Sokoine University of Agriculture

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.contributor.author Mugittu, Kefas
dc.contributor.author Ndejembi, Modesta
dc.contributor.author Malisa, Allen
dc.contributor.author Lemnge, Martha
dc.contributor.author Premji, Zulfikar
dc.contributor.author Mwita, Alex
dc.contributor.author Nkya, Watoky
dc.contributor.author Kataraihya, Johannes
dc.contributor.author Abdulla, Salim
dc.contributor.author Beck, Hans-Peter
dc.contributor.author Mshinda, Hassan
dc.date.accessioned 2016-11-17T08:10:15Z
dc.date.available 2016-11-17T08:10:15Z
dc.date.issued 2004
dc.identifier.uri https://www.suaire.sua.ac.tz/handle/123456789/926
dc.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 en_US
dc.description.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. en_US
dc.language.iso en en_US
dc.publisher The American Society of Tropical Medicine and Hygiene en_US
dc.subject Therapeutic efficacy en_US
dc.subject sulfadoxine-pyrimethamine en_US
dc.subject malaria treatment policy en_US
dc.subject Plasmodium falciparum dihydrofolate en_US
dc.subject dihydropteroate synthase mutations en_US
dc.subject Tanzania en_US
dc.subject Antimalarials en_US
dc.subject Molecular markers en_US
dc.subject SP resistance en_US
dc.subject SP efficacy en_US
dc.title 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 en_US
dc.type Article en_US


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