Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in Tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance
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Date
2004
Journal Title
Journal ISSN
Volume Title
Publisher
The American Society of Tropical Medicine and Hygiene
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 Plasmodium falciparum malaria patients (between 6 and 59 months old) were treated with SP and their
responses were assessed. Mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase
(pfdhps) 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 (pfdhfr 51 Ile, 59 Arg, and 108 Asn and pfdhps 437 Gly and 540 Glu) showed an association with treatment
outcome (odds ratio 2.1; 95% confidence interval 0.94–4.48, P 0.045). The prevalence of the triple pfdhfr 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%) (P 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 pfdhfr
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.
Description
Ifakara Health Research and Development Centre, Ifakara, Tanzania; National Institute for Medical Research, Amani, Tanga,
Tanzania; Muhimbili College of Health Sciences, Dar es Salaam, Tanzania; National Malaria Control Program, Dar es Salaam,
Tanzania; Kilimanjaro Christian Medical Centre, Moshi, Tanzania; Bugando Medical Centre, Mwanza, Tanzania; Swiss Tropical
Institute, Basel, Switzerland
Keywords
Therapeutic efficacy, sulfadoxine-pyrimethamine, malaria treatment policy, Plasmodium falciparum dihydrofolate, dihydropteroate synthase mutations, Tanzania, Antimalarials, Molecular markers, SP resistance, SP efficacy