MIN SAW, Myanmar (Thomson Reuters Foundation) - Ka Lar Nar caught malaria for the sixth time when he was working away from home on his small farm in the jungle of south-eastern Myanmar but this time it was a lot harder to get rid of it.
After testing positive for malaria he got a three-day course of drugs from a community health volunteer in his village but even though his fever subsided, he continued to be plagued by headaches and another test still showed positive results.
Experts say his case could be an indication of drug resistance to the mosquito-borne disease, which has been spreading in Myanmar and other countries in the Mekong River basin in what threatens to become the next big global health emergency if it marches on to India and Africa.
"This was a missed opportunity," said Eisa Hamid, an epidemiologist working with the United Nations in Myanmar, who specializes in monitoring and evaluating malaria programs.
Normally, after three days of treatment the farmer's blood should have been clear of malaria-transmitting parasites.
"With any patient showing positive test results after three days of treatment, we have to suspect drug resistance, and more sophisticated blood testing should have been done as he could still carry the parasites that cause malaria in his blood."
MALARIA'S NEW GROUND ZERO
Malaria death rates dropped by 47 percent between 2000 and 2014 worldwide but it still killed some 584,000 people in 2013, most of them in sub-Saharan Africa, according to the World Health Organization (WHO).
Much of the success in fighting the disease is due to the use of combination therapies (ACTs) based on artemisinin, a Chinese herb derivative, which is now under threat as malaria parasites have been building up resistance to the drugs.
Experts say Myanmar, which has the largest malaria burden in the region, is the next frontier in the spread of resistance to artemisinin.
Positioned between the Andaman Sea and the Himalayas and bordering India and China - home to 40 percent of the world's population - Myanmar is in a unique position to halt the spread of resistance to India and Africa.
"We need to act fast to avoid a big catastrophe," said Pascal Ringwald of the WHO's Global Malaria Programme. "The consequences could be disastrous."
If the problem spreads beyond the region, history would repeat itself for a third time, as resistance to other malaria drugs developed in the area before and spread to Africa to claim the lives of millions, especially children.
But the urgency is far greater this time as new drugs to replace ACTs are not yet available.
"Artemisinin resistance could wipe out a lot of the gains we've made in containing malaria and there is nothing yet to replace it," said Nyan Sint, an epidemiologist and regional malaria officer working with the government's national malaria control program.
Before being identified in Myanmar in 2008, signs of resistance were found in Cambodia and since have also been confirmed in Thailand, Laos and Vietnam, according to the WHO.
Why parasites become resistant to drugs is not entirely clear but prolonged civil conflict, dense jungles, migration and poor quality drugs are all believed to play a part.
The human and economic cost of failing to stop the spread would be huge, according to a model published in the Malaria Journal last month.
The study estimated an extra 116,000 deaths per year if artemisinin resistance is not stopped. Medical costs could exceed $32 million per year, while productivity losses from a rise in cases and deaths are estimated at $385 million.
WORSE THAN EBOLA?
Francois Nosten, a French malaria expert who has been studying the disease along the Myanmar-Thai border for about three decades, said drug-resistance is a quiet menace that is at risk of being overlooked as world attention focuses on the Ebola outbreak in West Africa.
"You don't see people dying in the streets, like with Ebola, but the consequences of it spreading further could be a lot worse," he said.
In Myanmar the partner drugs in ACTs are still working, but they are already failing in western Cambodia, a sign that the clock is ticking fast in the fight against drug-resistance.
Some 60 percent of Myanmar's 51 million people live in malaria-endemic areas, many of them migrants and people in hard-to-reach rural areas.
The number of people dying from the disease fell sharply after ACTs became more widely available but the country still recorded 333,871 malaria cases in 2013 and 236 deaths, WHO data shows.
In Kayin state, formerly known as Karen state, much progress has been made since a January 2012 ceasefire between the government and the Karen National Union (KNU), halting one of the world's longest-running civil wars.
Villages like Min Saw used to have lots of malaria cases but better access to health care workers since the ceasefire, ACTs, rapid diagnosis tests and mass distribution of insecticide-treated bed nets led to a sharp drop.
"We used to have much higher incidence rates," said Saw Ohn Myint, a community health worker. "But we need more training and more equipment to continue to make progress."
International aid organizations have been working with ethnic groups and the government to set up a network of 1,500 village health volunteers that can dispense ACTs.
But thousands of Kayin's state 1.5 million people remain uncovered because they are in hard-to-reach areas, sometimes still controlled by armed ethnic groups restricting access for government health workers.
Mistrust following five decades of military rule in Myanmar still runs deep in Kayin state as its people recover from shelling, land mines explosions and forced displacement.
The situation is also complicated by fake or low-quality anti-malaria medicines dispensed at village shops, which instead of killing the parasites only make them stronger.
"This is a big problem," said Kayin State Health Minister Aung Kyaw Htwe. "We're trying to educate shopkeepers not to sell these drugs and people not to take them."
In Min Saw, where a package a colorful tablets purportedly containing anti-malaria drugs sells for as little as 10 cents, villagers like Ka Lar Nar say sometimes it is easier to buy medication from the "village quack" than to see a health worker.
Under a $100 million, three-year initiative in the Greater Mekong region, the Global Fund to Fight AIDS, Tuberculosis and Malaria has allocated $40 million to Myanmar to fight artemisinin resistance.
Part of the plan is an all-out assault to eliminate plasmodium falciparum, the deadliest malaria parasite, as containment through bed nets, insecticides and treating only those who test positive no longer works.
Villages with a high number of infected people will be flooded with drugs to be taken by everybody, well and sick, to eliminate falciparum before treatments fail completely. The plan has received ethical clearance from the Myanmar government.
Nosten, whose team is mapping 800 villages on the Thai-Myanmar border for potential mass treatment, says elimination is a challenge, in particular as malaria is worst in remote rural areas and because of a large number of migrants in the region.
"Some of these villages are five days' walk from the nearest road," said Nosten, director of the Shoklo Malaria Research Unit in the Thai border town of Mae Sot. "But if we don't do it quickly, it will be too late and millions of people will die."
Mass drug treatments have been tried before with varying success. If the parasites are only cleared from half the population, the plan could backfire and boost resistance rather than eliminate it.
It also requires consent of the population but Nosten is confident that most villagers will participate.
Screening points have also been set up at key locations frequented by migrant workers where everyone can be tested, no matter whether they show malaria symptoms.
(Reporting By Astrid Zweynert; Editing by Ros Russell)