TROPICAL MEDICINE

DEPARTEMENT OF PARASITOLOGY
FACULTY OF MEDICINE
Unimal
Merina Panggabean 2
LEARNING ISSUES:

1. WHAT AGENT(S) OF THE DISEASE

2. PATHOGENESIS OF DISEASE
3. MANAGEMENT: DIAGNOSIS
4. PROGNOSIS

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References
• King, C.L. 2001. Transmission intensity and human immune
responses to lymphatic filariasis. Parasite Immunology 23 (7),
363–371

• Melrose, W.D. 2002. Lymphatic filariasis: new insights into an

old disease. International Journal for Parasitology 32(8), 947-
960.

• Muller, R. and Wakelin, D. 2002. Worm and Human Disease.

2th edition. London. CABI Publishing.

• Palumbo, E. 2008. Filariasis: diagnosis, treatment and

prevention. Acta biomedical. 79. 106-109.
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References
• Rahmah, N., Lim, B. H., Khairul Anuar, A., Shenoy, R. K.,
Kumaraswami, V., Lokman hakim, S., Chotechuang, P.,
Kanjanopas, K. & Ramachandran, C. P. 2001. A recombinant
antigen-based igg4 ELISA for the specific and sensitive detection
of brugia malayi infection. Transactions of the royal society of
tropical medicine and hygiene 95(3): 280-284.

World Health Organization. 1999. Collaborative global

programme to eliminate lymphatic filariasis: Programmes
backround and overview towards initiating a National
programme to eliminate lymphatic filariasis . WHO/CEE/FIL
World Health Organization, Geneva, 1 – 25.

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Lymphatic Filariasis
Caused by worms:
- Brugia malayi
Wuchereria
- Wuchereria bancrofti
bancrofti
Brugia
- Brugiamalayi
timori
Brugia timori

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Vector:
- Brugia malayi by Mansonia
uniformis (rural) and Anopheles spp.
(urban)
- Wuchereria bancrofti by Culex sp,
Aedes sp and Anopheles spp
- Brugia timori by Mansonia sp

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Brugia malayi
 The larva was first observed from a
native Sumatera by Brug (1927)
 Nocturnal periodicity and subperiodic
nocturnal

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B. malayi
Morphology
 Adult resembles that of W
bancrofti
 Female is 43-55 mm, male is 13-23
mm with spiral-shaped tail

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B.malayi
- Wrinkled body
curve
- Sheath stained
pinkish-red
- Overlapping body
nuclei
- Presence of sub-
terminal and
terminal nucleus

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Wuchereria bancrofti

 The larva was found by Demarquay

(1863) and Wucherer (1866)
 The adult was first found by Bancroft in
1876
 Nocturnal periodicity

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 W. bancrofti
Morphology:
 Adults look like thin and long threads
 Female is 80-100 mm, male is 25-45
mm with spiral-shaped tail
 Fertilized eggs is 30-40 x 20-25 m, the
egg cell develops rapidly to form a larva
(microfilaria) while in the uterus

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 W. bancrofti

 Microfilaria is 0.24-0.35
mm long
 Cephalic space: the
length is equal with the
width
 Sheath not well

stained
 Gracefull body curve

 Discrete body nuclei

 No terminal nucleus
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Brugia timori

- Overlapping body
nuclei
- Sheath does not
stain pinkish (bluish)
- Tapered tail
- Presence of sub-
terminal and terminal
nucleus

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LIFE CYCLE:
6. Resting mosquito (Development
L1-L3 in the vector)

1. Mosquito
feeding-
transmission

5. Mosquito
feeding
2. Human
lymphatic
system

4. Microfilaria
in the blood

3. Thoracic duct
Pathogenesis
Inflammation occurs when worms die, either drug-
induced or spontaneously.

Granulomas arise around those worms, characterized

by macrophages which develop into giant cells: as
plasma cells, eosinophils and neutrophils.

Clinical symptom is filarial fever starting when the

worm death and leads to retrograde lymphangitis
(painful with swelling), and lymphadenitis, which lasts
for ± 1 week .

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Pathogenesis
Lymph vessels dilation, not obliteration, is probably the
early event following antigenic stimulation, which
spring larvae are being released. These larvae are
degenerate and will be taken up by phagocytic cells.

These accompanied by triggering of the innate immune

system, release proinflammatory cytokines and
molecules that promote lymphangiogenesis.

The enlarge lymph vessels become less efficient at

transporting lymph from the periphery, which in the
legs is always oriented against gravity, more vulnerable
to exogenous microorganisms.
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Pathogenesis
Insufficient fluid transport will lead to fluid
extravasations, particularly in the lower limbs, and
eventually to lymphoedema.

L3 preferentially stimulate IL-4 and IL-13 release from

basophils as well as histamine release. In addition,
basophils comprise approximately 1% of cells in PBMC
(peripheral blood mononuclear cells) and their
contribution to the observed cytokine production can be
substantial. Therefore mast cells and basophils may plan
an important role in regulating the host response to
filarial infection by affecting T cell differentiation, local
blood flow, lymphocyte proliferation or by release of
histamine or other prostanoids
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Management
Diagnosis
1. Clinical manifestations
2. Laboratory diagnosis:
a) Microscopy for filaria
b) Immunodiagnosis
c) Molecular techniques (PCR)
d) Ultrasonography

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1. Clinical manifestations:
a). Acute filariasis
b). Chronic filariasis

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1.a). Acute manifestations
- Characterised by recurrent
attacks of
fever associated with inflammation
of lymph nodes (adenitis) and /or
lymph vessels adenolymphangitis, ADL)

- Red and swelling on the ancle

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- Involvement of genitalia lymphatic in male –
funiculitis, epididymitis or orchitis (specific on
parasite W. bancrofti)

- Lasting for 4-5 days

- Repeated episode important in the progression

of disease

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Acute manifestation: ADL

Acute filarial lymphangitis

- cord-like structure with retrograde lymphangitis:
painful, red and tenderness
- systemic reaction mild, distal oedema rare
- recurrent at same site common
- recurrent fever

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ADL with secondary bacterial infection

- most common form of ADL

- associated with fever, chills, myalgia
and headache
- cellulitis and oedematous, subside after
each attack

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1.b). Chronic manifestation
Major signs
Hydrocoele
Swelling of
scrotum due to
collection of
lymph fluid
Chyluria
Lymphoedema
Elephantiasis

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Chronic manifestation
Major signs:

 Hydrocoele

 Chyluria
- rupture of lymphatic lining
the bladder leading to passage
of lymph in the urine
- may resolve spontaneously
- lymphocytes in urine

 Lymphoedema
 Elephantiasis
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Chronic manifestation
Major signs
Hydrocoele
Chyluria
Lymphoedema
Swelling due to
collection of lymph
fluid in soft tissue
Pitting oedema, may
or may not be
reversible
Thickened skin
Elephantiasis
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Chronic manifestation
• Major signs
– Hydrocoele
– Chyluria
– Lymphoedema
– Elephantiasis
• Irreversible, non-pitting
oedema with fibrotic and
verrucous skin changes
(thickening, folding,
hyperkeratosis,
pigmentation, ulceration)
• Skin & soft tissue infection
common
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Chronic manifestation
• Rarely develop before 15 years
• Only a small proportion of filarial-infected
population affected
• Immigrants tend to develop chronic manifestation
more often and sooner than indigenous people
• Occurrence of major signs differ between places

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Lymphatic vessel dilatation, valve incompetency,
lymphatic back flow, pooling & oedema

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Adult worm in the lymphatic

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2. a) Microscopy for microfilaria

Detection mf in blood (known as definitive

diagnosis) by morphological characteristic mf.
The blood specimens should be collected at
night time (at 22.00 pm – 2.00 am):
- The Giemsa stained thick smears (20 µl– 60µl).
- Nukleopore Membran (Knott’s concentration
methods

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2.b) Immunodiagnosis:

- Antibody detection assay: Brugia Rapid

(IgG4 detection). Specific for B. malayi
- Antigen detection assay: ICT card for
bancroftian filariasis

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Volume of blood: standardisation

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2.c). Molecular techniques (PCR)
- DNA radioactive and non radioactive probes Hha 1,
capable detecting B. malayi in blood samples
- PCR amplifies DNA using specific primers. Detecting
B. malayi and W.bancrofti

2.d). Ultrasonography
Detect the motile adult worms within the
lymphatics, scrotum and breast (term as “filarial
dance” signs). Detecting W. bancrofti only.
.

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Ultrasonagraphy & Doppler’s Technique in
Filariasis

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Treatment

- Diethylcarbamazine citrate (DEC): drug of choice.

Effective in clearing mf from blood circulation.
Dose: B. malayi 6mg/kg single dose
W. bancrofti 6 mg/kg x 12 doses (72g/kg total)
TPE: 6mg/kg per day x 21 - 28 days.

- DEC-fortified salt is well tolerated and safely in

pregnancy, its very low daily doses : between 5 and
15 g/person/day

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- Ivermectin. Dose: single dose 120 µg/kg

- DEC + Albendazole (6mg/kg DEC + 400 µg/kg

Albendazole) for elimination programme.

Obligate endosymbiontic bacteria of the genera

Wolbachia spp. Common antibiotic Doxycycline
can eliminated microfilaraemia

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Side effect of DEC:

1. General reactions: headache, fever, dizziness,

decreased appetite, malaise, nausea, urticaria,
vomiting. Reactions occur during early treatment
and last more than 3 days.

2. Local reactions: Lymphadenitis, funiculitis,

epididymitis, orchalgia and lymphangitis. Usually
occuring 1 – 3 weeks after treatment.

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PROGNOSIS

Treatment to be effective in clearing mf for :

- stadium acute
- lymphoedema stadium 1 - 2
- chyluria

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THANK YOU