Early diagnosis of infectious disease is critical to patient outcome. An important early question is - """"""""is it a fungus, a bacterium or a virus?"""""""" A rapid answer to this question would allow preemptive treatment that can save lives. The goal of this project is a rapid and inexpensive immunoassay that will use serum as a sample to broadly identify the presence of invasive fungal disease (IFD). This is an unmet need for diagnosis of fungal infection, particularly for tests near the point of patient care. The target population willbe individuals for whom advanced medical intervention and use of potent immunosuppressive drugs has led to a proliferation of opportunistic and endemic fungal infection. The overall hypothesis is that selected polysaccharide and protein antigens are produced by pathogenic fungi that are shared across the genera that produce invasive disease. Moreover, a subset of these antigens is shed into blood in concentrations that would allow for detection. The approach will be immunoassay for the presence of two distinct antigens that i) are shared across fungal species that cause IFD and ii) are shed into blood during infection. Simultaneous detection of two distinct antigens will markedly enhance the predictive value. The product will be assays with the lateral flow immunoassay (LFA) and/or enzyme-linked immunoassay (ELISA) platforms. Criteria for success in this Phase I STTR would be production of mAbs reactive with two distinct fungal antigens, one a polysaccharide and the other a protein, that are shared by the major causes of IFD. Targeting of two independent antigens will produce an assay with a high predictive value. If this Phase I project is successful, a Phase II application would construct immunoassays in LFA or ELISA format and perform pre- clinical validation for broad diagnosis of invasive fungal disease. If successful, this translational research project could reduce mortality due to invasive fungal disease through earlier diagnosis and treatment.
Invasive fungal disease (IFD) is one of the most devastating complications of advanced medical care and use of powerful immunosuppressive drugs. IFD is difficult to diagnose and difficult to treat. This is a translational research study whose goal is n immunoassay for early, rapid, inexpensive and non-invasive diagnosis of IFD. If successful, the project could dramatically reduce morbidity and mortality from IFD through early diagnosis and treatment.
| Burnham-Marusich, Amanda R; Hubbard, Breeana; Kvam, Alexander J et al. (2018) Conservation of Mannan Synthesis in Fungi of the Zygomycota and Ascomycota Reveals a Broad Diagnostic Target. mSphere 3: |
| Kozel, Thomas R; Wickes, Brian (2014) Fungal diagnostics. Cold Spring Harb Perspect Med 4:a019299 |
