MAE SOT, Thailand -- Clipboard in hand, Dr Francois Nosten worked his way down a ward of malaria patients. He stopped in front of five-year-old Ayemyint Than, who sat to attention and smiled. The smile told Nosten as much as his lines of graphs and figures.

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Ayemyint Than, 5, is being treated for malaria in northwestern Thailand.

"She's doing well," he said, moving to an older man, whose pale face and dull sunken eyes told a very different story. "Day five, and he's still positive?" he asked another of the doctors. "That's not very good. It means he was very slow to clear the parasite, no?"

To Nosten, it was further evidence of an alarming rise in resistance to artemisinin, currently the front-line drug in the treatment of malaria. He fears it could be the start of a global "nightmare" in which millions of people could lose their lives.

"We have to beat this resistance, win this race and eliminate the parasite before it’s too late. That's our challenge now," he said.

He said that artemisinin should take about 24 hours to deal with the parasite, but it was now taking three or four days in some cases. "We are going to see patients that don't respond to the treatment anymore,” he warned.

Nosten runs the Shoklo Malaria Research Unit, which is part of the Faculty of Tropical Medicine at Thailand's Mahidol University.

The unit has a string of clinics on both sides of the Moi River, which marks the porous border between Thailand and Myanmar.

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Migrants cross the Moi River, marking the border between Myanmar and Thailand.

Nosten set up the first one in 1986, since when there has been a steady fall in the total number of cases of malaria, but most recently a worrying emergence of drug resistance.

He first sounded the alarm in research published earlier this year, following the emergence of similar drug resistance along the Thai-Cambodia border.

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Nosten’s not sure whether the resistance he's found has spread from the Cambodia border or is home-grown. Either way, he's worried.

"It means that all the progress of the last 10 to 15 years will be lost," he warned. "Now the resistance is here, we worry that we are running out of time."

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Staff examine a baby who has been brought to the clinic with a fever, suspected to be malaria.

The malaria parasite -- carried by infected mosquitoes from person to person -- still kills an estimated 655,000 people a year.

That's almost 2,000 a day, mostly in Africa, with children being most at risk.

If the world loses its front-line drug, the impact could be devastating.

"The nightmare scenario is that the resistance will travel," Nosten said.

"We know what will happen in Africa when resistance is bad because we've been there before in the 1990s with chloroquine (another anti-malarial drug) … millions of deaths," he warned.

"We must prevent artemisinin resistance reaching Africa, but we also need to control it for the people in Asia - for their future."

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Dr Francois Nosten, right, consults staff as he meets malaria patients at a clinic near Mae Sot, Thailand.

Resistance to just about every major anti-malarial drug has started in the border regions that have been home to Nosten for more than 25 years.

Nobody knows exactly why, but poverty, conflict and large migrant and refugee populations constantly on the move all likely play a part. As do fake drugs or a failure to properly complete a course of treatment.

In the case of chloroquine, once the anti-malarial drug of choice, it took less than 20 years for resistance to spread from the borders of Thailand to Africa.

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Nosten is worried that artemisinin resistance is growing much faster than he'd anticipated, with the drug failing initially to fully clear the parasite in more than half the cases he now sees.

"It initially goes after a few days, then it comes back. We see that more and more now," he said.

"In 2009, we still had 90 percent of patients cured. In 2010, it dropped to 60 to 70 percent. Now it's about 50 percent," he added.

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Migrants from Myanmar wait to be examined at a clinic on the Thai side of the border.

Some scientists claim this is too alarmist, since the parasite does eventually die, with longer treatment and higher drug doses, but Nosten sees no room for complacency.

"We have to respond quickly, not next year or three years' time. It's now or probably it will be too late," he said.

Artemisinin comes from a Chinese plant and is quick, potent and with no side effects. Little wonder it has been hailed as a wonder drug, the golden bullet in the global fight against malaria.

What makes the resistance so worrying is that there is no new drug ready to replace it.

Nosten said that although several drugs are in development, they could be five to 10 years away from deployment "if they make it  … and we haven't got five to 10 years.”

The Shoklo Malaria Research Unit runs its own labs fashioned out of a sprawling old Thai house in the border town of Mae Sot, where teams of research scientists are working to better understand the parasite and the mosquitoes that carry it from person to person.

It is here that Chiara Andolina keeps mosquitoes that are literally hand-reared -- fed from her arm, which she extends through a mesh hole into a container of the hungry creatures every three days.

"Usually I feed around 600 of them in a cage like this," she said.

Of course these are not infected mosquitoes, though watching them settle on her arm for a good lunch is not a sight for the squeamish.

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In another room, Nosten settled over photographs showing the rapid development of the parasite once it has invaded a blood cell.

"If you can kill them very, very young -- like these -- they don't have time to develop into big fatty ones," he said, his pen jabbing at the photo. "These fatty ones are the ones that get stuck in your brain and kill you."

In other rooms, the DNA of parasites was being isolated and sequenced and drugs were being tested as part of Nosten and his team’s efforts to figure out what's behind the emerging resistance.

They are also looking for vulnerabilities and new ways to attack their enemy.

"It's hugely important to understand what's going on and contain it if we can," Nosten said. "We need to try things. We need to explore. It’s like exploring new territories in malaria."

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The French scientist has spent most of his working life in the tropics, initially with the medical humanitarian group Médecins Sans Frontières.

He believes he is engaged in a vital battle -- "a race against malaria" -- as he puts it.

After so many years on the malarial front lines, the battle has become deeply personal.

He dreams of completely eliminating this familiar but wily enemy.

However, he also knows that with the emergence of artemisinin resistance the stakes have never been higher.

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After two African villages started using mosquito nets to fight malaria, the local mosquitoes seemed to change their biting habits to avoid the barriers, according to a French study.

Insecticide-treated bed nets are considered a key weapon in the global fight against malaria, which is transmitted by parasite-carrying mosquitoes and kills more than 650,000 people a year, according to the World Health Organization.

In the study, which appeared in the Journal of Infectious Diseases, French researchers examined mosquito behavior before and after all households in two villages in Benin were given insecticide-treated nets.

They found that mosquitoes seemed to change their hours of "peak aggression" from 2 a.m. or 3 a.m. to around 5 a.m. three years after nets were put up. And in one village, the proportion of mosquito bites inflicted outdoors rose.

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Outdoor bites accounted for 45 percent of all bites at the outset but rose to 68 percent one year later and 61 percent after three years.

The finding is "worrying since villagers usually wake up before dawn to work in crops, and as such they are not protected by mosquito nets," senior researcher Vincent Corbel, of the Montpellier, France-based Institute of Research for Development, said in an email.

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Still, the results come from just two villages in one country. "We cannot extrapolate to a wider geographical area and/or a different entomological context," Corbel warned.

Malaria rates climbing again
Mosquito nets have been credited with spurring big drops in malaria deaths, and a report for the Cochrane Collaboration, an international group that publishes rigorous reviews, estimated that for every 1,000 children protected by an insecticide-treated net, five to six lives would be saved every year.

But in recent years, malaria cases have started to climb again in certain African countries, Corbel said. Experts have mainly been concerned about mosquitoes' growing resistance to the insecticides used in bed nets and for indoor spraying.

A malaria researcher not involved in Corbel's study said the results of the study should be interpreted with caution.

One reason is the difficulty in getting reliable measures of mosquito "biting behavior" over time, according to Thomas Eisele, from the Tulane University School of Public Health and Tropical Medicine in New Orleans.

In this study, Corbel's team used the standard way of gauging mosquito activity -- the "human landing catch" -- which, as the name implies, means that a mosquito collector lets the pest land on his skin, then catches it.

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The researchers had mosquito collectors do three different rounds, indoors and outdoors, at each village: Once before the nets were given to all households, then again one year and three years afterwards.

Eisele said measuring biting behavior can be "fraught with error" and added: "This study was conducted over only a couple of years, which would likely be insufficient to detect evolutionary changes in biting behaviors within the same species."

Corbel said the study challenges the "dogma" that malaria-transmitting mosquitoes in Africa bite exclusively at night.

"Long-lasting insecticidal nets were developed to protect people at night when they are sleeping," he said, noting that if mosquitoes shift to early morning and outdoor biting, the nets might not be enough to keep malaria under control.