Exposure heterogeneity & environmental transmission dynamics of Escherichia coli

 描述(由申请人提供)：宿主行为和病原体特定的生活史产生复杂的病原体暴露模式，导致传播异质性。我们过分的假设是，病原体暴露的变化导致感染特征和传播的重要异质性，可用于控制目的。该项目将通过实验挑战研究、现场传播研究和动物运动监测系统与数学模型整合自然感染模型系统(大肠杆菌-牛)中产生的数据。具体目的是(1)确定牛生产系统中肠道疾病传播的异质性来源：收集与宿主相关的环境中病原体动态的变化、宿主之间、宿主与特定环境之间的接触结构以及感染特征的剂量依赖关系的数据。(2)开发一个模型框架，以集成和研究疾病传播的肠道病原体的异质性来源。将开发基于个体和餐场的模型，以调查接触结构和暴露的变化对人口传播模式的影响。模型将使用纵向实地研究中收集的数据进行参数化和验证。(3)评估以下项目的影响 肠道疾病控制中的暴露异质性。开发的模型将用于调查和确定可能导致减少传播的干预策略。这项拟议的研究将通过开发和分析模型来促进对肠道病原体传播的理解，这些模型以与传播相关的过程为基础，并与收集的关于宿主-宿主和宿主-环境接触的独特的高分辨率纵向数据、病原体的宿主外动态和病原体转移密切相关。总体而言，该项目将使人们更广泛地了解疾病传播中异质性来源之间的相互作用，以及如何将这些异质性来源纳入与研究影响疾病传播的生态因素相关的不同数学和计算模型中，并可推广到其他宿主-病原体系统。

 DESCRIPTION (provided by applicant): Host behavior and pathogen-specific life history generate complex patterns of pathogen exposure that drive transmission heterogeneity. Our overreaching hypothesis is that variation in pathogen exposure leads to important heterogeneities in infection traits and transmission that can be exploited for control purposes. The project will integrate data generated in a natural infection model system (Escherichia coli - cattle) through experimental challenge studies, field transmission studies, and animal movement monitoring systems with mathematical models. The specific aims are to (1) Characterize sources of heterogeneity for enteric disease transmission in cattle production systems: Data will be collected on the variation in pathogen dynamics in the host-associated environments, the contact structure among hosts, between host and specific environments, and the dose dependency of infection traits. (2) Develop a modeling framework to integrate and investigate the sources of heterogeneity for enteric pathogens for disease transmission. Individual-based and meal-field models will be developed to investigate the effect of the contact structure and variation of the exposure on population transmission patterns. Models will be parameterized and validated using data collected in longitudinal field studies. (3) Assessment of the implications of exposure heterogeneity in enteric disease control. The developed models will be used to investigate and identify intervention strategies that could lead to reduction in transmission. The proposed research will advance the understanding of the transmission of enteric pathogens by developing and analyzing models that are well-grounded in the processes associated with transmission and tightly connected to collected unique high-resolution, longitudinal data on host-host and host-environment contacts, extra-host dynamics of pathogens, and pathogen transfer. Overall this project will generate a broader understanding of the interaction between sources of heterogeneity on disease transmission and how to incorporate these sources of heterogeneity in different mathematical and computational models that is relevant to investigate ecological factors influencing disease transmission and generalizable to other host-pathogen systems.