The malaria fighters' nightmare has appeared in western Cambodia: parasites with resistance to the world's most effective drugs. The new find is a blow to hopes that humanity might eliminate the disease in the coming decades. It also highlights, say researchers, the urgent need for beefed-up malaria control along the Thai-Cambodian border and more action worldwide against misuse of malaria drugs.
Artemisinin, derived from the wormwood plant, is a key tool in the global fight against malaria. It kills malaria parasites especially quickly, which gives them fewer chances to develop resistance. As a bulwark against resistance, doctors combine artemisinin-based drugs with a second drug, such as mefloquine, so that any parasites that escape one treatment are killed by the other.
In Cambodia, however, use of artemisinin-based drugs without the backup of a second drug is widespread. Many people rely on local drug merchants who sell pills one at a time--many of them counterfeit, says Duong Socheat of the National Center for Parasitology, Entomology and Malaria Control in Phnom Penh. The incomplete treatment is the perfect recipe for the development of resistant strains, he says.
Scattered case reports of artemisinin-resistant malaria started to appear in the region over the past decade, and researchers have been watching carefully for signs that resistant strains might be taking hold. Socheat, with Arjen Dondorp of Mahidol University in Bangkok and other colleagues, took a closer look at the situation. They studied 40 malaria patients in Pailin in western Cambodia and compared them with 40 patients in Wang Pha in northwestern Thailand, a region where artemisinin-based therapies are known to be effective.
In a paper that will be published tomorrow in The New England Journal of Medicine, the team reports that it took much longer for drugs to clear parasites from the patients' blood in Pailin--a median time of 84 hours compared with 48 hours in Wang Pha. Because quick clearance is the hallmark of the artemisinins, "it is a very worrying situation," Dondorp says. Although the one-two punch of the combination therapy can still cure patients, allowing the parasites to survive an extra day or two leaves the therapy "very vulnerable for further development of resistance," he says, which could lead to even more dangerous strains.
Another paper in the same issue adds to the evidence for resistance: Socheat, Harald Noedl of the Medical University of Vienna, and Wichai Satimai of the Ministry of Public Health in Nonthaburi, Thailand, report that in lab tests, parasites from patients in Cambodia and eastern Thailand are less susceptible to artemisinin than are parasites from patients in western Thailand and Bangladesh.
Carlos Campbell of the Program for Appropriate Technology in Health in Seattle, Washington, who was not involved in either study, says in an accompanying commentary that the results leave no question that there is artemisinin resistance in western Cambodia. The World Health Organization has already started an intense campaign in the region to contain the emerging threat by for the first time intensively treating all malaria cases in the region and trying to eliminate the use of artemisinin-based monotherapies. Even if this campaign succeeds, Noedl says it is only a matter of time until resistance develops elsewhere. "It happened once and it can happen again," he says.