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 dihydropteroate synthase (DHPS) in in vivo PS resistance, 190 patients with uncomplicated P. falciparum malaria were treated with PS and monitored for 56 days. Mutation-specific polymerase chain reactions and digestion with restriction endonucleases were used to detect DHFR and DHPS mutations on filter paper blood samples from pretreatment and post-treatment infections. Only one case each of RI and RII level resistance and no cases of RIII resistance or therapeutic failure were observed. Post-PS treatment infections had significantly higher rates of DHFR mutations at codons 108 and 59. No significant selection for DHPS mutations was seen. Pyrimethamine-sulfadoxine is highly efficacious in Mali, and while the low level of resistance precludes assessing the utility of molecular assays for in vivo PS resistance, rapid selection of DHFR mutations supports their role in PS failure.
Diourté
Y
Y
Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odontostomatology, Bamako, Mali.
Djimdé
A
A
Doumbo
O K
OK
Sagara
I
I
Coulibaly
Y
Y
Dicko
A
A
Diallo
M
M
Diakité
M
M
Cortese
J F
JF
Plowe
C V
CV
D000818:Animals; D000962:Antimalarials / Q000592:standards* / Q000627:therapeutic use; D001769:Blood / Q000469:parasitology; D002648:Child; D004262:DNA Restriction Enzymes / Q000737:chemistry; D016054:DNA, Protozoan / Q000737:chemistry; D004094:Dihydropteroate Synthase / Q000235:genetics; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008302:Mali; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011739:Pyrimethamine / Q000592:standards* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000592:standards* / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D016896:Treatment Outcome
D000962:Antimalarials; D016054:DNA, Protozoan; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D004262:DNA Restriction Enzymes; D011739:Pyrimethamine