Abstract

Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. clinicaltrials.gov (NCT03163628).

Highlights

  • Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years

  • Serum concentrations of IFN-a were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001)

  • IFN-a is increased in blood of febrile infants with viral infections

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Summary

Methods

Paxgene tubes and serum were collected from febrile children (n 1⁄4 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the NanostringVR technology and plasma IFN-a quantified by digital ELISA technology. This was an ancillary study of the prospective multicenter protocol ANTOINE (NCT03163628) (Fig. 1). Patients were included prospectively in this multicenter study from June 2017 to June 2019 (NCT03163628). Written informed consent was obtained from parents or legal guardians for participation of the febrile children in the ANTOINE study. An additional specific written consent was needed to allow the participation of the present ancillary study.

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