Therapeutic efficacy of fixed dose artesunate-mefloquine for the treatment of acute, uncomplicated Plasmodium falciparum malaria in Kampong Speu, Cambodia

BACKGROUND: Cambodia stopped using co-blistered, non-fixed, artesunate-mefloquine (ASMQ) in 2008 when treatment failure rates approximated 20%. Fixed dose combination (FDC) ASMQ is efficacious against acute uncomplicated, drug resistant Plasmodium falciparum malaria in Southeast Asia but has not been tested in Cambodia. METHODS: A 42-day WHO therapeutic efficacy study (TES) was conducted in 2010 in Oral, Kampong Speu province, south-west Cambodia, in patients with acute uncomplicated P. falciparum. Daily administered FDC ASMQ for three days was dosed by age. Genotyping of isolates at day 0 and day of recrudescence by polymerase chain reaction (PCR) classified post-treatment recurrent falciparum parasitaemia. Ex vivo drug sensitivity testing ([(3)H] hypoxanthine method) was performed on baseline parasites and reported as the drug concentration inhibiting 50% parasite growth vs no drug (IC(50)). RESULTS: Recruited patients numbered 45; five aged <15 years. On day 3, five of 45 [11.1 (3.7-24.05)] % patients were still parasite-positive; one of whom later failed treatment on day 21. There were 5/45 (11.1%) late treatment failures on day 21, 28 and 35; all were PCR diagnosed recrudescent infections. The day 0 MQ IC(50)s ranged from 11.5-238.9 (median 58.6) nM. CONCLUSIONS: This TES demonstrated reasonable efficacy in an area of possible reduced artemisinin sensitivity and high MQ IC(50)s. Efficacy testing of FDC ASMQ should continue in Cambodia and be considered for reintroduction if efficacy returns.