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。H.例如，幽门螺杆菌在工业化国家已接近绝迹。然而，在发展中国家，慢性感染仍然很常见，并同时作用于宿主，导致对免疫系统的竞争信号。在我们之前的报告中，我们确定了H的保护作用。幽门螺杆菌对胃肠炎发病率的影响。这一发现证实了单一宿主中感染因子之间可能发生的复杂相互作用，从而影响疾病的结果。我们当前应用的目标是更好地表征感染如何在人体内相互作用。具体地说，我们希望看到宿主对H.幽门螺杆菌在Th 1应答的强慢性诱导物的环境中变化（M.结核）或Th 2应答（肠道蠕虫）。具体目的是：1）表征三种靶病原体在特定人群中的联合分布; 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，我们推测蠕虫引起细胞介导的免疫反应下调H。pylori，而潜伏性结核分枝杆菌（LTBI）上调反应。我们进一步假设，无论是蠕虫或LTBI根除逆转这些影响。在圣克拉拉县的新移民中进行，拟议的研究将有三个部分。在第一部分中，将进行社区调查，并将评估1750名受试者的感染分布。在第2部分中，来自第1阶段的200例受试者的子集将接受更广泛的免疫学分析，以评价个体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，参加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，并将评估全身免疫学结局的变化;在75名受试者的亚组中，对H.还将通过内窥镜检查和活组织检查评估胃中的幽门。人类如何应对他们所携带的慢性感染谱是疫苗开发和我们理解人类疾病表现变异性的关键问题。除了阐明为什么H. pylori在人与人之间和人群与人群之间存在差异，我们希望这项研究也将扩大免疫流行病学的工具包，用于在人群中进行进一步研究。