Evaluation of a Treponema pallidum transcription mediated amplification assay for Syphilis Screening

摘要 美国面临着不断增长的梅毒疫情，集中在与之发生性关系的男性中 男性(MSM)和变性人(TG)。我们用诊断工具来应对这一流行病，这些工具几乎没有 在半个多世纪里发生了变化，因为我们继续依赖于血清学测试，这些测试的窗口期从 感染检测阳性时间为3-5周。这项申请提出的研究将使用一个新的行业- 建立梅毒螺旋体(TP)的实验性转录介导扩增(TMA)方法 提高我们对梅毒自然病史的了解，并评估是否将TMA检测添加到 血清学筛查可以在梅毒感染的最早阶段识别血清阴性的梅毒患者， 血清学检测呈阳性。我们的初步数据显示，10%的梅毒男男性接触者是 咽或直肠标本血清阴性，但TMA阳性。这个应用程序建立在这一发现的基础上。我们 我将初步确定在活动性梅毒患者中进行TMA检测的最佳样本类型 TMA在咽部和口咽标本中呈阳性，在全血和血清中呈阳性(目标1)。贯穿始终 该项目将检测从性病门诊患者采集的残留血清、直肠和咽部样本。 诊断为梅毒，以确定TP RNA在不同解剖部位出现的频率 感染的不同阶段(目标2)。最后，我们将招募3350名MSM和TG性病门诊患者参加 确定是否增加血液、咽部和直肠标本的TP TMA检测的前瞻性研究 导致在血清学试验阴性的人中更早地识别梅毒(目标3)。为此，我们将 招募没有梅毒临床证据的血清阴性患者。参与者将获得标准的临床 在登记时进行评估和治疗，并将提供血清、直肠和咽部的研究 标本，研究小组将对其进行冷冻。注册12周后，我们将对这些标本进行测试 使用TMA，并将联系TMA阳性者进行面谈和重复血清学和 TMA检测，以确定研究对象自登记以来是否患上梅毒或血清转换。 这些研究的结果将确定患有不同阶段梅毒的人有多大可能 可传播，并将确定结合血清学和TMA检测的筛查是否优于 仅进行标准的血清学检测。

Abstract The U.S. faces a relentlessly growing syphilis epidemic that is concentrated among men who have sex with men (MSM) and transgender (TG) persons. We confront that epidemic with diagnostic tools that have barely changed in over half a century as we continue to rely on serological tests that have a window period from infection to test positivity of 3-5 weeks. This application proposes studies that will use a new, industry- developed experimental transcription mediated amplification (TMA) assay for Treponema pallidum (Tp) both to improve our understanding of the natural history of syphilis, and to assess whether adding TMA testing to serological screening can identify seronegative persons with syphilis in the earliest stage of infection, before serological tests become positive. Our preliminary data suggest that 10% of MSM with syphilis are seronegative, but TMA positive in pharyngeal or rectal specimens. This application builds on that finding. We will initially define the optimal specimen types for TMA testing among persons with active syphilis by comparing TMA positivity in pharyngeal vs. oropharyngeal specimens, and in whole blood vs. serum (Aim 1). Throughout the project, we will test remnant serum, rectal and pharyngeal specimens collected from STD clinic patients diagnosed with syphilis to define how often Tp RNA is present at different anatomic sites in persons with different stages of infection (Aim 2). Finally, we will enroll 3350 MSM and TG STD clinic patients in a prospective study to determine whether adding Tp TMA testing of blood, pharyngeal and rectal specimens leads to earlier identification of syphilis in persons with negative serological tests (Aim 3). For this aim, we will enroll seronegative patients without clinical evidence of syphilis. Participants will receive standard clinical evaluation and treatment at enrollment and will provide the study with serum, rectal and pharyngeal specimens, which the research team will freeze. Twelve weeks after enrollment, we will test these specimens using the TMA, and will contact persons with positive TMA results for interview and repeat serological and TMA testing in order to determine if study subjects developed syphilis or seroconverted since enrollment. Findings from these studies will define how often persons with different stages of syphilis are likely transmissible, and will determine whether screening that integrates serology with TMA testing is superior to standard serological testing alone.