Lymphatic filariasis is infection with any of 3 species of Filarioidea. Acute symptoms include fever, lymphadenitis, lymphangitis, epididymitis, and funiculitis (inflammation of the spermatic cord). 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 in lymphatics, or serologic testing. Treatment is with diethylcarbamazine; antibiotics are used for complicating bacterial cellulitis.
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.
Mass treatment programs have reduced the prevalence in many areas, but worldwide there are still an estimated 120 million people with lymphatic filariasis.
Lymphatic filariasis is caused by Wuchereria bancrofti (about 90% of cases), Brugia malayi, or 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 months. Females are 80 to 100 mm long; males are about 40 mm long. Gravid adult females produce microfilariae that circulate in blood.
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. Increased local susceptibility to bacterial and fungal infections further contributes to its development. Chronic pitting lymphedema of a lower extremity can progress to elephantiasis (chronic lymphatic obstruction). W. bancrofti can cause hydrocele and scrotal 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.
- Microscopic examination of blood samples
- Antigen test for W. bancrofti (available internationally, but not in the United States)
- Antibody tests
Microscopic detection of microfilariae in blood establishes the diagnosis of lymphatic filariasis. Filtered or centrifuged concentrates of blood are more sensitive than thick blood films. Blood samples must be obtained when microfilaremia peaks—at night in most endemic areas, but during the day in many Pacific islands. Viable adult worms can be visualized in dilated lymphatics by ultrasonography; their movement has been called the filarial dance.
Several blood tests are available:
- Antibody detection: Enzyme immunoassay tests for antifilarial IgG1 and IgG4
- Antigen detection: A rapid-format immunochromatographic test for W. bancrofti antigen
Patients with active filarial infection typically have elevated levels of antifilarial IgG4 in the blood. However, there is substantial antigenic cross-reactivity between filariae and other helminths, and a positive serologic test does not distinguish between past and current filarial infection. A rapid diagnostic test for W. bancrofti antigen is used internationally in filariasis elimination programs, but it is not licensed in the United States. Polymerase chain reaction (PCR) assays for W. bancrofti and B. malayi are available in research laboratories.
Diethylcarbamazine (DEC) kills microfilariae and a variable proportion of adult worms. In the United States, DEC is available from the Centers for Disease Control and Prevention (CDC) after laboratory confirmation of filariasis.
Pearls & Pitfalls
Treatment of acute lymphatic filariasis
DEC 2 mg/kg orally 3 times a day for 12 days has traditionally been used; 6 mg/kg orally once is an alternative. Generally, the 1-day regimen seems to be as effective as the 12-day regimen.
Adverse effects with DEC are usually limited and depend on the number of microfilariae in the blood. The most common are dizziness, nausea, fever, headache, and pain in muscles or joints, which are thought to be related to release of filarial antigens.
Before treatment with DEC, patients should be assessed for coinfection with Loa loa (loiasis) or Onchocerca volvulus (onchocerciasis) because DEC can cause serious reactions in patients with those infections. A single dose of albendazole 400 mg orally plus ivermectin (200 mcg/kg orally) can be used in areas where onchocerciasis is co-endemic, but ivermectin alone does not kill adult worms responsible for lymphatic filariasis. DEC should not be used in patients with high circulating Loa loa microfilarial levels due to risk of life-threatening side effects including encephalopathy.
A number of drug combinations and regimens have been used in mass treatment programs.
Also, doxycycline has been given long-term (eg, 100 mg orally twice a day for 4 to 6 weeks). Doxycycline kills Wolbachia endosymbiont bacteria within filaria, leading to death of adult filarial worms. It can be given with DEC or used alone.
Attacks of acute adenolymphangitis usually resolve spontaneously, although antibiotics may be required to control secondary bacterial infections.
Treatment of chronic lymphedema
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.
Whether DEC therapy prevents or lessens chronic lymphedema remains controversial.
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, but recurrence is common.
Treatment of tropical pulmonary eosinophilia
Tropical pulmonary eosinophilia (TPE) responds to DEC 2 mg/kg orally 3 times a day for 14 to 21 days, but relapses occur in up to 25% of patients and require additional courses of therapy.
Avoiding mosquito bites in endemic areas is the best protection for travelers (eg, by using diethyltoluamide [DEET] on exposed skin, permethrin-impregnated clothing, and bed nets).
The World Health Organization launched the Global Program to Eliminate Lymphatic Filariasis in 2000 to map endemic areas and treat entire at-risk populations with the following mass drug administration regimens: albendazole (400 mg) alone twice per year for areas co-endemic with loiasis, ivermectin (200 mcg/kg) and albendazole (400 mg) annually in areas with onchocerciasis, and diethylcarbamazine (DEC) (6 mg/kg) and albendazole (400 mg) plus ivermectin (200 mcg/kg) in some settings, annually in areas without onchocerciasis or loiasis. These regimens decrease microfilaremia and thereby reduce transmission of the parasite by mosquitoes. Table salt with DEC as an additive has also been used in a few areas. Transmission has been interrupted after 4 to 6 years of annual treatment. .
- Lymphatic filariasis is transmitted by mosquitoes; infective larvae migrate to the lymphatics, where they develop into adult worms.
- Adult worms inside the lymphatics can cause inflammation resulting in acute adenolymphangitis or epididymitis or in chronic lymphatic obstruction, which, in some patients, leads to elephantiasis or hydrocele.
- Diagnose based on microscopic detection of microfilariae in filtered or centrifuged concentrates of blood that is drawn at the time of day when microfilaremia peaks (varies by species).
- Tests for antigen, antibodies, and parasite DNA are alternatives to diagnosis by microscopy.
- Treat with diethylcarbamazine after excluding coinfection with Loa loa and Onchocerca volvulus.
- The Global Program to Eliminate Lymphatic Filariasis has reduced transmission in many endemic areas.
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