Growing failure of anti malaria drug treatment linked to parasite mutations

MORU Mae Sot by Gerhard Joren-056
Staff at work in the haematology lab, SMRU, Mae Sot, Thailand. © 2016 Mahidol Oxford Tropical Medicine Research Unit (MORU) and Shoklo Malaria Research Unit (SMRU)/Gerhard Jörén

22 June 2016, Mae Sot (Thailand) – The rapid decline in effectiveness of a widely used anti-malaria drug treatment on the Thailand-Myanmar border is linked to the increasing prevalence of specific mutations in the malaria parasite itself, according to a paper published in The Clinical infectious Disease Journal.

The mutations in specific regions of the parasite’s kelch gene – which are genetic markers of artemisinin resistance – were the decisive factor, the authors say, in the selection of parasites that are also resistant to mefloquine. This resulted in growing failure of the widely-used anti-malaria drug combination of mefloquine and artesunate, the first artemisinin combination therapy (ACT) on the Thai-Myanmar border.

Led by Dr. Aung Pyae Phyo of SMRU, the study used data from a 10-year study of 1,005 patients with uncomplicated P. falciparum malaria at Shoklo Malaria Research Unit (SMRU) clinics on the Thai-Myanmar border in northwest Thailand.

“This study demonstrates for the first time that artemisinin resistance leads to failure of the artemisinin partner drug, in this case, mefloquine. This means that the first line artemisinin combination therapy (ACT) introduced here in 1994 has finally fallen to resistance,” says François Nosten, Director of SMRU.

Resistance to artemisinin combination therapy drugs (ACTs) – the frontline treatments against malaria infection – poses a serious threat to the global control and eradication of malaria. If drug resistance spreads from Asia to the African sub-continent, or emerges in Africa independently, as has happened several times before, millions of lives, most of them children under the age of 5 in Africa, will be at risk.

The study shows that, contrary to the view sometimes expressed that resistance to artemisinin is not a direct threat, it is in fact responsible for the rapid demise of the partner drug and the failure of the drug combination, resulting in patients not being cured and further transmission of the malaria parasite.

MORU Mae Sot by Gerhard Joren-094
Reading malaria slides in one the SMRU field laboratories. © 2016 Mahidol Oxford Tropical Medicine Research Unit (MORU) and Shoklo Malaria Research Unit (SMRU)/Gerhard Jörén

"The evidence is clear: Artemisinin resistance leads to partner drug resistance and thereby the failure of artemisinin combination treatments,” said Oxford Professor Nicholas White, Chairman of the Mahidol Oxford Tropical Medicine Research Unit (MORU) and chair of the Worldwide Antimalarial Resistance Network (WWARN).

Given the very limited number of effective drugs, it is urgent to eliminate P. falciparum from the areas where it has developed resistance to the artemisinins, said Prof. White: "The spread of artemisinin resistant Plasmodium falciparum is perhaps the greatest threat to our current hopes of eliminating malaria from the world.”

A unit of the Bangkok-based MORU, SMRU is based in the refugee camps and migrant communities along the Thai-Myanmar border. Led by researchers based at SMRU (Thailand), the study was funded with the support of the Wellcome Trust (UK).

Reference:

Pyae Phyo A et al, Declining efficacy of artemisinin combination therapy against P. falciparum malaria on the Thai-Myanmar border (2003-2013): the role of parasite genetic factors, Clinical Infectious Diseases, published online 16 June 2016.

Link to full article: http://bit.ly/24YD2Ic

Link to Clinical Infectious Diseases abstract: http://bit.ly/28JhyLd

Authors and contributors: A. Pyae Phyo, E.A. Ashley, T.J. Anderson, Z. Bozdech, V.I. Carrara, K. Sriprawat, S. Nair, M.M. White, J. Dziekan, C. Ling, S. Proux, K. Konghahong, A. Jeeyapant, C.J. Woodrow, M. Imwong, R. McGready, K.M. Lwin, N.P. Day, N. J. White and F. Nosten.