Epidemiology of Helicobacter Pylori Transmission

描述（由申请人提供）：经济发展伴随着一些慢性传染病流行的急剧变化。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相互竞争的信号。在我们之前的报告中，我们确定了幽门螺杆菌对胃肠炎发病率的保护作用。这一发现举例说明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，我们希望看到宿主对胃幽门螺杆菌感染的反应在Th1反应（结核分枝杆菌）或Th2反应（肠蠕虫）的强慢性诱导剂的背景下是如何变化的。具体目的是1)表征三种目标病原体在特定人群中的联合分布；2)描述混合感染的胃和全身免疫特征，以及3)评估感染治疗后这些免疫特征的变化。在混合感染的情况下，我们推测蠕虫会导致细胞介导的对幽门螺杆菌的免疫反应下调，而潜伏性结核分枝杆菌（LTBI）则会上调这种反应。我们进一步假设，消灭蠕虫或LTBI可以逆转这些影响。这项研究将在圣克拉拉县的新移民中进行，研究将分为三个部分。在第一部分中，将进行社区调查，并评估1750名受试者的感染分布。在第二部分中，来自第一阶段的200名受试者将进行更广泛的免疫分析，以评估个体感染和共同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寄生虫、潜伏性结核感染或不治疗的治疗，并评估系统免疫结果的变化；在75个亚组中，胃对幽门螺杆菌的免疫反应也将通过内窥镜检查和活检进行评估。人类如何应对各种慢性感染，这对疫苗开发和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在人与人之间和人群之间不同之外，我们希望这项研究也将扩大免疫流行病学的工具包，以进一步研究人群。

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.