The incidence of invasive fungal infections and, in particular, Candida infections, the fourth most common nosocomial pathogen, has continued to increase over the past 40 years. This increase is due to the increasing numbers of patients subjected to severe immunosuppression as a result of transplant procedures, chemotherapy regimens, advances in medical and surgical therapies, and the increased use of invasive devices such as intravascular central lines. While the majority of invasive fungal disease (IFD) is caused by species of Candida and Aspergillus, other rare fungal pathogens such as Cryptococcus, Coccidioides, and Zygomycetes have become more prevalent in recent decades and are associated with exceedingly high mortalities (Candidiasis 20%; Aspergillosis 17%; Zygomycetes 14%; Cryptococcus 11%; Coccidioidomycosis 6%, and Blastomycosis 5%). Due to the slow turnaround time of current diagnostic methods, proper treatment of IFD is often delayed, contributing to the high mortality rates associated with this disease. Microbiologic culture, the current diagnostic standard, requires, on average, 48-72 hours for completion, and fails to detect roughly 50% of fungal species. As proper treatment of IFD calls for prompt and accurate diagnosis, an unmet need in the area of fungal diagnostics is a platform that can provide 1) early detection 2) sensitive results, 3) species level discrimination and 4) multiplex capability. Several molecular approaches have been developed to address this need but have failed to meet all these requirements. Immunetics' fungal microarray assay (IFM assay) uses PCR followed by hybridization on a microarray with species-specific probes, offering a solution to this unmet need by providing a sensitive and rapid (~5 hour) test for a range of fungal pathogens in a multiplex format, using whole blood samples rather than blood cultures. In this Phase II application we propose further development and clinical validation of the IFM assay for the detection and diagnosis of infection with 27 invasive fungal species. The clinical study will be carried out in collaboration with two medical institutions specializing in care and treatment of fungal infections, and will comprise prospective and retrospective evaluations on clinical blood samples obtained from patients at high risk for or with known fungal infections. Regulatory approval from FDA for in-vitro diagnostic use of the IFM assay will be sought upon successful completion of the clinical study, upon which the IFM kit will be commercialized as a standalone molecular diagnostic assay. This product offers a rapid, sensitive and multiplexed approach that meets the requirements of an ideal diagnostic platform for IFD. By significantly reducing time to detection, this innovative platform will lead to changes in the treatment of IFD, most notably, faster treatment with a targeted anti-fungal.
The incidence of fungal infections, most of which are associated with high mortality, has continued to increase over the past 40 years. Current fungal diagnostic methods are limited by number of pathogens detected, turnaround time and low sensitivity. We propose development and clinical validation of a rapid, multiplexed microarray based molecular test that will significantly improve the detection and treatment of invasive fungal disease.