Parasitic Evolution in Southeast Asia Leads to Growth of MDR Malaria

Public health officials in Southeast Asia are warning that the rapid evolution of drug-resistant parasites is rendering standard first-line malaria treatments ineffective there, and investigators warn the problem could soon spread to other parts of the globe.

The warnings come in the form of 2 studies, both of which were published in The Lancet Infectious Diseases.

The first study tracked a multidrug-resistant co-lineage of Plasmodium falciparum malaria that ravaged Cambodia between 2008 and 2013. Scientists used more than 1600 whole genome sequences to track the growth of the co-lineage, dubbed KEL1/PLA1, over time. Public health officials had seen that the first-line treatment combination of dihydroartemisinin and piperaquine (DHA-PPQ) had been effective against malaria until 2008, but its effectiveness began to decline over the subsequent years.

Mallika Imwong, PhD, a professor of tropical medicine at Mahidol University, in Thailand, reported that the drop in effectiveness of DHA-PPQ coincided with a spread of KEL1/PLA1. Although KEL1/PLA1 was found only in the western part of Cambodia in 2009, it quickly spread throughout Cambodia and its neighbors Vietnam, Laos, and Thailand.

“[B]y 2016—17 its prevalence had risen to higher than 50% in all of the surveyed countries except for Laos,” Imwong and colleagues wrote. “In northeastern Thailand and Vietnam, KEL1/PLA1 exceeded 80% of the most recent P falciparum parasites.”

In a press release, Imwong said public health officials need to continue to track KEL1/PLA1, as it is likely to spread and render well-established treatments ineffective in countries beyond southeast Asia.

“To stay 1 step ahead, continued surveillance, including genetic surveillance, is needed to map the spread of resistance in real time, so other countries can act quickly and switch drugs if needed,” Imwong said.

The second study helps to underscore why the spread of KEL1/PLA1 parasites is such a problem. Researchers evaluating the safety and efficacy of triple artemisinin combination therapies reported data they had tracked in relation to DHA-PPQ efficacy in the greater Mekong River basin.

Between September 2015 and January 2018, a total of 140 patients enrolled in the study received DHA-PPQ therapy as treatment for malaria. Overall, they found that DHA-PPQ therapy was effective just 50% of the time. The investigators stated bluntly that DHA-PPQ is “not treating malaria effectively” in the region and said it’s an urgent public health matter to eliminate P falciparum malaria.

In the press release, investigator Olivo Miotto, PhD, of the Wellcome Sanger Institute and the University of Oxford, said the findings are “worrying,” and not just for people in Southeast Asia.

“This highly successful resistant parasite strain is capable of invading new territories and acquiring new genetic properties, raising the terrifying prospect that it could spread to Africa, where most malaria cases occur, as resistance to chloroquine did in the 1980s, contributing to millions of deaths,” Miotto said.

Co-author Tran Tinh Hien, MD, of the Oxford University Clinical Research Unit in Vietnam, said 1 treatment option is to replace piperaquine with a drug such as mefloquine or pyronaridine, but he noted that resistance to these drugs could also develop quickly.

“Another option is to use triple ACTs, in which artemisinin is combined with 2 partner drugs instead of one,” he added.