Discovery of Knock‐Down Resistance in the Major African Malaria Vector <i>Anopheles funestus</i>
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.
Authors
- Gustav Mkandawile
- Emmanuel W. Kaindoa (ORCID: https://orcid.org/0000-0001-6170-5694)
- Nicodem J. Govella (ORCID: https://orcid.org/0000-0001-5460-9629)
- Brian Polo (ORCID: https://orcid.org/0009-0002-7505-9050)
- Eric Ochomo (ORCID: https://orcid.org/0000-0002-4042-4970)
- Anastasia Hernández-Koutoucheva (ORCID: https://orcid.org/0000-0002-0197-9092)
- Chris S. Clarkson (ORCID: https://orcid.org/0000-0002-8757-1660)
- Francesco Baldini (ORCID: https://orcid.org/0000-0002-2689-5952)
- Hamis Bwanary
- Joachim Nwezeobi (ORCID: https://orcid.org/0000-0002-7541-9186)
- Joel O. Odero (ORCID: https://orcid.org/0000-0002-8463-2122)
- Alistair Miles (ORCID: https://orcid.org/0000-0001-9018-4680)
- Fredros O. Okumu (ORCID: https://orcid.org/0000-0003-2731-5654)
- Heather M. Ferguson (ORCID: https://orcid.org/0000-0002-9625-5176)
- Tristan P. W. Dennis (ORCID: https://orcid.org/0000-0002-0895-3549)
- Sanjay C. Nagi (ORCID: https://orcid.org/0000-0003-1214-8523)
- Mara Lawniczak (ORCID: https://orcid.org/0000-0002-3006-2080)
- David Weetman (ORCID: https://orcid.org/0000-0002-5820-1388)
- Marilou Boddé (ORCID: https://orcid.org/0000-0003-2107-5100)
- Ismail H. Nambunga
Institutions
- Ifakara Health Institute (TZ)
- Liverpool School of Tropical Medicine (GB)
- Wellcome Sanger Institute (GB)
- Kenya Medical Research Institute (KE)
- University of Glasgow (GB)
Publication Details
- Journal
- Molecular Ecology
- Published
- 2024-10-07
- DOI
- https://doi.org/10.1111/mec.17542
- Citations
- 30
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 16.29
Funders
- Howard Hughes Medical Institute
- Bill and Melinda Gates Foundation
- Texas Parks and Wildlife Department
- Wellcome Trust
- Broad Institute
- Royal Society
- Academy of Medical Sciences
- European Commission
- China Scholarship Council
- Medical Research Council
- National Institute of Allergy and Infectious Diseases
- European and Developing Countries Clinical Trials Partnership