Theme V: Determinants of patient susceptibility, including immunity and co-morbidities, to enable directed diagnosis, treatment and prevention of fungal disease

We now possess considerable capacity in clinical mycology and in immunology and, with the recruitment of an individual with expertise in infectious co-morbidities, we will be uniquely placed to significantly advance our understanding of patient susceptibility to fungal infections. Under this theme we will elucidate key mechanisms of innate and adaptive antifungal immunity, how these systems contribute to susceptibility or protection from disease in healthy individuals, and how defects or alterations of these systems affect susceptibility to fungal infections in patients. We will determine how co-morbidities (especially co-infections with viruses, bacteria and helminths) influence immunity and disease pathology, and will establish improved approaches to diagnose, treat and prevent fungal infection in patients. Clinical trials feeding into research underlying aspects of this theme include AMBITION, “Targeting Immunotherapy for Fungal Infections in Cystic Fibrosis (TrIFIC)” [Co- PI:Warris], “Aspergillosis in patients with severe influenza or coronavirus (AspiFlu)” [ISRCTN 51287266, PI: Bicanic], and “Prospective validation & clinical evaluation of a new posaconazole dosing regimen for children with Cystic Fibrosis and Aspergillus infection (cASPerCF) [EUDRACT 2019-004511-31; CI: Warris].