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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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    S19ArtWeedallCytochromeInthomDev.pdf (1.398Mb)
    Date
    2019-03-20
    Author
    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.
    Type
    Journal Article
    Target Audience
    Scientists
    Metadata
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    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.
    https://dx.doi.org/10.1126/scitranslmed.aat7386
    Multi standard citation
    Permanent link to this item
    https://hdl.handle.net/20.500.12478/5539
    Non-IITA Authors ORCID
    Rousseau Djouakahttps://orcid.org/0000-0003-4772-0753
    Digital Object Identifier (DOI)
    https://dx.doi.org/10.1126/scitranslmed.aat7386
    Research Themes
    NUTRITION & HUMAN HEALTH
    IITA Subjects
    Nutrition
    Agrovoc Terms
    Africa; Pyrethroid; Resistance; Mosquitoes; Strain
    Regions
    Africa; Central Africa; East Africa; West Africa
    Countries
    Cameroon; Ghana; Malawi; Uganda
    Journals
    Science Translational Medicine
    Collections
    • Journal and Journal Articles4839
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