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

UAB 性传播感染合作研究中心 (STI CRC)

• 批准号: 8769786
• 负责人: EDWARD W HOOK
• 金额: $ 181.5万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8769786
• 关键词: Address; Affect; African American; Aftercare; Alabama; Bacteria; Bacterial Vaginosis; Bioinformatics; Biometry; Characteristics; Chlamydia trachomatis; Classification; Clinical; Clinical Management; Data; Development; Diagnosis; Diagnostic; Epithelial Cells; Evaluation; Female; Foundations; Future; Gardnerella vaginalis; Generations; Genetic; Genital system; Goals; Grouping; Health; Housing; Immune response; Infection; Infection Control; Infection prevention; Inflammation; Informatics; Investigation; Knowledge; Laboratories; Lead; Microbe; Molecular; Mucous Membrane; Names; Nonspecific urethritis; Organism; Outcome; Pathogenesis; Patients; Prevention strategy; Recurrence; Research; Research Personnel; Research Project Grants; Resources; Risk; Science; Services; Sexual Partners; Sexually Transmitted Diseases; Signs and Symptoms; Specimen; Subgroup; Symptoms; Syndrome; Testing; Translating; Translational Research; Trichomonas vaginalis; United States; Universities; Ureaplasma urealyticum biovar 1; Vagina; Virulence Factors; Virulent; Woman; Work; assay development; cohort; improved; innovation; men; microbial; microbial community; microbiome; multidisciplinary; novel; pathogen; repository; tool; treatment effect

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.

描述（由申请人提供）：阿拉巴马大学伯明翰分校的性传播感染 (STI) 合作研究中心申请由三个创新的多学科转化研究项目组成，旨在解决男性（非淋菌性尿道炎 [NGU]）和女性（细菌性阴道病 [BV]）中最常见的生殖器分泌物综合征的微生物起源和发病机制。 这些综合征与最常见的可治愈细菌性传播感染——沙眼衣原体 (CT) 之间存在相互作用。因此，我们将该提案命名为“出院综合征一致性和相互作用研究”（DiSCIS）。我们的高产、成熟的研究人员小组将共同开展 3 个项目，以评估来自独特性伴侣群体的患者：有（病例）或没有（对照）有 NGU 症状的男性及其女性伴侣。我们将使用最先进的微生物学和分子科学工具，并依靠综合临床、实验室和生物统计/生物信息学核心服务。项目 1 的目标是加深对性伴侣（“二元体”）内已知 STI 病原体和生殖器微生物组组成的一致性的了解，以及治疗对微生物组以及感染体征和症状的影响。项目 1 的假设是：1) 已知 STI 之间的一致性与炎症 (NGU) 相关，2) 没有 NGU 的患者之间以及接受 NGU 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（微小脲原体）或微生物组特征可能有助于防止粘膜感染/炎症。项目 2 的目标是通过全面评估导致阴道上皮细胞感染和 BV 进展的加德纳菌 (GV) 毒力因子来增进对 BV 发病机制的了解，并确定将强毒力和无毒力 GV 菌株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 的发展相关。项目 3 的目标是加深了解阴道毛滴虫 (TV) 感染和/或 BV 对性伴侣内 CT 感染一致性的影响，以及这些伴随感染对治疗后 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，在存在这些伴随感染的情况下，治疗后 CT 一致性率更高，CT 清除持续时间更长。正如 DiSCIS 概述中详细描述的，这些项目具有高度互补性，并且在同一队列中执行时可提供巨大的附加值。此外，这些项目还将创建一个数据和样本存储库，作为未来性传播感染研究的强大资源。 DiSCIS 的研究结果将为 NGU 和 BV 微生物的发病机制以及 TV 感染和/或 BV 对 CT 一致性和结果的影响提供新的知识。该研究的长期目标是将研究结果转化为性传播感染预防、诊断和/或管理的改进或新策略。