Artemether-lumefantrine for uncomplicated malaria: a systematic review

The World Health Organization (WHO) is promoting artemether-lumefantrine for treating uncomplicated malaria. The objective of this review is to summarize available evidence of its effects compared with other antimalarial regimens.

We sought randomized and quasi-randomized studies comparing artemether-lumefantrine with any other antimalarial drug regimen. Databases searched were MEDLINE (to February 2003), EMBASE (to February 2003), and the Cochrane Controlled Trials Register (issue 1, 2003). Conference proceedings and reference article lists were searched and malaria researchers and the drug manufacturer were contacted. Two reviewers independently applied inclusion criteria and extracted data.

Six trials (1698 participants) studied the four-dose regimen. Fever and parasite clearance tended to be shorter with artemether-lumefantrine, but parasitological failure on day 28 was more common with artemether-lumefantrine in comparison with mefloquine (one trial, n = 233), halofantrine (one trial, n = 86) and mefloquine-artesunate (one trial, n = 537); but less common with chloroquine (two trials, n = 378). For the six-dose regimen, two studies compared artemether-lumefantrine with mefloquine-artesunate, but there was insufficient data to demonstrate any meaningful comparative effects for day 28 parasitaemia, and no difference in parasite or fever clearance time was detected. There were 11 parasitological failures with artemether-lumefantrine and none with mefloquine-artesunate.

There is no evidence to demonstrate the four-dose regimen of artemether-lumefantrine results in a higher cure rate than other antimalarial regimens against which it has been tested, apart from chloroquine in areas with high chloroquine resistance. Artemether-lumefantrine has potential advantages over non-artemisinin regimens because of the faster clearance time and gametocyte clearance. There is insufficient evidence about the six-dose regimen to know whether it is less or more effective than current antimalarial drug regimens.