah areas.
 in 28 countries in Africa from Senegal in the
west to Uganda and Ethiopia in the east and as
far south as Zambia
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 The parasite is transmitted to humans through
the bite of a blackfly of the genus Simulium.

 When the worms die their Wolbachia symbionts

are released, triggering a host immune system
response that causes intense itching and can
destroy nearby tissue, such as the eye.

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  The vast majority of infections occur in sub-

Saharan Africa
 An estimated 18 million people suffer from
onchocerciasis, with approximately 270,000
cases of blindness.
 It ranks only second to Trachoma as an

infectious cause of blindness in the world.

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 Life -cycle

A Simulium female black fly takes a blood meal on

an infected human host ingesting microfilaria.

The microfilaria enter the gut and thoracic flight

muscles of the black fly progressing into the first

larval stage (L1).
The larvae mature into the second larval stage (L2)

and moves to the proboscis and into the saliva in its

57 third larval stage (L3)
 Life-cycle…
 The black fly takes another blood meal→L3
 The larvae migrate to the subcutaneous tissue
and undergo two more molts.

 adult worms mate in the subcutaneous tissue →

microfilaria

 The microfilaria migrate to the skin during the

day and the black flies only feed in the day.

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59
vector
the blackfly:Simulium damnosum

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 PATHOGENESIS
 Both microfilariae and adult worms →host
immune response

 Onchocercomas-noticeable subcutaneous
nodules
usually over bony prominences
adult worms

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  Two straians

African strain-the nodules are most

frequent in the pelvic area, with a few along
the chest, spine, and knees.
Central American strains- the nodules are

mostly found above the waist, especially on

the head and neck
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 Pathogenesis…
 A loss of the skin’s elasticity

drooping of the groin into hanging sacs

usually filled with lymph nodes

 Scrotum and testes are unaffected(no

hydrocoele)
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65
 Pathogenesis….
 The impairment of vision- sclerosing (scarring)
keratitis
 In some villages of Africa, the rate of impaired
vision may get to 30%.
it is typical to see a child with normal
vision leading a string of blind adults to the
local market.
 Eye impairment takes years to develop
affected individuals are those over 40 years
66 old
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  Phases of onchocerciasis:

 An acute phase characterized by

 swelling of the face with erythema and
itching

 A cutaneous condition characterized by

 inflammation accompanied by
hyperpigmentation

 Sowda
 a cutaneous condition, a localized type of
onchocerciasis
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  Additional skin changes

 Leopard skin
 spotted depigmentation of the skin

 Elephant skin
 thickening of human skin

 Lizard skin
 Thickened & wrinkled skin changes

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Leopard skin
  Signs and symptoms
 Skin involvement-intense itching, swelling,
and inflammation
 A grading system of skin involvement
 Acute papular onchodermatitis- scattered
pruritic papules
 Chronic papular onchodermatitis- larger
papule, resulting in hyperpigmentation

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  Lichenified onchodermatitis- hyperpigmented papules

and plaques, with edema, lymphadenopathy, pruritus and

common secondary bacterial infections

 Skin atrophy- loss of elasticity, skin resembles tissue

paper, 'lizard skin' appearance;

 Depigmentation- 'leopard skin' appearance, usually on

anterior lower leg.

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 Signs and symptoms…
 Ocular involvement-involve any part of the eye
from conjunctiva and cornea to uvea and retina
and optic nerve.

 Punctate keratitis occurs in the infected area

 Chronic- sclerosing keratitis,the affected area

become opaque

 Over time the entire cornea may become opaque-

blindness
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 The burden of onchocerciasis: children
leading blind adults in Africa.

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Lab Dx
 skin snips to identify microfiaria
procedure
• clean skin
• insert a sterile fine needle
into the skin & raise the
point of the needle, lift
small piece of skin
• cut off the piece of skin
with a sterile razor blade

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 Diagnosis….
 1 ml of fresh physiological saline in a

tube( 4 hours)
 using forceps, remove the skin snip, place

it on a slide
 centrifuge the contents of the tube

 examine skin snip and sediment

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 W.bancrofti
Onchocerca volvulus

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B. malayi Loa loa
  Treatment
◦ Ivermectin
 150 micrograms/kg, repeated every 6-12
months
◦ Diethylcarbamazine (DEC)
 Potentially sight-threatening inflammatory
reaction

◦ Doxycycline- is used to kill the Wolbachia

bacteria that lives in adult worms
 Prevention and control
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 Prevention

 Through the use of larvicide spraying of fast flowing

rivers
 Treating infected individuals

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Loa loa
 Microfilariae in human blood
 Caused by infection with Loa loa
Adult worms move under human
skin
Observed beneath skin or passing
through conjunctiva of eyes (‘eye
worms’)
 Transmitted by horse flies (Tabanidae)
in genus Chrysops Adult in human eye
Day-feeding & forest-dwelling
 Disease endemic to rain forest regions
of West & Central Africa

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 Clinical Manifestations
can cause a broad range of symptoms
 swelling in the face, extremities, and
periorbital areas
serious complications
renal failure & central nervous system
involvement
Infected individuals may develop pain
pruritis along the path of the traveling adult
worms
nonpitting edema(calabar swelling) develops
along the migratory path of the worm
 Epidemiology

endemic to the central and western regions of

Africa.
13 million people are affected

The vector, the Chrysops fly, breeds in mud near

shaded water sources of the rain forest

 Rubber tree plantations are especially prone to

infestation with Chrysops.

no nonhuman reservoirs
Loa loa
 a filarial nematode, the causative organism of

Loiasis.
 known as the African eye worm

 infection is characterized by transient swelling

of subcutaneous tissues_Calabar swellings

 Life Cycle
 the mango fly/ tabanid fly, belong to the genus
chrysops,
 the female fly feeds during daylight hours
 the microfilariae, circulate in the peripheral
blood during the day
 the adult worms develop within the
subcutaneous tissues of the host.
 The adult worms reproduce and deposit
microfilariae in the peripheral blood during the
day
88
 Clinical Manifestations
 can cause a broad range of symptoms
 swelling in the face, extremities, and
periorbital areas
 serious complications
renal failure & central nervous system
involvement
 Pain & pruritis along the path of the traveling
adult worms
 nonpitting edema(calabar swelling) develops
along the migratory path of the worm
 The swellings are believed to be
hypersensitivity reactions
 Repeated episodes of swelling are common.

Extremities

 ankles

 wrists

periorbital areas
 Eye involvement is the most well known clinical

manifestation
 Movement of the adult worm under the conjunctiva

• Conjunctivitis

• Pruritis

• pain & edema of the eyelid

 Occasionally, the transparent adult worm can be

seen migrating under the conjunctiva.

 Ocular complications-rare

 macular deterioration

 retinal artery occlusion

 Other infrequent complications

Lymphadenitis

pulmonary infiltrate

 hydroceles and joint involvement

 More serious complications

 Damage to the glomeruli as a result of

immune complex deposition

proteinuria and hematuria

 Central nervous system

Meningoencephalitis-microfi larial burden>

2,500 microfilaria/ml.