Chloroquine Strikes Back

A malaria drug rendered useless in most of the world by drug-resistant parasites is once again effective in the African country of Malawi. In a study in tomorrow's issue of the New England Journal of Medicine, researchers report that chloroquine cured all but one of the 80 uncomplicated malaria cases it was used to treat in Blantyre, the country's commercial capital.

Chloroquine was once one of the miracle drugs against malaria. Cheap, easy to administer, and with few side effects, it played an important role in eradicating the disease in southern Europe and the southern United States. But extensive use came with a high price. In the 1970s and 1980s, resistance that had arisen in South America and Asia spread rapidly across Africa, soon rendering the drug all but useless.

Malawi was one of the first countries to officially change its malaria policy, discouraging use of chloroquine by 1993. Few thought the drug would ever be useful again, but a few years ago, molecular analyses suggested that the mutation that confers resistance had nearly disappeared in the country, and preliminary studies of adults with asymptomatic malaria seemed to show that the drug could clear the parasite. The new study, by malaria experts Miriam Laufer and Christopher Plowe of the University of Maryland School of Medicine in Baltimore and their colleagues, is the first test of the drug in children with acute infections--the patients who need effective drugs the most.

Researchers treated these children with either chloroquine or sulfadoxine-pyrimethamine, still the standard first-line drug in Malawi. Chloroquine was effective in 79 of 80 children who received it, requiring just 2.6 days on average to clear the blood of parasites. In contrast, sulfadoxine-pyrimethamine failed in 71 of 87 children who received it. (Those children were given backup treatment, and all eventually made full recoveries.)

The result does not mean that Malawi should go back to using chloroquine, Plowe stresses. "Malawi is a little island of sensitivity surrounded by a sea of resistance," he says. "Resistance would come washing back in" if the drug were widely used. Instead, he says, Malawi should follow the world standard and switch to the newest--and more expensive--artemisinin-based combination therapies, to which resistance hasn't yet developed. But knowing that chloroquine can regain its usefulness if it is taken out of circulation gives researchers hope that the same might be true for other resistance-plagued drug regimes.

The result "is another argument for getting chloroquine out of Africa," says malaria geneticist Thomas Wellems of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. The best way to do that, says Plowe, is to make the newest artemisinin-based combination therapies available widely and at an affordable price.

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