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  • Clinical Research Article
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Early diagnosis of serious bacterial infection in febrile infants using type I interferon signature

Pediatric Research (2025)Cite this article

Abstract

Background

Febrile infants ≤90 days are at high risk of serious bacterial infections, but prompt differentiation between viral and bacterial infections remains a challenge. Host gene expression signatures, particularly those involving the type I interferon (IFN) pathway, show promise as diagnostic tools. This study evaluates the ability of IFN signature to differentiate bacterial from viral infections in this population.

Methods

This is a prospective, single-center study. Infants ≤90 days were enrolled. All patients underwent complete blood count, CRP, PCT, and IFN signature, assessed by analyzing the expression of six interferon-stimulated genes. Based on routine investigations, patients were divided into bacterial (BI, n = 8) and non-bacterial infection (non-BI, n = 39) and healthy controls (HC, n = 3). Regression analysis was used to determine the variable’s predictive correlation.

Results

Forty-seven febrile infants were enrolled. IFN signature resulted significantly elevated in non-BI compared to BI (p < 0.001) and HC (p = 0.008), even within 12 h of fever onset. IFN demonstrated the highest AUC for predicting BI. Combining IFN with CRP or PCT yielded the most robust predictive models (AUC = 0.99 and 0.98).

Conclusions

IFN signature resulted as a promising, reliable predictor of BI versus non-BI in febrile infants. This novel biomarker, combined with others, could improve the management of febrile infants reducing unnecessary antibiotics and hospitalizations.

Impact

  • This is the first study to focus on the IFN signature in febrile infants under 90 days old, adding novel insights into the potential of host immune responses as diagnostic biomarkers.

  • This study demonstrates that the peripheral blood interferon signature, specifically the expression of six IFN-stimulated genes, can distinguish bacterial from non-bacterial infections in febrile infants aged 90 days or younger in the very first hours of fever.

  • The IFN score, when combined with traditional inflammatory markers, offers high sensitivity and specificity, making it a potential diagnostic tool for optimizing treatment and reducing unnecessary interventions.

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Fig. 1: Comparison of inflammatory markers between bacterial infection (BI), non-bacterial infection (non-BI), and healthy controls (HC) groups.
Fig. 2: ROC curve analysis of inflammatory markers for bacterial infection prediction.
Fig. 3: Comparison of inflammatory markers and IFN score performed within 12 h of fever onset between bacterial infection (BI) and non-bacterial infection (non-BI) groups.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Author information

Authors and Affiliations

  1. Pediatric Emergency Room and Emergency Medicine Unit, Emergency Department, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Elena Fueri, Giovanna Villa, Marta Bustaffa, Emanuela Piccotti & Tommaso Bellini

  2. Rheumatology and Autoinflammatory Diseases, IRCCS Istituto Giannina Gaslini, Genova, Italy

    Paola Bocca, Riccardo Papa & Stefano Volpi

  3. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal, and Child Health (DINOGMI), University of Genoa, Genoa, Italy

    Federica Serafino, Stefano Volpi & Tommaso Bellini

Authors
  1. Elena Fueri
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  2. Paola Bocca
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  3. Giovanna Villa
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  5. Federica Serafino
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  6. Emanuela Piccotti
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  9. Tommaso Bellini
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Contributions

E.F., T.B., S.V., and R.P. conceived the idea; E.F., G.V., M.B., F.S., and E.P. collected the samples; P.B. performed the interferon signature analysis; E.F. and T.B. performed the experiments and analyzed the data; E.F. and T.B. prepared the first draft. S.V. and E.P. revised the manuscript. All the authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Tommaso Bellini.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Approval for this study was granted by the local Ethics Committee (CET - Liguria:262/2024 - DB id 13963). Informed consent was obtained from the parents of all patients.

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Fueri, E., Bocca, P., Villa, G. et al. Early diagnosis of serious bacterial infection in febrile infants using type I interferon signature. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04229-0

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