Modernizing Perinatal Syphilis Testing

摘要 近年来，孕产妇和先天性梅毒（CS）感染的重新出现， 这种性传播感染（STI）的政策讨论之间的前沿联邦和 州卫生和公共服务部出生时推荐的测试表明， 诊断CS的敏感性，需要纵向随访长达18个月， 可以明确排除感染。这一战略不可避免地导致延误，甚至 错过治疗，导致本可以预防的严重不良后果。与数据 提示漏诊率接近15%，迫切需要改进 通过直接鉴定T来检测CS的诊断模式。苍白球使用高度 敏感的当代核酸扩增测试（NAA Ts）。两种可能的选择包括： 实时定量聚合酶链反应（qPCR）和梅毒螺旋体Aptima 转录介导的扩增（TMA）测定。通过直接检测病原体 新生儿生物标本，这些测定可以提供更及时的CS检测，以便启动 及时评估和治疗。本研究的目的是进行一项大型、多中心、 对924例有CS风险的母亲和新生儿进行的前瞻性观察性队列试验， 与2021 STD CS相比，有效评估这些NAAT的测试性能 在出生时分配给患者的感染类别（已确认/已证实/高度可能，可能 CS、CS不太可能、CS不太可能），以确定是否存在上级诊断算法。 将进行纵向随访，确认感染状态，直至18个月龄。 基于现有的科学前提，我们的中心假设是，当代的NAA Ts将 提高了先天性弓形虫感染的敏感性、特异性和及时性。螺旋体 与标准推荐的测试算法相比。此外，我们计划利用 由此产生的临床队列更准确地定义了不良神经发育结局 与CS有关。这项研究将是第一个评估神经发育的结果， 受影响的儿童在18岁时进行贝利婴幼儿发展量表™ 对受感染妇女的后代进行数月的治疗。除了这项研究的重要性， 纯科学，结果可能具有深远的公共卫生影响，可能有助于 提高质量和指导方针的努力。

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.