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New Malaria Drug Shows Promise

Strips parasites' ability to colonize in monkeys

THURSDAY, Feb. 14, 2002 (HealthDayNews) -- A drug that blocks the ability of malaria parasites to colonize red blood cells may prove a novel way to treat the deadly infection.

An international team of scientists developing the compound, which they call G25, say it prevents the parasites from reproducing in infected monkey cells, killing them and sparing the animals' healthy tissue. The findings appear in tomorrow's issue of Science.

Malaria is caused by a cluster of parasites, most notably Plasmodium falciparum and P. vivax, which jump from person to person through the bite of carrier mosquitoes. Each year, between 300 million and 500 million people contract the illness, and 40 percent of the world's population lives in areas where the disease is endemic. More than a million people a year, most of them young children, die from the infection.

Malaria parasites pass through several life cycles in the course of an infection. They enter the body as spore-like organisms in the oral secretions of mosquitoes, and make their way to the liver. Once there, they multiply feverishly before taking to the bloodstream as merozoites with the mission of colonizing red blood cells, or erythrocytes.

G25 takes aim at the third (and most infectious) phase of plasmodium's growth, blocking it from turning blood cells into parasite factories. To reproduce itself in bulk, the organism must knit together scads of fatty outer membrane, much the way a house needs walls. However, G25 deprives the parasite of this protective shield by interfering with its access to a chemical in blood called choline.

The scientists, from France, Colombia and the Netherlands found G25 shielded cells in a dish from infection with two strains of malaria, P. falciparum and P. vivax. They then injected the drug into five rhesus monkeys infected with two forms of the parasites, and showed it completely cured the animals even at doses far below those used with existing malaria drugs. The compound was about 1,000-fold less toxic to uninfected cells.

Henri Vial, a biochemist at the Montpellier University in France and lead author of the study, says his group is now trying to develop an oral version of the drug. Not only would that be cheaper than a shot, it would be easier to administer in places like Africa, where malaria is endemic but the health infrastructure is typically thin. "We think in the next two years we may have this kind of compound," Vial says.

Vial says other tests show the drug can kill malaria parasites during their sexual reproduction phase, which occurs in the mosquito. More studies are needed to see if it is also effective at destroying the organisms in the liver.

The G25 project first received funding from the French government. Vial says his lab is now negotiating with a commercial partner to bring the drug to market.

The global push for a malaria vaccine has brought together governments, scientists and foundations. However, while various teams have reported successes, no inoculation against the killer disease has yet been approved. Even when a vaccine does arrive, experts say drugs will still be necessary.

"Drugs are a key component of a malaria control campaign, just like insecticides and bed nets," says Dr. N. Regina Rabinovich, director of the Malaria Vaccine Initiative.

The downside of drugs, she adds, is they're "hostage to the potential for the creation of resistance."

Indeed, resistance has crippled the effectiveness of the most common treatments for the infection, such as chloroquine and mefloquine, in many areas of the world.

What To Do

For more on the global threat of malaria, visit the World Health Organization or the Malaria Vaccine Initiative.

To find out more about malaria and how to avoid it while traveling to endemic areas, try the Centers for Disease Control and Prevention.

SOURCES: Interviews with Henri Vial, Ph.D., Montpellier University, France; N. Regina Rabinovich, M.D., director, Malaria Vaccine Initiative, PATH, Rockville, Md.; Feb. 15, 2002, Science
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