Resistance and counterfeits in Southeast Asia may doom artemisinins

From Paul Chinnock, TropIKA.net:

The antimalarial drug artemisinin - used in the form of artemisinin combination therapy (ACT) - is now the recommended treatment for malaria, replacing older drugs to which the malaria parasite is now resistant. At present there are no other drugs for malaria in the development "pipeline".

But the appearance of resistance to artemisinin in Southeast Asia has been described by malaria specialists as a "disaster". They speak of a "doom scenario" in which artemisinin-resistant strains of the parasite develop throughout the malaria-endemic world, including Africa where most malaria cases and deaths occur.

A report from Cambodia and Thailand, published on Bloomberg Press, features an interview with Arjen Dondorp of the Wellcome Trust-Mahidol University Oxford Tropical Medicine Research Programme, based in Bangkok. He says a flood of counterfeit pills from China and elsewhere is helping to breed artemisinin resistance. This development threatens to unleash a global malaria disaster and undo the decades of work required to develop ACT. In Dr Dondorp's view the present situation is a "time bomb".

Doom

WHO has yet to launch the Gates Foundation-funded initiative it plans in Cambodia and Thailand to combat the spread of resistance - see the earlier TropIKA.net story. It is hoped that work will begin in June. Dr Dondorp speaks of a "doom scenario" if the action taken is not successful. This would involve migrant workers carrying the bug throughout Thailand, and on to Myanmar and India. Later the strain would spread to Africa.

"If we lose the artemisinins at this stage, just now when we dare to mention the word ‘eradication' again, it would be a disaster for malaria control. It would cause millions of deaths, without exaggeration" said Dr Dondorp, lead author of an as yet unpublished study which demonstrates the extent of artemisinin resistance in the Pailin area of Cambodia, close to the Thai border.

Charles Delacollette, head of WHO's Mekong Malaria Programme, which covers Cambodia, Laos, Myanmar, Thailand, Vietnam and part of China said, however, that the doom scenario may be a decade away from materializing, giving the world time to prevent it.

Fighting the fakes

Resistance to earlier antimalarials also seems to have first begun in Cambodia but the massive scale of substandard and fake products now entering the country increases the likelihood that artemisinin-resistant strains will develop and spread. Some of the counterfeits contain low doses of artemisinin and many are artemisinin monotherapy products. Both promote the development of resistance. (Artemisinin should only be used in combination with an older antimalarial as this reduces the possibility that resistance will appear.)

The efforts of the local health system and WHO to prevent the appearance of Dr Dondorp's doom scenario must be accompanied by law enforcement to interrupt the supply of fake drugs.

From Simeon Bennett, Business Report:

Saron Samnith, 14, slouches in the doorway of his family's thatched hut off a dusty track near Pailin, a city in western Cambodia. He has chills, diarrhoea and a three-day-old headache - signs of malaria.

The bout of the mosquito-borne disease, for which he tested positive, is his second in a month. The first left him comatose and close to death, before medicines curbed the attack. Coursing through Saron's veins may be the strain so dangerous that health officials - and the billionaire Bill Gates - are racing to stop it from spreading before it kills millions.

In Pailin, a flood of counterfeit pills from China and elsewhere is helping to breed a superbug that resists even the most-effective medicine. The development threatens to unleash a global malaria "disaster" and undo decades of work to reduce illness, destitution and death, said Arjen Dondorp, a Thailand-based researcher.

"It's a time bomb," said Dondorp, the deputy director of the Wellcome Trust-Mahidol University Oxford Tropical Medicine Research Programme, with headquarters in Bangkok.

The World Health Organisation (WHO) plans to defuse the bomb with a screening and treatment programme to contain and eliminate the resistant strain in and near Pailin. The effort may begin next month. The programme is backed by $23 million (R192m) from the Bill & Melinda Gates Foundation, based in Seattle.

"There's more money put into baldness drugs than is put into malaria," Gates said in February. "Because the disease is only in the poor countries, it doesn't get much investment. You can't get the economies in these areas going, because it just holds things back so much."

The risk of failure raises what Dorndop calls a "doom scenario". In that sequence of events, migrant workers would first carry the bug to Thailand, Myanmar and India. Later, the strain would spread to Africa, which already has most of the world's malaria cases.

"We rang the warning bell in 2005 and nobody believed us," said Pascal Ringwald, the Geneva-based WHO's leading specialist in the malaria parasite's ability to resist drugs.

The doom scenario may be a decade away from materialising, giving the world time to prevent it, said Charles Delacollette, the head of WHO's Mekong Malaria Programme, which covers Cambodia, Laos, Myanmar, Thailand, Vietnam and part of China.

"We don't have many alternatives to the antimalarial drug artemisinin, to which the parasite is becoming resistant in western Cambodia, Delacollette said. "That drug should be protected."

Interpol, the international police organisation based in Lyon, France, traced counterfeit drugs in Southeast Asia to China in 2006 as part of an investigation called Operation Jupiter.

Last year, under Operation Storm, Interpol arrested 27 people in raids across Asia and seized more than 16 million fake pills valued at almost $7 million (R58.5m).

Chemical analysis of pills bought in Cambodia, Laos, Myanmar, Thailand and Vietnam found several other pharmaceutical ingredients, charcoal, and a precursor of the illicit drug ecstasy, according to an account of Operation Jupiter published in the journal Public Library of Science Medicine. Also present were spores and pollen from trees common in southern China, suggesting that at least some of the drugs were made there, the authors said.

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