Intestinal injury biomarkers predict mortality in pediatric severe malaria

Maithri L. Sarangam, Ruth Namazzi, Dibyadyuti Datta, Caitlin Bond, Charles Vanderpool, Robert Opoka, Chandy John, Andrea Conroy

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Severe malaria (SM) increases the risk of invasive bacterial infection,and there is evidence to suggest increased gastrointestinal permeability. Studieshave shown sequestration of infected erythrocytes in intestinal microvasculature,andin vivostudies of rectal mucosa have demonstrated disruption of microvascularbloodflow. However, the extent of intestinal injury in pediatric malaria is not wellcharacterized. In this study, two serum biomarkers of intestinal injury, trefoil factor 3(TFF3) and intestinal fatty acid binding protein (I-FABP), were analyzed in 598 chil-dren with SM and 120 healthy community children (CC), 6 months to 4 years of age.Serum was collected at enrollment and 1 month for laboratory studies, and partici-pants were monitored for 12 months. Intestinal injury biomarkers were significantlyelevated in children with SM, with 18.1% having levels of TFF3 and/or I-FABP greaterthan the 99th percentile of CC levels. TFF3 levels continued to be elevated at1 month, while I-FABP levels were comparable to CC levels. Both markers predictedin-hospital mortality {odds ratio (OR) (95% confidence interval [CI]), 4.4 (2.7, 7.3) and2.3 (1.7, 3.1)} for a natural log increase in TFF3 and I-FABP, respectively. TFF3 wasalso associated with postdischarge mortality (OR, 2.43 [95% CI, 1.1, 4.8]). Intestinalinjury was associated with acute kidney injury (AKI), acidosis (P,0.001 for both),and angiopoietin 2, a maker of endothelial activation. In conclusion, intestinal injuryis common in pediatric severe malaria and is associated with an increased mortality.It is strongly associated with AKI, acidosis, and endothelial activation.

Original languageUndefined/Unknown
JournalPaediatrics and Child Health, East Africa
Publication statusPublished - 1 Oct 2022

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