Bad news from this flurry of articles on malaria and drug resistance. Not all of them are clear, but I think I understand:
1) Artemisinin combination therapy, a major tool in the quixotic goal of malaria elimination in Myanmar, is losing its effectiveness. Perhaps hundreds of millions of dollars are riding on it. That money may very well be totally wasted.
2) Mainstream media sources are finally waking up to the fact that artemisinin resistance by malaria parasites will probably not 'spread' from Asia to Africa but will likely arise independently there. It already has.
Jamie
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New study adds urgency to concerns about drug-resistant malaria
Democratic Voice of Burma
24 June 2016
The rapid decline in effectiveness of a widely used anti-malaria drug treatment on the Thai-Burmese border is linked to the increasing prevalence of specific mutations in the malaria parasite itself, according to a paper published in the Clinical Infectious Disease Journal.
The mutations in specific regions of the parasite’s kelch gene — which are genetic markers of artemisinin resistance — were the decisive factor, the authors say, in the selection of parasites that are also resistant to mefloquine.
This resulted in the growing failure of the widely-used anti-malaria drug combination of mefloquine and artesunate, the first artemisinin combination therapy (ACT) used on the Thai-Burmese border.
Led by Dr Aung Pyae Phyo of the Shoklo Malaria Research Unit (SMRU), the study used data from a 10-year study of 1,005 patients with uncomplicated P. falciparum malaria at SMRU clinics on the border.
“This study demonstrates for the first time that artemisinin resistance leads to failure of the artemisinin partner drug, in this case, mefloquine,” says Prof François Nosten, director of SMRU.
“This means that the first line artemisinin combination therapy introduced here in 1994 has finally fallen to resistance,” he said.
Resistance to ACT drugs — the frontline treatments against malaria infection — poses a threat to the global control and eradication of malaria.
If drug resistance spreads from Asia to the African sub-continent, or emerges in Africa independently, as has happened several times before, millions of lives, most of them children under the age of five in Africa, will be at risk.
The study demonstrates that, contrary to the opinion sometimes expressed that resistance to artemisinin is not a direct threat, it is in fact responsible for the rapid demise of the partner drug and the failure of the drug combination, resulting in patients not being cured and further transmission of malaria.
“The evidence is clear that artemisinin resistance leads to partner drug resistance and thereby the failure of artemisinin combination treatments,” said Oxford Professor Nicholas White, chairman of the Mahidol Oxford Tropical Medicine Research Unit (MORU) and chairman of the Worldwide Antimalarial Resistance Network.
Given the limited number of effective drugs, it is urgent to eliminate P. falciparum from the areas where it has developed resistance to the artemisinins, said Prof White.
A unit of the Bangkok-based MORU, SMRU is based in refugee camps and migrant communities along the Thai-Burmese border.
Link: http://www.dvb.no/news/new-study-concerns-drug-resistant-malaria/67522
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Mutation key in malaria drug resistance along Myanmar-Thailand border: study
Dave Simpson
Myanmar Times
Thursday, 23 June 2016
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.
http://www.mmtimes.com/index.php/national-news/20998-mutation-key-in-malaria-drug-resistance-along-myanmar-thailand-border-study.html
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Anti-malaria drugs fail on Thailand-Myanmar border
Drugs that are widely used to treat malaria are rapidly becoming less effective at helping patients on the Thailand-Myanmar border.
Wellcome researchers have found that genetic mutations in the kelch gene of the malaria parasite have made the parasite resistant to the anti-malaria drug mefloquine and the drug artusenate.
These drugs are typically used in combination to treat malaria. This treatment, known as artemisinin combination therapy (ACT), is now failing.
Researchers analysed data from a ten-year study of 1,005 patients with uncomplicated Plasmodium falciparum malaria at Shoklo Malaria Research Unit (SMRU) clinics on the Thai-Myanmar border.
"This study demonstrates for the first time that artemisinin resistance leads to failure of the artemisinin partner drug, in this case, mefloquine. This means that the first-line artemisinin combination therapy introduced here in 1994 has finally fallen to resistance," said Professor François Nosten, Director of SMRU.
Resistance to ACTs poses a serious threat to the global control and eradication of malaria. If drug resistance spreads from Asia to the African sub-continent, or emerges in Africa independently, millions of lives will be at risk. Most of them will be children in Africa aged under five.
SMRU, which is a unit of the Bangkok-based MORU (opens in a new tab), is based in the refugee camps and migrant communities along the Thai-Myanmar border in northwest Thailand.
Read more about the research on the MORU website (opens in a new tab).
https://wellcome.ac.uk/news/anti-malaria-drugs-fail-thailand-myanmar-border
