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Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test
Aleksandra Leligdowicz1, Andrea L Conroy2, Michael Hawkes3
1Robarts Research Institute, University of Western Ontario, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Insights
A new study in Uganda shows that measuring Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) can accurately identify febrile children at risk of death. This biomarker can help create rapid triage tests for sepsis in low-resource settings.
Area of Science:
- Pediatrics
- Infectious Diseases
- Biomarkers
Background:
- Sepsis is a leading cause of mortality in febrile children, particularly in low-resource settings.
- Effective triage tools are needed to identify high-risk children early.
- Circulating markers of immune and endothelial activation are potential indicators of sepsis severity.
Purpose of the Study:
- To evaluate the predictive accuracy of Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) for in-hospital mortality in febrile children.
- To determine if sTREM-1 can be used to risk-stratify children with fever in low-resource settings.
Main Methods:
- A prospective cohort study of 2,502 febrile children in Uganda.
- Measurement of sTREM-1 and 10 other biomarkers at initial clinical presentation.
- Analysis of sTREM-1's predictive accuracy for all-cause mortality using AUROC and likelihood ratios.
Main Results:
- sTREM-1 demonstrated high predictive accuracy for in-hospital mortality (AUROC 0.893-0.901).
- sTREM-1 effectively classified children into low, intermediate, and high-risk zones with distinct mortality rates (0.5%, 3.9%, 31.8% respectively).
- sTREM-1 outperformed 10 other tested biomarkers.
Conclusions:
- sTREM-1 is a promising biomarker for identifying febrile children at risk of mortality in low-resource settings.
- Defined sTREM-1 cutoffs can serve as a basis for a rapid triage test for fever syndromes.
- This approach could improve survival by enabling timely intervention for high-risk children.
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.
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