The parasites are genetically different from other strains around the world and are able to withstand treatment by artemisinin - a front-line drug against malaria.
Reports of drug resistance of the parasites in western Cambodia first emerged in 2008. The problem has since spread to other parts of South East Asia, 'BBC News' reported.
"All the most effective drugs that we have had in the last few decades have been one by one rendered useless by the remarkable ability of this parasite to mutate and develop resistance," Dr Olivo Miotto from the University of Oxford and Mahidol University in Thailand, said.
"Artemisinin right now works very well. It is the best weapon we have against the disease, and we need to keep it," Miotto, the lead author of the study, said.
Scientists do not understand why, but since the 1950s parasites there have developed a resistance to a succession of malaria drugs.
They are worried the same will happen with artemisinin drug as well. This drug is used widely around the world against the mosquito-borne disease and can treat an infection in a few days when it is used in combination with other drugs.
Scientists sequenced the genomes of 800 malaria-causing parasites (Plasmodium falciparum) collected from around the world in order to investigate.
"When we compared the DNA of the parasites in Cambodia, they seem to have formed some new populations that we have not really seen elsewhere," Miotto said.
The international team found three distinct groups of drug-resistant parasites present in the area.
Researchers said they did not yet understand what genetic mutations had occurred that enabled the parasites to withstand artemisinin treatment, the report said.
However, they said that understanding their genetic fingerprint would help them to quickly spot and track these strains if they spread further.
"It could be a tool for detecting in real time the emergence of drug resistance," Miotto said.
The study was published in the journal Nature Genetics.
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