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）病例是由移植传播引起的 从母亲到儿童的细菌毛颗粒粒细胞以惊人的速度增加。目标 监视研究表明，从2014年到2018年，增长> 185％。在4年内获得梅毒的妇女 怀孕年会将感染传播到其胎儿的80％，十分之一的怀孕将结束 死胎或婴儿死亡。婴儿患婴儿可能是无症状的，但也可能遭受严重的痛苦 多体梅毒感染的早期（<3个月）和晚期（> 2年）的表现，包括皮肤 病变，骨骼畸形，肝脏异常和失明。 treponema菌株极为困难 培养，因此敏感和特定的诊断需要多步骤测试劳动密集型的范例， 受假阳性和假阴性的约束，并且可伸缩性限制。目前没有单一测试在商业上 可用的可用于梅毒感染的准确，快速，廉价和简单的宽度测试。然而， 这样的测试可以将梅毒相关的死胎和围产期死亡减少多达75％。在这里我们建议 扩展了我们新颖的病原体识别平台“ Meltseq”的功能，该平台是专门配备的 朝向新生儿感染和小体积血液样本。第一阶段以我们以前的工作为基础 基于单基因组水平的广泛病原体鉴定，以发展快速且可起作用 检测和应变分化测定。此外，我们将将测试时间从〜3小时减少到<1小时， 办公室访问的典型时间，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 新颖的血液样本制备技术。这些进步将使怀孕期间梅毒筛查。 最后，我们将从干血点（DB）中提取微生物DNA，这些DNA实际上是在 美国的所有新生儿，以实现普遍的新生儿梅毒筛查。第二阶段涉及两者 510（k）批准和商业化的回顾性和前瞻性临床评估 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个简单且廉价的梅毒测试，可用于 孕妇和新生儿筛查计划。