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

基本信息

批准号：
10580821
负责人：
DEBORAH Anne DEAN
金额：
$ 79.54万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
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/10580821
关键词：
16S ribosomal RNA sequencing 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 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 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 Taxonomy Teenagers Time Treatment Protocols Vagina Woman Work World Health Organization age group chemokine cohort cytokine design dysbiosis fitness genetic variant health disparity host microbiota human old age (65+)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

项目摘要

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.

概括虽然美国 CDC 对沙眼衣原体 (Ct) 性传播感染 (STI) 的年度估计为约 300 万，世界卫生组织 (WHO) 全球估计超过 1.31 亿。超过6100万人西太平洋太平洋岛屿国家和领土 (PICT) 中的感染者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感染是一种 PICT 以及世界其他地区健康差距的主要领域。在美国、夏威夷和其他地区太平洋岛民的性传播感染患病率排名第三，是白人的 3.7 倍。在这些资源中—— 在受限地区，Ct 综合征管理已成为常态。这是有问题的，因为约 80% 的女性 50%的男性没有症状并且不寻求医疗护理。来自这些无症状感染者的传播受感染的个人及其伴侣可能会加剧当前全球范围内的流行病。此外，缺乏治疗可能会导致盆腔炎、不孕、宫外孕、出血等严重后遗症直肠炎。虽然子宫颈内膜被认为是主要感染部位，但现在女性 Ct 直肠感染数量超过泌尿生殖道。如果没有充分的检测，直肠需要 7 至 21 天的时间复发率高的治疗是 Ct 在宿主内传播的潜在储存库合作伙伴。我们的统一假设是，Ct STI 的自然史是由以下相互作用定义的：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、宫颈内膜和直肠。我们将采用宏基因组鸟枪测序 (MSS) 来了解健康、失调和 Ct- 除了宿主免疫反应和 Ct 病原体特征之外，相关微生物群也具有高斐济妇女的发病队列。这项工作自然会转向改进未来的 CT 诊断，利用宏基因组方法，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。在事件发生前和事件发生时收集前瞻性样本和临床数据从我们的队列中检测到 Ct 感染（或无 Ct），我们的目标是：1）确定物种的分类多样性、丰富性和丰度使用 MSS 与 16S 测序交叉引用，研究宫颈内膜、阴道和直肠中基于 DNA 的生物体在两个时间点； 2) 定量每个位点、时间点微生物群背景下的免疫反应和临床结果； 3) 确定与事件 Ct 基因组相关的微生物群/免疫反应概况菌株以及菌株是否在每个部位的临床结果中发挥作用。我们的研究将有助于选择 Ct 筛查和设计策略（例如阴道和/或直肠治疗）的最佳部位微生物群，特别是对于后者，考虑到长期且通常无效的治疗方案。稳定的全球 CT 病例的增加需要进行研究，尤其是在那些遭受健康差异的人群中并且患性传播感染的风险增加。我们聚集了一群独特的斐济女性，她们的 Ct 发生率很高（高达 38%）如果没有它，就不可能研究 Ct 泌尿生殖和直肠 STI 的自然史。