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不成比例地受到性传播感染(STI)的影响 和艾滋病病毒。众所周知，性生活活跃的非洲青少年的阴道炎水平很高。我们 假设即使在性行为之前，非洲青春期女孩的阴道炎症和 阴道微生物多样性增加，这将影响她们的生殖器免疫成熟，微生物群， 以及后来对性传播感染的易感性。我们进一步假设，首次性行为可能会导致持续的生殖器 炎症和细菌多样性增加。我们将扩大现有的3岁青春期女孩队列 Thika，肯尼亚，在16-18岁到首次性行为前招募，并跟随他们另外两年，为期一年 共5年，并确定淋病、衣原体、滴虫感染情况。我们的首要目标是 进行一项病例对照研究，比较宫颈阴道灌洗液中的炎症情况(通过 细胞因子IL-6、IP-10、IL-1a和MIP-1b等)。我们还将 比较病例和对照组外阴活检标本中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宽范围聚合酶链式反应测量结果，以及 获得性传播感染的女孩和对照女孩之间存在特定的高危厌氧菌。我们的第二个目标是分析Pre 以及性交后炎症、微生物多样性和细胞密度的变化。我们还将分析 以孕激素为基础的避孕药和终生雌激素暴露(从初潮到首次性行为的时间)对 评估激素变化对性传播感染危险因素的影响。我们将与专家免疫学家合作， 对阴道炎标志物进行严格的MSD分析，使用尖端组织病理学方法 评估组织炎症，并提出创新的全长扩增微生物组测量 克服泌尿生殖系统物种鉴定不精确性的技术。我们的方法是高效的，因为 利用并扩展现有的青少年群体，保持较高的留存率，这是我们独一无二的 成功收集了性行为前的宫颈阴道灌洗，微生物区系和外阴活检样本 青春期的女孩。我们的结果将提供非洲人首次性行为前免疫学的全面图景 青春期女孩，确定促进性传播感染的因素，并将进一步展示女孩的进化 生殖道免疫和微生物群在它们开始性交时。我们预计，这种方法将确定 可改变的生物风险因素，以减少青春期女孩获得性传播感染，结果可用于 发展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.