A Novel Diagnostic Test for Clostridium difficile-Associated Diarrhea (CDAD)

DESCRIPTION (provided by applicant): The aim of this research SBIR application is to develop a paradigm shift in diagnostic testing for a globally important, yet poorly diagnosed, healthcare-associated infectious disease, namely Clostridium difficile-associated diarrhea, or CDAD. Current laboratory testing for CDAD is limited to detection of the organism and/or its toxin product(s) and does not differentiate infected from simply colonized patients, thus leading to inaccurate diagnosis as well as antibiotic miss/overuse. To overcome these limitations, an ultra-sensitive assay that detects both microbial and host response targets for CDAD will be developed using Nanosphere's bio-barcode assay technology. In phase I, protein and DNA-based Bio-barcode assays that target toxin B (microbial target) and tropomyosin (host-response) will be developed along with protocols for stool specimen preparation. The feasibility of this new approach will be established by testing for CDAD in stool samples. In phase II, the assays will be further optimized to maximize sensitivity and specificity, and instrumentation and software will be optimized to provide a stand-alone 'kit' format that is rapid (complete testing from specimen receipt to a final result in well under 4 hours), reliable (with sensitivity and specificity greater than 95%), easy to use (so that accredited laboratories can perform the assay), and cost efficient. Clostridium difficile-associated diarrhea, or CDAD, is a globally important, yet poorly diagnosed, healthcare-associated infectious disease. Importantly, the causative agent of this disease has become a crucial emerging pathogen with new virulent strains seen in the hospital, apparent emergence of community acquired disease and recognition of CDAD as a key pathogen for HIV-infected persons. A more specific and sensitive diagnostic platform will improve patient care by enabling specific, correct treatment at a very early time point, thus lowering the potential risk of severe disease and death as well as lower the overuse of antimicrobial agents.