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

Published online by Cambridge University Press:  09 November 2005

B. F. ARDELLI ,
S. B. GUERRIERO  and
R. K. PRICHARD
B. F. ARDELLI
Affiliation:
Institute of Parasitology, Macdonald Campus, McGill University, 21 111 Lakeshore Road, Ste. Anne de Bellevue, Quebec, Canada H9X 3V9
S. B. GUERRIERO
Affiliation:
Institute of Parasitology, Macdonald Campus, McGill University, 21 111 Lakeshore Road, Ste. Anne de Bellevue, Quebec, Canada H9X 3V9
R. K. PRICHARD
Affiliation:
Institute of Parasitology, Macdonald Campus, McGill University, 21 111 Lakeshore Road, Ste. Anne de Bellevue, Quebec, Canada H9X 3V9
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Abstract

Widespread use of ivermectin (IVM) as part of the Onchocerciasis Control Program (OCP) in West Africa could influence the evolution of the human filarial parasite Onchocerca volvulus. Use of IVM, in some areas for 15 years, 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 is 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 LD 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 genetic variation. The use of IVM for onchocerciasis control has imposed strong selection on O. volvulus populations, reducing genetic variation and disrupting LD.

Keywords

ivermectinOnchocerca volvulusP-glycoproteingenetic selection
Type
Research Article
Information
Parasitology , Volume 132 , Issue 3 , March 2006 , pp. 375 - 386
Copyright
© 2005 Cambridge University Press

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