Evaluation of leading combination regimens for treating malaria

May 24 2007

Ugandan children who received the combination therapy of artemether-lumefantrine experienced a lower rate of treatment failure compared to other combination therapies, according to a study in the May 23/30 issue of JAMA, a theme issue on malaria.

Malaria is one of the leading causes of death in children in Africa. One of the reasons the control of malaria has been difficult is because of increasing resistance to some drugs, leading to changes in antimalarial treatment recommendations, according to background information in the article. Combination therapies have replaced monotherapies as the recommended treatments for uncomplicated malaria. However, it is not clear which treatment regimens are most effective.

Grant Dorsey, M.D., Ph.D., of the University of California, San Francisco, and colleagues evaluated the three leading available combination regimens for treating uncomplicated falciparum malaria (one of the most severe types of malaria, with one of the highest death rates) and compared their efficacy, safety, and tolerability. The clinical trial, conducted between November 2004 and June 2006, included 601 healthy children (age 1-10 years) from an urban community in Kampala, Uganda. The children were randomized to receive 1 of 3 combination therapies (amodiaquine plus sulfadoxine-pyrimethamine, amodiaquine plus artesunate, or artemether-lumefantrine) when they were diagnosed with their first episode of uncomplicated malaria. The participants were followed-up for 13 to 19 months.

Of enrolled children, 329 of 601 were diagnosed with at least 1 episode of uncomplicated malaria, and 687 episodes of Plasmodium falciparum malaria were treated with study drugs. The risk of treatment failure after 28 days of follow-up was 26.1 percent with amodiaquine plus sulfadoxine-pyrimethamine, 17.4 percent for amodiaquine plus artesunate, and 6.7 percent for artemether-lumefantrine. When only treatment failures caused by recrudescent (becoming active again) parasites were considered, the risks of failure were 14.1 percent, 4.6 percent, and 1.0 percent for the same order of study drugs, respectively. There were no deaths or cases of severe malaria. Significant reductions in anemia and asymptomatic parasitemia (parasites in the blood) were observed.

“Considering the availability of resources such as light microscopy and rapid diagnostic tests, as well as increasing funding through such programs as the Global Fund and President's Malaria Initiative, it seems that improved malaria management, with evaluation and diagnosis-based treatment for all febrile children, is a reasonable goal for Africa. Continued research into malaria diagnostics, optimal antimalarial regimens, sustainable methods of drug delivery, and integration of treatment with prevention strategies will be necessary to establish effective and sustainable malaria control policies,” the authors conclude.

http://jama.ama-assn.org/