Friday, July 15, 2016

Myanmar - Mutation key in malaria drug resistance along Myanmar-Thailand border: study

Frontline anti-malaria drugs are failing and the rapid decline in their effectiveness is directly linked to increasing parasite mutations, a study released this week has found.

The mutations to a specific parasite gene, which is particularly prevalent along the Myanmar-Thailand border, may be responsible for the area’s spike in drug-resistant strains, according to the 10-year study by the Shoklo Malaria Research Unit and the Mahidol-Oxford Tropical Medicine Research Unit (MORU).

Researchers have long known that artemisinin, a Chinese herb derivative used to combat malaria, was facing growing resistance. But now partner drugs used in combination treatments are likewise proving impotent.

“This study demonstrates for the first time that artemisinin resistance leads to failure of the artemesinin partner drug, in this case, mefloquine. This means that the first-line artemisinin combination therapy [ACT] introduced here in 1994 has finally fallen to resistance,” said professor Francois Nosten, director of the Shoklo unit.

In 2003, 100 percent of the malaria patients in the study, conducted at clinics on the Myanmar-Thailand border, were cured when they took MAS3, a combination of drugs that had been highly effective in treating the mosquito-borne infectious disease since it was introduced in 1994.

By 2013, the drug worked for only 81.1pc of the study’s participants.

The study was focused on one of the most common types of malaria, called P falciparum. Over the span of the study, researchers found a more than 12-fold increase in the percentage of malaria cases that included the genetic mutation K13, which is more common along that border.

In 2003, when the drugs were still highly effective, only 6.7 percent of the cases contained a K13 mutation. But by 2013, 83.4pc of the cases included the mutation.

This, combined with a doubling of instances of a more universal mutation, is believed to be what caused the drug’s declining effectiveness.

When the K13 mutation is present, the drugs fail more frequently. The same is true of another mutation, Pfmdr. But when both mutations are present, the negative effects are multiplied, rather than added.

“Synergy between these two resistance determinants may help to explain why failure rate declined precipitously in 2009,” the authors wrote.

The connection between the appearance of K13 mutations and a strain’s resistance to artemisinin-based combination treatments, like MAS3, has been alluded to in past studies but, the MORU authors wrote, the link was not “clearly established” and some contested the claim.

“This uncertainty may have contributed to the failure to contain artemisinin resistance in the greater Mekong area,” the authors wrote in the study.

Malaria has been adapting to drugs in the area of the Myanmar-Thailand border for decades. The MAS3 treatment was itself a replacement for a previous drug that had lost its potency.

The treatment has had a much longer run than many of its predecessors but the authors warned that, as MAS3’s effectiveness declines, help, in the form of a new drug, is not on the way any time soon.

The spread of the strain needs to be stopped in the region, they said, with elimination the only option unless new treatments are made immediately available.

“Alternatives are needed desperately,” they wrote. “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.”

Reported deaths related to malaria have declined drastically over the last decade and a half in Myanmar, according to the World Health Organization.

In the year 2000, there were more than 2700 reported deaths related to the disease. By 2014 that number was down to 92, though WHO has warned that these totals are often underreported.

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 at risk for malaria, and 8.4 million were at high risk.

Dave Simpson

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