Pyrimethamine-sulfadoxine efficacy and selection for mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase in Mali

To assess pyrimethamine-sulfadoxine (PS) efficacy in Mali, and the role of mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihyd ropteroate synthase (DHPS) in in vivo PS resistance, 190 patients with unco mplicated P. falciparum malaria were treated with PS and monitored for 56 d ays. Mutation-specific polymerase chain reactions and digestion with restri ction endonucleases were used to detect DHFR and DHPS mutations on filter p aper blood samples from pretreatment and post-treatment infections. Only on e case each of RI and RII level resistance and no cases of RIII resistance or therapeutic failure were observed. Post-PS treatment infections had sign ificantly higher rates of DHFR mutations at codons 108 and 59. No significa nt selection for DHPS mutations was seen. Pyrimethamine-sulfadoxine is high ly efficacious in Mall, and while the low level of resistance precludes ass essing the utility of molecular assays for in vivo PS resistance, rapid sel ection of DHFR mutations supports their role in PS failure.