title: Plasmodium falciparum: higher incidence of molecular resistance markers for sulphadoxine than for pyrimethamine in Kasangati, Uganda.
abstract: In November of 2000, Uganda changed its anti-malarial policy to replace chloroquine (CQ) with a combination of CQ and sulphadoxine-pyrimethamine (SP) as the first line agents. Information was limited on the efficacy of either drug. The present study was designed to provide baseline information on the efficacy of SP and the prevalence of molecular markers that are associated with SP resistance. Blood samples were collected on filter paper from 169 consenting patients who were diagnosed with malaria. Patients were treated with SP and followed for 14 days using the WHO clinical guidelines. The samples were analysed for molecular resistance markers and correlation of the molecular markers with clinical findings was assessed. SP monotherapy was efficacious for 140 of 163 (85.9%) treated patients. We found a high level of mutations in alleles which have previously been reported to be associated with SP resistance, but there was no correlation between clinical outcomes and molecular markers. With the exception of codon S108 in dhfr (dhfr S108N was at 94.9%), frequencies of dihydropteroate synthase (dhps) mutant and mixed alleles combined (A437G 89% and K540E 83.9%) were higher than those of dihydrofolate reductase (dhfr) (N51I 58.4%, C59R 31.3%).
authors.affiliation: Department of Biochemistry, Makerere University, Kampala, Uganda. hsendagire@yahoo.com
authors.forename: Hakim
authors.initials: H
authors.lastname: Sendagire
authors.forename: Daniel
authors.initials: D
authors.lastname: Kyabayinze
authors.forename: Göte
authors.initials: G
authors.lastname: Swedberg
authors.forename: Fred
authors.initials: F
authors.lastname: Kironde
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D003062:Codon; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011739:Pyrimethamine / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome; D014454:Uganda
chemical_list: D000962:Antimalarials; D003062:Codon; D004338:Drug Combinations; D005819:Genetic Markers; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine