The National Malaria Control Programme of Cambodia (CNM) conducted three therapeutic efficacy studies at Sampovloun Referral Hospital, Battambang Province (western Cambodia): 1. artemether-lumefantrine between June and August 2002 (AL2002, N = 55), 2. artemether-lumefantrine between October 2003 and March 2004 (AL2003, N = 80) [
8] and 3. artesunate-mefloquine between October 2003 and March 2004 (AM2003, N = 55) [
9]. One therapeutic efficacy study of AM was conducted at Veal Veng Referral Hospital, Pursat Province (western Cambodia) between July and August 2004 (AM2004, N = 85) [
9]. The studies followed the WHO standard protocol for the assessment of the efficacy of anti-malarial drugs [
10]. Briefly, all patients over six years of age and weight > 16 kg presenting with fever, defined as axillary temperature ≥ 37.5°C or history of fever during 24 h prior to consultation, and a positive smear with
Plasmodium falciparum mono-infection, with parasite density of 1,000–150,000 parasites/μl, were included in the studies. Informed consent was given by the patient or by a parent/guardian for children. Enrolled patients had to stay in hospital until blood smear became negative and had to commit to completing the 28-day follow-up. Exclusion criteria are: one or more of the general danger signs or any sign of severe and complicated malaria, pregnancy, febrile diseases other than malaria and severe malnutrition, and known hypersensitivity or contraindication to the study drugs. A total dose of 12 mg/kg artesunate and 25 mg/kg mefloquine were given over 3 days (AM group). The daily 4 mg/kg of artesunate were divided into two equal doses, one in the morning and one in the evening on day 0, and 4 mg/kg single dose on day 1 and 2 with a maximum adult dose of 600 mg in total. The 25 mg/kg of mefloquine were also divided into two equal doses in the morning and in the evening on day 0. The maximum dose of mefloquine was limited to 1,500 mg for adults as the side effects are common beyond this dose [
9]). In the artemether-lumefantrine study group (AL group), subjects were treated with 20 mg/kg artemether and 120 mg/kg lumefantrine the first day at 0 and 8 hours and twice daily (morning and late afternoon) on the following two days (Coartem
®, Novartis, Switzerland), i.e. 8–12 h apart (the total dose of 24 tablets for an adult as recommended by the manufacturer). In the AL2003 study, each dose of artemether-lumefantrine was provided with 250 ml milk and 5 pieces of coconut biscuit [
8]. Patients were checked by malaria smear for the presence of parasites on study days 1, 2, 3, 7, 14, 21 and 28. If fever occurred at any time between the scheduled study days, a malaria smear was also done. People who did not present on their own were actively sought for. The therapeutic response was classified as early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR) according to WHO protocols.