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Virulence attenuation during an influenza A/H5N1 pandemic.

Boni MF, Nguyen TD, de Jong MD, van Doorn HR - Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2013)

Bottom Line: Evolutionary theory dictates that pathogens should evolve to be relatively benign, depending on the magnitude of the correlation between a pathogen's virulence and its transmissibility.Because the case fatality of H5N1 infections in humans is currently 60 per cent, it is doubtful that the current viruses are close to their evolutionary optimum for transmission among humans.We discuss two main epidemiological-evolutionary features of this system (i) the delaying or slowing of an epidemic which results in a majority of hosts experiencing an attenuated virulence phenotype and (ii) the strong evolutionary pressure for lower virulence experienced by the virus during a period of intense social distancing.

View Article: PubMed Central - PubMed

Affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam. mboni@oucru.org

ABSTRACT
More than 15 years after the first human cases of influenza A/H5N1 in Hong Kong, the world remains at risk for an H5N1 pandemic. Preparedness activities have focused on antiviral stockpiling and distribution, development of a human H5N1 vaccine, operationalizing screening and social distancing policies, and other non-pharmaceutical interventions. The planning of these interventions has been done in an attempt to lessen the cumulative mortality resulting from a hypothetical H5N1 pandemic. In this theoretical study, we consider the natural limitations on an H5N1 pandemic's mortality imposed by the virus' epidemiological-evolutionary constraints. Evolutionary theory dictates that pathogens should evolve to be relatively benign, depending on the magnitude of the correlation between a pathogen's virulence and its transmissibility. Because the case fatality of H5N1 infections in humans is currently 60 per cent, it is doubtful that the current viruses are close to their evolutionary optimum for transmission among humans. To describe the dynamics of virulence evolution during an H5N1 pandemic, we build a mathematical model based on the patterns of clinical progression in past H5N1 cases. Using both a deterministic model and a stochastic individual-based simulation, we describe (i) the drivers of evolutionary dynamics during an H5N1 pandemic, (ii) the range of case fatalities for which H5N1 viruses can successfully cause outbreaks in humans, and (iii) the effects of different kinds of social distancing on virulence evolution. We discuss two main epidemiological-evolutionary features of this system (i) the delaying or slowing of an epidemic which results in a majority of hosts experiencing an attenuated virulence phenotype and (ii) the strong evolutionary pressure for lower virulence experienced by the virus during a period of intense social distancing.

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Class diagram for the model. Individuals can be susceptible (S), exposed (E), infectious (I), infectious with severe disease (V), isolated (Q) and hospitalized (H). Each infected individual is infected with a particular strain (j,k), which corresponds to a rate of progression and probability of recovery for that individual. Note the distinction between fractions and rates among the parameters.
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RSTB20120207F1: Class diagram for the model. Individuals can be susceptible (S), exposed (E), infectious (I), infectious with severe disease (V), isolated (Q) and hospitalized (H). Each infected individual is infected with a particular strain (j,k), which corresponds to a rate of progression and probability of recovery for that individual. Note the distinction between fractions and rates among the parameters.

Mentions: We begin with a compartmental, deterministic differential-equations model, based on a classic SEIR-model in a closed population with no influx of additional susceptible hosts from other populations. Our model has additional classes for symptomatic individuals that have been placed under isolation (Q), severely infected individuals (V) and hospitalized individuals (H). Hosts in class I are infected and infectious. The basic flow diagram is shown in figureĀ 1.Figure 1.


Virulence attenuation during an influenza A/H5N1 pandemic.

Boni MF, Nguyen TD, de Jong MD, van Doorn HR - Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2013)

Class diagram for the model. Individuals can be susceptible (S), exposed (E), infectious (I), infectious with severe disease (V), isolated (Q) and hospitalized (H). Each infected individual is infected with a particular strain (j,k), which corresponds to a rate of progression and probability of recovery for that individual. Note the distinction between fractions and rates among the parameters.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675429&req=5

RSTB20120207F1: Class diagram for the model. Individuals can be susceptible (S), exposed (E), infectious (I), infectious with severe disease (V), isolated (Q) and hospitalized (H). Each infected individual is infected with a particular strain (j,k), which corresponds to a rate of progression and probability of recovery for that individual. Note the distinction between fractions and rates among the parameters.
Mentions: We begin with a compartmental, deterministic differential-equations model, based on a classic SEIR-model in a closed population with no influx of additional susceptible hosts from other populations. Our model has additional classes for symptomatic individuals that have been placed under isolation (Q), severely infected individuals (V) and hospitalized individuals (H). Hosts in class I are infected and infectious. The basic flow diagram is shown in figureĀ 1.Figure 1.

Bottom Line: Evolutionary theory dictates that pathogens should evolve to be relatively benign, depending on the magnitude of the correlation between a pathogen's virulence and its transmissibility.Because the case fatality of H5N1 infections in humans is currently 60 per cent, it is doubtful that the current viruses are close to their evolutionary optimum for transmission among humans.We discuss two main epidemiological-evolutionary features of this system (i) the delaying or slowing of an epidemic which results in a majority of hosts experiencing an attenuated virulence phenotype and (ii) the strong evolutionary pressure for lower virulence experienced by the virus during a period of intense social distancing.

View Article: PubMed Central - PubMed

Affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam. mboni@oucru.org

ABSTRACT
More than 15 years after the first human cases of influenza A/H5N1 in Hong Kong, the world remains at risk for an H5N1 pandemic. Preparedness activities have focused on antiviral stockpiling and distribution, development of a human H5N1 vaccine, operationalizing screening and social distancing policies, and other non-pharmaceutical interventions. The planning of these interventions has been done in an attempt to lessen the cumulative mortality resulting from a hypothetical H5N1 pandemic. In this theoretical study, we consider the natural limitations on an H5N1 pandemic's mortality imposed by the virus' epidemiological-evolutionary constraints. Evolutionary theory dictates that pathogens should evolve to be relatively benign, depending on the magnitude of the correlation between a pathogen's virulence and its transmissibility. Because the case fatality of H5N1 infections in humans is currently 60 per cent, it is doubtful that the current viruses are close to their evolutionary optimum for transmission among humans. To describe the dynamics of virulence evolution during an H5N1 pandemic, we build a mathematical model based on the patterns of clinical progression in past H5N1 cases. Using both a deterministic model and a stochastic individual-based simulation, we describe (i) the drivers of evolutionary dynamics during an H5N1 pandemic, (ii) the range of case fatalities for which H5N1 viruses can successfully cause outbreaks in humans, and (iii) the effects of different kinds of social distancing on virulence evolution. We discuss two main epidemiological-evolutionary features of this system (i) the delaying or slowing of an epidemic which results in a majority of hosts experiencing an attenuated virulence phenotype and (ii) the strong evolutionary pressure for lower virulence experienced by the virus during a period of intense social distancing.

Show MeSH
Related in: MedlinePlus