Artemether-lumefantrine (six-dose regimen) for treating uncomplicated falciparum malaria

Abstract

BACKGROUND The World Health Organization recommends artemether-lumefantrine for treating uncomplicated malaria. We sought evidence of superiority of the six-dose regimen over existing treatment regimens as well as its effectiveness in clinical situations. OBJECTIVES To evaluate the six-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria. SEARCH STRATEGY We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA Randomized controlled trials comparing six doses of artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination), or supervised with unsupervised treatment, for uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. MAIN RESULTS Nine trials (4547 participants) tested the six-dose regimen. Total failure at day 28 for artemether-lumefantrine was lower when compared with amodiaquine (270 participants, 1 trial), amodiaquine plus sulfadoxine-pyrimethamine (507 participants, 1 trial), but not with chloroquine plus sulfadoxine-pyrimethamine (201 participants, 2 trials). In comparisons with artemisinin derivative combinations, artemether-lumefantrine performed better than amodiaquine plus artesunate (668 participants, 2 trials), worse than mefloquine plus artesunate (270 participants, 4 trials), and no differently to dihydroartemisinin-napthoquine-trimethoprim (89 participants, 1 trial). AUTHORS' CONCLUSIONS The six-dose regimen of artemether-lumefantrine appears more effective than antimalarial regimens not containing artemisinin derivatives.