Epidemiology of Helicobacter Pylori Transmission

幽门螺杆菌传播的流行病学

• 批准号: 7574537
• 负责人: Julie Parsonnet
• 金额: $ 69.83万
• 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/7574537
• 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; 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

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 proposal 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 Thl 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 individualand 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 immunoepidemiology for further studies in human populations.

在经济发展的同时，一些慢性感染的流行率也发生了巨大变化。 例如，幽门螺杆菌在工业化国家正濒临灭绝。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，导致免疫系统收到相互竞争的信号。在……里面 我们先前提交的报告中，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 单个宿主中的感染性病原体之间可能发生的复杂相互作用，从而影响疾病结局。这个 我们目前建议的目标是更好地描述感染如何在人类内部相互作用。具体来说，我们希望 了解幽门螺杆菌对胃感染的宿主反应在Thl的强慢性诱因环境中的变化 应答(结核分支杆菌)或Th2应答(肠道蠕虫)。具体目标是1)描述关节的特征 三种目标病原体在特定人群中的分布；2)胃和全身免疫学特征 混合感染的概况，以及3)评估感染治疗后这些免疫学概况的变化。在 在混合感染的背景下，我们推测蠕虫导致对H. 幽门螺杆菌，而潜伏的结核分枝杆菌(LTBI)则上调这种反应。我们进一步假设 根除蠕虫或LTBI都可以逆转这些影响。将在圣克拉拉的新移民中进行 县，建议研究将分为三部分。在第一部分，将进行社区调查，并 将对1750名受试者的感染分布进行评估。在第二部分中，第一阶段的200个主题的子集将 进行更广泛的免疫学分析，以评估单独感染和联合感染对全身的影响 细胞因子和免疫球蛋白水平。在第三部分中，参与第二部分的受试者将接受以下两种治疗之一 蠕虫、潜伏的结核病感染或不接受治疗以及全身免疫结果的变化将是 评估；在75人的子集中，胃部对幽门螺杆菌的免疫反应也将通过内窥镜和 活组织检查。 人类如何应对他们所携带的各种慢性感染是一个至关重要的问题 疫苗的开发和我们对人类疾病表现的可变性的理解。除了……之外 我们希望能阐明为什么幽门螺杆菌的感染结果在人与人之间和人与人之间不同 这项研究还将扩展免疫流行病学工具包，用于在人类群体中进行进一步研究。