Half the world's population is exposed to malaria
International scientists say they have found the first evidence of resistance to the world's most effective drug for treating malaria.
They say the trend in western Cambodia has to be urgently contained because full-blown resistance would be a global health catastrophe.
Drugs are taking longer to clear blood of malaria parasites than before.
This is an early warning sign of emerging resistance to a disease which kills a million people every year.
Until now the most effective drug cleared all malaria parasites from the blood within two or three days but in recent trials this took up to four or five days.
The BBC's Jill McGivering, reporting from Cambodia, says it is unclear why the region has become a nursery for the resistance - but the local public health system is weak, and the use of anti-malaria drugs is not properly controlled.
The artemesinin family of drugs is the world's front-line defence against the most prevalent and deadly form of malaria.
Two teams of scientists, working on separate clinical trials, have reported seeing the disturbing evidence that the drugs are becoming much less effective.
There is particular concern because previous generations of malaria drugs have been undermined by resistance which started in this way, in this part of the world, our correspondent reports.
The World Health Organization warned in 2006 there was a possibility the malaria parasite could develop a resistance to artemesinin drugs, and that there was particular concern about a decreased sensitivity to the drug being seen in South East Asia.
It urged drug firms to stop selling artemesinin on its own in order to prevent resistance building up.
Early results from two studies by US and UK teams have both revealed the early stages of resistance.
Between a third and a half of patients in the US study saw delayed clearance of the malaria parasite.
In the UK study, patients in the Cambodia arm of the trial took almost twice as long to clear the parasite as a comparison group in Thailand.
Professor Nick Day, director of the Mahidol-Oxford Tropical Medicine Research Unit which is carrying out the UK study, said: "Twice in the past, South East Asia has made a gift, unwittingly, of drug resistant parasites to the rest of the world, in particular to Africa," he said.
"That's the problem. We've had chloroquine and SP (sulfadoxine pyrimethamine) resistance, both of which have caused major loss of life in Africa," he said in reference to earlier generation anti-malarial drugs.
"If the same thing happens again, the spread of a resistant parasite from Asia to Africa, that will have devastating consequences for malaria control," he said.
Prof Brian Greenwood, Professor of Tropical Medicine at the London School of Hygiene and Tropical Medicine, described the findings as a matter for concern, even though treatment still worked if a full course of artemisinin combination therapy (ACT) was taken.
"There is currently no need for panic but it would be serious if these partially resistant parasites reached Africa where great gains in malaria control are currently being made using ACTs and insecticide-treated bed nets," he said.
Cambodia has long been a laboratory for malaria investigators and a nursery of anti-malaria drug resistance.
The fight against malaria has lasted generations
Alongside a weak public health system and poorly-controlled drug use, there are many fake drugs, produced by international criminals.
These fakes often contain a small amount of the real drug to fool tests, which can also help to fuel resistance.
Those working to control malaria are calling for urgent action to contain this emerging resistance.
If it strengthens and spreads, they warn, many millions of lives will be at risk. About half the world's population faces exposure to the disease.