The chemotherapy of onchocerciasis VIII

Abstract

In two separate studies the antifilarial activity of levamisole, mebendazole and their combination, and of flubendazole combined with levamisole, were investigated in a total of 96 patients. Ten patients received levamisole 2·;5 mg kg⁻¹ on two occasions during the first week and then weekly for three weeks. Twelve patients received mebendazole 30 mg kg⁻¹ daily in divided doses for three weeks. Thirteen patients received a combination of levamisole and mebendazole. In 12 patients mebendazole was given after two ‘priming’ doses of levamisole. A control group of 11 patients received vitamin preparations. In the second study 20 patients received flubendazole 30 mg kg⁻¹ daily in divided doses for three weeks combined with levamisole 2·5 mg kg⁻¹ given on two occasions in the first week and then weekly. A control group of 18 patients received vitamin preparations. The microfilaricidal effect of the drug regimes was determined by weekly skin snips during and one week after completion of therapy. Levamisole was ineffective against the microfilariae and adult worms. Mebendazole caused microfilarial migration but was only feebly microfilaricidal. However, it had a marked embryotoxic effect on the adult females although this lasted less than three months. The combinations of levamisole and mebendazole were both microfilaricidal and embryotoxic. This embryotoxicity was more prolonged than that of mebendazole alone but lasted less than six months. The synergism of levamisole and mebendazole on the microfilariae and adults of Onchocerca volvulus was evident even in patients who received only two ‘priming’ doses of levamisole. Neither mebendazole alone nor its combinations with levamisole was macrofilaricidal. Given the poor and variable absorption of mebendazole and the mild and infrequent clinical reactions to microfilarial destruction which were observed, better absorbed formulations of mebendazole in combination with levamisole may cause permanent sterilization of the adult females and thus hold promise for the treatment of onchocerciasis. The macrofilaricidal or embryotoxic effects were studied indirectly by observing mf densities in the skin over a six to ten month period and directly by nodule examination. Flubendazole in combination with levamisole had no significant effect on O. volvulus.