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

描述（由申请方提供）：改善沙眼衣原体（Ct）感染的诊断是一项关键的未满足的医疗需求。Ct是全球细菌性传播疾病（STD）最常见的原因，疾病控制和预防中心估计美国每年有280万例病例。目前，40%未经治疗的感染妇女将发展为盆腔炎（PID），其中20%将成为不孕症，18%将经历衰弱，慢性盆腔疼痛，9%将发生危及生命的异位妊娠。如果受感染的孕妇不接受治疗，她的婴儿在出生后的前六个月内有50%的机会患结膜炎，20%的机会患肺炎。Ct也是宫颈浸润性鳞状细胞癌的危险因素，也是HIV-1感染和传播的复杂因素。在男性中，临床表现包括直肠炎、生殖器溃疡和/或腹股沟淋巴结病。阻止这种流行病的主要障碍是缺乏廉价的基于核酸的床旁（POC）诊断筛查。 目前的衣原体诊断主要基于核酸扩增测试（NAAT），其在不同的NAAT之间缺乏一致性，灵敏度不同（尽管特异性高），价格昂贵，需要技术专长，需要数天的结果，并且不能在POC进行。他们也无法区分侵袭性性病淋巴肉芽肿（LGV）与非侵袭性菌株，前者需要数周的抗生素治疗才能根除。我们的总体SBIR目标是开发一种快速、经济、灵敏和特异的Ct POC诊断系统能够增加早期发现，告知适当的治疗，降低感染率，从而减少后遗症。在SBIR第一阶段，我们开发了一个初始的微流控NAAT，并证明其灵敏度和特异性优于商业NAAT的上级。在SBIR第二阶段，我们建议：1）根据全基因组测序临床Ct菌株获得的信息优化我们的检测方法; 2）将所有检测过程纳入易于操作的试验板仪器; 3）将优化的系统与两种市售检测方法进行头对头比较。鉴于Tim Read博士的基因组专业知识和Dean博士的衣原体STD专业知识，以及Selden博士的分子生物学和微流体专业知识，该应用程序提供了一个独特的合作机会，最终获得基于核酸的快速POC诊断C。沙眼 公共卫生相关性：在美国，沙眼衣原体是导致性传播疾病的主要细菌。其中许多感染是无症状的，未被发现，这导致传播增加和盆腔炎、不孕症和异位妊娠的后遗症。目前的诊断需要广泛的技术专业知识，价格昂贵，需要几天的时间才能得出结果，导致失去后续行动。NetBio正在开发一种易于使用，具有成本效益的诊断方法，可以检测C。在一小时之内就能检测出沙眼

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.