By Jill McGivering
BBC News, Cambodia
In a small community in Western Cambodia, scientists are puzzling over why malaria parasites seem to be developing a resistance to drugs - and fearing the consequences.
Ten days ago, Chhem Bunchhin, a teacher in Battambang Province, became ill with chills, fever, headache and vomiting.
At a nearby health centre he was treated with drugs considered a "silver bullet" in the battle against falciparum malaria.
This treatment with artesunate drugs was part of a clinical study being carried out by the US Armed Forces Research Institute of Medical Science (AFRIMS).
In the past, artesunates have always cleared malaria parasites from the blood in two or three days. But after four days of monitored treatment, Chhem Bunchhin was still testing positive for parasites.
Dr Delia Bethell, an investigator working on the clinical trials, said he wasn't alone. Out of about 90 patients included in the study so far, roughly a third to half were still positive for malaria parasites after three days, some even after four or five days.
"It appears that the artesunate is working more slowly than previously," she said.
"It appears that the parasite probably is developing some kind of tolerance or is somehow less sensitive to the effects of the drug. But nobody knows why that might be."
These early results need to be more thoroughly investigated, she said.
The concern is that this could be the start of emerging resistance to the artemesinin family of drugs. If full-blown resistance did develop, it would be extremely dire.
"This is by far the most effective drug we have," explained Dr Bethell.
"And there are no new drugs coming through the system in the next few years."
Scientists are particularly concerned because the last two generations of anti-malarial drugs were undermined by resistance.
And in those earlier cases, resistance also started in Western Cambodia, and in a similar way.
No-one is sure why this area seems to have become a nursery for anti-malaria drug resistance.
One factor could be the inappropriate use of drugs, related to a lack of medical supervision.
The public health system is weak. Government clinics often run out of drugs or may be closed when patients want access to them.
Instead, many patients visit private pharmacies to buy anti-malarial drugs there.
Coloured tablets
I visited one small drugs stall in Pailin's general market, sandwiched between a clothes outlet and a general grocery store.
All pharmacies are supposed to be licensed. But the stallholder told me he didn't have a licence. He'd applied for one, he said, but the paperwork had never been processed.
Many others running pharmacies, he said, were in the same position.
I watched him and his wife make up their own packets of drugs on the glass-topped counter, shaking a variety of coloured tablets into unlabelled plastic bags.
In many such private pharmacies, the customers choose what they want, deciding partly by price.
The quality of the advice they get varies enormously. If, as a result, they end up taking the wrong drugs in the wrong combinations, this too can fuel drug resistance.
The availability of many counterfeit drugs on the market only compounds the problem.
Professor Nick Day, director of the Mahidol-Oxford Tropical Medicine Research Unit, is also running clinical trials in the region.
He and his team have also found that artesunate-type drugs are starting to become less effective.
This resistance must be contained urgently, because its spread would be a global health disaster, he said.
Resistance to previous malaria drugs caused major loss of life in Africa, he said.
"If the same thing happens again, the spread of a resistant parasite from Asia to Africa, then that will have devastating consequences for malaria control."
In a clearing in the jungle, about one and a half hours drive from Pailin along rough dirt roads, I watched health workers distribute mosquito nets to about 200 villagers.
It's one of a series of measures being rushed through to stop the spread of resistant parasites.
If they're not contained, history may repeat itself - and the fear is that many millions of people worldwide will lose their protection against this deadly disease.
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