After a study released last week narrowed the likely cause of drug-resistant malaria along the Myanmar-Thailand border to a mutation in a specific parasite gene, health officials are trying to figure out how best to respond.
The culprit, a K13 mutation, has caused the frontline cocktail of drugs (ACT) – a combination of artemisinin and partner medications that has worked for years – to fail in a significant number of the cases recorded by the Shoklo Malaria Research Unit and the Mahidol-Oxford Tropical Medicine Research Unit (MORU) from 2003 to 2013.
The MORU study found that when participants took the drug combination in 2003, the disease was always swiftly defeated. But by 2013, in nearly 20 percent of the cases, the parasite persisted, making comebacks or lingering for weeks.
In part to generate responses to the new findings, the Malaria Elimination Project (METF) are meeting with the Myanmar Ministry of Health, the World Health Organization (WHO), the Global Fund, Kayin health groups and other non-governmental organisations this week in Bangkok, according to Francois Nosten, director of the Shoklo unit and a member of the METF.
They plan to review the MORU study and other recent findings from groups that make up the Regional Artemisinin Initiative (RAI).
“We are gathering evidence on a strategy for rapid elimination of artemisinin-resistant falciparum parasites,” Dr Nosten said.
The WHO argues however that the combination treatment is still getting the job done.
“Delayed parasite clearance does not mean that the drug is failed,” WHO communications consultant Federica Maurizio said in an email. “For this, monitoring of the efficacy of the antimalarials is required and currently WHO is supporting National Malaria Control Programme.”
But Dr Nosten, director of the Shoklo unit, said the response did not address the full scale of the problem.
“It ignores the fact that artemisinin failure is putting pressure on the partner drug and then that this translate into ACT failure,” he said in an email.
The study’s authors concluded last week’s report with a warning that measures are urgently needed to fully wipeout the last vestiges of the parasite.
“Alternatives are needed desperately. With new antimalarials still years from deployment, there is an urgent need to eliminate P falciparum from the area before the recent and substantial gains in malaria control are reversed.”
Resistance has for years cropped up throughout the Mekong Region – which includes Cambodia, Myanmar, Thailand and Laos – and has particularly hit rural areas along the border. Many in the Mekong carry the parasite but have built up immunity to the symptoms. They go untreated and the disease continues to spread.
One controversial plan of attack put forth by some of the scientists behind the recent study, including Dr Nosten, is mass drug administration (MDA) where everyone, both the sick and the symptomless, would be given an ACT treatment. The goal is to wipe out the disease entirely, in the sick and the carriers, before it is given time to adapt to the failing medications. Critics of the method argue it will only speed up the problem of resistance.
Dr Aung Thi, the Malaria Control Program manager within the Ministry of Health and Sports, said that the RAI was started in 2014 to combat the rising resistance levels. The program, backed by the Global Fund, is active in 72 townships, mostly border towns near Thailand, Bangladesh, India and China. The initiative will expand to four more townships this year, in eastern Shan State along the Myanmar-China border.
“The main intention is to eliminate drug-resistant malaria,” he said. “We’re working to avoid allowing the disease to spread to other regions throughout the border areas. The project runs through 2017.”
The resistant malaria is mostly seen in migrant workers living in areas where there is less public awareness about health risks, which is further exacerbated by poor collaboration between public organisations, Dr Aung Thi said.
Dr Aung Pyae Phyo, the lead author the MORU study, agreed.
“Because of the highly mobile nature of the population … it is difficult to supervise, as well as to follow up the anti-malarial treatment especially in migrant people,” he said. “It is a major hindrance to [implementing] a malaria control/elimination program as well as the malaria efficacy research.”
In addition, many of Myanmar’s border states have been plagued by regional armed conflicts for decades.
The patients are often working in the forest and barely earning a living, said an official from the public health department who has worked on the elimination campaign. They get malaria, they take the medication, and, when they start to feel better, they don’t come back in for blood tests or to continue the treatment, Dr Aung Thi said.
“In some cases, [resistance occurs] because they’ve failed to take all their doses,” he said.
To combat drug resistant malaria, health official have been distributing insecticide-treated mosquito nets and clothing, as well as spray repellents, Dr Aung Thi added.
But the MORU study noted that uncertainty surrounding claims of failing ACT drugs may have caused reactions to be slow, which in turn could have “contributed to the failure to contain artemisinin resistance in the greater Mekong area”.
But Dr Nosten took a softer tone in an email sent to The Myanmar Times this week, leading up to the Bangkok meeting.
“We [researchers] are not here to tell the policy makers what to do, but to provide them with the evidence they need, to make informed decisions. With the paper published last week, we show that resistance to artemisinin leads to the demise of the partner drug and the failure of the ACT combination, something that was denied by WHO previously.”
The Myanmar Times reached out to the WHO seeking a response to this claim, but did not receive an answer by press time.*
Malaria-related deaths have drastically declined in Myanmar since 2000 but concerns about these new strains of drug-resistant malaria, and how to treat them if they become more widespread, are on the rise.
According to the WHO, Myanmar had 152,195 reported cases of malaria last year. In 2015, 31.8 million Myanmar people, more than half the population, were considered at risk for malaria.
Translation by Thiri Min Htun
*WHO provided the following clarification in repsonse to Dr Nosten: "In Myanmar, the antimalarials in use are effective, and the efficacy is more than 95% [the WHO's recommended threshold for efficacy of antimalarials is ≥90%] as per the results the study conducted in 2015 . The median treatment failure rate of 1.3%. Clinical and parasitological failure rate for artemisinin plus lumefatrine [currently used as first line antimalarials] and artesunate plus mefloquine is 6pc and 2.2pc respectively."