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    A cytochrome P450 allele confers pyrethroid resistance on a major African malaria vector, reducing insecticide-treated bednet efficacy

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    Authors
    Weedall, G.D.
    Mugenzi, L.M.
    Menze, B.D.
    Tchouakui, M.
    Ibrahim, S.S.
    Amvongo-Adjia, N.
    Irving, H.
    Wondji, M.J.
    Tchoupo, M.
    Djouaka, R.
    Riveron, J.M.
    Wondji, C.S.
    Date
    2019-03
    Language
    en
    Type
    Journal Article
    Review status
    Peer Review
    ISI journal
    Accessibility
    Limited Access
    Usage rights
    Copyrighted; all rights reserved
    Metadata
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    Citation
    Weedall, G.D., Mugenzi, L.M., Menze, B.D., Tchouakui, M., Ibrahim, S.S., Amvongo-Adjia, N., ... & Wondji, C.S. (2019). A cytochrome P450 allele confers pyrethroid resistance on a major African malaria vector, reducing insecticide-treated bednet efficacy. Science Translational Medicine, 11(484), 1-13.
    Permanent link to cite or share this item: https://hdl.handle.net/10568/101298
    DOI: https://doi.org/10.1126/scitranslmed.aat7386
    Abstract/Description
    Metabolic resistance to insecticides such as pyrethroids in mosquito vectors threatens control of malaria in Africa. Unless it is managed, recent gains in reducing malaria transmission could be lost. To improve monitoring and assess the impact of insecticide resistance on malaria control interventions, we elucidated the molecular basis of pyrethroid resistance in the major African malaria vector, Anopheles funestus. We showed that a single cytochrome P450 allele (CYP6P9a_R) in A. funestus reduced the efficacy of insecticide-treated bednets for preventing transmission of malaria in southern Africa. Expression of key insecticide resistance genes was detected in populations of this mosquito vector throughout Africa but varied according to the region. Signatures of selection and adaptive evolutionary traits including structural polymorphisms and cis-regulatory transcription factor binding sites were detected with evidence of selection due to the scale-up of insecticide-treated bednet use. A cis-regulatory polymorphism driving the overexpression of the major resistance gene CYP6P9a allowed us to design a DNA-based assay for cytochrome P450–mediated resistance to pyrethroid insecticides. Using this assay, we tracked the spread of pyrethroid resistance and found that it was almost fixed in mosquitoes from southern Africa but was absent from mosquitoes collected elsewhere in Africa. Furthermore, a field study in experimental huts in Cameroon demonstrated that mosquitoes carrying the resistance CYP6P9a_R allele survived and succeeded in blood feeding more often than did mosquitoes that lacked this allele. Our findings highlight the need to introduce a new generation of insecticide-treated bednets for malaria control that do not rely on pyrethroid insecticides.
    CGIAR Author ORCID iDs
    Rousseau Djouakahttps://orcid.org/0000-0003-4772-0753
    CGIAR Affiliations
    Agriculture for Nutrition and Health
    AGROVOC Keywords
    africa; pyrethroid; resistance; mosquitoes; strain
    Subjects
    NUTRITION
    Countries
    Cameroon; Ghana; Malawi; Uganda
    Regions
    Africa; Central Africa; Eastern Africa; Western Africa
    Collections
    • CRP A4NH outputs [908]
    • IITA Journal Articles [4248]

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