Most mosquitoes give malaria the boot

A University-headed team finds that malaria control measures may only have to target a few mosquitoes that are susceptible to the parasite

Microbiologist Kenneth Vernick led a team that discovered genes for resistance to the malaria parasite in mosquitoes.

By Deane Morrison

From M, fall 2006

For a long time, the mosquitoes that transmit malaria to humans were thought to be passive pipelines for the malaria parasite. Sure, most female Anopheles mosquitoes in the wild are uninfected with the parasite, but that was thought to be just because they hadn't encountered it.

Now a study led by the University's Kenneth Vernick shows that in fact most Anopheles mosquitoes are resistant to infection by the parasite and that the genes for resistance exist in a nest, or "island of resistance," on one chromosome.

The work suggests that malaria control measures could be designed to target only the susceptible minority of the mosquito population, avoiding ecologically riskier measures aimed at all mosquitoes. The research is published in the April 28, 2006, issue of Science.

Every year malaria kills an estimated 1 million people, mostly children and pregnant women, in tropical areas around the world. But its toll reaches beyond that.

"Besides the human cost, economists have found that malaria is a significant impediment to economic development in Africa," says Vernick, a microbiology professor in the Center for Microbial and Plant Genomics. People who get malaria may recover, but they develop only incomplete immunity and so may be sickened repeatedly, with death a possibility each time, he says.

The malarial parasite is a single-celled organism called Plasmodium. When transmitted by the bite of an Anopheles mosquito, it infects liver cells and then red blood cells. If an infected person is later bitten by a second mosquito, the parasite passes into the insect's gut and then its salivary glands, the launch pad for infection of a new human host.

Because the mosquitoes need blood to help their eggs develop, both resistant and susceptible females take the risk of a Plasmodium infection. Infected females are weakened by the parasite, which leaves them unable to fly as strongly or to lay as many eggs. This has exerted a strong evolutionary pressure for the mosquitoes to become resistant to it--so much so that resistance has become the norm.

"We think resistance is the majority state," says Vernick. "Susceptibility should be attributed to specific points of failure or loss of function in the mosquito immune system." According to the genetic analysis he and his colleagues performed, a mosquito's susceptibility to Plasmodium is caused by mutations in the genes for resistance.

Saddled with weakened immune systems, infected mosquitoes also may have less protection against other types of infection. One natural soil-dwelling fungus is known to kill Anopheles mosquitoes, particularly those infected with the Plasmodium parasite. The fungus does not infect people or other animals because it cannot grow at their body temperature. If that fungus could be safely applied, it could possibly eliminate a huge proportion of the malaria-susceptible mosquitoes while sparing the resistant ones. This would tip the balance away from susceptible mosquitoes, knocking them out of the breeding population and thus reducing future numbers of malaria carriers. Such a scenario would not require the introduction of new genes into the mosquito population, nor would it--unlike spraying a strong, general purpose insecticide--create a powerful evolutionary force driving the entire mosquito population to develop resistance.

Whatever control strategies are tested, there must be a way to tell whether they are cutting the numbers of potential malaria-carrying mosquitoes. With their discovery of resistance genes, the Vernick team has opened the door to creating an assay, or test, to distinguish resistant from susceptible mosquitoes and perform a census of their relative numbers.

"With a simple assay for resistance or susceptibility, we can see how the frequencies [proportions of resistant and susceptible mosquitoes in a population] change under different conditions and how they are affected by different possible control measures," says Vernick. He is now working to identify the exact genes that make mosquitoes either susceptible or resistant to malaria and to determine the differences in the gene sequences that make both versions of the gene or genes.

Authors with Vernick on the Science paper include Michelle Riehle, a postdoctoral associate at the Center for Microbial and Plant Genomics; researchers from the West African country of Mali, where Anopheles mosquitoes were collected for study; and a group of statistical geneticists at the Hutchinson Cancer Research Center and Princeton University.