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Genetic Fingerprints Track Drug-Resistant Malaria Parasites

New artemisinin-resistant strains of the malaria-causing parasite Plasmodium falciparum are spreading rapidly in Cambodia, an international group of scientists says in a research paper that also reveals how the drug-resistant strains can be identified from their genetic fingerprints.

Senior author Dominic Kwiatkowski, from the University of Oxford and the Wellcome Trust Sanger Institute near Cambridge, and colleagues, discovered the new artemisinin-resistant strains in western Cambodia, a known hotspot for drug-resistance. They write about this, and how they were able to identify distinct genetic patterns for each of the strains, in the 28 April online issue of Nature Genetics.

Artemisinin is the key drug against malaria, which is caused when the parasite P. falciparum gets into the bloodstream through a mosquito bite. However, according to the World Health Organization (WHO), the emergence of drug-resistant strains of the parasite is weakening the impact of artemisinin, putting hundreds of thousands of lives at risk.

Co-author Nicholas White, a professor from the Centre for Tropical Medicine at the University of Oxford, says in a statement:

"Artemisinin resistance is an emergency which could derail all the good work of global malaria control in recent years. We desperately need methods to track it in order to contain it, and molecular fingerprinting provides this."

Using new genome sequencing technologies, the international group sequenced the entire DNA of 825 P. falciparum samples from South East Asia and Africa and found an "unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia".

The technologies enabled them to pick out genetic patterns or "fingerprints" for each of the artemisinin-resistant strains.

Kwiatkowski tells the press:

"Our survey of genetic variation showed that western Cambodian malaria parasites had a population structure that was strikingly different to those of the other countries we analysed."

"Different not just from countries in Africa, but also different from malaria parasite populations in neighbouring Thailand, Vietnam, and even Eastern Cambodia," he adds.

The findings also give some important clues about how resistance emerges and persists in certain parasite populations.

The researchers suggest their approach offers a useful new way to detect and track the global emergence of drug resistance. One important benefit, for instance, is that you don't have to know the genetic causes of drug resistance to identify resistant strains.

This counts as an important step toward surveillance and efforts to eliminate malaria worldwide. Health authorities need fast and efficient tools for genetically detecting drug-resistant parasites in order to track their emergence and spread.

In their paper, the authors show that applying their techniques would allow the authorities to monitor the spread and evolution of drug-resistant parasites in real time.

At first the group thought they were just finding anomalies. But further investigations revealed three distinct artemisinin-resistant parasite populations that differed not just from the other populations that were still susceptible to the drug, but also from each other.

"It is as if there are different ethnic groups of artemisinin-resistant parasites inhabiting the same region," Kwiatkowski explains.

The findings also offer some new clues as to why western Cambodia is such a hotspot for the emergence of drug-resistant malaria parasites, something that has been puzzling researchers for some time. Resistance to other malaria drugs, chloroquine and sulfadoxine/pyrimethamine, first began in Southeast Asia and spread to Africa.

As well providing what the researchers describe as "a population-level genetic framework for investigating the biological origins of artemisinin resistance", they believe their findings also provide a way of "defining molecular markers to assist in its elimination".

White, who is also based at the Mahidol-Oxford Tropical Medicine Research Unit at Mahidol University, in Bangkok, Thailand, says:

"Whilst we have not yet identified the precise mechanism of action or resistance to artemisinin, this research represents substantial progress in that direction."

In its World Malaria Report 2012, the WHO suggests that the massive progress in the fight against malaria achieved over the last decade could stall because of lack of money.

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