Fine-Scale Spatial Variation in Pyrethroid Knockdown Resistance Mutations in Anopheles arabiensis from the Upper River Region, the Gambia

Pyrethroid resistance threatens the effectiveness of malaria vector control in sub-Saharan Africa. We assessed the spatial distribution of pyrethroid knockdown resistance (kdr) mutations in Anopheles gambiae populations from two sites approximately 9 km apart at the Upper River Region (URR) in The Gambia. Susceptibility to three insecticides was tested in mosquitoes collected from Gambissara and Sabi using WHO tube bioassays; and knockdown resistance (kdr) mutations (L1014F and L1014S) were determined using PCR assays. Allele and genotype frequencies were compared between sites, and associations between kdr genotypes and survival were assessed using standard statistical tests. Mosquito populations showed phenotypic resistance to permethrin (Mortality: Gambissara = 45.2%, Sabi = 48.4%), while frequencies of L1014F and L1014S were 6.95% and 12.16% respectively. There was a significant difference in L1014F frequency between sites (Gambissara: 11.85%, Sabi = 1.60%, P < 0.0001), but not in L1014S frequency (Gambissara= 12.96%, Sabi = 11.20%, P = 0.592). Both L1014F and L1014S were significantly associated with increased odds of survival following permethrin exposure (L1014F: OR = 4.74, 95% CI: 1.55-14.54, P = 0.006; L1014S: OR = 2.33, 95% CI: 1.10-4.90, P = 0.026). These findings highlight fine-scale spatial heterogeneity in the genetic basis of pyrethroid resistance and emphasize the need for resistance monitoring at a micro-geographic scale in malaria elimination settings.