Interplay among malnutrition, chemoprevention, and the risk of malaria in young Ugandan children: Longitudinal pharmacodynamic and growth analysis

Abstract

African children are at risk of malaria and malnutrition. We quantified relationships between malaria and malnutrition among young Ugandan children in a high malaria transmission region. Data were used from a randomized controlled trial where Ugandan HIV‐unexposed (n = 393) and HIV‐exposed (n = 186) children were randomized to receive no malaria chemoprevention, monthly sulfadoxine‐pyrimethamine, daily trimethoprim‐sulfamethoxazole, or monthly dihydroartemisinin‐piperaquine (DP) from age 6–24 months, and then were followed off chemoprevention until age 36 months. Monthly height and weight, and time of incident malaria episodes were obtained; 89 children who received DP contributed piperaquine (PQ) concentrations. Malaria hazard was modeled using parametric survival analysis adjusted for repeated events, and height and weight were modeled using a Brody growth model. Among 579 children, stunting (height‐for‐age z‐score [ZHA] < −2) was associated with a 17% increased malaria hazard (95% confidence interval [CI] 10–23%) compared with children with a ZHA of zero. DP was associated with a 35% lower malaria hazard (hazard ratio [HR] [95% CI], 0.65 [0.41–0.97]), compared to no chemoprevention. After accounting for PQ levels, stunted children who received DP had 2.1 times the hazard of malaria (HR [95% CI] 2.1 [1.6–3.0]) compared with children with a ZHA of zero who received DP. Each additional malaria episode was associated with a 0.4% reduced growth rate for height. Better dosing regimens are needed to optimize malaria prevention in malnourished populations, but, importantly, malaria chemoprevention may reduce the burden of malnutrition in early childhood.