Immunocompromised patients are at high risk for life-threatening invasive fungal infections (IFIs). Aspergillus and Candida species are the major causes for IFIs in Ireland, but occasionally IFIs are caused by unusual pathogens, such as Magnusiomyces/Geotrichum species. Unfortunately, established antifungal regimes are often less effective against these unusual species. For example, in cases of Magnusiomyces/Geotrichum-infections, none of the clinically available antifungals, even in combination, is capable of eliminating the pathogen from the host.
Granulocyte transfusions (GTs), although considered experimental, are therapeutic salvage interventions for such infections. While some studies see benefits from GTs, the evidence base is still low. One factor that could influence the efficacy of GTs is the antifungal activity of the granulocytes, which may vary greatly from donor to donor and batch to batch. Currently, a clinical gap exists as there is no standardised method of reliably assessing antifungal activity in GT batches.
This project aims to develop and optimise a robust and reliable assay for measuring the potency of GT batches against the aforementioned fungal pathogens. The central hypothesis is that such an assay will help 1) to optimise the quality of GT batches, and 2) to improve the quality of clinical studies on GTs by correlating the clinical outcome with the in vitro antifungal potency of the GT batches.