Microbial Correlates of Bacterial Vaginosis Treatment Failure and Recurrence in H

摘要 这项研究的长期目标是实现一个更合理、更现实的阴道细菌范例 物种及其对健康和疾病的影响。相关性：细菌性阴道病(BV)是最常见的 与阴道刺激有关的妇科就诊原因。更重要的是，这种非常常见的疾病是 与严重后遗症有关，包括早产和艾滋病毒感染风险增加。BV是一种 微生物学之谜。这似乎是定植在阴道上皮上的细菌种类的变化。 而不是由特定病原体引起的真正组织感染，然而原因尚不清楚。标准的治疗方法 甲硝唑经常失效，复发率很高。目前推荐的治疗方法是 相对无效的可能解释了为什么抗生素治疗试验针对预防BV并发症 都失败了。虽然来自处女研究的证据表明BV可以内源性产生，但对性行为的研究 活跃的女性强烈表明它是通过性传播的。治疗后的复发感染率很高 尽管伴侣待遇似乎并不能降低这些比率，但数据有力地表明，男性 在将BV相关生物重新引入阴道的过程中起到的作用。洞察：最近的培养非依赖性聚合酶链式反应 对阴道菌群的分析表明，阴道微环境比 之前的理解是这样的。分子工具现在可以用来更好地了解BV的病因，如何 导致人类疾病，以及为什么目前的治疗如此不足。假设：BV治疗失败是 与迄今未研究过的、唯一可定义的细菌物种联盟有关，而复发是 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20种特定物种的实时定量聚合酶链式反应分析来获得 临床确诊为BV的妇女的细菌种类组成和相对丰度的详细情况 以及他们的男性伴侣身上。(2)接受口服甲硝唑治疗的一夫一妻制妇女队列 BV和它们未经处理的雄性伴侣将被跟踪，以确定微生物物种之间的相关性 成分、治疗失败和复发性BV。这些分析将受控于下列行为因素 可能会影响结果以及治疗依从性。意义：结果应该会带来更多 诊断和治疗BV的有效方法，预防与此相关的严重后遗症 常见综合症。

Abstract 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 metronidazol 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.