Impact of suppressive antimicrobial therapy on the vaginal microbiota and BV

描述(申请人提供)：细菌性阴道病(BV)是世界上最流行的阴道感染，每年影响数亿育龄妇女。这是一种多菌疾病，在成功治疗后经常复发，并与艾滋病毒-1感染、其他性传播感染(STI)和不良生殖健康后果有关。许多细菌种类与BV有关。然而，确切的病因仍不清楚。需要创新的治疗和预防方法，以减轻BV及其相关并发症造成的疾病负担。目前正在评估周期性推定治疗(PTT)作为一种减少包括BV在内的阴道感染发生率的新策略。2011年5月，我们开始招募参与者参加一项多点随机对照试验，以评估PPT+甲硝唑750 mg+咪康唑200 mg阴道栓与匹配的安慰剂在减少阴道感染方面的有效性(预防阴道感染试验；DMID方案#09-0070)。在整个试验过程中，我们将对阴道液样本进行存档，以便将来用分子方法测试阴道微生物区系。目前的提案将利用作为PVI试验的一部分收集的数据和样本，使用尖端分子技术评估PPT与安慰剂对可培养和耐培养阴道微生物群的影响。在目标1中，我们将使用高灵敏的物种特异性定量聚合酶链式反应方法来测量PPT对与阴道健康相关的细菌种类的检测和浓度的影响(L.crispatus、L.jensenii和L.iners)。目的2将使用类似的实验室方法评估PPT对BV相关细菌(BVAB1、BVAB2、BVAB3、阴道加德纳氏菌、阴道阿托波氏菌、羊毛细毛杆菌和巨型杆菌)检测和浓度的影响。目的3将利用一种互补的方法，使用广泛的聚合酶链式反应和高通量焦磷酸测序来评估PPT对阴道内总体细菌群落组成和多样性的影响。通过增加乳杆菌菌种的流行率和数量以及减少与BV相关的菌种的流行率和数量来促进阴道健康的干预措施可能会对妇女的生殖健康产生重大影响。这项建议将产生独特和有价值的信息，有助于我们全面了解阴道环境，并将为未来使用这种PPT方案作为一种干预措施提供信息，以减少艾滋病毒-1、其他性传播感染和不良生殖健康后果的风险。

DESCRIPTION (provided by applicant): Bacterial vaginosis (BV) is the world's most prevalent vaginal infection, affecting hundreds of millions of reproductive-aged women every year. It is a polymicrobial condition that frequently recurs following successful treatment and is associated with HIV-1 infection, other sexually transmitted infections (STIs), and adverse reproductive health outcomes. A number of bacterial species are associated with BV. However, the exact etiology remains unknown. Innovative treatment and prevention approaches are needed to reduce the burden of disease caused by BV and its associated complications. Periodic presumptive treatment (PTT) is currently being evaluated as a novel strategy to reduce the incidence of vaginal infections, including BV. In May 2011, we began enrolling participants into a multi-site, randomized controlled trial to evaluate the effectiveness of PPT with intravaginal metronidazole 750mg plus miconazole 200mg vaginal suppositories versus matching placebo in reducing vaginal infections (Preventing Vaginal Infections [PVI] trial; DMID protocol #09-0070). Throughout the trial, we will archive vaginal fluid specimens for future testing of vaginal microbiota by molecular methods. The current proposal will utilize data and specimens collected as part of the PVI trial to assess the effects of PPT versus placebo on both cultivable and cultivation-resistant vaginal microbiota using cutting-edge molecular technologies. In Aim 1, we will use highly sensitive species-specific quantitative PCR assays to measure the effect of PPT on the detection and concentrations of bacterial species associated with vaginal health (L. crispatus, L. jensenii, and L. iners). Aim 2 will use similar laboratory methods to assess the effect of PPT on the detection and concentration of BV-associated bacterial species (BVAB1, BVAB2, BVAB3, Gardnerella vaginalis, Atopobium vaginae, Leptotrichia amnionii, and Megasphaera species). Aim 3 will utilize a complementary approach, employing broad range PCR with high throughput pyrosequencing to assess the impact of PPT on overall bacterial community composition and diversity in the vagina. Interventions that promote vaginal health by increasing the prevalence and quantity of Lactobacillus species and reducing the prevalence and quantity of species associated with BV could have a substantial impact on women's reproductive health. This proposal will generate unique and valuable information that will contribute to our overall understanding of the vaginal environment, and will inform future use of this PPT regimen as an intervention to reduce the risk of HIV-1, other STIs, and adverse reproductive health outcomes.