Plasma amino acid concentrations in children with severe malaria are associated with mortality and worse long-term kidney and cognitive outcomes

J Infect Dis. 2022 Sep 30;jiac392. doi: 10.1093/infdis/jiac392. Online ahead of print.


Background: Global changes in amino acid levels have been described in severe malaria (SM) but the relationship between amino acids and long-term outcomes in SM have not been evaluated.

Methods: We measured enrollment plasma concentrations of twenty amino acids using high-performance liquid chromatography in 500 Ugandan children aged 18 months to 12 years, including 122 community children and 378 children with SM. The Kidney Disease: Improving Global Outcomes criteria were used to define acute kidney injury (AKI) at enrollment and chronic kidney disease (CKD) at one-year follow-up. Cognition was assessed over two years follow-up.

Results: Compared to laboratory defined age-specific reference ranges, there were deficiencies in sulfur-containing amino acids (methionine, cysteine) in both community children and children with SM. Among children with SM, global changes in amino acid concentrations were observed in the context of metabolic complications including acidosis and AKI. Increases in threonine, leucine and valine were associated with in-hospital mortality, while increases in methionine, tyrosine, lysine, and phenylalanine were associated with post-discharge mortality and CKD. Increases in glycine and asparagine were associated with worse attention in children <5 years of age.

Discussion: Among children with SM, unique amino acid profiles are associated with mortality, CKD, and worse attention.

Keywords: acute kidney injury; amino acids; cerebral malaria; chronic kidney disease; cognition; mortality; pediatric; severe anemia; severe malaria.