Antimalarial medication

Resistance to Malaria Drugs Has Spread in SE Asia.

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International experts raised the alarm Tuesday over the spread of drug-resistant malaria in several Southeast Asian countries, saying it endangers major global gains in fighting the mosquito-borne disease that kills more than 600,000 people annually.

While the disease wreaks its heaviest toll in Africa, it’s in nations along the Mekong River where the most serious threat to treating it has emerged.

The availability of therapies using the drug artemisinin has helped cut global malaria deaths by a quarter in the past decade. But over the same period, resistance to the drug emerged on Thailand’s borders with Myanmar and Cambodia and has spread. It has been detected in southern Vietnam and likely exists in southern Laos, said Prof. Nick White of the Thailand-based Mahidol Oxford Tropical Medicine Research Unit.

White, a leading authority on the subject, said that while there’s no confirmed evidence of resistance in Africa, there’s plenty of risk of transmission by air travelers from affected countries, such as construction laborers, aid workers or soldiers serving on peacekeeping missions.

“We have to take a radical approach to this. It’s like a cancer that’s spreading and we have to take it out now,” White told a conference at the Center for Strategic and International Studies think tank in Washington. He said no alternative anti-malarial drug is on the horizon.

The U.N. World Health Organization, or WHO, is also warning that what seems to be a localized threat could easily get out of control and have serious implications for global health.

Mosquitoes have developed resistance to antimalarial drugs before.

It happened with the drug chloroquine, which helped eliminate malaria from Europe, North America, the Caribbean and parts of Asia and South-Central America during the 1950s. Resistance first began appearing on the Thai-Cambodia border, and by the early 1990s it was virtually useless as an antimalarial in much of the world.

Resistance to artemisinin is caused by various factors, such as use of substandard or counterfeit drugs, or prescribing artemisinin on its own rather than in combination with another longer-acting drug to ensure that all malaria-carrying parasites in a patient’s bloodstream are killed off.

Scientists have been working for decades to develop a malaria vaccine, but none is yet available.

Nowhere are the challenges to countering drug resistance greater than in Myanmar, also known as Burma, which accounts for most of malaria deaths in the Mekong region, according to a report for the conference by Dr. Christopher Daniel, former commander of the U.S. Naval Medical Research Center.

Myanmar’s public health system is ill-equipped to cope, although once-paltry government spending on it has increased significantly under the quasi-civilian administration that took power in 2011.

Dr. Myat Phone Kyaw, assistant director of the Myanmar Medical Research Center, said malaria drug resistance first emerged in the country’s east where migrant workers cross between Myanmar and Thailand, and is assumed to have spread to other regions. Death rates have dropped as effective treatments have become more available, but more aid and research is needed as transient workers in industries like mining and logging pose a continuing transmission risk, he said.

White said it is critical to prevent drug resistance creeping across Myanmar’s northwestern border with densely populated India. “In my view, once it gets into the northeast part of India, that’s it, it’s too late, you won’t be able to stop it,” he said.

The Center for Strategic and International Studies is advocating greater U.S. involvement and aid for health and fighting malaria in the Mekong region, particularly in Myanmar, where Washington has been in the vanguard of ramping up international aid. The think tank says that can increase America’s profile in Southeast Asia in a way that will benefit needy people and not be viewed as threatening to strategic rival, China.

But securing more funds won’t be easy at a time when Washington is cutting back on programs for its own poor. The U.S. is already a major contributor to international anti-malaria efforts, and in Myanmar, is promising $20 million per year in health assistance under its recently resumed bilateral aid program.

White said the problem was less one of lack of funds, than in countries having the will to take quick action to fight a disease that hits the rural poor, which have less of a political voice than urban populations.

He said infection rates have been dropping but the disease needs to be wiped out entirely or it could be distilled to the most resistant parasites and infection rates will rise again. “Once it reaches a higher level of resistance where the drugs don’t work, we are technically stuffed,” White said.

Malaria programme gets kiss of death from Global Fund.

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It appears that the Affordable Medicines Facility — Malaria (AMFm) is being scuttled by the Global Fund to Fight AIDS, Tuberculosis and Malaria. The AMFm is a multimillion-dollar programme to get effective drugs — artemisinin-based combination therapies (ACTs) — to remote rural villages, where local stores are often the main providers of medicines.

That’s my first take on the Global Fund’s announcement this afternoon, delivered towards the end of a two-day meeting of its board, which began yesterday in Geneva, Switzerland. The fund intends to end AMFm’s stand-alone status, and instead “integrate” the AMFm into its existing core system of providing grants to countries to purchase drugs, bed nets and other malaria-control measures.

Meanwhile, just in: the Fund announced a few minutes ago that it has nominated as its new executive director Mark Dybul, a former head of the President’s Emergency Program for AIDS Relief (PEPFAR), who now co-directs the Global Health Law Program at the O’Neill Institute for National and Global Health Law at Georgetown University in Washington DC. It follows the resignation of Michel Kazatchkine in February (see ‘Global health hits crisis point‘).  More on that later.

The idea behind the AMFm was to make ACTs the frontline treatment, something which has been badly hindered by their much higher price than older antimalarials. Although these older drugs, such as chloroquine, are cheap, they are often ineffective because the parasite has developed resistance to them.

AMFm’s strategy was to first guarantee a market of large bulk orders, allowing it to negotiate large cuts in the price of the drugs from pharmaceutical companies. It then gave importers in affected countries — both in the public and private sector — a subsidy on their purchases, to bring the final price to the consumer down to a level competitive with older drugs. It was also intended to compete with artemisinin monotherapies, which are a recipe for generating drug resistance against the only drug class that is truly effective against malaria.

A full-blown country-level trial of the AMFm concept in eight countries — Cambodia, Ghana, Kenya, Madagascar, Niger, Nigeria, Tanzania (including Zanzibar) and Uganda — began in July 2010 and runs until December 2012. It has had its critics — see ‘Malaria plan under scrutiny’ — but in anyone’s reasonable terms it has already been remarkably successful in many important ways within a very short period ( see the 31 October Lancet paper ‘Effect of the Affordable Medicines Facility—malaria (AMFm) on the availability, price, and market share of quality-assured artemisinin-based combination therapies in seven countries: a before-and-after analysis of outlet survey data’).

The Global Fund’s press release detailing its plans is entitled ‘Board approves integration of AMFm into core Global Fund grant processes‘, and much of its soothingly reassuring content would perhaps have many thinking that the AMFm’s integration into the Global Fund’s core grants system is good news. But it is in effect being killed. There’s will be no new money ringfenced for the AMFm once it runs through its current funding up to the end of 2013, which means that any countries wanting to set aside cash for the private sector will be required to take this from their country grants from the Global Fund. In reality, that will probably translate into AMFm activities simply being terminated in most countries, leading to local price rises in ACTs, and the drugs disappearing off the shelves of local pharmacies. AMFm’s clout in negotiating bulk pricing deals internationally will also probably be weakened.

Here’s what a group of AMFm’s supporters wrote in the Lancet on 31 October about what ‘integration’ of the AMFm into the Global Fund would mean (from’The Affordable Medicines Facility—malaria: killing it slowly‘):

“In November, 2012, the Board of the Global Fund will vote to either continue AMFm in a modified form after December, 2013, or terminate the programme. There is a strong push from donors (though not from countries) to integrate AMFm into the regular Global Fund model, whereby countries would choose how much of their country budget envelopes, which are already committed to other priorities supporting the public sector, to reallocate to AMFm. We believe that this approach will create instability in artemisinin demand, lower the number of ACT manufacturers, increase ACT prices, and abandon the millions who depend on AMFm-subsidised ACTs. Most importantly, it will kill a programme that, when fully implemented, rapidly met its benchmarks despite the many constraints, expectations, and unrealistic timelines imposed on it. We must acknowledge that an efficient approach to subsidising antimalarial drugs has worked, making them available in the private sector where people go to buy them.”

The Global Fund’s board has decided AMFm’s fate, and there is probably no going back on that. But the world now urgently needs a strategy that works with the private sector to keep down ACT prices, particularly in Africa.

Souce: Nature blog