Background: Falciparum malaria is a significant problem for Afghan refugees in Pakistan. Refugee treatment guidelines recommended standard three-day chloroquine treatment (25 mg/kg) for first episodes and extended five-day treatment (40 mg/kg) for recrudescent infections, based on the assumption that a five-day course would more likely achieve a cure. An in-vivo randomized controlled trial was conducted among refugees with uncomplicated falciparum malaria to determine whether five-day treatment (CQ40) was more effective than standard treatment (CQ25). Methods. 142 falciparum patients were recruited into CQ25 or CQ40 treatment arms and followed up to 60 days with regular blood smears. The primary outcome was parasitological cure without recrudescence. Treatment failures were retreated with CQ40. PCR genotyping of 270 samples, from the same and nearby sites, was used to support interpretation of outcomes. Results: 84% of CQ25 versus 51% of CQ40 patients experienced parasite recrudescence during follow-up (adjusted odds ratio 0.17, 95%CI 0.08-0.38). Cure rates were significantly improved with CQ40, particularly among adults. Fever clearance time, parasite clearance time, and proportions gametocytaemic post-treatment were similar between treatment groups. Second-line CQ40 treatment resulted in higher failure rates than first-line CQ40 treatment. CQ-resistance marker pfcrt 76T was found in all isolates analysed, while pfmdr1 86Y and 184Y were found in 18% and 37% of isolates respectively. Conclusions: CQ is not suitable for first-line falciparum treatment in Afghan refugee communities. The extended-dose CQ regimen can overcome 39% of resistant infections that would recrudesce under the standard regimen, but the high failure rate after directly observed treatment demonstrates its use is inappropriate. © 2011 Howard et al; licensee BioMed Central Ltd.

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genetics pyrimethamine Pakistan parasitology genotype sulfadoxine Afghanistan refugee controlled clinical trial clinical trial dose response drug treatment failure follow up human Refugees middle aged controlled study blood smear clinical trial (topic) randomized controlled trial Aged Animals drug efficacy animal Young Adult school child treatment duration Humans Treatment Outcome Adolescent Infant, Newborn Antimalarials gametocyte female Aged, 80 and over preschool child male Infant newborn Child, Preschool antimalarial agent parasite clearance polymerase chain reaction DNA, Protozoan isolation and purification Article blood genetic analysis protozoal DNA major clinical study adult Malaria, Falciparum malaria falciparum Plasmodium falciparum drug resistance drug effect chloroquine Child