Treatment history and treatment dose are important determinants of sulfadoxine-pyrimethamine efficacy in children with uncomplicated malaria in western Kenya

This study retrospectively studied amendable determinants of sulfadoxine-pyrimethamine (SP) efficacy involving 2869 treatments among 1072 Kenyan children <5 years old who had uncomplicated malaria. The dose was based on age: one-quarter tablet was given to infants <1 year old, one-half tablet was given to 1-3-year-old children, and a full tablet was given to 4-year-old children. Only 23.5% received the internationally recommended target dose of 25/1.25 mg of SP per kg of body weight. SP intake in the previous 15-35 days (adjusted relative risk, 1.67; 95% confidence interval, 1.35-2.07) and low SP dose (<27.5/1.375 mg/kg) (adjusted relative risk, 1.58; 95% confidence interval, 1.17-2.13) explained 38% of parasitological treatment failures by day 7. Patients with recent SP intake are likely to have recrudescent infections and may need close follow-up if treated with SP or alternative treatment. Applying our weight-for-age data to 31 existing age-based SP dose recommendations predicted that 22 of them would result in underdosing of >25% of children <5 years. Many age-based dose recommendations need urgent revision, because SP is increasingly used as first-line treatment in sub-Saharan Africa.