Pediatric Fungal Network's (PFN) STudy of Rare Invasive Fungal DisEases in Immunocompromised Pediatric Patients (STRIDE) Project 2

Children'S Hosp Of Philadelphia, Philadelphia PA

Investigators

Abstract

PROJECT 2 SUMMARY/ABSTRACT Invasive fungal diseases (IFDs) represent a range of infections caused by rare fungi that are opportunistic in immunocompromised pediatric hosts. While these infections are relatively rare, they are associated with significant morbidity and mortality. Furthermore, as the care for underlying conditions such as hematologic malignancies, hematopoietic cell transplantation, solid organ transplantation, and patients with primary or acquired immune deficiency evolves, the patient population vulnerable to IFD will increase. The World Health Organization has recently highlighted fungi as a significant force impacting global public health. The WHO specifically underscored emerging pathogens and those for which antifungal resistance is a concern; fungal pathogens that are a focus in this proposal. Alarmingly, there is a lack of centralized resources to better understand the genomics and resistance profiles of these pathogens, information that would help guide therapeutic approaches and future clinical trials. To our knowledge, there are no large-scale, comprehensive collections of banked isolates of disease-related fungi that are integrated with genomic, phenotypic, and clinical data. Our goal is to establish a central biorepository to operationally receive and process rare fungal pathogens from newly diagnosed IFD cases among immunocompromised pediatric patients as well as isolates banked in existing fungal pathogen repositories, and establish a system that integrates genomic, phenotypic, and clinical information. In Aim 1 we will establish this biorepository and produce whole-genome sequences for approximately 350 fungal pathogens from the four rare IFD groups identified as foci for this proposal. In Aim 2 we will perform comprehensive antifungal susceptibility testing and these phenotypic results will be matched with genomic and clinical data. In Aim 3 we will quantify cohort-wide genomic diversity, pilot genome-wide association studies to prospectively identify novel antifungal resistance mechanisms, and directly investigate distribution of known antifungal resistance variants. This project will establish an innovative biorepository that addresses a critical gap in rare disease infrastructure and pioneer foundational knowledge for future work on IFD genomics, resistance, and clinical outcomes.