1. Epidemiology and Global Health
  2. Microbiology and Infectious Disease
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Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster

  1. Benson Ogunjimi  Is a corresponding author
  2. Lander Willem
  3. Philippe Beutels
  4. Niel Hens
  1. University of Antwerp, Belgium
  2. Hasselt University, Belgium
  3. University of New South Wales, Australia
Research Article
Cite this article as: eLife 2015;4:e07116 doi: 10.7554/eLife.07116
9 figures and 3 tables

Figures

Observed (open circles) and simulated (continuous lines) Belgian herpes zoster (HZ) incidence data by age.
https://doi.org/10.7554/eLife.07116.004
Figure 1—source data 1

Observed Belgian HZ incidence per age group and per person-year.

https://doi.org/10.7554/eLife.07116.005
Figure 2 with 1 supplement
Observed (open circles) and simulated (continuous lines) Belgian HZ incidence data by age.
https://doi.org/10.7554/eLife.07116.006
Figure 2—figure supplement 1
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.
https://doi.org/10.7554/eLife.07116.007
Normalized varicella-zoster virus (VZV)-specific CMI averaged over 80 simulation years and over all individuals for the two best parameter sets.

Caption: note that this figure shows average dynamics although some individuals will have VZV-specific CMI values below 1 (making them susceptible to HZ).

https://doi.org/10.7554/eLife.07116.008
Predicted HZ incidence (aggregated for all ages) over time with a CP vaccine for 1 year olds using the best-fitting parameter sets.

The red line indicates the moment of CP vaccine introduction, which is assumed to be 100% effective.

https://doi.org/10.7554/eLife.07116.009
Time-evolution of the relative contribution to HZ incidence per age group before and after introduction of 100% effective varicella vaccination for 1 year olds.
https://doi.org/10.7554/eLife.07116.010
Simplified dynamics of VZV-CMI, VZV reactivation and boosting events as modeled.

The sequence of exogenous boosting and VZV reactivation can be switched.

https://doi.org/10.7554/eLife.07116.011
Three different boosting scenarios.

(A) Illustrates the exponential decline parameterized by a peak (+120%) at 6 weeks, (+60%) 1 year later, (50%) 2 years later and (+40%) 3 years later as presented by the Zostavax vaccine trial by Levin et al. (B) Illustrates the exponential decline from peak (+120%) to (+60%) 1 year later and constant for x years (as defined by the parameter set) after wards, as a modified interpretation of the results of the Zostavax vaccine trial by Levin et al. (C) Illustrates the increase to a peak value as defined by the parameter set that is followed by an exponential decline so that the pre-boosting value is reached after x years.

https://doi.org/10.7554/eLife.07116.014
Different cumulative distribution functions (CDF) for Force of Reactivation (FoR).
https://doi.org/10.7554/eLife.07116.015

Tables

Table 1

Best fitting parameter sets

https://doi.org/10.7554/eLife.07116.003
Parameter setDeviance*Annual waning rate (%)Boosting scenarioDuration of boosting (years)Peak fold increase following exogenous boostingVZV weekly reactivation probability (%)Distribution threshold VZV-CMI for HZPeak fold increase following endogenous boosting
Original Search (obtained after Step 2 in Table 1)
 19262.03101.31.541
 29391.5331.31.541
 39492.0371.31.541
 49512.03121.31.541
 59682.0371.31.041
 69701.0321.31.041
 79692.03151.31.541
 89341.0312.55.041
Border search
 97511.0312.85.041
 107991.0313.15.041
 119651.5323.45.041
 128041.5323.75.041
 137221.5324.05.041
  1. *

    Results shown are averaged results per parameter set.

  2. VZV, varicella-zoster virus; HZ, herpes zoster.

Table 2

Initial parameter sets

https://doi.org/10.7554/eLife.07116.013
ParametersStep 1Step 2
Annual waning rate (%)2.00.5
3.01.0
4.01.5
2.0
2.5
Boosting scenario13
2
3
Duration of boosting (years)11
22
43
74
125
7
10
12
15
Peak fold increase following exogenous boosting11.3
1.61.6
2.21.9
2.2
2.5
VZV weekly reactivation probability (%)0.010.001
0.10.05
0.30.01
0.50.015
0.1
0.2
0.3
0.4
Distribution threshold VZV-CMI for HZ11
22
34
4
Peak fold increase following endogenous boosting11
1.41.2
1.8
2.2
Table 3

Step 2 parameter set selection

https://doi.org/10.7554/eLife.07116.016
ParametersBest parameter sets + deviance +5%Most prevalent parameters in Q2.5
Annual waning rate (%)2.02.0
Boosting scenario33
Duration of exogenous boosting (years)11
42
4
7
12
Peak fold increase following exogenous boosting1.61.6
2.2
VZV weekly reactivation probability (%)0.010.01
0.10.3
Distribution threshold VZV-CMI for HZ21
42
Peak fold increase following endogenous boosting11

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