Evidence map›Paper›PMID 39374937›Full record

ArticleMolecular ecology2024

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

Joel O Odero, Tristan P W Dennis, Brian Polo, Joachim Nwezeobi, Marilou Boddé, Sanjay C Nagi, Anastasia Hernandez-Koutoucheva, Ismail H Nambunga, Hamis Bwanary, Gustav Mkandawile and 10 more

Abstract read
In one paragraph

Article in Molecular ecology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

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  15. An atlas of positive selection in the genomes of major malaria vectors.bioRxiv : the preprint server for biology · 2025
    Article
  16. Article
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  18. Article
  19. The origin, invasion history and resistance architecture ofbioRxiv : the preprint server for biology · 2025
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Joel O OderoDepartment of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.ORCID 0000-0002-8463-2122
Tristan P W DennisDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
Brian PoloEntomology Section, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Joachim NwezeobiWellcome Sanger Institute, Hinxton, UK.
Marilou BoddéWellcome Sanger Institute, Hinxton, UK.
Sanjay C NagiDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0000-0003-1214-8523
Anastasia Hernandez-KoutouchevaWellcome Sanger Institute, Hinxton, UK.
Ismail H NambungaDepartment of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.
Hamis BwanaryDepartment of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.
Gustav MkandawileDepartment of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.
Nicodem J GovellaDepartment of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.
Emmanuel W KaindoaDepartment of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.
Heather M FergusonSchool of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK.
Eric OchomoEntomology Section, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Chris S ClarksonWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0002-8757-1660
Alistair MilesWellcome Sanger Institute, Hinxton, UK.
Mara K N LawniczakWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0002-3006-2080
David WeetmanDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
Francesco BaldiniDepartment of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.
Fredros O OkumuDepartment of Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.

Funding

Genome-based diagnostics for monitoring and evaluation of insecticide resistance in Anopheles gambiaeR01AI116811 · NIAID · TMLIVERPOOL SCHOOL OF TROPICAL MEDICINE · PI Martin James Donnelly · 2016 to 2026
$4.6M
Academy of Medical Sciences SBF007\100094Gates Foundation INV-002138Gates Foundation INV-031595Howard Hughes Medical Institute OPP 1099295Medical Research Council MR/P02520X/1National Institute of Allergy and Infectious Diseases [NIAID] R01-AI116811NIAID NIH HHS R01 AI116811Royal Society RSWF\FT\180003Wellcome TrustWellcome Trust 220540/Z/20/A
6 · The paper itself

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.

Indexed as

AnophelesInsecticide ResistanceInsecticidesMalariaMosquito VectorsVoltage-Gated Sodium ChannelsAmino Acid SubstitutionAnimalsDDTLinkage DisequilibriumMutationPyrethrinsTanzaniaWhole Genome SequencingDDTInsecticidesPyrethrinsVoltage-Gated Sodium ChannelsAnopheles funestusinsecticide resistanceknock‐down resistanceTanzaniavoltage‐gated sodium channel

Identifiers

PMID39374937
PMCPMC11537839

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.