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Assessing mathematical models of influenza infections using features of the immune response.

Dobrovolny HM, Reddy MB, Kamal MA, Rayner CR, Beauchemin CA - PLoS ONE (2013)

Bottom Line: Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions.We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed.Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, Texas, USA.

ABSTRACT
The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

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Duration of viral shedding in immunocompromised patients.(Left) The reported duration of viral shedding for individual immunocompromised patients infected with influenza as chronicled in the literature is indicated by bar length. Infection outcome is indicated (died or recovered) when known, or labelled as unreported with ‘?’. (Right) Viral titer time courses of immunocompromised patients infected with influenza. Since all patients were treated with various courses of antivirals and given the prolonged shedding in these patients, recovery is most likely due to the eventual success of antiviral therapy rather than to clearance of the infection by the limited host immune response.
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pone-0057088-g001: Duration of viral shedding in immunocompromised patients.(Left) The reported duration of viral shedding for individual immunocompromised patients infected with influenza as chronicled in the literature is indicated by bar length. Infection outcome is indicated (died or recovered) when known, or labelled as unreported with ‘?’. (Right) Viral titer time courses of immunocompromised patients infected with influenza. Since all patients were treated with various courses of antivirals and given the prolonged shedding in these patients, recovery is most likely due to the eventual success of antiviral therapy rather than to clearance of the infection by the limited host immune response.

Mentions: The infection of immunocompromised individuals provides a window into the course of the infection when the immune response is severely attenuated. In many reported cases of immunocompromised patients with influenza, virus was shed for long periods of time, i.e., in some cases more than a year [43]–[60], (Fig. 1). Underlying medical conditions, the influenza viral strain, and antivirals used to treat immunocompromised patients are given in Table 1.


Assessing mathematical models of influenza infections using features of the immune response.

Dobrovolny HM, Reddy MB, Kamal MA, Rayner CR, Beauchemin CA - PLoS ONE (2013)

Duration of viral shedding in immunocompromised patients.(Left) The reported duration of viral shedding for individual immunocompromised patients infected with influenza as chronicled in the literature is indicated by bar length. Infection outcome is indicated (died or recovered) when known, or labelled as unreported with ‘?’. (Right) Viral titer time courses of immunocompromised patients infected with influenza. Since all patients were treated with various courses of antivirals and given the prolonged shedding in these patients, recovery is most likely due to the eventual success of antiviral therapy rather than to clearance of the infection by the limited host immune response.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585335&req=5

pone-0057088-g001: Duration of viral shedding in immunocompromised patients.(Left) The reported duration of viral shedding for individual immunocompromised patients infected with influenza as chronicled in the literature is indicated by bar length. Infection outcome is indicated (died or recovered) when known, or labelled as unreported with ‘?’. (Right) Viral titer time courses of immunocompromised patients infected with influenza. Since all patients were treated with various courses of antivirals and given the prolonged shedding in these patients, recovery is most likely due to the eventual success of antiviral therapy rather than to clearance of the infection by the limited host immune response.
Mentions: The infection of immunocompromised individuals provides a window into the course of the infection when the immune response is severely attenuated. In many reported cases of immunocompromised patients with influenza, virus was shed for long periods of time, i.e., in some cases more than a year [43]–[60], (Fig. 1). Underlying medical conditions, the influenza viral strain, and antivirals used to treat immunocompromised patients are given in Table 1.

Bottom Line: Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions.We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed.Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, Texas, USA.

ABSTRACT
The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

Show MeSH
Related in: MedlinePlus