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

肯尼亚女孩的性传播感染事件：跨越首次性行为的前瞻性队列

• 批准号: 10001556
• 负责人: Alison Christina Roxby
• 金额: $ 32.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001556
• 关键词: Adolescence; Adolescent; Adult; Affect; Africa; Africa South of the Sahara; African; Age; Anaerobic Bacteria; Atopobium vaginae; Bacteria; Bacterial Vaginosis; Behavioral; Biologic Characteristic; Biological; Biopsy; Biopsy Specimen; Blood; CCR5 gene; CXCL10 gene; Case-Control Studies; Cell Density; Cells; Chlamydia Infections; Chlamydia trachomatis; Contraceptive Agents; Data; Dendritic Cells; Development; Ensure; Estrogens; Event; Evolution; Exposure to; Female; Female Adolescents; Genital system; Genitourinary system; Gonorrhea; HIV; HIV Infections; HIV Seronegativity; Histologic; Hormonal; Hormones; Human Herpesvirus 2; Immune response; Immunity; Immunologics; Immunologist; Immunology; Infection Control; Inflammation; Inflammatory; Infrastructure; Interleukin-1; Interleukin-6; Intervention; Irrigation; Kenya; Length; Leptotrichia; Longitudinal cohort; Macrophage Inflammatory Protein-1; Measurement; Measures; Menarche; Methods; Multiple Partners; Neisseria gonorrhoeae; Outcome; Plant Roots; Poverty; Predisposition; Prevention; Prevention strategy; Prevotella; Process; Progesterone; Progestins; Prospective cohort; Public Health; Publishing; Risk; Risk Factors; Role; STI prevention; Seminal fluid; Sex Behavior; Sexually Transmitted Diseases; Specimen; Swab; Techniques; Technology; Testing; Time; Tissues; Trichomonas Infections; Trichomonas vaginalis; Ursidae Family; Vagina; Variant; Vulva; Woman; base; case control; cervicovaginal; chemokine; cohort; cytokine; density; design; dysbiosis; girls; high risk; infection risk; inflammatory marker; innovation; macrophage; microbial; microbiome; microbiota; modifiable risk; prevent; prospective; rRNA Genes; recruit; reproductive tract; retention rate; sex; sexual debut; sexual violence; sexually active; vaginal microbiota; young woman

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.

项目概要 撒哈拉以南非洲地区的青春期女孩尤其容易受到性传播感染 (STI) 的影响 和艾滋病毒。众所周知，性活跃的非洲青少年阴道炎症程度较高。我们 假设即使在首次性行为前，非洲青春期女孩的阴道炎症也可能升高，并且 阴道微生物多样性升高，这将影响其生殖器免疫成熟、微生物组、 以及随后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性生殖器 炎症和细菌多样性增加。我们将在以下地区扩展现有的 3 年少女队列： 肯尼亚锡卡，招募年龄在 16 至 18 岁之间、性行为前首次亮相的人，并再跟踪他们 2 年，以获得 总共5年，并确定发生淋病、衣原体和滴虫感染。我们的首要目标是 进行病例对照研究，比较宫颈阴道灌洗中的炎症特征（通过测量 感染性传播感染的女孩的细胞因子 IL-6、IP-10、IL-1a 和 MIP-1b 等）。我们还将 比较病例和对照之间外阴活检标本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广泛 PCR 测量结果和 PCR 定量结果 感染性传播感染的女孩和对照组之间的特定高危厌氧菌。我们的第二个目标是分析预 首次性行为后炎症、微生物多样性和细胞密度的变化。我们还将分析 基于孕激素的避孕药和终生雌激素暴露（从初潮到首次性行为的时间）的作用 评估荷尔蒙变化对性传播感染风险因素的影响。我们将与免疫学家专家合作 对阴道炎症标志物进行严格的 MSD 分析，使用尖端的组织病理学方法 评估组织炎症，并提出创新的全长扩增子微生物组测量 克服泌尿生殖物种鉴定不精确的技术。我们的方法非常有效 利用并扩展现有的具有高保留率的青少年群体，并且是独一无二的 成功收集首次性行为前的子宫颈阴道灌洗液、微生物群和外阴活检标本 青春期少女。我们的结果将提供非洲人首次性行为前免疫学的全面了解 青春期女孩，确定促进性传播感染感染的因素，并将进一步展示女孩性传播感染的演变 当他们开始性行为时，生殖道免疫力和微生物组。我们期望这种方法能够确定 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的机会，结果可用于 开发性传播感染预防方法和多用途技术。