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.

摘要 而美国疾控中心对沙眼衣原体(CT)性传播感染(STI)的年度估计是 据世界卫生组织(WHO)估计，全球约有300万人。超过6100万人 在西太平洋的太平洋岛国和领土(PICT)中感染 青少年和青壮年的患病率约为40%。这些百分比反映了性传播感染是一种 信息和通信技术中心以及世界其他地区健康差距的主要领域。在美国，夏威夷人和其他人 太平洋岛民的性传播感染患病率位居第三，是白人的3.7倍。在这些资源中- 受地域限制，CT的综合管理是常态。这是有问题的，因为~80%的女性 50%的男性没有症状，不寻求医疗服务。从这些无症状的传播到现在 将感染者转移到伴侣可能会加剧正在进行的全球疫情。此外，缺乏治疗可能 导致盆腔炎、不孕不育、宫外孕、出血等严重后遗症 结肠炎。虽然宫颈内感染被认为是主要的感染部位，但现在女性CT直肠感染 数量超过了泌尿生殖道的数量。如果没有足够的检测，直肠，这需要7到21天 复发率高的治疗是沙眼衣原体潜在的宿主内传播和 合伙人。我们的统一假设是，CT STI的自然历史是由 阴道、子宫内膜三个关键部位的微生物群、免疫反应和病原体种群 还有直肠。我们将使用超基因组鸟枪测序(MSS)来了解健康、不良生物和CT- 相关微生物区系除了宿主免疫反应和CT病原体特征外，还具有高- 斐济妇女发病队列。这项工作将自然过渡到改进未来的CT诊断 利用基因组学方法，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。在事故发生前和事故发生时收集的预期样本和临床数据 从我们的队列中发现CT感染(或没有CT感染)，我们的目标是：1)确定分类多样性、丰富性和丰度 利用与16S测序交叉参考的MSS在宫颈、阴道和直肠中的DNA生物 在两个时间点；2)在微生物区系背景下对每个地点、时间点的免疫反应进行量化 和临床结果；3)确定与发生的CT基因组相关的微生物区系/免疫反应谱 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筛查的最佳部位和设计的策略，如阴道和/或直肠治疗 微生物区系，特别是对于后一部位，给予漫长且往往无效的治疗方案。稳重的 全球CT病例的增加需要进行研究，特别是在那些患有健康差距的人中 并面临更高的性传播感染风险。我们聚集了一支独特的斐济妇女队伍，她们的CT发生率很高 (高达38%)，如果没有它，就不可能研究CT泌尿生殖系统和直肠性传播疾病的自然历史。