The detection and management of ivermectin resistance in human onchocerciasis. (360G-Wellcome-092677_Z_10_Z)

Global neglected tropical disease control has intensified the use of mass drug administration against major human helminthiases, raising concerns that anthelmintic resistance may develop. Although no resistance cases have been confirmed in human onchocerciasis, molecular genetic markers of drug-induced selection are being identified in ivermectin-treated Onchocerca volvulus populations, and suboptimal host responses to treatment have been characterized. Yet, evidence of drug resistance remains i nconclusive due to scarcity of longitudinal studies, difficulties in assessing ongoing transmission and treatment coverage, and lack of studies linking host response to treatment phenotype with parasite phenotype and genotype. Genetic analysis of (already collected) parasites from Ghana and Cameroon (looking at a number of loci under selection) will be conducted and the resulting data will be used to fit mathematical models to individual host responses to treatment to link suboptimal responses w ith molecular markers for drug resistance. Mathematical models for O. volvulus, merging population dynamics and population genetics, will be refined to quantify the impact, upon ongoing control programmes, of ivermectin resistance were it confirmed, and formulate strategies to mitigate such an impact and delay its spread. Results are anticipated to be of major significance for the protection of investments already made in onchocerciasis control.