The Why Files The Why Files -- whyfiles.org

Mosquitoes maul malaria
27 APRIL 2006

Mosquitoes transmit malaria, but a study published this week shows that many mosquitoes kill malaria parasites instead of spreading the disease. One week after these mosquitoes drank blood laced with the parasites, the parasites were absent.

Map of Africa with country just south of the Sahara highlighted.The study could explain one oddity of malaria: Why it may require many mosquito bites to cause infection. More important, it might suggest a change in tactics in the war against one of the globe's worst diseases.

Malaria infects more people than any other major disease. This research was conducted in Mali. Revised from original USAID map.

In the conventional view, malaria parasites are villains, humans are victims, and mosquitoes are innocent vectors (carriers). But it may be more accurate to view mosquitoes as fellow victims, says Kenneth Vernick, an associate professor of microbiology at the University of Minnesota, St. Paul.

Lab workers dressed in flowing African robes site at microscopes, cutting open mosquitoes. Globally, malaria infects half a billion people, kills an estimated 1 to 3 million annually, and is a huge social and economic parasite in countries already short of money and resources. In "some countries with a heavy malaria burden, the disease may account for as much as 40 percent of public health expenditure, 30 to 50 percent of inpatient admissions, and up to 50 percent of outpatient visits," says the World Health Organization.

One week after mosquitoes drank infected blood, researchers at the University of Bamako counted new malaria parasites. Oumou Niare (front) and Sekou Traore, were two authors of the Science paper. Courtesy Kenneth Vernick

Neutralizing the parasite
In collaboration with the Malaria Research and Training Center at the University of Bamako, Mali (West Africa), Vernick's research group collected mosquitoes, then hatched eggs from each one to create a "lineage" of related offspring. These offspring got a blood meal from a villager who carried the malaria parasite. Such people are easily found, since malaria is epidemic in West Africa.

Seven or eight days later, the researchers cut the insects apart to search for Plasmodium falciparum, the primary malaria parasite. Twenty two of 101 lineages did not carry the deadly parasite. Because the insect cannot transmit malaria until the parasite develops and reaches its salivary glands, they were inert, Vernick says. "There is nothing infectious in the salivary gland, and that means they are not involved in malaria transmission," even though they fed on blood that contained infectious forms of malaria.

Graphic shows how parasite infects human body, starting with a mosquito bite
Much of the malaria parasite's complicated life cycle occurs inside the mosquito. Feeding these parasites costs the insect in terms of energy. Did that create an evolutionary force for disease resistance in mosquitoes? Diagram: CDC

Such resistance may have evolved because the mosquito must expend energy for the parasite as goes through its developmental transformations, Vernick explained. And the need to power the parasite creates evolutionary pressure for the insects to kill the parasites instead, he adds, because mosquitoes without malaria will have more offspring.

Mosquitoes are not flying hypodermic syringes.Mosquitoes, Vernick says, "are not passive, flying hypodermic syringes." Instead, they are caught in an evolutionary tug-of-war with a tenacious parasite.

Because some mosquito lineages showed both susceptibility and resistance, the researchers could identify the location of the resistance genes, which appeared to reside on a genetic "island of resistance." Vernick and his colleagues did not learn exactly how the resistance island kills the parasites, but the genetic location did include some "leucine-rich repeat" genes. That was riveting, Vernick says, because these genes apparently make surveillance proteins that notify an organism if parasites or pathogens are present.

These genes are common, Vernick says. "These are a motif that has been replayed evolutionarily as an important host defense -- an anti-pathogen factor -- from plants to vertebrates. It's reasonably likely that we have placed the invertebrate response to pathogens in a context that does tie together eukaryotes as different as plants and mammals, with a common mechanism" for protecting against pathogens. (Eukaryotes, organisms with a nucleus inside their cells, includes virtually all life forms except bacteria.)

Mosquitoes crawl inside white netting, feasting on blood in a jar.
Mosquitoes feed on a membrane containing blood from people in Mali who carried the malaria parasite, Plasmodium falciparum. One week later, these mosquitoes are dissected to determine if they were infected with malaria. Courtesy Kenneth Vernick

Down the line: Malaria control?
The study could also foster a futuristic public-health strategy, Vernick said. For years, researchers have wanted to enlist mosquitoes in the battle against the deadly blood parasite. The discovery that some mosquitoes naturally resist Plasmodium falciparum could transform that goal into one less daunting: Could we just increase the proportion of whiners that naturally resist malaria, thus reducing the odds of infection from each mosquito bite?

Perhaps. New studies indicate that a fungus that is already approved for killing African locusts may also kill some malarial mosquitoes -- but only those that are susceptible to malaria. With luck and a lot more research, Vernick says, the fungus may eventually help shift the mosquito population toward insects that kill the malaria instead of spreading it.

Mosquitoes -- and billions of humans living in malarial regions -- could benefit.
-- David Tenenbaum

Bibliography
• Natural Malaria Infection in Anopheles gambiae Is Regulated by a Single Genomic Control Region, M.M. Riehle et al, Science, 28 April 2006.

Related Why Files
Mosquito
Malaria
Fast Evolution
Infection Dissection


©2008, University of Wisconsin, Board of Regents.