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Mosquito Isn't a Happy Host for Malaria, Tests Indicate
Many mosquitoes seem to kill naturally the malaria parasites they ingest, and it may be possible to exploit that genetic trait to fight malaria, according to a study being published today.
Researchers have long dreamed of inserting an antimalaria gene into mosquitoes, but this study suggests for the first time that this may be unnecessary because "most mosquitoes are malaria-resistant and the susceptible ones are the oddballs," said Dr. Kenneth D. Vernick, a microbiologist at the University of Minnesota and the lead author.
The study, appearing in the journal Science, is a "major step forward"
in understanding mosquito genetics, said Dr. Allan Schapira, a coordinator of the World Health Organization's malaria program. Dr. Dyann F. Wirth, chief of the malaria program at the Harvard School of Public Health, called it "a nice piece of work."
The discovery changes the terrain in the war on malaria, which kills more than a million people a year, most of them children and pregnant women. On this shifting battlefield, mutating parasites and mosquitoes eventually outwit each ingenious new drug or pesticide created to destroy them.
Natural resistance in mosquitoes to the malaria parasite, plasmodium falciparum, is good news for researchers because it is theoretically easier to bolster an existing gene than to implant one from another species. Also, the study found that the resistance centers on a small section of one chromosome, rather than on many diverse sites, making gene manipulation easier.
However, even if a better mosquito could
be created in a lab, the idea of releasing manipulated bugs into the wild to hunt human blood would be fraught with political perils. After lobbying by environmental groups, some African countries now refuse food aid containing genetically modified corn and are skeptical of genetically modified seeds that may confer drought resistance.
As an alternative, Dr. Vernick suggested that a soil fungus that devoured insects, whose mosquito-killing powers were described by British scientists last year, could be used to hunt down the most malaria-susceptible bugs in any swarm and knock them out of the gene pool.
Dr. Schapira called the idea "interesting," but he cautioned that years of testing would be needed to see if it was practical and safe.
The fungus, Beauveria bassiana, is harmless to humans and approved for use on aphids. It grows in insects that land on surfaces where it has been sprayed.
It has long been known that fewer
than 10 percent of any swarm of mosquitoes in the wild will transmit malaria. The conventional wisdom has been that this is just chance: a female must first bite a human unlucky enough to be infected already, then it takes about 14 days for the parasites to develop in her gut and migrate to her salivary glands, from which they exit into her next victim. Mosquitoes have short lives, and a female is usually infectious for only her last few days.
This study makes it clear that genetics play a part, too, and that mosquitoes are not just passive squirt guns for malaria parasites.
Plasmodium parasites do hurt mosquitoes, Dr. Vernick and Dr. Wirth said. They damage salivary tissue, make the mosquitoes fly less vigorously and lay fewer eggs and, to gain a toehold in the insect, may depress its immune system.
"The mosquito doesn't want to be infected, so it has responded with this very powerful mechanism," Dr. Vernick said, referring to what he
called the "resistance island" on the mosquito genome.
By a very different route, the fungus also weakens mosquitoes; they fly badly and bite less, and many die within 14 days. For unknown reasons, it weakens plasmodium-carrying mosquitoes more than it does others, Dr. Vernick said, so if a strain of the fungus just strong enough to kill off old, weak, malarial mosquitoes could be developed, it could "tip the balance," he said. It would suppress the malaria-susceptible mosquitoes without creating mutation pressure on all mosquitoes to evolve a fungus-resistant form, as DDT created pressure to evolve pesticide-resistant forms.
For the study, scientists from the University of Minnesota, the University of Bamako in Mali, the Fred Hutchinson Cancer Research Center in Seattle and Princeton University collected wild anopheles gambiae mosquitoes, the species most likely to spread malaria in Africa, in villages in Mali.
They let each produce a generation of offspring, then let them suck malaria-infected blood (drawn from a villager, but fed through a plastic membrane). A week later, they dissected them to see where the parasites grew. They were surprised to find that 22 percent had no parasites at all, and that many others had low numbers. Then they compared mosquito genomes and narrowed the search with a gene they named APL1. When they disabled it, they found that parasites grew well.
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