Modeling the evolutionary and epidemiological patterns of infectious diseases

拟议的研究计划集中于传染病的进化和流行病学模式建模，重点是流感。流感是人类发病和死亡的主要原因。流感病毒经历快速突变以逃避人体免疫系统。剧烈的基因变化不时发生。流感大流行（如1918年、1957年和1968年）就是由这些剧烈变化引起的。因此，流感大流行规划和大流行间控制已成为重要的公共卫生问题。本研究旨在估计流感传播率等重要流行参数，了解流感死亡模式和估计流感死亡负担，估计疫苗接种和抗病毒药物使用的有效性，了解流感流行过程与进化过程的相互作用。长期目标是建立一个数学上易于处理的模型，可以解释流感的进化和流行模式。这些都是与控制大流行性和非大流行性流感密切相关的基本问题。这些技术包括收集肺炎和流感相关的医院访问数据和流感血清学监测数据，将肺炎和流感死亡率曲线拟合到控制流行病的机制模型中，基于agent的模拟，以及开发结合流行病和进化过程的新模型。虽然这项研究的动机主要是流感，但它将导致适合研究任何快速进化的病原体的控制策略的模型。我将把这些技术应用于其他传染病，如艾滋病毒/艾滋病。

The proposed research program concentrates on modeling the evolutionary and epidemiological patterns of infectious diseases, with an emphasis on influenza. Influenza is a major cause of human morbidity and mortality. Influenza viruses undergo rapid mutations to evade human immune system. Drastic genetic changes occur from time to time. Influenza pandemics (e.g. in 1918, 1957 and 1968) were caused by these drastic changes. Hence, both influenza pandemic planning and inter-pandemic control have become important public health concerns.This proposed research aims to estimate important influenza epidemic parameters such as transmission rates, understand the mortality patterns and estimate the influenza mortality burden, estimate the effectiveness of vaccination and antiviral drug usage, understand the interaction between the epidemic process and the evolutionary process. The long-term objective is to develop a mathematically tractable model that can explain the influenza evolutionary and epidemic patterns. These are fundamental questions closely related to the control of pandemic and nonpandemic influenza. The techniques involve compiling pneumonia and influenza related hospital visitation data and influenza serological surveillance data,  fitting the pneumonia and influenza mortality curves to mechanistic models that govern the epidemics, agent-base simulations, and developing new models that combines the epidemic and evolutionary processes.While this research is motivated primarily by influenza, it will lead to models suitable for studying control strategies for any fast-evolving pathogens. I will apply the techniques to other infectious diseases, such as HIV/AIDS.