Avian Influenza: Modeling, Analysis and Implications for Control

这项跨学科研究融合了数学家和生物学家在开发模型和解决与禽流感的复杂生态和进化有关的问题方面的努力。H5N1亚型高致病性禽流感(HPAI)是由在家禽中传播的低致病性禽流感(LPAI)演变而来的，目前有可能发生突变并引发一场大流行。要了解病毒病原体的进化，需要在宿主种群结构的背景下详细分析不同遗传类型病毒之间的相互作用。该项目的第一部分研究了HPAI和LPAI在野生鸟类和家禽中的相互作用，特别是与LPAI潜在地向HPAI提供交叉免疫有关的问题。首席研究员和她的同事开发并分析了两宿主物种系统(对应于家禽种群和野生鸟类种群)中的多菌株年龄结构模型，以研究HPAI和LPAI菌株的竞争排除和持久性。此外，还发展了解释系统动力学行为的数学方法。初步结果表明，当鸟类中存在LPAI和HPAI共存时，恢复以来的时间结构与交叉免疫可能是导致LPAI和HPAI更复杂、更振荡行为的原因。该项目的第二部分建立在这些模型的基础上，以研究应用多种控制策略控制家禽高致病性H5N1流感的共生效应。初步结果表明，在减少H5N1在人类中的流行方面，应用于家禽的策略，如接种疫苗和扑杀，应比应用于人类的策略，如穿戴防护装备，明显更有效。进一步了解作为当今应用的两种主要控制措施的家禽疫苗接种和扑杀的相互作用，以便为替代潜在的疾病控制措施提供定量的洞察力。本项目制作了高致病性禽流感(由H5N1流感病毒引起的禽流感)模型，这些模型以病毒的复杂生物学为基础，并用现有数据进行验证。这样的模型既是理解基本疾病动态以及制定和实施有效控制措施所必需的。这些模型旨在符合关于人类H5N1病例累积数量的现有数据，并能够对未来病例进行合理预测。此外，H5N1引起的全球人类流行病(大流行)的威胁需要对病毒采取严格的控制措施。这些控制措施(特别是扑杀，即在检测到H5N1感染时扑杀家禽作业中的所有禽类)在世界许多地区给家禽业造成重大经济损失。作为该项目的一部分开发的模型和方法评估替代控制措施在减少H5N1人间病例数量方面的有效性。对这些数学模型的分析扩大了我们选择最佳控制措施的能力。此外，该项目还研究了低致病性菌株中高致病性菌株的出现及其在野生鸟类和家禽中的传播。能够感染人类的高致病性毒株的进化是出现大流行毒株的主要途径。了解促进这种演变的环境有助于我们做好准备，以识别和抗击禽流感造成的潜在大流行威胁。

This interdisciplinary study integrates the efforts of mathematicians and biologists in developing models and addressing questions related to the complex ecology and evolution of avian influenza. Highly pathogenic avian influenza (HPAI) of the subtype H5N1, which now threatens to mutate and cause a major pandemic, evolves from the low pathogenic avian influenza (LPAI) while circulating in poultry. Understanding evolution of viral pathogens requires a detailed analysis of interactions between different genetic types of the virus in the context of host population structure. The first part of this project studies the interplay of HPAI and LPAI in wild birds and domestic birds, particularly questions related to the cross-immunity that LPAI potentially provides to HPAI. The principal investigator and her colleagues develop and analyze multi-strain age-structured models in a two-host-species system (corresponding to domestic bird stocks, and wild bird populations) to study competitive exclusion and persistence of HPAI and LPAI strains. Furthermore, mathematical techniques are developed that elucidate the dynamical behavior of the system. Preliminary results suggest that time-since-recovery structure coupled with cross-immunity may be responsible for more complex, oscillatory behavior of LPAI and HPAI when there is coexistence in birds. The second part of the project builds on these models to study the symbiotic effect of multiple control strategies applied to control highly pathogenic H5N1 influenza in poultry. Preliminary results suggest that strategies applied to poultry, such as vaccination and culling, should be significantly more efficient than strategies applied to humans, such as wearing protective gear, in reducing the prevalence of H5N1 among humans. Further efforts are made to understand the interplay of vaccination of poultry and culling as the two primary control measures applied today, in order to provide quantitative insight into alternative potential measures of disease control.This project produces models of highly pathogenic avian influenza (bird flu, caused by an H5N1 influenza virus) that are well-grounded in the complex biology of the virus and validated with available data. Such models are required both to understand the basic disease dynamics, and to develop and implement effective control measures. The models are designed to fit available data on the cumulative number of human H5N1 cases and to be able to perform reasonable projections of future cases. Furthermore, the threat of a world-wide human epidemic (pandemic) caused by H5N1 requires strict control measures for the virus. These control measures (especially culling, the killing of all birds in a poultry operation when H5N1 infection is detected) cause significant economic losses in the poultry industry in many parts of the world. The models and methods developed as a part of this project evaluate the effectiveness of alternative control measures in reducing the number of H5N1 human cases. Analysis of these mathematical models expands our ability to choose the best control measures. In addition, the project studies the emergence of highly pathogenic strains from low pathogenic strains and their circulation in wild birds and domestic birds. The evolution of highly pathogenic strains capable of infecting humans is a major pathway through which a pandemic strain can emerge. Understanding the circumstances that foster such evolution increases our preparedness in identifying and combating potential pandemic threats caused by avian influenza.