The effects of high-dose ivermectin regimens on Onchocerca volvulus in onchocerciasis patients

Ivermectin, at the standard dose of 150 mu g/kg bodyweight, does not kill t he adult worms of Onchocerca volvulus and does not disrupt embryogenesis or spermatogenesis. Repeated standard doses, if maintained, arrest microfilar ial production but result in only a mild-to-modest macrofilaricidal effect. We investigated whether high doses would effectively kill the adult worms, and whether cessation of microfilarial production could be reproduced by a n equivalent, single, high dose. One hundred men participated in a double-b lind placebo-controlled trial and received increasing doses of ivermectin f rom 150 mu g/kg to 1600 mu g/kg bodyweight. Nodules were excised at day 180 and examined by histopathology. Total doses of ivermectin up to 1600 mu g/ kg were not significantly more effective than 150 mu g/kg. Moreover, they d id not reproduce the marked inhibitory effects of the repeat standard-dose regimens on embryogenesis, nor the modest effect on adult worm viability, a t comparable total doses. These effects may be functions of multiplicities of dosages rather than of the total dose. Our findings also suggest that re peated high-dose regimens are unlikely to be more effective than a similar number of 150 mu g/kg doses. This deficiency of ivermectin requires that th e search for macrofilaricides remains a top priority.