The puzzle of pediatric infections Challenges and opportunities for improving diagnosis of children with suspected infection

The puzzle of pediatric infection is to distinguish severe infections with potential life-threatening consequences from the many self-limiting and harmless infections. Despite the development of guidelines and risk prediction tools, variation in management of children with suspected infection is still substantial and may lead to overuse of diagnostic resources and subsequent burden on children. Therefore, this thesis aims to describe challenges in diagnosis of children with suspected infection, and explore opportunities to improve current management in the emergency department. Part I evaluates challenges of clinical recognition of infection and sample collection for diagnostic testing specifically from the perspective of congenital syphilis, neonatal herpes simplex virus (HSV) infection, and pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. From the perspective of children presenting with fever without a source (FWS), part II of this thesis explores challenges of FWS guidelines through retrospective and prospective evaluation of adherence to the current Dutch national guideline and its clinical outcomes. The Dutch guideline definitions and recommendations were additionally compared to national and regional guidelines for children with FWS from other high-income countries.