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Sci Transl Med. 2019 Mar 20;11(484). pii: eaat7386. doi: 10.1126/scitranslmed.aat7386.

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

Author information

1
Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
2
School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L3 3AF, U.K.
3
LSTM Research Unit at the Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), P.O. Box 288, Yaoundé, Cameroon.
4
Centre for Research in Infectious Diseases (CRID), P.O. Box 13591, Yaoundé, Cameroon.
5
Department of Biochemistry, Bayero University, PMB 3011, Kano, Nigeria.
6
Centre for Medical Research, Institute of Medical Research and Medicinal Plants Studies (IMPM), P.O. Box 13033, Yaoundé, Cameroon.
7
International Institute of Tropical Agriculture (IITA), Cotonou 08 BP 0932, Benin.
8
Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. charles.wondji@lstmed.ac.uk.

Abstract

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.

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