Abstract
BACKGROUND: The Aedes aegypti mosquito, a primary vector of arboviruses such as dengue, Zika, yellow fever, and chikungunya, poses a significant public health threat worldwide. Its adaptability and genetic diversity complicate control efforts, enabling rapid resistance evolution. Pyrethroid insecticides, a cornerstone of vector control, target voltage-gated sodium channels, yet resistance driven by knockdown resistance (kdr) mutations and detoxification mechanisms have undermined their efficacy. METHODS: This review summarizes findings from a targeted literature search, exploring the genetic and molecular mechanisms driving pyrethroid resistance worldwide, focusing on kdr mutations. RESULTS: Over twenty distinct kdr alleles were reported across global populations, including those functionally confirmed on the recombinant sodium channel such as V253F, V410L, L982W, I1011M, V1016G and F1534C. Indicators of the global impact of pyrethroid resistance include the field selection of highly resistant populations in which kdr mutation frequencies exceed 90%, deltamethrin resistance ratios as high as 249-fold, and permethrin resistance exceeding 500-fold. In laboratory-selected pyrethroid-resistant strains, resistance ratios can surpass 1,000-fold. CONCLUSIONS: We provide an updated status of pyrethroid resistance in Ae. aegypti and a framework on how the results of molecular tests and toxicity bioassays can be applied to practical mosquito control programs. Control strategies must integrate multidisciplinary approaches, including Integrated Vector Management (IVM), which emphasizes targeted interventions, community engagement, and sustainable practices. Despite advances in analyzing resistance, very few studies measure frequency of genotypes, determine phenotypic resistance (resistance ratios), and assess standardized field efficacy in the same populations, including field measurements of pesticide deposited, leaving a critical implementation gap. This lack of integration creates major gaps in translating laboratory resistance diagnostics into actionable field control decisions. Empirical data on how cuticular thickening and behavioral avoidance alter post-treatment survivorship are especially sparse, limiting the predictive power of current methodologies. By assessing the current understanding of pyrethroid resistance in Ae. aegypti, this review informs the development of resilient, evidence-based interventions to mitigate the public health impact of diseases transmitted by Ae. aegypti.