4.1 Article

Reduced genetic variation of an Onchocerca volvulus ABC transporter gene following treatment with ivermectin

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OXFORD UNIV PRESS
DOI: 10.1016/j.trstmh.2005.03.019

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Onchocerca volvulus; ivermectin; ABC transporters; P-glycoproteins; genetic polymorphism; drug resistance

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In some trichostrongyloid nematodes, the early stages of ivermectin (IVM) resistance have been characterized by a shift in allele frequency and reduced polymorphism at loci of P-glycoprotein genes, glutamate-gated chloride channel genes and gamma-aminobutyric acid receptor genes. Mass treatment with IVM is an integral component of the onchocerciasis control programmes. Genetic variation of an Onchocerca volvulus ABC transporter homologue (OvABC-3) from several populations in Africa was examined to determine whether an association exists between alleles of this gene and IVM treatment. Allelic variation in a non-treated population from Ghana showed this locus to be highly polymorphic. However, variability was reduced in IVM-treated populations. chi(2) analysis of polymorph frequencies showed significant differences between untreated and treated samples collected in Ghana in 1999. There was less variability in this gene in samples collected in 2002 compared with the 1999 samples. In some treated populations, there appeared to be selection on OvABC-3-C. The observed reduction in variability could be expected in a control programme in which prevalence and intensity of infections are markedly reduced after years of vector control and IVM distribution. The reduction in polymorphism may not in itself indicate that these O. volvulus are IVM resistant, although it could indicate that selection for resistance is occurring. (C) 2007 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

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