Journal
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 158, Issue 2, Pages 101-111Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbiopara.2007.11.017
Keywords
ABC transporters; ivermectin; Onchocerca volvulus; drug selection; DNA marker
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Ivermectin (IVM) is the only safe drug for mass-treatment of onchocerciasis. IVM resistance has been reported in gastrointestinal nematode parasites of animals. A reduction in response to IVM in Onchocerca volvulus could have significant consequences for the onchocerciasis control programs. We have found evidence that, in O. volvulus, repeated IVM treatment selects for specific alleles, of P-glycoprotein-like protein (PLP), a half-sized ABC transporter. In this study, O. volvulus samples were derived from a clinical trial in Cameroon, in which patients were sampled before, and following 3 years (1994-1997) of IVM treatments. There were four treatment groups: 150 mu g/kg (1 x p.a. or 4 x p.a.) and 800 mu g/kg (1 x p.a. or 4 x p.a.). DNA of O. volvulus macrofilariae was genotyped over a 476 bp region of the PLP gene and at two control genes. Of the six polymorphic positions found in the PLP amplicon, three of them showed significant selection after 4 x p.a. treatment with IVM (total of 13 IVM treatments) in female worms, and one of the same single nucleotide polymorphisms (SNPs) showed significant selection in the male worms. One of the selected SNPs in the female worms caused an amino acid coding change in the putative protein sequence. We found a clear selection of some genotypes, a high SNPs association and a loss of polymorphism following 4 x p. a. treatment with IVM. These PLP SNPs and genotypes could be useful markers to follow selection for IVM resistance in the field. (c) 2007 Elsevier B.V. All rights reserved.
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