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
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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  1. Benson Ogunjimi
  2. Lander Willem
  3. Philippe Beutels
  4. Niel Hens
(2015)
Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster
eLife 4:e07116.
https://doi.org/10.7554/eLife.07116