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

AI Article Synopsis

  • Metabolic resistance to insecticides, particularly pyrethroids, in mosquitoes poses a risk to malaria control efforts in Africa, potentially reversing recent progress against the disease.
  • A key cytochrome P450 allele (_R) contributes to decreased effectiveness of insecticide-treated bednets, with evidence of this resistance varying by region across Africa.
  • The study developed a DNA-based assay to track the spread of resistance, revealing it’s nearly fixed in southern Africa but not in other areas, underscoring the urgent need for new malaria control strategies that don’t depend on pyrethroids.

Article 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, We showed that a single cytochrome P450 allele (_R) in 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 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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Source
http://dx.doi.org/10.1126/scitranslmed.aat7386DOI Listing

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