YANGON, Myanmar - One of the world's most challenging and deadly races is underway in the forests of this turbulent country.
A new strain of drug-resistant malaria has emerged in Myanmar just as the country is emerging from a half-century of isolation, increasing the risk that the lethal scourge will spread into India and Africa.
If the strain reaches other regions, it could undo huge gains made over the past decade - at a cost of billions - to corral the illness.
Malaria mortality has fallen 42 percent worldwide since 2000, but the disease continues to sicken more than 200 million people and kill 500,000 children a year, or about one every minute of every day, according to the World Health Organization (WHO).
Fighting malaria has been a Sisyphean task over the past century. Major attempts to eradicate the disease - caused by a parasite transmitted by a particular mosquito species - failed in part because it's a moving target that evolves and develops resistance to drugs and pesticides.
Yet the latest push has brought eradication in sight, at least for some experts and for the Seattle-based Bill & Melinda Gates Foundation. Eliminating the disease is one of the most ambitious projects the world's largest philanthropy has undertaken.
With more than $2 billion committed, the foundation is the leading private supporter of research into new treatments, vaccines, diagnostic tools, disease mapping and other weapons to fight malaria.
This research should help the foundation press the global community for a renewed attack that could begin about 2020, putting to use new drugs now in the pipeline.
As long as the drug-resistant strain spreading in the forests of Myanmar can be contained, that is.
"Myanmar is the linchpin country, really," said Tom Kanyok, a former WHO scientist and now the foundation's senior malaria program officer for the Greater Mekong region, which includes Myanmar, Thailand, Cambodia and Vietnam.
This comes as Myanmar - formerly called Burma - emerges from 50 years of repression, moves toward a democratic state and opens to trade, tourism and foreign investors.
"People are flooding in," Kanyok said. "All the business-class seats are full and the other seats are full of tourists wanting to go see the country. After the opening up of the country it's just a sea change."
In the commercial capital of Yangon, formerly known as Rangoon, ancient golden pagodas share the skyline with dozens of construction cranes. Shoeless children play soccer in dusty side streets below stately, crumbling buildings built a century ago under British rule.
Burma was the most prosperous country in Southeast Asia until a military coup in 1962. It's now one of the poorest in all of Asia.
Myanmar borders 40 percent of the world's population, with China to the north, Thailand and Laos to the east and India and Bangladesh to the west.
Being a crossroads may help the country catch up to the economic growth that Vietnam and Thailand have seen, but it also positions Myanmar to export drug-resistant malaria.
After decades of spending little on health care, the country is especially hard hit by the disease. Myanmar accounts for nearly 80 percent of malaria cases and 75 percent of malaria deaths in the Mekong region, according to a 2012 assessment funded by the Gates Foundation and Australia.
Overall, more than 40 million of Myanmar's about 60 million people live in malaria-endemic areas, according to WHO.
As the economy grows, people may travel and unwittingly bring malaria parasites along. One carrier may infect 100 others, who may infect 1,000 others.
Migrants may follow the path of Than Toe of Yangon. As a teen, he worked in the fishing industry along the border with Thailand, where drug resistance is concentrated.
Toe was sickened by malaria and treated with a cheap medicine. Later he moved to the city to drive a cab and start a marketing business.
Timing was on his side. Toe, now 43, was infected before the resistant strain emerged. His treatment worked and he's now raising three girls in the city.
Hard-won gains at risk Myanmar's government appears to be moving in the right direction as it builds up a health care system. It's working with WHO, the Gates Foundation and other groups to tackle malaria.
"From our region we're now trying to scale up our activities - all our activities," said Dr. Thaung Hlaing, deputy director of the Ministry of Health's National Malaria Control Programme.
Hlaing said the plan is to contain the resistant strain and eliminate it before it spreads west to India and then to Africa, creating "more disaster."
"This is not about a Myanmar problem; this is a global concern," he said.
The risk that this strain of malaria could spread and reverse hard-fought gains isn't hypothetical. It happened before with tragic results.
Eradication was in sight in the 1950s and succeeded in the U.S. and southern Europe.
But the effort faltered because of funding shortfalls, war, scattershot participation - and the emergence in the 1960s of a drug-resistant strain in Southeast Asia. It reached India and Africa, where severe cases and deaths doubled or tripled in some countries.
Research in China led to artemisinin, a derivative of wormwood and traditional herbal treatment. It took years for this medicine to emerge from China, and it wasn't widely used until after 2000.
Then it became a key part of a renewed attack on malaria funded largely by the Global Fund, a coalition of governments and private funders to which the Gateses have given $1.4 billion. Over the past decade, this attack saved more than 3 million lives.
"Now it's such a magical drug we're doing everything we can to avoid drug-resistance," Bill Gates said at an April health product forum in Seattle. "We're super dependent on it."
He's helping fund a new arsenal for the malaria fight, including next-generation drugs, but they won't be ready for perhaps four or five years. A single-dose malaria pill isn't expected until 2023.
"I think there probably isn't the right tool kit yet to say with confidence that we can get to elimination and eradication, but there's an entire field pointed in this direction," said Dyann Wirth, chair of Harvard's Department of Immunology and Infectious Disease.
Artemisinin resistance was detected in Cambodia in 2006, and has since been found around the Mekong region. Today, with international travel more common, resistance could spread farther and faster.
"If it happens now, we are going to have a big problem," said Dr. Gawrie Nirdoshi Loku Galappaththy, malaria technical officer in the WHO Yangon office. "That's why it's really important. We have to stop (it) here."
Gawrie has a team of 15 funded partly by a $100 million Global Fund grant to fight drug-resistant malaria in the Mekong. The largest share, $40 million, went to Myanmar, but it will last only until 2016.
Gawrie has been an intermediary of sorts between the ambitious attack on malaria the Gates Foundation is pursuing and the government's measured approach.
Somewhat controversial is the foundation's interest in mass administration of drugs, carpet-bombing parasites by treating everyone in problem areas whether they seem sick or not, an approach it's testing in the region.
In April, Bill and Melinda Gates flew to Cambodia to see progress firsthand. They talked to people about whether they understood they could be carrying the disease.
Success with pilot programs could help make the case for a new, aggressive malaria-eradication plan. The work also helps them learn about drug distribution and other aspects of the challenge.
"I think this is going to be a great learning time for our team as we start to look at these very local eliminations - about all the pieces in the chain that need to get done," Melinda Gates said at the Seattle forum.
While Myanmar supports the malaria work, it's also sensitive to being used as a laboratory for new approaches.
Locally, the malaria crisis is overshadowed by ethnic tensions and a highly anticipated election in 2015, seen as a test of whether Myanmar is truly reforming and legitimizing its government.
The country also struggles with other health risks.
"There's a lot of other things that kill not just children but all ages," said Simon Khin, a former software engineer who as a child lived in border areas. "That includes the war, dengue fever, TB, typhoid."
Khin, who immigrated to Seattle 30 years ago and now runs a refugee-assistance program, said people who live around malaria generally aren't as alarmed by its prevalence.
"It's pretty much a fact of life," he said.
Such acceptance complicates the issue of administering drugs to masses of people, including those without symptoms. WHO isn't yet pursuing this approach. But with drug resistance now an emergency, it has called for large-scale pilot studies.
Meanwhile, the Gates Foundation is testing mass drug administration in border areas and hopes to treat 250,000 people by 2016.
"There's a little bit (of) unhappiness or misunderstanding about this with the national program, but we were not consulted by anyone," Gawrie said.
The foundation's Kanyok said he meets regularly with the health ministry and they have a good relationship. In Myanmar, it's deferring to the government, he said.
"It's a health and humanitarian issue that everyone can grab on to because people see the results of malaria in the country," he said.
It's largely a question of timing, deciding how much longer new approaches should be researched versus using them sooner, according to Chris White, a British tropical-medicine expert in Yangon.
White is senior malaria technical adviser with Population Services International (PSI), a Washington, D.C.-based charity.
Myanmar's government, he said, is right to want evidence before plunging ahead, yet it's also time to "get very aggressive in our control efforts" and "possibly taking some risks."
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Being a top priority among charities when it comes to malaria is a big opportunity for Myanmar.
Maps and infrastructure created to track malaria and deliver drugs will help provide other care, and eliminating malaria would bring economic gains.
At the same time, there's a risk that Myanmar's broader progress could stall and interrupt the malaria fight at a critical point.
The country began opening up after the 2010 election of its current president, Thein Sein, a relatively moderate former general.
Reforms he initiated led the U.S. and Europe in 2012 to end sanctions for human-rights violations.
But it's a country in transition, with lawless regions controlled by drug traffickers and militias, concerns about corruption and harsh oppression of ethnic minorities.
"I would say this is without doubt the most challenging operational environment I've ever worked in my entire career," said White, who earlier spent 12 years in Africa.
"All the places where you really need to reach in terms of malaria transmission are often forested, mountainous border areas that are also areas of high sensitivity politically, areas with conflict, internal displacement, let alone logistically difficult," White said.
PSI uses private-sector approaches to improve global health, including a franchising model to build a network of clinics in Myanmar.
Now PSI is attempting to stem the use of substandard malaria drugs, a $25 million project funded mostly by the Gates Foundation and the U.K.
Of particular concern are cheap "monotherapy" drugs with a single active ingredient, currently artemisinin. They may treat malaria but increase the risk of parasites mutating to resist that ingredient, as they have in the Mekong.
Malaria monotherapies are banned in much of the world and are steadily being replaced with more effective drugs that have multiple active ingredients.
PSI works with drug companies to flood the market with better drugs. It packages them in boxes mimicking those of the older drugs people recognize and trust - like putting carrots in a Cheetos bag.
Donors subsidize the cost, so a full course of drugs sells for 50 cents - about what people had been paying for a partial dose of monotherapy.
So far it's working better than expected. In the first nine months, the market share of good malaria drugs in Myanmar grew from 3 to 73 percent.
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Funding and research are only part of the story, though.
Bill and Melinda Gates also brought a new perspective, leading to "a major paradigm shift," said Wirth, of Harvard.
The field previously thought of malaria as a disease to be mitigated or controlled. Now it's looking more at how it's transmitted, with an eye toward elimination.
Wirth said the turning point was having the Gateses "basically say, ‘Why don't we think about elimination and eradication? It's the right thing to do from a moral standpoint and let's figure out what the technical and implementation obstacles are.' "
This thinking is influencing researchers from South Lake Union to Switzerland.
It's even reaching through to the opaque leadership of Myanmar, where Seattle's outsized role and research are changing the malaria conversation and potentially helping snuff out the emerging threat.
"Seattle," said WHO's Dr. Gawrie, "is always there."
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