Experimentally Guided Modeling and Simulation for Cholera Dynamics

项目摘要/摘要 霍乱是一种由霍乱弧菌强毒力菌株引起的严重水源性感染，目前仍在 在发展中国家，这是一个重大的公共卫生负担。近年来，它在非洲和 南亚和美洲重新出现，估计每年有200-400万个病例由 世界卫生组织(WHO)。霍乱疫情的有效应对和控制策略 病原、宿主、环境三联体的流行病学分析及对该病的深刻认识 他们潜在的动力。目前，检验这一动态的研究很少。尤其是， 与霍乱弧菌相关的细菌动力学是一个关键的，但尚未被很好地了解， 形成复杂的霍乱流行和地方病的因素。这项提案的总体目标是 是建立一个新的数学和计算霍乱建模框架，以生物学为指导 实验，研究环境和人体内的病原体动态。至 为了实现这一目标，我们将追求三个具体目标：(1)对环境细菌进行建模 动力学；(2)模拟寄主内细菌动态；以及(3)连接和计算- 主机/主机内动态。这项拟议的研究具有重要意义，因为预计它将垂直 促进我们目前对霍乱动态的理解，特别是霍乱中的细菌进化 环境和人体内，这跨越了非常不同的时间尺度，这一点很重要 用于控制和管理霍乱。该方法在开发一种 复杂的多尺度数学框架，结合了病原体的详细动态 环境的进化和人体内病原体-宿主的相互作用，以及在整合中 严谨的数学建模和分析，密集的高级计算，精心设计 生物实验和真实的流行病数据。该项目代表了一种跨学科的 一位长期对霍乱感兴趣的应用和计算数学家之间的合作 模特儿、微生物学家和生物工程师。这一项目的成功不仅将为 为复杂的霍乱动态提供知识库，也为公众提供重要的指导 卫生行政部门在疾病管理和政策制定方面的作用。

Project Summary/Abstract Cholera, a severe waterborne infection caused by virulent strains of the bacterium Vibrio cholerae, remains a significant public heath burden in the developing world. In recent years, it has expanded in Africa and South Asia and re-emerged in the Americas, with an estimated 2 -- 4 million of cases per year reported by the World Health Organization (WHO). Effective outbreak response and control strategies for cholera rely on an analysis of the epidemiologic triad of pathogen, host, and environment and a deep understanding of their underlying dynamics. There is currently a paucity of research examining such dynamics. Particularly, the bacterial dynamics associated with the pathogen Vibrio cholerae are a critical, yet not well understood, factor that shapes the complex epidemics and endemics of cholera. The overall objective of this proposal is to establish a new mathematical and computational cholera modeling framework, guided by biological experiments, to investigate the pathogen dynamics in the environment and within the human body. To achieve this objective, we will pursue three specific aims: (1) Modeling the environmental bacterial dynamics; (2) Modeling the within-host bacterial dynamics; and (3) Linking and computing the between- host/within-host dynamics. The proposed research is significant because it is expected to vertically advance our current understanding of cholera dynamics, particularly the bacterial evolution in the environment and within the human body, which spans vastly different time scales and which is important for the control and management of cholera. The approach is innovative in the development of a sophisticated, multi-scale mathematical framework that incorporates detailed dynamics of the pathogen evolution in the environment and pathogen-host interaction within the human body, and in the integration of rigorous mathematical modeling and analysis, intensive and advanced computation, carefully designed biological experiments, and realistic epidemic data. The project represents an interdisciplinary collaboration among an applied and computational mathematician with long-term interest in cholera modeling, a microbiologist, and a bioengineer. The success of this project will not only build a solid knowledge base for the complex dynamics of cholera, but also provide important guidelines for the public health administrations in disease management and policy development.