Pediatric Fungal Network STudy of Rare Invasive Fungal DisEases in Immunocompromised Pediatric Patients (PFN-STRIDE)

Children'S Hosp Of Philadelphia, Philadelphia PA

Investigators

Abstract

OVERALL PROJECT SUMMARY/ABSTRACT Invasive fungal diseases (IFD) are infections caused by opportunistic fungi that are ubiquitous in the environment and often prey selectively on vulnerable populations, including patients who are immunocompromised. Although rare, IFDs are associated with significant morbidity and short-term case fatality rates of more than 30%. Current diagnostic approaches are extremely limited, often requiring risky invasive procedures, and management is often prolonged and sometimes ineffective. In immunocompromised children, IFDs are rarer and even more complicated to diagnose and manage than those in adults. IFDs most often impact pediatric patients with serious underlying immune-compromising conditions (e.g., primary immunodeficiency, malignancy), meaning that diseases that would otherwise be cured or managed long-term often turn deadly with concomitant IFD. Despite this obvious burden, there is a dearth of research aimed at advancing diagnostic approaches and management protocols for pediatric IFDs, and a persistent absence of data on patient and caregiver perspectives of the impact of these infections. This lack of knowledge is a direct result of the rarity of these events and the patient populations they impact. The Rare Diseases Clinical Research Consortium outlined in this proposal, the Pediatric Fungal Network STudy of Rare Invasive Fungal DisEases in Immunocompromised Pediatric Patients (PFN-STRIDE), will leverage the existing Pediatric Fungal Network that is dedicated to studying fungal infections in pediatric patients. The PFN-STRIDE RDCRC overall objective is to further the foundational work of prior PFN studies to advance the diagnostic and management approaches for rare IFD in children. This objective will be accomplished through three linked clinical and translational research projects. The first, a natural history study, will generate foundational epidemiologic data on IFDs in immunocompromised children by capturing clinical and patient- reported outcome data. The second will create a central fungal pathogen biorepository for genetic sequencing and susceptibility testing to correlate with clinical outcomes recorded in the natural history study. The third will explore novel IFD diagnostics by applying artificial intelligence algorithms on CT and MRI imaging studies and -omics analyses on blood specimens from immunocompromised pediatric patients with IFD. Additionally, Administrative, Career Development, and Pilot/Feasibility Governance Cores will support the completion of the three projects, as well as engage trainees and junior faculty interested in developing careers and research portfolios in pediatric mycology. Collectively, the RDCRC projects and cores will yield evidence to change clinical practice and inform design of future clinical trials.