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A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis

In a novel approach, the standard birth–death process is extended to incorporate a fundamental mechanism undergone by intracellular bacteria, phagocytosis. The model accounts for stochastic interaction between bacteria and cells of the immune system and heterogeneity in susceptibility to infection o...

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Detalles Bibliográficos
Autores principales: Wood, R. M., Egan, J. R., Hall, I. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006251/
https://www.ncbi.nlm.nih.gov/pubmed/24671937
http://dx.doi.org/10.1098/rsif.2014.0119
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author Wood, R. M.
Egan, J. R.
Hall, I. M.
author_facet Wood, R. M.
Egan, J. R.
Hall, I. M.
author_sort Wood, R. M.
collection PubMed
description In a novel approach, the standard birth–death process is extended to incorporate a fundamental mechanism undergone by intracellular bacteria, phagocytosis. The model accounts for stochastic interaction between bacteria and cells of the immune system and heterogeneity in susceptibility to infection of individual hosts within a population. Model output is the dose–response relation and the dose-dependent distribution of time until response, where response is the onset of symptoms. The model is thereafter parametrized with respect to the highly virulent Schu S4 strain of Francisella tularensis, in the first such study to consider a biologically plausible mathematical model for early human infection with this bacterium. Results indicate a median infectious dose of about 23 organisms, which is higher than previously thought, and an average incubation period of between 3 and 7 days depending on dose. The distribution of incubation periods is right-skewed up to about 100 organisms and symmetric for larger doses. Moreover, there are some interesting parallels to the hypotheses of some of the classical dose–response models, such as independent action (single-hit model) and individual effective dose (probit model). The findings of this study support experimental evidence and postulations from other investigations that response is, in fact, influenced by both in-host and between-host variability.
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spelling pubmed-40062512014-06-06 A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis Wood, R. M. Egan, J. R. Hall, I. M. J R Soc Interface Research Articles In a novel approach, the standard birth–death process is extended to incorporate a fundamental mechanism undergone by intracellular bacteria, phagocytosis. The model accounts for stochastic interaction between bacteria and cells of the immune system and heterogeneity in susceptibility to infection of individual hosts within a population. Model output is the dose–response relation and the dose-dependent distribution of time until response, where response is the onset of symptoms. The model is thereafter parametrized with respect to the highly virulent Schu S4 strain of Francisella tularensis, in the first such study to consider a biologically plausible mathematical model for early human infection with this bacterium. Results indicate a median infectious dose of about 23 organisms, which is higher than previously thought, and an average incubation period of between 3 and 7 days depending on dose. The distribution of incubation periods is right-skewed up to about 100 organisms and symmetric for larger doses. Moreover, there are some interesting parallels to the hypotheses of some of the classical dose–response models, such as independent action (single-hit model) and individual effective dose (probit model). The findings of this study support experimental evidence and postulations from other investigations that response is, in fact, influenced by both in-host and between-host variability. The Royal Society 2014-06-06 /pmc/articles/PMC4006251/ /pubmed/24671937 http://dx.doi.org/10.1098/rsif.2014.0119 Text en http://creativecommons.org/licenses/by/3.0/ © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research Articles
Wood, R. M.
Egan, J. R.
Hall, I. M.
A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis
title A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis
title_full A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis
title_fullStr A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis
title_full_unstemmed A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis
title_short A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis
title_sort dose and time response markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to francisella tularensis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006251/
https://www.ncbi.nlm.nih.gov/pubmed/24671937
http://dx.doi.org/10.1098/rsif.2014.0119
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