A rapid test for congenital syphilis screening

项目总结 自2014年以来，美国先天性梅毒(CS)病例由胎盘传播引起 从母亲到孩子的梅毒螺旋体细菌以惊人的速度增加。目标明确 监督研究表明，仅从2014年到2018年，这一数字就上升了185%。在4小时内感染梅毒的妇女 怀孕数年会将感染传播给80%的胎儿，十分之四的怀孕将以 死产或婴儿死亡。患有CS的婴儿可能没有症状，但他们也可能患有严重的 多系统梅毒感染的早期(&lt；3个月)和晚期(&gt；2年)表现，包括皮肤 病变、骨骼畸形、肝脏异常和失明。密螺旋体菌株极难 培养，因此敏感和具体的诊断需要劳动密集型的多步骤检测范例， 易受假阳性和假阴性的影响，并限制可伸缩性。目前没有一种单一的测试是商业化的 可用于对梅毒感染进行准确、快速、廉价和简单的广泛检测。然而， 这样的测试可以将梅毒相关的死产和围产儿死亡减少高达75%。在此，我们建议 扩展我们的新型病原体鉴定平台“MeltSeq”的功能，该平台专门针对 新生儿感染和少量血液样本。第一阶段建立在我们先前在 在单基因组水平上广泛鉴定病原体以发展快速和可操作的密螺旋体 检测和菌株鉴定。此外，我们将把测试时间从~3小时减少到&lt；1小时， 典型的办公室访问时间，通过使用我们独特的设备来实现快速放大和优化我们的 新的血样制备技术。这些进展将使怀孕期间进行梅毒筛查成为可能。 最后，我们将推进从干血斑(DBS)中提取微生物DNA的工作，这些DNA是在虚拟环境中收集的 所有新生儿都在美国，以实现新生儿梅毒的普遍筛查。第二阶段包括两个阶段 510(K)计划批准和商业化的前瞻性临床评估 设备。我们的多学科团队方法结合了临床新生儿学、生物工程和 商业产品开发，以创建一种简单且廉价的梅毒检测方法，可用于 孕妇和新生儿筛查计划。

PROJECT SUMMARY Since 2014, Congenital Syphilis (CS) cases in the United States, caused by the transplacental transmission of the bacterium Treponema pallidum from mother to child, have increased at an alarming rate. Targeted surveillance studies indicate a rise >185% from 2014 to 2018 alone. Women who acquire syphilis within 4 years of pregnancy will transmit the infection to 80% of their fetuses, and 4 in 10 pregnancies will end in stillbirth or infant death. Infants contracting CS may be asymptomatic, but they can also suffer from serious early- (< 3 months) and late-stage (>2 years) manifestations of multisystemic syphilis infection, including skin lesions, bone deformities, liver abnormalities, and blindness. Treponema strains are extremely difficult to culture, thus sensitive and specific diagnosis requires multi-step testing paradigms that are labor intensive, subject to false-positives and false-negatives, and limited in scalability. No single test is currently commercially available that enables accurate, rapid, inexpensive, and simple widespread testing for syphilis infection. Yet, such a test could reduce syphilis-associated stillbirth and perinatal death by up to 75%. Here we propose to extend the capabilities of “MeltSeq”, our novel pathogen identification platform that is specifically geared towards neonatal infections and small-volume blood samples. Phase I builds upon our previous work in broad-based pathogen identification at single-genome levels to develop a fast and actionable Treponema detection and strain differentiating assay. In addition, we will reduce testing times from ~3 hours to <1 hour, the typical time of an office visit, by using our unique device to achieve rapid amplification and by optimizing our novel blood sample preparation technology. These advances will enable syphilis screening during pregnancy. Finally, we will advance microbial DNA extraction from dried blood spot (DBS), which are collected on virtually all newborns in the United States, to enable universal newborn syphilis screening. Phase II involves both retrospective and prospective clinical evaluation for 510(k) approval and commercialization of a point-of-care device. Our multidisciplinary team approach combines expertise in clinical neonatology, bioengineering, and commercial product development to create a simple and inexpensive syphilis test that can be utilized for pregnant women and newborn screening programs.