Existing malaria control insecticides - without the evolution of insecticide-resi

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DESCRIPTION (provided by applicant): Insecticides are among the cheapest, most effective and best proven methods of controlling malaria but as historical and contemporary experience shows, mosquitoes can rapidly evolve resistance. We wish to test the hypothesis that existing public health insecticides could be made to deliver excellent malaria control without driving the evolution of insecticide resistant mosquitoes simply by using their active ingredients at lower concentrations. This hypothesis, which is completely opposite to conventional wisdom, derives from the observation that current insecticide paradigms indiscriminately target all adult mosquitoes and thus impose immense selection for resistance, whereas malaria is actually transmitted by only a small faction of mosquitoes (old, infected individuals). If insecticides targeted only those dangerous mosquitoes, and avoided all the others, particularly the young reproductively-active mosquitoes most responsible for evolutionary change, then it would be possible to impose strong disease control without imposing strong 'natural' selection for insecticide resistance. It is our contention that old, diseased mosquitoes will be vulnerable to insecticide concentrations that are too low to kill young vigorous mosquitoes. We therefore want to experimentally determine whether lower concentrations of active ingredients can be used to selectively excise the dangerous mosquitoes. If this lateral idea is correct, then very simple, easy to implement changes in current formulations could be used to ensure that our existing insecticides - which demonstrably provide excellent malaria control when used on bed nets or in house spraying campaigns - can continue as leading malaria control tools for the foreseeable future. PUBLIC HEALTH RELEVANCE: Insecticides for house spraying and bed nets are vital components of global malaria control efforts. As currently used, existing insecticides work extremely well, but only by creating the conditions which undermine their future: they confer an immense evolutionary advantage on resistant mosquitoes. We seek to test an idea that would retard or completely prevent the evolution of insecticide resistance while still delivering excellent malaria control.