Rapid Molecular Diagnostic for Chlamydia and Gonorrhea at the Point-of-Care

衣原体和淋病的即时快速分子诊断

• 批准号: 8897723
• 负责人: CATHERINE M. KLAPPERICH
• 金额: $ 40.38万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-05 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8897723
• 关键词: Acquired Immunodeficiency Syndrome; Bacterial Infections; Bedside Testings; Biological Assay; Biology; Care Technology Points; Centers for Disease Control and Prevention (U.S.); Chlamydia; Clinic; Clinical; Clinical Research; Clinical Trials; DNA; Detection; Devices; Diagnosis; Diagnostic; Early Diagnosis; Ectopic Pregnancy; Ensure; Epidemiology; Genitourinary system; Goals; Gold; Gonorrhea; Health; Health Personnel; Human; Hybrids; Immune; Improve Access; Individual; Infection; Infertility; Laboratories; Lateral; Learning; Literature; Mammalian Oviducts; Microfluidics; Molecular; Molecular Diagnostic Testing; Multi-Drug Resistance; Neisseria gonorrhoeae; Nucleic Acids; Organism; Paper; Pathogen detection; Patients; Pelvic Inflammatory Disease; Point-of-Care Systems; Preparation; Process; Protocols documentation; Reagent; Reporting; Research; Running; Sampling; Sensitivity and Specificity; Sexually Transmitted Diseases; Simulate; Specimen; Sterility; Swab; Symptoms; System; Technology; Test Result; Testing; Time; United States; Universities; Urine; Uterus; Virus; Virus Diseases; Visual; Woman; Work; chronic pelvic pain; commercialization; cost; cross reactivity; design; diagnosis quality; innovation; instrument; instrumentation; internal control; pathogen; point of care; prospective; scale up; success; transmission process; validation studies

DESCRIPTION (provided by applicant): More than 4 million people in the United States are infected with chlamydia (CT) and gonorrhea (NG). These sexually transmitted infections (STIs) have few early symptoms but cause serious complications that range from sterility and infertility to multidrug resistance and increased HIV infection and transmission. Reducing the spread of these STIs will require early diagnosis, and treatment of infected individuals. Success requires the wide availability of low-cost, robust, and easy to use molecular diagnostics for use at the point-of-care (POC) for the earliest detection of the causative organism. We have developed sample-to-answer molecular diagnostic assays for CT and for NG detection in simulated urine. The hypothesis to be tested is that molecular diagnostic chips can detect and differentiate CT and NG in microliter-scale human urogenital samples with specificity and sensitivity better than presently available POC testing. We have previously demonstrated at the bench that the components of the chip work with simulated samples. Our goal is to develop a portable, inexpensive molecular diagnostic that can be used at the POC to diagnose and differentiate CT and NG infections. We have teamed up with Dr. Charlotte Gaydos at Johns Hopkins University Center for Point-of-Care Technologies Research for Sexually Transmitted Diseases to perform an intermediate sized sensitivity and specificity study using previously collected and stored urogenital specimens that have been de-identified and well characterized. We will develop a low-cost, integrated sample-to-result molecular diagnostic assay system to detect chlamydia and gonorrhea that uses a simple, visual means of detecting nucleic acid amplification products. In order to develop this technology for real-world clinical and field use, the following aims are proposed: 1. To adapt our current test to a multiplexed CT and NG assay, we will optimize sample preparation, amplification, and detection of CT, NG, and a competitive internal control (CIC). 2. To enable testing at the POC, we will optimize the chip design and instrumentation to integrate sample-to-answer processes. 3. To clinically validate the new POC molecular diagnostic, we will determine if the integrated assay is comparable in specificity and sensitivity to gold standard real- time NAATs using human urogenital samples. The ultimate deliverable of the project is a fully-integrated, clinically validated molecular diagnostic for POC testing of STI that is ready for commercialization and scale- up to prospective clinical trials.

描述（由申请人提供）：在美国有超过400万人感染了衣原体（CT）和淋病（NG）。这些性传播感染几乎没有早期症状，但会引起严重的并发症，从不育和不孕症到多药耐药性和艾滋病毒感染和传播增加。减少这些性传播感染的传播需要早期诊断和对感染者进行治疗。要想取得成功，就需要广泛使用低成本、可靠且易于使用的分子诊断方法，以便在医疗现场（POC）尽早发现致病生物。我们开发了用于CT和模拟尿液中NG检测的样本到答案的分子诊断分析。要验证的假设是，分子诊断芯片可以在微升尺度的人类泌尿生殖器样本中检测和区分CT和NG，其特异性和敏感性优于目前可用的POC检测。我们之前已经在实验台上证明了芯片的组件可以与模拟样品一起工作。我们的目标是开发一种便携、廉价的分子诊断方法，可用于POC诊断和区分CT和NG感染。我们与约翰霍普金斯大学性传播疾病护理技术研究中心的Charlotte Gaydos博士合作，使用先前收集和储存的已去识别并具有良好特征的泌尿生殖器标本进行中等规模的敏感性和特异性研究。我们将开发一种低成本、从样品到结果的综合分子诊断分析系统，以检测衣原体和淋病，该系统使用一种简单、直观的方法检测核酸扩增产物。为了使这项技术在现实世界的临床和现场应用，提出了以下目标：为了使我们目前的测试适应多路CT和NG分析，我们将优化样品制备、扩增和检测CT、NG和竞争性内部控制（CIC）。2. 为了能够在POC进行测试，我们将优化芯片设计和仪器，以集成样品到答案的过程。3. 为了临床验证新的POC分子诊断，我们将确定该综合检测方法在特异性和敏感性上是否与使用人类泌尿生殖器样本的金标准实时NAATs具有可比性。该项目的最终成果是一种完全集成的、经过临床验证的用于STI POC测试的分子诊断方法，该方法已准备好商业化并扩大到前瞻性临床试验。