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Dominant malaria parasite threatens global malaria control

1 February 2017

A lineage of multidrug resistant P. falciparum malaria superbugs has widely spread and is now established in parts of Thailand, Laos and Cambodia, causing high treatment failure rates for the main falciparum malaria medicines, artemisinin combination therapies (ACTs), according to a study published today in The Lancet Infectious Diseases.

The emergence and spread of artemisinin drug resistant P falciparum lineage represents a serious threat to global malaria control and eradication efforts. The authors warn that malaria parasites resistant to both artemisinin and its widely used partner drug piperaquine are now spreading quickly throughout Cambodia, with fitter multidrug resistant parasites spreading throughout western Cambodia, southern Laos and northeastern Thailand.

We now see this very successful resistant parasite lineage emerging, outcompeting its peers, and spreading over a wide area. It has also picked up resistance to the partner drug piperaquine, causing high failure rates of the widely used artemisinin combination therapy DHA-piperaquine” says study lead author Prof. Arjen Dondorp, Head of Malaria and Deputy Head of the Mahidol Oxford Tropical Medicine Research Unit (MORU) in Thailand, Asia. “We hope this evidence will be used to reemphasize the urgency of malaria elimination in the Asia-region before falciparum malaria becomes close to untreatable.

Noting that the further spread of these multidrug resistant parasites through India to sub-Saharan Africa would be a global public health disaster, the study authors call for accelerated efforts in the Greater Mekong Sub-region and closer collaboration to monitor any further spread in neighbouring regions.

We are losing a dangerous race to eliminate artemisinin resistant falciparum malaria before widespread resistance to the partner antimalarials makes that impossible,” said study contributor and Oxford and Mahidol University Prof Sir Nicholas White. “The consequences of resistance spreading further into India and Africa could be grave if drug resistance is not tackled from a global public health emergency perspective.”

After examining blood spot samples from patients with uncomplicated falciparum malaria from sites in Cambodia, Laos, Thailand and Myanmar, the study team found that PfKelch13 C580Y, a single mutant parasite lineage, has spread across three countries, replacing parasites containing other, less ACT-resistant mutations. Although the C580Y mutation does not confer a higher level of artemisinin resistance than many other PfKelch13 mutations it appears to be fitter, more transmissible and spreading more widely.

It isn’t that the C580Y mutation itself makes the malaria parasites fitter, it is the other genetic changes that go along with it – hence the critical emphasis on the term “lineage”. This is what makes superbugs – the evolution of multiple factors that make them fitter and more transmissible,” explains Prof. Sir Nicholas White of Mahidol and Oxford Universities. “The spread and emergence of drug resistant malaria parasites across Asia into Africa has occurred before. Last time it killed millions. We need to work with our policy, research and funding partners to respond to this threat in Asia urgently to avoid history repeating itself.

Dr Mike Turner, Head of Infection and Immunobiology at Wellcome Trust concurs: “Already hundreds of thousands of people every year die from drug resistant infections, including malaria. If nothing is done, this will increase to millions of people every year by 2050. The Oxford and Mahidol-led results show a worrying spread of malaria parasite resistance. Data to help track resistance to drugs, such as this study, are vital for improving treatment, diagnosis and prevention of drug resistant infections.”

This study was led by researchers at the Mahidol-Oxford Tropical Medicine Research Unit (MORU), the Mahidol University in Bangkok, Thailand and Oxford University, UK. The study was funded by the Wellcome Trust (UK) and the Bill and Melinda Gates Foundation.

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Study Reference:

Link to go live February 1st 2017 23h30 UK time.

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30048-8/fulltext

The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong Subregion: a molecular epidemiology observational study. Imwong M, Suwannasin K, Kunasol C, Sutawong K, Mayxay M, Rekol H, Smithuis FM, Hlaing TM, Tun KM, van der Pluijm RW, Tripura R, Miotto O, Menard D, Dhorda M, Day NPJ, White NJ, Dondorp AM. Published online 23:30 GMT 1st February 2017 in the Lancet Infectious Diseases, THELANCETID-D-16-01360R2 S1473-3099(17)30048-8. http://dx.doi.org/10.1016/S1473-3099(17)30048-8

Additional notes:

The Mahidol-Oxford Tropical Medicine Research Unit (MORU), www.tropmedres.ac is a research collaboration between Mahidol University in Thailand and Oxford University. This study was developed in partnership with multiple research groups and experts from across the Asia-region including the WorldWide Antimalarial Resistance Network and The Institute Pasteur in Cambodia.

The WorldWide Antimalarial Research Network (WWARN) mission is to support the WHO and national governments by providing comprehensive, timely, quality-assured evidence to track the emergence and spread of malaria drug resistance, and improve drug efficacy of existing antimalarial medicines and new drugs in development. Our international partnerships with MORU and Oxford University play an important role in gathering the evidence needed to inform malaria treatment policy and practice. Through this collaborative approach, WWARN will continue to provide valuable evidence to help save more lives and support the global effort to control, eliminate and eventually, eradicate malaria. Visit www.wwarn.org

WHO Global Malaria Report

http://www.wwarn.org/news/news-articles/who-releases-2016-world-malaria-report

WHO Greater Mekong Sub-region Report

http://www.wwarn.org/news/news-articles/new-report-details-who-efforts-eliminate-malaria-greater-mekong-subregion

Prof Sir Nicholas White honoured in UK Queen’s New Year’s List January 2017

http://www.wwarn.org/news/news-articles/prof-nicholas-white-recognised-contributions-global-health-uks-new-years-honours

Surveillance of molecular markers - http://www.wwarn.org/news/news-articles/new-programme-launches-molecular-and-vitro-surveillance-act-partner-drug-efficacy

Two other recent Lancet ID studies report on molecular markers of resistance

http://www.wwarn.org/news/news-articles/two-lancet-infectious-diseases-papers-highlight-importance-monitoring-failure