Countering the evolutionary threat to malaria vector control in Africa - Major changes to national malaria elimination strategy in the Senegambia region as a model system for investigating strategies to block adaptation in Anopheles mosquito populations

Vector control has significantly reduced the burden of malaria in Africa. However, reliance on bednets impregnated with pyrethroid insecticides has caused rapid evolution of pyrethroid resistance in Anopheles mosquitoes. To combat this threat, dual active ingredient insecticide-treated nets (dual AI ITNs) have been developed and proven effective against pyrethroid-resistant mosquitoes. Furthermore, dual AI ITNs combining a pyrethroid with the proinsecticide chlorfenapyr are promising for resistance management, because molecular mechanisms which cause pyrethroid resistance also activate and increase susceptibility to chlorfenapyr. This potential for antagonistic pleiotropy could create an evolutionary trap, delaying the evolution of resistance. However, little is known about how Anopheles mosquitoes will evolve in response to dual AI ITNs. We will exploit the first mass distribution of dual AI ITNs across the Senegambian region to study the evolutionary response of Anopheles mosquito populations to combined use of pyrethroid and chlorfenapyr insecticides. To complement this, we will use directed evolution experiments to investigate and validate the selective pressures generated by insecticide combinations. Finally, we will develop models to forecast the evolutionary risk of different insecticide combinations and intervention strategies. These advances will accelerate the design of future vector control interventions that exploit evolutionary vulnerabilities to ensure long term efficacy.