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      Generalizations of the ‘Linear Chain Trick’: incorporating more flexible dwell time distributions into mean field ODE models

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          Abstract

          In this paper we generalize the Linear Chain Trick (LCT; aka the Gamma Chain Trick) to help provide modelers more flexibility to incorporate appropriate dwell time assumptions into mean field ODEs, and help clarify connections between individual-level stochastic model assumptions and the structure of corresponding mean field ODEs. The LCT is a technique used to construct mean field ODE models from continuous-time stochastic state transition models where the time an individual spends in a given state (i.e., the dwell time) is Erlang distributed (i.e., gamma distributed with integer shape parameter). Despite the LCT’s widespread use, we lack general theory to facilitate the easy application of this technique, especially for complex models. Modelers must therefore choose between constructing ODE models using heuristics with oversimplified dwell time assumptions, using time consuming derivations from first principles, or to instead use non-ODE models (like integro-differential or delay differential equations) which can be cumbersome to derive and analyze. Here, we provide analytical results that enable modelers to more efficiently construct ODE models using the LCT or related extensions. Specifically, we provide (1) novel LCT extensions for various scenarios found in applications, including conditional dwell time distributions; (2) formulations of these LCT extensions that bypass the need to derive ODEs from integral equations; and (3) a novel Generalized Linear Chain Trick (GLCT) framework that extends the LCT to a much broader set of possible dwell time distribution assumptions, including the flexible phase-type distributions which can approximate distributions on \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt}

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          and can be fit to data.

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            Realistic distributions of infectious periods in epidemic models: changing patterns of persistence and dynamics.

            Most mathematical models used to study the epidemiology of childhood viral diseases, such as measles, describe the period of infectiousness by an exponential distribution. The effects of including more realistic descriptions of the infectious period within SIR (susceptible/infectious/recovered) models are studied. Less dispersed distributions are seen to have two important epidemiological consequences. First, less stable behaviour is seen within the model: incidence patterns become more complex. Second, disease persistence is diminished: in models with a finite population, the minimum population size needed to allow disease persistence increases. The assumption made concerning the infectious period distribution is of a kind routinely made in the formulation of mathematical models in population biology. Since it has a major effect on the central issues of population persistence and dynamics, the results of this study have broad implications for mathematical modellers of a wide range of biological systems. Copyright 2001 Academic Press.
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              Generality of the Final Size Formula for an Epidemic of a Newly Invading Infectious Disease

              The well-known formula for the final size of an epidemic was published by Kermack and McKendrick in 1927. Their analysis was based on a simple susceptible-infected-recovered (SIR) model that assumes exponentially distributed infectious periods. More recent analyses have established that the standard final size formula is valid regardless of the distribution of infectious periods, but that it fails to be correct in the presence of certain kinds of heterogeneous mixing (e.g., if there is a core group, as for sexually transmitted diseases). We review previous work and establish more general conditions under which Kermack and McKendrick's formula is valid. We show that the final size formula is unchanged if there is a latent stage, any number of distinct infectious stages and/or a stage during which infectives are isolated (the durations of each stage can be drawn from any integrable distribution). We also consider the possibility that the transmission rates of infectious individuals are arbitrarily distributed—allowing, in particular, for the existence of super-spreaders—and prove that this potential complexity has no impact on the final size formula. Finally, we show that the final size formula is unchanged even for a general class of spatial contact structures. We conclude that whenever a new respiratory pathogen emerges, an estimate of the expected magnitude of the epidemic can be made as soon the basic reproduction number ℝ0 can be approximated, and this estimate is likely to be improved only by more accurate estimates of ℝ0, not by knowledge of any other epidemiological details.
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                Author and article information

                Contributors
                +775-784-4655 , phurtado@unr.edu
                Journal
                J Math Biol
                J Math Biol
                Journal of Mathematical Biology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0303-6812
                1432-1416
                13 August 2019
                13 August 2019
                2019
                : 79
                : 5
                : 1831-1883
                Affiliations
                [1 ]GRID grid.266818.3, ISNI 0000 0004 1936 914X, University of Nevada, Reno, ; Reno, USA
                [2 ]GRID grid.168010.e, ISNI 0000000419368956, Stanford University, ; Stanford, USA
                Author information
                http://orcid.org/0000-0002-8499-5986
                http://orcid.org/0000-0003-0500-9269
                Article
                1412
                10.1007/s00285-019-01412-w
                6800873
                31410551
                09f510c4-e308-40ed-8597-e7dab8fc2a0d
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 22 August 2018
                : 10 June 2019
                Funding
                Funded by: Sloan Scholars Mentoring Network of the Social Science Research Council with funds provided by the Alfred P. Sloan Foundation
                Categories
                Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Quantitative & Systems biology
                gamma chain trick,linear chain trick,distributed delay,mean field model,phase-type distributions,time lag,37n25,92b05,92d25,92d30,92d40,45d05,60j28

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