Incident STIs in Kenyan Girls: a prospective cohort spanning sexual debut

项目摘要 撒哈拉以南非洲的少女受性传播感染的影响特别大 和艾滋病病毒。众所周知，性活跃的非洲青少年有很高的阴道炎症。我们 假设即使是性行为前的首次亮相，非洲青春期女孩也可能有阴道炎症， 阴道微生物多样性增加，这将影响他们的生殖器免疫成熟，微生物组， 以及对性传播感染的易感性。我们进一步假设，首次性行为可能导致持续的生殖器 炎症和细菌多样性增加。我们将在2015年延长一个已有的3年青春期女孩队列， 肯尼亚的蒂卡，招募了16-18岁和性行为前的青少年，并对他们进行了2年的随访， 总共5年，并确定淋病，衣原体和滴虫感染事件。我们的首要目标是 进行一项病例对照研究，比较宫颈阴道灌洗中的炎症特征（通过 细胞因子IL-6、IP-10、IL-1a和MIP-1b及其他）。我们还将 比较病例组和对照组外阴活检标本的炎症细胞的基线密度，以及 我们将比较阴道微生物多样性的大范围PCR测量，以及 感染性传播感染的女孩和对照组女孩之间的特定高危厌氧菌。我们的第二个目标是分析前- 以及初次性交后炎症、微生物多样性和细胞密度的变化。我们还将分析 孕激素避孕药和终生雌激素暴露（从初潮到首次性行为的时间）对 评估荷尔蒙变化对STI风险因素的影响。我们将与免疫专家合作， 对阴道炎症标志物进行严格的MSD分析，使用最先进的组织病理学方法， 评估组织炎症，并提出创新的全长扩增子微生物组测量 技术，以克服不精确的泌尿生殖物种鉴定。我们的方法是有效的， 利用和扩展现有的青少年群体，保持高保留率，并且是独一无二的，因为我们有 成功地收集了首次性行为前的宫颈阴道灌洗、微生物群和外阴活检标本， 青春期女孩我们的研究结果将为非洲人性行为前的免疫学提供一个全面的图景。 青春期女孩，确定促进性传播感染获得的因素，并将进一步展示女孩 当他们开始发生性行为时，生殖道免疫力和微生物组。我们预计，这种方法将确定 可改变的生物风险因素，以减少青春期女孩的性传播感染，结果可用于 开发性传播感染预防方法和多用途技术。

Project Summary Adolescent girls in sub-Saharan Africa are disproportionately affected by sexually transmitted infections (STIs) and HIV. Sexually active African adolescents are known to have high levels of vaginal inflammation. We hypothesize that even pre-sexual debut, African adolescent girls may have elevated vaginal inflammation and elevated vaginal microbial diversity, which will influence their genital immunological maturation, microbiome, and later susceptibility to STIs. We further hypothesize that sexual debut may result in persistent genital inflammation and increased bacterial diversity. We will extend a pre-existing 3 year cohort of adolescent girls in Thika, Kenya, recruited between ages 16-18 and pre-sexual debut, and follow them 2 additional years, for a total of 5 years, and determine incident gonorrhea, chlamydia, and trichomonas infection. Our first aim is to conduct a case-control study comparing the inflammatory profiles in cervicovaginal lavage (measured by cytokines IL-6, IP-10, IL-1a and MIP-1b and others) of girls who acquire STIs with controls. We will also compare baseline density of inflammatory cells of vulvar biopsy specimens between cases and controls, and we will compare broad-range PCR measurements of vaginal microbial diversity, and quantification by PCR of specific high-risk anaerobes between girls who acquire STIs and controls. Our second aim is to analyze pre- and post-sexual debut changes in inflammation, microbial diversity, and cell density. We also will analyze the role of progestin-based contraceptives and lifetime estrogen exposure (time from menarche to sexual debut) to evaluate the effects of hormonal variation on STI risk factors. We will collaborate with expert immunologists to perform rigorous MSD analysis of vaginal inflammatory markers, use cutting edge histopathological methods to evaluate tissue inflammation, and propose innovative full-length amplicon microbiome measurement techniques to overcome imprecision in urogenital species identification. Our approach is efficient as it leverages and extends an existing adolescent cohort with high retention rates, and is unique as we have successfully collected pre-sexual debut cervicovaginal lavage, microbiota and vulvar biopsy specimens from adolescent girls. Our results will provide a comprehensive picture of pre-sexual debut immunology of African adolescent girls, identify factors that promote STI acquisition, and will further demonstrate evolution of girls' genital tract immunity and microbiome as they begin having sex. We expect that this approach will identify modifiable biological risk factors to reduce STI acquisition among adolescent girls, and results can be used to develop STI prevention methods and multi-purpose technologies.