Drug-Resistant Malaria Spreading Through Southeast Asia

A new study confirms that drug-resistant malaria parasites have spread to critical border regions of Southeast Asia, seriously threatening global malaria control and elimination programs.

Researchers at the Mahidol Oxford Tropical Medicine Research Unit (MORU; United Kingdom) and the Tracking Resistance to Artemisinin Collaboration (TRAC) enrolled 1,241 adults and children with acute, uncomplicated P. falciparum malaria at 15 sites in 10 countries (7 in Asia and 3 in Africa). The patients received artesunate, administered orally for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts were measured every 6 hours to determine clearance half-lives.

The results showed that the median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo, to seven hours at the Thailand-Cambodia border. Slowly clearing infections, i.e., parasite clearance half-life of over five hours, were found in mainland Southeast Asia, from southern Vietnam to central Myanmar. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy cure rate was reduced to 97.7%. The study was published on July 31, 2014, in the New England Journal of Medicine (NEJM).

“The artemisinin drugs are arguably the best antimalarials we have ever had. But we need to be vigilant as cure rates have fallen in areas where artemisinin resistance is established,” said lead author Elizabeth Ashley, PhD, of MORU, and chief investigator at TRAC. “Action is needed to prevent the spread of resistance from Myanmar into neighboring Bangladesh and India.”
“It may still be possible to prevent the spread of artemisinin-resistant malaria parasites across Asia and then to Africa by eliminating them, but that window of opportunity is closing fast,” said senior author Prof. Nicholas White, MD, chairman of MORU and chair of the Worldwide Antimalarial Resistance Network (WWARN). “Conventional malaria control approaches won’t be enough: we will need to take more radical action and make this a global public health priority, without delay.”

In the 1990s, resistance to antimalarial drugs such as chloroquine and sulfadoxine–pyrimethamine worsened across areas of the world where malaria is endemic. As a direct consequence, morbidity and mortality associated with malaria increased, especially among African children. The artemisinin-based combination therapies were introduced in the mid-1990s, when there was an imminent prospect of untreatable malaria in Southeast Asia, where resistance to all available antimalarial drugs had developed.

Artemisinin derivatives are highly potent, clearing parasitemia more rapidly than all other currently available antimalarial agents. But the prospects for the elimination of malaria are now threatened by the emergence of artemisinin resistance in Plasmodium falciparum, linked with point mutations in the “propeller” region of a P. falciparum kelch protein.

Related Links:

Mahidol Oxford Tropical Medicine Research Unit
Tracking Resistance to Artemisinin Collaboration
Worldwide Antimalarial Resistance Network