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

描述（由申请人提供）：改进沙眼衣原体（Ct）感染的诊断代表了一个关键的未满足的医疗需求。Ct是全球范围内细菌性传播疾病（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会发展为盆腔炎（PID），其中20%会不孕，18%会经历衰弱，慢性盆腔疼痛，9%会有危及生命的异位妊娠。如果受感染的孕妇没有得到治疗，她的孩子在出生后的头六个月里有50%的几率患结膜炎，20%的几率患肺炎。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。男性的临床表现包括直肠炎、生殖器溃疡和/或腹股沟淋巴结病。遏制这一流行病的主要障碍是缺乏一种廉价的基于核酸的即时诊断方法进行筛查。目前的衣原体诊断主要基于核酸扩增试验（NAAT），不同的NAAT之间缺乏一致性，灵敏度不同（尽管特异性很高），价格昂贵，需要专业技术知识，需要几天才能得到结果，并且不能在POC进行。它们也无法区分侵袭性性病淋巴肉芽肿（LGV）与非侵入性菌株，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、敏感和特异性的Ct

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.