The macrofilaricidal efficacy of repeated doses of ivermectin for the treatment of river blindness

Walker, M and Pion, S D S and Fang, H and Gardon, J and Kamgno, J and Basáñez, M-G and Boussinesq, M (2017) The macrofilaricidal efficacy of repeated doses of ivermectin for the treatment of river blindness. CLINICAL INFECTIOUS DISEASES, 65 (12). pp. 2026-2034.

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Abstract

Background: Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females. However, rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques. Methods: Using a novel mathematical modeling approach, we analyzed, at an individual participant level, longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing 3-monthly with annual treatments administered for 3 years in Cameroon.

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