Global Prevalence of Varicella-Associated Complications: A Systematic Review and Meta-Analysis

Abstract

Introduction: Varicella (chickenpox) is an infectious disease caused by the varicella zoster virus affecting children, adolescents, and adults. Varicella symptoms are usually self-limiting; however, different complications with widespread and systemic manifestations can occur. This systematic literature review aims to explore and quantify varicella-associated complication rates. Methods: Two databases (Embase and MEDLINE), congress abstracts, and reference lists of systematic reviews were screened to identify evidence on varicella complications. Complications were identified and grouped into 14 clinically relevant categories. Proportional meta-analyses were conducted using a random-effects model and tests for heterogeneity and publication bias were performed. Subgroup, sensitivity, and meta-regression analyses were also conducted. A total of 78 studies, spanning 30 countries, were included in the meta-analysis. Results: Pooled prevalence was highest in severe varicella (22.42%; 95% confidence interval [CI] 10.13–37.77), skin-related complications (20.12%; 95% CI 15.48–25.20), and infection-related complications (10.03%; 95% CI 7.47–12.90). Cardiovascular (0.55%; 95% CI 0.08–1.33), genitourinary (1.17%; 95% CI 0.55–1.99), and musculoskeletal (1.54%; 95% CI 1.06–2.11) complications had the lowest pooled prevalence. The remaining complication categories ranged between 1% and 10%. Subgroup analysis showed that complications were more prevalent in children versus adults and in hospitalized patients versus outpatients. Meta-regression analysis found that no ecological level covariates were accurate predictors for the overall prevalence of varicella-associated complications. There was substantial heterogeneity and publication bias across all meta-analyses. Conclusion: Results suggest that different types of varicella-associated complications could be frequent, impacting quality of life, and healthcare resource utilisation and budgets. These findings are crucial to raise awareness of the health and economic burden of varicella disease.