on state-space reduction in multi-strain pathogen models, with an application to antigenic drift in influenza a一系列病原体模型中状态空间减少,一个应用程序在甲型流感抗原漂移.pdfVIP

On State-Space Reduction in Multi-Strain Pathogen Models, with an Application to Antigenic Drift in Influenza A 1* 2 3 3,4 Sergey Kryazhimskiy , Ulf Dieckmann , Simon A. Levin , Jonathan Dushoff 1 Program in Applied and Computational Mathematics, Princeton University, Princeton, New Jersey, United States of America, 2 Evolution and Ecology Program, International Institute for Applied Systems Analysis, Laxenburg, Austria, 3 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America, 4 Fogarty International Center, National Institute of Health, Bethesda, Maryland, United States of America Many pathogens exist in phenotypically distinct strains that interact with each other through competition for hosts. General models that describe such multi-strain systems are extremely difficult to analyze because their state spaces are enormously large. Reduced models have been proposed, but so far all of them necessarily allow for coinfections and require that immunity be mediated solely by reduced infectivity, a potentially problematic assumption. Here, we suggest a new state-space reduction approach that allows immunity to be mediated by either reduced infectivity or reduced susceptibility and that can naturally be used for models with or without coinfections. Our approach utilizes the general framework of status-based models. The cornerstone of our method is the introduction of immunity variables, which describe multi-strain systems more naturally than the traditional tracking of susceptible and infected hosts. Models expressed in this way can be approximated in a natural way by a truncation method that is akin to moment closure, allowing us to sharply reduce the size of the state space, and thus to consider models with many strains in a tractable manner. Applying o