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

Odero, Joel O., Dennis, Tristan, Polo, Brian, Nwezeobi, Joachim, Boddé, Marilou, Nagi, Sanjay, Hernandez‐Koutoucheva, Anastasia, Nambunga, Ismail H., Bwanary, Hamis, Mkandawile, Gustav, Govella, Nicodem J., Kaindoa, Emmanuel W., Ferguson, Heather M., Ochomo, Eric, Clarkson, Chris S., Miles, Alistair, Lawniczak, Mara K. N., Weetman, David ORCID: https://orcid.org/0000-0002-5820-1388, Baldini, Francesco and Okumu, Fredros O. (2024) 'Discovery of Knock‐Down Resistance in the Major African Malaria Vector Anopheles funestus'. Molecular ecology, e17542. (In Press)

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Abstract

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.

Item Type: Article
Subjects: QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1111/mec.17542
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 23 Oct 2024 07:49
Last Modified: 23 Oct 2024 07:49
URI: https://archive.lstmed.ac.uk/id/eprint/25447

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