Drug-resistant malaria appears to have taken hold in much of Myanmar, and scientists aren’t exactly sure how. It may have spread here from elsewhere, or it may have emerged independently, but in any case, the strategy to fight it seems set for a major change.

More than a decade ago, the deadliest type of malaria-causing parasite, Plasmodium falciparum, evolved in Cambodia, becoming resistant to the main anti-malaria drug, artemisinin.

For several years, resistant parasites have also been detected along the Myanmar-Thailand border, as well as in Bago Region, but earlier this year, scientists revealed that the problem may be much greater than was previously realized.

In February, a study published in The Lancet Infectious Diseases journal showed that at 55 malaria treatment centers across the country, nearly 40 percent of parasite samples had genetic mutations linked to artemisinin resistance. In fact, these mutations were found in seven of the country’s 10 administrative regions, including in Homalin, Sagaing Region, only 15 miles from the Indian border.

And that’s a big deal. Myanmar—stretching from the Bay of Bengal and the Andaman Sea in the south to the Himalayan mountains in the north—offers the only known path for resistant parasites to make their way contiguously to the Indian subcontinent, and from there to Africa, where the disease already kills hundreds of thousands of children every year. This has happened in the past with other anti-malarial drugs that were once powerful but are now ineffective, resulting in the loss of millions of lives.

“Clearly, Myanmar is an important part of the frontline in the battle to contain artemisinin resistance,” the scientists wrote in the study. But “the pace at which the geographical extent of artemisinin resistance is spreading is faster than the rate at which control and elimination measures are being developed and instituted, or new drugs being introduced.”

Translation: Current strategies for fighting the disease aren’t working, and, should artemisinin fail completely, there’s no other medicine ready to replace it.

Artemisinin-combination therapies are still 95 percent effective in Sagaing, according to Dr. Pascal Ringwald of the World Health Organization’s Global Malaria Program. But in the event that they begin to fail, the results could be catastrophic in Myanmar, whose health-care system is still in shambles after half a century of neglect during military rule. The country also faces Southeast Asia’s largest malaria burden, with more than 333,000 confirmed cases reported in 2013, down from 480,000 cases in 2012.

Scientists caution that more testing is needed to confirm whether drug resistance is present so close to India. The sample size from the study was relatively small, and debate is ongoing over whether the genetic mutations discovered are directly linked to resistance, or are merely indirect indicators of possible resistance, according to Dr. Francois Nosten, a Thailand-based malaria expert who contributed to the study.

Jumping or Popping

If history repeats itself and drug resistance winds up in Africa again, it’s unclear whether it will spread there from Southeast Asia or emerge independently.

Dr. Christopher Plowe, director of the Institute for Global Health at the University of Maryland, which has major programs in Myanmar, says a sort of “paternity testing” for malaria parasites allows scientists to determine whether they are related to parasites in other locations. In Southeast Asia, he says, it appears resistant parasites are sometimes spreading from one place to another, in a process known as “jumping.” But in other cases, he says, they’re emerging independently, in a process known as “popping.”

“There are jumps between Cambodia and Vietnam, and in the published literature only pops so far in Myanmar,” he says, adding that jumps have also been seen across the border between western Thailand and southeastern Myanmar. “The fact that both are happening is indeed the worst possible scenario.”

“It may be just a matter of time until artemisinin resistance takes hold in Africa, whether it is by popping or jumping… Great progress is being made in some African countries, less in others, but there is a nightmare scenario around the corner if we lose artemisinins: huge resurgences everywhere with no effective drugs to offer for treatment, and millions of deaths, as we had in the 1980s and 1990s.”

Earlier this year, scientists said they had detected malaria parasites in Kenya with mutations linked to resistance, and those mutations were different from the mutations found on parasites in Cambodia.

If resistance is popping up independently, Dr. Plowe says, it makes no sense to put up a firewall to block it, as countries in Southeast Asia have been trying to do for years. “A strategy of containment—the so-called firewall—is not likely to work, and we need to move fast to eliminate malaria” from the Greater Mekong Subregion and Africa, he says.

In 2011, the World Health Organization (WHO) called for a containment strategy to fight malaria globally, and two years later it launched an emergency initiative to contain drug resistance in the Greater Mekong Subregion—by distributing bednets, spraying insecticide and treating anyone who tested positive for the disease. Heavyweight donors like the Bill & Melinda Gates Foundation and the Global Fund to Fight AIDS, Tuberculosis and Malaria were eager to help; the latter put down US$100 million over three years to fight malaria in the region. The WHO estimated at the time that $350 million more would be needed for Southeast Asia’s containment effort through 2015.

Elimination

Francois Nosten, the Thailand-based malaria expert, isn’t convinced that drug-resistant malaria has only emerged independently in Myanmar, as Dr. Plowe suggests.

“The jury is still out,” Dr. Nosten says. But he’s sure that containment is not working well enough, and that it’s time for a strategy change. “We need to eliminate as much malaria as we can,” he says.

Others agree. In mid-May, the WHO was preparing to ask member states in the Greater Mekong Subregion to adopt a strategy of complete elimination—taking steps to prevent any new cases of malaria from arising.

With the new strategy, health workers would continue to distribute bed nets, spray insecticide and treat people with the disease, but they could also go a step further: In some cases, they could give anti-malarial medicine to entire villages in malaria hotspots, including to people who don’t show any symptoms or feel sick.

This technique, known as mass drug administration, is set to be included in the elimination strategy, according to Izaskun Gaviria, the Myanmar portfolio manager at the Global Fund, which launched a pilot project for mass drug administration in Southeast Asia last year, including in Myanmar.

“No adverse effects have been documented so far, none whatsoever, which is quite encouraging,” she said. “Initial data indicates that the pilot project has been successful.”

Southeast Asian governments have already set a goal to eliminate malaria from the region over the next 15 years, Gaviria added. “Of course, some countries can do it faster than others—Myanmar being for obvious reasons the last one—but we are hoping that by 2030 all the countries will have eliminated malaria,” she said.

But developments in Cambodia could point to new problems. There, parasites are starting to show resistance to piperaquine, a partner drug that’s used in combination with artemisinin.

“It is extremely concerning,” Gaviria said, noting that piperaquine resistance has not yet been detected in other countries. “Artemisinin makes you feel good within a very short period of time, but it does not kill all the parasite flow—it is the partner drug that does that—so if we lose the partner drug, we will be in big trouble.”

A British pharmaceutical company is also developing what could be the world’s first malaria vaccine, but it has only protected about one-third of children vaccinated during testing, and the research and licensing for it are focused on Sub-Saharan Africa. “So its use in Asia, while possible, is less likely in the near term,” Gaviria said.

http://www.irrawaddy.org/magazine/malaria-battle-set-to-ramp-up.html