Study: Malaria Drugs Are Failing At An 'Alarming' Rate In Southeast Asia

Jul 22, 2019
Originally published on July 23, 2019 7:42 am

Malaria drugs are failing at an "alarming" rate in Southeast Asia as drug-resistant strains of the malaria parasite emerge.

That's the conclusion of researchers in two new reports — one based on a randomized trial and the other on a genetic study — that have just been released in the medical journal The Lancet. And there's concern that this drug resistance could spread around the globe.

Global health officials get nervous when new strains of drug-resistant malaria turn up in Southeast Asia, because it's a dreaded pattern that they've seen before.

Resistance that has hatched in this region has doomed previous malaria medications since the middle of the 20thcentury.

"Somehow antimalarial drug resistance always starts in that part of the world," says Arjen Dondorp, who leads malaria research at the Mahidol Oxford Tropical Medicine Research Unit in Bangkok and who was a lead author of the report about the randomized trial.

"In the past, chloroquine resistance originated there. Sulfadoxine-pyrimethamine, the next generation of antimalarials — resistance to that originated there. And now the artemisinin resistance also was first detected in western Cambodia."

And it's hard to underscore the significance of this. In modern times, the death spiral for malaria drug after malaria drug has begun in the Mekong Delta. The reasons for this are complicated. Some scientists say that one reason could have something to do with the relatively low levels of malaria there. When resistant parasites emerge, they are not competing against a dominant nonresistant strain of malaria and are possibly able to spread easier.

Currently, the World Health Organization recommends treating the majority of malaria cases with artemisinin-based combination therapies, or ACTs. These are usually single pills that combine fast-acting artemisinin with another longer-acting antimalarial drug. Currently one of the most widely used ACTs globally is dihydroartemisinin-piperaquine. And this is the artemisinin combo that Dondorp found to be failing in Southeast Asia.

These drugs have been highly effective at treating malaria, one of the world's most burdensome diseases. According to the World Health Organization, each year there are more than 200 million cases of malaria and 400,000 people die from the disease. Those deaths are primarily among children in Africa.

The two-drug artemisinin combos continue to be the first-line drugs for treating most malaria cases around the world, including in Africa. And they have been credited with helping to bring global malaria deaths down to an all-time low. But now it looks like their future effectiveness is in question.

Dondorp, in the midst of a study in the greater Mekong region, was comparing a new three-drug malaria regimen against the conventional two-drug artemisinin combo. And it was in the middle of that study that he and his colleagues saw that the current antimalarial drugs weren't fully wiping out the potentially deadly parasites.

"We noticed incredible high failure rates with the first-line treatment, and that was the reason to publish this first before we can publish the results of the efficacy of the triple combinations," he says. Basically, the current drugs were performing so badly that the researchers felt it imperative to sound the alarm about what was the control side of the study.

The overall failure rate was 50%. But in some parts of the region, the drugs weren't working nine times out of 10.

Dondorp says the resistance was even worse than they'd expected.

"We knew already [resistance] was in Cambodia and it had increased dramatically over the years," he says. "What was new was that it was also present in northeastern Thailand and southern Vietnam."

Health officials in Cambodia were aware that the drugs were failing and had switched back to an older medicine in 2014. Now Vietnam and Thailand are also moving away from the World Health Organization's recommended first-line malaria treatment.

So far this drug resistance has been mainly found in the areas around the Mekong Delta, but there's no reason these parasites couldn't spread to India or other parts of Asia or even Africa.

That has been the case with every other first-line malaria drug. If a person who was infected with chloroquine-resistant parasites, say in Cambodia, traveled to India and got bitten by mosquitoes there, the resistant parasites could start spreading in India. Then someone else in India could carry the parasites to Kenya. Soon, the chloroquine-resistant malaria bugs would have gone global.

And if that happens with the latest line of artemisinin combination treatments, it could be a major setback to global efforts to control the mosquito-borne disease.

"It is really worrying," says Shunmay Yeung, an associate professor at the London School of Hygiene & Tropical Medicine. Yeung studies malaria and malaria drug resistance, though she wasn't involved in these new studies in The Lancet. She says there has been incredible progress against malaria over the past 15 years. "We've halved the number of deaths due to malaria globally," she says.

And artemisinin-based antimalarials, along with increased distribution of mosquito bed nets, have been a major force in achieving that. They are "wonderfully effective drugs," she says.

"It's three days of treatment and you're better." They work quickly. They have few side effects. "To lose these first-line drugs, the artemisinin combination therapies, would be disastrous," Yeung says. "If this [resistance] emerged or spread to Africa, it would be a disaster."

Globally the majority of malaria cases occur in Africa.

So far, however, the mutant malaria parasites that have built up a resistance to artemisinin-based drugs haven't taken hold on the continent.

But if the histories of other antimalarial drugs are any guide to the future, they eventually will.

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STEVE INSKEEP, HOST:

Malaria drugs are failing at an alarming rate. It's happening in Southeast Asia, where drug-resistant strains of malaria emerge. Researchers have published two new reports in the medical journal The Lancet. So what if this drug resistance spreads?

NPR's Jason Beaubien reports.

JASON BEAUBIEN, BYLINE: Global health officials get nervous when they see new strains of drug-resistant malaria developing in Southeast Asia because it's a dreaded pattern that they've seen before.

ARJEN DONDORP: Somehow antimalarial drug resistance always starts in that part of the world, especially western Cambodia is notorious.

BEAUBIEN: Arjen Dondorp leads malaria research at the Mahidol Oxford Tropical Medicine Research Unit in Bangkok.

DONDORP: In the past, chloroquine resistance originated there. Sulfadoxine-pyrimethamine, the next generation of very good antimalarial - resistance to that originated there.

BEAUBIEN: And now resistance to artemisinin-based drugs has erupted there. These are the drugs that are currently the World Health Organization's recommended treatment for the majority of malaria cases. These drugs have been credited with helping to bring global malaria deaths down to an all-time low. But now malaria parasites are becoming immune to them.

Dondorp was in the midst of a study comparing the conventional, first-line artemisinin drugs in the greater Mekong region to a new generation of antimalarials. And it was in the middle of that study that he and his colleagues saw the dramatic rise in drug resistance.

DONDORP: We noticed incredible high failure rates with the first-line treatment.

BEAUBIEN: The overall failure rate was 50%. But in some places, the drugs weren't working nine times out of 10. Dondorp says the resistance was even worse than they'd expected.

DONDORP: We knew already it was in Cambodia, but it had increased dramatically over the years. And what was new, that it was also present in northeastern Thailand and southern Vietnam.

BEAUBIEN: Health officials in Cambodia were aware that the drugs were failing and had switched back to an older medicine. Now Vietnam and Thailand are also moving away from the WHO's recommended first-line malaria treatment. Shunmay Yeung is an associate professor at the London School of Hygiene and Tropical Medicine who studies malaria and malaria drug resistance.

SHUNMAY YEUNG: It is really worrying. I mean, there's been massive success, really. In the last 15 years, we've halved the number of deaths due to malaria globally.

BEAUBIEN: That's also due to an increased use of bed nets and other efforts. But Yeung stresses that the artemisinin-based antimalarials have been, in her words, wonderfully effective drugs.

YEUNG: You know, three days' treatment and you're better. So they're really great drugs. So it's really worrying. If this emerged or spread to Africa, it would be a disaster.

BEAUBIEN: That's because the majority of malaria cases globally are in Africa. So far, the drug-resistant mutations haven't turned up in Africa, but the fear is that they could. Yeung says there are new antimalarials in the development pipeline. But if drug resistance spreads quickly, patients would have to rely, at least temporarily, on older, potentially less effective medicines. And that could be a major setback to global progress against the disease.

Jason Beaubien, NPR News.

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