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

摘要 沙眼衣原体(CT)是全世界最常见的细菌性性传播感染(STI)， 对女性造成不可逆转的生殖道损伤。由于大多数感染CT的妇女没有任何症状和 没有意识到自己被感染，疾控中心建议对25岁及以上的女性进行年度CT检查 风险女性发现和治疗无症状感染并预防并发症；在男性，常规筛查是 不推荐使用。尽管实施了30年的筛查计划，但美国的CT率仍大幅上升， 主要是由于CT再感染增加所致。因为大多数感染CT的女性是异性恋和例行公事 不建议对男性进行筛查，男性未被检测到的CT感染是推动 女性的再感染。为了遏制CT的流行，我们必须了解男性是否可以 对CT的免疫力，并确定促进CT再次感染的因素(例如，无症状的男性 CT生物体)。约1/3的男性作为CT接触者(即，他们的性伴侣是 被确认为CT感染的)都没有感染，这表明这些人要么通过免疫- 介导的机制或具有抵抗CT获取的尿路微生物群。预防沙眼衣原体再感染 女性，这项建议侧重于与感染CT的女性的男性接触，并将研究CT感染是否与 具有特定的微生物群组成、共病的性传播感染或适应性T细胞和抗体免疫。为了做到这一点，我们 将招募多达400名男性CT接触者，采集血液和尿液样本，用疾病预防控制中心进行治疗-推荐 一线抗生素，并要求他们回来进行为期1个月的治疗试验(TOC)访问(目标1)。研究CT是否未感染 接触CT的人有长期的免疫力，以及尿路微生物群和免疫系统是如何改变的 时间，我们将重新招募100名男性进行为期6个月的纵向研究，收集每周的尿样和 3个月和6个月筛查时的症状/性行为日记和血液和尿液样本。 每周的尿样将被储存并在研究完成时进行测试，以创建自然历史研究。通过 研究随着时间推移发生的CT感染率，我们将能够阐明对CT感染的耐药性， 在目标1中定义的，与(1)两次探视之间自然通过率增加；(2)事故减少相关 3个月或6个月的CT感染；(3)发生CT感染的机体负荷减少；(4)发病率下降 同源CT基因分型。研究结果将为预防男性传播的新方法提供信息 并有助于遏制不断上升的CT发病率和并发症。

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.