Ecology of Infectious Diseases (EID)-Immune Landscapes of Human Influenza in Hous

描述(申请人提供)：流感病毒是人类最易遗传突变的病原体之一。我们的免疫反应给病毒带来了巨大的压力，导致基因谱系年复一年的快速更替。我们的免疫反应还包含以菌株特异性抗体的形式感染过的菌株的记录。虽然已经对流感病毒进行了一些前瞻性研究，但很少有人调查免疫学特征在空间或时间上的分布。这些模式为研究人类社会互动和人口结构对流感传播的影响提供了丰富的数据来源，这些影响因素是流感病毒生态的关键决定因素。广东省广州和东莞及其附近的城市和农村地区，中国，提供了一个独特的机会。该项目团队将对流感的免疫状况进行研究，将个人层面的免疫状况与家庭结构、旅行行为和社交网络的数据联系起来。除了是最近紧急感染(SARS和H5N1)的关键人群外，研究人群还显示出重要的社会结构异质性，这将使我们能够研究新的和有趣的假设。例如，人口密度和平均社会经济地位在相对较小的距离内差别很大。项目小组将使用先前经过验证的关于家庭结构、旅行和社会联系的问卷，在两个不同的场合(相隔一年)从50个小社区的20个家庭的每个成员那里收集数据。他们还将在这两种情况下采集血样。将对项目开始前10年的具有代表性的12种毒株进行所有血液样本的病毒中和试验。这些社会结构和血清学数据将与传染病传播的数学模型一起使用，以帮助回答关于人类行为如何影响疾病传播的基本问题。例如，流感是否在给定的一年跳过了一些小城镇，但感染了大城市的所有地理区域，儿童给家庭带来的感染是否比成年人多，我们能否利用过去季节的血清学数据预测，未来几个季节某些地理区域可能会受到更严重的影响？用来帮助回答这些问题的数学模型将从简单的微分方程模型到大规模的基于个人的模拟模型。除了是一个有价值的研究工具，大型模拟模型可能被证明是有价值的公共卫生工具，当它们可以使用该团队将在该项目中收集的那种血清学和社会结构数据进行准确校准时。与公共卫生相关：虽然这里提出的工作将产生比发表高质量同行评议的科学文章更广泛的影响，但应该记住，发表的结果本身将在发生大流行时直接用于公共卫生政策制定者。这项研究将对中国南部人群中突发流感大流行的可能流行病学提供比以往任何研究(在任何人群中)更准确的估计。广州疾病控制中心和香港卫生防护中心等主要利益攸关方将在专门为他们举行的会议上获悉这些结果。

DESCRIPTION (provided by applicant): The influenza virus is one of the most genetically mutable pathogens of humans. Our immune response places substantial pressure on the virus, resulting in rapid turnover of genetic lineages from year to year. Our immune response also contains a record of the strains we have been infected with in the form of strain-specific antibodies. Though some prospective studies of influenza viruses have been conducted, little has been done to investigate the distribution of immunological profiles in space or time. These patterns present a rich data source for investigation of the impact of human social interactions and demographics on influenza transmission, key determinants of the ecology of the influenza virus. The urban and rural areas in and near Guangzhou and Dongguan in Guangdong province, China, provide a unique opportunity. The project team will conduct a study of the immune landscape of influenza, linking that immune landscape, at the individual-level, to data on household structure, travel behavior and social networks. As well as being a key human population for recent emergent infections (SARS and H5N1) the study population also exhibits important heterogeneities in social structure which will allow us to investigate novel and interesting hypotheses. For example, both population density and average socio-economic status vary massively over relatively small distances. The project team will use previously-validated questionnaires on household structure, travel and social contacts to gather data from each member of 20 households in 50 small communities on two separate occasions (one year apart). They will also gather blood samples on both occasions. Viral neutralization assays will be conducted for all blood samples against a representative set of 12 strains from the 10 years prior to the start of the project. These social structure and serological data will be used alongside mathematical models of infectious disease transmission to help answer fundamental questions about how human behavior influences disease transmission. For example, does influenza skip some small towns on a given year but infect all geographical areas of large cities, do children bring much more infection into households than adults, and can we predict that some geographical areas might be harder hit in future seasons using serological data from past seasons? The mathematical models used to help answer these questions will vary from simple differential equation models to large-scale individual-based simulation models. As well as being a valuable research tool, large simulation models may prove to be valuable public health tools when they can be accurately calibrated using serology and social structure data of the kind the team will gather in this project. PUBLIC HEALTH RELEVANCE: Although the work proposed here will have broader impact beyond the publication of high quality peer-reviewed scientific articles, it should be remembered that the published results themselves will be of direct use to public health policy makers in the event of a pandemic. This study will provide more accurate estimates of the likely epidemiology of an emergent pandemic of influenza in the human population of southern China than any previous studies (in any population). Key stakeholders such as the Center for Disease Control in Guangzhou and the Center for Health Protection in Hong Kong will be made aware of these results during meetings held specifically for them.