Description of selected prospective longitudinal studies on VZV-immunity post exposure and other selected studies.

<p><i>RE</i> re-exposed; <i>CP</i> chickenpox; <i>CO</i> controls; <i>VZV</i> varicella-zoster virus; <i>RIA</i> radioimmunoassay; <i>PBMC</i> peripheral blood mononuclear cells; <i>TT</i> tetanus toxine; <i>PHA</i> phytohemagglutin; <i>IFN</i> interferon; <i>Cpm</i> counts per minute; <i>FAMA</i> fluorescent antibody to membrane antigen; <i>FCM</i> flow cytometry; <i>ICS</i> intracellular cytokine staining; <i>ELISPOT</i> enzyme-linked immunosorbent spot; <i>GMR</i> geometric mean response; <i>ELISA</i> enzyme-linked immunosorbent assay; <i>RCF</i> responder cell frequency; <i>HCW</i> health-care workers.</p>*<p>H = High: the quality of methods used in this paper permits the results, within the scope of the study design, to be interpreted with at the most a few remarks. M = Medium: the quality of methods used in this paper permits the results, within the scope of the study design, to be interpreted, but with some caution. L = Low: the quality of methods used in this paper urges the reader to interpret the results, even within the scope of the study design, with sufficient caution.</p><p>£See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066485#pone.0066485.s002" target="_blank">Table S2</a>.</p>**<p>The ‘B’ statement expresses whether the study supported the existence of exogenous boosting (‘+) or not (‘−’).</p

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review

<div><p>Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field.</p></div

Description of selected observational studies on HZ incidence in populations with a widespread chickenpox vaccination program.

<p><i>HMO</i> health maintenance organization; <i>HZ</i> herpes zoster; <i>CP</i> chickenpox; <i>RR</i> relative risk; <i>PY</i> person-years; <i>MMDS</i> Melbourne Medical Deputising Service; <i>ER</i> emergency room.</p>§<p>Descriptions of vaccination uptake are as reported in the respective original papers.</p>*<p>H = High: the quality of methods used in this paper permits the results, within the scope of the study design, to be interpreted with at the most a few remarks. M = Medium: the quality of methods used in this paper permits the results, within the scope of the study design, to be interpreted, but with some caution. L = Low: the quality of methods used in this paper urges the reader to interpret the results, even within the scope of the study design, with sufficient caution.</p><p>£See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066485#pone.0066485.s002" target="_blank">Table S2</a>.</p>**<p>The ‘B’ statement expresses whether the study supported the existence of exogenous boosting (‘+) or not (‘−’).</p

Description of selected mathematical modeling studies.

<p><i>S</i> susceptibles compartment; force of infection; reactivation rate; <i>HZ</i> herpes zoster; <i>PDE</i> partial differential equations; <i>WAIFW</i> who-acquires-infection-from-whom; <i>CP</i> chickenpox; <i>R</i> CP recovered compartment; <i>S_boost</i> susceptible to boosting compartment; <i>ODE</i> ordinary differential equations.</p>*<p>H = High: the quality of methods used in this paper permits the results, within the scope of the study design, to be interpreted with at the most a few remarks. M = Medium: the quality of methods used in this paper permits the results, within the scope of the study design, to be interpreted, but with some caution. L = Low: the quality of methods used in this paper urges the reader to interpret the results, even within the scope of the study design, with sufficient caution.</p><p>£See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066485#pone.0066485.s002" target="_blank">Table S2</a>.</p>**<p>The ‘B’ statement expresses whether the study supported the existence of exogenous boosting (‘+) or not (‘−’).</p

Description of selected epidemiological risk factor studies.

<p><i>VZV</i> varicella-zoster virus; <i>HZ</i> herpes zoster; <i>CP</i> chickenpox; <i>HH</i> household; <i>OR</i> odds ratio; <i>aOR</i> adjusted odds ratio; <i>NS</i> not significant; <i>PY</i> person-years.</p>*<p>H = High: the quality of methods used in this paper permits the results, within the scope of the study design, to be interpreted with at the most a few remarks. M = Medium: the quality of methods used in this paper permits the results, within the scope of the study design, to be interpreted, but with some caution. L = Low: the quality of methods used in this paper urges the reader to interpret the results, even within the scope of the study design, with sufficient caution.</p><p>£See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066485#pone.0066485.s002" target="_blank">Table S2</a>.</p>**<p>The ‘B’ statement expresses whether the study supported the existence of exogenous boosting (‘+) or not (‘−’).</p

Predicted proportion of seropositive patients according to time post vaccination from the plasma-cell driven kinetics model (full blue line: Havrix™ 1440 dataset , dashed green line: Havrix™ 720 dataset).

<p>Predicted proportion of seropositive patients according to time post vaccination from the plasma-cell driven kinetics model (full blue line: Havrix™ 1440 dataset , dashed green line: Havrix™ 720 dataset).</p

Parameter estimates according to the modeling assumptions: complete, asymptotic or plasma-cell driven kinetics (PCDK) model (95% confidence intervals determined using bootstrap percentile intervals).

<p>Parameter estimates according to the modeling assumptions: complete, asymptotic or plasma-cell driven kinetics (PCDK) model (95% confidence intervals determined using bootstrap percentile intervals).</p

Parameter estimates using power-law model (95% confidence intervals determined using bootstrap percentile intervals).

<p>Parameter estimates using power-law model (95% confidence intervals determined using bootstrap percentile intervals).</p

Individual prediction plots with a focus around the positivity threshold (20 mIU/ml, black line).

<p>(a,c,b) Havrix™ 1440 dataset, (d,e,f) Havrix™ 720 dataset; (a,d) complete model, (b,e) plasma-cell driven kinetics model, (c,f) asymptotic model.</p

Observations <i>Vs</i>. model predictions (left) and residuals Vs Time (right) plots using individual parameters (Havrix™ 720 dataset, Asymptotic model, log₁₀ scale).

<p>Observations <i>Vs</i>. model predictions (left) and residuals Vs Time (right) plots using individual parameters (Havrix™ 720 dataset, Asymptotic model, log₁₀ scale).</p