The dangerous form of the malaria parasite which cannot be killed with the main anti-malaria drugs emerged in Cambodia but has since spread through parts of Thailand, Laos and has arrived in southern Vietnam.
Researchers at Oxford Tropical Medicine Research Unit in Bangkok in a letter, published in The Lancet Infectious Diseases, detail the "recent sinister development" that has seen resistance to the drug artemisinin emerge.
"We think it is a serious threat. It is alarming that this strain is spreading so quickly through the whole region and we fear it can spread further and eventually jump to Africa," Arjen Dondorp, professor at Oxford Tropical Medicine Research Unit was quoted as saying by the BBC.
The first choice treatment for malaria is artemisinin in combination with piperaquine. But as artemisinin has become less effective, the parasite has now evolved to resist piperaquine too, researchers said.
There have now been alarming rates of failure. The treatment was failing around a third of the time in Vietnam while in some regions of Cambodia the failure rate was closer to 60 per cent, Dondorp said.
Resistance to the drugs would be catastrophic in Africa, where 92 per cent of all malaria cases happen, researchers warn.
About 212 million people are infected with malaria each year. It is caused by a parasite that is spread by bloodsucking mosquitoes and is a major killer of children.