Résumé
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
μg/kg (1
×
p.a. or 4
×
p.a.) and 800
μg/kg (1
×
p.a. or 4
×
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
×
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
×
p.a. treatment with IVM. These
PLP SNPs and genotypes could be useful markers to follow selection for IVM resistance in the field.