The malaria parasite is a wily organism, shifting its life stages as it flits from human to mosquito and back again. It still kills some 600,000 people each year and has outwitted eradication efforts, having developed resistance to previously popular drugs and, thus far, eluded vaccine-induced immunity.
The arrival of a powerful drug in the late-20th century gave researchers new hope. Called artemisinin and based on a traditional Chinese herbal remedy, it cleared the parasite faster and more thoroughly than any other current antimalarial. Researchers are still somewhat uncertain about exactly how it works, but they know that it targets the parasite as it infects red blood cells.
But the hope that artemisinin would serve as a final, exterminanting blow against malaria has begun to fade. Since 2008 patients in Southeast Asia have been slower to lose the malaria parasite Plasmodium falciparum than they once were. And this precursor to resistance seems to be spreading, despite efforts to carefully use artemisinin (by giving it in combination with other drugs) to avoid the emergence of resistance.
Researchers have been tracking that spread—and looking into the genetic basis of the trait—to try to develop more effective ways of keeping the disease in check. The findings, described in two related papers published online April 5 in Science and The Lancet, were called "a tour de force" by David Sullivan, an associate professor at Johns Hopkins Malaria Research Institute, who was not involved in the new research.
Loci of resistance
The confirmation of additional resistance will likely be a blow to malaria battlers. "Artemisinin-based compounds have really been the key to success in pushing back malaria in recent years," says Timothy Anderson, of the Texas Biomedical Research Institute and a co-author on both new studies. "But there's been a cloud on the horizon: patients in western Cambodia have been showing very, very slow parasite clearance." As a result, such patients have a greater chance of having the parasite return. They also provide a wider window for mosquitoes to bite them and then transmit their (more resistant) infection to other people.
For their Lancet study, Anderson and his colleagues (from the U.S. and Southeast Asia) studied the infections of 3,202 malaria patients on the western border of Thailand over the course of a decade. They found that the time it took the artemisinin-based combination therapy to clear the parasites steadily increased, from a mean of 2.6 hours in 2001 to 3.7 hours in 2010. They also found that the infections that persisted with a half-life of more than 6.2 hours jumped from 0.6 percent at the beginning of the study to 20 percent at the end.
These numbers might look small, but they are quickly creeping toward those figures already present in the resistance epicenter of western Cambodia, about 800 kilometers away, where the mean clearance time in 119 different patients was 5.5 hours, and 42 percent of the infections had a half-life of more than 6.2 hours. The researchers predict that the Thailand border area, which has used the artemisinin-based therapy since the mid-1990s, will see these levels of resistance within the next two to six years.
"Slow-clearing, resistant parasites are not restricted to western Cambodia as everyone had hoped," Anderson says. "Our approach to containment really has to be rethought."