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Threadlike adult filarial worms reside in 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. Only a few filarial species infect humans.
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. The patient may have chest pain, cough, and occasionally hemoptysis. Many patients remain asymptomatic, and a pulmonary nodule is discovered on routine chest x-ray, which may be suggestive of a tumor. Diagnosis is by histologic examination of a surgical specimen. No treatment is indicated in humans; infection is self-limited.
Dracunculiasis
(Guinea Worm Disease; Fiery Serpent)
Dracunculiasis
is infection with Dracunculus medinensis.
Symptoms are a painful, inflamed skin lesion containing an adult
worm and debilitating arthritis. Diagnosis is by inspection. Treatment
is slow removal of the adult worm.
Twenty years ago dracunculiasis was endemic in much of tropical Africa, Yemen, India, and Pakistan. Today, infection occurs mainly within a narrow belt of African countries and Yemen.
Humans become infected by drinking water containing infected microcrustaceans (copepods). The larvae are released, penetrate the bowel wall, and mature into adult worms in about 1 yr. The gravid female migrates through subcutaneous tissues, usually to the distal lower extremities. The cephalic end of the worm produces an indurated papule that vesiculates and eventually ulcerates. On contact with water, a loop of the uterus prolapses through the skin and discharges motile larvae. Worms that fail to reach the skin die and disintegrate or become calcified. In most endemic areas, transmission is seasonal and each infectious episode lasts about 1 yr.
Symptoms and Signs
Infection is initially asymptomatic; symptoms usually develop with eruption of the worm. Local symptoms include intense itching and a burning pain at the site of the skin lesion. Urticaria, erythema, dyspnea, vomiting, and pruritus are thought to reflect allergic reactions to worm antigens. If the worm is broken during expulsion or extraction, a severe inflammatory reaction ensues with disabling pain. Symptoms subside and the ulcer heals once the adult worm is expelled. In about 50% of cases, secondary bacterial infections occur along the track of the emerging worm. Chronic sequelae include fibrous ankylosis of joints and contraction of tendons.
Diagnosis,
Treatment, and Prevention
Diagnosis is obvious once the white, filamentous adult worm appears at the cutaneous ulcer. Calcified worms can be localized with x-ray examination (they have been found in Egyptian mummies). Serodiagnostic tests are not specific.
Treatment consists of slow removal of the adult worm over days to weeks by rolling it on a stick. Surgical removal under local anesthesia is an option but is seldom available in endemic areas. The beneficial effect of metronidazole (250 mg tid for 10 days) has been ascribed to the drug's anti-inflammatory and antibacterial properties rather than to anthelmintic effects.
Filtering drinking water through a piece of cheesecloth, chlorination, or boiling effectively protects against dracunculiasis.
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. Loa loa are transmitted by tabanid flies (Chrysops, the deerfly, or horsefly). Adults migrate in subcutaneous tissues and the eye, and microfilariae circulate in blood. Occasionally, infection causes cardiomyopathy, nephropathy, or encephalitis.
Symptoms,
Signs, and Diagnosis
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 may be unsettling, but residual eye damage is uncommon.
Nephropathy generally presents 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.
Microscopic detection of microfilariae in peripheral blood establishes the diagnosis. Blood samples should be drawn around noontime, when microfilaremia levels are the highest. Serodiagnostic tests do not differentiate Loa
loa from other filarial nematode infections.
Treatment
and Prevention
Diethylcarbamazine (DEC) is the only drug that kills microfilariae and adult worms. DEC is given as 50 mg po on day 1, 50 mg po tid on day 2, 100 mg tid on day 3, then 3 mg/kg tid on days 4 through 14. A single dose of 6 mg/kg once has been used in mass treatment programs and is recommended by some. Multiple courses may be necessary before there is complete resolution. DEC transiently exacerbates proteinuria and, in heavily infected patients, may trigger encephalopathy, leading to coma and death. Lower doses of DEC (0.5 to 1.0 mg/kg once/day) and simultaneous corticosteroids may be used in heavily infected people. Such patients may benefit from apheresis or initial treatment with albendazole . Ivermectin administration in heavily infected patients may also cause encephalopathy and death.
DEC (300 mg po once/wk) can be used to prevent infection. Insect repellents may reduce exposure to infected flies.
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 serology. Treatment
is with diethylcarbamazine; antibiotics are used for complicating
bacterial cellulitis.
Etiology
and Pathophysiology
Lymphatic filariasis is caused by Wuchereria bancrofti
, Brugia malayi, and B. timori, which are spread by mosquitoes. Infective larvae from the mosquito migrate to the lymphatics, where they develop into threadlike adult worms within 6 to 12 mo. 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 129 million people are infected.
Symptoms and Signs
Infection often leads to microfilaremia without overt clinical manifestations. However, 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 an affected limb may result in an abscess that drains externally and leaves a scar. ADL is often associated with secondary bacterial infections.
Extralymphatic signs include chronic microscopic hematuria and proteinuria and mild polyarthritis, all presumed to result from immune complex deposition.
Chronic filarial disease develops insidiously after many years. In most patients, asymptomatic lymphatic dilatation occurs, but chronic inflammatory responses to adult worms and secondary bacterial infections may result in chronic lymphedema of the affected body area or to scrotal hydroceles. Chronic pitting lymphedema of the 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.
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. Microfilaremia gradually disappears after leaving the endemic area.
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 peak microfilaremia occurs—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 sensitive and specific rapid antigen test is available for W.
bancrofti but not for other filariae. Measurement of antifilarial IgG is available from the National Institutes of Health and is very sensitive as an initial screen, but it cannot differentiate past exposure from current active infection; thus, it is most helpful in visitors to endemic areas. PCR-based assays for DNA of W. bancrofti and B. malayi are available in research settings.
Treatment
and Prevention
Diethylcarbamazine (DEC) kills microfilariae and a variable proportion of adult worms. A recommended dose is 50 mg po on day 1, 50 mg po tid on day 2, 100 mg po 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 alone does not kill adult worms. Acute attacks of ADL generally 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, which 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 may occur in up to 25% of cases, requiring additional courses of therapy.
Avoiding mosquito bites in endemic areas is the best protection. Chemoprophylaxis with DEC or combinations of antifilarial drugs ( ivermectin / albendazole or ivermectin /DEC) can suppress microfilaremia. 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 and lymphatic obstruction, chronic skin disease, and
eye lesions that may lead to blindness. Diagnosis is by finding
microfilariae in skin snips, the cornea, or anterior chamber of
the eye; identifying adult worms in subcutaneous nodules; or using
PCR or DNA probes. Treatment is with ivermectin.
Etiology
and 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. Mature female worms produce microfilariae that migrate mainly through the skin and invade the eyes.
About 18 million people are infected, of whom 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 is fairly rare in the Americas.
Symptoms and Signs
The subcutaneous (or deeper) nodules (onchocercoma) that contain adult worms may be visible or palpable but otherwise asymptomatic. They are composed of inflammatory cells and fibrotic tissue in various proportions. Old nodules may caseate or calcify.
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 ranges from mild visual impairment to complete blindness. Lesions of the anterior eye include punctate (snowflake) keratitis, an acute inflammatory infiltrate surrounding dying microfilariae that resolves without causing permanent damage; sclerosing keratitis, an ingrowth of fibrovascular scar tissue that may cause subluxation of the lens and blindness; and anterior uveitis or iridocyclitis that may deform the pupil. 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 by 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. Serodiagnostic tests are also available in specialty laboratories, but the specificity depends on the antigen, and substantial cross-reactivity exists between Onchocerca and other helminths. Serology cannot differentiate past from current infection.
Palpable nodules (or deep nodules detected by ultrasonography or MRI in industrialized countries) can be excised and examined for adult worms.
Treatment
and Prevention
Ivermectin is given as a single oral dose of 150 μg/kg, repeated q 6 to 12 mo until asymptomatic. Ivermectin reduces microfilariae in the skin and eyes and decreases production of microfilariae for several 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. Doxycycline , which targets an endosymbiont of the adult filaria, is still being studied.
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 reduce skin microfilaria counts, but it has been replaced by ivermectin therapy.
In theory it is possible to minimize Simulium bites by avoiding fly-infested areas, wearing protective clothing, and liberally using insect repellents.
Last full review/revision November 2005
Content last modified November 2005
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