Pyrethroid resistance in Aedes vectors: A comprehensive narrative review

Background & objectives: Pyrethroid resistance in Aedes aegypti and Ae. albopictus , including super-resistance phenotypes exceeding 1,000-fold resistance ratios, threatens global arboviral control programmes. This review synthesizes current evidence on resistance mechanisms, geographic distribution, and management strategies. Methods: Systematic literature review (2014-2025) synthesizing WHO/CDC bioassay results, molecular characterization studies, randomized field trials, and economic evaluations from 23 studies across Southeast Asia, South Asia, East Asia, Latin America, Africa, and Oceania, focusing on pyrethroid resistance mechanisms and cross-resistance with organochlorines. Results: Resistance arises through four synergistic mechanisms: voltage-gated sodium channel kdr mutations (F1534C, V1016G, S989P, L982W); cytochrome P450, esterase, and GST-mediated metabolic detoxification; cuticular thickening reducing insecticide penetration; and microbiome-mediated xenobiotic degradation. In Asia, 58% of surveyed Ae. aegypti populations and 6% of surveyed Ae. albopictus populations have been classified as pyrethroid-resistant, whilst DDT resistance has been documented in 68% and 64% of surveyed Ae. aegypti and Ae. albopictus populations, respectively, based on WHO bioassay mortality thresholds. Southeast Asia exhibits pronounced super-resistance hotspots. Wolbachia population replacement interventions achieved 73-76% dengue incidence reductions independent of resistance status; economic evaluations indicate favourable cost-effectiveness, with benefit-cost ratios ranging from 1.75× in Vietnam to 110× in Brazil, reflecting differences in local deployment costs and dengue burden. Interpretation & conclusion: Addressing pyrethroid obsolescence requires integrated management combining Wolbachia deployment, insecticide rotation, agricultural regulation, and molecular surveillance of sentinel mutations (V410L, L982W). Critical priorities include surveillance expansion into Central Africa and other data-deficient regions, and characterization of climate-resistance interactions affecting metabolic detoxification and Wolbachia thermal stability.