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

基本信息

批准号：
10295688
负责人：
Matthew R Golden
金额：
$ 73.3万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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/10295688
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 Diagnostic 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 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

项目摘要

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.

抽象的美国面临着一种不懈地生长的梅毒流行，集中在与男人（MSM）和变性人（TG）人。我们面对几乎没有的诊断工具的流行病在半个多世纪以来，我们继续依靠具有窗口时期的血清学测试的变化感染以测试阳性3-5周。该应用程序提出了将使用新的行业的研究开发了针对毛毛虫（TP）的实验转录介导的扩增（TMA）测定提高我们对梅毒自然历史的理解，并评估是否将TMA测试添加到血清学筛查可以在最早的感染阶段鉴定出具有梅毒的血清症患者血清学检查成为阳性。我们的初步数据表明，梅毒的MSM中有10％是咽或直肠标本中的血清调子，但TMA阳性。此应用程序以该发现为基础。我们最初将通过比较活性梅毒的人之间定义用于TMA测试的最佳标本类型咽与口咽标本中的TMA阳性，以及全血和血清（AIM 1）。自始至终该项目，我们将测试从性病诊所患者收集的残余血清，直肠和咽标本被诊断为梅毒以定义在不同的解剖部位中tp RNA的频率感染的不同阶段（AIM 2）。最后，我们将在A中注册3350 MSM和TG STD诊所患者前瞻性研究，以确定添加TP TMA测试是否对血液，咽和直肠标本进行导致早期鉴定出具有阴性血清学检查的人的梅毒（AIM 3）。为此，我们将没有梅毒的临床证据注册血清神经患者。参与者将获得标准的临床注册时的评估和治疗将为研究提供血清，直肠和咽部标本，研究团队将冻结。入学后十二周，我们将测试这些标本使用TMA，并将与具有阳性TMA结果的人联系，以进行访谈和重复血清学和 TMA测试是为了确定研究对象是自入学以来的梅毒还是血清转化。这些研究的发现将定义梅毒阶段不同的人的频率可传播，并将确定将血清学与TMA测试相结合的筛查是否优于仅标准血清学测试。