A Rapid Point-of-care Diagnostic for C. trachomatis STDs

沙眼衣原体 STD 的快速护理点诊断

• 批准号: 8250620
• 负责人: DEBORAH Anne DEAN
• 金额: $ 100万
• 依托单位: NETWORK BIOSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8250620
• 关键词: Accident and Emergency department; Antibiotic Therapy; Antibiotics; Antigens; Bacterial Sexually Transmitted Diseases; Binding Sites; Biological; Biological Assay; Centers for Disease Control and Prevention (U.S.); Cervical; Cervical Squamous Cell Carcinoma; Chlamydia trachomatis; Clinic; Clinical; Clinical Trials; Conjunctivitis; DNA; DNA Sequence; Detection; Diagnosis; Diagnostic; Dideoxy Chain Termination DNA Sequencing; Drug resistance; Early Diagnosis; Ectopic Pregnancy; Electrophoresis; Ensure; Epidemic; Equipment; Female; Genetic; Genital system; Genome; Genomics; Goals; HIV-1; Head; Hospitals; Hour; Human; Infection; Infertility; Intervention; Laboratories; Lead; Life; Lymphatic Diseases; Lymphogranuloma Venereum; Medical; Microfluidics; Molecular; Nucleic Acid Amplification Tests; Nucleic Acids; Organism; Outpatients; Patients; Patients' Rooms; Pelvic Inflammatory Disease; Phase; Plasmids; Pneumonia; Predictive Value; Pregnant Women; Process; Proctitis; Product Approvals; Reaction; Reading; Reliance; Risk Factors; Running; Sampling; Screening procedure; Sensitivity and Specificity; Sexually Transmitted Diseases; Site; Small Business Innovation Research Grant; Specificity; Squamous cell carcinoma; Swab; System; Technical Expertise; Testing; Training; Ulcer; Urethra; Urine; Vagina; Woman; base; biochip; chronic pelvic pain; comparative; cost effective; design; disorder prevention; experience; follow-up; genome sequencing; head-to-head comparison; improved; instrument; instrumentation; male; pathogen; point of care; point-of-care diagnostics; rectal; stem; transmission process

DESCRIPTION (provided by applicant): Improved diagnosis of Chlamydia trachomatis (Ct) infections represents a critical unmet medical need. Ct is the most common cause of bacterial sexually transmitted diseases (STD) worldwide, and the Centers for Disease Control and Prevention estimate that there are 2.8 million US cases annually. Currently, 40% of women with untreated infection will develop pelvic inflammatory disease (PID), 20% of whom will become infertile, 18% will experience debilitating, chronic pelvic pain, and 9% will have a life-threatenig ectopic pregnancy. If an infected pregnant woman is not treated, her baby has a 50% chance of developing conjunctivitis and a 20% chance of pneumonia in the first six months of life. Ct is also a risk factor for invasive squamous-cell carcinoma of the cervix and a complicating factor in HIV-1 infection and transmission. In males, the clinical presentation includes proctitis, genital ulcer and/or inguinal lymphadenopathy. The main obstacle to stemming this epidemic is the lack of an inexpensive nucleic acid-based point-of-care (POC) diagnostic for screening. Current chlamydial diagnostics are primarily based on nucleic acid amplification tests (NAAT) that lack concordance across the different NAATs, vary in sensitivity (although specificity is high), are expensive, require technical expertise, take days for results, and cannot be performed at the POC. They are also unable to differentiate between invasive lymphogranuloma venereum (LGV) versus non-invasive strains, the former of which require weeks of antibiotic therapy for eradication. Our overall SBIR goal is to develop a rapid, cost-effective, sensitive and specific Ct POC diagnostic system to increase early detection, inform appropriate treatment, reduce the rate of infections, and thereby reduce sequelae. In SBIR Phase I, we developed an initial microfluidic NAAT and demonstrated that its sensitivity and specificity are superior to those of a commercial NAAT. In SBIR Phase II, we propose to: 1) Optimize our assay based on information gained by whole genome sequencing clinical Ct strains; 2) incorporate all assay processes in an easy-to operate breadboard instrument; and 3) do a head-to-head comparison of the optimized system against two commercially available assays. Given the genomic expertise of Dr. Tim Read and the chlamydial STD expertise of Dr. Dean, and the molecular biological and microfluidic expertise of Dr. Selden, the application provides a unique collaborative opportunity to finally obtain a rapid nucleic-acid based POC diagnostic for C. trachomatis. PUBLIC HEALTH RELEVANCE: Chlamydia trachomatis is the leading bacterial cause of sexually transmitted diseases in the US. Many of these infections are asymptomatic and go undetected, which leads to increased transmission and the sequelae of pelvic inflammatory disease, infertility and ectopic pregnancy. Current diagnostics require extensive technical expertise, are expensive and take days for results, leading to loss of follow up. NetBio is developing an easy to use, cost effective diagnostic that detects C. trachomatis within one hour at the point-of-care.

描述（由申请人提供）：改善沙眼衣原体（CT）感染的诊断代表了至关重要的未满足医疗需求。 CT是全球细菌性传播疾病（STD）的最常见原因，疾病控制和预防中心每年有280万例美国病例。目前，有40％的未经治疗感染的妇女将出现盆腔炎症性疾病（PID），其中20％将变得不育，18％的女性会感到衰弱，慢性骨盆疼痛，而9％的人将患有生命危害生命。如果未治疗感染的孕妇，她的婴儿有50％的结膜炎的机会，在生命的头六个月内有20％的肺炎。 CT还是子宫颈侵入性鳞状细胞癌的危险因素，也是HIV-1感染和传播中的复杂因素。在男性中，临床表现包括直肠炎，生殖器溃疡和/或腹股沟淋巴结肿大。阻止这种流行病的主要障碍是缺乏廉价的基于核酸的护理点（POC）诊断进行筛查。 当前的衣原体诊断主要基于核酸扩增测试（NAAT），这些测试在不同的NAAT上缺乏一致性，其灵敏度各不相同（尽管特异性很高），价格昂贵，需要技术专业知识，需要花费几天的结果，并且无法在POC上进行。他们也无法区分侵入性淋巴结瘤（LGV）与非侵入性菌株，前者需要数周的抗生素治疗来消除。我们的总体SBIR目标是开发快速，成本效益，敏感和特定的CT POC诊断系统以增加早期检测，为适当的治疗，降低感染率，从而减少后遗症。在SBIR I期中，我们开发了初始的微流体NAAT，并证明其敏感性和特异性优于商业NAAT。在SBIR II期中，我们建议：1）根据由整个基因组测序临床CT菌株获得的信息优化测定； 2）将所有测定过程纳入易于操作的面包板仪器中； 3）对优化系统与两个市售测定法进行面对面的比较。鉴于蒂姆·雷德（Tim Read）博士的基因组专业知识以及迪恩（Dean）博士的衣原体性病专业知识，以及塞尔登（Selden）博士的分子生物学和微流体专业知识，因此该应用提供了独特的协作机会，以最终获得基于核酸的快速核酸aciD POC的POC C. c. trachatomis。 公共卫生相关性：沙眼衣原体是美国性传播疾病的主要原因。这些感染中的许多是无症状的，未被发现，这导致骨盆炎症性疾病，不育和异位妊娠的后遗症增加。当前的诊断需要广泛的技术专业知识，昂贵，并需要几天的结果，从而导致随访损失。 Netbio正在开发一种易于使用的，具有成本效益的诊断，该诊断可在护理点的一小时内检测到沙眼炎。