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New malaria treatment guidelines issued

Washington, D.C., 20 January 2006 (PAHO)—The World Health Organization (WHO) has issued new guidelines on malaria treatment and 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.


On the right, PAHO Deputy Director, Dr. Joxel García. On the left, Dr. Arata Kochi, the director of WHO's malaria department. (Photo by Armando Waak/PAHO)

Malaria, an infection caused by a parasite and transmitted by Anopheles mosquitoes, continues to be a serious global health problem, causing acute illness in more than 350 million people each year and killing more than a million persons, mostly children. It can be cured by combined treatment with artemisinin, a medicine derived from the sweet wormwood plant, and a second anti-malarial drug. 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."

Q&A with Dr. Keith Carter

As the top expert at PAHO on the fight against malaria in the Americas, how would you evaluate this fight? What in your opinion needs to happen prior to finally declaring the hemisphere malaria-free?
As a result of the malaria eradication program which began in the Americas and globally in the late 1950's, transmission was eliminated from a number of countries in the Americas; although these have remained free of malaria, there is still need for surveillance to prevent reintroduction of transmission. At the same time, a number of endemic countries have been reporting reduction in transmission and while a few could be aiming at eliminating transmission in the not too distant future, the hemisphere can only become malaria free when persons living in all endemic areas have access to malaria diagnosis, appropriate treatment, interventions to prevent malaria transmission and sufficient health service coverage.

What is the most important aspect of the new malaria guidelines launched by WHO in Washington for the health sector as it strives to keep up the fight against the disease?
They provide policy makers with a framework for the development of treatment protocols which take into account different population risk groups as well as national malaria situations and health service capacities.

How best can the Americas, and most particularly those countries most affected by malaria, make use of the new guidelines?
In the Americas, most of the P. falciparum cases (the most pathogenic parasite which has developed resistance) occur in the Amazon basin. Countries which share that area have all taken the decision to use ACT's and some are already using these as first line treatment.

WHO supports the use of a new line of Artemisinin-based combination therapies. What does this therapy consist of? What is Artemisinin?
Artemisinin-based combination therapy (ACT) is essentially the combination of artemisinin or one of its derivatives with an antimalarial or antimalarials of a different class.

Artemisinin, also known as qinghaosu, is a sesquiterpene lactone extracted from the leaves of Artemisia annua (sweet wormwood), used in China for treatment of fever for over a thousand years. It is a potent and rapidly-acting blood schizontozide and is active against all Plasmodium species. It has an unusually broad activity against asexual parasites, killing all stages from young rings to schizonts. In P. falciparum malaria, artemisinin also kills the gametocytes - including the stage 4 gametocytes, which are otherwise sensitive only to primaquine.

Artemisinin and its derivatives inhibit an essential calcium adenosine triphosphatase, PfATPase 6. Artemisinin has now given way to the more potent dihydroartemisinin and its derivatives, artemether, artemotil and artesunate. The three latter derivatives are converted back in vivo to dihydroartemisinin. These drugs should be given as combination therapy to protect them from resistance.

Please explain the effectiveness of the new combination therapy manufactured by Novartis (Coartem).
Coartem is the combination of Artemether and Lumefantrine. It is the only fixed-dose combination available and is available in blisters according to body weight. This allows an appropriate dose and facilitates treatment, which are important factors in making an efficacious treatment effective.

According to the new malaria treatment guidelines, uncomplicated falciparum malaria must be treated with ACTs and not by artemisinin alone or any other monotherapy because the use of single-drug artemisinin treatment, or monotherapy, hastens development of resistance by weakening but not killing the parasite.

"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."

Speaking at the Pan American Health Organization at the launching of the guidelines, Dr. Kochi said, "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, and it will probably be at least ten years before a new one can be discovered."

PAHO Deputy Director Dr. Joxel García, who welcomed participants from WHO and pharmaceutical companies to the technical briefing on the guidelines, said "We have to deal with public health basics and it is essential to reduce the suffering and death caused by this disease."

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.

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.

Additionally, to anticipate and prevent the onset and spread of drug resistance in the long term, WHO urged 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.

PAHO was established in 1902 and is the world's oldest international health organization. It works with all the countries of the Americas to improve the health and raise the living standards of their peoples.

For more information please contact , PAHO, Public Information, 202-974-3459.