PATHOGEN-IMMUNE INTERACTIONS OF ACUTE INFECTIONS: THE ROLE OF WANING IMMUNITY IN

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 理解病原体和宿主免疫之间的历史相互作用对于清楚地了解当代疾病动态是至关重要的。美国电报病例报告的公开记录是一种广泛和未开发的资源，我们将利用它来填补我们对疫苗前流感和百日咳动态的了解的一个重要空白。使用以前开发的数据库和基于网络的用户界面，我们将数字化1930-1950年各州和城市的流感和百日咳发病率和流感死亡率的病例报告。 该项目的目的是评估在大规模接种疫苗之前对流感和百日咳免疫力减弱的程度和意义。这两种疾病继续导致显著的发病率和死亡率，部分原因是病原体进化或免疫反应不完善。我们将开发一种简约的宿主间疾病传播模型，使用免疫力减弱的灵活表示法。我们将评估模型对有关免疫力减弱的替代假设的敏感性，并根据疫苗前的数据测试模型预测。 公共数据库是数据驱动的生物科学中的重要协作工具。该病例报告数据库，以及随后的分析和建模，填补了宿主-病原体研究的关键空白，补充了现有的生物信息学数据库和人类微寄生虫的研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. An understanding of the historical interaction between pathogens and host immunity is essential to a clear view of contemporary disease dynamics. The public record of United States telegraphic case reports is an extensive and unexploited resource that we will use to fill an important gap in our understanding of pre-vaccine influenza and pertussis dynamics. Using a previously developed database and web-based user interface, we will digitize case reports of influenza and whooping cough morbidity and influenza mortality from states and cities for 1930 - 1950. The aim of this project is to assess the magnitude and significance of waning immunity to influenza and pertussis prior to mass vaccination. Both of these diseases continue to cause significant morbidity and mortality, partly due to pathogen evolution or an imperfect immune response. We will develop a parsimonious between-host model of disease transmission using a flexible representation of waning immunity. We will assess model sensitivity to alternative assumptions about waning immunity and test model predictions against pre-vaccine data. Public databases are important collaborative tools in data-driven biological sciences. This case report database, along with the subsequent analysis and modeling fills a critical gap in host-pathogen research that complements existing bioinformatics databases and research of human microparasites.