Evidence map›Paper›PMID 39509710›Full record

ArticleGenetics2025

A single mutation G454A in the P450 CYP9K1 drives pyrethroid resistance in the major malaria vector Anopheles funestus reducing bed net efficacy.

Carlos S Djoko Tagne, Mersimine F M Kouamo, Magellan Tchouakui, Abdullahi Muhammad, Leon J L Mugenzi, Nelly M T Tatchou-Nebangwa, Riccado F Thiomela, Mahamat Gadji, Murielle J Wondji, Jack Hearn and 3 more

Abstract read
In one paragraph

Article in Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed.

  1. Article
  2. Article
  3. Synergistic action of different molecular mechanisms causes striking levels of insecticide resistance in the malaria vectorProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Complex Roles of Insect Cytochrome P450s in Chemical Adaptation.International journal of biological sciences · 2026
    Review
  11. Spatial Heterogeneity ofJournal of parasitology research · 2026
    Review
  12. Article
  13. Distinct Genetic Footprint of Adaptation Observed WithinResearch and reports in tropical medicine · 2026
    Article
  14. Article
  15. Article
  16. Article
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  18. An atlas of positive selection in the genomes of major malaria vectors.bioRxiv : the preprint server for biology · 2025
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Carlos S Djoko TagneMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.ORCID 0000-0002-4752-5344
Mersimine F M KouamoMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.
Magellan TchouakuiMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.
Abdullahi MuhammadVector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
Leon J L MugenziSyngenta Crop Protection Department, Werk Stein, Schaffhauserstrasse, Stein CH4332, Switzerland.
Nelly M T Tatchou-NebangwaMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.
Riccado F ThiomelaMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.
Mahamat GadjiMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.ORCID 0000-0002-5671-2299
Murielle J WondjiMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.
Jack HearnCentre for Epidemiology and Planetary Health, Scotland's Rural College (SRUC), RAVIC, Inverness IV2 5NA, UK.
Mbouobda H DesireDepartment of Biochemistry, Faculty of Science, University of Bamenda, P.O. Box 39 Bambili, Bamenda, Cameroon.
Sulaiman S IbrahimMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.ORCID 0000-0003-0744-802X
Charles S WondjiMedical Entomology Department, Centre for Research in Infectious Diseases (CRID), P.O. Box 13501, Yaoundé, Cameroon.ORCID 0000-0003-0791-3673

Funding

Gates Foundation INV-006003Wellcome TrustWellcome Trust Senior Research Fellowships in Biomedical Sciences 217188/Z/19/Z
6 · The paper itself

Abstract

Metabolic mechanisms conferring pyrethroid resistance in malaria vectors are jeopardizing the effectiveness of insecticide-based interventions, and identification of their markers is a key requirement for robust resistance management. Here, using a field-lab-field approach, we demonstrated that a single mutation G454A in the P450 CYP9K1 is driving pyrethroid resistance in the major malaria vector Anopheles funestus in East and Central Africa. Drastic reduction in CYP9K1 diversity was observed in Ugandan samples collected in 2014, with the selection of a predominant haplotype (G454A mutation at 90%), which was completely absent in the other African regions. However, 6 years later (2020) the Ugandan 454A-CYP9K1 haplotype was found predominant in Cameroon (84.6%), but absent in Malawi (Southern Africa) and Ghana (West Africa). Comparative in vitro heterologous expression and metabolism assays revealed that the mutant 454A-CYP9K1 (R) allele significantly metabolizes more type II pyrethroid (deltamethrin) compared with the wild G454-CYP9K1 (S) allele. Transgenic Drosophila melanogaster flies expressing 454A-CYP9K1 (R) allele exhibited significantly higher type I and II pyrethroids resistance compared to flies expressing the wild G454-CYP9K1 (S) allele. Furthermore, laboratory testing and field experimental hut trials in Cameroon demonstrated that mosquitoes harboring the resistant 454A-CYP9K1 allele significantly survived pyrethroids exposure (odds ratio = 567, P < 0.0001). This study highlights the rapid spread of pyrethroid-resistant CYP9K1 allele, under directional selection in East and Central Africa, contributing to reduced bed net efficacy. The newly designed DNA-based assay here will add to the toolbox of resistance monitoring and improving its management strategies.

Indexed as

AnophelesCytochrome P-450 Enzyme SystemInsecticide ResistanceMalariaMosquito VectorsPyrethrinsAnimalsDrosophila melanogasterHaplotypesInsecticidesInsecticide-Treated BednetsInsect ProteinsMosquito ControlMutationCytochrome P-450 Enzyme SystemInsecticidesInsect ProteinsPyrethrinsAnopheles funestusbed net efficacyCYP9K1insecticide resistanceinsecticide-treated netsmalariapyrethroid

Identifiers

PMID39509710
PMCPMC11708915

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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 Socratic graph.