Malaria-carrying parasites in parts of Cambodia have developed resistance to a major drug used to treat the disease in Southeast Asia.
The drug piperaquine, used in combination with the drug artemisinin, has been the main form of malaria treatment in Cambodia since 2008.
The combination is also one of the few treatments still effective against multi drug-resistant malaria which has emerged in Southeast Asia in recent years, and which experts fear may spread to other parts of the world.
"(Treatment) failures are caused by both artemisinin and piperaquine resistance, and commonly occur in places where dihydroartemisinin-piperaquine has been used in the private sector," researchers said.
Artemisinin resistance has been found in five countries in Southeast Asia - Cambodia, Laos, Myanmar, Thailand and Vietnam.
Resistance to both artemisinin and drugs used in combination with it has developed in parts of Cambodia and Thailand.
Experts are particularly concerned that artemisinin resistance will spread to sub-Saharan Africa where about 90 percent of malaria cases and deaths occur.
"Because few other artemisinin combination therapies are available, and because artemisinin resistance will probably accellerate resistance to any partner drug, investigations of alternative treatment approaches are urgently needed," the researchers said.
They suggest an alternative treatment should be tested, comprising artesunate, a form of artemisinin, combined with mefloquine, a different long-acting partner drug.
"The intensive spread of artemisinin resistance in Cambodia is rapidly threatening to reduce the efficacy of all artemisinin combination therapies used in this country and in bordering areas of Vietnam, Laos, and Thailand," the article said.
Malaria patients in areas with drug-resistant malaria should be treated in hospital, the researchers said.
"Intensified efforts are needed to discourage what appears to be a highly ineffective approach of self-treatment in the private sector."
The research was produced by the US National Institute of Allergy and Infectious Diseases and published on Thursday in The Lancet Infectious Diseases journal.
About 3.2 billion people - almost half the world's population - are at risk of malaria, according to the World Health Organisation.