How to make evolution-proof insecticides for malaria control

Insecticides are one of the cheapest, most effective, and best proven methods of controlling malaria, but mosquitoes can rapidly evolve resistance. Such evolution, first seen in the 1950s in areas of widespread DDT use, is a major challenge because attempts to comprehensively control and even eliminate malaria rely heavily on indoor house spraying and insecticide-treated bed nets. Current strategies for dealing with resistance evolution are expensive and open ended, and their sustainability has yet to be demonstrated. Here we show that if insecticides targeted old mosquitoes, and ideally old malaria-infected mosquitoes, they could provide effective malaria control while only weakly selecting for resistance. This alone would greatly enhance the useful life span of an insecticide. However,such weak selection for resistance can easily be overwhelmed if resistance is associated with fitness costs. In that case, late-life-acting insecticides would never be undermined by mosquito evolution.We discuss a number of practical ways to achieve this, including different use of existing chemical insecticides,biopesticides, and novel chemistry. Done right, a one-off investment in a single insecticide would solve the problem of mosquito resistance forever.