Ivermectin imposes selection pressure on P-glycoprotein from Onchocerca volvulus:: linkage disequilibrium and genotype diversity

Widespread use of ivermectin (IVM) its part of the Onchocerciasis Control Program (OCP) in West Africa could influence the evolution of the human filaria I parasite Onchocerca volvulus. Use of IVM, in some areas for 15,,cars, may have restricted genetic diversity of O. volvulus, resembling effects attributed to a Population bottleneck. Large population-based chemotherapy programmes, Such as the OCP, may impose strong selection pressure on parasites and an examination of possible genetic selection by IVM in O. volvulus warranted. IVM is a substrate for P-glycoprotein; a homologue from O. volvulus (OvPGP) has been linked with IVM sensitivity. Linkage disequilibrium (LD) patterns of 28 genetic markers spanning the OvPGP locus were examined in 4 O. volvulus populations from the Volta Region of Ghana, West Africa. Reduced gene diversity, increased heterozygosity and an increase in the number of markers not in Hardy-Weinberg equilibrium were associated with increasing IVM treatment. The number of regions in LID decreased with treatment and with time. However, between 1999 and 2002, seven regions of OvPGP were always in complete LD, while surrounding areas showed a reduction in genectic variation. The use of IVM for onchocerciasis control has imposed strong selection oil O. volvulus populations, reducing genetic variation and disrupting LD.