LYMPHATIC FILARIASIS
Lymphatic filariasis is a bloodstream and lymphatic infection caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. The disease is endemic in the tropics and subtropics of both hemispheres. A mosquito serves as an intermediate host and vector; the peak blood parasitemia and optimum time of the day or night for obtaining blood smears differ in various parts of the world, corresponding to the feeding pattern of the local mosquito vectors. After deposition by mosquitoes of infectious microfilariae into humans during a blood meal, 6-12 mo are required before adult worms mature and begin producing numerous circulating microfilariae to continue the life cycle. Symptoms of acute disease generally occur 8-16 mo after infection in nonindigenous peoples, but the incubation period may be longer in indigenous peoples.
Clinical & Laboratory Findings
Indigenous persons with filariasis are often asymptomatic. In the first few years after infection, variably present clinical manifestations include recurrent episodes of lymphangitis, notable for progression proximally to distally, unlike typical bacterial lymphangitis. These episodes may be accompanied by high fever and resolve within 7-10 d. Epididymitis or orchitis may occur intermittently. Other patients, especially travelers, may have allergic symptoms including urticaria, rashes, and eosinophilia. Chronic infection may result in lymphatic insufficiency, with lymphedema involving the extremities or external genitalia. Hydroceles may also occur. The term elephantiasis refers to advanced changes of chronic lymphedema, including subcutaneous thickening, skin hyperkeratosis, and fissuring.
Tropical pulmonary eosinophilia refers to a syndrome of nocturnal cough and wheezing with diffuse miliary chest x-ray infiltrates, eosinophilia, elevated immunoglobulin E concentrations, and high antifilarial antibody titers. The syndrome is caused by sequestration of W bancrofti or B malayi microfilariae in the lungs and responds to treatment with diethylcarbamazine citrate (DEC).
Diagnosis of filariasis is usually clinical in endemic areas. Confirmation requires demonstration of microfilaria in filtered blood samples, the timing of which should be adjusted to match the nocturnal or diurnal periodicity of the peak parasitemia in the region in which the infection was acquired. The organisms adapt their periodicity to local time zones, but this requires 10-14 d.
Microfilariae are more commonly seen in the bloodstream during the early stages of disease (1-2 years after infection) and are rare in the bloodstream during the lymphatic obstructive stage of disease. Administration of 50 mg of DEC may result in positive blood smears immediately (within 1 h) after administration in otherwise smear-negative individuals. Serologic testing may also be helpful, but both false positive and false negative test results occur.
Treatment
Symptomatic treatment of acute filarial lymphangitis (eg, antihistamines and aspirin) may be helpful in reducing the intensity of symptoms. DEC is an effective microfilaricidal drug, but the adult worms require a longer course of therapy and sometimes multiple courses of therapy to be eradicated. DEC (2 mg/kg) is administered 3 times daily for 2-3 wk. Allergic reactions (eg, fever, urticaria, or lymphangitis) to injured parasites may occur early in therapy; some authorities suggest smaller doses of DEC (50 mg on the first day, increasing to full dosage over 3-4 d) to minimize these reactions. Antihistamines may also be of benefit. Nonspecific side effects include headache, vertigo or dizziness, malaise, fever, or myalgias. Onchocerciasis should be excluded before DEC treatment. DEC is available in the United States from Lederle Laboratories (800-934-5556).
Prevention
Because transmission depends on mosquito vectors, control measures are directed at reducing mosquito populations and reducing the number of bites by mosquitoes.
OTHER FILARIAL INFECTIONS
LOIASIS
Loiasis (African eye worm infection) occurs in rainy areas of central and West Africa. The filarial parasites are transmitted by the bite of an infected Chrysops spp. horsefly. Organisms mature in the subcutaneous tissues, where adult worms may live for more than a decade and release microfilariae into the circulation.
Clinical Findings
Adult worms migrate through subcutaneous tissues at rates = 1 cm/min. This may be asymptomatic, or, especially when migration occurs around or across the eye, noted as conjunctivitis or eyelid edema. Calabar swellings are subcutaneous edematous areas of 3-10 cm that are nonerythematous and do not pit; local pain, pruritus, and mild fever may be present. Calabar swellings are transient, resolving after 2-3 d or 1 wk, only to reappear at irregular intervals in different locations. Calabar swellings do not necessarily contain worms at the time that they appear.
Symptoms of loiasis vary depending on the host. Indigenous populations typically have relatively mild symptoms or are asymptomatic even though they are microfilaremic. Travelers typically have a more symptomatic course, with an increased number and severity of Calabar swellings, marked eosinophilia, leukocytosis, hypergammaglobulinemia, and elevated immunoglobulin E antibodies.
Treatment
Treatment is with DEC, 3 mg/kg 3 times daily for 21 d. Localized inflammatory reactions to dying adult worms in tissues are common. In patients with microfilaremia, reactions may be more severe including severe neurologic complications and death. Gradually escalating doses of DEC and in some patients systemic corticosteroids may be used. Ivermectin and albendazole have been investigated as alternative therapies to DEC.
ONCHOCERCIASIS
Infection with Onchocerca volvulus causes African river blindness, which is the second leading cause of blindness worldwide. Onchocerciasis is transmitted by the Simulium spp. blackfly and is found in equatorial West, central, and East Africa and portions of Central and South America. Larval forms penetrate the skin after the bite of the blackfly, where they mature into adults in the subcutaneous tissues. Microfilariae from mature females migrate back to the dermis where they are ingested by blackflies to continue the life cycle.
Clinical Findings
Cutaneous and connective tissue manifestations of onchocerciasis include the formation, usually within a year, of mobile nodules encapsulating the adult worms in a fibrous tissue mass. Multiple nodules may be present in subcutaneous or connective tissues, especially over bony prominences. Depigmentation, wrinkling, and thickening of skin may be seen with chronic infection. Visual loss is the most serious complication. The earliest eye lesions are punctate keratitis associated with microfilariae within the cornea and anterior chamber. Iridocyclitis and posterior synechiae may develop, which may result in a fixed and distorted pupil. Lesions of the posterior chamber of the eye are less common, including optic atrophy and choroiditis.
Diagnosis is suspected clinically and confirmed by examination of a skin snip obtained without anesthesia from the shoulder or buttock areas, demonstrating microfilariae. Adult worms may be found in biopsied or excised nodules. Slit-lamp examination of the cornea or anterior chamber of the eye may demonstrate microfilariae. Microfilariae are identifiable in urine in 17%-30% of patients > 10 years old.
Treatment
The treatment of choice is ivermectin, 150 5g/kg orally as a single dose, which kills microfilariae but is less effective against adult worms. Treatment is repeated at 3-mo intervals for 2-3 years. Diethylcarbamazine has been used historically but is less effective and more toxic than ivermectin, and it is no longer recommended by the World Health Organization. Cutaneous nodules, especially on the scalp, may be surgically excised.