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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dc.creatorMugittu, Kefas
dc.creatorNdejembi, Modesta
dc.creatorMalisa, Allen
dc.creatorLemnge, Martha
dc.creatorPremji, Zulfikar
dc.creatorMwita, Alex
dc.creatorNkya, Watoky
dc.creatorKataraihya, Johannes
dc.creatorAbdulla, Salim
dc.creatorBeck, Hans-Peter
dc.creatorMshinda, Hassan
dc.date2016-11-17T08:10:15Z
dc.date2016-11-17T08:10:15Z
dc.date2004
dc.date.accessioned2022-10-25T08:53:34Z
dc.date.available2022-10-25T08:53:34Z
dc.descriptionIfakara 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
dc.descriptionPrior 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.
dc.formatapplication/pdf
dc.identifierhttps://www.suaire.sua.ac.tz/handle/123456789/926
dc.identifier.urihttp://hdl.handle.net/123456789/93886
dc.languageen
dc.publisherThe American Society of Tropical Medicine and Hygiene
dc.subjectTherapeutic efficacy
dc.subjectsulfadoxine-pyrimethamine
dc.subjectmalaria treatment policy
dc.subjectPlasmodium falciparum dihydrofolate
dc.subjectdihydropteroate synthase mutations
dc.subjectTanzania
dc.subjectAntimalarials
dc.subjectMolecular markers
dc.subjectSP resistance
dc.subjectSP efficacy
dc.titleTherapeutic 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
dc.typeArticle

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