Knockdown Resistance Mutations and Pyrethroid Resistance in Anopheles Mosquitoes in Sub-Saharan Africa: A Systematic Review and Meta-analysis

Abstract

Resistance to pyrethroids is conferred in voltagegated sodium channels through the mechanism of kdr mutation, which also decreases the insecticides' binding affinity to their targets, making them less effective. These mutations affect the efficacy of indoor residual spraying (IRS), which are encoded in the VGSC gene, including the effectiveness of insecticide-treated nets (ITNS). This study represents the first meta-analysis to evaluate the resistance impact of L1014F and L1014S mutations in Anopheles mosquitoes within sub-Saharan Africa. Eight studies that meet with the inclusion criteria were analyzed, encompassing 4,690 mosquito samples. Due to substantial between-study heterogeneity, random effects (R.E) models were applied. The pooled odds ratio (OR) for L1014F (L vs F) was 2.14(95% CI: 1.17-2.93), and for L1014S (S vs F), it was 0.899 (95% CI: 0.297- 1.293), indicating a significant association with resistance. Sensitivity analysis revealed that excluding a study with high variability decreased the ORs, showing the influence of publication bias and small sample size. Funnel plot asymmetry and Egger’s test confirmed the presence of publication bias, affecting effect estimates. Due to high heterogeneity and limited studies, the observed resistance effects of L1014F and L1014S mutations are inconclusive. In addition, validating the relevance of these genotype alleles in insecticide resistance and malaria control initiatives in endemic regions requires extensive research