Type I Interferon in Children with Viral or Bacterial Infections

BACKGROUND: 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. METHODS: 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 (R) technology and plasma IFN-alpha quantified by digital ELISA technology. RESULTS: Serum concentrations of IFN-alpha 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-alpha concentrations and IFN score were significantly higher in viral compared to bacterial infection (P< 0.001). There was a strong correlation between serum IFN-alpha concentrations and IFN score (p-pearson = 0.83). Both serum IFN-alpha 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 3 (0.83). CONCLUSIONS: IFN-alpha is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-alpha femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse.