Epidemiology of Helicobacter Pylori Transmission

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。 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， 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 在我们先前的报告中，我们确定了H.幽门螺杆菌对胃肠炎发病率的影响。这一发现证实了 在单一宿主中的感染因子之间可能发生复杂的相互作用，从而影响疾病的结果。的 我们目前提案的目的是更好地描述感染如何在人体内相互作用。具体来说，我们希望 观察宿主对H.幽门螺杆菌在Thl的强慢性诱导物的环境中变化 响应（M.结核）或Th 2应答（肠道蠕虫）。具体目标是：1）表征关节 3种靶病原体在特定人群中的分布; 2）表征胃和全身免疫学 混合感染的特征，和3）评估治疗感染后这些免疫学特征的变化。在 在混合感染的情况下，我们推测蠕虫引起细胞介导的对H. pylori，而潜伏性结核分枝杆菌（LTBI）上调反应。我们进一步假设， 根除蠕虫或LTBI可逆转这些作用。将在圣克拉拉的新移民中进行 县，建议的研究将有三个部分。在第一部分，将进行社区调查， 将评估1750名受试者的感染分布。在第2部分中，来自第一阶段的200名受试者的子集将 进行更广泛的免疫分析，以评估个体和合并感染对系统性 细胞因子和免疫球蛋白水平。在第三部分，参加第二部分的受试者将接受以下治疗： 寄生虫、潜伏性结核感染或不治疗以及全身免疫学结果的变化将是 评估;在75个亚组中，对H.胃中的幽门螺杆菌也将通过内窥镜检查进行评估， 活检 人类如何应对他们所携带的慢性感染谱是一个至关重要的问题， 疫苗的发展和我们对人类疾病表现的变异性的理解。除了 揭示了为什么H.幽门螺杆菌在人与人之间和人群与人群之间是不同的，我们希望 这项研究还将扩大免疫流行病学工具包，以便在人群中进行进一步研究。

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.