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Critical time in anti-malaria fight

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Researchers say a rogue strain of malaria native to western Cambodia is

quickly developing resistance to the only drug that is able to treat

it, threatening fresh outbreaks of the disease

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Sy Mon sells a three-person bed net, manufactured in Cambodia with Vietnamese fabric, for US$5 at her shop in Phsar Cha. She said she sells about 20 bed nets a month.

NEAR the Thai-Cambodian border, one fatal strain of malaria shows signs of overcoming the most potent drug designed to destroy it, say malaria researchers.

Artemisinin, a drug first isolated by Chinese scientists four decades ago but only recently adopted internationally, is seen as the front line defence against malaria, and in Cambodia is the only effective drug against the most lethal malaria strain, Plasmodium falciparum.

"Artemisinin combination therapies are ... central to global efforts to control malaria," said Shunmay Yeung, a researcher at the London School of Hygiene and Tropical Medicine.

"They are safe and well tolerated ... and can be used in both uncomplicated and severe malaria."

But for five decades, western Cambodia has been a hotbed of drug-resistant malaria, and artemisinin appears to be following the same path of older antimalarials - such as chloroquine and mefloquine - which have been made obsolete by adaptive malaria strains.

Drug of last resort

"If the parasite becomes resistant to artemisinin, we don't have another drug.... Artemisinin is the only one that is strong enough to kill enough parasites," said Duong Socheat, the director of the National Centre for Malaria (NCM).

"If malaria becomes resistant to artemisinin, many in the world will die."

Amir Attaran, professor of law and population health at the University of Ottawa, echoed Duong Socheat's fears.

"If the artemisinin drugs were lost to resistance before an alternative was found - and none is on the horizon - then there's nothing else and malaria is untreatable," he said.

Every year since 2000, the NCM has run tests determining the effectiveness of artemisinin in western Cambodia, and every year the drug gradually loses its punch.

"The drug used to take 24 hours to clear the parasite. Now it can take more than 72 hours," Duong Socheat said.

A few factors conspire to make western Cambodia the epicentre for malaria drug resistance. A transient population of gem miners and itinerant workers from across Southeast Asia allow different malaria strains to mix together, increasing the likelihood of gene mutation.

If malaria becomes resistant to artemisinin, many in the world will die.

And almost all the pharmacies in the region are unregulated private providers who often prescribe improper treatments and dosages.

But even if patients avoid improper treatments and counterfeit drugs, monotherapy dosages of artemisinins - which rapidly increase the tolerance rate of the malaria parasite - are still widely prescribed.

As a fast-acting, potent drug, artemisinin needs to be prescribed with a slower partner drug to wipe out any residual malaria parasites that might have developed resistance.

"Artemisinin and its derivatives ... are recommended for use in combination with other groups of antimalarial drugs," said Awash Teklehaimanot, director of the malaria program at Columbia University.

Currently, the Cambodian government does emphasise combination therapy, but experts with local experience say more needs to be done.

"A ban on the import and selling of oral artemisinin monotherapies is going to be issued, but everybody agrees that this is not enough," said Yeung.

"It needs to be accompanied by enforcement, training, lots of communication and incentives to change the behaviour of providers and consumers."

The NCM, with the help of the World Health Organisation, has been working closely to educate private pharmacists about the importance of combination therapies. But with pharmaceutical distribution still relying on unlicensed distributors, the NCM faces an uphill battle.

There is also evidence that some patients avoid taking the partner drug even when combination therapy is properly prescribed. Currently, the recommended therapy is artemisinin and mefloquine blister-packaged together, allowing people to avoid taking the partner drug, mefloquine, which has more adverse side effects.

"Ideally, the drugs should be co-formulated: ie, both drugs in one tablet so they cannot be taken separately," Yeung said.

A critical period

The rising threat follows a decade of real gains that have been made against the parasite in Cambodia. Ten years ago, more than 1,000 Cambodians died each year from malaria, a figure that has been reduced to fewer than 200.

But modeling done by the Mahidol-Oxford Tropical Medicine Research Unit suggests that the only way to stop a resistant malaria parasite in Cambodia is to eradicate the most fatal strain of malaria completely.

"All strategies tested reveal that the only way to get rid of the resistant phenotype is by getting rid of all falciparum malaria in western Cambodia," said Arjen Dondorp, the unit's deputy director.

Dondorp advocated a three- pronged attack, stressing the need to get artemisinin monotherapies out of the private sector, distribute treated bed nets,  and repeatedly carry out mass screenings and treat the infected with combination therapy.

Although Duong Socheat is optimistic that Cambodia can eliminate malaria by 2015, the University of Ottawa's Attaran paints a darker picture.

Though reduction is possible, he said that talk of eradicating malaria is "nonsense".



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