Evolution-proof insecticides may stall malaria forever

Every year malaria—spread through mosquito bites—kills about a million people around the globe. The deadly insects are widely combated with insecticides, but many of these chemicals eventually become ineffective, as repeated exposure breeds resistance.

"Insecticides sprayed on house walls or bed nets are some of the most successful ways of controlling malaria," says Andrew Read, professor of biology and entomology at Penn State. "But they work by killing the insects or denying them the human blood they turn into eggs. This imposes an enormous selection in favor of insecticide-resistant mosquitoes."

Read and his colleagues Matthew Thomas, professor of entomology at Penn State, and Penelope Lynch, a doctoral student at Open University in the United Kingdom, argue that insecticides that kill only older mosquitoes are a more sustainable way to fight the deadly disease.

Female Anopheles mosquitoes spread malaria by biting infected humans and ingesting the malaria parasites along with the blood they need to reproduce other mosquitoes, the researchers explain. The parasites are then implanted in the mosquito’s gut wall, where they mature and eventually migrate to the mosquito's salivary glands. The next time the mosquito bites a human, the disease is transmitted.

All told, this process takes at least 10 to 14 days. Fortunately for humans, most mosquitoes are dead by the end of that time—their normal lifespan is only two to three weeks. It’s the outliers, mosquitoes that live up to eight weeks, that are the problem. "It is one of the great ironies of malaria," says Read. "Most mosquitoes do not live long enough to transmit the disease. To stop malaria, we only need to kill the old mosquitoes."

He and Thomas are working on a new fungal pesticide that will do just that. "We could spray it onto walls or onto treated materials such as bed nets, from where the mosquito would get infected by the fungal spores," says Thomas. The fungi then take 10 to 12 days to do their work.

To study the impact of such late-acting insecticides, the researchers constructed a mathematical model of malaria transmission. Using data from disease hotspots in Africa and Papua New Guinea they showed that insecticides that kill only older mosquitoes reduce the number of infectious bites by about 95 percent.

Critically, the researchers also found that resistance to late-acting insecticides spreads much more slowly than resistance to conventional insecticides, and that in many cases, it never spreads at all.

Since most mosquitoes die before they become dangerous, late-acting insecticides do not have much impact on breeding, so there is much less pressure for the mosquitoes to evolve resistance, explains Read. "This means that late-life insecticides will be useful for much, much longer than conventional insecticides—maybe forever," he adds.

Andrew Read, Ph.D., is professor of biology and entomology and Matthew Thomas, Ph.D. is professor of entomology in the Eberly College of Science. Both are affiliated with the Penn State Center for Infectious Disease Dynamics. Their email addresses are andrew.read@psu.edu and mbt13@psu.edu. Penelope Lynch, a doctoral student at Open University in the United Kingdom. The findings reported above appeared in the April 7, 2009 issue of PLoS Biology.

Last Updated May 18, 2009