Researchers map genes of malaria parasite and the mosquito that spreads it

WASHINGTON (AP) _ Researchers have sequenced the genes both for the parasite that causes malaria and for the mosquito that spreads it to humans. <br><br>The double triumph gives medical science new weapons

Wednesday, October 2nd 2002, 12:00 am

By: News On 6

WASHINGTON (AP) _ Researchers have sequenced the genes both for the parasite that causes malaria and for the mosquito that spreads it to humans.

The double triumph gives medical science new weapons in the war on a disease that kills almost 3 million people a year.

In parallel efforts that involved more than 160 researchers in 10 countries, scientists mapped the genes for Plasmodium falciparum, the deadliest form of malaria, and for Anopheles gambiae, a mosquito that prefers human prey and spreads malaria to millions with its bloodsucking bite.

The British journal Nature is publishing the complete genetic sequence of P. falciparum, and the U.S. journal Science is publishing the mosquito gene sequence. The two publications jointly announced completion of the double-pronged research at news conferences on Wednesday in London and in Washington.

Researchers hope that gene mapping will reveal genetic vulnerabilities that can be exploited to control the mosquito that is essential to the parasite's deadly work. Already scientists have identified gene weaknesses that may be exploited to disrupt the life cycle of the malaria parasite. For the mosquito, researchers have found genes that may lead to better insecticides or repellents, and to a better understanding of why the insect prefers humans for its blood meal.

Completing the gene mapping of malaria and its vector comes at a critical time in international public health, officials said. Studies show malaria is becoming increasingly resistant to chloroquine, a drug that has helped hold the line on the disease for decades. At the same time, the mosquito has become tougher to control with current insecticides.

The advances also come in an era when some experts fear a warming climate will allow the resistant malaria parasite to move into areas where it has been rare or unknown for many years. Officials said that malaria, though of a different strain, was detected in both humans and mosquitoes in Virginia recently, the first time in two decades that a wild reservoir of malaria has been found in this country.

``We are hopeful that this wealth of information will translate into new drugs, vaccines and insecticides that will more effectively control malaria and, ultimately, lift a burden of suffering from millions,'' said Dr. Michael Gottlieb, a parasite expert at the National Institute of Allergy and Infectious Diseases, one of the National Institutes of Health.

``This is an extraordinary moment in the history of science,'' Dr. Carlos Morel, head of a World Health Organization group that supported the gene-mapping effort, said in a statement.

Worldwide, about 2.7 million people die annually of malaria, 90 percent of them in Africa. Most victims are under the age of five and world health experts estimate that a child dies of malaria somewhere on the planet every 30 seconds. The number of malaria victims is rising, according to some experts, as the result of the growing ineffectiveness of chloroquine.

The mosquito is a key part of the three-stage life cycle of the malaria parasite.

The female A. gambiae requires a blood meal to mature its eggs and the preferred source of that meal is humans. An infected mosquito spreads malaria by injecting saliva into a human bite as it sucks up blood equal to about four times its weight. The saliva contains the P. faliciparum protozoa. Once in the blood stream, the parasite flows to the liver where it multiplies, forming dense cysts filled with parasites. These cysts burst, flooding the blood stream with parasites which then enter red blood cells.

When another mosquito bites, the parasite flows into the new insect with the blood. The parasite reproduces and its young migrate to the mosquito salivary glands where the cycle begins anew.

Malaria causes chills and fever, with temperatures rising to 105 or higher. An acute attack may last two hours or more, and then may repeat again in 48 hours. The attack often includes headaches, muscle pain and vomiting, leaving patients weak and anemic from the destruction of red blood cells. Repeated attacks can cause death.

There are four types of malaria of malaria, all in the genus Plasmodium, but P. falciparum, the type that was genetically sequenced, is considered the deadliest and most common worldwide.

Using computer-driven techniques similar to way the human gene pattern was mapped, the two teams of researchers in separate labs broke up the malaria and mosquito DNA, sequenced small stretches and then reassembled the segments by matching overlaps.

In Nature, researchers say they identified about 5,300 genes distributed across the 24 million base pairs of DNA that make up the malaria parasite genome. In the mosquito, Science researchers found about 14,000 genes among 278 million base pairs of DNA.

Researchers say in the mosquito they have already found genes that are turned on or off by the insect's blood meal and are important in developing eggs. They also have found genes that may give the mosquito its ability to sense and find human victims.

``Those are the pathways that are likely to be useful in finding points of intervention for developing new insecticides or ... vaccines,'' said Robert A. Holt, a researcher at Celera Genomics Inc. in Rockville, Md. and the lead author of the Science study.

Dr. Neil Hall, who led a 50-member team at the Wellcome Trust Sanger Institute in the U.K., where much of the malaria genome was sequenced, called the work ``a major breakthrough in malaria research'' that, for the first time, gives scientists the genetic information to understand how the parasite works and to ``find the weak spots in its armor.''