John R. Wingard, M.D.,University of Florida Shands Cancer Center, Barbara D. Alexander, M.D., M.H.S., Duke University Medical Center, Durham, NC 27710
Candida and Aspergillus are the two most common invasive fungal pathogens in hospitalized patients in the United States (U.S.). They cause considerable morbidity and case fatality rates are high in immunocompromised patients. For Candida, effective therapeutics have quelled the threat to life for many, but for Aspergillus, mortality rates continue to rise. For Invasive Aspergillosis (IA), diagnosis is difficult. effective control occurs in only half of infected patients, and control rates are even worse in certain highly immunocompromised patient groups. Deaths due to IA in U.S. hospitalized patients have mounted10 and costs to the U.S. health care system are enormous with incremental costs per IA case estimated to range between $30,000 - $100,000, depending on the underlying disease condition. Aspergillus accounts for the most deaths due to mold pathogens and is among the top 3 fungal killers in the world. The lack of accurate diagnostics for Aspergillus is the most important unmet need in clinical mycology. IA is most commonly initiated by inhalation of ubiquitous, airborne fungal spores that establish a primary pulmonary disease and which can relatively quickly disseminate via the blood to involve multiple organ systems. Despite hematogenous dissemination, fungal blood cultures are rarely positive and the form of the pathogen that circulates in the blood in disseminated infection is not known. It is hoped that new diagnostic assays will offer a more accurate and earlier diagnosis resulting in earlier therapy and improved outcomes.
The principal goal of this project is to determine if pathogen and/or host response proteins can be identified in clinical samples which can be used as specific biomarkers of IA in future diagnostic tests. Secondary goals are to determine how early in the course of IA these biomarkers can be found, whether protein signatures can be identified as markers of treatment response, and whether different protein signatures are characteristic of different IA infection sites.