Next to Africa, Asia is the second region to have been mutilated by drug-resistant malaria, warn experts.
Resistance to the drug used everywhere to cure the life-threatening disease has emerged in Cambodia, Thailand and Myanmar, said Richard Feachem, director of global health at the University of California, San Francisco.
"In the Mekong Basin there is a growing and spreading problem of resistance... to the drug artemisinin which is the frontline drug worldwide," he said ahead of "Malaria 2012: Saving Lives in the Asia-Pacific" in Sydney.
"The danger is that at some time this resistance may break out of Southeast Asia and crop up in Africa," added Feachem, the former founding head of the Global Fund to Fight AIDS, Tuberculosis and Malaria.
Some 22 countries in the Asia-Pacific still have malaria, but enormous progress has been made in combatting the devastating disease with the number of infections falling by about 50 percent in the past decade, he said.
Yet there were still an estimated 30 million cases in the Asia-Pacific in 2010, and more than 40,000 deaths in Southeast Asia and the Western Pacific, according to the World Health Organisation (WHO).
Drug-resistant malaria was found on the Thailand-Cambodia border eight years ago, and has also been found along the Thailand-Myanmar frontier and in parts of Vietnam, prompting an urgent call for action from the WHO in September.
The Sydney conference of politicians, scientists and health experts will seek consensus on the actions needed to strengthen the region's response to malaria.
Fatoumata Nafo-Traore, who leads the Roll Back Malaria Partnership which aims to provide a coordinated global approach to fighting the disease, said the resistance was most troubling in border areas.
"The current concern is that even though it is localised in those border areas, there is a potential to have it spreading to other parts of the world, because of the population inflow, because of the migrant workers and so on," she told AFP.
"This is really why we are getting concerned, because this is the only class of anti-malarial drug available to cure all uncomplicated malaria cases."
Resistance to artemisinin currently does not prevent patients being cured, thanks to other drugs it is used in concert with, but treatment typically takes longer than normal.
It is not known why the resistance has emerged in Cambodia, one of the first countries to deploy the treatment some 30 years ago.
But Ric Price, from the Centre of Tropical Medicine at Oxford in Britain, said high levels of counterfeit drugs and people not taking the full course of treatment could be factors.
"Artemisinin still remains the treatment of choice but it's under threat and we have to monitor where those areas are, where it is declining," he said.
The conference will discuss the need for vigilance against malaria, with Feachem saying there had been numerous cases in the past when the disease had almost been eradicated but complacency saw it come sweeping back.
"It's the penalty of success," he said. "Some countries in the region now have very little malaria. When you're down to 100 cases a year, the politicians (lose interest) and malaria comes surging back."
He said one of the conference goals was for half of the malaria-afflicted countries in the Asia-Pacific to eradicate the disease by 2025.
"That would be a huge historic step forward," he said.
Malaria is a life-threatening disease caused by parasites that are transmitted through the bites of infected mosquitoes. It killed an estimated 655,000 people in 2010, mostly African children.