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

• 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
• 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

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 骨盆炎症性疾病（PID）是上生殖道经常感染和炎症 经常导致不育症，慢性骨盆疼痛和复发性PID的年轻女性。 PID是公认的 沙眼衣原体和淋病奈瑟氏菌感染的并发症，但多达70％的病例为 特发性。认识到细菌性阴道病（BV）和PID之间的关联，但是很少有研究的研究 检查了与PID最相关的特定阴道细菌，特别是专注于阴道细菌 抵抗实验室种植。横截面证据暗示了支原体生殖器（MG）和原生动物 阴道（TV）是PID的潜在原因，但缺乏前瞻性研究。 我们提出了一项对1,199名被认为具有性传播高风险的妇女的前瞻性队列研究 在PID开发中积极关注三年的感染。我们将开发并应用于样品 可疑病原体的定量（QPCR）测定面板，包括新鉴定的BV相关细菌， MG和电视基于我们的试验研究和下一代测序的宽范围16S rRNA基因PCR 在发现阶段进行shot弹枪测序。我们将将纳米弦ncounter炎症面板应用于 子宫内膜样品确定特定炎症基因是否过表达来自 与没有PID的女性相比，具有细菌特异性的女性。我们将补充 我们对输卵管和子宫内膜器官模型的人类研究，使我们能够直接评估 候选病原体与女性上部生殖道的组织相互作用，诱发炎症。我们的 目的是：1）开发一个使用宽范围16S rRNA预测PID的候选微生物面板 具有高通量测序（细菌）和元基因组shot弹枪测序（所有微生物）的基因PCR； 2）确定我们候选面板中阴道病原体的存在和数量是否相关 使用敏感QPCR的入射PID，以及这些候选病原体是否存在 子宫内膜组织与PID患者的炎症基因信号有关。 3）开发一个模型 为了预测PID； 4）确定由于每种病原体引起的PID的归因于PID的种群 在我们的面板中，CT和NG； 5）确定候选PID病原体在输卵管中的炎症潜力 接种微生物和炎症基因的管和子宫内膜器官培养模型 评估表达。 这将是对PID进行最新QPCR分析和阴道微生物组的第一项前瞻性研究 分析，创造了病原体发现的潜力，并对PID病因有了更大的了解。 此外，我们提出了第一项使用输卵管类器官和纳米串技术来研究PID的研究。 对非群局，非卫生病原体的测试不是常规的，我们的研究中获得的知识可能 确定PID的新型诊断靶标，具有优化未来诊断，预防和治疗的潜力 方法。

项目成果

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: 10.21203/rs.3.rs-2891189/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Yu,Bo;McCartney,Stephen;Strenk,Susan;Valint,Daniel;Liu,Congzhou;Haggerty,Catherine;Fredricks,DavidN
• 通讯作者: Fredricks,DavidN