The UAB Sexually Transmitted Infections Cooperative Research Centers (STI CRC)

描述(由申请人提供)：阿拉巴马大学伯明翰分校的这项性传播感染(STI)合作研究中心申请由三个创新的多学科转换研究项目组成，旨在研究男性(非淋球菌性尿道炎[NGU])和女性(细菌性阴道病[BV])中最常见的生殖器排泄综合征的微生物来源和发病机制，以及这些症状与最普遍的可治愈细菌性STI沙眼衣原体(CT)的相互作用。因此，我们将该提案命名为“出院综合征协调与相互作用研究”(DiSCIS)。我们这组高生产力、成熟的研究人员将共同开展3个项目，评估来自一群独特的性伴侣的患者：有(病例)或没有(对照)有症状的非淋菌性尿道炎的男性及其女性伴侣。我们将使用尖端的微生物学和分子科学工具，并依托综合临床、实验室和生物统计/生物信息学核心服务。项目1的目标是促进对已知性传播感染病原体与性伴关系内生殖器微生物组组成的一致性(“二联体”)以及治疗对微生物组和感染体征和症状的影响的了解。项目1的假设是：1)已知性传播感染之间的一致性与炎症(NGU)有关，2)非NGU患者和NGU患者在接受治疗后的伙伴关系中微生物群落组成将更加一致，3)某些微生物(微小解脲支原体)或微生物群特征可能有助于保护黏膜免受感染/炎症。项目2的目标是通过综合评估导致阴道上皮细胞感染和发展为BV的加德纳菌(GV)毒力因子，提高对BV发病机制的认识，并确定将强毒和无毒GV毒株划分为不同分支的分类方案。项目2的主要假设是，特定的GV毒力因子与BV的发展有关。项目3的目标是促进对阴道毛滴虫(TV)感染和/或BV感染对CT感染的影响的了解，以及这些伴发感染对治疗后CT清除的影响，以及CT感染持续和/或复发的风险。项目3的主要假设是，在存在这些合并感染的情况下，治疗后CT符合率更高，CT清除时间更长。正如DiSCIS概述中详细描述的那样，这些项目具有很强的互补性，在同一批人中执行时提供了可观的附加值。此外，将从这些项目中创建一个数据和标本储存库，作为未来科学、技术和创新研究的强大资源。DiSCIS的发现将为了解导致NGU和BV的微生物的发病机制以及TV感染和/或BV对CT一致性和预后的影响提供新的知识。这项研究的长期目标是将研究结果转化为STI预防、诊断和/或管理的改进或新战略。

DESCRIPTION (provided by applicant): This Sexually Transmitted Infections (STI) Cooperative Research Center application from the University of Alabama at Birmingham is comprised of three innovative, multidisciplinary translational research projects addressing the microbial origins and pathogenesis of the most prevalent genital discharge syndromes in men (non-gonococcal urethritis [NGU]) and women (bacterial vaginosis [BV]), as well as interactions of these syndromes with the most prevalent curable bacterial STI, Chlamydia trachomatis (CT). Thus, we named the proposal the "Discharge Syndrome Concordance and Interactions Study" (DiSCIS). Our group of highly productive, established investigators will work together to conduct 3 projects to evaluate patients from a unique cohort of sexual partners: men with (cases) or without (controls) symptomatic NGU and their female partners. We will use cutting edge microbiological and molecular science tools, and rely on integrated clinical, laboratory, and biostatistics/bioinformatics core services. The goal of Project 1 is to advance understanding of the concordance of known STI pathogens and genital microbiome composition within sexual partnerships ("dyads") and the effect of treatment on the microbiome and signs and symptoms of infection. Project 1 hypotheses are: 1) concordance among known STIs is associated with inflammation (NGU), 2) there will be more concordance in microbial community composition within partnerships among those without NGU and following treatment among those with NGU and 3) that certain organisms (Ureaplasma parvum) or microbiome characteristics may help protect from mucosal infection/inflammation. The goal of Project 2 is to advance knowledge of BV pathogenesis through comprehensive evaluation of Gardnerella vaginalis (GV) virulence factors that contribute to infection of vaginal epithelial cells and progression to BV and also to determine classification schema for grouping virulent and avirulent GV strains into distinct clades. The main Project 2 hypothesis is that specific GV virulence factors are associated with BV development. The goal of Project 3 is to advance understanding of the influence of Trichomonas vaginalis (TV) infection and/or BV on CT infection concordance within sexual dyads and the effect of these concomitant infections on CT clearance after treatment and risk for CT infection persistence and/or recurrence. The main Project 3 hypothesis is that CT concordance rates are higher and CT clearance duration longer after therapy in the presence of these concomitant infections. As described in detail in the DiSCIS Overview, the projects are highly complementary and provide substantial value added when performed from the same cohort. Further, a data and specimen repository will be created from these projects that will serve as a powerful resource for future STI studies. DiSCIS findings will provide new knowledge on the pathogenesis of microbes contributing to NGU and BV, and the influence of TV infection and/or BV on CT concordance and outcomes. The long-term goal of the research is to translate findings into improved or new strategies for STI prevention, diagnosis, and/or management.