Filariasis, Lymphatic

Essentials of Diagnosis

• Episodic attacks of lymphangitis, lymphadenitis, and fever

• Chronic progressive swelling of extremities and genitals; hydrocele; chyluria; lymphedema

• Microfilariae in blood, chyluria, or hydrocele fluid; positive serologic tests

General Considerations

• Caused by filarial nematodes

  • Wuchereria bancrofti

  • Brugia malayi

  • Brugia timori

  • Mansonella perstans

  • Onchocerca volvulus

  • Loa loa

  • Mansonella streptocerca

  • Mansonella ozzardi

• Humans are infected by bites of infected mosquitoes

• Larvae move to the lymphatics and lymph nodes where they mature over months

• The thread-like adult worms can live for many years and produce large numbers of microfilariae, which are infective to mosquitoes

• Microfilariae are released into the circulation, usually at night except in the South Pacific where microfilaremia peaks during daylight hours

Demographics

• Approximately 120 million people are infected with these organisms in tropical and subtropical countries

  • About one-third of these people suffer clinical consequences of the infections

  • Many are seriously disfigured

• W bancrofti

  • Causes about 90% of episodes of lymphatic filariasis

  • Tansmitted by Culex, Aedes, and Anopheles mosquitoes

  • Widely distributed in the tropics and subtropics, including subsaharan Africa, southeast Asia, the western Pacific, India, South America, and the Caribbean

• B malayi

  • Transmitted by Mansonia and Anopheles mosquitoes

  • Endemic in parts of China, India, southeast Asia, and the Pacific

• B timori is found only in islands of southeastern Indonesia

• Mansonella are filarial worms transmitted by midges and other insects in Africa and South America

Symptoms and Signs

• Many infections remain asymptomatic despite circulating microfilariae

• Clinical consequences of infection are principally due to inflammatory responses to developing, mature, and dying worms

Acute disease

• Initial manifestation is often acute lymphangitis, with fever, painful lymph nodes, edema, and inflammation spreading peripherally from involved lymph nodes

• Lymphangitis and lymphadenitis of the upper and lower extremities is common

• Genital involvement occurs with W bancrofti infection

  • Epididymitis

  • Orchitis

  • Scrotal pain and tenderness

• Acute attacks of lymphangitis last for a few days to a week and may recur a few times per year

• Filarial fevers may also occur without lymphatic inflammation

Chronic disease

• Most common manifestation is swelling of the extremities or genitals due to chronic lymphatic inflammation and obstruction

• Extremities become increasingly swollen, with a progression from pitting edema to nonpitting edema to elephantiasis

• Genital involvement, particularly with W bancrofti, occurs more commonly in men

  • Progresses from painful epididymitis to hydroceles, which are usually painless but can become very large

  • Inguinal lymphadenopathy

  • Thickening of the spermatic cord

  • Scrotal lymphedema

  • Thickening and fissuring of the scrotal skin

  • Chyluria (occasionally)

• Lymphedema of the female genitalia and breasts may also occur

Tropical pulmonary eosinophilia

• Infects young adult males with either W bancrofti or B malayi infection but typically without microfilaremia

• Characterized by asthma-like symptoms, with cough, wheezing, dyspnea, and low-grade fevers (usually at night)

• Mansonella

  • Can inhabit serous cavities, the retroperitoneum, the eye, or the skin

  • Can cause abnormalities related to inflammation at these sites

Differential Diagnosis

• Bacterial lymphangitis

• Loiasis (Loa loa infection)

• Idiopathic hydrocele

• Lower extremity edema due to other cause

  • Heart failure

  • Cirrhosis

  • Nephrotic syndrome

• Lymphoma

Laboratory Tests

• Diagnosis confirmed by finding microfilariae, usually in the blood

• Microfilariae may be absent, especially early in disease progression (first 2–3 years) or with chronic obstructive disease

• To increase yields, obtain blood samples at midnight in most areas but during daylight hours in South Pacific

• Smears are evaluated by wet mount to identify motile parasites and by Giemsa staining

• Microfilariae may also be identified in hydrocele fluid or chylous urine

• Eosinophilia usually absent, except during acute inflammatory syndromes

• Serologic tests may be helpful but cannot distinguish past and active infections

• Rapid antigen tests with sensitivity and specificity over 90% are available

Imaging Studies

• Adult worms can be detected by ultrasound of a scrotal hydrocele or lymphedematous breast

Diagnostic Procedures

• Lymph node biopsy specimens (although not usually clinically indicated) may show adult worms

Medications

• Diethylcarbamazine

  • Drug of choice, but cannot cure infections due to its limited action against adult worms

  • Give 2 mg/kg orally three times daily for 10–14 days for asymptomatic infection and acute lymphangitis

  • Therapy may be accompanied by allergic symptoms (eg, fever, headache, malaise, hypotension, and bronchospasm) probably due to release of antigens from dying worms

  • Therefore, begin treatment with lower dosage and escalate over first 4 days

• Single annual dose of diethylcarbamazine (6 mg/kg orally) alone or with ivermectin (400 mcg/kg orally) or albendazole (400 mg orally) may be as effective as longer courses of diethylcarbamazine

• When onchocerciasis or loiasis is suspected

  • May be appropriate to withhold diethylcarbamazine to avoid severe reactions to dying microfilariae

  • Use ivermectin plus albendazole instead

• Drainage of hydroceles provides symptomatic relief, but they will recur

• Doxycycline (100–200 mg/day orally for 4–6 weeks)

  • Kills obligate intracellular Wolbachia bacteria, leading to death of adult filarial worms

  • Currently under study

• Doxycycline was also effective at controlling M perstans infection, which does not respond well to standard antifilarial drugs

• Secondary bacterial infections much be treated

Surgery

• May be helpful in some cases

Complications

• Untreated tropical pulmonary eosinophilia can progress to interstitial fibrosis and chronic restrictive lung disease

Prognosis

• Good with treatment of early and mild cases (including low-grade lymphedema, chyluria, small hydrocele)

• Poor in advanced infection

When to Refer

• All patients should be referred to a specialist

When to Admit

• Debilitating filarial fever

• Progressive and disseminated disease

Prevention

• Avoid mosquitoes by using

  • Screens

  • Bed nets (ideally treated with insecticide)

  • Insect repellents

• Once or twice yearly diethylcarbamazine plus albendazole was accompanied by decreased lymphatic pathology in children with W bancrofti infection

• Mass treatment of at-risk communities with single annual doses of diethylcarbamazine plus albendazole is current strategy of World Health Organization