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

• 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
• 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

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）是全球最常见的细菌性传播感染（STI）和 导致女性不可逆的生殖道损害。由于大多数受CT感染的妇女没有症状，并且 疾病预防控制中心建议他们不知道自己被感染了，建议在年龄<25岁且高的女性中进行年度CT筛查 风险妇女检测和治疗无症状感染并防止并发症；在男人中，常规筛查是 不建议。尽管筛选计划进行了30年，但美国的CT率却大大提高， 主要通过增加CT恢复而驱动。由于大多数受CT感染的女性是异性恋和例行公事 不建议在男性中进行筛查，男性未检测到的CT感染是推进的水库 妇女恢复。要遏制CT流行病，至关重要的是我们了解男人是否可以发展 对CT的免疫力并确定促进CT恢复的因素（例如，无症状的男性显着 CT生物）。大约有1/3的男性作为CT接触接受治疗（即，他们的性伴侣是 未感染的确认是CT感染的），表明这些男性要么通过免疫清除CT感染 介导的机制或具有抵抗CT采集的尿道微生物组。防止CT重新感染 妇女，该提案的重点是与CT感染的妇女的男性接触，并将研究CT感染是否相关 具有特定的微生物组组成，合并性性传播感染或自适应T细胞和抗体免疫。为此，我们 最多将注册400个男性CT接触，收集血液和尿液标本 一线抗生素，并要求他们返回进行1个月的治疗测试（TOC）访问（AIM 1）。研究CT是否未感染 与CT的接触具有长期的免疫力，以及尿道微生物组和免疫系统如何变化 时间，我们将重新注册100名男性进行6个月的纵向研究，以收集每周的尿液标本和 症状/性行为日记，血液和尿液标本在3个月和6个月的筛查访问中。 每周的尿液标本将在研究完成中存储和测试，以创建自然历史研究。经过 研究了随着时间的推移的CT感染率，我们将能够阐明是否对CT感染的抗性， 在AIM 1中定义，与（1）访问之间的自然清除率提高相关； （2）事件减少 3个月或6个月的CT感染； （3）入射CT感染生物体负荷的减少； （4）速率降低 同源CT GENOVAR。研究结果将为防止男性传播的新颖方法提供信息 给妇女并帮助遏制CT率上升的率和并发症。