Pathogen virulence and host response: A systematic review of severe illness in childhood musculoskeletal infection.

Background: Severe forms of childhood bone and joint infection (BJI) involve multifocal sepsis, often requiring multiple surgeries and intensive care. Dysregulation of the Acute Phase Response (APR) occurs, as bacterial virulence factors disrupt protective inflammatory and coagulation mechanisms. Methods: A systematic review of the literature was undertaken from 01/01/2000-1/08/2025. Studies reporting host or pathogen factors associated with BJI severity for children </ = 18 years were included. Studies focussed on Results: Literature search of electronic databases returned 1171 articles, of which 38 met full criteria. These comprised 10,084 patients across multiple continents. Pathogen factors associated with severe illness included Methicillin-resistant Conclusion: These findings indicate that severe pediatric BJI results from complex interactions between bacterial virulence factors and host response capacity. Awareness of these factors should equip clinicians to recognise potentially high-risk cases early in the course of illness. Future research should ascertain how virulence factors dysregulate the host APR, guiding therapeutic interventions targeting the underlying pathophysiology.