WHO Calls For End to 
"Single-Drug" Artemisinin Treatment

Mozambique News Agency (AIM) i.3952 20jan2006

London — The World Health Organisation (WHO) on Thursday called for pharmaceutical companies to stop producing "single-drug" artemisinin malaria medicines, warning that they could set back the fight against the killer disease for over a decade.

Malaria, along with tuberculosis and HIV/AIDS, is a key disease that must be tackled in Africa if chronic poverty and sickness are to be overcome. It has been estimated that the economic cost of malaria in Africa is 12 billion US dollars annually. Worldwide, there are an estimated half a billion cases of malaria each year, resulting in the deaths of over a million people.

Artemisinin is a highly effective anti-malarial plant extract that is hailed as the drug that holds out hope for millions of people. But the WHO fears that if it is used alone the malaria parasites will soon build up resistance to the drug.

This is because in some cases the parasite could be weakened but not killed, leading to the development of immunity to the drug. This has already happened to three previous anti-malarial therapies, sulfadoxine-pyrimethanime, chloroquine and andatovaquone (which was only introduced in 1997).

In its place, WHO recommends the use of Artemisinin Combination Therapies (ACTs), which use the addition of other anti-malarial drugs to kill any parasites that survive the artemisinin. According to WHO, when used correctly in combination with other anti-malarial drugs, artemisinin is "nearly 95 per cent effective in curing malaria and the parasite is highly unlikely to become drug resistant".

In announcing the new guidelines, the WHO Director General, Dr Lee Jong-wook, said "it is critical that artemisinins be used correctly. We request pharmaceutical companies to immediately stop marketing single-drug artemisinin tablets and instead market artemisinin combination therapies only".

The head of the WHO malaria department, Dr Arata Kochi, warns that although there have so far been no treatment failures due to artemisinin drug resistance, "we are concerned about decreased sensitivity to the drug in South-East Asia which is the region that has traditionally been the birthplace of anti-malarial drug resistance".

However, if companies continue to produce and sell "single-drug" artemisinin pills, it threatens to make the drug worthless in just a few years. According to Dr Kochi, "if we lose ACTs, we'll no longer have a cure for malaria, and it will probably be at least ten years before a new one can be discovered".

Not surprisingly, the drug companies concerned are not happy with the announcement. Herwig Jansen, president of the Belgian company Dafra, told "The Guardian" newspaper "we're a bit surprised about this and we have not been involved in the process of decision making. What are we to do? Stop production and destroy our stocks? It is not the function of WHO to insist on these things. This has to be worked out together with the academic experts and the industry".

"The Guardian" [below] went on to suggest that "the WHO's tough line will be interpreted in some quarters as an attempt by the UN agency to re-assert its authority in the field of malaria after years of criticism for its failing "Roll Back Malaria" programme".

In Mozambique last year the health authorities decided to switch to ACT therapy. Although much more expensive than chloroquine, the new treatment has proved to be highly effective.

In parts of Maputo province the number of children infected with the malaria parasite has been slashed by as much as 88 per cent.

Part of the cost of the switch has been offset by Mozambique importing the drug through WHO at a discount. The cost of the change is also supported in some regions by the Global Fund to Fight AIDS, Tuberculosis and Malaria.

Meanwhile, research is continuing to find a vaccine for malaria. Last December the London-based medical journal "The Lancet" published further evidence that a malaria vaccine tested on over two thousand children in Maputo province provides partial protection for at least 18 months.

The team working at the Health Research Centre in Manhica, about 80 kilometres north of the Mozambican capital, found that the vaccine reduces the risk of clinical malaria by 35 per cent, and nearly halves the risk of severe malaria over a period of a year and a half.

By the end of the decade it is feared that half the world's population - nearly 3.5 billion people - will be living in areas where malaria is transmitted.

source: http://allafrica.com/stories/200601200332.html 20jan2006

Drug firms could 'destroy effect of malaria pills' 

SARAH BOSELEY / The Guardian (UK) 20jan2006

The World Health Organisation warned pharmaceutical companies yesterday that they risked destroying the effectiveness of the drug which has brought fresh hope to millions of people across the world in the fight against malaria. Lee Jong-wook, the WHO's director-general, told drug companies they must not market the drugs made from the Chinese plant artemisinin except in combination with other, older malaria drugs.

If used alone experts fear resistance would soon build up in the malaria parasite which causes the disease and the drugs would become useless.

"It is critical that artemisinins be used correctly," said Dr Lee. "We request pharmaceutical companies to immediately stop marketing single-drug artemisinin tablets and instead market artemisinin combination therapies (ACTs) only." But the drug firms were given no warning and reacted with some anger to an announcement which, as far as they were concerned, came out of the blue.

"We're a bit surprised about this and we have not been involved in the process of decision making," said Herwig Jansen, president of the Belgian company Dafra. "What are we to do? Stop production and destroy our stocks? It is not the function of WHO to insist on these things. This has to be worked out together with the academic experts and the industry."

The WHO's tough line will be interpreted in some quarters as an attempt by the UN agency to re-assert its authority in the field of malaria after years of criticism for its failing Roll Back Malaria programme. Behind the new stance is the WHO's newly-appointed head of malaria, Arata Kochi. "Our biggest concern right now is to treat patients with safe and effective medication and to avoid the emergence of drug resistance," said Dr Kochi yesterday. "If we lose ACTs we'll no longer have a cure for malaria and it will probably be at least 10 years before a new one can be discovered."

Drug resistance has badly damaged the fight against malaria. Sulfadoxine-pyrimethamine was initially 100% effective when it was introduced to Thailand in 1977. But within five years, it was effective in only 10% of cases. Chloroquine has lost its effectiveness throughout the world. Between 1999 and 2004 it was given to 95% of African children with malaria even though in many countries it cured only half of them.

As yet, there is little evidence of any problem with the artemisinin drugs. "So far, no treatment failures due to artemisinin drug resistance have been documented, but we are watching the situation very attentively," said Dr Kochi.

"We are concerned about decreased sensitivity to the drug in south-east Asia which is the region that has traditionally been the birthplace of anti-malarial drug resistance."

The companies which manufacture artemisinin single pill drugs include Sanofi-Aventis in France and Mepha in Switzerland as well as many generic manufacturers in India, China and Vietnam.

Deadly enemy

• Malaria kills more than 1 million a year in Africa, mostly children
• The parasites which cause the disease have become resistant to anti-malarial drugs over the years
• The plant artemisinin has been used to treat malaria in China for years and the WHO urges all countries to use drugs derived from it
• The WHO's Roll Back Malaria campaign has done "more harm than good", a Lancet editorial has said

source: http://www.guardian.co.uk/medicine/story/0,,1690818,00.html 20jan2006

WHO Asks Firms To 
Stop Marketing Malaria Regimen 

BETSY MCKAY / Wall Street Journal 20jan2006

In a rare move, the World Health Organization (WHO) called on 18 manufacturers of a promising malaria drug to halt marketing and sales practices that the agency claims will make the treatment ineffective and deprive health officials of their most powerful weapon against the killer disease.

The United Nations health agency wants makers of a drug called artemisinin to stop selling it immediately as a single, or so-called monotherapy, because WHO officials are concerned that the malaria parasite could become resistant to it.

Drug resistance is a growing problem in treating a number of diseases, from influenza to HIV/AIDS, and has been a particularly difficult thorn in the treatment of malaria, which infects as many as 500 million people annually, killing about one million of them.

Older Treatments Ineffective

Older monotherapy treatments already have become ineffective in many parts of the world, leaving artemisinin as the only reliable medication, according to the WHO.

The WHO said artemisinin, which is based on an ancient Chinese herbal remedy, should be sold and taken only as a combination drug therapy with other, older antimalarial drugs. When used in that form, artemisinin is nearly 95% effective in curing malaria, and the parasite is unlikely to become drug-resistant, the agency said.

"If we lose artemisinin, we will no longer have an effective cure for malaria," Arata Kochi, the WHO's malaria chief, said in a statement yesterday in Washington. "The only way to beat malaria is to be ahead of the parasite and counter drug resistance before it develops."

At least one manufacturer of the drug said it will comply with the new policy. French pharmaceutical company Sanofi-Aventis said it had been gradually phasing out production of artemisinin as a monotherapy in favor of the combination form, anyway. "Now, we will go a little quicker," said Robert Sebbag, a company official in Paris.

Other manufacturers include a handful of smaller European companies as well as several companies in China and India, the WHO said.

The WHO's change in policy comes as big donors are turning more attention and dollars to controlling malaria. For drug manufacturers, the combination antimalarial medications, known as ACTs, are a growing business.

Warning Signs From Lab Studies

The Global Fund to Fight AIDS, Tuberculosis, and Malaria has bought and supplied countries with large quantities of ACTs in recent years in a campaign to replace monotherapies. But artemisinin as a monotherapy remains popular in the private sector in poor countries, where it is plentiful, easy to take and offers quick relief.

While resistance to artemisinin has yet to develop, Dr. Kochi said the WHO is already seeing some warning signs from laboratory studies in Southeast Asia and South America that the drug could lose its potency. Developing a new generation of drugs will take as long as 10 years, WHO officials say.

One risk of a sudden halt to production and distribution of artemisinin monotherapies is that some countries could be left temporarily without needed treatments, Dr. Sebbag said.

"We have to be sure at the same time that the local authorities will give a good supply of the combination therapy," Dr. Sebbag added.

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WHO calls for an immediate halt to provision of single-drug artemisinin malaria pills

Press Release / WHO 19jan2006

New malaria treatment guidelines issued by WHO

WASHINGTON, DC — The World Health Organization (WHO) today requested pharmaceutical companies to end the marketing and sale of “single-drug” artemisinin malaria medicines, in order to prevent malaria parasites from developing resistance to this drug.

The use of single-drug artemisinin treatment – or monotherapy – hastens development of resistance by weakening but not killing the parasite. When used correctly in combination with other anti-malarial drugs in Artemisinin Combination Therapies (ACTs), artemisinin is nearly 95% effective in curing malaria and the parasite is highly unlikely to become drug resistant. ACTs are currently the most effective medicine available to treat malaria.

"It is critical that artemisinins be used correctly," said Dr LEE Jong-wook, WHO's Director-General. "We request pharmaceutical companies to immediately stop marketing single-drug artemisinin tablets and instead market artemisinin combination therapies only. The new treatment guidelines we are releasing today provide countries with clear and evidence-based direction on the best treatment options for malaria."

According to the new WHO malaria treatment guidelines, uncomplicated falciparum malaria must be treated with ACTs and not by artemisinin alone or any other monotherapy.

“So far, no treatment failures due to artemisinin drug resistance have been documented, but we are watching the situation very attentively,” said Dr Arata Kochi, the newly appointed director of WHO's malaria department. “We are concerned about decreased sensitivity to the drug in South-East Asia which is the region that has traditionally been the birthplace of anti-malarial drug resistance.”

In Thailand, sulfadoxine-pyrimethanime (SP) was initially almost 100% effective in curing malaria when introduced in 1977, but within five years was curing only 10% of cases due to drug resistance. The once-popular chloroquine has lost its effectiveness in almost every part of the world. Between 1999 and 2004, 95% of African children treated for malaria were given chloroquine, even though the drug only cured half of malaria cases in many countries. Resistance to atovaquone developed within one year of introduction in 1997.

WHO also announced other measures it will take to maximize the benefits and correct use of ACTs. In order to contain the circulation and use of counterfeit antimalarial medicines, WHO plans to strengthen its collaboration with international and national health and regulatory authorities. It is estimated that up to 25% of medicines consumed in developing countries are counterfeit or sub-standard. In parts of Africa and Asia this figure exceeds 50%, according to a WHO report on counterfeit drugs.

Additionally, to anticipate and prevent the onset and spread of drug resistance in the long term, WHO urges the global malaria research community and the pharmaceutical industry to rapidly invest in the design of the next generation of antimalarial drugs. By creating ACTs with multiple-drug combinations and transmission blocking components, resistance can be prevented.

“Our biggest concern right now is to treat patients with safe and effective medication and to avoid the emergence of drug resistance. If we lose ACTs, we’ll no longer have a cure for malaria,” said Dr Arata Kochi,“ and it will probably be at least ten years before a new one can be discovered.”

For more information contact: Melanie Zipperer Communications Officer Mobile phone: +41 79 477 1722 E-mail: zippererm@who.int

More on malaria: http://www.who.int/topics/malaria/en/index.html

source: http://www.who.int/mediacentre/news/releases/2006/pr02/en/index.html 20jan2006