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DNA reveals roots of drug-resistant malaria

Fighting malaria Western Cambodia harbours ideal conditions for the malaria parasite to evolve to resistance to frontline antimalarial drugs, reveals an international study.

The study, led Dr Olivo Miotto of Oxford University in the UK, reveals three different populations of parasites that are resistant to artemisinin, have evolved in the area.

Drug resistance to three earlier anti-malarial drugs -- chloroquine, primethamine and sulfadoxine -- is thought to have evolved in western Cambodia too.

The new findings, reported in the journal Nature Genetics , may unravel the mystery of why the region nurtures drug-resistant parasites.

The team made their discovery of the unusual Cambodian parasite populations by comparing the genomes of 825 malaria parasites taken from South East Asia and West Africa.

Within each population, the parasites appeared to be clones of each other -- suggesting that they had come from one 'founder' organism.

Inbreeding the key

The chances of catching malaria in western Cambodia are fairly small, and this may be one of the clues to the region's role in developing drug-resistance, says Miotto.

"In that region you will get bitten by an infected mosquito say, once a year, as opposed to once a week or once a day in many areas of Africa," he says.

As part of its life cycle, the parasite multiplies inside the human, cloning itself, and this means that when a mosquito takes a feed from a person in western Cambodia, it likely gets only one genetic version of the parasite.

The parasite then reproduces sexually inside the mosquito, but since it can only mate with its own clones, the genome remains unchanged, which means that if it has become drug-resistant, it will stay drug-resistant.

In Africa, on the other hand, a blood-thirsty mosquito will imbibe a cocktail of genetic variants of the parasite. These will mate within the mosquito, and the offspring may no longer be drug-resistant.

"Artemisinin is currently the frontline drug used against malaria almost world-wide," says Miotto. He says the current levels of resistance are just slowing down the response to the drug, but the danger is that the parasite may evolve further and make the drug ineffective.

"What we really want to avoid is getting to the stage where artemisinin is actually failing. That would really be disastrous because, right now, artemisinin is literally saving millions of children in Africa."

The techniques the team have developed will enable surveillance of the spread of drug-resistant forms, he adds.

Light-bulb moment

Dr Alyssa Barry of the Walter and Eliza Hall Institute in Melbourne says the study is "very impressive".

"This is the largest malaria genome sequencing project ever done. That means you can really look at malaria parasite populations in a lot of detail," says Barry who was not involved in the research.

Although the team's theory for why drug resistance tends to develop in the region is still just a hypothesis, she says finding the three separate populations of drug-resistant parasites was a "light-bulb moment."