Modernizing Perinatal Syphilis Testing

现代化围产期梅毒检测

• 批准号: 10585755
• 负责人: Irene A. Stafford
• 金额: $ 72.42万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-21 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585755
• 关键词: Address; Adult; Affect; Age Months; Algorithms; Biological Assay; Birth; Blinded; Blood; Categories; Centers for Disease Control and Prevention (U.S.); Central Nervous System; Cerebrospinal Fluid; Child; Childhood; Clinical; Collaborations; Congenital Syphilis; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Intervention; Enrollment; Evaluation; Exclusion; Exposure to; Gestational Age; Globus Pallidus; Guidelines; Healthcare; Hour; Individual; Infant; Infection; Interdisciplinary Study; Intervention; Laboratory Finding; Lesion; Letters; Linear Regressions; Live Birth; Mann-Whitney U Test; Methods; Modality; Modernization; Molecular; Mucous Membrane; Neonatal; Newborn Infant; Nucleic Acid Amplification Tests; Outcome; Pathogen detection; Patients; Perinatal; Physical Examination; Policies; Polymerase Chain Reaction; Postpartum Period; Pregnancy; Prevalence; Probability; Prospective cohort; Public Health; Recommendation; Recording of previous events; Regression Analysis; Research; Risk; Sample Size; Science; Seizures; Serodiagnoses; Serology test; Sexually Transmitted Diseases; Side; Students; Swab; Symptoms; Syphilis; Syphilis Serodiagnosis; Techniques; Test Result; Testing; Time; Toddler; Treatment Protocols; Treponema pallidum; United States Dept. of Health and Human Services; Urine; Woman; adverse outcome; care burden; co-infection; cohort; congenital infection; diagnostic algorithm; early childhood; follow-up; head-to-head comparison; improved; innovation; intervention program; neonatal infection; neonatal morbidity; neonate; neurodevelopment; novel; novel diagnostics; offspring; performance tests; prevent; primary outcome; prospective; recruit; screening; sex; transcription mediated amplification; Address; Adult; Affect; Age Months; Algorithms; Biological Assay; Birth; Blinded; Blood; Categories; Centers for Disease Control and Prevention (U.S.); Central Nervous System; Cerebrospinal Fluid; Child; Childhood; Clinical; Collaborations; Congenital Syphilis; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Intervention; Enrollment; Evaluation; Exclusion; Exposure to; Gestational Age; Globus Pallidus; Guidelines; Healthcare; Hour; Individual; Infant; Infection; Interdisciplinary Study; Intervention; Laboratory Finding; Lesion; Letters; Linear Regressions; Live Birth; Mann-Whitney U Test; Methods; Modality; Modernization; Molecular; Mucous Membrane; Neonatal; Newborn Infant; Nucleic Acid Amplification Tests; Outcome; Pathogen detection; Patients; Perinatal; Physical Examination; Policies; Polymerase Chain Reaction; Postpartum Period; Pregnancy; Prevalence; Probability; Prospective cohort; Public Health; Recommendation; Recording of previous events; Regression Analysis; Research; Risk; Sample Size; Science; Seizures; Serodiagnoses; Serology test; Sexually Transmitted Diseases; Side; Students; Swab; Symptoms; Syphilis; Syphilis Serodiagnosis; Techniques; Test Result; Testing; Time; Toddler; Treatment Protocols; Treponema pallidum; United States Dept. of Health and Human Services; Urine; Woman; adverse outcome; care burden; co-infection; cohort; congenital infection; diagnostic algorithm; early childhood; follow-up; head-to-head comparison; improved; innovation; intervention program; neonatal infection; neonatal morbidity; neonate; neurodevelopment; novel; novel diagnostics; offspring; performance tests; prevent; primary outcome; prospective; recruit; screening; sex; transcription mediated amplification

Abstract The re-emergence in maternal and congenital syphilis (CS) infection in recent years has brought this sexually transmitted infection (STI) to the forefront of policy discussions among federal and state health and human services departments. The recommended tests at birth demonstrate poor sensitivity for the diagnosis of CS, necessitating longitudinal follow up for up to 18 months until infection can be definitively excluded. This strategy inevitably results in cases of delayed or even missed treatment, leading to serious adverse outcomes that could have been prevented. With data suggesting a missed diagnosis rate approaching 15%, there is an urgent need for improved diagnostic modalities to detect CS through direct identification ofT. pallidum using highly sensitive contemporary nucleic acid amplification tests (NAA Ts). Two potential options include: real-time quantitative polymerase chain reaction (qPCR) and the Aptima Treponema pallidum transcription-mediated amplification (TMA) assay. By directly detecting the pathogen in neonatal biospecimens, these assays may provide more timely detection of CS in order to initiate timely evaluations and treatment. The aim of this study is to conduct a large, multicenter, prospective observational cohort trial of 924 maternal and neonatal dyads at risk for CS to effectively evaluate the test performance of these NAATs compared to the 2021 STD CS infection categories assigned to that patient at birth ( confirmed proven/highly probable, possible CS, CS less likely, CS unlikely) to determine if a superior diagnostic algorithm exists. Longitudinal follow up confirming infection status will be performed up to 18 months of age. Based on existing scientific premise, our central hypothesis is that the contemporary NAA Ts will result in a more sensitive, specific and timely diagnosis of congenital infection with T. pallidum compared to the standard recommended testing algorithms. In addition, we plan to leverage the resulting clinical cohort to more accurately define adverse neurodevelopmental outcomes associated with CS. This study will be the first to evaluate neurodevelopmental outcomes of affected children by performing Bayley Scales of Infant and Toddler Development™ at 18 months on the offspring of infected women. Beyond the importance of this research in terms of pure science, the results could have far-reaching public health implications that may contribute to improved quality and guideline efforts.

抽象的 近年来，孕产妇和先天性梅毒（CS）感染的重新出现已带来 这种性传播感染（STI）在联邦和 国家卫生与公共服务部门。出生时推荐的测试表明很差 对CS诊断的敏感性，必要的纵向跟进长达18个月直到 可以绝对排除感染。这种策略不可避免地会导致延迟甚至 错过的治疗，导致可能被阻止的严重不良结果。与数据 建议错过的诊断率接近15％，迫切需要改进 诊断方式通过高度直接鉴定粒子来检测CS 敏感的当代核酸扩增测试（NAA TS）。两个潜在的选项包括： 实时定量聚合酶链反应（QPCR）和Aptima treponema Pallidum 转录介导的扩增（TMA）测定法。通过直接检测病原体 新生儿生物测量，这些测定可能会提供更及时的CS检测，以启动 及时的评估和治疗。这项研究的目的是进行大型多中心 924个母校和新生儿二元组的前瞻性观察队列试验有CS的风险 与2021 STD CS相比，有效评估了这些NAAT的测试性能 出生时分配给该患者的感染类别（确认证明/非常有问题，可能 CS，CS的可能性较小，CS不太可能）确定是否存在出色的诊断算法。 纵向随访确认感染状况将长达18个月大。 基于现有的科学信念，我们的中心假设是当代的NAA TS将 导致先天性感染的更敏感，具体和及时的诊断剂。 与标准建议的测试算法相比。此外，我们计划利用 导致的临床队列更准确地定义了不良神经发育结果 与CS相关。这项研究将是第一个评估神经发育结果的研究 通过在18岁时表演婴儿和幼儿发展™的Bayley量表。 几个月的被感染妇女的后代。除了这项研究的重要性之外 纯科学，结果可能具有深远的公共卫生影响，可能有助于 提高了质量和指导工作。