(Adapted from JAMA news release) Malaria is one of the leading causes of death in African children, with about a million dying each year mostly in the sub-Saharan part of the continent. Increasing resistance to some widely used drugs has made it hard to control the disease, and has led to changes in antimalaria treatment. Combination therapies have replaced single drugs as the recommended treatment for many children with malaria. But it is not clear which treatment regimen is most effective. A UCSF-led team in Uganda compared three combination therapies. They found that one worked best, but they all worked well, and that the single-most important factor in the treatment success was not so much which drug combination was used, but that the children received consistent, good quality care. The combination that worked best was artemether-lumefantrine, according to the study in the May 23/30 issue of JAMA. It appears in a theme issue on malaria. Grant Dorsey, MD, PhD, an expert in infectious diseases and assistant professor of medicine at UCSF, and colleagues evaluated the three leading available combination regimens for treating uncomplicated falciparum malaria -- the most severe type of malaria, which is responsible for almost all malaria deaths -- and compared their efficacy, safety, and tolerability. Dorsey was lead author on the paper reporting the results. 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, and treated with their assigned treatment for each subsequent episode of malaria. 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 parasites (in other words, those due to drug resistance) 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 presence of 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. Philip Rosenthal, MD, UCSF professor of medicine, was the paper's senior author.
Combination Therapy for Uncomplicated Falciparum Malaria in Ugandan Children: A Randomized Trial Grant Dorsey, MD, PhD; Sarah Staedke, MD; Tamara D. Clark, MPH; Denise Njama-Meya, MB ChB, MSc; Bridget Nzarubara, MB ChB; Catherine Maiteki-Sebuguzi, MB ChB; Christian Dokomajilar, BA; Moses R. Kamya, MB ChB, MMed; Philip J. Rosenthal, MD JAMA. 2007;297:2210-2219 Abstract | Full Text | Full Text (PDF)