1921
Volume 71, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Prior to the 2001 malarial treatment policy change in Tanzania, we conducted trials to assess the efficacy of sulfadoxine-pyrimethamine (SP) and the usefulness of molecular markers in monitoring resistance. A total of 383 uncomplicated malaria patients (between 6 and 59 months old) were treated with SP and their responses were assessed. Mutations in the dihydrofolate reductase () and dihydropteroate synthase () genes in admission day blood samples were analyzed. Results indicated that 85.6% of the patients showed an adequate clinical response, 9.7% an early treatment failure, and 4.7% a late treatment failure. The quintuple mutant genotype ( 51 Ile, 59 Arg, and 108 Asn and 437 Gly and 540 Glu) showed an association with treatment outcome (odds ratio = 2.1; 95% confidence interval = 0.94–4.48, = 0.045). The prevalence of the triple mutant genotype (51 Ile, 59 Arg, and 108 Asn) at a site of high SP resistance (23.6%) was four times higher compared with that observed at sites of moderate SP resistance (6.8–14.4%) ( = 0.000001). The genotype failure index calculated by using this marker was invariable (1.96–2.1) at sites with moderate SP resistance, but varied (3.4) at a site of high SP resistance. In conclusion, our clinical and molecular findings suggest that SP may have a short useful therapeutic life in Tanzania; thus, its adoption as an interim first-line antimalarial drug. The findings also point to the potential of the triple mutant genotype as an early warning tool for increasing SP resistance. These data form the baseline SP efficacy and molecular markers profile in Tanzania prior to the policy change.

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2004-12-01
2017-09-22
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  • Received : 17 Nov 2003
  • Accepted : 16 Jun 2004

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