BV ETIOLOGY, NATURAL HISTORY, AND SEXUAL TRANSMISSION

这项拟议的研究将测试有关细菌性阴道病(BV)发展的微生物、病毒学和行为风险因素的假设。细菌性阴道病是一种常见的阴道疾病，越来越多地被认为具有严重的健康后遗症，包括不良妊娠结局、盆腔炎和艾滋病毒感染风险增加。BV的病原学和自然病史知之甚少。这项研究将在乌干达的Rakai区进行，那里的育龄妇女总人口中约有50%患有BV。我们建议进行两项相辅相成的研究活动：I，对250名妇女(有和没有BV、艾滋病毒和既往性经验)进行BV自然史研究；II，对50个一夫多妻制家庭单位进行研究，将丈夫、他的妻子和其他居住在家庭中的妇女纳入研究范围。在这两项研究中，重复访谈和样本收集将被用来评估BV发病、持续、退化和复发的过渡概率，涉及以下方面：a)详细的社会人口学、行为和健康数据；b)阴道微生物区系，特别是乳杆菌菌种(将使用DNA同源性对其进行表征，并评估过氧化氢的产生)；c)乳杆菌噬菌体的潜在存在，其在乳杆菌枯竭中可能发挥的作用将被探索。在一夫多妻制家庭研究中，我们将确定与正常阴道菌群或BV相关的因素(包括乳杆菌、厌氧菌和噬菌体)是否可能通过性传播或通过密切的家庭接触传播，例如通过共用洗澡用具或水，通过比较具有一夫多妻性网络的妇女与家庭中的其他妇女。Rakai人群为评估BV提供了一个独特的机会。我们之前招募并跟踪了大约7,000名妇女参加了一项以人群为基础的性病控制艾滋病预防试验，证明了携带BV的妇女感染艾滋病毒和不良生育结果的风险增加，并有证据表明STD/BV治疗改善了妊娠结局。拟议的研究将提供独特的流行病学、微生物学和病毒学数据，涉及非洲农村人口的正常阴道菌群、BV的自然病史以及这种流行状况的潜在原因。这些信息将对未来BV预防、治疗和控制试验的设计至关重要，包括选择要测试的干预措施、样本量要求和研究终点的定义。

The proposed study will test hypotheses regarding microbiological, virological and behavioral risk factors for the development of bacterial vaginosis (BV), a common vaginal condition which is increasingly recognized as having serious health sequelae, including adverse pregnancy outcomes, pelvic inflammatory disease, and increased risk of HIV infection. The etiology and natural history of BV are poorly understood. The study will be conducted in Rakai District, Uganda, where approximately 50 percent in the general population of women of reproductive age have BV. We propose to conduct two complementary research activities: I, a BV natural history study in a cohort of 250 women (with and without BV, HIV and prior sexual experience), and II, a study in 50 polygamous family units which will enrol the husband, his wives and other women residing in the household. Repeated interview and sample collection in the two studies will be used to assess transition probabilities of BV onset, persistence, regression and recurrence in relation to: a) detailed sociodemographic, behavioral and health data; b) vaginal microflora, particularly Lactobacillus species (which will be characterized using DNA homology and assessed for H2O2 production) and c) the potential presence of lactobacillus bacteriophages, whose possible role in Lactobacillus depletion will be explored. In the polygamous household study, we will determine whether factors associated with normal vaginal flora or with BV (including lactobacilli, anaerobes and phages) may be transmitted sexually or via close household contact such as through the sharing of bathing utensils or water, by comparing women with a polygamous sexual network to other women within the household. The Rakai population offers a unique opportunity to assess BV. We previously enrolled and followed approximately 7,000 women in a population-based trial of STD control for AIDS prevention, have documented increased risk of HIV and adverse birth outcomes in women with BV, and have evidence of improved pregnancy outcomes with STD/BV treatment. The proposed study will provide unique epidemiological, microbiological and virological data regarding normal vaginal flora in this rural African population, the natural history of BV, and on potential causes of this prevalent condition. Such information will be critical for the design of future BV prevention, treatment and control trials, including selection of interventions to be tested, sample size requirements and definition of study end points.