Tracking the spread of artemisinin drug resistance in Southeast Asia

Clinical researchers from the Mahidol Oxford Tropical Medicine Research Unit (MORU) have published a study in the New England Journal of Medicine, which shows that drug-resistant malaria parasites have spread to critical border regions of Southeast Asia. If we are not able to contain these parasites, it is possible that resistance will spread into malaria endemic regions of Africa and could derail the global drive to control and eventually eliminate malaria altogether.

Currently over half of the world’s population are at risk of malaria infection. Although there has been a substantial reduction in the number of people suffering and dying from malaria – with approximately 3.3 million deaths prevented since 2000 – it is estimated that more than 600,000 people still die from the disease each year, most of them small children under five years of age from Africa1.

Photography by Philippe Guérin. Mae Sot field site in Western Thailand where resistance is confirmed.

The study confirms that resistance to the world’s most effective antimalarial drug, artemisinin, is now established in Western Cambodia, Thailand, Vietnam, Eastern Myanmar and Northern Cambodia. Emerging once again from the same region along the Cambodia-Thailand border, it looks like history may be repeated for a third time. If drug resistance spreads further westwards into Africa it could affect the lives of millions as it did from the 1950s-1970s. At present there is no evidence of resistance in three African sites in Kenya, Nigeria and Democratic Republic of the Congo, but this may not be the case for much longer.

NDM Professor Nicholas White, chair of MORU and of the Worldwide Antimalarial Resistance Network (WWARN), describes the situation: "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. 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."

The research teams found that by extending the course of treatment from three to six days - with an artemisinin derivative followed by an artemisinin combination therapy (ACT)– patients responded well, but this only offers a short-term solution as more parasites become resistant.

The Tracking Resistance to Artemisinin Collaboration (TRAC) was led by Dr Elizabeth Ashley, a clinical researcher at MORU, together with multiple other research partners and institutes. The research teams analysed blood samples from 1241 patients treated across 15 sites in 10 malaria-endemic countries and found: “Frontline ACTs are still very effective at curing the majority of patients. But we need to be vigilant as cure rates have fallen in areas where artemisinin resistance is established,” said Dr Ashley, “Action is needed to contain resistance and avoid any further spread from Myanmar into neighbouring Bangladesh and India.”

The Director of the Wellcome Trust and tropical medicine expert, Dr Jeremy Farrar, said of the study results: “If resistance spreads out of Asia and into Africa much of the great progress in reducing deaths from malaria will be reversed. Our ability to respond to these rapidly emerging health problems depends on swift gathering of evidence, which can be quickly translated into public health and clinical interventions that are then implemented. Antimicrobial resistance is happening now. This is not just a threat for the future, it is today's reality.”

A significant amount of research in NDM is conducted on malaria, from studies of resistance to development of vaccines and treatments. To learn more about our work in this area, view our series of Translational Medicine podcasts on malaria, with Prof White and other leading scientists describing their work and its impact. Find out more about antimalarial resistance from the Worldwide Antimalarial Resistance Network.

Publication details: Elizabeth A Ashley et al. Spread of Artemisinin Resistance in Plasmodium falciparum Malaria. Advanced online publication in New England Journal of Medicine. July 31 2014; 371:411-23. DOI: 10.1056/NEJMoa1314981.

The TRAC project was funded by the UK Department for International Development (DFID). Additional support was given by the Worldwide Antimalarial Resistance Network (WWARN) and the Bill & Melinda Gates Foundation. The study was coordinated by MORU, the Mahidol Oxford Research Programme, which is funded by the Wellcome Trust.

1 Malaria burden estimates from the WHO World Malaria Report 2013.