There are eight filarial species that can infect humans and out of them four (4) of them causes most serious filarial infections and they are Wuchereria bancrofti, Brugia malayi, Onchocerca volvulus, and Loa loa (the other 4 species are B. timori, Mansonella ozzardi, M. streptocerca and M. perstans). The causative agents of filaria are nematodes and they dwell in the subcutaneous tissues and the lymphatic channels of humans.

Filarial parasites infect approximately 170 million people worldwide, are transmitted by specific species of mosquitoes or other arthropods (different in different countries). Filarial parasites have a complex life cycle which include infective larval stages inside insects and adult worms that reside in either lymphatic or subcutaneous tissues of humans. The microfilariae (offspring of adults) are about 200–250 µm (micrometer) long and 5–7 µm wide, with or without enveloped by a loose sheath. The microfilariae either circulate in the blood or migrate through the skin and the circulating microfilariae are taken up by the arthropod vector (mosquito, midges, flies etc.) and develop over 1–2 weeks into new infective larvae. Microfilariae live for 3 months to 3 years, whereas adult worms live for many year. Filarial infection generally occurs with repeated and prolonged exposures to infective larvae only. The clinical manifestations of filariasis develop slowly; the infection can induce chronic disease with possible long-term debilitating effects. The nature and severity of clinical manifestations of filariasis in individuals who are native to endemic areas (as they undergo lifelong exposure) may differ significantly from the travelers or who have recently moved to these areas and filariasis is more acute and intense in newly exposed individuals than in natives of endemic areas.

How filariasis is transmitted?

Filariasis is mainly transmitted by mosquito (different species in different areas) bites and other insect bites like deerflies, blackflies, midges etc.

For W. bancrofti in cosmopolitan areas worldwide the mosquito involved is culex. In India Anopheles mosquito is the main culprit and in China, Indonesia and Eastern Pacific it is the aedes mosquito.

For Brugia malayi in India, Indonesia and Southeast Asia the mosquitoes involved in transmission are Mansonia & Anopheles in nocturnal periodicity and for subperiodic periodicity the insect involve in Indonesia and Southeast Asia are Coquillettidia & Mansonia. B. timori (found only in Indonesia) the mosquito involved in transmission is Anopheles.

For Loa loa (found in West and Central Africa) the insect involved in transmission is deerfly Chrysops.

For Onchocerca volvulus found in Africa, South and Central America the insect involved in transmission is blackfly Simulium.

For Mansonella ozzardi the insect involved in transmission is midge Culicoides in South and Central America and blackfly Simulium in Caribbean. For M. perstans the found in Africa and South and Central America the insect involved in transmission is midge Culicoides and for M. streptocerca found in West and Central Africa the insect is the same midge Culicoides.

Lymphatic filariasis:

Lymphatic filariasis is caused by W. bancrofti, B. malayi, or B. timori. The adult parasites which are threadlike reside in lymphatic channels or lymph nodes. They can live there for more than two decades and cause lymphatic filariasis.

What is global incidence of lymphatic filariasis?

Wuchereria bancrofti alone affects approximately 115 million people worldwide. The Wuchereria bancrofti is most widely distributed human filarial parasite and found in the tropics and subtropics (Asia and the Pacific Islands, Africa, South America, and the Caribbean region). Humans are the only definitive host (where sexual development takes place) for the parasite. Natural vectors for W. bancrofti are Culex fatigans mosquitoes in urban areas and anopheles or aedes mosquitoes in rural areas. The microfilariae of W. bancrofti are of two types according to periodicity which are nocturnally periodic (microfilariae are scarce in peripheral blood during day time and microfilariae are large number at night) and subperiodic (microfilariae are present in peripheral blood at all times and reach largest numbers in the afternoon). Brugian filariasis due to B. malayi generally occurs in India, Indonesia, China, Korea, Japan, Malaysia, and the Philippines. The periodicity of microfilariae are same as W. bancrofti and the nocturnal form (commoner) is transmitted in areas of coastal rice fields, while the subperiodic form is found in forest areas.

What is the pathology involved in lymphatic filariasis?

The main pathological changes in lymphatic filariasis are seen in lymphatics system which results from inflammatory damage, which are due to the adult worms (not by the microfilariae). The adult worms live in afferent lymphatics or sinuses of lymph nodes and cause dilatation and thickening of the lymphatic vessels. Lymph valves are damaged or become incompetent due to tortuosity of the lymphatics, which results from infiltration of plasma cells, eosinophils, and macrophages in and around the infected lymph vessels and also there is endothelial and connective tissue proliferation. Lymphedema and chronic-stasis occurs and the overlying skin becomes edematous and brawny. All these changes in lymphatic filariasis are due to direct effects of the adult worms as well as inflammatory response of the host to the worms. Lymphatic obstruction occurs because of granulomatous and proliferative processes that occur due to inflammatory responses. The lymphatic vessels remains patent as long as the worm remains alive (viable) inside the vessels and death of the worm leads to enhanced granulomatous reaction and fibrosis which causes obstruction of lymph vessels. Collateral circulation of lymphatics occurs, but the lymphatic function is compromised despite development of collateral circulation.

What are the clinical manifestations of lymphatic filariasis?

Most of the lymphatic filariasis are asymptomatic (subclinical). The most common presenting manifestations of filariasis are hydrocele, acute adenolymphangitis (ADL), and chronic lymphatic disease. In filaria endemic areas the large majority of infected individuals have few overt clinical manifestations of filarial infection even if there are large numbers of circulating microfilariae in the peripheral blood. But all the individuals with filarial infection have some degree of subclinical manifestations like microscopic hematuria (blood in urine detectable under microscope only) and/or proteinuria (protein in urine), dilated and tortuous lymphatics (visualized by imaging), and in men scrotal lymphangiectasia which can only be detected by ultrasound. But despite the subclinical findings most of the individuals with filarial infection remains asymptomatic for years and only a minority of them progress to acute or chronic disease.

Adenolymphangitis causes high fever, lymphatic inflammation (lymphangitis and lymphadenitis) and local edema. Lymphangitis extends from lymph nodes to the draining the area where the adult worms are present. Sometimes regional lymph nodes are enlarged, and the lymphatic channels can become indurated (hard) and inflamed. Lymphangitis and lymphadenitis can involve both the upper and lower extremities. Involvement of genital lymphatics occurs exclusively with W. bancrofti infection and with brugian filariasis (Brugia malayi & B. timori infection) there may be a single local abscess along the involved lymphatic tract and subsequently rupture to the surface.

How filariasis is diagnosed?

The definitive diagnosis of filariasis is possible only by demonstration of the parasites (worms) in the body, which may be very difficult. Adult worms are difficult to demonstrate as they reside inside lymphatic vessels or lymph nodes. But microfilaria can be demonstrated in body blood, fluid present in hydrocele or sometimes in other body fluids. Such fluids can be examined under microscope directly or after concentration of the parasites by the centrifugation of fluid fixed in 2% formalin known as Knott's concentration technique (here chances of finding the microfilaria is greater than direct microscopy). Microfilaria can also be concentrated by passing the fluid through a polycarbonate cylindrical pore filter (pore size, 3 micrometer) To increase the chance of finding microfilaria in blood, it is essential to collect blood at the right time when concentration of microfilaria is greatest in blood, which depends on the periodicity of microfilaria in that particular endemic region. Many patients with filariasis may not have microfilaria in blood and definitive diagnosis may be very difficult in these patients and assays for circulating antigens of filarial parasites (W. bancrofti, but not for brugian filariasis) can aid diagnosis. Two types of assay are commercially available at present one is ELISA (enzyme-linked immunosorbent assay) and the other is rapid-format immunochromatographic card test. The tests are highly sensitive (the ability to give positive result if disease is present or no false negative result) which is 96-100% and specific (ability to give negative result if no disease is present or no false positive result) which is almost 100%. PCR or polymerase chain reaction based assays for DNA of both W. bancrofti and B. malayi is also present and is as good as any other diagnostic test for filariasis.

Eosinophilia (high eosinophil count in blood) and raised serum IgE and antifilarial antibody support the diagnosis of lymphatic filariasis. But there is, extensive cross-reactivity between antigens of filaria and other helminths (common intestinal roundworms and other worms); so, interpretations of serologic findings can be difficult. The residents of endemic areas of filariasis can become serologically positive through exposure to infected mosquitoes without having patent filarial infections which also make interpretation of serologic findings more difficult.

Role of ultrasound and other imaging techniques in diagnosis of filariasis:

In suspected lymphatic filariasis the examination of breast in females and scrotum in males with high-frequency ultrasound with Doppler techniques may show motile adult worms within dilated lymphatics. Worms can also be visualized in the lymphatic vessels of the spermatic cord of approximately 80% of infected males by use of ultrasound. In the lymphatic vessels the live worms have a distinctive movement pattern known as “filarial dance sign”. Radionuclide lymphoscintigraphic imaging (this is basically a research tool) of limbs can demonstrate lymphatic abnormalities in both asymptomatic microfilaremic persons as well as in persons with clinical manifestations of lymphatic pathology.

How lymphatic filariasis is treated?

Treatment of active lymphatic filariasis:

Diethylcarbamazine (DEC) 6mg/kg body weight daily for 12 days is the treatment of choice in active lymphatic filariasis (microfilaremia, antigen positivity, or adult worms on ultrasound), as it has both macro (adult) and microfilaricidal (able to kill) properties. Other alternative drugs are albendazole (400 mg two times a day for 21 days), although the macrofilaricidal efficacy is less than that of DEC, doxycycline for 8 weeks (200 mg daily) and one week course of DEC and albendazole combined (DEC 6mg/kg per day and albendazole 400 mg two times per day).

Treatment of asymptomatic filariasis:

Asymptomatic filariasis should be treated as there are clear evidences that all persons with W. bancrofti or B. malayi microfilaremia have some degree of subclinical disease manifested as hematuria (blood in urine), proteinuria (presence of proteins in urine), and abnormalities on lymphoscintigraphy etc. Early treatment of asymptomatic filarial infection should be done in all persons to prevent lymphatic damage. Treatment of acute adenolymphangitis (ADL), should be done with supportive care (antipyretics and analgesics) and antibiotics (in secondary bacterial infection is present) and DEC 6 mg/kg per day for 12 days.

What general measures should be taken for filariasis?

General measures like good personal hygiene, prevention of secondary bacterial infections, and physiotherapy are all important, especially in persons with chronic lymphatic filariasis. If there is hydrocele, it can be drained repeatedly (especially in very old and debilitating people in whom surgery can not be done) or drained surgically. With chronic manifestations of lymphatic filariasis, drug treatment is ideally reserved for individuals with evidence of active infection.

Finally the standard treatment regimen is diethylcarbamazine (DEC) for 12 days and a total of 72 mg/kg body weight of the patient of filariasis, which is being used as standard treatment for many years. Other regimens can also give satisfactory results. The side effects of DEC are nausea, vomiting, fever, chills, arthralgias, headaches etc. The development and severity of these side effects are directly related to the number of microfilariae circulating in the bloodstream. Thus, these side effects of DEC may be due to acute hypersensitivity reaction to the antigens being released by dead and dying parasites or an inflammatory reaction induced by lipopolysaccharides.

How to control & prevent filariasis?

To prevent filariasis, the travelers should use insect repellent and mosquito nets to prevent mosquito bites (in endemic areas), but for local residents of endemic areas it is not possible to prevent mosquito bite. Use of mosquito nets impregnated in repellent liquid gives very good result.

In filaria endemic areas where it is a public health problem, community based programs can be used to prevent and control filaria. The mass annual distribution of antimicrofilarial chemotherapy of albendazole with DEC (for all areas except those where onchocerciasis is coendemic) or ivermectin can give very good result and reduce microfilaremia to a great extent. If the suppression of microfilaremia is sustained, then transmission can be interrupted (as microfilarias are responsible for transmission). These combinations have secondary effects on gastrointestinal helminths and reduce worm infestation also as added benefit.

An alternative approach to the control and prevent lymphatic filariasis, is the use of salt fortified with DEC. Mass use of DEC-fortified salt can dramatically reduce microfilarial density with no apparent adverse reactions. Persons who are already suffering from the chronic sequelae of lymphatic filariasis should be treated appropriately as they are important components of filariasis control and elimination programs.