Discovery of Knock-Down Resistance in the Major African Malaria Vector Anopheles funestus.

Autor: Odero JO; Department of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.; School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK., Dennis TPW; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK., Polo B; Entomology Section, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya., Nwezeobi J; Wellcome Sanger Institute, Hinxton, UK., Boddé M; Wellcome Sanger Institute, Hinxton, UK., Nagi SC; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK., Hernandez-Koutoucheva A; Wellcome Sanger Institute, Hinxton, UK., Nambunga IH; Department of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania., Bwanary H; Department of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania., Mkandawile G; Department of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania., Govella NJ; Department of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania., Kaindoa EW; Department of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania., Ferguson HM; School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK., Ochomo E; Entomology Section, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya., Clarkson CS; Wellcome Sanger Institute, Hinxton, UK., Miles A; Wellcome Sanger Institute, Hinxton, UK., Lawniczak MKN; Wellcome Sanger Institute, Hinxton, UK., Weetman D; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK., Baldini F; Department of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.; School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK., Okumu FO; Department of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.; School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK.
Jazyk: angličtina
Zdroj: Molecular ecology [Mol Ecol] 2024 Oct 07, pp. e17542. Date of Electronic Publication: 2024 Oct 07.
DOI: 10.1111/mec.17542
Abstrakt: A major insecticide resistance mechanism in insect pests is knock-down resistance (kdr) caused by mutations in the voltage-gated sodium channel (Vgsc) gene. Despite being common in most malaria Anopheles vector species, kdr mutations have never been observed in Anopheles funestus, the principal malaria vector in Eastern and Southern Africa, with resistance mainly being conferred by detoxification enzymes. In a parallel study, we monitored 10 populations of An. funestus in Tanzania for insecticide resistance unexpectedly identified resistance to a banned insecticide, DDT, in the Morogoro region. Through whole-genome sequencing of 333 An. funestus samples from these populations, we found eight novel amino acid substitutions in the Vgsc gene, including the kdr variant, L976F (equivalent to L995F in An. gambiae), in tight linkage disequilibrium with another (P1842S). The mutants were found only at high frequency in one region and were accompanied by weak signatures of a selective sweep, with a significant decline between 2017 and 2023. Notably, kdr L976F was strongly associated with survivorship to exposure to DDT insecticide, while no clear association was noted with a pyrethroid insecticide (deltamethrin). The WHO prequalifies no DDT products for vector control, and the chemical is banned in Tanzania. Widespread DDT contamination and a legacy of extensive countrywide stockpiles may have selected for this mutation. Continued monitoring is necessary to understand the origin of kdr in An. funestus, and the threat posed to insecticide-based vector control in Africa.
(Molecular Ecology© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: