At a recent conference, antimalaria crusader Bill Gates explained why researchers must continually renew their arsenal of weapons against the disease: “The parasite evolves and the mosquito evolves, so every tool we’ve ever had in the past has eventually become ineffective.” The evolution of resistance has resulted in a multimillion-dollar treadmill of new drugs and pesticides continually replacing older ones. Pennsylvania State University evolutionary biologist Andrew Read wants to end this cycle. “The harder we squeeze the parasite and mosquito, the more they’re going to evolve and respond,” he says.
The crux of the problem is that the Plasmodium malaria parasites and mosquitoes most resistant to drugs or insecticides are the ones most likely to survive treatment and reproduce. But Read has demonstrated that targeting older mosquitoes—those nearing the end of their reproductive lives, which are also the most likely to be disease carriers—could largely eliminate the problem of insecticide resistance. Focusing on older mosquitoes could be as simple as applying less insecticide or using fungal biopesticides that kill mosquitoes up to two weeks after contact, when a large portion of the insect’s short lifespan has passed. Allowing younger mosquitoes to continue reproducing reduces the development of resistance while keeping infection rates low.
Another approach focuses on the malaria parasite, which jumps from one red blood cell to another, killing the cells in the process. Traditionally, researchers have focused on keeping malaria from entering the cells in the first place. But now University of Pennsylvania biochemist Doron Greenbaum has found a way to lock malaria inside the cells by blocking the action of a key host protein, called calpain, that allows its escape. Greenbaum believes it might be more difficult for malaria to evolve resistance to a drug aimed at a protein in its host rather than at one of its own. In the evolutionary arms race to defeat the disease, subtle and indirect maneuvers like these may ultimately prove most effective.