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Evolution-Proof Insecticides May Stall Malaria Forever

November 19, 2017

Killing only older mosquitoes could be a more sustainable way of controlling malaria, and has the potential to lead to evolution-proof insecticides that never become obsolete, according to an article in this week's issue of PLoS Biology. Each year, malaria - spread through mosquito bites - kills around a million people, and many of the chemicals used to kill the insects become ineffective as the mosquito's resistance to them evolves. New theoretical work, by Andrew Read and Matt Thomas (both at Penn State), and Penelope Lynch (Open University, UK), predicts that simple changes to the way insecticides are used could prevent the evolution of resistance and thereby reduce the burden of malaria. The authors argue that insecticides - chemical or biological - which kill only older mosquitoes, are a more sustainable way to fight the deadly disease.

Read says the development of biological or chemical insecticides that target older, malaria-infected mosquitoes could save millions dollars that would otherwise be spent endlessly looking for new insecticides to replace ones that have become ineffective. "Done right, a one-off investment could create a single insecticide that would solve the problem of mosquito resistance forever."

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

However, once malaria parasites infect a mosquito, they need at least 10 to 14 days - or two to six cycles of egg production - to mature and migrate to the insect's salivary glands. From there they can pass into humans when a mosquito bites. Therefore, as Read explains, "Most mosquitoes do not live long enough to transmit the disease. To stop malaria, we only need to kill the old mosquitoes." To study the impact of late-acting insecticides on mosquito populations, the researchers constructed a mathematical model of malaria transmission using factors such as the egg laying cycle of the mosquito and the development of parasites within the insect. Analyses of the model using data on mosquito lifespan and malaria development from hotspots in Africa and Papua New Guinea reveal that insecticides killing only mosquitoes that have completed at least four cycles of egg production 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 among mosquitoes, compared to conventional insecticides, and that in many cases, it never spreads at all.

Aging mosquitoes are easier to kill with insecticides like DDT but new generation pesticides could do it too. Read and his colleagues are working with a biopesticide that kills older mosquitoes. Since most mosquitoes die before they become dangerous, late-acting insecticides will not have much impact on breeding, so there is much less pressure for the mosquitoes to evolve resistance, explained Read. "This means that late-life insecticides will be useful for much, much longer - maybe forever - than conventional insecticides." He added, "Insects usually have to pay a price for resistance, and if only a few older mosquitoes gain the benefits, evolutionary economics can stop resistance from ever spreading."

"We are working on fungal pesticide that kills mosquitoes late in life," said Thomas. "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." The fungi take 10 to 12 days to kill the insects. This achieves the benefit of killing the old, dangerous mosquitoes, while dramatically reducing the selection for the evolution of resistance, Thomas explained.

The next step is to test the approach in the field. The main challenge to overcome might be human perception, says Read. "Young mosquitoes aren't dangerous, though they are a nuisance. Our approach won't make mosquito bites a thing of the past - we're about malaria control, not mosquito control." Getting rid of all mosquitoes comes at a high price, he says. "Insecticides that kill indiscriminately impose maximal selection for mosquitoes that render those insecticides useless. Late-life acting insecticides would avoid that fate."

Citation: "How to make evolution-proof insecticides for malaria control."
Read AF, Lynch PA, Thomas MB (2009)
PLoS Biol 7(4): e1000058. doi:10.1371/journal.pbio.1000058

Source
Plos Biology