DESCRIPTION (provided by applicant): Invasive aspergillosis is a leading cause of morbidity and mortality in immunocompromised patients. Patients at high-risk for this opportunistic fungal infection include those with hematologic malignancies, patients undergoing hematopoietic stem cell transplantation, and solid organ transplant recipients. Despite the increased availability of newer antifungal agents response rates to treatment are suboptimal with only 50% of patients having a complete or partial response to voriconazole, the drug of choice for the primary treatment of this invasive disease. Prophylaxis with antifungal agents has been shown to reduce the incidence of invasive fungal disease in heavily immunocompromised patients and improve patient outcomes. However, this strategy is costly and exposes patients to significant adverse effects and clinically relevant drug-drug interactions associated with extended antifungal exposure. Early diagnosis and initiation of appropriate therapy based on radiographic assessment and serial screening of diagnostic biomarkers, such as galactomannan and (1->3)-?- D-glucan, has also been shown to improve outcomes and reduce the unnecessary use of antifungal therapy. However, this approach of pre-emptive treatment has not yet been confirmed in larger clinical trials. Furthermore, the sensitivity of these diagnostic biomarkers may be reduced in patients with antifungal exposure, and it is unknown how well they correlate with response to antifungal therapy. Thus, the development of new surrogate markers for the early diagnosis of invasive aspergillosis and for measuring response to antifungal therapy is needed to improve treatment outcomes in patients with this highly invasive disease. Our objective is to assess a new candidate biomarker of invasive aspergillosis, an extracellular glycoprotein antigen secreted during invasive disease caused by Aspergillus, in relation to disease development and time of diagnosis. Furthermore, we will determine the utility of incorporating monoclonal antibodies against this biomarker into lateral-flow devices in order to allow for point-of-care diagnosis of this opportunistic infection. We will also develop enzyme-linked immunosorbent assays (ELISA) for quantitative analysis as a means of establishing a threshold above which patients are classified as being positive for invasive disease. The ELISA assays will also serve as a confirmatory test to the lateral-flow devices to ensure the accuracy of the diagnosis. The sensitivity and specificity of these assays will be determined in an established animal model of invasive pulmonary aspergillosis as well as in samples collected from patients with proven or probable disease. We will also determine the utility of these assays in following therapeutic response to antifungal agents.
|Effective start/end date||6/17/10 → 5/31/12|
- National Institutes of Health: $144,637.00
- National Institutes of Health: $179,403.00
- Immunology and Microbiology(all)