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Genetic Breakthrough in Malaria

Scientists map genome of parasite and mosquito that carries it

WEDNESDAY, Oct. 2, 2002 (HealthDayNews) -- In a breakthrough against one of the world's leading infectious killers, scientists have mapped the genetic blueprints of both the chief malaria parasite and the mosquito that most frequently shuttles it into people.

Knowing the genome of Plasmodium falciparum, one of four microbes that cause malaria, and Anopheles gambiae, the principal mosquito that transmits the microbe in Africa, could help doctors find better treatments and vaccines for the infection.

Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, which helped fund the research, calls the sequenced parasite and mosquito species "equal partners in this crime of ill health" that claims the lives of nearly 3 million people a year worldwide. A third of malaria's victims are young children and infants in Africa. Roughly half a billion people a year contract the infection, which causes high fevers, chills, headaches, coma and other symptoms.

"The numbers are staggering," says Robert Holt, of Celera Genomics and leader of the team that mapped the mosquito.

Scientists now have complete or virtually complete genetic portraits of all three players in the malaria triangle: the parasite that causes the disease, the mosquito that transmits it, and the human hosts they combine to kill.

Drugs can treat malaria, but the three most commonly used medicines are 50 to 2,000 years old. Resistance to these treatments is a growing problem. Researchers have also noted an alarming rise in insecticide-resistant mosquitoes.

As the latest research reveals, A. gambiae -- one of seven related malaria-bearing mosquitoes -- has some 14,000 genes. Humans, its principal source of blood meals, have upwards of 30,000.

Compared with the genetic makeup of fruit flies, from which they split 250 million years ago, the malaria mosquito has many more genes apparently devoted to immunity, likely reflecting its "intimate" relationships with parasites and its animal hosts, the researchers say. It also contains many genes that rev up during blood feeding.

Holt said a main focus of future research will be analyzing the genes that allow A. gambiae to elude pesticides. Another promising route involves studying genes that help mosquitoes recognize and react to odors in the environment and using that navigation system to kill the insects. It may also be possible to replace native mosquito populations with strains that are resistant to plasmodium parasites, though Holt says he doesn't advocate such an approach right now.

Frank Collins, a malaria expert at the University of Notre Dame who participated in the gene mapping, says scientists would also like to learn why A. gambiae has a unique lust for human blood.

A report on the mosquito gene-sequencing effort appears in an upcoming issue of Science.

In a separate paper, published in tomorrow's issue of Nature, an international team of scientists unveiled the genetic layout of the main malaria parasite. Plasmodium falciparum consists of about 5,300 genes, a bit shy of yeast, on 14 chromosomes. Many code for proteins that help it elude immune systems and survive in its hosts.

Malcolm J. Gardner of the Institute for Genomic Research, who led the parasite mapping effort -- which he called one of the most difficult yet attempted -- says 60 percent of the pathogen's proteins have no clear kin in other known organisms. "We don't really know as much about the parasite," says Gardner. However, the team did identify hundreds of potential protein targets for future vaccines.

Throughout its life, the parasite undergoes radical changes, each phase requiring different treatment strategies. Knowing the parasite's total array of genes and proteins should help defeat it, says Stephen Hoffman, of Sanaria, a research group that participated in the plasmodium sequencing project. "What we really want is new and better drugs and, most importantly, vaccines."

Dr. Regina Rabinovich, director of the Malaria Vaccine Initiative, says the genetic maps may one day benefit the search for immunizations against the infection -- but they won't necessarily speed the process. "There's probably a shorter line between genomic data and drugs than there is for vaccines," Rabinovich says.

The problem for immunologists fighting malaria hasn't been a shortage of targets, Rabinovich adds. Rather, the bottleneck has been coming up with proteins that effectively attack those targets, then testing them in the right groups of people. "The whole sequence of making a vaccine and testing it remains daunting," she says.

Dr. Lee Hall, who leads malaria vaccine development at the National Institute of Allergy and Infectious Diseases, was somewhat more optimistic. "I think the genome gives you the complete set of genes and products of those genes, which you can then start to look at from the perspective of: Are they viable?"

Scientists still must sift and sort through those proteins, Hall says, and coverting those molecules into an effective vaccine will be challenging. But "it's going to give us a lot more information we can work with."

The United States sees up to 2,000 cases of imported malaria each year, brought into this country by travelers to areas where the disease is endemic. However, health officials in Loudoun County, Va., where two teenagers developed the disease this summer, have captured mosquitoes carrying plasmodium parasites. The discovery marked the first time in 20 years that parasites in the United States have been linked to a human case of malaria, officials say.

What To Do

For more on the global threat of malaria, visit the World Health Organization or the Malaria Vaccine Initiative. Learn about how to avoid malaria while traveling to endemic areas from the U.S. Centers for Disease Control and Prevention.

SOURCES: Anthony Fauci, M.D., director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Stephen Hoffman, M.D., Ph.D., D.Sc., Sanaria, Gaithersburg, Md.; Malcolm J. Gardner, Ph.D., associate investigator, Institute for Genomic Research, Rockville, Md., Frank Collins, Ph.D., Department of Biological Sciences, University of Notre Dame, South Bend, Ind.; Robert Holt, Ph.D., Celera Genomics, Rockville, Md.; Regina Rabinovich, M.D., director, Malaria Vaccine Initiative, Washington, D.C.; Lee Hall, M.D., Ph.D., chief, malaria vaccine development section, National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Oct. 3, 2002, Nature; Oct. 4, 2002, Science
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