Modified Mosquitoes May Be Anti-Malaria Allies

The enemy of our enemy may be our new partner in stopping a global health crisis.

With World Malaria Day (April 25) around the corner, new discoveries suggest our greatest allies in the fight against malaria may be the mosquitoes themselves.

Although saddled with a lousy public image, mosquitoes have immune systems that actually kill 80 to 90 percent of the malaria parasites that enter the insect's bodies, a new study says.

The discovery is part of an international effort to create a new generation of malaria treatments.

Genetically modified, malaria-fighting mosquitoes or even antibodies injected into humans and "fed" back to mosquitoes could someday be more effective at slowing the disease than today's simple mosquito nets, researchers say.

Triple Threat to Malaria

Malaria-parasite populations are lower when the parasites are inside mosquitoes, so some experts think it may be more effective to attack malaria inside the insects—before it enters human hosts.

Understanding how the mosquito immune system fends off malaria is an important part of bringing such a plan to fruition.

Now researchers say they've worked out the mechanism that drives one of the mosquitoes' defenses.

Three proteins in mosquito blood form a complex that "binds to a malaria parasite and punches holes through its membrane," destroying the layer that protects the parasite and holds all its important parts together, said Imperial College London biologist George Christophides, who co-authored the report, published in the April 10 issue of the journal Science.

Previously researchers had identified the three proteins and noticed that one of them seemed similar to microbe-killing proteins in other animals and in humansBut nobody had put the three together," Christophides said. "Now we can show that there's a pathway in effect."
How It Might Work

A mosquito-up approach to malaria control is feasible in the long term, researchers say. There are a couple of ways it could work.

In one scenario, scientists could create genetically modified mosquitoes, granting their immune systems pumped-up malaria-killing abilities.

The key would be to find a genetic drive mechanism—some factor that would give the new, malaria-fighting genes a selective advantage and help them spread quickly through wild mosquito populations via breeding, said Gregory Lanzaro, director of the Vector Genetics Lab at the University of California, Davis.

No one has figured this out for mosquitoes yet. But the U.S. Centers for Disease Control and Prevention is already testing a similar concept in blood-sucking assassin bugs as a way to stop the spread of deadly, difficult-to-cure Chagas disease, Lanzaro said.

The other option would be to develop antibodies that can fight the parasites' early, mosquito-dwelling forms—and "feed" the antibodies to the insects via human blood.

Mosquito immune systems don't produce antibodies on their own. And by the time the parasites reach humans, they have matured and found ways to hide out from human antibodies, said Marcelo Jacobs-Lorena, professor of molecular microbiology and immunology at the Johns Hopkins Malaria Research Institute in Baltimore.

But if we vaccinate humans with antibodies that target mosquito-stage malaria, those antibodies could be passed on to the mosquitoes when they feed on treated human blood, Jacobs-Lorena said.

Combined with a second, protective vaccine, this could be a real possibility, he said.

"There's a partially effective vaccine that protects humans that's being tested," Jacobs-Lorena said. "Neither it, nor the transmission-blocking vaccine would be 100 percent effective, but the combination may work."

No Quick Fix

Getting to these paradigm-shifting malaria prevention techniques isn't likely to be quick or easy.

The three-protein mechanism isn't the only factor involved in mosquitoes' malaria-fighting powers. And the new study might not provide the full picture.

The work was done using a model parasite—a version of malaria adapted to rodents, rather than humans—and laboratory mosquitoes, which are often genetically different from their wild cousins.

Studies done this way haven't always reflected what happens in nature, the University of California's Lanzaro said. Johns Hopkins's Jacobs-Lorena agreed.

"Research in recent years has shown that mosquitoes react differently to a parasite they aren't used to seeing, as opposed to the ones they've co-adapted with in the field," Jacobs-Lorena said.

The new discovery, he added, "is an important finding, but it must be validated with human parasites."