Immunity to Varicella Zoster Virus in Healthcare Workers: A Systematic Review and Meta-Analysis (2024)

doi:10.3390/vaccines12091021

Review

. 2024 Sep 6;12(9):1021.

doi: 10.3390/vaccines12091021.

Immunity to Varicella Zoster Virus in Healthcare Workers: A Systematic Review and Meta-Analysis (2024)

Affiliations

¹ Servizio di Prevenzione e Sicurezza Negli Ambienti di Lavoro (SPSAL), AUSL-IRCCS di Reggio Emilia, Via Amendola n.2, 42122 Reggio Emilia, Italy.
² Occupational Medicine Unit, Direzione Sanità, Italian Railways' Infrastructure Division, RFI SpA, 00161 Rome, Italy.
³ Occupational Medicine Unit, Bambino Gesù Children's Hospital IRCCS, 00165 Rome, Italy.
⁴ Department of Medicine and Surgery, University of Parma, Via Gramsci, 14, 43126 Parma, Italy.
⁵ AST Ancona, Prevention Department, UOC Sorveglianza e Prevenzione Malattie Infettive e Cronico Degenerative, 60127 Ancona, Italy.
⁶ Post-Graduate School of Occupational Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
⁷ Department of Woman, Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
⁸ Department of Interdisciplinary Medicine, Aldo Moro University of Bari, 70121 Bari, Italy.

PMID: 39340051
PMCID: PMC11436139
DOI: 10.3390/vaccines12091021

Review

Immunity to Varicella Zoster Virus in Healthcare Workers: A Systematic Review and Meta-Analysis (2024)

Matteo Riccò et al. Vaccines (Basel). 2024.

. 2024 Sep 6;12(9):1021.

doi: 10.3390/vaccines12091021.

Authors

Affiliations

¹ Servizio di Prevenzione e Sicurezza Negli Ambienti di Lavoro (SPSAL), AUSL-IRCCS di Reggio Emilia, Via Amendola n.2, 42122 Reggio Emilia, Italy.
² Occupational Medicine Unit, Direzione Sanità, Italian Railways' Infrastructure Division, RFI SpA, 00161 Rome, Italy.
³ Occupational Medicine Unit, Bambino Gesù Children's Hospital IRCCS, 00165 Rome, Italy.
⁴ Department of Medicine and Surgery, University of Parma, Via Gramsci, 14, 43126 Parma, Italy.
⁵ AST Ancona, Prevention Department, UOC Sorveglianza e Prevenzione Malattie Infettive e Cronico Degenerative, 60127 Ancona, Italy.
⁶ Post-Graduate School of Occupational Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
⁷ Department of Woman, Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
⁸ Department of Interdisciplinary Medicine, Aldo Moro University of Bari, 70121 Bari, Italy.

PMID: 39340051
PMCID: PMC11436139
DOI: 10.3390/vaccines12091021

Abstract

Healthcare workers (HCWs) are occupationally exposed to varicella zoster virus (VZV), and their inappropriate vaccination status could contribute to an outbreak involving both professionals and the patients they care for, with a potential impact on the general population. Therefore, since 2007, the Advisory Committee on Immunization Practices (ACIP) recommends that all HCWs have evidence of immunity against varicella. The present meta-analysis was therefore designed to collect the available evidence on the seronegative status of VZV among HCWs. PubMed, Scopus, and Embase databases were searched without backward limit for articles reporting on the seroprevalence of VZV among HCWs, and all articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 1744 initial entries, a total of 58 articles were included in the quantitative analysis (publication range: 1988 to 2024), for a pooled sample of 71,720 HCWs. Moreover, the included studies reported on seroprevalence data on measles (N = 36,043 HCWs) and rubella (N = 22,086 HCWs). Eventually, the pooled seronegative status for VZV was estimated to be 5.72% (95% confidence interval [95% CI] 4.59 to 7.10) compared to 6.91% (95% CI 4.79 to 9.87) for measles and 7.21% (5.36 to 9.64) for rubella, with a greater risk among subjects younger than 30 years at the time of the survey (risk ratio [RR] 1.434, 95% CI 1.172 to 1.756). Interestingly, medical history of either VZV infection/vaccination had low diagnostic performances (sensitivity 76.00%; specificity 60.12%; PPV of 96.12% but PNV of 18.64%). In summary, the available data suggest that newly hired HCWs are increasingly affected by low immunization rates for VZV but also for measles and rubella, stressing the importance of systematically testing test newly hired workers for all components of the measles-pertussis-rubella-varicella vaccine.

Keywords: chickenpox; healthcare workers; shingles; varicella zoster; varicella zoster vaccine.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**Figure A1**
Correlation of seronegative status (i.e., naïve) for varicella zoster virus (VZV) plotted against the proportion of naïve healthcare workers for measles (Spearman’s rho = 0.479, 95% CI 0.133 to 0.721, p = 0.007) or rubella (Spearman’s rho = 0.192, 95% CI −0.241 to 0.561, p = 0.369) (a) and correlation between seronegative status for measles and rubella (Spearman’s rho = 0.326, 95% CI −0.112 to 0.658, p = 0.129) (b).

**Figure A2**
Forrest plot for prevalence of naïve status for varicella zoster virus (VZV) among sampled healthcare workers (pooled prevalence: 5.72%, 95% confidence interval [95% CI] 4.59 to 7.10; tau² 0.7376; tau 0.8589; I² 98.1% [97.8%; 98.3%]; H = 7.18 [6.77; 7.61]; Q 2939.67, p < 0.001) [46,55,58,61,62,63,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129].

**Figure A3**
Pooled prevalence of seronegative status (naïve) for varicella zoster virus (VZV) in healthcare workers (HCWs) aged less than 30 years at the time of the study. A pooled prevalence of 9.78% (95% CI 6.91 to 13.66) was calculated, with substantial heterogeneity (96%) [57,58,61,80,86,91,93,98,100,105,107,108,110,114,118,120,127,129].

**Figure A4**
Pooled prevalence of seronegative status (naïve) for varicella zoster virus (VZV) in healthcare workers (HCWs) aged 30 years or more at the time of the study. A pooled prevalence of 6.31% (95% CI 4.24 to 9.28) was calculated, with substantial heterogeneity (96%) [57,58,61,80,86,91,93,98,100,105,107,108,110,114,118,120,127,129].

**Figure A5**
Pooled prevalence of seronegative status (naïve) for varicella zoster virus (VZV) in healthcare workers (HCWs) of male gender. A pooled prevalence of 7.39% (95% CI 5.18 to 10.44) was calculated, with substantial heterogeneity (92%) [55,61,62,80,83,84,86,88,91,92,100,102,105,106,107,109,110,114,118,120,121,122,125,127].

**Figure A6**
Pooled prevalence of seronegative status (naïve) for varicella zoster virus (VZV) in healthcare workers (HCWs) of male gender. A pooled prevalence of 6.98% (95% CI 4.95 to 9.77) was calculated, with substantial heterogeneity (97%) [55,61,62,80,83,84,86,88,91,92,100,102,105,106,107,109,110,114,118,120,121,122,125,127].

**Figure A7**
Risk ratio (RR) for seronegative status (naïve) for varicella zoster virus (VZV) in healthcare workers (HCWs) aged less than 30 years vs. professionals aged 30 years or older. An RR of 1.434 (95% CI 1.172 to 1.755) was eventually calculated, with substantial heterogeneity (79.9% (68.9 to 86.9) [57,58,61,80,86,91,93,98,100,105,107,108,110,114,118,120,127,129].

**Figure A8**
Risk ratio (RR) for seronegative status (naïve) for varicella zoster virus (VZV) in healthcare workers (HCWs) of female gender vs. professionals of male gender. An RR of 0.946 (95% CI 0.788 to 1.136) was eventually calculated, with substantial heterogeneity (70.8% (55.8 to 80.7) [61,62,80,83,84,86,88,91,93,100,102,105,106,107,109,110,114,118,120,121,122,125].

**Figure A9**
Pooled prevalence of seronegative status (naïve) for measles in healthcare workers (HCWs). A pooled prevalence of 6.91% (95% CI 4.78 to 9.87) was calculated, with substantial heterogeneity (99%) [46,63,79,80,81,83,84,85,88,94,97,98,102,103,104,106,107,108,109,110,113,114,115,117,119,123,124,126,128,129].

**Figure A10**
Pooled prevalence of seronegative status (naïve) for rubella in healthcare workers (HCWs). A pooled prevalence of 7.21% (95% CI 5.36 to 9.64) was calculated, with substantial heterogeneity (96%) [46,63,80,81,83,84,85,88,97,102,103,104,106,108,109,113,114,115,117,118,123,124,126].

**Figure A11**
Pooled risk ratio (RR) for measles vs. varicella zoster virus (VZV) seronegative status (naïve) among sampled healthcare workers (HCWs). A pooled RR of 1.326 (95% CI 0.952 to 1.846) was calculated, with substantial heterogeneity (98%) [46,63,79,80,81,83,84,85,88,94,97,98,102,103,104,106,107,109,110,113,114,115,117,119,123,124,126,128,129].

**Figure A12**
Pooled risk ratio (RR) for rubella vs. varicella zoster virus (VZV) seronegative status (naïve) among sampled healthcare workers (HCWs). A pooled RR of 1.335 (95% CI 0.932 to 1.910) was calculated, with substantial heterogeneity (96%) [46,63,79,80,81,83,84,85,88,97,102,103,104,106,108,109,113,114,115,117,123,124,126].

**Figure A13**
Sensitivity of medical history regarding vaccination status for varicella zoster virus (VZV) as ascertained by laboratory analyses. TP = true positive; FN = false negative; Prev = prevalence; 95% CI = 95% confidence interval [55,57,85,89,90,95,96,99,100,105,106,107,110,113,114,116,117,119,120,121,122,124,125,126].

**Figure A14**
Specificity of medical history regarding vaccination status for varicella zoster virus (VZV) as ascertained by laboratory analyses. TN = true negative; FP = false positive; Prev = prevalence; 95% CI = 95% confidence interval [55,57,85,89,90,95,96,99,100,105,106,107,110,113,114,116,117,119,120,121,122,124,125,126].

**Figure A15**
Diagnostic odds ratio (DOR) of medical history regarding vaccination status for varicella zoster virus (VZV) as ascertained by laboratory analyses. TP = true positive; FN = false negatives; Prev = prevalence; 95% CI = 95% confidence interval [55,57,85,89,90,95,96,99,100,105,106,107,110,113,114,116,117,119,120,121,122,124,125,126].

**Figure A16**
Sensitivity analysis for the prevalence of varicella zoster virus (VZV) seronegative status in sampled healthcare workers. The analysis was performed through removing one study at time [46,55,58,61,62,63,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129].

**Figure A17**
Sensitivity analysis for the prevalence of measles seronegative status in sampled healthcare workers. The analysis was performed through removing one study at time [46,63,79,80,81,83,84,85,88,94,97,98,102,103,104,106,107,109,110,113,114,115,117,119,123,124,126,128,129].

**Figure A18**
Sensitivity analysis for the prevalence of rubella seronegative status in sampled healthcare workers. The analysis was performed through removing one study at time [46,63,79,80,81,83,84,85,88,97,102,103,104,106,108,109,113,114,115,117,123,124,126].

**Figure A19**
Sensitivity analysis for the sensitivity of medical story in recalling protection of healthcare workers against varicella zoster virus by previous vaccination and/or natural infection. The analysis was performed through removing one study at time [55,57,85,89,90,95,96,99,100,105,106,107,110,113,114,116,117,119,120,121,122,124,125,126].

**Figure A20**
Sensitivity analysis for the specificity of medical story in recalling protection of healthcare workers against varicella zoster virus by previous vaccination and/or natural infection. The analysis was performed through removing one study at time [55,57,85,89,90,95,96,99,100,105,106,107,110,113,114,116,117,119,120,121,122,124,125,126].

**Figure A21**
Sensitivity analysis for the diagnostic odds ratio (DOR = of medical story in recalling protection of healthcare workers against varicella zoster virus by previous vaccination and/or natural infection. The analysis was performed through removing one study at time [55,57,85,89,90,95,96,99,100,105,106,107,110,113,114,116,117,119,120,121,122,124,125,126].

**Figure A22**
Radial plots for the findings included in the meta-analysis: proportion of naïve (i.e., seronegative) healthcare workers for varicella zoster virus (a), measles (b), rubella (c), and for sensitivity (d) and specificity (e) estimates for medical history on the effective protection against VZV due to previous vaccination or infection [46,55,58,61,62,63,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129].

**Figure 1**
Flow chart of included studies [46,55,57,58,61,62,63,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129]. Notes: HCWs = healthcare workers; other reasons = reports in languages other than English, Italian, French, German, Spanish, Portuguese, Turkish.

**Figure 2**
Summary of the risk of bias (ROB) estimates for observational studies [72,130]. Analyses were performed according to the National Toxicology Program (NTP)’s Office of Health Assessment and Translation (OHAT) handbook and respective risk of bias (ROB) tool.

**Figure 3**
Receiver Operating Characteristics (ROCs) curve for diagnostic performance of medical history on identifying the varicella zoster virus (VZV) seropositive status in healthcare workers. A corresponding area under curve (AUC) equal to 0.642 was eventually calculated (i.e., a 64.2% chance that the medical history was able to discriminate between true positive and false positive status) [55,57,85,89,90,95,96,99,100,105,106,107,110,113,114,116,117,119,120,121,122,124,125,126].

**Figure 4**
Funnel plots on the seroprevalence studies for varicella zoster virus (VZV) (a), measles (b), and rubella (c) in healthcare workers [46,55,58,61,62,63,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129].

**Figure 5**
Funnel plots on the sensitivity (a) and specificity (b) of medical history for identifying healthcare workers without effective protection against varicella zoster virus (VZV; i.e., “naïve”) [55,57,85,89,90,95,96,99,100,105,106,107,110,113,114,116,117,119,120,121,122,124,125,126].

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References

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1. Arvin A.M. Varicella-Zoster Virus. Clin. Microbiol. Rev. 1996;9:361–381. doi: 10.1128/CMR.9.3.361. - DOI - PMC - PubMed
1. Gershon A.A., Breuer J., Cohen J.I., Cohrs R.J., Gershon M.D., Gilden D., Grose C., Hambleton S., Kennedy P.G.E., Oxman M.N., et al. Varicella Zoster Virus Infection. Nat. Rev. Dis. Primers. 2015;1:15016. doi: 10.1038/nrdp.2015.16. - DOI - PMC - PubMed
1. Tommasi C., Breuer J. The Biology of Varicella-Zoster Virus Replication in the Skin. Viruses. 2022;14:982. doi: 10.3390/v14050982. - DOI - PMC - PubMed
1. Heininger U., Seward J.F. Varicella. Lancet. 2006;368:1365–1376. doi: 10.1016/S0140-6736(06)69561-5. - DOI - PubMed

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[1] Rahaus M., Schünemann S., Wolff M.H. General Aspects Morphological and Biological Characteristics of Varicella-Zoster Virus. In: Wolff M., Schünemann S., Schmidt A., editors. Pathogenesis, and Clinical Aspects. Contrib Microbiol. Volume 3. Karger; Basel, Switzerland: 1999. pp. 1–9. - PubMed

[2] Rahaus M., Schünemann S., Wolff M.H. General Aspects Morphological and Biological Characteristics of Varicella-Zoster Virus. In: Wolff M., Schünemann S., Schmidt A., editors. Pathogenesis, and Clinical Aspects. Contrib Microbiol. Volume 3. Karger; Basel, Switzerland: 1999. pp. 1–9. - PubMed

[3] Arvin A.M. Varicella-Zoster Virus. Clin. Microbiol. Rev. 1996;9:361–381. doi: 10.1128/CMR.9.3.361. - DOI - PMC - PubMed

[4] Arvin A.M. Varicella-Zoster Virus. Clin. Microbiol. Rev. 1996;9:361–381. doi: 10.1128/CMR.9.3.361. - DOI - PMC - PubMed

[5] Gershon A.A., Breuer J., Cohen J.I., Cohrs R.J., Gershon M.D., Gilden D., Grose C., Hambleton S., Kennedy P.G.E., Oxman M.N., et al. Varicella Zoster Virus Infection. Nat. Rev. Dis. Primers. 2015;1:15016. doi: 10.1038/nrdp.2015.16. - DOI - PMC - PubMed

[6] Gershon A.A., Breuer J., Cohen J.I., Cohrs R.J., Gershon M.D., Gilden D., Grose C., Hambleton S., Kennedy P.G.E., Oxman M.N., et al. Varicella Zoster Virus Infection. Nat. Rev. Dis. Primers. 2015;1:15016. doi: 10.1038/nrdp.2015.16. - DOI - PMC - PubMed

[7] Tommasi C., Breuer J. The Biology of Varicella-Zoster Virus Replication in the Skin. Viruses. 2022;14:982. doi: 10.3390/v14050982. - DOI - PMC - PubMed

[8] Tommasi C., Breuer J. The Biology of Varicella-Zoster Virus Replication in the Skin. Viruses. 2022;14:982. doi: 10.3390/v14050982. - DOI - PMC - PubMed

[9] Heininger U., Seward J.F. Varicella. Lancet. 2006;368:1365–1376. doi: 10.1016/S0140-6736(06)69561-5. - DOI - PubMed

[10] Heininger U., Seward J.F. Varicella. Lancet. 2006;368:1365–1376. doi: 10.1016/S0140-6736(06)69561-5. - DOI - PubMed

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Immunity to Varicella Zoster Virus in Healthcare Workers: A Systematic Review and Meta-Analysis (2024)

Affiliations

Immunity to Varicella Zoster Virus in Healthcare Workers: A Systematic Review and Meta-Analysis (2024)

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Affiliations

Abstract

Conflict of interest statement

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Abstract

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