Natural History of C. trachomatis urogenital and rectal infections

沙眼衣原体泌尿生殖道和直肠感染的自然史

• 批准号: 10356116
• 负责人: DEBORAH Anne DEAN
• 金额: $ 80万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-20 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10356116
• 关键词: 16S ribosomal RNA sequencing; Address; Age; Anatomy; Area; Caring; Centers for Disease Control and Prevention (U.S.); Characteristics; Chlamydia Infections; Chlamydia trachomatis; Clinical; Clinical Data; Communities; Country; DNA; Data; Detection; Diagnostic; Ectopic Pregnancy; Endocervix; Epidemic; Ethnic Origin; Female; Fiji; Future; Genetic; Genitourinary System Infection; Genitourinary system; Genome; Genomics; Guam; Hawaiian; Hemorrhage; Heterosexuals; High Prevalence; Immune; Immune response; Incidence; Individual; Infection; Infertility; Inflammation; Inflammatory Response; Intervention; Knowledge; Lead; Life; Lymphogranuloma Venereum; Medical; Methods; Modeling; Natural History; Organism; Other Genetics; Outcome; Pacific Islander; Pacific Islands; Pacific Ocean; Papua New Guinea; Pathogenicity; Pelvic Inflammatory Disease; Persons; Play; Population; Premature Birth; Prevalence; Prevention; Proctitis; Rectum; Recurrence; Reporting; Research; Resource-limited setting; Risk; Role; Samoa; Sampling; Severities; Severity of illness; Sexually Transmitted Diseases; Shotgun Sequencing; Signs and Symptoms; Site; Syndrome; Taxonomy; Teenagers; Time; Treatment Protocols; Vagina; Woman; Work; World Health Organization; age group; base; chemokine; cohort; cytokine; design; dysbiosis; fitness; genetic variant; health disparity; host microbiota; improved; ineffective therapies; infection rate; innovation; male; men who have sex with men; metagenome; metagenomic sequencing; microbiome; microbiota; neglect; pathogen; prospective; rectal; rectal microbiota; screening; transmission process; treatment duration; urogenital tract; vaginal microbiota; young adult

SUMMARY While U.S. CDC annual estimates of Chlamydia trachomatis (Ct) sexually transmitted infections (STIs) are about 3 million, global World Health Organization (WHO) estimates are >131 million. Over 61 million people are infected among the Pacific Island Countries and Territories (PICT) of the Western Pacific Ocean with a prevalence rate of ~40% among teens and young adults. These percentages reflect the fact that STIs are a major area of health disparity in the PICT as well as in other parts of the world. In the U.S., Hawaiian and other Pacific Islanders have the 3rd highest prevalence of STIs, which is 3.7 times that of Whites. In these resource- constrained regions, syndromic management of Ct is the norm. This is problematic because ~80% of females and 50% of males are asymptomatic and do not seek medical care. Transmission from these asymptomatic yet infected individuals to partners likely fuels the ongoing worldwide epidemic. Further, lack of treatment can result in serious sequelae such as pelvic inflammatory disease, infertility, ectopic pregnancy, and hemorrhagic proctitis. While the endocervix is considered the primary site of infection, female Ct rectal infections now outnumber those in the urogenital tract. Without adequate detection, the rectum, which requires 7 to 21 days of treatment with high rates of recurrence, is a potential reservoir of Ct for transmission within the host and to partners. Our unifying hypothesis is that the natural history of Ct STIs is defined by the interaction of the microbiomes, immune responses and pathogen populations of three key body sites: the vagina, endocervix and rectum. We will employ metagenome shotgun sequencing (MSS) to understand healthy, dysbiotic and Ct- associated microbiota in addition to host immune responses and Ct pathogen characteristics for a high- incidence cohort of Fijian women. This work will naturally transition to improving future Ct diagnostics that utilize metgenomic methods, and we will determine whether these data can predict protection from Ct and/or incident Ct and infection severity. With prospective samples and clinical data collected prior to and at incident Ct infection (or no Ct) from our cohort, we aim to: 1) identify taxonomic diversity, richness and abundance of DNA-based organisms in the endocervix, vagina and rectum using MSS cross-referenced to 16S sequencing at both time points; 2) quantitate immune responses in the context of the microbiota for each site, time point and clinical outcome; 3) determine microbiota/immune response profiles that correlate with incident Ct genomic strains and whether strain plays a role in clinical outcome at each site. Our research will aid in selecting optimal sites for Ct screening and designing strategies such as vaginal and/or rectal therapy with beneficial microbiota, especially for the latter site given the long and often ineffective treatment regimens. The steady global increase in Ct cases necessitates research especially among those who suffer from health disparities and are at increased risk for STIs. We have assembled a unique cohort of Fijian women with high rates of Ct (up to 38%) without which it would not be possible to study the natural history of Ct urogenital and rectal STIs.

概括 美国疾病预防控制中心的沙眼衣原体（CT）性传播感染（STIS）的年度估计值为 大约300万，全球世界卫生组织（WHO）估计> 1.31亿。超过6100万人 在西太平洋的太平洋岛屿国家和地区（PICT）中被感染 青少年和年轻人的患病率约为40％。这些百分比反映了性传播疾病是一个事实 PICT以及世界其他地区的健康差异的主要领域。在美国，夏威夷人和其他 太平洋岛民的性病患病率是第三高，是白人的3.7倍。在这些资源中 - 受限区域，CT的综合症管理是规范。这是有问题的，因为约有80％的女性 50％的男性无症状，不寻求医疗服务。从这些无症状的传播 受感染的人向伴侣感染，可能会促进正在进行的全球流行病。此外，缺乏治疗可以 导致严重的后遗症，例如骨盆炎性疾病，不育，异位妊娠和出血 临床炎。虽然内cix被认为是感染的主要部位，但雌性CT直肠感染现在 超过泌尿生殖道的人。没有足够的检测，直肠需要7至21天 以高复发率处理，是CT在宿主内传播的潜在储层和 合作伙伴。我们统一的假设是，CT性传播感染的自然历史是由 三个关键身体部位的微生物组，免疫反应和病原体种群：阴道，内骨 和直肠。我们将采用元基因组shot弹枪测序（MSS）来了解健康，失调和CT- 除了宿主免疫反应和CT病原体特征外，相关的菌群 斐济妇女的发病率队列。这项工作自然会过渡到改善未来的CT诊断， 利用属基因组方法，我们将确定这些数据是否可以预测CT和/或 事件CT和感染严重程度。在事件前后收集的前瞻性样品和临床数据 CT感染（或没有CT），我们的目标是：1）确定分类的多样性，丰富性和丰富性 使用MSS交叉引用16S测序的内部内核，阴道和直肠的基于DNA的生物 在两个时间点； 2）在每个位点的微生物群中定量免疫反应，时间点 和临床结果； 3）确定与入射CT基因组相关的微生物群/免疫反应曲线 菌株以及应变是否在每个部位的临床结果中起作用。我们的研究将有助于选择 CT筛查和设计策略（例如阴道和/或直肠疗法）具有有益的最佳位点 微生物群，特别是对于后一个部位，考虑到长期且通常无效的治疗方案。稳定 CT案例的全球增加需要研究，特别是在患有健康差异的人中 并且处于性传播感染的风险增加。我们组装了一个独特的斐济妇女队列，CT率很高 （高达38％），如果没有这种情况，就无法研究CT泌尿生殖器和直肠性传播感染的自然史。