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

描述(由申请人提供)：这项研究SBIR应用的目的是为一种全球重要但诊断较差的医疗保健相关传染病，即艰难梭菌相关性腹泻，或CDAD，开发一种诊断测试的范式转变。目前对CDAD的实验室检测仅限于检测生物体和/或其毒素产物(S)，不能将感染患者与单纯定植的患者区分开来，从而导致诊断不准确以及抗生素的误用/过度使用。为了克服这些限制，将利用纳米球的生物条形码检测技术开发一种超灵敏的检测CDAD的微生物和宿主反应目标的检测方法。在第一阶段，将开发以蛋白质和DNA为基础的生物条形码分析，目标毒素B(微生物靶标)和原肌球蛋白(宿主反应)以及粪便标本制备方案。这一新方法的可行性将通过检测粪便样本中的CDAD来确定。在第二阶段，分析将进一步优化，以最大限度地提高灵敏度和特异度，仪器和软件将进行优化，以提供快速(从收到样本到最终结果在4小时内完成测试)、可靠(灵敏度和特异度大于95%)、易于使用(以便经认可的实验室可以进行分析)和成本效益的独立“试剂盒”形式。 艰难梭菌相关性腹泻，或CDAD，是一种全球重要但诊断较差的医疗保健相关传染病。重要的是，这种疾病的病原体已经成为关键的新出现的病原体，在医院看到了新的毒力菌株，明显出现了社区获得性疾病，并认识到CDAD是艾滋病毒感染者的关键病原体。更具体和更敏感的诊断平台将改善患者护理，使其能够在非常早的时间点进行具体和正确的治疗，从而降低严重疾病和死亡的潜在风险，并减少抗菌剂的过度使用。

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.