Estimation of the burden of varicella in Europe before the introduction of universal childhood immunization

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Abstract

Background

Varicella is generally considered a mild disease. Disease burden is not well known and country-level estimation is challenging. As varicella disease is not notifiable, notification criteria and rates vary between countries. In general, existing surveillance systems do not capture cases that do not seek medical care, and most are affected by underreporting and underascertainment. We aimed to estimate the overall varicella disease burden in Europe to provide critical information to support decision-making regarding varicella vaccination.

Methods

We conducted a systematic literature review to identify all available epidemiological data on varicella IgG antibody seroprevalence, primary care and hospitalisation incidence, and mortality. We then developed methods to estimate age-specific varicella incidence and annual number of cases by different levels of severity (cases in the community, health care seekers in primary care and hospitals, and deaths) for all countries belonging to the European Medicines Agency (EMA) region and Switzerland.

Results

In the absence of universal varicella immunization, the burden of varicella would be substantial with a total of 5.5 million (95% CI: 4.7–6.4) varicella cases occurring annually across Europe. Variation exists between countries but overall the majority of cases (3 million; 95% CI: 2.7–3.3) would occur in children <5 years. Annually, 3–3.9 million patients would consult a primary care physician, 18,200–23,500 patients would be hospitalised, and 80 varicella-related deaths would occur (95% CI: 19–822).

Conclusions

Varicella disease burden is substantial. Most cases occur in children <5 years old but adults require hospitalisation more often and are at higher risk of death. This information should be considered when planning and evaluating varicella control strategies. A better understanding of the driving factors of country-specific differences in varicella transmission and health care utilization is needed. Improving and standardizing varicella surveillance in Europe, as initiated by the European Centre for Disease Prevention and Control (ECDC), is important to improve data quality to facilitate inter-country comparison.

Electronic supplementary material

The online version of this article (doi:10.1186/s12879-017-2445-2) contains supplementary material, which is available to authorized users.

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Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement.

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In the course of performing systematic reviews on the prevalence of low back and neck pain, we required a tool to assess the risk of study bias. Our objectives were to (1) modify an existing checklist and (2) test the final tool for interrater agreement. The final tool consists of 10 items addressing four domains of bias plus a summary risk of bias assessment. Two researchers tested the interrater agreement of the tool by independently assessing 54 randomly selected studies. Interrater agreement overall and for each individual item was assessed using the proportion of agreement and Kappa statistic. Raters found the tool easy to use, and there was high interrater agreement: overall agreement was 91% and the Kappa statistic was 0.82 (95% confidence interval: 0.76, 0.86). Agreement was almost perfect for the individual items on the tool and moderate for the summary assessment. We have addressed a research gap by modifying and testing a tool to assess risk of study bias. Further research may be useful for assessing the applicability of the tool across different conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

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Varicella-zoster virus.

A M Arvin (1996)

Varicella-zoster virus (VZV) is a ubiquitous human alphaherpesvirus that causes varicella (chicken pox) and herpes zoster (shingles). Varicella is a common childhood illness, characterized by fever, viremia, and scattered vesicular lesions of the skin. As is characteristic of the alphaherpesviruses, VZV establishes latency in cells of the dorsal root ganglia. Herpes zoster, caused by VZV reactivation, is a localized, painful, vesicular rash involving one or adjacent dermatomes. The incidence of herpes zoster increases with age or immunosuppression. The VZV virion consists of a nucleocapsid surrounding a core that contains the linear, double-stranded DNA genome; a protein tegument separates the capsid from the lipid envelope, which incorporates the major viral glycoproteins. VZV is found in a worldwide geographic distribution but is more prevalent in temperate climates. Primary VZV infection elicits immunoglobulin G (IgG), IgM, and IgA antibodies, which bind to many classes of viral proteins. Virus-specific cellular immunity is critical for controlling viral replication in healthy and immunocompromised patients with primary or recurrent VZV infections. Rapid laboratory confirmation of the diagnosis of varicella or herpes zoster, which can be accomplished by detecting viral proteins or DNA, is important to determine the need for antiviral therapy. Acyclovir is licensed for treatment of varicella and herpes zoster, and acyclovir, valacyclovir, and famciclovir are approved for herpes zoster. Passive antibody prophylaxis with varicella-zoster immune globulin is indicated for susceptible high-risk patients exposed to varicella. A live attenuated varicella vaccine (Oka/Merck strain) is now recommended for routine childhood immunization.

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Seroprevalence of Cytomegalovirus, Epstein Barr Virus and Varicella Zoster Virus among Pregnant Women in Bradford: A Cohort Study

Lucy Pembrey, Pauline Raynor, Paul Griffiths … (2013)

Objective To estimate the seroprevalence of cytomegalovirus (CMV), Epstein Barr virus (EBV) and varicella zoster virus (VZV) among pregnant women in Bradford by ethnic group and country of birth. Methods A stratified random sample of 949 pregnant women enrolled in the Born in Bradford birth cohort was selected to ensure sufficient numbers of White UK born women, Asian UK born women and Asian women born in Asia. Serum samples taken at 24-28 weeks’ gestation were tested for CMV IgG, EBV IgG and VZV IgG. Each woman completed a questionnaire which included socio-demographic information. Results CMV seroprevalence was 49% among the White British women, 89% among South Asian UK born women and 98% among South Asian women born in South Asia. These differences remained after adjusting for socio-demographic factors. In contrast, VZV seroprevalence was 95% among women born in the UK but significantly lower at 90% among South Asian women born in Asia. EBV seroprevalence was 94% overall and did not vary by ethnic group/country of birth. Conclusions Although about half of White British women are at risk of primary CMV infection in pregnancy and the associated increased risk of congenital infection, most congenital CMV infections are likely to be in children born to South Asian women with non-primary infection during pregnancy. South Asian women born in South Asia are at risk of VZV infection during pregnancy which could produce congenital varicella syndrome or perinatal chickenpox. Differences in CMV and VZV seroprevalence by ethnic group and country of birth must be taken into account when universal immunisation against these viruses is contemplated.

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Author and article information

Contributors

Margarita Riera-Montes: +34-691-109-602 , margarita.riera@p-95.com

Kaatje Bollaerts:

ORCID: http://orcid.org/0000-0001-7704-0527

kaatje.bollaerts@p-95.com

Ulrich Heininger: ulrich.heininger@ukbb.ch

Niel Hens: niel.hens@uhasselt.be

Giovanni Gabutti: giovanni.gabutti@unife.it

Angel Gil: angel.gil@urjc.es

Bayad Nozad: bayad.nozad@nhs.net

Grazina Mirinaviciute: Grazina.Mirinaviciute@fhi.no

Elmira Flem: Elmira.Flem@fhi.no

Audrey Souverain: ASouverain.externe@spmsd.com

Thomas Verstraeten: thomas.verstraeten@p-95.com

Susanne Hartwig: SHartwig@spmsd.com

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 18 May 2017

Publication date PMC-release: 18 May 2017

Publication date Collection: 2017

Volume: 17

Electronic Location Identifier: 353

Affiliations

[1 ]P95 Pharmacovigilance and Epidemiology Services, Koning Leopold III Laan 1, 3001 Leuven, Belgium

[2 ]ISNI 0000 0004 1937 0642, GRID grid.6612.3, Division of Paediatric Infectious Diseases and Vaccinology, , University of Basel Children’s Hospital, ; CH-4056 Basel, Switzerland

[3 ]ISNI 0000 0001 0604 5662, GRID grid.12155.32, Interuniversity Institute for Biostatistics and statistical Bioinformatics, , Hasselt University, ; Antwerp, Belgium

[4 ]ISNI 0000 0001 0790 3681, GRID grid.5284.b, Centre for Health Economics Research and Modelling Infectious Diseases and Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, , University of Antwerp, ; Antwerp, Belgium

[5 ]ISNI 0000 0004 1757 2064, GRID grid.8484.0, Department of Medical Sciences, , University of Ferrara, ; Ferrara, Italy

[6 ]ISNI 0000 0001 2206 5938, GRID grid.28479.30, , Universidad Rey Juan Carlos, ; Madrid, Spain

[7 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Department of Primary Care and Public Health, , Imperial College London, ; London, UK

[8 ]ISNI 0000 0001 1541 4204, GRID grid.418193.6, Department of Infectious Disease Epidemiology and Modelling, , Norwegian Institute of Public Health, ; Oslo, Norway

[9 ]Aixial, 4 rue Danjou, 92513 Boulogne-Billancourt, France

[10 ]GRID grid.417924.d, , Sanofi Pasteur MSD, ; 162 avenue Jean Jaurès, 69007 Lyon, France

Author information

Kaatje Bollaerts http://orcid.org/0000-0001-7704-0527

Article

Publisher ID: 2445

DOI: 10.1186/s12879-017-2445-2

PMC ID: 5437534

PubMed ID: 28521810

SO-VID: ba441bcc-d73a-42cf-83d6-c4878b35946e

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.