Filariasis is an infectious tropical disease caused by three thread-like parasitic filarial worms, Wuchereria bancrofti, Brugia malayi, and Brugia timori, all transmitted by mosquitoes. Lymphatic Filariasis, known as Elephantiasis puts at risk more than a billion people in more than 80 countries. Over 120 million are already affected by and over 40 million of them are seriously incapacitated and disfigured by the disease. One-third of the infected people live in India, one third in Africa and the rest are in South Asia, the Pacific and the Americas.
Pathogenic filarial parasites affect the lives of millions of people, especially those living in tropical countries. The filarial parasites that pose the most serious public health threats are Wuchereria bancrofti, Brugia malayi, Brugia timori, Onchocerca volvulus, and Loa loa. All of these cause cutaneous manifestations. One filarial nematode, Mansonella streptocerca, also causes cutaneous changes but is not a significant public health threat.
Human Filarial Parasites and Their Vectors
Blackflies: Simulium species
Mosquitoes: Anopheles, Aedes, Culex, and Mansonia species
B. malayi and B. timori
Mosquitoes: Anopheles, Aedes, Culex, and Mansonia species
Red flies: Chrysops species
Midges: Culicoides species
Mosquitoes: Culex species
The thread-like, parasitic filarial worms Wuchereria bancrofti and Brugia malayi that cause lymphatic filariasis live almost exclusively in humans. These worms are lodged in the lymphatic system, the network of nodes and vessels that maintain the delicate fluid balance between the tissues and blood and are an essential component for the body’s immune system. They live for 4-6 years, producing millions of immature microfilariae (minute larvae) that circulate in the blood.
The disease is transmitted by mosquitoes that bite infected humans and pick up the microfilariae that develop, inside the mosquito, into the infective stage in a process that usually takes 7-21 days. The larvae then migrate to the mosquitoes’ mouth-parts, ready to enter the punctured skin following the mosquito bite and completing the cycle.
Patients suffer from hydrocoel (fluid-filled balloon-like enlargement of scrotal sacs) and elephantiasis of the legs and penis. Elephantiasis of the entire leg, the entire arm, the vulva or the breast (swelling up to several times normal size) can take place.
Elephantiasis affects mainly the lower extremities and is caused when the parasites are lodged in the lymphatic systemand block lymph flow. W. bancrofti can affect the legs, arms, vulva, breasts, while Brugia timori rarely affects the genitals. Infection by Onchocerca volvulus and the migration of its microfilariae through the cornea of eye is a major cause of blindness.
Until very recently, diagnosing lymphatic filariasis had been extremely difficult, since parasites had to be detected microscopically in the blood, and in most parts of the world, the parasites have a “nocturnal periodicity” that restricts their appearance in the blood to only the hours around midnight. The diagnosis is made by identifying microfilariae on a stained blood film. Blood must be drawn at night, since the microfilariae circulate at night when their vector, the mosquito, is most likely to bite.
The new development of a very sensitive, very specific simple “card test” to detect circulating parasite antigens without the need for laboratory facilities and using only finger-prick blood droplets taken anytime of the day has completely transformed the approach to diagnosis.
Vector control, use of mosquito nets, and improved living conditions are still vital for the control of these infections.
The drugs of choice for killing adult worms are Albendazole and Ivermectin.
Ivermectin (dihydroavermectin) is the drug of choice for the treatment of onchocerciasis. It is a macrocyclic lactone derived from the actinomycete, Streptomyces avermitilis found in soil. It functions as a single dose and is effective microfilaricide for O.volvulus.
Unlike diethylcarbamazine (DEC), ivermectin does not produce reaction in onchocerciasis because it acts by paralyzing the microfilariae in the skin tissue spaces and lymphatics. They are then swept away into the local lymph nodes, which may swell up and only cause some local limb edema. On the other hand, DEC “unmasks” the microfilariae in the tissue spaces where they are attacked by the various protective cells which cause reaction in the skin.
The addition of oral doxycycline (100 mg/d) given for 6 weeks from the start of ivermectin to kill off Wolbachia organisms enhanced the effects of ivermectin.
Diethylcarbamazine or DEC (Hetrazan) is a microfilaricide with no effect on the adult worm. It produces Mazzotti reactions that become severe in heavily infected persons. A low dose of dexamethasone (3 mg/d) after onset of Mazzotti reaction controls the progression of reaction without interfering with the macrofilaricidal efficacy of DEC.
Suramin is a microfilaricide given intravenously, starting with a test dose of 100 mg of fresh 10% solution over 2 minutes. If no hypersensitivity develops, weekly dosages of 0.2 g, 0.4 g, 0.6 g, 0.8 g, and 1 g are given to adult patients. Rarely, patients experience eye lesions, dermatitis, kidney damage, a Mazzotti-like reaction and/or death. Thus, the use of suramin requires great caution and hence is generally not recommended.
Amocarzine is a new oral macrofilaricidal compound that has promising effects on onchocerciasis in Latin America.
Doramectin (Dectomax, Pfizer) is a new drug related to ivermectin. Its efficacy and safety in onchocerciasis are untested.
A useful adjunct to chemotherapy popular in South America is removal of the palpable nodules. In Africa, nodulectomy has never been practiced widely because the nodules tend to be deeper and located near delicate joint spaces. Alternatively, chloroquine can be injected into young nodules that kill the worms.
Wolbachia organisms appear to play a critical role in the biology and metabolism of filarial worms. The use of tetracycline to kill Wolbachia appears to be lethal to the adult O. ochengi and recent evidences suggest that it is also effective against O.volvulus and perhaps other filarial worms.