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：
9001246
负责人：
DAVID Neal FREDRICKS
金额：
$ 77.66万
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/9001246
关键词：
Address Adenoviruses Anal Sex Awareness Bacteria Bacterial Vaginosis Biota Chlamydia trachomatis Clinical Clinical Management Communities Data Detection Development Disease Etiology Female Health 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 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 microbiota novel novel diagnostics novel therapeutics pathogen programs pyrosequencing rRNA Genes reproductive tract 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，但多达50％的病例尚无已知病因。最近，我们发现，新描述的细菌的瘦素/Sneathia spp。对女性的细菌性阴道病（BV）高度敏感，与男性特发性尿道炎显着相关。在特发性尿道炎的男性中，发现其他两种新描述的细菌（BV相关细菌[BVAB] 2和BVAB3）比对照男性更频繁地发现，这表明所有这些细菌中的所有三种可能在尿道炎中起作用。此外，患有特发性尿道炎的男性具有与健康男性不同的尿道微生物群落，而尿道炎的男性的相对丰富性始终更高，这表明尿道菌群的变化也可能在尿素炎发育中起因作用。鉴于男性尿道炎的相对常见性质，其复发的倾向以及无法解释的病例的高比例，我们提出了一种2级策略，以鉴定这种情况的新病因。在一种特定物种的方法中，我们将前瞻性地评估3种新描述的细菌（Leptrichia/Sneathia spp。，BVAB2，BVAB3）与使用物种特异性定量PCR的发生率，分辨率和复发性之间的关系。在一种宏基因组方法中，我们将使用焦磷酸测序使用广泛的范围16S rRNA基因PCR来描述男性的尿道细菌性生物群，并评估微生物群落中细菌的物种组成的变化和/或特定细菌的相对丰度（L. iners等）是否与Incurnoluction，rethrecrence ostrecrence oftrecrience and urethrecrience and urethrecrience and urethrecrience and urethrivelsive相关。最后，我们假设这些细菌和细菌群落是性传播的，并将评估特定性暴露之间的关系，获得3种新描述的细菌中的任何一个和/或微生物群落的变化，以及临床体征的新发作和尿道炎的症状。这些研究将增强男性尿道炎的临床管理，并可能导致开发新的诊断工具，疗法和预防策略。鉴于大多数生殖道细菌的性传播性质，对于女性生殖道疾病的临床管理。