Understanding the within-host dynamics of influenza A virus: from theory to clinical implications

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Title: Understanding the within-host dynamics of influenza A virus: from theory to clinical implications
Authors: Hadjichrysanthou, C
Cauët, E
Lawrence, E
Vegvari, C
De Wolf, F
Anderson, RM
Item Type: Journal Article
Abstract: Mathematical models have provided important insights into acute viral dynamics within individual patients. In this paper, we study the simplest target cell-limited models to investigate the within-host dynamics of influenza A virus infection in humans. Despite the biological simplicity of the models, we show how these can be used to understand the severity of the infection and the key attributes of possible immunotherapy and antiviral drugs for the treatment of infection at different times post infection. Through an analytic approach, we derive and estimate simple summary biological quantities that can provide novel insights into the infection dynamics and the definition of clinical endpoints. We focus on nine quantities, including the area under the viral load curve, peak viral load, the time to peak viral load and the level of cell death due to infection. Using Markov chain Monte Carlo methods, we fitted the models to data collected from 12 untreated volunteers who participated in two clinical studies that tested the antiviral drugs oseltamivir and zanamivir. Based on the results, we also discuss various difficulties in deriving precise estimates of the parameters, even in the very simple models considered, when experimental data are limited to viral load measures and/or there is a limited number of viral load measurements post infection.
Issue Date: 8-Jun-2016
Date of Acceptance: 16-May-2016
ISSN: 1742-5689
Publisher: The Royal Society
Journal / Book Title: Journal of the Royal Society Interface
Volume: 13
Issue: 119
Copyright Statement: © 2016 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License, which permits unrestricted use, provided the original author and source are credited.
Keywords: acute viral infection
immune control
influenza A
viral kinetics
within-host modelling
General Science & Technology
MD Multidisciplinary
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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