Distribution of kdr-west and kdr-east resistance alleles in Anopheles gambiae s.l. across contrasting transmission settings in central and southern Senegal
TL;DR
The limited association between kdr-east and resistance phenotypes suggests the involvement of additional resistance mechanisms, and the need for resistance-informed vector control strategies and support the integration of complementary interventions in areas with high pyrethroid resistance.
Abstract
The effectiveness of malaria vector control in sub-Saharan Africa is increasingly threatened by insecticide resistance in Anopheles gambiae sensu lato (s.l.). Knockdown resistance ( kdr ) mutations L1014F ( kdr-west ) and L1014S ( kdr-east ) are key target-site mechanisms associated with resistance to pyrethroids, the primary insecticide class currently approved for long-lasting insecticidal nets. This study assessed insecticide susceptibility and compared the distribution and phenotypic associations of kdr-west and kdr-east mutations in An. gambiae s.l. populations from two health districts in Senegal. Larvae were collected from four sites in Nioro and Velingara health districts and reared to adulthood. Adult females (3–5 days old) were tested against permethrin, deltamethrin, alphacypermethrin, bendiocarb, and pirimiphos-methyl using WHO susceptibility assays. Molecular identification of sibling species and detection of kdr mutations were performed by PCR. Allelic frequencies were compared between sites and species, and associations between kdr alleles and pyrethroid resistance phenotypes were assessed using odds ratios. Populations of An. gambiae s.l. from both districts exhibited high resistance to permethrin (9.18%; 13.08%), deltamethrin (46.08%; 48.08%) and alphacypermethrin (75%; 56%) in Nioro and Velingara, respectively. While remaining fully susceptible to bendiocarb (99.06%; 100%) and pirimiphos-methyl (100%; 100%) in Nioro and Velingara, respectively. Anopheles arabiensis was the predominant species in both districts, with higher proportions of An. gambiae sensu stricto (s.s.) and An. coluzzii in Velingara. A total of 85 and 90 An. gambiae s.l. specimens were genotyped to determine kdr-west and kdr-east alleles frequencies, respectively in Nioro and Velingara. Both kdr-west and kdr-east alleles were detected, with marked spatial and species-specific variation. The kdr-west allele was significantly associated with pyrethroid resistance in both Nioro (OR = 5.68, p < 0.01) and Velingara (OR = 2.81, p < 0.01), indicating that mosquitoes carrying kdr-west allele are more likely to survive exposure to pyrethroids than those that do not carry it. Whereas no significant association was observed for the kdr-east allele. Pyrethroid resistance is widespread in An. gambiae s.l. populations from central and southern Senegal and is significantly associated with the kdr-west mutation. The limited association between kdr-east and resistance phenotypes suggests the involvement of additional resistance mechanisms. These findings highlight the need for resistance-informed vector control strategies and support the integration of complementary interventions in areas with high pyrethroid resistance.