Exploratory Serum Metabolomic Profiling of Asymptomatic Malaria Children Infected with <i>Plasmodium falciparum</i> in Tanzania

Asymptomatic <i>Plasmodium falciparum</i> infections are prevalent in malaria-endemic regions, yet their metabolic consequences remain poorly understood. In this exploratory study, we investigated the serum metabolomic profiles of 48 asymptomatic school-aged children from a high-transmission area in Tanzania (27 malaria-positive, 21 malaria-negative), using proton nuclear magnetic resonance (¹H NMR) spectroscopy and multivariate statistical analyses. Participants were matched by age, sex, and place of residence to control for confounding factors. Group-level comparisons revealed only modest and heterogeneous metabolic alterations in malaria-positive children, including lower concentrations of lactate, pyruvate, branched-chain amino acids, and threonine. However, KODAMA algorithm identified a metabolically distinct subgroup (18.5%) within the malaria-positive cohort. This subgroup displayed specific shifts in amino acid and lipid metabolism, such as reduced phenylalanine and alanine and increased glycerophospholipids, resembling profiles seen in symptomatic malaria, suggesting that a subset of asymptomatic individuals may exhibit biologically meaningful responses. In contrast, urinary tract infections (UTIs), detected in a subset of children, were associated with more consistent and malaria-independent metabolic signatures, particularly involving mannose and carbohydrate metabolism. These findings highlight the complexity of host responses to asymptomatic infections and emphasize the importance of accounting for coinfections and intragroup variability when interpreting metabolomic data in endemic settings.