Natural History of C. trachomatis urogenital and rectal infections

总结 虽然美国疾病控制和预防中心对沙眼衣原体（Ct）性传播感染（STI）的年度估计是 世界卫生组织（WHO）估计全球约有300万人，超过1.31亿人。超过6100万人 在西太平洋的太平洋岛屿国家和领土中， 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 这是太平洋岛屿发展中国家和世界其他地区健康差距的主要领域。在美国，夏威夷和其他 太平洋岛屿居民的性传播感染率位居第三，是白人的3.7倍。在这些资源中- 在受限制的地区，Ct的综合征管理是常态。这是一个问题，因为大约80%的女性 50%的男性没有症状，也不寻求医疗护理。从这些无症状的人身上传播 感染的个体到伴侣可能会助长正在进行的全球流行病。此外，缺乏治疗可能 导致严重的后遗症，如盆腔炎，不孕，宫外孕，出血， 直肠炎虽然子宫颈内被认为是感染的主要部位，但女性直肠感染现在 数量超过了泌尿生殖道如果没有足够的检测，直肠，这需要7至21天的 复发率高的治疗，是一个潜在的宿主内传播的Ct库， 伙伴我们的统一假设是，Ct STI的自然史是由以下因素的相互作用定义的： 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、子宫颈内膜 和直肠我们将采用宏基因组鸟枪测序（MSS）来了解健康，生态失调和Ct- 除了宿主免疫应答和Ct病原体特征外， 斐济妇女发病率队列。这项工作将自然过渡到改善未来的Ct诊断， 利用metgenomic方法，我们将确定这些数据是否可以预测对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的前瞻性样本和临床数据 我们的目标是：1）鉴定Ct感染的分类多样性、丰富性和丰度， 使用MSS与16 S测序交叉参考的宫颈内膜、阴道和直肠中基于DNA的微生物 2）在微生物群的背景下定量每个部位、时间点的免疫应答 和临床结果; 3）确定与偶发Ct基因组相关的微生物群/免疫应答谱 菌株以及菌株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筛查和设计策略的最佳部位，如阴道和/或直肠治疗， 微生物，特别是对于后一个部位，考虑到长期和往往无效的治疗方案。稳步 全球Ct病例的增加需要研究，特别是在那些遭受健康差异的人中 患性病的风险也会增加我们聚集了一个独特的斐济妇女队列， (up至38%），否则不可能研究Ct泌尿生殖道和直肠STI的自然史。

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.