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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Greek authorities must urgently step up control of mosquitoes and surveillance of infected people to stop malaria from re-establishing itself in the crisis-hit country, scientists said on Friday.

Writing in online journal Eurosurveillance, they said recent outbreaks of the disease in the southern regions of Lakonia and East Attica were worrying.

Tackling malaria requires measures such as insecticide spraying, eliminating standing water and tracking mosquito populations as well as people infected with the disease.

"It is clear that surveillance and vector control programs should be strengthened and rapidly intensified," said the study, led by researchers at the Hellenic Centre for Disease Control and Prevention (HCDCP) in Athens.

Greece's healthcare system is under extreme pressure from budget cuts, and experts fear groups such as the poor, unemployed or homeless, many of them immigrants, are not getting treatment they need.

Malaria, which causes high fever and chills and kills hundreds of thousands of people a year worldwide, was once endemic in Greece but was officially eliminated in 1974.

Most cases since then have been imported by travelers, mainly from Africa and Asia.

But Greece has established populations of potentially malarial mosquito species, and last year, 40 cases of locally-acquired malaria were reported, mainly in Lakonia and Attica.

Between January 1 and October 22 this year Greece reported 75 cases in total, 16 of which were locally acquired.

Other mosquito-borne diseases, including West Nile virus carried by Culex modestus mosquitoes, also occur in Greece.

Apostolos Veizis, director of medical-operational support for Medecins Sans Frontieres in Greece, warned in a statement earlier this month that any malaria plan could not work properly unless access to healthcare was available to all.

"It is very important to monitor the situation and invest in mosquito control," he said. "But medically speaking if people cannot be examined and properly diagnosed, it's easy to lose sight of the problem."

The HCDCP experts said a coordinated effort had begun with the collaboration of Greek authorities, the European Centre for Disease Prevention and Control and World Health Organisation (WHO) experts to prevent malaria returning.

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 An experimental malaria vaccine once thought promising is turning out to be a disappointment, with a new study showing it is only about 30 percent effective at protecting infants from the killer disease.

That is a significant drop from a study done last year in slightly older children, which suggested the vaccine cut the malaria risk by about half — and even that is far below the protection provided by most vaccines. The three-shot regimen reduced malaria cases by about 30 percent in infants aged 6 to 12 weeks, the target age for immunization, researchers reported Friday.

“We're all a bit frustrated that it has proven so hard to make a malaria vaccine," said Eleanor Riley of the London School of Hygiene and Tropical Medicine. She said a malaria vaccine might be useful if combined with other strategies, like bed nets.

"The question is how much money are the funders willing to keep throwing at it,” said Riley, who was involved in an earlier study of the vaccine and had hoped for better results.

Dr. Jennifer Cohn, a medical coordinator at Doctors Without Borders, described the vaccine's protection levels as "unacceptably low." She was not involved in the study.

Scientists have been working for decades to develop a malaria vaccine, a complicated endeavor since the disease is caused by five different species of parasites. There has never been an effective vaccine against a parasite. Worldwide, scientists are working on several dozen malaria vaccine candidates.

In 2006, a group of experts led by the World Health Organization said a malaria vaccine should cut the risk of severe disease and death by at least half and should protect for longer than one year. Malaria is spread by mosquitoes and kills more than 650,000 people every year, mostly young children and pregnant women in Africa. Without a vaccine, officials have focused on distributing insecticide-treated bed nets, spraying homes with pesticides and ensuring access to good medicines.

In the new study, scientists found 30 percent fewer cases of malaria among babies who got three doses of the vaccine compared to those who didn't get immunized. The research included more than 6,500 infants in Africa. Experts also found the vaccine reduced the number of cases of  severe malaria by about 26 percent for up to 14 months after the babies were immunized.

Scientists said they needed to analyze the data further to understand why the vaccine may be working differently in different regions. For example, babies born in areas with high levels of malaria might inherit some antibodies from their mothers that could interfere with the vaccine.

"Maybe we should be thinking of a first-generation vaccine that is targeted only for certain children," said Dr. Salim Abdulla of the Ifakara Health Institute in Tanzania, one of the study investigators.

Results were presented at a conference in South Africa on Friday and released online by the New England Journal of Medicine. The study is scheduled to continue until 2014 and is being paid for by GlaxoSmithKline and the PATH Malaria Vaccine Initiative.

"The results look bad now, but they will probably be worse later," said Adrian Hill of Oxford University, who is developing a competing malaria vaccine. He noted the study showed the Glaxo vaccine lost its potency after several months. Hill said the vaccine might be a hard sell, compared to other vaccines like those for meningitis and pneumococcal disease — which are both effective and cheap.

"If it turns out to have a clear 30 percent efficacy, it is probably not worth it to implement this in Africa on a large scale," said Genton Blaise, a malaria expert at the Swiss Tropical and Public Health Institute in Basel, who also sits on a WHO advisory board.

Glaxo started developing the vaccine in 1987 and has invested $300 million in it so far.

WHO said it couldn't comment on the incomplete results and would wait until the trial was finished before drawing any conclusions.

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.