A rapid test for congenital syphilis screening

先天性梅毒筛查的快速检测

• 批准号: 10385576
• 负责人: Stephanie Irene Fraley
• 金额: $ 29.99万
• 依托单位: MELIOLABS INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385576
• 关键词: Address; Bacteria; Big Data; Biological Assay; Biomedical Engineering; Blinded; Blindness; Blood; Blood Volume; Blood specimen; California; Cessation of life; Child; Clinical; Clinics and Hospitals; Communicable Diseases; Complex; Congenital Syphilis; Contracts; DNA; Data; Deformity; Detection; Devices; Diagnosis; Diagnostic; Dyes; Female; Fetus; Funding; Genome; Genotype; Goals; Gold; Hour; Incidence; Individual; Infant; Infant Mortality; Infection; Liver; Mass Screening; Methods; Microbe; Mission; Modality; Morbidity - disease rate; Mothers; Neonatal; Neonatal Screening; Neonatology; Newborn Infant; Nucleic Acids; Office Visits; Organism; Outcome; Patients; Pediatrics; Perinatal mortality demographics; Phase; Population; Predictive Value; Pregnancy; Pregnant Women; Preparation; Prevention; Public Health; RNA; Resolution; Sampling; Sensitivity and Specificity; Spottings; Step Tests; Sum; Syphilis; Syphilis Serodiagnosis; Technology; Testing; Time; Treponema; Treponema pallidum; United States; University Hospitals; Validation; Woman; Work; aged; artificial intelligence algorithm; base; bone; clinically relevant; commercialization; cost effective; cross reactivity; design; detection limit; diagnostic screening; diagnostic tool; digital; emerging pathogen; infant death; melting; microbial; mid-career faculty; mortality; multidisciplinary; neonatal infection; neonate; next generation sequencing; novel; pathogen; point of care; product development; prospective; rapid test; reproductive; research clinical testing; screening; screening program; skin lesion; stillbirth; surveillance study; transmission process; virtual

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.

项目摘要 自2014年以来，美国的先天性梅毒（CS）病例，由胎盘传播引起， 梅毒螺旋体从母亲传染给孩子，以惊人的速度增长。针对性 监测研究表明，仅从2014年到2018年就上升了185%。4岁以内感染梅毒的妇女 10年的怀孕将把感染传给80%的胎儿，10次怀孕中有4次将在10年内结束。 死胎或婴儿死亡。感染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（< 3个月）和晚期（>2年）表现，包括皮肤 病变、骨畸形、肝脏异常和失明。密螺旋体菌株很难被 培养，因此敏感和特异的诊断需要多步骤的测试范例，其是劳动密集型的， 容易出现假阳性和假阴性，并且可扩展性有限。目前还没有一种测试是商业化的。 提供了一种能够准确，快速，廉价和简单广泛检测梅毒感染的方法。然而， 这样的测试可以减少梅毒相关的死胎和围产期死亡高达75%。在此，我们建议 扩展“MeltSeq”的功能，这是我们专门针对 针对新生儿感染和少量血液样本。第一阶段建立在我们以前的工作， 在单基因组水平上进行广泛的病原体鉴定，以开发快速和可操作的密螺旋体 检测和菌株鉴别试验。此外，我们还将测试时间从约3小时缩短到不到1小时， 通过使用我们独特的设备来实现快速放大，并通过优化我们的 新的血液样品制备技术。这些进展将使怀孕期间的梅毒筛查成为可能。 最后，我们将推进从干血斑（DBS）中提取微生物DNA，这是在虚拟环境中收集的。 在美国的所有新生儿，使普遍新生儿梅毒筛查。第二阶段涉及两个 510（k）批准的回顾性和前瞻性临床评价以及床旁医疗的商业化 设备.我们的多学科团队方法结合了临床肿瘤学，生物工程和 商业产品开发，以创建一个简单和廉价的梅毒测试，可用于 孕妇和新生儿筛查计划。