Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test

• Published in: Nature communications Vol. 12; no. 1; p. 6832
• Main Authors: Leligdowicz, Aleksandra, Conroy, Andrea L, Hawkes, Michael, Richard-Greenblatt, Melissa, Zhong, Kathleen, Opoka, Robert O, Namasopo, Sophie, Bell, David, Liles, W Conrad, da Costa, Bruno R, Jüni, Peter, Kain, Kevin C
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 25.11.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: At risk youth; Biomarkers; Child, Preschool; Children; Cohort Studies; Communicable Diseases; Death; Female; Fever; Humans; Infant; Likelihood ratio; Male; Markers; Mortality; Myeloid cells; Prediction models; Prospective Studies; Recognition; Risk; Sepsis; Survival; Triage - methods; Triggering Receptor Expressed on Myeloid Cells-1 - genetics; Triggering Receptor Expressed on Myeloid Cells-1 - metabolism; Uganda; Uganda
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27215-6

Identifying febrile children at risk of sepsis in low-resource settings can improve survival, but recognition triage tools are lacking. Here we test the hypothesis that measuring circulating markers of immune and endothelial activation may identify children with sepsis at risk of all-cause mortality. In a prospective cohort study of 2,502 children in Uganda, we show that Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) measured at first clinical presentation, had high predictive accuracy for subsequent in-hospital mortality. sTREM-1 had the best performance, versus 10 other markers, with an AUROC for discriminating children at risk of death of 0.893 in derivation (95% CI 0.843-0.944) and 0.901 in validation (95% CI 0.856-0.947) cohort. sTREM-1 cutoffs corresponding to a negative likelihood ratio (LR) of 0.10 and a positive LR of 10 classified children into low (1,306 children, 53.1%), intermediate (942, 38.3%) and high (212, 8.6%) risk zones. The estimated incidence of death was 0.5%, 3.9%, and 31.8%, respectively, suggesting sTREM-1 could be used to risk-stratify febrile children. These findings do not attempt to derive a risk prediction model, but rather define sTREM-1 cutoffs as the basis for rapid triage test for all cause fever syndromes in children in low-resource settings.