Waning immunity, an age shift, and rising adult burden of varicella after two decades of single-dose vaccination in South Korea

BACKGROUND: Many countries have not adopted universal varicella vaccination (UVV), citing concerns that it could shift disease burden toward older, higher-risk age groups and be insufficiently cost-effective. Long-term data under sustained single-dose vaccination remain scarce. We assessed the immunological, epidemiological, and healthcare cost consequences of two decades of South Korea's single-dose National Immunization Program, which has maintained >95% coverage since 2005 without the anticipated decline in incidence. METHODS: We analyzed varicella-zoster virus immunoglobulin G titers in 3765 healthcare personnel (HCP) by birth group. We also examined national surveillance (Korea Disease Control and Prevention Agency) and insurance claims (Health Insurance Review and Assessment Service) data from 2010 to 2024. RESULTS: Seronegativity was highest among HCP born during 1990-1994 (adjusted odds ratio, 3.83), and geometric mean titers declined across successive birth groups (geometric mean ratio, 0.70 [95% confidence interval, 0.63-0.77], 2000-2004 vs. pre-1980), indicating waning immunity. In 2024, adolescents surpassed children aged <10 years as the largest proportion of cases for the first time. Age-specific incidence rates increased approximately ninefold in adolescents and threefold in adults while remaining unchanged in children. Among adults, the proportion of varicella meningitis cases rose from 16.4% to 72.9%, and their share of varicella-related healthcare costs rose from 21.2% to 41.9%. CONCLUSIONS: After two decades of sustained high single-dose coverage, these findings provide evidence relevant to concerns about age shift and disease severity in settings yet to adopt UVV and support reassessment of the single-dose schedule.