Differentiating between viral and bacterial infections in children is a diagnostic challenge, often leading to antibiotic overuse and driving antimicrobial resistance. Current diagnostic methods have notable limitations, highlighting the need for novel tools. Blood myxovirus resistance protein A (MxA) is a promising biomarker for viral infections, given its broad antiviral activity and rapid induction during viral illness. Host gene expression analysis further expands diagnostic possibilities by identifying biosignatures unique to viral or bacterial infections.

This thesis comprises four studies. Study I assessed respiratory viruses and antiviral MxA responses in children with febrile urinary tract infections (UTIs). Study II evaluated MxA as a biomarker for viral infection in children hospitalised with a suspected serious infection. Study III investigated the accuracy of a novel point-of-care (POC) MxA test and its ability to differentiate viral from bacterial infections in febrile children at the emergency department. Study IV explored host gene expression signatures to distinguish bacterial from viral infections.

In this study, respiratory viruses were frequently detected in children with febrile UTIs and other serious bacterial infections. Blood MxA levels were significantly higher in viral infections and viral-bacterial coinfections compared to bacterial infections. In children with a suspected serious infection, a blood MxA cutoff of 256 μg/L differentiated viral from bacterial infections with a sensitivity of 74% and specificity of 80%. The novel POC MxA test provided rapid results with acceptable accuracy compared to the reference method, supporting its use in acute care settings. A POC MxA level of 101 μg/L differentiated between viral and bacterial infections with 92% sensitivity and 91% specificity. A 2-transcript host gene expression signature (TSPO and SECISBP2) distinguished bacterial and viral-bacterial coinfections from viral infections with 77% sensitivity and 87% specificity.

This thesis highlights MxA and host gene expression analysis as promising advancements in paediatric infectious disease diagnostics. The high prevalence of viral-bacterial coinfections challenges novel diagnostic approaches and supports the use of MxA in combination with bacterial biomarkers.