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GLOBAL HEALTH | July 30, 2009

No Longer Irresistible

A critical weapon in the fight against Malaria is growing less effective, study says.

KRISTI EATON

“Artemisinin should clear the parasites at an early stage, preventing further maturing and reproducing. When the drug’s action is impaired, it becomes more difficult to eliminate the parasites from the body.”
Poor regulations and substandard use could be to blame for growing resistance to a leading anti-malaria drug, researchers say. A study published in the New England Journal of Medicine says malaria parasites, which are injected into the bloodstream by infected mosquitoes, are growing more resistant to artemisinin, the leading drug used to fight the disease. The increasing resistance to the drug threatens to render it less effective and could eventually make it obsolete, putting millions of lives at risk. Malaria kills more than 1 million people a year, many of whom are young children or pregnant women.
 
Researchers studied 40 patients in Pailin, western Cambodia, and 40 patients in Wang Pha, north-western Thailand following reports that the efficacy of artemisinin, single drug therapies, and combination therapies were declining in western Cambodia,
 
In randomized trials, the patients were given a dosage of artesunate, an artemisinin drug, another anti-malarial drug, mefloquine, or a combination of the two.
On average, patients in Thailand were clear of parasites in 48 hours; in western Cambodia it took 84 hours. Of the 20 patients in each country treated with only one of the drugs, there were recurrences of the infection in six patients in western Cambodia, compared to just one person in Thailand. A recurrence occurred in two patients from Cambodia who used combination therapy and one patient from Thailand. This suggests, the scientists say, that artemisinin was less effective on the Cambodian parasites.

“Our study suggests that malaria parasites in Cambodia are less susceptible to artemisinin than those in Thailand,” says Arjen Dondorp, the lead author of the study. “This means that it takes longer to kill the parasites. Artemisinin should clear the parasites at an early stage, preventing further maturing and reproducing. When the drug’s action is impaired, it becomes more difficult to eliminate the parasites from the body.”

As fears about possible resistance to artemisinin grow, the World Health Organization has begun recommending patients take artemisinin-based combination therapies, although that might not even be enough.

Cambodia was one of the first countries to switch to artemisinin-based combination treatments in 2001, the researchers note. However, the majority of patients in the region receive their medication from the private sector, which is less well regulated. Also, patients in the private sector are often provided with single therapy treatments or incomplete treatment courses. These factors, as well as the use of counterfeit drugs, may have contributed to the emergence of resistance, the researchers say.

“With artesunate losing its potency, artemisinin-based combination therapies rely much more on the weaker partner drug, increasing the risk that resistance also evolves towards the partner drug,” Dondorp says. “This has very important consequences for the lifespan of artemisinin-based combination therapies. Losing artemisinin-based combination therapies would be a disaster for malaria control."

He says it’s imperative action is taken to combat the resistance and argues for a ban on atesunate monotherapy in most cases because of the crucial role combination therapies play in preventing the spread of resistant parasites.

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