Emergence of Artemisinin Resistance On Thai-Myanmar Border Raises Spectre of Untreatable Malaria

Eliminating malaria might then prove impossible

Evidence that the most deadly species of malaria parasite, Plasmodium falciparum, is becoming resistant to the front line treatment for malaria on the border of Thailand and Myanmar was reported in The Lancet April 5. This increases concern that resistance could now spread to India and then Africa as resistance to other antimalarial drugs has done before. Eliminating malaria might then prove impossible.

The study coincides with research recently published in Science in which researchers in south east Asia and the USA identify a major region of the malaria parasite genome associated with artemisinin resistance. This region, which includes several potential candidate genes for resistance, may provide researchers with a tool for mapping resistance.

Both studies, funded by the Wellcome Trust and the National Institutes of Health, follow reports in 2009 of the emergence of artemisinin-resistant malaria parasites in western Cambodia, 800km away from the Thailand-Myanmar border where the new cases of resistance have been observed. Resistance to artemisinin makes the drugs less effective and could eventually render them obsolete, putting millions of lives at risk.

According to the World Malaria Report 2011, malaria killed an estimated 655,000 people in 2010, mainly young children and pregnant women. It is caused by parasites that are injected into the bloodstream by infected mosquitoes. Plasmodium falciparum is responsible for nine out of ten deaths from malaria.

The most effective antimalarial drug is artemisinin; the artemisinin derivatives, most commonly artesunate, have the advantage over other antimalarial drugs such as chloroquine and mefloquine, of acting more rapidly and having fewer side-effects and, until recently, malaria parasites have shown no resistance against them. Although the drugs can be used on their own as a monotherapy, and these can still be obtained, fears over the possible development of resistance led to recommendations that they should only be used in conjunction with one or more other drugs as artemisinin-based combination therapies (ACTs). These are now recommended by the World Health Organization as the first-line treatment for uncomplicated falciparum malaria in all endemic countries. ACTs have contributed substantially to the recent decline in malaria cases in most tropical endemic regions.

In the Lancet study, researchers at the Shoklo Malaria Research Unit on the border of Thailand and Myanmar, part of the Wellcome Trust-Mahidol University-Oxford University Tropical Medicine Research Programme, measured the time taken to clear parasites from the blood stream in 3,202 patients with falciparum malaria using oral artesunate-containing medications over a ten year period between 2001 and 2010.

Over this period, the average time taken to reduce the number of parasites in the blood by a half — known as the ‘parasite clearance half-life’ — increased from 2.6 hours in 2001 to 3.7 hours in 2010, a clear sign that the drugs were becoming less effective. The proportion of slow-clearing infections — defined as a half-life of over 6.2 hours — increased over this same period from six to 200 out of every 1000 infections.

By examining the genetic make-up of the parasites, the researchers were able to provide compelling evidence that the decline in the parasite clearance rates was due to genetic changes in the parasites which had made them resistant to the drugs.