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Filariasis

12 June 2012, by DEVELOUX M.

1 - LYMPHATIC FILARIASIS

Lymphatic filariasis is a helminthiasis transmitted by mosquitoes belonging to several genera. These are tropical diseases whose chronic manifestations result from obstruction of the lymph ducts by adult filariae [1].

An estimated 120 million people are infected worldwide. Wuchereria bancrofti and its pacifica variety is the most common species and is found throughout the intertropical zone. Brugia malayi, is the second most common species and is only found in certain regions of South Asia. Brugia timori is restricted to certain Indonesian islands. It is a rarely notified imported parasitosis in Metropolitan France. It is no longer reported in France’s overseas departments or territories with the exception of Mayotte and certain islands of French Polynesia where it is still hypoendemic.

The adult filariae measuring 4 to 8 cm long live in the lymphatic ducts. Microfilariae, or the embryos emitted by the female worms, pass into the bloodstream with a periodicity that varies from species to species and strain to strain. W. bancrofti is mainly nocturnal. The vectors are female mosquitoes of the Culex, Aedes, Anopheles and Mansonia genera. The microfilariae are absorbed by a vector during a blood-meal taken from an infected human. Inside the mosquito vector or intermediate host, the microfilariae mature into motile larvae which are then egested into a human host’s blood when the mosquito has its next blood-meal.

The clinical manifestations become apparent after an incubation period carrying from a few months to several years. In man, W. bancrofti frequently causes genital symptoms including lymphangitis of the scrotum, orchitis and vaginal hydrocele. Limb lymphangitis progresses centrifugally. Adenitis may be seen alone or with lymphangitis. After one or more years of repeated episodes, the lymphatic ducts become blocked, giving rise to the clinical signs of the disease. Sometimes spectacular, these signs have become increasingly rare as patients now receive prompt treatment. The disorder affects the genitals and lymphatic system, causing hydroceles, orchi-epididyimitis, adenopathies, adenolymphoceles and superficial or deep lymph varices, of which elephantiasis is the most common manifestation. Filarian elephantiasis particularly affects the leg and foot. The skin is lumpy, irregular and vegetant. It is to be distinguished from streptococcal elephantiasis, diffuse lymphangiomas, Kaposi’s disease or chromoblastomycosis. Filarian elephantiasis may also spread to the arm, scrotum, vulva and breast.

A non-negligible proportion of infected subjects remain asymptomatic.

The diagnosis is confirmed by the detection of microfilariae in the blood. The time the sample is obtained must take into account the periodicity of the species. Several methods with varying sensitivity can be used to detect microfilariae. These include smears, thick smears, the leukoconcentration test and membrane filtration. The blood eosinophilia is only present at the early phase of the infection. The serology is non specific and the test is often negative by the time the disease becomes clinically manifest.

1.1 - TREATMENT OPTIONS

The specific treatments are diethylcarbamazine and ivermectin.

Diethylcarbamazine (Notézine®) is the older of the two and has an essentially microfilaricide effect when administered to treat lymphatic filariasis. It acts by sensitising the microfilariae to the phagocytic activity of the reticular histiocyte system and to the destructive potential of platelets. Diethylcarbamazine has common but limited side effects, including headaches, asthenia, arthralgia, anorexia, nausea and vomiting. Patients must be warned against the risk of somnolence after taking the product. Some reactions related to microfilariae lysis may also be observed. These are particularly marked when serum microfilaraemia is high, and are more frequent with B. malayi. These reactions may present as an exacerbation of the local lymphatic signs or general symptoms arising a few hours after the first intake, for instance, fever, headaches, diffuse pain, pruritus and urticaria. They regress within 48 hours through a combination of symptomatic treatment and rest. Although no teratogenic effects have been described in animals, it is preferable not to use diethylcarbamazine during pregnancy. Notézine® is available in France as 100 mg tablets. It can be obtained from central hospital pharmacies or, for local pharmacies, directly from the pharmaceutical company Aventis.

Ivermectin (Stromectol®) is a macrolide antibiotic whose mechanism of action in lymphatic filariasis is poorly understood. Its effects are believed to be essentially microfilaricidic, resulting in the eradication of the microfilariae from the blood more rapidly than with diethylcarbamazine; however, it is known to be less effective than diethylcarbamazine in the mid-term, making several courses of treatment necessary. Hypersensitivity reactions are also observed with ivermectin. These vary in intensity, depending on the microfilaraemia. Ivermectin is contraindicated in children aged less than 5 and in pregnant and breastfeeding women. Stromectol® is available as 6 mg tablets. In France, this medication is licensed for the treatment of W. bancrofti microfilaraemia.

Albendazole is proposed for the treatment of some cases of lymphatic filariasis in combination with DEC or ivermectin, whose activity it enhances.

The discovery of Wolbachia genus bacteria in the pathophysiology of filariasis, Loa loa  excepted, has been fundamental. These symbiotic bacteria are always detected when the nematodes are present. They are fundamental to the survival of the nematode and play a role in the inflammatory phenomena observed with these infections. Wolbachia are sensitive to several antibiotics, including certain tetracyclines such as doxycycline. Doxycycline therefore constitutes a new, single-agent treatment option for lymphatic filariasis as it also has macrofilaricide activity. It can also be combined with other standard filariasis treatments.

1.2 - TREATMENT STRATEGY

Antiparasite treatment is first and foremost indicated for asymptomatic patients with microfilaraemia and patients with initial-stage clinically manifest disease. Whatever the antifilarian agent used, treatment must be given at a distance from an acute infection.

The recommended treatment regimen with diethylcarbamazine is one 6 mg/kg dose every three months. Courses of 10 to 21 days of diethylcarbamazine at a dose gradually incremented to reach 6 mg/kg a day are indicated for patients with tropical pulmonary eosinophilia or who also present with loa loa filariasis or hypersensitivity to diethylcarbamazine.

Ivermectin may be used at a dose of 200 mg/kg for six months [1]. The number of courses given depends on the clinical and biological course of the disease.

Doxycycline cures the disease permanently. It is prescribed at a dose of 200 mg/day for 6 weeks followed by a course of ivermectin, repeated 3 to 6 months later.

Treatment for an acute manifestation is symptomatic, combining rest, wet bandages, pain relief and antibiotics, etc.

In patients with chronic-stage disease, antifilarian treatment may be of use if the lesions are relatively recent since regression is still achievable. Some simple measures will help prevent the onset of acute infectious flares which aggravate lymphoedema or elephantiasis: the interdigital spaces must be kept scrupulously clean and cracked or broken skin must be treated with local antiseptics, antibiotics and/or antifungal agents. Acute infection must always be treated with antibiotics. Physical treatments (drainage) and binding can be used to help reduce swelling. Surgery is mainly indicated for elephantiasis of the genitals.

On an individual level, prevention consists in avoiding mosquito bites. Mass treatment campaigns in endemic zones are the best option for rapidly reducing the incidence of lymphatic filariasis. The worldwide lymphatic filariasis reduction program was launched in 2000 and covers 51 countries. Treatment consists of an annual 200-400 µg/kg dose of ivermectin combined with 400 mg albendazole. In loa loa free areas, DEC can be given alone or at a dose of 6 mg/kg in combination with 400 mg albendazole. The courses of treatment must be given for at least 5 years. Annual courses of ivermectin (400 mg/kg) or a combination of ivermectin (400 mg/kg)-diethylcarbamazine (6 mg/kg) may be used [1].

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