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

梅毒螺旋体转录介导的扩增测定对梅毒筛查的评估

• 批准号: 10424562
• 负责人: Matthew R Golden
• 金额: $ 70.64万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-08 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10424562
• 关键词: Adoption; Affect; Anatomy; Biological Assay; Blood; Blood Tests; Centers for Disease Control and Prevention (U.S.); Chlamydia; Clinic; Clinical; Clinical Treatment; Computerized Medical Record; Congenital Syphilis; Consent; Cross-Sectional Studies; Data; Development; Diagnosis; Early Diagnosis; Early identification; Early treatment; Enrollment; Epidemic; Evaluation; Face; Freezing; Generations; Gonorrhea; HIV; HIV Seronegativity; HIV Seropositivity; Heterosexuals; Immunoglobulin G; Immunoglobulin M; Incubated; Industry; Infection; Interview; Laboratories; Lead; Lesion; Measurable; Medical; Molecular; Morbidity - disease rate; Mucous Membrane; Natural History; Nucleic Acid Amplification Tests; Oropharyngeal; Participant; Patients; Persons; Pilot Projects; Play; Population; Population Surveillance; Prospective Studies; Provider; RNA; Research; Ribosomal RNA; Role; Sampling; Serology; Serology test; Serum; Sexual Health; Sexually Transmitted Diseases; Specimen; Study Subject; Swab; Syphilis; Syphilis Serodiagnosis; Testing; Treponema pallidum; Urine; Vagina; Whole Blood; antibody detection; antigen detection; base; diagnostic strategy; diagnostic tool; high risk; impression; improved; men who have sex with men; mucosal site; patient screening; pre-exposure prophylaxis; prevent; rectal; research clinical testing; screening; surveillance data; symposium; synthetic polymer Bioplex; tool; transcription mediated amplification; transgender; transmission process

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.

摘要 美国面临着无情增长的梅毒流行病，主要集中在与男性发生性关系的男性中。 男性（MSM）和跨性别者（TG）。我们用诊断工具来对付这种流行病， 改变了超过半个世纪，因为我们继续依赖血清学测试，有一个窗口期， 3-5周内检测阳性。该应用程序提出的研究，将使用一个新的，工业- 建立了梅毒螺旋体（Tp）的实验性转录介导扩增（TMA）试验， 提高我们对梅毒自然史的理解，并评估是否增加TMA检测， 血清学筛查可以在感染的最早阶段， 血清学检测呈阳性。我们的初步数据表明，10%的男男性接触者患有梅毒， 血清阴性，但在咽部或直肠标本中TMA阳性。本申请是在这一发现的基础上提出的。我们 将通过比较，初步确定活动性梅毒患者进行TMA检测的最佳标本类型 咽部与口咽部样本以及全血与血清中的TMA阳性（目的1）。在整个 在本项目中，我们将检测从性病门诊患者收集的残留血清、直肠和咽部标本 诊断为梅毒，以确定在梅毒患者的不同解剖部位出现Tp RNA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 STD门诊患者， 前瞻性研究，以确定是否增加Tp TMA检测的血液，咽和直肠标本 使血清学测试呈阴性的人士更早发现梅毒（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。参与者将获得标准临床 评估和治疗，并将提供研究血清，直肠和咽 研究小组将冷冻这些标本。入组后12周，我们将对这些标本进行检测 使用TMA，并将接触TMA阳性结果的人进行面谈和重复血清学检查， TMA检测，以确定研究受试者自入组以来是否发生梅毒或血清转化。 这些研究的结果将确定患有不同阶段梅毒的人有可能 传染性，并将确定是否筛选整合血清学与TMA测试是上级， 仅进行标准血清学检测