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

Aleksandra Leligdowicz, Andrea L. Conroy, Michael Hawkes, Melissa Richard-Greenblatt, Kathleen Zhong, Robert O. Opoka, Sophie Namasopo, David Bell, W. Conrad Liles, Bruno R. Costa, Peter Jüni and Kevin C. Kain ()
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Aleksandra Leligdowicz: Robarts Research Institute, University of Western Ontario
Andrea L. Conroy: Indiana University School of Medicine
Michael Hawkes: 3-593 Edmonton Clinic Health Academy, University of Alberta
Melissa Richard-Greenblatt: Toronto General Hospital, University Health Network, Sandra Rotman Centre for Global Health, MaRS Centre
Kathleen Zhong: Toronto General Hospital, University Health Network, Sandra Rotman Centre for Global Health, MaRS Centre
Robert O. Opoka: Mulago Hospital and Makerere University
Sophie Namasopo: Kabale District Hospital
David Bell: Independent consultant
W. Conrad Liles: Global Health, and Pharmacology, 1959 NE Pacific Street; HSB RR-511, Box 356420, University of Washington
Bruno R. Costa: Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Institute of Health Policy, Management and Evaluation, University of Toronto
Peter Jüni: Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Institute of Health Policy, Management and Evaluation, University of Toronto
Kevin C. Kain: Tropical Disease Unit, Sandra Rotman Centre for Global Health, Toronto General Hospital, University Health Network, Department of Medicine, University of Toronto, MaRS Centre

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-27215-6

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