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Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster.

Ogunjimi B, Willem L, Beutels P, Hens N - Elife (2015)

Bottom Line: A reduction in exogenous re-exposure 'opportunities' through universal chickenpox vaccination could therefore lead to an increase in HZ incidence.This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI.A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation.

View Article: PubMed Central - PubMed

Affiliation: Centre for Health Economics Research and Modeling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.

ABSTRACT
Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure 'opportunities' through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed.

No MeSH data available.


Related in: MedlinePlus

Observed (open circles) Belgian HZ incidence data by age and simulated HZ incidence data (continuous lines) for the 13 best parameter sets with a sensitivity analysis for the HZ infectiousness parameter (values: 0.03, 0.10, 0.17, 0.24, 0.31, 0.38 and 0.45) and three runs per parameter set.DOI:http://dx.doi.org/10.7554/eLife.07116.007
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fig2s1: Observed (open circles) Belgian HZ incidence data by age and simulated HZ incidence data (continuous lines) for the 13 best parameter sets with a sensitivity analysis for the HZ infectiousness parameter (values: 0.03, 0.10, 0.17, 0.24, 0.31, 0.38 and 0.45) and three runs per parameter set.DOI:http://dx.doi.org/10.7554/eLife.07116.007

Mentions: The FoR defines the VZV-CMI needed to resist clinical reactivation and if VZV-CMI < FoR, reactivation will lead to HZ. The reader should imagine the FoR to represent independent reactivation behavior of VZV and whether this reactivation will lead to HZ or endogenous boosting will depend on the value of VZV-CMI. The FoR deviates per time step and individual by means of a gamma probability density function. This gamma function is chosen as it represents the summation of unknown biological phenomena that are assumed to have an exponential distribution. The parameter set includes four different gamma distributions (see Table 2 and Figure 9). HZ individuals are assumed to be infectious for 1 week and receive a VZV-CMI reset to 1 ± random factor (normally distributed, cf. primary infection). There exists no data on the relative infectiousness of HZ patients nor is it likely that this can be estimated through experiments. We chose to approximate the relative infectiousness of HZ patients by the relative infectiousness of breakthrough CP patients (Bernstein et al., 1993). This has previously been estimated at 0.17 (Brisson et al., 2002). Although HZ infectiousness was needed to maintain circulation of VZV in our model, the relative effects on overall VZV transmission are—compared to CP—marginal. Figure 2—figure supplement 1 shows the results of a sensitivity analysis in which we varied HZ infectiousness from 0.03 to 0.45 for the 13 best fitting parameter. As can be seen in Figure 2—figure supplement 1 our results are quite robust. Reinstallation of VZV-specific immunity after HZ is based on experimental data showing that a second case of HZ only occurs in about 5% of individuals (Yawn et al., 2011) and that VZV-CMI is higher in recovered HZ patients than in age-matched controls (Weinberg et al., 2009).10.7554/eLife.07116.015Figure 9.Different cumulative distribution functions (CDF) for Force of Reactivation (FoR).


Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster.

Ogunjimi B, Willem L, Beutels P, Hens N - Elife (2015)

Observed (open circles) Belgian HZ incidence data by age and simulated HZ incidence data (continuous lines) for the 13 best parameter sets with a sensitivity analysis for the HZ infectiousness parameter (values: 0.03, 0.10, 0.17, 0.24, 0.31, 0.38 and 0.45) and three runs per parameter set.DOI:http://dx.doi.org/10.7554/eLife.07116.007
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4530225&req=5

fig2s1: Observed (open circles) Belgian HZ incidence data by age and simulated HZ incidence data (continuous lines) for the 13 best parameter sets with a sensitivity analysis for the HZ infectiousness parameter (values: 0.03, 0.10, 0.17, 0.24, 0.31, 0.38 and 0.45) and three runs per parameter set.DOI:http://dx.doi.org/10.7554/eLife.07116.007
Mentions: The FoR defines the VZV-CMI needed to resist clinical reactivation and if VZV-CMI < FoR, reactivation will lead to HZ. The reader should imagine the FoR to represent independent reactivation behavior of VZV and whether this reactivation will lead to HZ or endogenous boosting will depend on the value of VZV-CMI. The FoR deviates per time step and individual by means of a gamma probability density function. This gamma function is chosen as it represents the summation of unknown biological phenomena that are assumed to have an exponential distribution. The parameter set includes four different gamma distributions (see Table 2 and Figure 9). HZ individuals are assumed to be infectious for 1 week and receive a VZV-CMI reset to 1 ± random factor (normally distributed, cf. primary infection). There exists no data on the relative infectiousness of HZ patients nor is it likely that this can be estimated through experiments. We chose to approximate the relative infectiousness of HZ patients by the relative infectiousness of breakthrough CP patients (Bernstein et al., 1993). This has previously been estimated at 0.17 (Brisson et al., 2002). Although HZ infectiousness was needed to maintain circulation of VZV in our model, the relative effects on overall VZV transmission are—compared to CP—marginal. Figure 2—figure supplement 1 shows the results of a sensitivity analysis in which we varied HZ infectiousness from 0.03 to 0.45 for the 13 best fitting parameter. As can be seen in Figure 2—figure supplement 1 our results are quite robust. Reinstallation of VZV-specific immunity after HZ is based on experimental data showing that a second case of HZ only occurs in about 5% of individuals (Yawn et al., 2011) and that VZV-CMI is higher in recovered HZ patients than in age-matched controls (Weinberg et al., 2009).10.7554/eLife.07116.015Figure 9.Different cumulative distribution functions (CDF) for Force of Reactivation (FoR).

Bottom Line: A reduction in exogenous re-exposure 'opportunities' through universal chickenpox vaccination could therefore lead to an increase in HZ incidence.This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI.A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation.

View Article: PubMed Central - PubMed

Affiliation: Centre for Health Economics Research and Modeling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.

ABSTRACT
Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure 'opportunities' through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed.

No MeSH data available.


Related in: MedlinePlus