A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand.
BACKGROUND
The use of antimalarial drug combinations with artemisinin derivatives is recommended to overcome drug resistance in Plasmodium falciparum. The fixed combination of oral artemether-lumefantrine, an artemisinin combination therapy (ACT) is highly effective and well tolerated. It is the only registered fixed combination containing an artemisinin. The trial presented here was conducted to monitor the efficacy of the six-dose regimen of artemether-lumefantrine (ALN) in an area of multi-drug resistance, along the Thai-Myanmar border.


METHODS
The trial was an open-label, two-arm, randomized study comparing artemether-lumefantrine and mefloquine-artesunate for the treatment of uncomplicated falciparum malaria with 42 days of follow up. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish recrudescent from newly acquired P. falciparum infections. The PCR adjusted cure rates were evaluated by survival analysis.


RESULTS
In 2001-2002 a total of 490 patients with slide confirmed uncomplicated P. falciparum malaria were randomly assigned to receive artemether-lumefantrine (n = 245) or artesunate and mefloquine (n = 245) and were followed for 42 days. All patients had rapid initial clinical and parasitological responses. In both groups, the PCR adjusted cure rates by day 42 were high: 98.8% (95% CI 96.4, 99.6%) for artemether-lumefantrine and 96.3% (95% CI 93.1, 98.0%) for artesunate-mefloquine. Both regimens were very well tolerated with no serious adverse events observed attributable to either combination.


CONCLUSIONS
Overall, this study confirms that these two artemisinin-based combinations remain highly effective and result in equivalent therapeutic responses in the treatment of highly drug-resistant falciparum malaria.
Hutagalung
Robert
R
Shoklo Malaria Research Unit, Mae Sod, Tak Province, Thailand. robert@shoklo-unit.com
Paiphun
Lucy
L
Ashley
Elizabeth A
EA
McGready
Rose
R
Brockman
Alan
A
Thwai
Kaw L
KL
Singhasivanon
Pratap
P
Jelinek
Thomas
T
White
Nicholas J
NJ
Nosten
François H
FH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use; D000077549:Artemether; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D015767:Mefloquine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*; D013785:Thailand / Q000453:epidemiology
D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes; D000077332:Artesunate; D000077549:Artemether; D000078102:Lumefantrine; D015767:Mefloquine