Exploring Knockdown Resistance (kdr) Mutation in Anopheles gambiae and Anopheles coluzzii Malaria Vectors in the Mountainous Plains Across the Cameroonian Great-West Domain

Abstract

Malaria control programmes across Africa and beyond are threatened by increasing insecticide resistance in the major anopheline vectors. In the malaria vectors Anopheles gambiae sensu lato, two point-mutations (L1014F and L1014S) in the voltage-dependent sodium channel gene that confer target-site knockdown resistance (kdr) to DDT and pyrethroid insecticides, have been described in several studies across the northern sudano-sahelian and the southern forested ecological zones of Cameroon. Contrarily, there is an unclear kdr status in anophelines of mountainous agro-ecosystems across the Cameroon Great-west domain. In order to determine the evolutionary profile of kdr alleles in An. gambiae and An. coluzzii sibling species both found in the Cameroon Great West domain, genotyping of the kdr locus on a total of 1172 individual specimen across five mountainous massifs, and sequencing on a minimum-size of 10 individuals per localities of a 510 base pairs fragment of the downstream exon-20, were performed. Knockdown resistance 1014F allele was found to be widespread with An. gambiae having high frequencies compared to An. coluzzii. Meanwhile 1014S-kdr allele was confined in An. gambiae populations. The results suggest that kdr alleles may have arisen through introgression. Estimates of genetic variability provided evidence of selection acting on these alleles, particularly the 1014F which was driven to fixation. Spatial occurrence of 1014F was heterogenous, being seemingly influenced by land elevation and gene flow. This study delineates the comprehensive distribution of kdr mutations in An. gambiae and An. coluzzii across Cameroonian mountainous ecosystems. Taking action to limit the spread of kdr alleles into mountainous landscapes would be helpful for the management and sustainability of malaria vector control.