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Cited by 49Malaria Research and ControlInsect Resistance and GeneticsAntibiotic Resistance in Bacteria

Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Côte d’Ivoire

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Oumbouke, Welbeck A., Pignatelli, Patricia, Barreaux, Antoine M. G., Tia, Innocent Z., Koffi, Alphonsine A., Ahoua Alou, Ludovic P., Sternberg, Eleanore D., Thomas, Matthew B. +2 more·2020·Scientific Reports
DOI 10.1038/s41598-020-71933-8PMC PMC7493912
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Abstract

Routine monitoring of occurrence, levels and mechanisms of insecticide resistance informs effective management strategies, and should be used to assess the effect of new tools on resistance. As part of a cluster randomised controlled trial evaluating a novel insecticide-based intervention in central Côte d’Ivoire, we assessed resistance and its underlying mechanisms in Anopheles gambiae populations from a subset of trial villages. Resistance to multiple insecticides in An. gambiae s.s. and An. coluzzii was detected across villages, with dose–response assays demonstrating extremely high resistance intensity to the pyrethroid deltamethrin (> 1,500-fold), and mortality following exposure to pyrethroid-treated bednets was low (< 30% mortality in cone bioassays). The 1014F kdr mutation was almost fixed (≥ 90%) in all villages but the 1575Y kdr-amplifying mutation was relatively rare (< 15%). The carbamate and organophosphate resistance-associated Ace-1 G119S mutation was also detected at moderate frequencies (22–43%). Transcriptome analysis identified overexpression of P450 genes known to confer pyrethroid resistance (Cyp9K1, Cyp6P3, and Cyp6M2), and also a carboxylesterase (COEAE1F) as major candidates. Cyp6P3 expression was high but variable (up to 33-fold) and correlated positively with deltamethrin resistance intensity across villages (r 2 = 0.78, P = 0.02). Tools and strategies to mitigate the extreme and multiple resistance provided by these mechanisms are required in this area to avoid future control failures.

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  • There was a high frequency of both kdr and ace1R genes in An. gambiae and An. coluzzii, with a higher frequency for An. gambiae.

    “Consistent with recent studies carried out in the area of Bouaké [7, 9, 13, 36], there was a high frequency of both kdr and ace1R genes in An. gambiae and An. coluzzii, with a higher frequency for An. gambiae; probably due to selection pressure through the use of insecticide.”

    From Entomological indicators of malaria transmission prior to a cluster-randomized controlled trial of a 'lethal house lure' intervention in central Côte d'Ivoire (2022) · cites this paper as [9]

    The Results (Species identification and target-site resistance; page not provided) report very high frequency of the kdr 1014F mutation (>0.9) and Ace-1 G119S frequencies of 22–43% across villages. They do not establish higher frequencies in An. gambiae than in An. coluzzii; in the mixed-species village of Kouakro, the paper found no evidence of a difference in G119S frequency. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The situation is particularly worrying with an increase in intensity and mechanisms of insecticide resistance detected over time.

    “The situation is particularly worrying with an increase in intensity and mechanisms of insecticide resistance detected over time [8, 9].”

    From Entomological indicators of malaria transmission prior to a cluster-randomized controlled trial of a 'lethal house lure' intervention in central Côte d'Ivoire (2022) · cites this paper as [9]

    The Discussion (Phenotypic resistance; page not provided) describes deltamethrin resistance intensity as among the highest reported and identifies it as a concern. The paper also identifies target-site and metabolic resistance mechanisms, but it does not show that their number or resistance intensity increased over time; the Introduction predicts a future increase rather than documenting one. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The similarity between indoor and outdoor transmission of malaria is inconsistent with LLIN use in the area.

    “The similarity between indoor and outdoor transmission of malaria is inconsistent with LLIN use in the area [9].”

    From Entomological indicators of malaria transmission prior to a cluster-randomized controlled trial of a 'lethal house lure' intervention in central Côte d'Ivoire (2022) · cites this paper as [9]

    The Results section reports poor LLIN performance against local mosquitoes, and the Methods section describes LLIN coverage in the study area. Neither reports or compares indoor and outdoor malaria transmission. Searches for indoor–outdoor transmission and outdoor biting found no passage addressing the claimed inconsistency with LLIN use. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 47

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Authors
Oumbouke, W. A., Pignatelli, P., Barreaux, A. M. G., Tia, I. Z., Koffi, A. A., Ahoua Alou, L. P., Sternberg, E. D., Thomas, M. B., Weetman, D., & N’Guessan, R.
Affiliations
  • London School of Hygiene & Tropical Medicine (GB)
  • Liverpool School of Tropical Medicine (GB)
  • Pennsylvania State University (US)
  • Institut National de Santé Publique (CI)
Corresponding author
Oumbouke, Welbeck A.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-09-15
Volume
10
Issue
1
Pages
15066-15066
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-71933-8
PMC
PMC7493912
OpenAlex
W3086746938
Cited by
49
References
60
Citations by year
2026: 8 · 2025: 9 · 2024: 7 · 2023: 9 · 2022: 11 · 2021: 5
FWCI
4.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • HAL (submittedVersion, cc-by)
  • Agritrop (Cirad) (submittedVersion, cc-by)
  • Explore Bristol Research (submittedVersion, cc-by)
Funders
Bill and Melinda Gates Foundation (OPP1131603)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Insect Resistance and Genetics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Keywords
Anopheles gambiae, Anopheles coluzzii, insecticide resistance, pyrethroid resistance, deltamethrin, kdr mutation, carbamate resistance, organophosphate resistance, cytochrome P450, carboxylesterase, metabolic resistance, malaria vector control, Côte d'Ivoire
MeSH terms
Animals, Anopheles, Cytochrome P-450 Enzyme System, Insecticide Resistance, Insecticides, Cote d'Ivoire, Mosquito Control, Nitriles, Pyrethrins, Insect Proteins, Carboxylesterase

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