Low-Cost Instrument-free Point-of-Care Test for Chlamydia and Gonorrhea

摘要 沙眼衣原体(Ct)和淋球菌(Ng)导致300多万人通过性传播 美国每年的性传播感染(STI)。据估计，全球的STI发病率分别为约1.31亿和7800万。 在过去的几年里，这些税率一直在增长6%到18%。两人都对严重的 发病率，包括盆腔炎、不孕症、宫外孕、慢性盆腔疼痛和 早产，仅在美国每年就要花费数十亿美元。CT和Ng是经验性的， 依赖抗生素治疗算法，因为CT和Ng的诊断在 关怀(PoC)。无法在PoC诊断和治疗意味着许多患者失去了后续行动， 助长未经治疗或不当治疗的性传播疾病的传播。这一问题因高利率而加剧 个人中无症状的CT和Ng感染率(男性约10-50%，女性约70-80%) 他们不太可能寻求治疗。目前的诊断依赖于商业核酸(NA)扩增测试 (NAAT)，价格昂贵，一天或几天就能收到结果。大多数患者不愿等待超过 20-30分钟就能得到结果。目前，还没有FDA批准的CLIA豁免的针对CT或Ng的POC测试。 我们的团队一直在开发针对感染病原体的免仪器POC测试，这种测试可以利用不同的 样品类型使用我们专有的裂解缓冲液和易于阅读的微流控扩增分析 比色结果在&lt；30分钟内得出。没有设备、样本采集或检测试剂盒，也没有技术专长 都是必需的。因为现在女性中CT直肠感染的人数超过了泌尿生殖道的感染人数，而且 男男性行为者(MSM)的感染人数继续增加，Ng感染也是如此，迫切需要 用于可以利用这些样本进行CT/Ng筛查以及用于固化测试的快速POC测试 用于治疗泌尿生殖道感染的抗生素剂量不足以治疗直肠感染。我们的目标 因此，我们将在我们的POC测试平台上进一步开发我们的裂解缓冲液和微流控分析，以 提供一种快速、一次性、灵敏和特异的CT/Ng POC检测，可以适应宫颈腔内， 阴道、尿路、直肠和尿液样本。世卫组织全球防控性传播疾病行动计划强调“ 开发负担得起的护理点性传播感染诊断技术。美国疾病控制与预防中心强调，“提供者应使 性传播疾病筛查是医疗保健的标准部分。我们的CT/Ng POC诊断测试将满足这一紧急医疗需求 需要通过增加早期检测、通知在POC的治疗以及降低感染率， 传播和后遗症，能够在家中使用并部署到各种类型的诊所、医疗保健 世界上最大的车站、急诊室和资源受限的环境。

Summary Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) cause over 3 million sexually transmitted infections (STI) annually in the U.S. The estimated global rates are ~131 million and 78 million, respectively. These rates have been increasing 6% to 18% over the last few years. Both are responsible for severe morbidity, including pelvic inflammatory disease, infertility, ectopic pregnancy, chronic pelvic pain, and preterm birth, with an annual cost of several billion dollars in the U.S. alone. Ct and Ng are treated empirically, relying on antibiotic treatment algorithms because diagnostics for Ct and Ng are not available at the point-of- care (POC). The inability to diagnose and treat at the POC means that many patients are lost to follow up, fueling the transmission of untreated or inappropriately treated STIs. This problem is exacerbated by the high rates of asymptomatic Ct and Ng infections (~10-50% for males & ~70-80% for females) among individuals who are unlikely to seek care. Current diagnostics rely on commercial nucleic acid (NA) amplification tests (NAAT) that are expensive and provide results in a day or days. Most patients are unwilling to wait more than 20-30 minutes for a result. Currently, there is no FDA approved CLIA-waived POC test for either Ct or Ng. Our team has been developing instrument-free POC tests for infectious pathogens that can utilize different sample types with our proprietary lysis buffer and microfluidic amplification assays with easy-to-read colorimetric results in <30 minutes. No equipment, sample collection or detection kits, or technical expertise are required. Because Ct rectal infections now outnumber those in the urogenital tract among women, and continue to increase among men who have sex with men (MSM) as do Ng infections, there is an urgent need for a rapid POC test that can utilize these samples for Ct/Ng screening and also for test-of-cure since a single dose of an antibiotic that is used for urogenital infections is inadequate to treat rectal infections. Our aim therefore is to build on our POC test platform to further develop our lysis buffer and microfluidic assays to provide a rapid, disposable, sensitive and specific Ct/Ng POC test that can accommodate endocervical, vaginal, urethral, rectal and urine samples. The WHO global action plan to control STDs emphasizes “the development of affordable point-of-care STI diagnostics.” And the CDC stresses that, “Providers should make STD screening a standard part of medical care.” Our Ct/Ng POC diagnostic test will meet this urgent medical need by increasing early detection, informing treatment at the POC, and reducing infection rates, transmission, and sequelae with the capability for in-home use and deployment to every type of clinic, health station, emergency room and resource constrained setting in the world.