Old Drug May Yield New Malaria Treatment

Amid mounting fears that resistance to the best available malaria drug combinations may spread from the Thai-Cambodian border, researchers say the effectiveness of the current combination therapy will likely wane in the coming years.

“For the moment, right now, we’re still OK,” Dr Steven Bjorge, a malaria researcher with the World Health Organization, said of the current drug regimen being used to combat the malaria parasite. But that is not likely to last, he said.

“There’s probably going to have to be a change in a year or two.”

Health workers started noticing the first signs of resistance to artemisinin combination therapy–presently the most powerful malaria treatment–two years ago along Cambodia’s western border with Thailand.

And while the two-drug combination can still rid a malaria patient of all parasites, the time it takes to do so has grown. Where ACT could cure just about any patient within three days, about 10 percent of patients along the Thai-Cambodian border now need up to five, sometimes more.

Dr Bjorge said the numbers still only suggest drug tolerance. But that is how outright resistance begins, as it has done at least twice with other front-line antimalarial medicines that have since lost their bite.

In both cases, resistance first showed up along the Thai-Cambodian border before spreading to the rest of Asia and moving on to Africa, where the disease has historically taken its greatest toll.

Health officials alike are trying to keep that from happening again. Malaria already claims nearly one million lives around the world each year.

“Preventing the export of artemisinin resistant strains from Cambodia is of vital importance to malaria endemic countries worldwide,” the government noted in a June 2009 report.

With $22.5 million from the Bill and Melinda Gates Foundation, Cambodia teamed up with the WHO a year ago to do just that. And despite signs of success with the two drugs used now, Dr Bjorge said, they hope to add a third.

“The fact that the two-drug combination still works suggests that if we add a third drug…we might be OK,” he said.

That drug is primoquine.

It is the only drug that kills the malaria parasite at the stage where it can infect mosquitoes and break the cycle of transmission between humans, according to Dr Bjorge.

While countries around the world, including Cambodia’s neighbors, have been using it for decades, the drug was banned here some 20 years ago because of its side effects. In patients with a particular genetic condition, primoquine can increase the risk of hemolysis, the premature breakup of red blood cells.

Cambodians are more likely to have the condition than most. According to Dr Chea Nguon, deputy director of Cambodia’s National Malaria Center, primoquine could pose such problems for more than a quarter of the population.

However, doctors still believe the drug could prove a viable option for Cambodia. They hope a three-month test run will prove them right. Dr Bjorge expects to secure approval from both the WHO and the Government of Cambodia within months.

On the government side, the plan must meet the approval of the National Ethics Committee. Dr Nguon, who sits on the committee, anticipates approval.

According to Dr Nguon, researchers want to find out if they can shorten the standard two-week treatment term for primoquine and keep the drug effective. The shorter the term, the easier it will be for patients to finish treatment. They will also be looking for a quick, easy and effective way to screen for hemolysis-prone patients.

“We want to know if we have to tool to test the people,” he said. “If we have the test I think we can approve [primoquine] for use.”

None of this is to say Cambodia is giving up on the current artemisinin combination therapy, though. Dr Nguon expects the Global Fund to sign off soon on a $9.4 million project that aims to crowd fake and expired versions out of the market by making the real things cheaper. He said patients should begin to see ACT prices fall by June.


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