Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 25;5(1):310.
doi: 10.1038/s43856-025-01014-2.

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

Núria Balanza  1   2 , Bàrbara Baro  1 , Sara Ajanovic  1   2   3 , Zumilda Boca  3 , Justina Bramugy  2   3 , Anelsio Cossa  3 , Elizabeth Ja Fitchett  4 , Heidi Hopkins  4 , Suzanne H Keddie  4 , Sham Lal  4 , David C W Mabey  4 , Tegwen Marlais  4 , Hridesh Mishra  5 , Campos Mucasse  3 , Marta Valente  1   2   3 , Andrea M Weckman  5 , Julie K Wright  5   6   7 , Shunmay Yeung  4 , Kathleen Zhong  5 , Kevin C Kain  5   6   7 , Quique Bassat  8   9   10   11   12   13   14
Affiliations

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

Núria Balanza et al. Commun Med (Lond). .

Abstract

Background: 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.

Methods: 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.

Results: 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).

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

Plain language summary

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare the following competing interests: K.C.K. is a named inventor on a patent “Biomarkers for early determination of a critical or life-threatening response to illness and/or treatment response” held by the University Health Network. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Plasma concentrations of host biomarkers at clinical presentation among enrolled paediatric and adult patients with febrile illness in southern Mozambique.
Panel a shows biomarker concentrations in all outpatients (N = 1040) and inpatients (N = 915). Panel b shows biomarker concentrations in outpatients alive at day 28 (N = 852), inpatients alive at day 28 (N = 648), and deaths within 28 days (N = 93). Boxplots display the median and interquartile range, with whiskers extending to 1.5 times the interquartile range. Concentrations are in pg/mL, except for CRP (μg/mL) and suPAR (ng/mL). suPAR values are missing for 16 participants in Panel a and for 12 participants in Panel b. p values were calculated using Mann–Whitney U tests. Angpt-2 angiopoietin-2, CHI3L1 chitinase-3-like protein 1, CRP C-reactive protein, IL-6 interleukin-6, IL-8 interleukin-8, PCT procalcitonin, sFlt-1 soluble fms-like tyrosine kinase-1, sTNFR1 soluble tumour necrosis factor receptor 1, sTREM-1 soluble triggering receptor expressed on myeloid cells 1, suPAR soluble urokinase-type plasminogen activator receptor.
Fig. 2
Fig. 2. AUROC of each host biomarker for 28-day mortality among enrolled paediatric and adult patients with febrile illness in southern Mozambique.
Plots display the AUROC (dot) with 95% CI (horizontal line) of each biomarker for 28-day mortality in the entire cohort (Panel a) and in each patient subgroup according to age group (Panel b), sex (Panel c), and HIV status (Panel d). Corresponding numerical values of the AUROCs, with 95% CIs in parentheses, are shown to the right of each plot. For suPAR, the total sample size is N = 1581 (91 deaths); restricting analyses to this population does not affect the overall ranking of AUROCs or the AUROC values of sTREM-1. Angpt-2 angiopoietin-2, AUROC area under the receiver operating characteristic curve, CHI3L1 chitinase-3-like protein 1, CI confidence interval, CRP C-reactive protein, HIV human immunodeficiency virus, IL-6 interleukin-6, IL-8 interleukin-8, PCT procalcitonin, sFlt-1 soluble fms-like tyrosine kinase-1, sTNFR1 soluble tumour necrosis factor receptor 1, sTREM-1 soluble triggering receptor expressed on myeloid cells 1, suPAR soluble urokinase-type plasminogen activator receptor.
Fig. 3
Fig. 3. Kaplan-Meier survival curves by sTREM-1 categories among enrolled paediatric and adult patients with febrile illness in southern Mozambique.
Kaplan-Meier curves with 95% CIs illustrate the survival probability over time by sTREM-1 categories for the entire cohort (Panel a), HIV-negative individuals (Panel b), and HIV-positive individuals (Panel c). We applied sTREM-1 cut-offs previously derived with data from hospitalized febrile children in Uganda for mortality prediction, stratifying participants into three risk categories based on sTREM-1 levels: low-risk (sTREM-1 < 239 pg/mL), intermediate-risk (sTREM-1 239–628 pg/mL), and high-risk (sTREM-1 ≥ 629 pg/mL). Inpatients with unknown vital status at day 28 were included in the analyses and censored when discharged alive from hospital. CI confidence interval, HIV human immunodeficiency virus, sTREM-1 soluble triggering receptor expressed on myeloid cells 1.
Fig. 4
Fig. 4. AUROC of each clinical severity score alone and combined with sTREM-1 for 28-day mortality among enrolled paediatric and adult patients with febrile illness in southern Mozambique.
Plots display the AUROC (dot) with 95% CI (horizontal line) of sTREM-1, each clinical severity score, and the combination of sTREM-1 and each clinical severity score for 28-day mortality in children (Panel a) and in adults (Panel b). Corresponding numerical values of the AUROCs, with 95% CIs in parentheses, are shown to the right of each plot. We included all participants with a known vital status at day 28 and clinical data for the calculation of all clinical severity scores. AUROC area under the receiver operating characteristic curve, CI confidence interval, ED-PEWS Emergency Department Paediatric Early Warning Score, LODS Lambaréné Organ Dysfunction Score, LqSOFA Liverpool quick Sequential Organ Failure Assessment, MEWS Modified Early Warning Score, qSOFA Quick Sequential (Sepsis-Related) Organ Failure Assessment, sTREM-1 soluble triggering receptor expressed on myeloid cells 1, UVA Universal Vital Assessment.
See this image and copyright information in PMC

References

    1. World Health Organization. WHO informal consultation on fever management in peripheral health care settings: A global review of evidence and practice. Geneva: World Health Organization, (2013).
    1. Buntinx, F., Mant, D., Van den Bruel, A., Donner-Banzhof, N. & Dinant, G.-J. Dealing with low-incidence serious diseases in general practice. Br. J. Gen. Pr.61, 43–46 (2011). - PMC - PubMed
    1. Chandna, A. et al. Anticipating the future: prognostic tools as a complementary strategy to improve care for patients with febrile illnesses in resource-limited settings. BMJ Glob. Health6, e006057 (2021). - PMC - PubMed
    1. Achan J. et al. Case management of severe malaria - A Forgotten Practice: Experiences from Health Facilities in Uganda; 6:e17053. (2011). - PMC - PubMed
    1. Chang, J. L. et al. Who stays and who goes: Predictors of admission among patients presenting with febrile illness and a positive malaria rapid diagnostic test in a rural Ugandan health center. Am. J. Trop. Med. Hyg.99, 1080–1088 (2018). - PMC - PubMed

LinkOut - more resources