Epidemiology of Helicobacter Pylori Transmission

幽门螺杆菌传播的流行病学

• 批准号: 7176199
• 负责人: Julie Parsonnet
• 金额: $ 67.92万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7176199
• 关键词: Address; Affect; Aftercare; Animal Model; Antigens; Area; Biopsy; California; China; Chronic; Cirrhosis; Colombia; Community Surveys; Complement Factor H; Complex; County; Developed Countries; Developing Countries; Development; Diagnostic; Diarrhea; Disease; Disease Outcome; Down-Regulation; Economic Development; Endoscopy; Epidemiology; Equilibrium; Esophageal Adenocarcinoma; Extinction (Psychology); Family; Feces; Funding; Gastric Adenocarcinoma; Gastric lymphoma; Gastroenteritis; Gastroesophageal reflux disease; Helicobacter; Helicobacter Infections; Helicobacter pylori; Helminths; Hepatitis Viruses; Household; Human; Immigrant; Immune response; Immune system; Immunity; Immunoglobulins; Immunologics; Incidence; Individual; Infection; Infectious Agent; Inflammation; Interferon Type II; Intestines; Iron deficiency anemia; Joints; Light; Malignant neoplasm of liver; Methodology; Mycobacterium tuberculosis; Organism; Outcome; Pathogenesis; Patients; Pattern; Peptic Ulcer; Peripheral Blood Mononuclear Cell; Persons; Phase; Play; Population; Prevalence; Production; Purpura; Pylorus; Research; Research Personnel; Risk; Risk Factors; Sampling; Signal Transduction; Stimulus; Stomach; Thinking; Tuberculosis; Vaccines; body system; cell mediated immune response; cytokine; human disease; latent infection; malignant stomach neoplasm; microbial; pathogen; programs; protective effect; response; transmission process; treatment effect; vaccine development

DESCRIPTION (provided by applicant): Economic development has been accompanied by dramatic changes in the prevalence of some chronic infections. H. pylori, for example, is nearing extinction in industrialized countries. In developing countries, however, chronic infections remain common and act on the host simultaneously, resulting in competing signals to the immune system. In our prior submission, we identified protective effects of H. pylori on gastroenteritis incidence. This finding exemplifies the complex interactions that can occur among infectious agents in a single host to affect disease outcome. The objective of our current application is to better characterize how infections interact within humans. Specifically, we wish to see how host response to gastric infection with H. pylori varies in the setting of strong chronic inducers of Th1 response (M. tuberculosis) or Th2 response (intestinal helminths). Specific aims are 1) to characterize the joint distribution of the three target pathogens in a defined population; 2) to characterize gastric and systemic immunologic profiles of mixed infections, and 3) to assess changes in these immunologic profiles after treatment of infection. In the setting of mixed infection, we speculate helminths cause down-regulation of cell-mediated immune responses to H. pylori whereas latent Mycobacterium tuberculosis (LTBI) upregulates the response. We further hypothesize that eradication of either helminths or LTBI reverses these effects. To be conducted in recent immigrants in Santa Clara County, the proposed research will have three parts. In Part 1, community surveys will be carried out and the distributions of infection in 1750 subjects will be evaluated. In Part 2, a subset of 200 subjects from phase one will undergo more extensive immunologic profiling to evaluate the effects of individual and co-infection on systemic cytokine arid immunoglobulin levels. In Part three, subjects who participated in Part II will undergo treatment of either helminths, latent tuberculosis infection or no treatment and changes in systemic immunologic outcomes will be assessed; in a subset of 75, immune responses to H. pylori in the stomach will also be assessed with endoscopy and biopsy. How humans respond to the spectrum of chronic infections that they harbor is a question of critical importance to vaccine development and to our understanding of the variability in manifestations of human disease. In addition to shedding light on why outcomes of H. pylori differ from person-to-person and from population-to-population, we hope this study will also expand the toolkit of immuno-epidemiology for further studies in human populations.

描述（由申请人提供）：经济发展伴随着一些慢性感染流行率的巨大变化。例如，幽门螺杆菌在工业化国家已接近灭绝。然而，在发展中国家，慢性感染仍然很常见，并且同时作用于宿主，导致向免疫系统发出竞争信号。在我们之前提交的文件中，我们确定了幽门螺杆菌对胃肠炎发病率的保护作用。这一发现例证了单个宿主中感染因子之间可能发生的复杂相互作用，从而影响疾病结果。我们当前应用程序的目标是更好地描述感染在人体内如何相互作用。具体来说，我们希望了解在 Th1 反应（结核分枝杆菌）或 Th2 反应（肠道蠕虫）的强慢性诱导剂环境中，宿主对幽门螺杆菌胃部感染的反应如何变化。具体目标是 1) 描述特定人群中三种目标病原体的联合分布； 2) 表征混合感染的胃和全身免疫学特征，3) 评估感染治疗后这些免疫学特征的变化。在混合感染的情况下，我们推测蠕虫会导致细胞介导的幽门螺杆菌免疫反应下调，而潜伏结核分枝杆菌 (LTBI) 会上调该反应。我们进一步假设根除蠕虫或 LTBI 可以逆转这些影响。拟议的研究将在圣克拉拉县的新移民中进行，分为三个部分。第1部分将进行社区调查，评估1750名受试者的感染分布情况。在第 2 部分中，第一阶段的 200 名受试者将接受更广泛的免疫学分析，以评估个体感染和合并感染对全身细胞因子和免疫球蛋白水平的影响。在第三部分中，参与第二部分的受试者将接受蠕虫、潜伏性结核感染的治疗或不接受治疗，并将评估全身免疫结果的变化；在 75 名患者中，还将通过内窥镜检查和活检来评估胃中幽门螺杆菌的免疫反应。人类如何应对自身携带的一系列慢性感染，对于疫苗开发以及我们对人类疾病表现变异性的理解至关重要。除了阐明为什么幽门螺杆菌的结果因人而异、因人群而异之外，我们希望这项研究还将扩展免疫流行病学的工具包，以便在人群中进行进一步的研究。