Artemether-lumefantrine (four-dose regimen) for treating uncomplicated malaria

Malaria is a parasitic disease spread by mosquitoes. It affects millions of people worldwide and causes significant illness and mortality. Uncomplicated malaria presents with symptoms such as fever, headache, muscle pain, and vomiting. The parasite has become resistant to a number of previously effective drugs, and so combinations of drugs are used to try to prevent further resistance. Artemether-lumefantrine is one such drug combination. This review of trials showed that, although the four-dose artemether-lumefantrine regimen was superior to chloroquine, in general the four-dose regimen was less effective compared with the six-dose regimen or other drug combinations. The fact that the four-dose regimen is generally less effective means it is unlikely that it would be used for treating uncomplicated malaria.

Authors' conclusions: 

The four-dose regimen of artemether-lumefantrine seems to be less effective than regimens against which it has been tested. The six-dose regimen is superior to four-dose regimen.

2008: This review will not be updated because the four-dose regimen is no longer recommended; see 'What's new' for details.

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Background: 

The World Health Organization recommends artemether-lumefantrine, an expensive drug, as a treatment for uncomplicated malaria. We sought evidence of the superiority of the four-dose regimen over existing treatments.

Objectives: 

To evaluate the four-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria.

Search strategy: 

We searched the Cochrane Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to October 2005), EMBASE (1988 to October 2005), LILACS (1982 to October 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 four doses of artemether-lumefantrine with standard treatment regimens (single drug or combination), or six doses of artemether-lumefantrine, for treating 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: 

Seven trials (2057 participants) tested a four-dose regimen. More people tended to fail treatment with artemether-lumefantrine than with other drugs, including sulfadoxine-pyrimethamine (247 participants, 1 trial), halofantrine (86 participants, 1 trial), and mefloquine (233 participants, 1 trial; difference statistically significant for mefloquine). When compared with chloroquine, artemether-lumefantrine was better in two trials (378 participants), but over 50% of the participants treated with chloroquine had total failure by day 28. Fewer people failed treatment with the six-dose regimen compared to the four-dose regimen (RR 7.71, 95% CI 2.99 to 19.88; 306 participants, 1 trial).

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