To beat malaria, don’t rely on one drug

For the first two weeks of my trip, the Jungle Formula successfully kept the mosquitoes at bay. But by the third week, a significant population of mosquitoes had moved in to my room. And by the fourth week, they would routinely fly over and sit on my killer unit, resting for hours at a time on top of the Jungle Formula bottle, as if to say, “Is this all you’ve got?”

Though the mosquitoes’ defeat of my Jungle Formula was a problem, the much more serious issue is the resistance of the malaria parasites they carry.

These protozoan parasites are notorious throughout the medical and pharmaceutical world for their speedy ability to acquire resistance to anti-malaria drugs. Chloroquine, once the treatment of choice for patients with malaria, has been rendered almost obsolete as malarial resistance to the drug spread from South Asia to Africa.

Today, we rely very heavily on a drug called artemisinin. But, because it has been the most effective and popular anti-malaria drug for several years now, many scientists have become increasingly anxious about how much longer the medication will remain effective before malarial parasites develop resistance.

A team of researchers has suggested a possible solution to this problem: Give malaria patients different treatments instead of relying on only one. Differential treatment, as this approach is called, is often not a popular strategy, however.

Patients may wonder why they’re not receiving the same medicine as their friends and whether they’re receiving inferior treatment, and when faced with multiple possible treatments, most people demand the best one.

But the best treatment for everyone might be having a different one from your neighbors, according to a report by a group of University researchers, led by former postdoctoral fellow Maciej Boni ’99, now a staff member at the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam.

“It’s better to give different people different drugs to help slow down the spread of resistance,” Boni said. “The more exposure parasites have to a single drug the faster they can adapt to it and become resistant.”

In its recent article in the Proceedings of the National Academy of Sciences, the research team recommended the adoption of multiple first-line therapies (MFT) to combat malaria.

The MFT approach, which consists primarily of prescribing different treatments to different patients, could dramatically reduce the risk of treatment failure or resistance development in the parasites, the scientists said.

“If you’re dealing with heart disease, you certainly want to give everyone the cheapest drug that is effective,” said Ramanan Laxminarayan, a member of the research team and visiting research scholar at the Princeton Environmental Institute. “With malaria, if you give everyone the cheapest drug or the best drug, then the drugs quickly lose their effectiveness.”

The strategy of throwing as many drugs as possible at a single disease has met with some success in the past. AIDS, for instance, is now treated with a variety of “cocktail” therapies, combination treatments consisting of multiple drugs.

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These cocktails have been crucial in preventing HIV from developing resistance to any single treatment and have helped dramatically increase the life expectancy of AIDS patients.

Some countries do use artemisinin combination therapies to delay parasite resistance, Boni said, but a successful implementation of MFT would require the development of at least a second and third effective anti-malaria drug — a feat Boni said scientists are “not close” to achieving.

“We have a few cocktails that are available or in the pipeline, but they all rely on artemisinin in combination with other things,” Laxminarayan explained. “There’s a real chance that resistance could arise to these combinations because of that, and if we lose artemisinin then we really don’t have an effective first-line drug to treat malaria.”

If the parasites develop that resistance before a new drug is found, he added, the consequences could be devastating.

“In the ’90s malaria deaths went up dramatically while we were looking for a new drug,” he said. “The increase in deaths practically outnumbered the lives that had been saved by the old drugs.”

Recently, malaria research has received more funding and attention than it has in the past, thanks especially to the efforts of the Bill and Melinda Gates Foundation, which funds the University team’s research.

“This is an exciting time for people working with malaria,” Laxminarayan said. “We’ve made a lot of progress,” he explained, adding that eliminating malaria by 2015 may be possible.

Historically, though, mosquitoes and malaria parasites have been one step ahead.

Every treatment to date has been beaten back by either the mosquitoes or the protozoa, dating back to the ’50s when the World Health Organization launched a malaria eradication initiative that relied on killing the parasites’ mosquito vectors with the now-infamous chemical DDT.

Though that worked for a little while, just like my Jungle Formula, the mosquitoes became resistant.

The current state of malaria treatment is perhaps best described by the Red Queen evolutionary hypothesis, so named for the character in Lewis Carroll’s “Through the Looking Glass” who advised Alice that, “It takes all the running you can do, to keep in the same place.”

Right now, it’s taking all the drug development work that researchers can do just to keep from slipping further behind.