FILARIASISDEPARTEMENT OF PARASITOLOGY

CLINICAL CASE*A 28-year old male came to Community Health Centre with complaints swelling of right leg from thigh to toes. The swelling occurred once every 5-6 months. It started 4 years ago along with hardness and swelling of inguinal lymph nodes. He also developed chills and fever. About 4-5 days later the fever stopped, but the swelling of the leg increased. At this stage he had chills with severe pain in the right leg. This lasted for 10-12 days, after which the pain subsided. During this time he had ulcers on the swollen leg with bleeding and a yellow discharge. This remained for 2 days. Later the swelling decreased and the ulcers started healing.

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Learning issues*Agents of the diseasePathogenesisDiagnosis

References*King, C.L. 2001. Transmission intensity and human immune responses to lymphatic filariasis. Parasite Immunology 23 (7): 363371Melrose, W.D. 2002. Lymphatic filariasis: new insights into an old disease. International Journal for Parasitology 32(8), 947-960Muller, R. and Wakelin, D. 2002. Worm and Human Disease. 2th edition. London. CABI PublishingPalumbo, E. 2008. Filariasis: diagnosis, treatment and prevention. Acta biomedical. 79. 106-109Rahmah, N., Lim, B. H., Khairul Anuar, A., et al. 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): 280-284World 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

Lymphatic Filariasis

Causative agents*Brugia malayiWuchereria bancroftiBrugia timori

*Wuchereria bancroftiThe larva was found by Demarquay (1863) and Wucherer (1866)The adult was first found by Bancroft in 1876Nocturnal periodicityVector: Culex and Aedes

Wuchereria bancrofti Morphology*Adults look like thin and long threadsFemale is 80-100 mm, male is 25-45 mm with spiral-shaped tailFertilized eggs is 30-40 x 20-25 m, the egg cell develops rapidly to form a larva while in the uterus

Wuchereria bancrofti Morphology*Microfilaria is sheated and smooth-shaped, 0.24-0.35 mm longRegular nucleus, no terminal nucleus Cephalic space: the length is equal with the width

*Wuchereria bancrofti Morphology

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L3 enter human body*The L3 enter the skin of the human host through the puncture site of the mosquito when it takes its second blood meal.Details of larvae molting and development in humans are largely unknown, but it is thought the larvae almost a year to:Migrate to the lymphaticsMature undergoing two molts and to become an adult MateProduces microfilariae

Brugia malayi*The larva was first observed from a native Sumatera by Brug (1927)Nocturnal periodicityVector: Mansonia uniformis (rural) and Anopheles spp. (urban)

Brugia malayi Morphology*Adult resembles that of W bancroftiFemale is 43-55 mm, male is 13-23 mm with spiral-shaped tail

Brugia malayi Morphology*The larva is sheated and slightly winding (kinky), 0.18-0.23 mm longIrregular nucleus, 2 terminal nucleusCephalic space: the length is twice as the width

*Brugia malayi Morphology

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

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.

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 and their contribution to the observed cytokine production can be substantial. Therefore mast cells and basophils may play 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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ManagementDiagnosis*Clinical manifestationsLaboratory diagnosisMicroscopicImmunodiagnosisMolecular techniqueUltrasonography

Clinical Manifestations*Acute filariasisChronic filariasisAtypical presentationAsymptomatic carrier

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

*Adult worms in the lymphatic system

Microscopy for FilariaNucleopore membran (Knotts concentration)Staining thick blood film with GiemsaSpecific but not sensitive, depends on:Timing of sampling (periodicity)Volume of blood (volume increase sensitivity increase)Nucleopore membrane (knotts concentration)Staining of the blood filmMorphological characteristics*

PeriodicityDefinition:Relative density of microfilaria in peripheral circulation> 24 hours per cycleNocturnal periodic: peak microfilaria at around mid-night but very low or absence during the dayDiurnal periodic: peak microfilaria during the day but low or absence at nightNocturnal subperiodic: peak microfilaria density at night with lower density during the day

PeriodicityMicrofilariae stay in the lung during the daytime and come rarely out to the peripheral vessels, but soon after sunset they begin to appear in the peripheral blood, increasing in number from 10 p.m. until 6 a.m. (nocturnal periodicity)There are a number of theoriesPhotodynamic substance theory by MasuyaFluorescent substances in the microfilarias body are injured by the sunlight (W bancrofti and B malayi)Microfilaria of Loa loa has no fluorescent substance at all

Ultrasonography*Detect the motile adult worms within the lymphatics, scrotum and breast (term filarial dance signs). Detecting W bancrofti only.

Immunodiagnosis*Brugia rapidAntibody detection assayDetects IgG4

Immunodiagnosis*Antigen detection assayFor bancroftian filariasis

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