There is a growing risk that malaria parasites will develop resistance to artemisinin because almost half of both its manufacturers and malaria-affected countries are failing to comply with World Health Organization (WHO) demands to sell it only in combination with other drugs. Artemisinin and its derivatives are the leading treatments for the disease, being the only antimalarials that have not yet seen widespread resistance in malaria parasites.

The full scale of the problem is revealed in a soon-to-be-published WHO briefing seen by Nature, "Stop the marketing of oral artemisinin monotherapies", which calls for governments to empower national drug-regulatory authorities to clamp down on offending companies.

Treatments that use only artemisinin need to be taken for seven days to kill all parasites, but patients often stop treatment after a few days when they begin to feel much better. This leaves the remaining parasites in contact with low levels of the drug — a recipe for resistance. The WHO recommended in January 2006 that artemisinin should always be given in combination with other drugs for at least three days, because a cocktail reduces the chances of resistance. The need to move away from monotherapies has become all the more urgent with recent reports of resistance arising in Cambodia.

Although artemisinin-based combination therapies (ACTs) have become the treatment of choice for malaria, with a three-day programme curing more than 95% of patients, monotherapies are cheaper to produce and sell.

Of the 69 manufacturers of artemisinin monotherapies that the WHO has identified, 21 have withdrawn monotherapies, and 14 say they intend to comply with the WHO's recommendations. But the remaining 34 have not yet disclosed their intentions. Many have not even replied to multiple WHO e-mail and fax requests for information, says Andrea Bosman, an official at the WHO's Global Malaria Programme (see

Regulatory authorities in just 39 of the 76 countries using malaria drugs have so far complied or said they intend to comply with the WHO's recommendations (see National regulatory authorities could help by banning monotherapies, says Bosman, but many are weak, understaffed and lack expertise.

"It's terrible," says Bosman, adding that every country where malaria is endemic is affected by the problem. "Who says there is no profit to be made in malaria? When you see the number of companies operating in Africa, and the diversity of products, you'd just be amazed."