Emergence of Mutations Associated with Resistance to Sulfadoxine-Pyrimethamine (SP) After Single Therapeutic Dose: Implications on the Useful Therapeutic Life of SP in Malaria Holoendemic Areas

According to this study, drugs with long elimination half-lives such as Sulfadoxine -Pyrimethamine (SP) maintain sub-curative levels in blood for a long time such that in high malaria transmission areas, re-infecting parasites are continuously under selection pressure for resistant genotypes. The objective of this study was to assess SP efficacy and post therapeutic in-vivo selection for Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) mutations associated with SP resistance. The results found that DHFR & DHPS mutations associated with SP resistance exist in P. falciparum infections in a background of high SP efficacy. Despite optimal dosage, in holoendemic areas, these mutations will be selected by SP at re-infection; cumulatively shortening the useful therapeutic life of SP due to resistance.