Tracing the genetic origins of insecticide resistance in malaria-transmitting mosquitoes

Researchers have identified a single genetic alteration in a malaria-transmitting mosquito species that confers resistance to a widely-used insecticide, according to a new study. The research, which combines genetic sequencing with field studies of mosquito feeding, underscores the need to develop new insecticides for bed nets, a cornerstone of malaria control efforts. Bed nets are devices that prevent mosquitoes from feeding on humans at night, and are often coated with insecticides such as pyrethroids to enhance their effectiveness. They have been credited with more than 70% of the decrease in malaria deaths in the past 15 years, and one study has estimated that they have helped to avoid more than 663 million cases of malaria. However, mosquitoes have become increasingly resistant to several of the most common insecticides, a development that poses a major threat to current malaria control efforts. Furthermore, attempts to assess or track the impact of insecticide resistance have been hindered by a lack of information about the genes that drive resistance mechanisms. Here, Gareth Weedall and colleagues set out to pinpoint the genetic drivers of pyrethroid resistance in Anopheles funestus, one of the major insect vectors of malaria in Africa. Using a combination of sequencing techniques, they identified a single allele in the gene CYP6P9a that heightened its activity and promoted resistance to pyrethroids. The authors then designed and used a DNA-based field test that detects the presence of this allele, and discovered the allele was common among A. funestus from southern Africa, but was absent in mosquitoes collected in Central and West Africa. What’s more, a field study in Cameroon revealed that mosquitoes carrying the resistance allele were better able to feed on human volunteers who slept in huts with pyrethroid-coated bed nets. In a related transcript Q&A, Weedall et al. say their findings represent the first molecular diagnostic for metabolic resistance, 20 years after scientists identified a major cause of insecticide resistance (a modified sodium channel in mosquitos). They further note that their discovery may help inform efforts to better understand how metabolic resistance is spreading across the African continent.

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