Multi-drug-resistant malaria parasite causing high rates of treatment failure in Vietnam

21 September 2017

A new study shows that a dominant multidrug-resistant strain of falciparum malaria poses a serious threat to malaria control and eradication efforts.

Antimalarial efficacy of artemisinin-based combination therapies, the first-line treatment against Plasmodium falciparum malaria, relies on both fast-acting artemisinin derivatives and long-lasting partner drugs. The Mekong sub-region of Southeast Asia is currently the epicentre of P. falciparum multidrug resistance and is facing high rates of dihydroartemisinin-piperaquine (DP) treatment failures, one of the most commonly used treatments against malaria.

A new study out this week in the Lancet Infectious Diseases, has found that a dominant strain of multi-drug-resistant P. falciparum malaria is now present in Vietnam. This dangerous strain of malaria is causing wide-spread treatment failures across Southern Vietnam. This study was led by a group of researchers from the Mahidol Oxford Research Unit (MORU) based in Bangkok.

This dominant strain, known as the C580Y mutant lineage, initially arose in Cambodia with resistance to artemisinin, but it has subsequently acquired resistance to the partner drug piperaquine; and it has outcompeted other strains of drug-resistant malaria to show dominance in the regions affected.

"A single mutant strain of very drug-resistant malaria has now spread from western Cambodia to north-eastern Thailand, southern Laos and into southern Vietnam and caused a large increase in treatment failure of patients with malaria," says co-author University of Oxford Prof. Arjen Dondorp, Head of Malaria and Deputy Head of the Mahidol Oxford Tropical Medicine Research Unit (MORU) in Thailand, Asia.

DP was the first-line treatment in Cambodia when the multi-drug resistant malaria strain appeared, but as a consequence of increased treatment failures, Cambodia has since switched its first line artemisinin combination treatment back to artesunate mefloquine (ASMQ). However, DP is still the National first line treatment against malaria in Vietnam.

“We are losing a dangerous race. The spread of this malaria “superbug” has caused an alarming rise in treatment failures forcing changes in drug policy and leaving few options for the future,” said co-author from the Mahidol-Oxford Research Unit, Prof Sir Nicholas White. “We need to tackle this public health emergency urgently.”

The evolution and subsequent spread of this dominant multi-drug-resistant malaria parasite lineage across the Mekong region is of international concern.

The identification of the K13 molecular markers of artemisinin resistance, such as this dominant C580Y mutation, has transformed our ability to monitor the spread and emergence of artemisinin resistance. WWARN has developed an interactive map to show the global distribution of K13 molecular markers across time. This tool equips policy makers with up to date information on the spread and emergence of K13 markers to better inform elimination efforts.

A recent pooled analysis from WWARN and MORU provided robust evidence to support revised dosing regimens for DP to prolong its efficacy for as long as possible. Results from this study were used by the WHO expert review panel’s decision to update the Guidelines for the treatment of malaria.

“If resistance moves beyond Asia and into Africa much of the recent progress in reducing deaths from malaria will be reversed. The spread of a single lineage in the Mekong region is a demonstration of the reality of this threat, and no longer a hypothetical scenario; it requires increased attention.” says Professor Philippe Guérin, Director of the WorldWide Antimalarial Resistance Network.

Publication details:

Imwong M, Hien TT, Thuy-Nhien N, White NJ, Dondorp AM. Spread of a single multidrug resistant malaria parasite lineage (PfPailin) to Vietnam. Published online 23:30 GMT 20 September 2017 in the Lancet Infectious Diseases, 17TLID1086 Vol 17 Oct 2017 issue.