CLINICAL AND THERAPEUTIC STUDIES IN HUMAN FILARIASIS

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Ivermectin has been shown in trials in South India to be effective in clearing microfilaremia in patients with bancroftian filariasis. A placebo-controlled trial of ivermectin and the currently used drug, diethylcarbamazine (DEC), has shown equivalent efficacy for ivermectin and DEC for 3 months, but by 6 months the (approximately) 18-20% microfilarial recurrence rate in the ivermectin-treated patients was significantly greater than the (approximately) 6% recurrence rate in the DEC group. Side effects were essentially identical for both groups. Thus, though ivermectin appeared somewhat less effective than DEC at 6 months, its single-oral-dose mode of administration and toxicity no greater than that of DEC means that this drug should engender greater patient compliance and, therefore, have the potential to be much more effective in mass-treatment filariasis control programs than DEC. Current trials in South India and Brazil (coordinated with trials elsewhere in the world) indicate that very low doses of ivermectin (10 mcg/kg) clear microfilariae with even fewer side reactions and, when followed by a second higher dose, may lead to extremely prolonged microfilarial clearance. Loiasis acquired by expatriate visitors to endemic areas has been characterized in earlier studies at NIH as showing marked clinical and immunologic hyperresponsiveness to the filarial parasite. The hypothesis that this hyperresponsive syndrome contrasted with a hyporesponsive ('tolerized') state, both clinical and immunologic that appeared in those infected individuals native to the endemic regions was proven by clinical and laboratory studies in Benin, West Africa.