Microbial Correlates of Bacterial Vaginosis Treatment Failure and Recurrence in H

细菌性阴道病治疗失败和复发的微生物相关性

• 批准号: 7800959
• 负责人: MICHAEL J FERRIS
• 金额: $ 47.51万
• 依托单位: CHILDREN'S HOSPITAL (NEW ORLEANS)
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7800959
• 关键词: Address; Amniotic Fluid; Antibiotic Therapy; Antibiotics; Bacterial Vaginosis; Behavior Control; Biological Assay; Communities; Complex; DNA; Data; Development; Diagnosis; Disease; Ecology; Ecosystem; Endometritis; Environment; Epithelium; Etiology; Evaluation; Failure; Female; Genital system; HIV Infections; Health; Human; Human Characteristics; Infant; Infection; Infection of amniotic sac and membranes; Knowledge; Lead; Methods; Metronidazole; Metronidazole resistance; Minor; Molecular; Molecular Analysis; Nature; One-Step dentin bonding system; Oral; Organism; Outcome; Pelvic Inflammatory Disease; Play; Postpartum Period; Premature Birth; Premature Labor; Premature Rupture Fetal Membranes; Prevention strategy; Pruritus; Recurrence; Regimen; Relative (related person); Research; Risk; Role; Sequence Analysis; Sexually Transmitted Diseases; Smell Perception; Syndrome; Time; Tissues; Treatment Failure; Treatment outcome; Vagina; Vaginal Discharge; Visit; Weight; Woman; abortion; base; cohort; compliance behavior; follow-up; human disease; improved; insight; irritation; male; member; microbial; pathogen; prevent; public health relevance; rRNA Genes; sexually active; standard care; tool; treatment trial

DESCRIPTION (provided by applicant): The long term objective of this research is to achieve a more rational, realistic paradigm of vaginal bacterial species and their influence on health and disease. Relevance: Bacterial Vaginosis (BV) is the most frequent cause of gynecological visits relating to vaginal irritation. More significantly, this very common ailment is associated with severe sequelae including preterm delivery and increased risk of HIV infection. BV is a microbiologic enigma. It appears to be a change in bacterial species that colonize the vaginal epithelium rather than a true tissue infection by a specific pathogen, however the cause is unknown. Standard treatment with metronidazole often fails, and recurrence rates are high. The fact that currently recommended therapy is relatively ineffective may explain why antibiotic treatment trials directed at preventing the complications of BV have failed. While evidence from studies of virgins suggests BV can arise endogenously, studies of sexually active women strongly suggest it is sexually transmitted. Recurrent infection rates following treatment are high and though partner treatment appears not to reduce these rates, the data strongly suggest that the male plays a role in re introducing BV associated organisms into the vagina. Insight: Recent cultivation-independent PCR analyses of vaginal flora have shown that the vaginal micro environment is much more complex than previously understood. Molecular tools are now available begin to better understand the etiology of BV, how it causes human disease and why current treatment is so inadequate. Hypothesis: BV treatment failures are associated with here-to-fore unstudied, uniquely definable, bacterial species consortia while recurrence is related to sexual contact with male partners who harbor these previously unknown BV-associated species. Specific Aims: (1) A panel of twenty species-specific quantitative real time PCR assays will be used to obtain detailed profiles of bacterial species-composition, and relative abundance, in women with clinically defined BV and in their male partners. (2) A cohort of monogamous women receiving oral metronidazole for treatment of BV, and their untreated male partners, will be followed to determine correlations between microbial species composition, treatment failure and recurrent BV. These analyses will be controlled for behavioral factors that might influence outcomes as well as treatment compliance. Significance: The results should lead to more effective methods of diagnosing and treating BV, and preventing the serious sequelae associated with this common syndrome. PUBLIC HEALTH RELEVANCE: Bacterial Vaginosis (BV) is the most frequent cause of gynecological visits relating to vaginal irritation. More significantly, this very common ailment is associated with severe sequelae including preterm delivery and increased risk of HIV infection. The results of this study should improve our understanding of vaginal bacterial flora in health and disease, and lead to more effective methods of diagnosing and treating bacterial vaginosis and preventing the serious sequelae associated with this common syndrome.

描述（由申请人提供）：这项研究的长期目标是实现阴道细菌物种的更合理，现实的范式及其对健康和疾病的影响。相关性：细菌性阴道病（BV）是与阴道刺激有关的妇科访问的最常见原因。更重要的是，这种非常常见的疾病与严重的后遗症有关，包括早产和艾滋病毒感染的风险增加。 BV是微生物学的谜。它似乎是细菌物种的一种变化，它在特定的病原体中定居于阴道上皮，而不是真正的组织感染，但是原因是未知的。甲硝唑的标准处理通常会失败，并且复发率很高。当前推荐的治疗相对无效的事实可以解释为什么旨在防止BV并发症的抗生素治疗试验失败。虽然对处女研究的证据表明BV可以内源性出现，但对性活跃女性的研究强烈表明它是性传播的。治疗后的反复感染率很高，尽管伴侣治疗似乎并不能降低这些率，但数据强烈表明，男性在将BV相关的生物重新引入阴道中起着作用。洞察：阴道菌群的最新培养的PCR分析表明，阴道微环境比以前所理解的要复杂得多。现在可以使用分子工具，可以更好地理解BV的病因，如何导致人类疾病以及为什么当前治疗如此不足。假设：BV治疗失败与此前未研究，独特的细菌物种伴侣有关，而复发与与携带这些先前未知BV相关物种的男性伴侣有关。具体目的：（1）将使用二十个物种特异性的定量实时PCR分析来获取具有临床定义BV及其男性伴侣的女性的细菌种类组成和相对丰度的详细概况。 （2）将遵循一群接受口服甲硝唑治疗BV的一夫一妻制的妇女及其未经治疗的男性伴侣，以确定微生物物种组成，治疗衰竭和复发性BV之间的相关性。这些分析将受到可能影响结果和治疗依从性的行为因素的控制。意义：结果应导致更有效的诊断和治疗BV的方法，并防止与该常见综合征相关的严重后遗症。公共卫生相关性：细菌性阴道病（BV）是与阴道刺激有关的妇科访问的最常见原因。更重要的是，这种非常常见的疾病与严重的后遗症有关，包括早产和艾滋病毒感染的风险增加。这项研究的结果应提高我们对健康和疾病中阴道细菌菌群的理解，并导致更有效的诊断和治疗细菌性阴道病的方法，并防止与该常见综合征相关的严重后遗症。