Prospective Epidemiologic Study of Novel Etiologic Agents of Pelvic Inflammatory Disease

盆腔炎新病因的前瞻性流行病学研究

基本信息

批准号：
10668432
负责人：
DAVID Neal FREDRICKS
金额：
$ 78.17万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
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：
2020-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10668432
关键词：
16S ribosomal RNA sequencing Abscess Adnexal Mass Affect Anaerobic Bacteria Archives Atopobium vaginae Bacteria Bacterial Vaginosis Behavioral Biological Assay Case Study Cell Culture Techniques Cervical Characteristics Chlamydia trachomatis Clinical Complement Complication Detection Development Diagnosis Diagnostic Direct Costs Ectopic Pregnancy Endometrial Endometritis Endometrium Etiology Facilities and Administrative Costs Female Fever Future Gene Expression Genes Growth Gynecologic High Risk Woman High-Throughput Nucleotide Sequencing Histologic Human Infection Infertility Inflammation Inflammatory Knowledge Link Literature Mammalian Oviducts Measures Metagenomics Methods Microbe Mobiluncus Modeling Molecular Mycoplasma genitalium Neisseria gonorrhoeae Organism Organoids Ovarian Patients Pelvic Inflammatory Disease Phase Pilot Projects Population Population Attributable Risks Postpartum Period Prevention strategy Preventive Prevotella Primary Prevention Prospective Studies Prospective, cohort study Publishing Recording of previous events Recurrence Reporting Risk Role Salpingitis Sampling Secondary Prevention Sexually Transmitted Diseases Shotgun Sequencing Specimen Surveys System Technology Testing Time Tissues Translating Trichomonas vaginalis Vagina Woman aged bacterial community case control chronic pelvic pain clinical practice cohort comparison control design disease diagnosis disorder risk endometrial organoid epidemiology study follow-up genetic signature high risk microorganism nano-string next generation sequencing novel novel diagnostics overexpression pathogen predictive modeling prevent prospective rRNA Genes reproductive reproductive tract response routine screening tubal infertility vaginal microbiome vaginal microbiota young woman

项目摘要

Haggerty, Catherine L. Project Abstract Pelvic Inflammatory Disease (PID) is the frequent infection and inflammation of the upper genital tract among young women that often results in infertility, chronic pelvic pain, and recurrent PID. PID is a recognized complication of Chlamydia trachomatis and Neisseria gonorrhoeae infections, yet up to 70% of cases are idiopathic. An association between bacterial vaginosis (BV) and PID is recognized, however few studies have examined the specific vaginal bacteria most linked to PID, particularly focusing on vaginal bacteria that may resist lab cultivation. Cross-sectional evidence implicates Mycoplasma genitalium (MG) and the protozoan Trichomonas vaginalis (TV) as potential causes of PID, but prospective studies are lacking. We propose a prospective cohort study of 1,199 women considered at high risk for sexually transmitted infection who were actively followed three years for PID development. We will develop and apply to samples a panel of quantitative (qPCR) assays for suspect pathogens, including newly identified BV-associated bacteria, MG, and TV based on our pilot studies and broad-range 16S rRNA gene PCR with next generation sequencing and shotgun sequencing in the discovery phase. We will apply the NanoString nCounter inflammation panel to endometrial samples to determine whether particular inflammatory genes are overexpressed in samples from women with PID compared to women without PID in a bacterial species-specific fashion. We will complement our human studies with fallopian tube and endometrial organoid models, allowing us to directly assess how candidate pathogens interact with tissues of the female upper reproductive tract to induce inflammation. Our aims are to: 1) Develop a panel of candidate microbes for the prediction of PID using broad-range 16S rRNA gene PCR with high throughput sequencing (bacteria) and metagenomics shotgun sequencing (all microbes); 2) Determine whether the presence and quantity of vaginal pathogens in our candidate panel are associated with incident PID using sensitive qPCR, and whether the presence of these candidate pathogens in endometrial tissue is associated with an inflammatory gene signature in patients with PID; 3) Develop a model for the prediction of PID; 4) Determine the population attributable fraction (PAF) of PID due to each pathogen in our panel, CT, and NG; and 5) Determine the inflammatory potential of candidate PID pathogens in fallopian tube and endometrial organoid culture models where microbes are inoculated and inflammatory gene expression is assessed. This will be the first prospective study of PID to apply state-of-the-art qPCR assays and vaginal microbiome profiling, creating the potential for pathogen discovery and imparting a greater understanding of PID etiology. Further, we propose the first study to use fallopian tube organoids and NanoString technology to study PID. Testing for non-gonococcal, non-chlamydial pathogens is not routine, and knowledge gained from our study may identify novel diagnostic targets for PID with the potential to optimize future diagnostic, preventive, and treatment approaches.

哈格蒂，凯瑟琳·L. 项目摘要盆腔炎（PID）是女性上生殖道常见的感染和炎症。年轻女性经常会导致不孕、慢性盆腔疼痛和复发性盆腔炎。 PID是公认的沙眼衣原体和淋病奈瑟菌感染的并发症，但高达 70% 的病例是特发性的。人们认识到细菌性阴道病 (BV) 与 PID 之间存在关联，但很少有研究表明检查了与盆腔炎最相关的特定阴道细菌，特别关注可能导致盆腔炎的阴道细菌。抵制实验室培养。横断面证据表明生殖支原体 (MG) 和原生动物阴道毛滴虫 (TV) 是 PID 的潜在原因，但缺乏前瞻性研究。我们提议对 1,199 名被认为具有性传播高风险的女性进行一项前瞻性队列研究感染者积极随访三年以了解 PID 的发展情况。我们将开发并应用于样品对可疑病原体（包括新发现的 BV 相关细菌）进行定量 (qPCR) 检测 MG 和 TV 基于我们的试点研究和采用下一代测序的广泛 16S rRNA 基因 PCR 以及发现阶段的鸟枪法测序。我们将应用 NanoString nCounter 炎症面板子宫内膜样本以确定特定炎症基因是否在来自子宫内膜的样本中过度表达患有盆腔炎的女性与没有盆腔炎的女性以细菌种类特异性的方式进行比较。我们将补充我们对输卵管和子宫内膜类器官模型进行的人体研究，使我们能够直接评估如何候选病原体与女性上生殖道组织相互作用，诱发炎症。我们的目标是： 1) 开发一组候选微生物，用于使用广泛的 16S rRNA 预测 PID 基因 PCR 与高通量测序（细菌）和宏基因组鸟枪测序（所有微生物）； 2) 确定我们的候选组中阴道病原体的存在和数量是否相关使用敏感 qPCR 分析事件 PID，以及这些候选病原体是否存在子宫内膜组织与 PID 患者的炎症基因特征相关； 3）开发模型用于PID的预测； 4) 确定每种病原体引起的 PID 的群体归因分数 (PAF) 在我们的面板中，CT 和 NG； 5) 确定输卵管中候选 PID 病原体的炎症潜力接种微生物和炎症基因的输卵管和子宫内膜类器官培养模型评估表达。这将是第一个应用最先进的 qPCR 检测和阴道微生物组的 PID 前瞻性研究分析，创造病原体发现的潜力，并加深对 PID 病因学的了解。此外，我们提出第一个使用输卵管类器官和 NanoString 技术来研究 PID 的研究。对非淋菌、非衣原体病原体的检测并不常规，从我们的研究中获得的知识可能会确定 PID 的新诊断目标，有可能优化未来的诊断、预防和治疗接近。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Identification of fallopian tube microbiota and its association with ovarian cancer.

输卵管微生物群的鉴定及其与卵巢癌的关系。

DOI：
发表时间：
2024-03-07
期刊：
影响因子：
7.7
作者：
Yu, Bo;Liu, Congzhou;Proll, Sean C;Manhardt, Enna;Liang, Shuying;Srinivasan, Sujatha;Swisher, Elizabeth;Fredricks, David N
通讯作者：
Fredricks, David N

Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease.

阴道细菌在输卵管类器官中引起急性炎症反应：盆腔炎的模型。

DOI：
发表时间：
2023-05-23
期刊：
影响因子：
0
作者：
Yu, Bo;McCartney, Stephen;Strenk, Susan;Valint, Daniel;Liu, Congzhou;Haggerty, Catherine;Fredricks, David N
通讯作者：
Fredricks, David N