By Deborah Gilbert
News and Information Services
A U-M researcher studying artemisinin, an ancient Chinese fever remedy now recognized as an effective anti-malarial drug, has discovered the biochemical mechanism that makes it work. The drug turns the malaria parasite’s food into poison.
Steven R. Meshnick, a parasitologist at the School of Public Health, also reports that in his clinical study of the drug, artemisinin eliminated virtually all malaria parasites within 24 hours. Better yet, it did so without significant side effects.
His clinical study, which included 638 malarial patients in Vietnam, confirmed other studies of the efficacy of the drug.
According to Meshnick, who also is a biochemist, the malaria parasite survives in the host by consuming approximately 25 percent of the hemoglobin in the host’s red blood cells.
“However,” he explains, “it does not metabolize the heme—the iron—in the hemoglobin. Instead, it stores the iron, in the form of a polymer called hemozoin, inside a food vacuole.
“We discovered that when artemisinin comes into contact with the iron in the hemozoin, the iron converts the drug into a toxic chemical, releasing a free radical that destroys the parasite.”
It is a significant addition to the anti-malarial arsenal, he added, because “malaria is not resistant to artemisinin, even though it has been widely prescribed by physicians in China and Southeast Asia to treat malaria for the past 20 years, and was first used by the Chinese for fevers some 1,500 years ago.”
Malaria has become resistant in recent years to nearly all other anti-malarial drugs—chloroquine, quinine, mefloquine and Fansidar. Malaria currently afflicts an estimated 270 million people worldwide and kills 2 million people a year. About 80 percent of the world’s malaria cases now occur in Africa.
Artemisinin is derived from the leaves of “Artemisia annua,” a prolific tropical weed that can grow to 10 feet in six months.
In his clinical study in Vietnam, Meshnick found that artemisinin derivatives administered in capsules or tablets destroyed 98 percent of the parasite within 24 hours, without significant side effects.
“The parasite appeared again in only 10 percent to 23 percent of the group that took the drug for five to 10 days. It may well be, too, that the re-appearance of the disease was due to a new infection rather than a flare-up of the prior one,” Meshnick said.
“We also found that those who followed a regimen of artemisinin for three days followed by five days of the antibiotic tetracycline recovered well. Malaria re-appeared in only 9.5 percent of that group,” he adds.
The drug was equally effective with both the falciparum and vivax strains of malaria. “The vivax strain hides in the liver and can recur over the years, but it is not fatal. Artemisinin cures the symptoms of vivax and allows patients to lead normal lives.
“The falciparum strain, on the other hand, lives in blood cells and leads to coma and death. But it can be cured by artemisinin,” Meshnick explains. “Almost all of African malaria is falciparum.”
Seventeen nations now have licensed artemisinin derivatives, most within the past year, and more than one million people have been treated with the drug. It is not yet licensed in the United States.
“The beauty of the drug is that it is very easy to cultivate ‘Artemisinin annua’ and relatively simple to extract the drug, so it could be an economic as well as a medical boon to underdeveloped countries,” Meshnick adds.
Meshnick’s biochemical findings are reported in the May 1993 issue of Antimicrobial Agents and Chemotherapy. His clinical findings appeared in the March 1993 issue of the American Journal of Tropical Medicine and Hygiene.
