Discovery of knock-down resistance in the major African malaria vector .

A major mechanism of insecticide resistance in insect pests is knock-down resistance () caused by mutations in the voltage-gated sodium channel () gene. Despite being common in most malaria vector species, mutations have never been observed in , the principal malaria vector in Eastern and Southern Africa. While monitoring 10 populations of in Tanzania, we unexpectedly found resistance to DDT, a banned insecticide, in one location. Through whole-genome sequencing of 333 samples from these populations, we found 8 novel amino acid substitutions in the gene, including the variant, L976F (L1014F in ), in tight linkage disequilibrium with another (P1842S). The mutants were found only at high frequency in one region, with a significant decline between 2017 and 2023. Notably, L976F was strongly associated with survivorship to the exposure to DDT insecticide, while no clear association was noted with a pyrethroid insecticide (deltamethrin). Further study is necessary to identify the origin and spread of in , and the potential threat to current insecticide-based vector control in Africa.