Avian Flu: Modeling, Analysis, and Simulations

禽流感：建模、分析和模拟

• 批准号: 0817789
• 负责人: Maia Martcheva
• 金额: $ 26.99万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0817789&HistoricalAwards=false
• 关键词: Avian; Flu; Modeling; Analysis; Simulations

The relatively benign human influenza virus strain that infects many of us year-round, albeit with seasonal pulses in frequency, can sometimes evolve into a potentially deadly strain that is capable of triggering a pandemic. The three recent human flu pandemics of 1918, 1957 and 1968--respectively known as the "Spanish flu", "Asian flu", and "Hong Kong flu"--caused huge devastation both in terms of the loss of human lives and consequent economic impacts. For each of these, genetic evidence suggests that a novel influenza strain evolved from the genetic recombination ("shift") of an animal flu strain and a human flu strain within a common host species that was co-infected by these two strains. This newly evolved strain had catastrophic effects on humans because of the absence of natural immunity by the host to this strain. The recent cases of human infection and death from avian influenza virus in several parts of the world, and the fact that humans and other animal species (such as swine) can act as a shared host to both avian flu and human flu strains, has raised concern that we may face a near-term emergence of another novel and highly virulent strain, thus another potential pandemic. Mathematical models provide crucial tools for understanding and possibly predicting and controlling the emergence and subsequent spread of novel pathogen strains. In this project we develop and analyze mathematical and simulation models to study real-world biological scenarios, in which there is co-infection of human host by avian flu and human flu strains. We will focus in particular on characterizing conditions for invasion and persistence of emergent virulent strains within human populations. This project will significantly advance our knowledge of the transmission dynamics and evolution of avian influenza from bird to human populations in particular, and of multi-species epidemic systems in general. It will provide a series of usable, realistic models that are grounded on available data. These models can serve as a solid background for future extensions incorporating and testing the efficacy of various control measures (such as vaccination, chemotherapy, and social distancing) for pandemic influenza, and suggest avenues of empirical study that are particularly important to pursue for disease prediction.In terms of technical approaches, this project unites the efforts of mathematicians and biologists in developing models based on integrated partial differential equations (PDE), ordinary differential equations (ODE), and stochastic individual-based simulations (IBS), to study the evolutionary epidemiology and population biology of avian influenza (AI). The research goal will be pursued along two main directions. 1) The "drift" and "shift" mechanisms of genomic evolution of an influenza virus will be simultaneously incorporated within a multi-strain PDE model that then will be used to predict the epidemiological consequences in a human population of an evolved influenza variant -- a novel avian influenza strain with both high pathogenicity and high human-to-human transmission efficiency. ODE versions of this model will be fitted to available World Health Organization (WHO) data of the cumulative number of human cases of avian influenza infection. Mathematical analysis of the best fitting ODE and PDE models will then be carried out, to rigorously characterize conditions for spread and persistence. 2) Complementary individual-based simulation (IBS) models of a human population will be developed on a small-world type network that incorporate explicit social interaction (contact) neighborhoods of each individual, and stochastic processes of birth, death and infection events. The pattern of flu outbreaks in these IBS models will be studied with respect to the underlying network structure, and related to the predictions of the corresponding ODE models. This will help elucidate the role of stochastic factors likely to be important in the early stages of strain emergence.

相对温和的人类流感病毒株全年感染我们许多人，尽管频率有季节性脉冲，但有时可能演变成能够引发大流行的潜在致命毒株。 最近在1918年、1957年和1968年发生的三次人类流感大流行-分别被称为“西班牙流感”、“亚洲流感”和“香港流感”-在人命损失和随之而来的经济影响方面造成了巨大的破坏。 对于每一种病毒，遗传学证据表明，一种新的流感病毒株是由动物流感病毒株和人类流感病毒株在共同感染这两种病毒株的共同宿主物种中的基因重组（“转变”）进化而来的。这种新进化的菌株对人类产生了灾难性的影响，因为宿主对这种菌株缺乏天然免疫力。 最近在世界几个地方发生的人类感染禽流感病毒和死亡病例，以及人类和其他动物物种（如猪）可以作为禽流感和人类流感病毒株的共同宿主的事实，引起了人们的担忧，即我们可能面临另一种新的高毒性毒株的出现，从而另一种潜在的大流行。数学模型为理解、预测和控制新型病原体菌株的出现和随后的传播提供了重要工具。在该项目中，我们开发和分析数学和模拟模型来研究现实世界的生物场景，其中人类宿主同时感染禽流感和人流感病毒株。我们将特别关注人群中出现的强毒株的入侵和持久性的特征条件。 该项目将大大提高我们对禽流感从鸟类到人类的传播动力学和演变的认识，特别是对多物种流行系统的认识。 它将提供一系列以现有数据为基础的可用、现实的模型。 这些模型可以作为一个坚实的背景，为未来的扩展纳入和测试各种控制措施的效力（如疫苗接种、化疗和社交距离），并提出了对疾病预测特别重要的实证研究途径。在技术方法方面，这个项目联合了数学家和生物学家的努力，开发基于集成偏微分方程（PDE），常微分方程（ODE），和基于个体的随机模拟（IBS），研究禽流感（AI）的进化流行病学和种群生物学。研究目标将沿着沿着两个主要方向进行。 1)流感病毒基因组进化的“漂移”和“转移”机制将同时纳入多毒株PDE模型，然后将用于预测进化的流感变体-一种既具有高致病性又具有高人传人效率的新型禽流感毒株-在人群中的流行病学后果。 该模型的ODE版本将与世界卫生组织（WHO）关于人类感染禽流感病例累积数的现有数据相拟合。 然后将对最佳拟合的常微分方程和偏微分方程模型进行数学分析，以严格描述扩散和持久性的条件。 2)将在一个小世界类型的网络上开发人类群体的补充基于个体的模拟（IBS）模型，该网络包含每个个体的显式社会互动（接触）社区以及出生，死亡和感染事件的随机过程。 这些IBS模型中的流感爆发模式将被研究的基础网络结构，并与相应的ODE模型的预测。 这将有助于阐明在菌株出现的早期阶段可能是重要的随机因素的作用。