Efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Cambodia.
OBJECTIVE
To determine the efficacy of artemether-lumefantrine malaria treatment, as an alternative to artesunate + mefloquine, which is becoming ineffective in some areas of the Thai-Cambodian border.


METHODS
Two studies were conducted to monitor the efficacy of artemether-lumefantrine in Sampov Lun referral hospital, Battambang Province, in 2002 and 2003, and one study was conducted to assess the efficacy of mefloquine + artesunate in 2003 for comparison. The studies were performed according to the WHO standardized protocol with a follow-up of 28 days. The therapeutic efficacy tests were complemented with in vitro tests and in 2003, with the measurement of lumefantrine plasma concentration at day 7 for the patients treated with artemether-lumefantrine.


RESULTS
A total of 190 patients were included: 55 were treated with artemether-lumefantrine in 2002 (AL2002), 80 with artemether-lumefantrine and food supplementation in 2003 (AL2003) and 55 with artesunate + mefloquine in 2003 (AM2003). With the per-protocol analysis, the cure rate was 71.1% in study AL2002, 86.5% in study AL2003 and 92.4% in study AM2003. All the data were PCR corrected. The artemether-lumefantrine cure rate was unexpectedly low in 2002, but it increased with food supplementation in 2003. There was a significant difference (P = 0.02) in lumefantrine plasma concentrations between adequate clinical and parasitological responses and treatment failure cases. In vitro susceptibility to lumefantrine was reduced for isolates sampled from patients presenting with treatment failure, but the difference was not statistically different from isolates sampled from patients who were successfully treated.


CONCLUSIONS
Treatment failure cases of artemether-lumefantrine are most probably because of low levels of lumefantrine blood concentration. Further investigations are necessary to determine whether resistance of Plasmodium falciparum isolates to lumefantrine is present in the region.
Denis
Mey Bouth
MB
National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
Tsuyuoka
Reiko
R
Lim
Pharath
P
Lindegardh
Niklas
N
Yi
Poravuth
P
Top
Sophoan Narann
SN
Socheat
Duong
D
Fandeur
Thierry
T
Annerberg
Anna
A
Christophel
Eva Maria
EM
Ringwald
Pascal
P
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000097:blood / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D019587:Dietary Supplements; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes; D000077332:Artesunate; D000078102:Lumefantrine; D015767:Mefloquine