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Male urethritis: Novel etiologies and natural history

男性尿道炎：新的病因和自然史

基本信息

批准号：
8672151
负责人：
DAVID Neal FREDRICKS
金额：
$ 80.99万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-03 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8672151
关键词：
Address Adenoviruses Anal Sex Awareness Bacteria Bacterial Vaginosis Biota Chlamydia trachomatis Clinical Clinical Management Communities Data Detection Development Disease Etiology Female Genital system Heterosexuals Human Impact evaluation Incidence Individual Infection Intervention Lactobacillus Lead Leptothrix Leptotrichia Link Male Genital Organs Male urethral structure Metagenomics Mycoplasma genitalium Natural History Nature Oral Sex Organism Partner Notification Play Prevalence Prevention strategy Preventive Intervention Prospective Studies Public Health Recurrence Relapse Relative (related person)Reproductive Health Research Resolution Resources Risk Role Signs and Symptoms Simplexvirus Syndrome Time Treatment outcome Trichomonas vaginalis Ureaplasma urealyticum Urethra Urethritis Vagina Woman improved male men microbial microbial community novel novel diagnostics pathogen programs public health relevance pyrosequencing rRNA Genes reproductive screening sex tool treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Urethritis is the most common male reproductive tract syndrome, yet up to 50% of cases have no known etiology. Recently, we found that Leptotrichia/Sneathia spp., newly described bacteria that are highly sensitive and specific for bacterial vaginosis (BV) in women, were significantly associated with idiopathic urethritis in men. Two other newly described bacteria (BV-associated bacterium [BVAB] 2, and BVAB3) were found more often in men with idiopathic urethritis than in control men, suggesting that all 3 of these bacteria may play a role in urethritis. Furthermore, men with idiopathic urethritis had urethral microbial communities that were distinct from those in healthy men, and relative abundance of Lactobacillis iners was consistently higher in men with urethritis, suggesting that changes in the urethral microbiota may also play a causal role in the development of urethritis. Given the relatively common nature of male urethritis, its propensity to recur, and the high proportion of unexplained cases, we propose a 2-tiered strategy to identify novel etiologies of this condition. In a species-specific approach, we will prospectively assess the relationship between 3 newly described bacteria (Leptotrichia/Sneathia spp., BVAB2, BVAB3) and the incidence, resolution and recurrence of urethritis using species-specific quantitative PCR. In a metagenomic approach, we will use broad range 16S rRNA gene PCR with pyrosequencing to describe the urethral bacterial biota in men over time and to assess whether changes in species composition of bacteria in microbial communities and/or relative abundance of specific bacteria (L. iners, among others) are associated with incidence, resolution and recurrence of urethritis. Finally, we hypothesize that these bacteria and bacterial communities are sexually transmitted and will assess the relationships between specific sexual exposures, acquisition of any of the 3 newly described bacteria and/or changes in microbial communities, and new onset of clinical signs and symptoms of urethritis. These studies will enhance the clinical management of male urethritis, and may lead to the development of new diagnostic tools, therapies and prevention strategies. Given the sexually transmitted nature of most genital tract bacteria, parallel benefits for clinical management of female reproductive tract disease may follow.

描述（由申请人提供）：尿道炎是最常见的男性生殖道综合征，但高达 50% 的病例病因不明。最近，我们发现纤毛菌属/Sneathia spp.是一种新描述的细菌，对女性细菌性阴道病（BV）高度敏感和特异，与男性特发性尿道炎显着相关。另外两种新描述的细菌（BV 相关细菌 [BVAB]2 和 BVAB3）在患有特发性尿道炎的男性中比在对照男性中更常见，这表明所有这 3 种细菌可能在尿道炎中发挥作用。此外，患有特发性尿道炎的男性的尿道微生物群落与健康男性不同，并且患有尿道炎的男性中惰性乳杆菌的相对丰度始终较高，这表明尿道微生物群的变化也可能在尿道炎的发展中发挥因果作用。鉴于男性尿道炎相对常见的性质、其复发倾向以及不明原因病例的高比例，我们提出了一个两层策略来识别这种疾病的新病因。在物种特异性方法中，我们将使用物种特异性定量 PCR 前瞻性评估 3 种新描述的细菌（细毛菌/Sneathia spp.、BVAB2、BVAB3）与尿道炎的发病率、消退和复发之间的关系。在宏基因组方法中，我们将使用广泛的 16S rRNA 基因 PCR 和焦磷酸测序来描述男性尿道细菌生物群随时间的变化，并评估微生物群落中细菌物种组成的变化和/或特定细菌（惰性乳杆菌等）的相对丰度是否与尿道炎的发病、消退和复发相关。最后，我们假设这些细菌和细菌群落是通过性传播的，并将评估特定性接触、获得 3 种新描述的细菌和/或微生物群落的变化以及新出现的尿道炎临床体征和症状之间的关系。这些研究将加强男性尿道炎的临床管理，并可能导致新的诊断工具、疗法和预防策略的开发。鉴于大多数生殖道细菌的性传播性质，平行的好处女性生殖道疾病的临床管理可能遵循。