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Threadlike adult filarial worms reside in lymphatic or subcutaneous tissues. Gravid females produce live offspring (microfilariae) that circulate in blood or migrate through tissues. When ingested by a suitable bloodsucking insect (mosquitoes or flies), microfilariae develop into infective larvae that are inoculated or deposited in the skin of the next host during the insect bite. Life cycles of all filarial worms are similar except for the site of infection. Only a few filarial species infect humans.
Subcutaneous filariasis is caused by Loa loa (the African eye worm) and Onchocerca volvulus.
Lymphatic filariasis is caused by Wuchereria bancrofti, Brugia malayi, and B. timori.
Dirofilariasis
(Dog Heartworm Infection)
Dirofilaria immitis is the dog heartworm, which is transmitted to humans by infected mosquitoes.
Symptomatic human infection is very rare, but larvae may become encapsulated in infarcted lung tissue and produce well-defined pulmonary nodules.
Patients may have chest pain, cough, and occasionally hemoptysis. Many patients remain asymptomatic, and a pulmonary nodule, which may suggest a tumor, is discovered during routine chest x-ray.
Diagnosis is by histologic examination of a surgical specimen. No treatment is indicated in humans; infection is self-limited.
Loiasis
Loiasis is infection with Loa loa. Symptoms include localized angioedema (Calabar swellings) and subconjunctival migration of adult worms. Diagnosis is by detecting microfilariae in peripheral blood or seeing worms migrating across the eye. Treatment is with diethylcarbamazine.
Loiasis is confined to the rain forest belt of western and central Africa. Humans are the only known natural reservoir for this parasite.
Loa loa microfilariae are transmitted by day-biting tabanid flies (Chrysops [deerfly or horsefly]). Microfilariae mature to adult worms in the subcutaneous tissues of the human host; females are 40 to 70 mm long, and males are 30 to 34 mm long. The adults produce more microfilariae. Adults migrate in subcutaneous tissues and the eye, and microfilariae circulate in blood. Flies become infected when they ingest blood from a human host during the day (when microfilaremia levels are the highest).
Occasionally, infection causes cardiomyopathy, nephropathy, or encephalitis.
Symptoms and Signs
Infection produces areas of angioedema (Calabar swellings) that develop anywhere on the body but predominantly on the extremities; they are presumed to reflect hypersensitivity reactions to allergens released by migrating adult worms. In native residents, swellings usually last 1 to 3 days but are more frequent and severe in visitors. Worms may also migrate subconjunctivally across the eyes. This migration may be unsettling, but residual eye damage is uncommon.
Nephropathy generally manifests as proteinuria with or without mild hematuria and is believed to be due to immune complex deposition. Encephalopathy is usually mild, with vague CNS symptoms.
Diagnosis
Microscopic detection of microfilariae in peripheral blood establishes the diagnosis. Blood samples should be drawn around noontime, when microfilaremia levels are the highest. Serologic tests for antibodies do not differentiate Loa loa from other filarial nematode infections.
Treatment
Diethylcarbamazine (DEC) is the only drug that kills microfilariae and adult worms. Patients with microfilariae in the blood are given DEC 50 mg po on day 1, 50 mg po tid on day 2, 100 mg tid on day 3, then 2 mg/kg tid on days 4 through 14. A single dose of 6 mg/kg has been used in mass treatment programs. Multiple courses may be necessary before resolution is complete.
DEC transiently exacerbates proteinuria and, in heavily infected patients, may trigger encephalopathy, leading to coma and death. Such patients may benefit from apheresis or initial treatment with albendazole, and multiple courses of therapy may be necessary. Ivermectin has also been used to reduce microfilaremia, but albendazole is preferred because its onset of action is slower and risk of precipitating encephalopathy is lower.
Prevention
DEC 300 mg po once/wk can be used to prevent infection. Using insect repellents (including permethrin-impregnated clothing) and wearing long-sleeved and long-legged clothing may reduce the number of bites by infected flies. Because the flies are day-biting, mosquito (bed) nets do not help.
Bancroftian and Brugian Lymphatic Filariasis
Lymphatic filariasis is infection with any of 3 species of Filarioidea. Acute symptoms include fever, lymphadenitis, lymphangitis, funiculitis, and epididymitis. Chronic symptoms include abscesses, hyperkeratosis, polyarthritis, hydroceles, lymphedema, and elephantiasis. Tropical pulmonary eosinophilia with bronchospasm, fever, and pulmonary infiltrates is another manifestation of infection. Diagnosis is by detection of microfilariae in blood, ultrasound visualization of adult worms, or serologic testing. Treatment is with diethylcarbamazine; antibiotics are used for complicating bacterial cellulitis.
Etiology
Lymphatic filariasis is caused by Wuchereria bancrofti, Brugia malayi, and B. timori. Transmission is by mosquitoes. Infective larvae from the mosquito migrate to the lymphatics, where they develop into threadlike adult worms within 6 to 12 mo. Females are 80 to 100 mm long; males are about 40 mm long. Gravid adult females produce microfilariae that circulate in blood.
Bancroftian filariasis is present in tropical and subtropical areas of Africa, Asia, the Pacific, and the Americas, including Haiti. Brugian filariasis is endemic in South and Southeast Asia. Current estimates suggest that about 120 million people are infected.
Symptoms and Signs
Infection can result in microfilaremia without overt clinical manifestations. Symptoms and signs are caused primarily by adult worms. Microfilaremia gradually disappears after people leave the endemic area.
Acute inflammatory filariasis consists of 4- to 7-day episodes (often recurrent) of fever and inflammation of lymph nodes with lymphangitis (termed acute adenolymphangitis [ADL]) or acute epididymitis and spermatic cord inflammation. Localized involvement of a limb may cause an abscess that drains externally and leaves a scar. ADL is often associated with secondary bacterial infections. ADL episodes usually precede onset of chronic disease by ≥ 2 decades. Acute filariasis is more severe in previously unexposed immigrants to endemic areas than in native residents.
Chronic filarial disease develops insidiously after many years. In most patients, asymptomatic lymphatic dilation occurs, but chronic inflammatory responses to adult worms and secondary bacterial infections may result in chronic lymphedema of the affected body area or in scrotal hydroceles. Chronic pitting lymphedema of a lower extremity can progress to elephantiasis. Increased local susceptibility to bacterial and fungal infections contributes to the development of elephantiasis. Other forms of chronic filarial disease are caused by disruption of lymphatic vessels or aberrant drainage of lymph fluid, leading to chyluria and chyloceles.
Extralymphatic signs include chronic microscopic hematuria and proteinuria and mild polyarthritis, all presumed to result from immune complex deposition.
Tropical pulmonary eosinophilia (TPE) is an uncommon manifestation with recurrent bronchospasm, transitory lung infiltrates, low-grade fever, and marked eosinophilia. It is most likely due to hypersensitivity reactions to microfilariae. Chronic TPE can lead to pulmonary fibrosis.
Diagnosis
Microscopic detection of microfilariae in blood establishes the diagnosis. Filtered or centrifuged concentrates of blood are more sensitive than thick blood films. Blood samples must be obtained when microfilaremia peaks—at night where W. bancrofti is endemic, but during the day in many Pacific islands where B. malayi and B. timori occur. Viable adult worms can be visualized in dilated lymphatics by ultrasonography; their movement has been called the filarial dance.
A rapid-format immunochromatographic antigen test specific for W. bancrofti has recently been evaluated in the field. Antibody detection is of limited value; there is substantial antigenic cross-reactivity between filariae and other helminths, and a positive serologic test does not distinguish between past and current infection. PCR-based assays for DNA of W. bancrofti and B. malayi are available in research settings.
Treatment
Optimal treatment is uncertain. Diethylcarbamazine (DEC) kills microfilariae and a variable proportion of adult worms. The DEC dose in patients with heavy microfilaremia is 50 mg po on day 1, 50 mg tid on day 2, 100 mg tid on day 3, then 2 mg/kg tid on days 4 to 14. A single dose of albendazole (400 mg po) with either ivermectin (200 μg/kg po) or DEC (6 mg/kg) rapidly reduces microfilaremia levels, but ivermectin does not kill adult worms.
Also, doxycycline has been given long-term (eg, 8 wk). Doxycycline kills Wolbachia endosymbiont bacteria within filaria, leading to death of the worms.
Acute attacks of ADL usually resolve spontaneously, although antibiotics may be required to control secondary bacterial infections. Whether DEC therapy prevents or lessens chronic lymphedema remains controversial.
Chronic lymphedema requires meticulous skin care, including use of systemic antibiotics to treat secondary bacterial infections; these antibiotics may slow or prevent progression to elephantiasis. Conservative measures such as elastic bandaging of the affected limb reduce swelling. Surgical decompression using nodal-venous shunts to improve lymphatic drainage offers some long-term benefit in extreme cases of elephantiasis. Massive hydroceles can also be managed surgically.
TPE responds to DEC (2 mg/kg tid for 12 to 21 days), but relapses occur in up to 25% of patients and require additional courses of therapy.
Prevention
Avoiding mosquito bites in endemic areas is the best protection (eg, by using diethyltoluamide [DEET], permethrin-impregnated clothing, and bed nets). Chemoprophylaxis with DEC or combinations of antifilarial drugs (ivermectin/albendazole or ivermectin/DEC) can suppress microfilaremia and thereby reduce transmission of the parasite by mosquitoes in endemic communities. DEC has even been used as an additive to table salt in some endemic areas.
Onchocerciasis
(River Blindness)
Onchocerciasis is infection with the filarial nematode Onchocerca volvulus. Symptoms are subcutaneous nodules, pruritus, adenopathy, lymphatic obstruction, chronic skin disease, and eye lesions that may lead to blindness. Diagnosis is by finding microfilariae in skin snips, the cornea, or the anterior chamber of the eye; identifying adult worms in subcutaneous nodules; or using PCR or DNA probes. Treatment is with ivermectin.
Pathophysiology
Onchocerciasis is spread by blackflies (Simulium sp) that breed in swiftly flowing streams (hence, the term river blindness). Infective larvae inoculated into the skin during the bite of a blackfly develop into adult worms in 12 to 18 mo. Adult female worms may live up to 15 yr in subcutaneous nodules. Females are 33 to 50 cm long; males are 19 to 42 mm long. Mature female worms produce microfilariae that migrate mainly through the skin and invade the eyes.
Etiology
About 18 million people are infected; about 270,000 are blind and an additional 500,000 are visually impaired. Onchocerciasis is the 2nd leading cause of blindness worldwide (after trachoma). Onchocerciasis is most common in tropical and sub-Saharan regions of Africa. Small foci exist in Yemen, southern Mexico, Guatemala, Ecuador, Colombia, Venezuela, and the Brazilian Amazon. Blindness due to onchocerciasis is fairly rare in the Americas.
Symptoms and Signs
Onchocerciasis typically affects
Nodules
The subcutaneous (or deeper) nodules (onchocercoma) that contain adult worms may be visible or palpable but are otherwise asymptomatic. They are composed of inflammatory cells and fibrotic tissue in various proportions. Old nodules may caseate or calcify.
Dermatitis
Onchocercal dermatitis is caused by the microfilarial stage of the parasite. Intense pruritus may be the only symptom in lightly infected people. Skin lesions usually consist of a nondescript maculopapular rash with secondary excoriations, scaling ulcerations and lichenification, and mild to moderate lymphadenopathy. Premature wrinkling, skin atrophy, enlargement of inguinal or femoral nodes, lymphatic obstruction, patchy hypopigmentation, and transitory localized areas of edema and erythema can occur.
Onchocercal dermatitis is generalized in most patients, but a localized and sharply delineated form of eczematous dermatitis with hyperkeratosis, scaling, and pigment changes (Sowdah) is common in Yemen and Saudi Arabia.
Eye disease
Ocular involvement ranges from mild visual impairment to complete blindness. Lesions of the anterior portion of the eye include
Chorioretinitis, optic neuritis, and optic atrophy may also occur.
Diagnosis
Demonstration of microfilariae in skin snips is the traditional diagnostic method (see Table 1: Approach to Parasitic Infections: Collecting and Handling Specimens for Microscopic Diagnosis of Parasitic Infections ). Microfilariae may also be visible in the cornea and anterior chamber of the eye during slit-lamp examination. PCR-based methods to detect parasite DNA in skin snips may be more sensitive than standard techniques but are available only in research settings. Antibody detection is of limited value; there is substantial antigenic cross-reactivity among filaria and other helminths, and a positive serologic test does not distinguish between past and current infection. Palpable nodules (or deep nodules detected by ultrasonography or MRI) can be excised and examined for adult worms, but this procedure is rarely necessary.
Treatment
Ivermectin is given as a single oral dose of 150 μg/kg, repeated q 6 to 12 mo until patients are asymptomatic. Ivermectin reduces microfilariae in the skin and eyes and decreases production of microfilariae for many months. It does not appear to kill adult worms in standard regimens but inhibits microfilarial release from female worms. Adverse effects are qualitatively similar to those of diethylcarbamazine (DEC) but are much less common and less severe. DEC is no longer used for onchocerciasis because it can cause a severe hypersensitivity (Mazzotti) reaction, which can further damage skin and eyes and lead to cardiovascular collapse.
Long-term use (eg, 6 wk) of doxycycline, which targets Wolbachia endosymbiont bacteria, with or without a single dose of ivermectin has produced long periods of amicrofilaremia.
Prevention
No drug has been shown to protect against infection with O. volvulus. However, annual or semiannual administration of ivermectin effectively controls disease and may decrease transmission. Surgical removal of accessible onchocercomas can also reduce skin microfilaria counts, but it has been replaced by ivermectin therapy.
Simulium bites can be minimized by avoiding fly-infested areas, by wearing protective clothing, and possibly by liberally applying insect repellents.
Last full review/revision December 2009 by Richard D. Pearson, MD
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