Filariasis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2]
Pathophysiology
Infective larvae are transmitted by infected biting arthropods during a blood meal. The larvae migrate to the appropriate site of the host's body, where they develop into microfilariae-producing adults. The adults dwell in various human tissues where they can live for several years. The agents of lymphatic filariasis reside in lymphatic vessels and lymph nodes; Onchocerca volvulus in nodules in subcutaneous tissues; Loa loa in subcutaneous tissues, where it migrates actively; Brugia malayi in lymphatics, as with Wuchereria bancrofti; Mansonella streptocerca in the dermis and subcutaneous tissue; Mansonella ozzardi apparently in the subcutaneous tissues; and M. perstans in body cavities and the surrounding tissues. The female worms produce microfilariae which circulate in the blood, except for those of Onchocerca volvulus and Mansonella streptocerca, which are found in the skin, and O. volvulus which invade the eye. The microfilariae infect biting arthropods (mosquitoes for the agents of lymphatic filariasis; blackflies [Simulium] for Onchocerca volvulus; midges for Mansonella perstans and M. streptocerca; and both midges and blackflies for Mansonella ozzardi; and deerflies [Chrysops] for Loa loa). Inside the arthropod, the microfilariae develop in 1 to 2 weeks into infective filariform (third-stage) larvae. During a subsequent blood meal by the insect, the larvae infect the vertebrate host. They migrate to the appropriate site of the host's body, where they develop into adults, a slow process than can require up to 18 months in the case of Onchocerca.
Life Cycle of Wuchereria Bancrofti
Different species of the following genera of mosquitoes are vectors of W. bancrofti filariasis depending on geographical distribution. Among them are: Culex (C. annulirostris, C. bitaeniorhynchus, C. quinquefasciatus, and C. pipiens); Anopheles (A. arabinensis, A. bancroftii, A. farauti, A. funestus, A. gambiae, A. koliensis, A. melas, A. merus, A. punctulatus and A. wellcomei); Aedes (A. aegypti, A. aquasalis, A. bellator, A. cooki, A. darlingi, A. kochi, A. polynesiensis, A. pseudoscutellaris, A. rotumae, A. scapularis, and A. vigilax); Mansonia (M. pseudotitillans, M. uniformis); Coquillettidia (C. juxtamansonia). During a blood meal, an infected mosquito introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound (1). They develop in adults that commonly reside in the lymphatics (2) . The female worms measure 80 to 100 mm in length and 0.24 to 0.30 mm in diameter, while the males measure about 40 mm by .1 mm. Adults produce microfilariae measuring 244 to 296 μm by 7.5 to 10 μm, which are sheathed and have nocturnal periodicity, except the South Pacific microfilariae which have the absence of marked periodicity. The microfilariae migrate into lymph and blood channels moving actively through lymph and blood (3) . A mosquito ingests the microfilariae during a blood meal (4) . After ingestion, the microfilariae lose their sheaths and some of them work their way through the wall of the proventriculus and cardiac portion of the mosquito's midgut and reach the thoracic muscles (5) . There the microfilariae develop into first-stage larvae (6) and subsequently into third-stage infective larvae (7). The third-stage infective larvae migrate through the hemocoel to the mosquito's prosbocis (8) and can infect another human when the mosquito takes a blood meal (1).
Life Cycle of Brugia Malayi
The typical vector for Brugia malayi filariasis are mosquito species from the genera Mansonia and Aedes. During a blood meal, an infected mosquito introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound (1). They develop into adults that commonly reside in the lymphatics (2). The adult worms resemble those of Wuchereria bancrofti but are smaller. Female worms measure 43 to 55 mm in length by 130 to 170 μm in width, and males measure 13 to 23 mm in length by 70 to 80 μm in width. Adults produce microfilariae, measuring 177 to 230 μm in length and 5 to 7 μm in width, which are sheathed and have nocturnal periodicity. The microfilariae migrate into lymph and enter the blood stream reaching the peripheral blood (3) . A mosquito ingests the microfilariae during a blood meal (4) . After ingestion, the microfilariae lose their sheaths and work their way through the wall of the proventriculus and cardiac portion of the midgut to reach the thoracic muscles (5) . There the microfilariae develop into first-stage larvae (6) and subsequently into third-stage larvae (7) . The third-stage larvae migrate through the hemocoel to the mosquito's prosbocis (8) and can infect another human when the mosquito takes a blood meal (1).
Life Cycle of Mansonella Perstans
During a blood meal, an infected midge (genus Culicoides) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound (1) . They develop into adults that reside in body cavities, most commonly the peritoneal cavity or pleural cavity, but less frequently in the pericardium (2) . The size range for female worms is 70 to 80 mm in length and 120 μm in diameter, and the males measure approximately 45 mm by 60 μm. Adults produce unsheathed and subperiodic microfilariae, measuring 200 by 4.5 μm that reach the blood stream (3) . A midge ingests microfilariae during a blood meal (4) . After ingestion, the microfilariae migrate from the midge's midgut through the hemocoel to the thoracic muscles of the arthropod (5) . There the microfilariae develop into first-stage larvae (6) and subsequently into third-stage infective larvae (7) . The third-stage infective larvae migrate to the midge's proboscis (8) and can infect another human when the midge takes a blood meal (1) .
Life Cycle of Mansonella Ozzardi
During a blood meal, an infected arthropod (midges, genus Culicoides, or blackflies, genus Simulium) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound (1) . They develop into adults that commonly reside in subcutaneous tissues (2) . Adult worms are rarely found in humans. The size range for females worms is 65 to 81 mm in length and 0.21 to 0.25 mm in diameter but unknown for males. Adults worms recovered from experimentally infected Patas monkeys measured 24 to 28 mm in length and 70 to 80 μm in diameter (males) and 32 to 62 mm in length and .130 to .160 mm in diameter (females). Adults produce unsheathed and non-periodic microfilariae that reach the blood stream (3) . The arthropod ingests microfilariae during a blood meal (4) . After ingestion, the microfilariae migrate from the arthropod's midgut through the hemocoel to the thoracic muscles (5) . There the microfilariae develop into first-stage larvae (6) and subsequently into third-stage infective larvae (7) . The third-stage infective larvae migrate to arthropod's proboscis (8) and can infect another human when the arthropod takes a blood meal (1)
Life Cycle of Mansonella Streptocerca
During a blood meal, an infected midge (genus Culicoides) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound (1) . They develop into adults that reside in the dermis, most commonly less than 1 mm from the skin surface (2) . The females measure approximately 27 mm in length. Their diameter is 50 μm at the level of the vulva (anteriorly) and ovaries (near the posterior end), and up to 85 μm at the mid-body. Males measure 50 μm in diameter. Adults produce unsheathed and non-periodic microfilariae, measuring 180 to 240 μm by 3 to 5 μm, which reside in the skin but can also reach the peripheral blood (3) . A midge ingests the microfilariae during a blood meal (4) . After ingestion, the microfilariae migrate from the midge's midgut through the hemocoel to the thoracic muscles (5) . There the microfilariae develop into first-stage larvae (6) and subsequently into third-stage larvae (7) . The third-stage larvae migrate to the midge's proboscis (8) and can infect another human when the midge takes another blood meal(1) .