Towards evolution-proof malaria control with insecticides.

As many strategies to control malaria use insecticides against adult mosquitoes, control is undermined by the continual evolution of resistant mosquitoes. Here we suggest that using alternative insecticides, or conventional insecticides in alternative ways might enable effective control, but delay considerably or prevent the evolution of resistance. Our reasoning relies on an epidemiological and an evolutionary principle: (i) the epidemiology of malaria is strongly influenced by the life-span of mosquitoes, as most infected mosquitoes die before the malaria parasite has completed its development; and (ii) evolutionary pressure is strongest in young individuals, for selection on individuals that have completed most of their reproduction has little evolutionary effect. It follows from these principles, first, that insecticides that kill mosquitoes several days after exposure can delay considerably the evolution of resistance and, second, that the evolution of resistance against larvicides can actually benefit control, if it is associated with shorter life-span or reduced biting in adults. If a late-acting insecticide and a larvicide are combined, the evolution of resistance against larvicides can in some circumstances prevent the evolution of resistance against the more effective, late-acting insecticide, leading to sustainable, effective control. We discuss several potential options to create such insecticides, focussing on biopesticides.