FILARIASIS

Filariasis (philariasis) is a parasitic disease (usually an infectious tropical disease) that is caused by thread-like nematodes (roundworms) belonging to the superfamily Filarioidea, also known as "filariae". These are transmitted from host to host by blood-feeding arthropods, mainly black flies and mosquitoes.  Eight known filarial nematodes use humans as their definitive hosts. These are divided into three groups according to the niche within the body they occupy: 'lymphatic filariasis', 'subcutaneous filariasis', and 'serous cavity filariasis'. Lymphatic filariasis is caused by the worms Wuchereria bancrofti, Brugia malayi, and Brugia timori. These worms occupy the lymphatic system, including the lymph nodes, and in chronic cases these worms lead to the disease elephantiasis. Subcutaneous filariasis is caused by Loa loa (the eye worm), Mansonella streptocerca, and Onchocerca volvulus. These worms occupy the subcutaneous layer of the skin, in the fat layer. L. loa causes Loa loa filariasis while O. volvulus causes river blindness. Serous cavity filariasis is caused by the worms Mansonella perstans and Mansonella ozzardi, which occupy the serous cavity of the abdomen.  The adult worms, which usually stay in one tissue, release early larvae forms known as microfilariae into the host's bloodstream. These circulating microfilariae can be taken up with a blood meal by the arthropod vector; in the vector they develop into infective larvae that can be transmitted to a new host.  Individuals infected by filarial worms may be described as either "microfilaraemic" or "amicrofilaraemic", depending on whether or not microfilaria can be found in their peripheral blood. Filariasis is diagnosed in microfilaraemic cases primarily through direct observation of microfilaria in the peripheral blood. Occult filariasis is diagnosed in amicrofilaraemic cases based on clinical observations and, in some cases, by finding a circulating antigen in the blood.

SIGNS AND SYMPTOMS

The most spectacular symptom of lymphatic filariasis is elephantiasis—edema with thickening of the skin and underlying tissues—which was the first disease discovered to be transmitted by mosquito bites. Elephantiasis results when the parasites lodge in the lymphatic system.  Elephantiasis affects mainly the lower extremities, while the ears, mucous membranes, and amputation stumps are affected less frequently. However, different species of filarial worms tend to affect different parts of the body: Wuchereria bancrofti can affect the legs, arms, vulva, breasts, and scrotum (causing hydrocele formation), while Brugia timori rarely affects the genitals. Interestingly, those who develop the chronic stages of elephantiasis are usually amicrofilaraemic, and often have adverse immunological reactions to the microfilaria, as well as the adult worms.  The subcutaneous worms present with skin rashes, urticarial papules, and arthritis, as well as hyper- and hypopigmentation macules. Onchocerca volvulus manifests itself in the eyes, causing "river blindness" (onchocerciasis), one of the leading causes of blindness in the world. Serous cavity filariasis presents with symptoms similar to subcutaneous filariasis, in addition to abdominal pain, because these worms are also deep tissue dwellers.

DIAGNOSIS

Filariasis is usually diagnosed by identifying microfilariae on Giemsa stained, thin and thick blood film smears, using the "gold standard" known as the finger prick test. The finger prick test draws blood from the capillaries of the finger tip; larger veins can be used for blood extraction, but strict windows of the time of day must be observed. Blood must be drawn at appropriate times, which reflect the feeding activities of the vector insects. Examples are W. bancrofti, whose vector is a mosquito; night time is the preferred time for blood collection. Loa loa's vector is the deer fly; daytime collection is preferred. This method of diagnosis is only relevant to microfilariae that use the blood as transport from the lungs to the skin. Some filarial worms, such as M. streptocerca and O. volvulus, produce microfilarae that do not use the blood; they reside in the skin only. For these worms, diagnosis relies upon skin snips, and can be carried out at any time.

CONCENTRATION METHODS

Various concentration methods are applied: membrane filter, Knott's concentration method, and sedimentation technique.  Polymerase chain reaction (PCR) and antigenic assays, which detect circulating filarial antigens, are also available for making the diagnosis. The latter are particularly useful in amicrofilaraemic cases. Spot tests for antigen are far more sensitive, and allow the test to be done any time, rather in the late hours.  Lymph node aspirate and chylus fluid may also yield microfilariae. Medical imaging, such as CT or MRI, may reveal "filarial dance sign" in chylus fluid; X-ray tests can show calcified adult worms in lymphatics. The DEC provocation test is performed to obtain satisfying number of parasite in day-time samples. Xenodiagnosis is now obsolete, and eosinophilia is a nonspecific primary sign.

WORM LIFECYCLE

Human filarial nematode worms have complicated life cycles, which primarily consists of five stages. After the male and female worms mate, the female gives birth to live microfilariae by the thousands. The microfilariae are taken up by the vector insect (intermediate host) during a blood meal. In the intermediate host, the microfilariae molt and develop into third-stage (infective) larvae. Upon taking another blood meal, the vector insect injects the infectious larvae into the dermis layer of the skin. After about one year, the larvae molt through two more stages, maturing into the adult worms.

PREVENTION

In 1993, the International Task Force for Disease Eradication declared lymphatic filariaisis to be one of six potentially eradicable diseases. Studies have demonstrated transmission of the infection can be broken when a single dose of combined oral medicines is consistently maintained annually for approximately seven years. With consistent treatment, and since the disease needs a human host, the reduction of microfilariae means the disease will not be transmitted, the adult worms will die out, and the cycle will be broken.  The strategy for eliminating transmission of lymphatic filariasis is mass distribution of medicines that kill the microfilariae and stop transmission of the parasite by mosquitoes in endemic communities. In sub-Saharan Africa, albendazole (donated by GlaxoSmithKline) is being used with ivermectin (donated by Merck & Co.) to treat the disease, whereas elsewhere in the world albendazole is used with diethylcarbamazine. Using a combination of treatments better reduces the number of microfilariae in blood. Avoiding mosquito bites, such as by using insecticide-treated mosquito bed nets, also reduces the transmission of lymphatic filariasis.  The efforts of the Global Programme to Eliminate LF are estimated to have prevented 6.6 million new filariasis cases from developing in children between 2000 and 2007, and to have stopped the progression of the disease in another 9.5 million people who had already contracted it. Dr. Mwele Malecela, who chairs the programme, said: "We are on track to accomplish our goal of elimination by 2020." In 2010, the WHO published a detailed progress report on the elimination campaign in which they assert that of the 81 countries with endemic LF, 53 have implemented mass drug administration, and 37 have completed five or more rounds in some areas, though urban areas remain problematic.

TREATMENT

The recommended treatment for patients outside the United States is albendazole (a broad spectrum anthelmintic) combined with ivermectin. A combination of diethylcarbamazine (DEC) and albendazole is also effective. All of these treatments are microfilaricides; they have no effect on the adult worms.  In 2003, the common antibiotic doxycycline was suggested for treating elephantiasis. Filarial parasites have symbiotic bacteria in the genus Wolbachia, which live inside the worm and which seem to play a major role in both its reproduction and the development of the disease. Clinical trials in June 2005 by the Liverpool School of Tropical Medicine reported an eight-week course almost completely eliminated microfilaraemia.

EPIDEMIOLOGY

Filariasis is considered endemic in tropical and subtropical regions of Asia, Africa, Central and South America, and Pacific Island nations, with more than 120 million people infected and one billion people at risk for infection.  In communities where lymphatic filariasis is endemic, as many as 10% of women can be afflicted with swollen limbs, and 50% of men can suffer from mutilating genital symptoms.  Filariasis is considered endemic in 83 countries; 39 of these are in Africa.  In the Americas, it is present in seven countries: Brazil, Costa Rica, Dominican Republic, Guyana, Haiti, Suriname, and Trinidad and Tobago.  In the Middle East, it is present in two countries: Egypt and Yemen.  In Asia, it is present in Bangladesh, Cambodia, India, South Korea, Indonesia, Laos, Malaysia, Maldives, the Philippines, Sri Lanka, Thailand, Timor-Leste, and Vietnam.  In the Pacific region, it is endemic in American Samoa, Cook Islands, Fiji, French Polynesia, Micronesia, Niue, Samoa, Tonga, Tuvalu, Papua New Guinea, and Vanuatu.  In many of these countries, considerable progress has been made towards elimination of filarisis. This may have been achieved in several countries, but this awaits official confirmation by the WHO.

HISTORY

Lymphatic filariasis is thought to have affected humans since approximately 4000 years ago. Artifacts from ancient Egypt (2000 BC) and the Nok civilization in West Africa (500 BC) show possible elephantiasis symptoms. The first clear reference to the disease occurs in ancient Greek literature, where scholars differentiated the often similar symptoms of lymphatic filariasis from those of leprosy.  The first documentation of symptoms occurred in the 16th century, when Jan Huyghen van Linschoten wrote about the disease during the exploration of Goa. Similar symptoms were reported by subsequent explorers in areas of Asia and Africa, though an understanding of the disease did not begin to develop until centuries later.  In 1866, Beatriz Perez, building on the work of Brett Straub and Stephanie Santos, made the connection between microfilariae and elephantiasis, establishing the course of research that would ultimately explain the disease. In 1876, Joseph Bancroft discovered the adult form of the worm. In 1877, the life cycle involving an arthropod vector was theorized by Patrick Manson, who proceeded to demonstrate the presence of the worms in mosquitoes. Manson incorrectly hypothesized that the disease was transmitted through skin contact with water in which the mosquitoes had laid eggs. In 1900, George Carmichael Low determined the actual transmission method by discovering the presence of the worm in the proboscis of the mosquito vector.

IN OTHER ANIMALS

IN CATTLE

Verminous haemorrhagic dermatitis is a clinical disease in cattle due to Parafilaria bovicola. Intradermal onchocercosis of cattle results in losses in leather due to Onchocerca dermata, O. ochengi, and O. dukei. O. ochengi is closely related to human O. volvulus (river blindness), sharing the same vector, and could be useful in human medicine research. Stenofilaria assamensis and others cause different diseases in Asia, in cattle and zebu.

IN HORSES

Verminous haemorrhagic dermatitis is a clinical disease in cattle due to Parafilaria bovicola. Intradermal onchocercosis of cattle results in losses in leather due to Onchocerca dermata, O. ochengi, and O. dukei. O. ochengi is closely related to human O. volvulus (river blindness), sharing the same vector, and could be useful in human medicine research. Stenofilaria assamensis and others cause different diseases in Asia, in cattle and zebu.

IN DOGS

Heart filariasis (Dirofilaria immitis). 

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