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


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


METHODS
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.


METHODS
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.


METHODS
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.


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).


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.
Omari
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Countess of Chester Hospital, NHS Foundation Trust, Paediatric Department, Countess of Chester Health Park, Liverpool Road, Chester, Cheshire, UK, CH2 1UL. aika@omari1677.freeserve.co.uk
Gamble
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Garner
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D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes