Host-Directed Medicine in invasive FUNgal infections

Despite novel treatment options and diagnostic tools, invasive fungal infections are still associated with an unacceptably high mortality and morbidity. Experts believe that a host-directed approach is needed to overcome this clinical challenge. No study to date in invasive fungal infection has integrated a host-directed strategy into a clinical trial. This consortium proposes for the first time a trans-disciplinary approach to identify personalized therapeutic and prophylactic strategies based on host-pathogen factors. We believe that we need such a personalized medicine approach in order to advance the aim of improved outcome in invasive fungal infection, and that, together with the exponential knowledge that has been gained in host-fungal interaction over the last two decades, it is time to move towards proof-of-principle clinical trials that can save lives of patients.

In this project, we aim to identify host-pathogen factors (HPFs) and to dissect their contribution to the development of invasive fungal infection (IFI). Such knowledge is invaluable to guide host-directed immunotherapy and antifungal prophylaxis in patients with IFI in the intensive care unit. Conceptually we believe that immunotherapy guided by host immune status as well as an individualized antimicrobial prophylaxis approach based on host-pathogen factors are the two most promising host-directed medicine approaches that will have the biggest impact on outcome of infectious disease burden in the near future. Both approaches are addressed in HDM-FUN via two independent clinical trials that will result in a unique biobank of clinical samples for host-directed research. Both clinical studies on host-directed medicine are the first of their kind in this area. Hitherto, it is unknown which host-pathogen factors are optimal to stratify patients for immunotherapy or antimicrobial prophylaxis.