Using a combination of two drugs - artemether and lumefantrine - is the most effective way to treat malaria in the areas of Africa where resistance to commonly used malaria drugs is high, concludes a randomised trial published in this week's issue of The Lancet.

Cheap and effective treatment for malaria with one drug is no longer an option for most countries in Africa because of the rapid emergence of drug resistance. The parasite that causes the most severe form of malaria, Plasmodium falciparum, is resistant to the antimalaria drug chloroquine in nearly all the areas where the disease is rife. This, along with the fact that resistance to sulfadoxine-pyrimethamine is spreading rapidly, has led to strong calls for the introduction of combination treatments. However, there is little data on the effectiveness of these combinations when used in routine practice.

Theonest Mutabingwa (London School of Hygiene and Tropical Medicine, UK) and colleagues compared the effectiveness of three drug combinations that are available in Africa, can be used in children, and stand a realistic chance of being deployed. Around 1800 children in Tanzania aged 4-59 months with malaria were recruited onto the trial between September 2002 and October 2004. They were randomly assigned to amodiaquine alone (270), amodiaquine and sulfadoxine-pyrimethamine (507), amodiaquine and artesunate (515), or artemether-lumefantrine (519). The drugs were taken orally at home to test their use under real-life conditions. Around 1700 children were followed-up 14 days after the start of treatment. Failure to clear malaria parasites from the blood was found in 42% of patients on amodiaquine, 20% on amodiaquine and sulfadoxine-pyrimethamine, 11% on amodiaquineartesunate, and 1% on artemether-lumefantrine. Recruitment to the amodiaquine group was stopped early because of the high failure rate. 28 days after treatment, failure rates were higher in all groups but the failure rate was only 3% in the children who received artemetherlumefantrine. The investigators conclude that six doses of arthemether-lumefantrine, packaged by the World Health Organisation, was highly effective when taken at home in an area where the levels of resistance to sulfadoxine-pyrimethamine and amodiaquine is high.

Dr Mutabingwa concludes: "We found that the artemether-lumefantrine combination is effective taken unsupervised. The cost of the drug means that it is likely to reach only a fraction of those who need it, unless the price is substantially reduced either through market mechanisms or, more realistically, through subsidy."

Further evidence to show drug combination works in realistic African setting

Also this week's issue of The Lancetan article by Patrice Piola (Epicentre, Paris France) and colleagues describes the results of a randomised trial, which found that the effectiveness of the artemether-lumefantrine drug combination was very high, exceeding 96%, whether given supervised or unsupervised. Adherence to the complicated, twice-daily, three-day regimen might be sub optimal and could reduce the effectiveness of the drug combination. The investigators compared the effectiveness and safety of the drug combination in patients who had all their doses supervised with fatty food intake and in patients who only had their first dose supervised and were given nutritional advice. The trial involved around 960 patients, of all ages, with uncomplicated falciparum malaria in Mbarara, Uganda.

Dr Piola concludes: "We believe that the six-dose regimen of artemether-lumefantrine is a very promising option for the replacing failing antimalarial therapies in Uganda and other African countries. Our experience suggests that providing systematically a short explanation on drug intake to patients at the point of prescription is a simple but important intervention to enhance adherence."

In an accompanying CommentPeter Gottfried Kremsner (Institute of Tropical Medicine, Tubingen, Germany) states: "Together these two papers convincingly show that the effectiveness of arthemether-lumefantrine is excellent in the artificial real-world condition in a research trial. How effectively such trials can show the effectiveness of antimalarial drugs in Africa is still an open question."

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