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- W2023863798 abstract "Background: Drugs with long elimination half-lives such asSulfadoxine –Pyrimethamine (SP) maintain sub-curative levels inblood for a long time such that in high malaria transmission areas,re-infecting parasites are continuously under selection pressure forresistant genotypes. Objective: To assess SP efficacy and posttherapeutic in-vivo selection for Plasmodium falciparum dihydrofolatereductase (DHFR) and dihydropteroate synthetase (DHPS) mutationsassociated with SP resistance.Design: SP efficacy trial withprospective follow up for selection of parasites with DHFR and DHPSmutations at re-infection in the resistance selection period (RSP). Subjects: Children aged < 5 years attending the outpatientreproductive and child health clinic of Kibaha district hospital withuncomplicated malaria fulfilling the inclusion criteria for efficacytrials in holoendemic settings. Main outcome measures: Clinical ¶sitological efficacy, pre-treatment and post-treatment prevalenceof P. falciparum DHFR & DHPS mutations. Results: Very high(98.2%) clinical & parasitological cure rates. DHFR single, doubleor triple mutations occurred in 46.7% of pre-treatment infections;triple c108/51/59 & double c108/51 mutations being commonest. Few(15.9%) DHPS mutations occurred in pre-treatment infections at c436 andc437. DHFR & DHPS mutations were significantly higher in post- thanpre- SP treatment parasites. In a Poisson regression analysis, DHFRmutations at c108, c51 & c59 and the exclusive c108/51/59 triplemutations were strongly associated with exposure to SP at re-infection. Conclusion: DHFR & DHPS mutations associated with SP resistanceexist in P. falciparum infections in a background of high SP efficacy.Despite optimal dosage, in holoendemic areas, these mutations will beselected by SP at re-infection; cumulatively shortening the usefultherapeutic life of SP due to resistance." @default.
- W2023863798 created "2016-06-24" @default.
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- W2023863798 date "2007-01-17" @default.
- W2023863798 modified "2023-09-27" @default.
- W2023863798 title "Emergence of mutations associated with resistance to Sulfadoxine-Pyrimethamine (SP) after single therapeutic dose: Implications on the useful therapeutic life of SP in malaria holoedemic areas" @default.
- W2023863798 doi "https://doi.org/10.4314/eajph.v2i2.38961" @default.
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