HTEE KAW HTAW, Karen State — Seventeen-year-old Ma Win was exhausted, to put it mildly. During the rainy season this year, the young woman fell sick with chills, body aches, joint pain and dizziness—not once, but twice, within two months. “I couldn’t walk,” she said in July, just days after recovering. She had malaria again, a common illness in this Karen State village that was isolated for several decades by armed conflict and poverty. In the past she might have been hard-pressed to find medicine without crossing the border to Thailand, but today it’s a different story. Htee Kaw Htaw, a small community of farmers near the Moei River, may seem an unlikely place for some of the world’s top malaria experts to focus their attention. But the village is now at the epicenter of a massive global push to beat the mosquito-borne disease that already kills 660,000 people every year, and which, if left to follow its current course, could soon do much greater damage. Race Against Resistance During the rainy season here, the air is fresh as cows graze in a lush green valley of the Dawna Mountains, while barefooted children walk to school on a dirt path. Htee Kaw Htaw seems calm these days, perhaps belying tensions still simmering under the surface as it recovers from a civil war that left its people vulnerable to land mines, shelling and forced displacement. A ceasefire almost three years ago ended clashes between the government and the Karen National Union (KNU), and today most of the village’s 650 people make their living as farmers, growing corn, beans and rubber. But they say this land was once covered with virgin forest—a fertile breeding ground for the mosquitoes that still proliferate in rice fields and streams, making malaria a normal part of life. [irrawaddy_gallery] As common as it may be, the disease is not always easy to identify in its early stages. Passed from person to person through the bite of infected mosquitoes, it often begins like the flu, with headaches, fatigue, fever and nausea. But as parasites from the mosquito spread to the kidneys, lungs and brain, the symptoms can be horrifying: bone-piercing chills, uncontrollable trembling and severe pain that was described by one victim as akin to stings from an electric shock gun. If left untreated, organs can fail, leading to seizures, coma and death, sometimes less than 24 hours after the onset of symptoms. For a while, people living in malaria hotspots around the world seemed to have found some relief. A so-called malaria wonder drug was discovered in China, and when it came to the Myanmar-Thailand border in the 1990s the number of cases dropped dramatically. But lately the news has been less rosy—indeed, recent developments in Southeast Asia have left some scientists feeling panicked—and in the turn of events, Htee Kaw Htaw and other Karen villages have landed on the world health radar. The deadliest type of malaria-causing parasite, Plasmodium falciparum, has been evolving here along the border and elsewhere in the Mekong region, and in doing so it has developed resistance to drugs. Today, the wonder drug, known as artemisinin, is taking longer to clear parasites from the blood of infected people. If it fails to work completely, the results could be catastrophic. Scientists fear that if malaria is not totally eliminated from the region soon, resistance to artemisinin could make its way west to India and then Africa, where the disease already kills hundreds of thousands of people every year, mostly children. Resistance has spread this way at least three times in the past with other drugs, but this time there is a greater sense of urgency: Currently, no other replacement drugs are available. And while some new options are in the pipeline, it will likely be years before they are on the market and available for widespread use. “This is an emergency,” says Prof. François Nosten, a French malaria expert who has been studying the disease along the Myanmar-Thailand border for about three decades. “We are in a race against resistance, and we are losing because we are too slow to react.” Governments and international donors have spent billions of dollars trying to stop drug resistance from spreading, but it’s not working. The wonder drug is taking longer to clear parasites in northern Cambodia, Thailand, Vietnam and here in eastern Myanmar, while there are indications that resistance is also emerging in central Myanmar, southern Laos and northeastern Cambodia. “We need to do something different,” Dr. Nosten says. He and other scientists are turning their attention to Myanmar, which, at a crossroads between India and China, borders about 40 percent of the world’s population. ‘Healthy’ Carriers More than two-thirds of Myanmar’s population lives in malaria-endemic areas, from the upper reaches of Kachin State to Myeik in the far south. The number of people dying from the disease fell sharply after artemisinin-based combination therapies became more widely available, but the country still has by far the largest malaria burden in the Mekong region, with more than 480,000 cases reported in 2012, leading to about 400 deaths, according to statistics from the World Health Organization (WHO). And the toll goes beyond health: By keeping people away from school and work, malaria hits education and the economy, making it tougher for already impoverished villages to develop. Worldwide, the cost in lost economic growth from the disease is likely higher than US$12 billion every year, according to the Centers for Disease Control and Prevention in the United States. In Myanmar, many people lack access to medicine, particularly in rural states along the country’s borders that are still recovering from war. “Government hospitals are far away, and most people are too poor to spend on health care,” says Saw Soe Win Kyaw, director of the Back Pack Health Worker Team, a network of medics who carry supplies on their backs from village to village. While the government’s health budget remains minimal, one of the leading international funders for malaria control is stepping in to help. The Global Fund to Fight AIDS, Tuberculosis and Malaria has pledged $100 million to fight drug resistance over the next three years in the Greater Mekong region, and of that money, $40 million is going to Myanmar. Another $3.3 million will be spent along the Myanmar-Thailand border, in part to set up hundreds of malaria clinics throughout Kayin State, where medics can test anyone with a fever and offer medicine to those who are infected. But even with more manpower, a serious challenge remains. Not everyone with malaria shows symptoms, so many are never tested. In some villages, more than half the population carries parasites in their blood, though they appear healthy. They go about their daily lives without the slightest awareness that something is wrong, but there is a chance they will pass parasites to mosquitoes that bite them, and those mosquitoes can infect other people down the line. Medicine for the Masses That’s why the Global Fund has set aside $400,000 of its $3.3 million cross-border interventions for a more controversial strategy: giving medicine to everybody in malaria hotspots, including those who are not sick. This strategy, known as mass drug administration, is a departure from current efforts to control the disease in Southeast Asia. It has been tried in the past but with mixed results, leading the WHO to stop recommending it decades ago. Debate is ongoing, but some scientists believe it is the only feasible option left to tackle drug resistance. “Targeted malaria elimination is considered a pilot,” says Izaskun Gaviria, a senior fund portfolio manager at the Global Fund, using another name for mass drug administration along the Myanmar-Thailand border, and adding that other partners were funding similar pilots in Cambodia and Vietnam. “If successful, it might be expanded to all the borders.” In Myanmar, perhaps before the year’s end, mass drug administration will be proposed in villages where a high number of people are found to be infected with the Plasmodium falciparum parasite. In small villages, everyone might line up at a clinic for treatment, while people in larger villages might receive it from medics traveling from house to house. Whenever possible, the medics will also watch to ensure that the medicine has been taken properly: once per day for three days, and with a meal such as rice, vegetables and curry to reduce possible side effects like stomachaches and dizziness. The three-day supply will be distributed once every month for three months, but only after the plan is approved by an ethics committee under Myanmar’s Department of Medical Research, and only with consent from the villagers themselves. Before any medicine is given out, medics will hold focus group discussions with community leaders, school teachers and other residents, who can ask questions about mass drug administration and why it has been recommended. If the plan goes forward, everyone will be given a chance to participate except pregnant women and babies, and at any point—even during the second or third months—anyone can decide to opt out. Dr. Nosten, the French malaria expert, will help implement the project with his Thailand-based malaria research team, the Shoklo Malaria Research Unit. He hopes eight out of every 10 people in selected villages will take the medicine, but it might be tough to reach migrant workers who are on the move. “If you clear the malaria parasite only from half the population, the other half may continue to transmit,” he says. Not Black and White Mass drug administration is nothing new. It’s an accepted strategy for fighting other diseases, including river blindness in Africa and filariasis in Asia, but for malaria it’s more controversial. Since the 1930s, mass drug administration has been tried in malaria hotspots around the world, including in Europe, back when Italy still saw cases of the disease, but the results have not been black and white. That’s partly because there are so many variables. In each attempt, different drugs and regimens have been used, while the mosquitoes carrying the parasites have been different depending on the location, as have the people taking the medicine. On some islands the strategy has been successful, according to Dr. Nosten, but in other cases it has led to undesired consequences, including a worsening of drug resistance. This happened in the 1950s in Cambodia, when experts from the WHO mixed antimalarial drugs with cooking salt and distributed it to villages. People ate the salt and absorbed the drugs into their blood, but the parasites grew resistant because the doses were low and uncontrolled. Myanmar also tried mass drug administration in the 1990s. The number of malaria cases dropped initially, but the disease later came back, and with even greater force. That might have been due to the medicine that was used: sulfadoxine-pyrimethamine, an antimalarial drug that turned out to encourage, rather than prevent, the passing of parasites from infected people to mosquitoes. Two years ago, a small study of mass drug administration began in four villages along the Myanmar-Thailand border, with a different combination therapy that contains the wonder drug artemisinin and is recommended by the WHO. Led by Dr. Nosten, the study is ongoing until mid-2015, but preliminary results are encouraging. “Before, many people were sick. Now it’s very rare to find malaria here,” says Saw Slight Naw Nyo, a medic who works for Dr. Nosten in Htee Kaw Htaw, one of the four villages. Still, some have continued to fall ill. “I was out in the fields when the medicine was given out,” says Ma Win, the 17-year-old who suffered through two bouts of the disease this rainy season. “But none of my friends have been sick,” she adds. U Ohn Myint, a Buddhist community leader, says he was glad to participate, even though he did not feel ill. “If there was any malaria in my body, I wanted to make it disappear,” he says. Buying Time Under normal circumstances, before launching a larger pilot project with the Global Fund, Dr. Nosten would wrap up this study along the border and publish the results. “But that would be in three years’ time, and in three years it will be too late,” he says. “Next year will be too late—resistance will already have reached a proportion that we cannot control.” It may seem premature to try mass drug administration elsewhere, but in the race against resistance, he says it’s the only option. The current strategy to control malaria—distributing bed nets, spraying insecticides and treating only those who test positive for the disease—can eventually eliminate malaria, “but it takes many, many years, and we don’t have those many years,” he says. It would be too expensive and technically impossible to identify “healthy” carriers by testing everyone in villages, he adds, so “the only alternative is to treat everyone.” “No one knows for sure that it’s going to work, but it depends what we mean by working. If we manage at least to reduce malaria so much that for the next five years there are virtually no more cases—if every time there is a case, we can detect it and treat it—at least we buy time. Maybe we buy five years, maybe 10. Maybe in 10 years we have a vaccine or a new drug.” Dr. Thaung Hlaing, deputy director of Myanmar’s national malaria control program, says that despite the uncertainties, he supports the Global Fund’s pilot of mass drug administration and is eager to see results after one year. “We are optimistic,” he says. Meanwhile, the US government—the biggest donor country to the Global Fund—is not yet ready to integrate the strategy into its own international malaria program. “The jury is still out, from our perspective. The science isn’t there for us to be ready to invest funding and deviate from what we know are proven, effective interventions,” says Rear Admiral Timothy Ziemer, who leads the President’s Malaria Initiative, launched by former US President George W. Bush in 2005, adding that he would consider supporting mass drug administration in the future if it was found to work well. “The current Global Fund-supported pilot … will provide valuable information that will inform the [Myanmar] Ministry of Health and the global malaria community on whether this strategy is effective,” he told The Irrawaddy. The WHO, which discouraged mass drug administration for routine malaria control after its failure in Cambodia, is now also considering whether the strategy is necessary. “We are in a critical period of losing the powerful drug. It is an exceptional situation, and we are looking at old interventions and bringing them back to see if this would help,” says Krongthong Thimasarn, a malaria specialist at the WHO office in Yangon. But because Myanmar is such a dangerous place for artemisinin resistance, she adds, mass drug administration should be applied with extreme caution. “It is like a surgeon operating at the heart of a patient.” This story first appeared in the October 2014 issue of The Irrawaddy magazine.
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