Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus:: a randomised controlled trial

Background At present, control of onchocerciasis depends almost entirely on yearly treatments with 150 mug/kg ivermectin. We aimed to compare the effect of higher doses, more frequent doses, or both with the standard regimen on adult Onchocerca volvulus. Methods We randomly allocated 657 patients who had onchocerciasis to 150 mug/kg ivermectin yearly (reference group), 150 mug/kg every 3 months, 400 then 800 mug/kg yearly, or 400 then 800 mug/kg every 3 months. We took skin snip samples from every patient before, and 3 years and 4 years after the first dose, and, at the same time excised one subcutaneous 0 volvulus nodule, which was examined histologically. The primary outcome was the vital status of the female worms. Analysis was done per protocol. Findings We obtained nodules from 511 patients. After 3 years of treatment, more female worms had died in the groups treated every 3 months than in the reference group (odds ratio=1.84 [95% CI 1.23-2.75], p=0.003 for 150 mug/kg; and 2.17 [1.42-3.31], p<0.001 for high doses). Female worms were also less fertile in these groups than in the reference group (0.24 [0.14-0.43], p<0.0001; and 0.14 [0.06-0.29], p<0.0001, respectively). No difference was recorded between groups treated yearly (p=0.83 for the proportion of dead females). Unexpected side-effects consisted of mild, temporary, subjective visual changes in patients on high-dose regimens. Interpretation Treatment with 3-monthly ivermectin could greatly reduce the number of female worms and acute itching and skin lesions; lower transmission of 0 volvulus; and change the duration of control programmes.