# Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) predicts mortality in patients with febrile illness in southern Mozambique

## TL;DR

The study finds that measuring sTREM-1 in blood can help predict which febrile patients are at higher risk of dying, especially in resource-limited settings like Mozambique.

## Contribution

sTREM-1 is shown to be a superior biomarker for predicting mortality in febrile illness compared to commonly used markers like PCT and CRP.

## Key findings

- sTREM-1 outperforms PCT, CRP, and lactate in predicting 28-day mortality with an AUROC of 0.82.
- High sTREM-1 levels correlate with longer hospital stays and increased risk of further care or hospitalization.
- sTREM-1's predictive power is slightly reduced in HIV-positive individuals but still significant.

## Abstract

Fever is a leading reason for seeking healthcare globally. Early in the course of febrile illness, it is challenging to identify patients at risk of severe and fatal infections. Quantifying biomarkers of immune and endothelial activation may facilitate patient triage.

We prospectively enrolled children ≥2 months and adults with fever visiting two Mozambican hospitals from December 2018 to February 2021. Standard clinical and laboratory parameters, including lactate levels, were assessed at presentation. Plasma levels of Angpt-2, CHI3L1, CRP, IL-6, IL-8, PCT, sFlt-1, sTNFR1, sTREM-1, and suPAR at presentation were retrospectively quantified. Clinical outcomes were evaluated up to 28 days. We assessed the prognostic performance of biomarkers for 28-day mortality and explored their association with other adverse outcomes.

This study includes 1955 participants, with 93 deaths occurring within 28 days. We show that all biomarker levels are elevated in inpatients compared to outpatients and are associated with 28-day mortality (all p < 0.001). sTREM-1 is the best biomarker predicting 28-day mortality with an AUROC of 0.82 (95% CI: 0.78-0.86), superior to that of PCT (p < 0.001), CRP (p < 0.001), and lactate (p = 0.0033). Its prognostic performance is consistent across age and sex, but is reduced in HIV-positive individuals (AUROC = 0.73, 95% CI: 0.66-0.80). Adding sTREM-1 improves the discrimination of clinical severity scores for 28-day mortality. Among discharged inpatients, sTREM-1 is positively correlated with duration of hospitalisation (p < 0.001). Among outpatients, sTREM-1 levels are higher in those seeking further care (p = 0.0022) or subsequently hospitalised (p = 0.012).

sTREM-1 is a promising biomarker for risk stratification of all-age, all-cause febrile illnesses in resource-limited settings.

Fever is a common reason people seek healthcare, but at presentation it is often difficult to determine which individuals are at risk of becoming seriously ill. This study followed children and adults with fever presenting to hospital in Mozambique to assess whether measuring certain blood biomarkers could help identify those at risk of severe and fatal infections. One biomarker, called sTREM-1, was the best predictor of mortality and added prognostic information beyond usual clinical signs in both children and adults. sTREM-1 was slightly less accurate in HIV-positive patients but remained a good predictor. High levels of sTREM-1 were also linked to other adverse outcomes besides mortality. Measuring sTREM-1 could help healthcare workers in resource-limited settings recognize febrile patients who require closer monitoring or advanced treatment.

Balanza et al. study biomarkers of immune and endothelial activation in children and adults with febrile illness presenting to hospital in Mozambique. They find that sTREM-1 predicts 28-day mortality and represents a promising biomarker for patient risk stratification.