The natural history of C. trachomatis urethral infections in men who have sex with women

男男性行为者沙眼衣原体尿道感染的自然史

基本信息

批准号：
10703828
负责人：
Stephen J. Jordan
金额：
$ 75.05万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-05 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10703828
关键词：
Address Antibiotics Antibodies Antibody-mediated protection Automobile Driving Bacteria Behavioral Biological Biological Assay Blood Centers for Disease Control and Prevention (U.S.)Characteristics Chlamydia Chlamydia trachomatis Clinical Cross-Sectional Studies Disease Enrollment Enzyme-Linked Immunosorbent Assay Epidemic Epidemiology Exposure to Female Heterosexuals High Risk Woman Immune Immune response Immune system Immunity Immunologics Immunology Incubated Infection Inflammation Knowledge Longitudinal Studies Measures Mediating Microbiology Microscopy Natural History Nucleic Acid Amplification Tests Organism Outcome Participant Patient Self-Report Persons Play Predisposition Prevention Prospective Studies Recommendation Recording of previous events Resistance Risk Role Sex Behavior Sexual Partners Sexual Transmission Sexually Transmitted Diseases Shapes Signs and Symptoms Slide Specimen Surveys Symptoms T cell response T-Cell Activation T-Lymphocyte Testing Time Urethra Urethritis Urine Visit Woman adaptive immune response adaptive immunity aged care seeking cervicovaginal microbiome comorbidity diaries experience improved infection risk insight male men metagenomic sequencing microbiome composition microorganism novel strategies pathogen prevent reproductive tract routine screening screening screening program seropositive sex transmission process urethral microbiome

项目摘要

ABSTRACT Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) worldwide and causes irreversible reproductive tract damage in women. As most CT-infected women have no symptoms and are unaware that they are infected, the CDC recommends annual CT screening in women aged <25 and high risk women to detect and treat asymptomatic infections and prevent complications; in men, routine screening is not recommended. Despite 3 decades of screening programs, CT rates in the U.S. have dramatically increased, driven primarily by increasing CT reinfections. As most CT-infected women are heterosexual and routine screening in men is not recommended, undetected CT infections in men are the reservoir that propels reinfections in women. To curb the CT epidemic, it is critical that we understand whether men can develop immunity to CT and identify factors that promote CT reinfections (e.g., asymptomatic men who shed significant CT organisms). Approximately 1/3 of men who present for treatment as a CT contact (i.e., their sex partner was confirmed to be CT-infected) are uninfected, suggesting that these men either cleared CT infection by immune- mediated mechanisms or have a urethral microbiome that resists CT acquisition. To prevent CT reinfections in women, this proposal focuses on male contacts to CT-infected women and will study if CT infection is associated with specific microbiome compositions, comorbid STIs, or adaptive T-cell and antibody immunity. To do this, we will enroll up to 400 male CT-contacts, collect blood and urine specimens, treat them with the CDC-recommend first-line antibiotic, and ask them to return for a 1-month test of cure (TOC) visit (Aim 1). To study if CT uninfected contacts to CT have long-lasting immunity and how the urethral microbiome and immune system change over time, we will re-enroll 100 men for a 6-month longitudinal study to collect weekly urine specimens and symptom/sexual behavior diaries and blood and urine specimens at 3-month and 6-month screening visits. Weekly urine specimens will be stored and tested at study completion to create a natural history study. By studying the rates of incident CT infection over time, we will be able to elucidate if resistance to CT infection, defined in Aim 1, correlates with (1) increased rate of natural clearance between visits; (2) decrease in incident CT infection at 3- or 6-months; (3) decrease in incident CT infection organism load; and (4) decrease in the rate of homologous CT genovars. Study findings will inform novel approaches to preventing transmission from men to women and help curb rising CT rates and complications.

抽象的沙眼衣原体 (CT) 是世界范围内最常见的细菌性传播感染 (STI) 对女性生殖道造成不可逆转的损伤。由于大多数感染 CT 的女性没有任何症状，并且如果不知道自己已被感染，CDC 建议对 25 岁以下及高龄女性每年进行一次 CT 筛查使妇女面临风险，发现和治疗无症状感染并预防并发症；对于男性，常规筛查是不推荐。尽管筛查计划已有 3 年历史，美国的 CT 率仍大幅上升，主要是由于 CT 再感染的增加所致。由于大多数感染 CT 的女性都是异性恋且循规蹈矩不建议对男性进行筛查，男性中未被发现的 CT 感染是推动健康的水库女性再次感染。为了遏制 CT 流行，我们必须了解男性是否可以发展增强对 CT 的免疫力，并确定促进 CT 再感染的因素（例如，无症状的男性大量排毒） CT 生物）。大约 1/3 的男性作为 CT 接触者（即他们的性伴侣是确认为 CT 感染者）并未被感染，这表明这些人要么通过免疫清除了 CT 感染，介导的机制或具有抵抗 CT 采集的尿道微生物组。为防止 CT 再次感染女性，该提案重点关注男性与感染 CT 的女性的接触，并将研究 CT 感染是否相关具有特定的微生物组组成、共病性传播感染或适应性 T 细胞和抗体免疫。为此，我们将招募多达 400 名男性 CT 接触者，收集血液和尿液样本，并按照 CDC 的建议进行治疗一线抗生素，并要求他们返回进行为期 1 个月的治愈测试 (TOC) 就诊（目标 1）。研究CT是否未感染接触 CT 具有持久的免疫力以及尿道微生物群和免疫系统如何变化届时，我们将重新招募 100 名男性进行为期 6 个月的纵向研究，每周收集尿液样本并 3 个月和 6 个月筛查访视时的症状/性行为日记以及血液和尿液样本。每周的尿液样本将被储存并在研究完成时进行测试，以创建自然历史研究。经过研究一段时间内 CT 感染的发生率，我们将能够阐明是否对 CT 感染具有抵抗力，目标 1 中定义，与 (1) 两次访问之间的自然清除率增加相关； (2) 事件减少 3或6个月时CT感染； (3) 减少CT感染微生物负荷； (4) 利率下降同源 CT 基因型。研究结果将为预防男性传播的新方法提供信息为女性提供帮助，并帮助遏制不断上升的 CT 率和并发症。