Microbial Correlates of Bacterial Vaginosis Treatment Failure and Recurrence in H

描述(申请人提供)：这项研究的长期目标是实现对阴道细菌种类及其对健康和疾病的影响的更合理、更现实的范例。相关性：细菌性阴道病(BV)是与阴道刺激有关的妇科就诊的最常见原因。更重要的是，这种非常常见的疾病与包括早产和艾滋病毒感染风险增加在内的严重后遗症有关。BV是一个微生物之谜。这似乎是细菌种类的变化，定植于阴道上皮，而不是真正的组织感染，由特定的病原体，但原因尚不清楚。甲硝唑的标准治疗经常失败，复发率很高。目前推荐的治疗相对无效的事实可能解释了为什么旨在预防BV并发症的抗生素治疗试验失败了。虽然对处女的研究证据表明，BV可以内源性产生，但对性行为活跃的女性的研究强烈表明，它是通过性传播的。治疗后的复发感染率很高，尽管伴侣治疗似乎不能降低这些比率，但数据强烈表明，男性在将BV相关生物重新引入阴道的过程中发挥了作用。洞察：最近对阴道菌群的培养无关的聚合酶链式反应分析表明，阴道微环境比之前了解的要复杂得多。现在有了分子工具，可以更好地了解BV的病因，它是如何导致人类疾病的，以及为什么目前的治疗如此不足。假设：BV治疗失败与迄今未被研究的、唯一可定义的细菌物种联盟有关，而复发与与携带这些以前未知的BV相关物种的男性伴侣的性接触有关。具体目标：(1)将使用一组20种特定物种的实时定量聚合酶链式反应分析，以获得临床明确的BV女性及其男性伴侣的细菌物种组成和相对丰度的详细概况。(2)一组接受口服甲硝唑治疗BV的一夫一妻制妇女及其未经治疗的男性伴侣将被跟踪调查，以确定微生物种类组成、治疗失败与BV复发之间的相关性。这些分析将控制可能影响结果和治疗依从性的行为因素。意义：这些结果将导致更有效的诊断和治疗BV的方法，并防止与这种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就诊的最常见原因。更重要的是，这种非常常见的疾病与包括早产和艾滋病毒感染风险增加在内的严重后遗症有关。这项研究的结果将提高我们对健康和疾病中阴道细菌菌群的了解，并导致更有效的诊断和治疗细菌性阴道病的方法，并预防与这种常见综合征相关的严重后遗症。

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.