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The rapid decline in effectiveness of a widely used anti-malaria drug treatment on the Thai-Burmese 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 the growing failure of the widely-used anti-malaria drug combination of mefloquine and artesunate, the first artemisinin combination therapy (ACT) used on the Thai-Burmese border.
Led by Dr Aung Pyae Phyo of the Shoklo Malaria Research Unit (SMRU), the study used data from a 10-year study of 1,005 patients with uncomplicated P. falciparum malaria at SMRU clinics on the border.
“This study demonstrates for the first time that artemisinin resistance leads to failure of the artemisinin partner drug, in this case, mefloquine,” says Prof François Nosten, director of SMRU.
“This means that the first line artemisinin combination therapy introduced here in 1994 has finally fallen to resistance,” he said.
Resistance to ACT drugs — the frontline treatments against malaria infection — poses a 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 five in Africa, will be at risk.
The study demonstrates that, contrary to the opinion 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 malaria.
“The evidence is clear that 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 chairman of the Worldwide Antimalarial Resistance Network.
Given the 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.
A unit of the Bangkok-based MORU, SMRU is based in refugee camps and migrant communities along the Thai-Burmese border.