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 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 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

Comparisons between the lymphocyte subpopulation counts at different sampling sites.

<p>Lymphocyte subpopulation counts are shown for all comparisons with P<.10 for both the relative and absolute cell counts. The univariate T/W method shows the P value for the two-sided paired t-test ‘T’ (‘Ln’ when a natural logarithm was applied) or Wilcoxon paired-matched signed rank (‘W’) in case normality didn’t hold. The Bonferroni and Benjamini columns show the adjusted significance levels according to the method applied. Sensitivity for outliers was performed for the relative cell counts. The mixed column shows all comparisons with P<.10 assessed as contrasts within a multivariate analysis for the relative counts for the lymphocyte subpopulations using SAS 9.2. The mixed joint column shows the multivariate P value. See Materials & Methods for more information.</p><p>Results annotated with ‘*’ are considered significant for the method applied. <i>Sites</i> comparison between sampling sites; <i>ARD</i> average relative difference; <i>PLT</i> platelets; <i>NGC</i> neutrophils; <i>WBC</i> white blood cells; <i>RBC</i> red blood cells; <i>HCT</i> hematocrit; <i>RD</i> radial artery vs. dorsal hand veins; <i>RE</i> radial artery vs. antecubital veins; <i>DE</i> dorsal hand veins vs. antecubital veins.</p>a<p>After omission of outliers the P value from the paired t-test was 0.093 with ARD 6.7%. The multivariate analysis showed a P value of 0.014.</p>b<p>After omission of outliers the P value from the paired t-test was 0.11 with ARD 3.3%. The multivariate analysis showed a P value of 0.042.</p

Comparisons between the hematocytological counts at different sampling sites.

<p>Hematocytological counts are shown for all comparisons with P<.10 for both the raw and normalized cell counts. The univariate T/W method shows the P value for the two-sided paired t-test ‘T’ (‘Ln’ when a natural logarithm was applied) or Wilcoxon paired-matched signed rank (‘W’) in case normality didn’t hold. The Bonferroni and Benjamini columns show the adjusted significance levels according to the method applied. Sensitivity for outliers was investigated for the raw cell counts. See Materials & Methods for more information.</p><p>Results annotated with ‘*’ are considered significant for the method applied. <i>Sites</i> comparison between sampling sites; <i>ARD</i> average relative difference; <i>PLT</i> platelets; <i>MON</i> monocytes; <i>BAS</i> basophils; <i>NGC</i> neutrophils; <i>LEU</i> leukocytes; <i>RBC</i> red blood cells; <i>HCT</i> hematocrit; <i>RD</i> radial artery vs. dorsal hand veins; <i>RE</i> radial artery vs. antecubital veins; <i>DE</i> dorsal hand veins vs. antecubital veins; <i>NA</i> not applicable.</p>a<p>After omission of outliers the ARD for RE reduced to 3.4% and for DE to 3.7% with significances similar to before.</p

CD80 expression on the surface of circulating monocytes, myeloid and plasmacytoid DCs.

<p>The different subpopulations were gated as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010407#s2" target="_blank">Material and Methods</a> section. Expression was compared in samples from the different age groups: Cord blood (CB, n = 10), 3-month (3 m, n = 10), 6 and 9-month (6–9 m, pooled data from n = 4 and 8, respectively), 12-month (12 m, n = 9) old infants and healthy adults (n = 16). Data are represented as median+interquartile range. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001.</p

Comparisons between the lymphocyte subpopulation median fluorescence intensities of the skin homing marker CLA at different sampling sites.

<p>Lymphocyte subpopulations with comparisons between sampling sites for the CLA median fluorescence intensities with P<.10 are shown for the raw data and in addition for the data after omission of outliers. Comparisons with P>.10 after omission of outliers and with P<.10 for the raw data are also shown. The univariate T/W method shows the P value for the two-sided paired t-test ‘T’ (‘Ln’ when a natural logarithm was applied) or Wilcoxon paired-matched signed rank (‘W’) in case normality didn’t hold. The Bonferroni and Benjamini columns show the adjusted significance levels according to the method applied See Materials & Methods for more information.</p><p>Results annotated with ‘*’ are considered significant for the method applied. <i>Sites</i> comparison between sampling sites; <i>ARD</i> average relative difference; <i>RD</i> radial artery vs. dorsal hand veins; <i>RE</i> radial artery vs. antecubital veins; <i>DE</i> dorsal hand veins vs. antecubital veins; <i>NO</i> no outliers.</p

HLA DR expression on the surface of circulating monocytes, myeloid and plasmacytoid DCs.

<p>Blood samples were incubated with PBS or the indicated stimulant. The different subpopulations were gated as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010407#s2" target="_blank">Material and Methods</a> section. Expression was compared in samples from the different age groups: Cord blood (CB, n = 10), 3-month (3 m, n = 10), 6&9-month (6–9 m pooled data from n = 4 and 8, respectively), 12-month (12 m, n = 9) old infants and healthy adults (n = 16). Data are represented as median+interquartile range. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 as compared to stimulated adult samples.</p