ArticlesRandomised community-based trial of annual single-dose diethylcarbamazine with or without ivermectin against Wuchereria bancrofti infection in human beings and mosquitoes
Introduction
Lymphatic filariasis has been identified by WHO as a public-health problem and targeted for elimination.1, 2 The disease is a major cause of morbidity, primarily lymphoedema of the legs and hydroceles, and impedes socioeconomic development in 73 endemic countries, in which 1·1 billion people are at risk and 120 million are infected.3 Filariasis-control programmes aimed at interrupting transmission of Wuchereria bancrofti have relied wholly or mainly on community-level drug administration. For nearly 50 years, diethylcarbamazine has been the drug of choice because it significantly decreases the intensity of microfilaraemia. However, many people remain microfilaraemic after taking full courses of the drug, and where culicine mosquitoes are vectors, these individuals may serve as reservoirs for continued transmission.4 Studies have shown that treatment with ivermectin leads to more substantial and sustained reductions in microfilaraemia than diethylcarbamazine.5, 6 Limited clinical trials on selected individuals suggest that combined ivermectin and diethylcarbamazine is more effective than ivermectin alone, possibly because diethylcarbamazine is active against the adult stage of W bancrofti7, 8, 9 or the combination has greater microfilaricidal activity than either drug alone. Community-wide treatment with combined ivermectin and diethylcarbamazine has, therefore, been identified as a possibly means for elimination of lymphatic filariasis.10
Analyses of the relation between W bancrofti and its mosquito vector suggest that reductions in vector density and intensity of microfilaraemia below certain thresholds could lead to breaks in transmission and, ultimately, eradicate anopheline-transmitted filariasis.11, 12 In areas where anopheline mosquitoes are the main vectors of W bancrofti, such as the Solomon Islands and Togo, transmission was completely interrupted through a reduction in vector density by the spraying of residual insecticides aimed at controlling malaria.13, 14 Since vector control alone is impractical or ineffective in many areas of the world endemic for filariasis, reduction of the microfilarial reservoir through community-wide chemotherapy has been proposed as a cost-effective alternative to limit or break transmission of W bancrofti.10 Chemotherapy without vector control or a natural decline in vector density has not yet been shown to lead to breaks in transmission of W bancrofti.11
We compared, in a randomised study, the impact of community-wide treatment with annual single dose of diethylcarbamazine or combined diethylcarbamazine and ivermectin on bancroftian filariasis in a highly endemic area of East Sepik Province, Papua New Guinea. We studied the effects of treatment on infection, disease, and transmission and the prospects of achieving WHO's goal of elimination.
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Study population
In 1994 we carried out parasitological and clinical surveys of people in 14 communities in the East Sepik Province, Papua New Guinea, located within 20 km of the Dreikikir government station (figure 1). The average annual rainfall in East Sepik Province is 1600 mm, and relative humidity varies between 80% and 100%. Rainfall is seasonal and most abundant between December and June (wet season). Lymphatic filariasis is highly endemic in these conditions, and anopheline mosquitoes are the main
Results
The first round of parasitological and physical examinations and treatment occurred between June and October, 1994. Randomisation by transmission zone ensured that communities receiving different treatments were comparable for rate of microfilaria and mean intensity of microfilaraemia before treatment. Parasitological variables were generally greater in the higher than the lower transmission zones before treatment (table). 1 year after drug administration, microfilarial rate and intensity were
Discussion
WHO has stated that elimination of lymphatic filariasis is achievable within 10 years.1, 2 In this trial, our main objective was to find out the efficacy of annual single-dose diethylcarbamazine alone compared with combined treatment with ivermectin in limiting the transmission of W bancrofti in a highly endemic area of Papua New Guinea. By monitoring entomological indices of transmission and the rate and intensity of microfilaraemia before and after treatment, we were also able to gain new
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