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December 1, 2007

Drug Treatment for Malaria: Could Less Be More?

In a recent medical article appearing exclusively on TheDoctor, malaria expert Dr. Joel G. Breman states: "While mosquito control has eliminated it from the U.S. and Canada, malaria has survived and even made a comeback in many parts of the world. The main reasons for this are increasing drug resistance of the malaria parasite and increasing insecticide resistance of the mosquitoes that transmit the parasite to humans."

Now, a newly released study concludes that current drug treatments may be worsening this drug-resistance problem. It also suggests that more intelligent use of anti-malarial drugs could slow the spread of drug resistance without doing any harm to patients.

Most malaria is caused by a combination of different parasite strains, so that drug-resistant parasites often share their human hosts with other parasites that are susceptible to drugs. As each malarial infection progresses, these bugs are locked in competition for a limited amount of space — and blood cells — within the same human body.

In the absence of anti-malarial drugs, the presence of susceptible malaria parasites limits the proliferation of the drug-resistant ones. But when infections are treated with drugs, the dynamic changes.

"Drugs kill off the susceptible parasites, letting their competitors, the resistant ones, fill the vacant space and expand their numbers," says Andrew Read, professor of biology at Penn State, and an associate at the Center for Infectious Disease Dynamics.

Constantly occurring mutations regularly create new resistant parasite strains, but Read and his fellow researchers argue that the ways anti-malarial drugs are used could be accelerating the spread of such strains. Read and his team infected mice with malaria to see how the parasites respond to drug treatment. Their findings appeared online in the November 26, 2007 Proceedings of the National Academy of Sciences.

It turned out that once the drugs wiped out the susceptible parasites, the population of resistant bugs exploded. "Resistant parasites not only survive but do much better because the drugs have successfully removed their competitors," Read explained. "We suspect this is what is causing the short lifespan of many anti-malarial drugs," he added.

For instance, the usefulness of anti-malarial drugs such as chloroquine lasted for decades, while newer drugs such as pyrimethamine have lost their effectiveness in less than a decade.

On the bright side, these findings may offer a way to slow the spread of drug resistance.

"We should examine patterns of drug use that lead to stronger or less stronger selection for drug resistance," explains Read. "What you actually want is to use less drugs, after the point where you are still making people healthy." In other words, the ideal is to kill just enough susceptible malaria parasites to make a person healthy, but keep enough of them to compete with the resistant strain.

"The standard claim that one should take a very large dose designed to annihilate every single parasite in the body may not always be the best thing to do," he added.

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