Universal Childhood Varicella Vaccination Research Articles

801. IDSA Featured Oral Abstract: 25 Years of Varicella Vaccination Program in the United States: Health Impact during 1995–2019

Abstract Background In 1995, the United States was the first country to introduce universal childhood varicella vaccination. High vaccine coverage was attained among young children, ≥ 90% since 2007. In 2007, the policy was changed from 1-dose to a 2-dose program. We describe the impact of 25 years of the U.S. varicella vaccination program on varicella disease nationally. Methods We reviewed published data and analyzed overall and age-specific trends for rates from the pre-vaccine period (1990–1994) through 2019 for varicella incidence using National Notifiable Diseases Surveillance System data, hospitalizations using National Inpatient Sample data, and deaths using National Center for Health Statistics data. We present trends in persons aged < 50 years, which captures most varicella burden and avoids misclassified herpes zoster in older people. Outbreak (≥ 5 varicella cases epidemiologically linked) characteristics were assessed for 1995–2019 and were informed by published data and analysis of surveillance data reported to CDC. Results Within the 10 years of the 1-dose program, varicella incidence, hospitalization, and mortality rates declined dramatically (71%–90%) vs. pre-vaccine. However, limited transmission continued in school settings which informed the change to a 2-dose policy. By 2019, declines reached > 97% for incidence and 94% and 97% for hospitalizations and deaths, respectively. The greatest decline occurred among persons aged < 20 years, born during the varicella vaccination program, with 99%, 97%, and > 99% reduction in incidence, hospitalizations, and deaths, respectively. The 2-dose program further reduced the number, size, and duration of outbreaks vs. the 1-dose program; over the entire program, the proportion of outbreaks with < 10 cases increased from 28% to 73%. Conclusion The varicella vaccination program significantly reduced varicella morbidity and mortality in the U.S. Twenty-five years into the program, pediatric varicella hospitalization has become a rare event and varicella deaths in persons aged < 20 years are practically eliminated in the U.S. Annually, > 3.8 million cases, 10,500 hospitalizations, and 100 deaths from varicella are now prevented in the United States due to the varicella vaccination program. Disclosures All Authors: No reported disclosures.

Safety of varicella vaccination strategies: An overview of reviews.

The safety of new vaccines under development as well as existing vaccines is a key priority for national and international public health agencies. A number of countries have implemented universal childhood varicella vaccination programmes over the past 30years. However, strategies differ in terms of the number of doses, type of vaccine(s) recommended, age at vaccination and interval between doses for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the safety of varicella vaccination strategies. The review was restricted to immunocompetent children aged 9months to 6years inclusive. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. Overlap of included reviews was also assessed. A total of 17 reviews, incorporating both the monovalent varicella only and quadrivalent measles-mumps-rubella-varicella (MMRV) vaccines were included in the overview; six assessed the safety of one-dose strategies, four assessed the safety of two-dose strategies and 14 reviews did not specify the dosing strategy. The evidence suggests that mild local and systemic reactions are relatively common with varicella vaccination. Febrile seizures are also possible adverse effects of both the monovalent and quadrivalent MMRV vaccine, but serious adverse reactions are rare. While most reviews contained methodological flaws, and analysis by vaccine type and dosing strategy was restricted due to lack of detail in reporting of the reviews, there was clear and consistent evidence from a substantial evidence base, comprising 34 randomised controlled trials and 62 other primary studies/reviews, that varicella vaccination is safe.

Clinical efficacy and effectiveness of alternative varicella vaccination strategies: An overview of reviews.

A number of countries have implemented universal childhood varicella vaccination programmes over the past 30years. However, strategies differ in terms of dosing schedule (one- or two-dose), type of vaccine(s) recommended (monovalent, quadrivalent measles-mumps-rubella-varicella, or both), age at vaccination, and dosing interval for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the clinical efficacy/effectiveness of alternative varicella vaccination strategies. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. A total of 20 reviews were included in the overview; 17 assessed the efficacy/effectiveness of one-dose strategies and 10 assessed the efficacy/effectiveness of two-dose strategies. Although the quality of most reviews was deemed 'critically low', there was clear and consistent evidence that vaccination is very effective at reducing varicella. While the analysis was restricted due to lack of detail in reporting of the reviews, the evidence suggests that two-dose strategies are more efficacious/effective than one-dose strategies in preventing varicella of any severity, but that both strategies have similar high efficacy/effectiveness in preventing moderate or severe varicella. Based on this evidence in this overview of reviews, a key consideration for policymakers on the possible introduction of a childhood varicella vaccination programme and the choice between a one- or two-dose strategy, will be whether the objective of a programme is to prevent varicella of any severity or to prevent moderate to severe varicella.

Varicella-zoster virus seroprevalence in children and adolescents in the pre-varicella vaccine era, Germany

BackgroundIn 2004, universal childhood varicella vaccination was introduced in Germany. We aimed to determine the age-specific prevalence of anti-varicella zoster virus (VZV) IgG-antibodies among children in the pre-varicella vaccine era in Germany, to identify factors associated with VZV seropositivity, and to assess the suitability of a commercially available ELISA for VZV seroepidemiological studies by comparing it with an in-house fluorescent antibody to membrane antigen test (FAMA) as the gold standard.MethodsSerum samples of 13,433 children and adolescents aged 1–17 years included in the population-based German Health Interview and Examination Survey for Children and Adolescents (KiGGS; conducted 2003–2006) were tested for anti-VZV IgG by ELISA. All samples with equivocal ELISA results and a random selection of ELISA-negative and -positive samples were tested by FAMA. Statistical analyses were conducted using a weighting factor adjusting the study population to the total population in Germany. Seroprevalences were calculated as percentages (%) with a 95% confidence interval (CI). Odds ratios (OR) were computed by multivariate logistic regression to determine the association between socio-demographic factors and VZV seropositivity.ResultsThe VZV seropositivity rate was 80.3% (95% CI: 79.3–81.3) in varicella-unvaccinated children and adolescents. VZV seropositivity rates differed significantly between age groups up to age 6 years, but not by gender. Of 118 retested serum samples with an equivocal ELISA result, 45.8% were FAMA-positive. The proportion of samples tested as false-negative in by ELISA varied by age group: 2.6% in children aged 1–6 and 9% in children aged 7–17 years. Multivariate analyses showed that age, having older siblings, and early daycare start were associated with seropositivity in preschoolers; migration background reduced the chance of VZV seropositivity in schoolchildren (OR: 0.65; 0.43–0.99) and adolescents (OR: 0.62; 0.4–0.97).ConclusionIn the pre-varicella vaccine era, most children in Germany contracted varicella by age six. Schoolchildren with a migration background and children without siblings have an increased risk of being VZV seronegative and should be targeted for catch-up vaccination, if they have no history of chickenpox. ELISAs are suitable for use in population-level serosurveys on VZV, but samples with equivocal ELISA results should be retested by FAMA.

Children Hospitalized With Varicella in Denmark: Sensitivity of the National Patient Register.

Varicella, common in childhood and most often self-limiting, may cause complications including bacterial superinfection, pneumonia and encephalitis. Universal childhood varicella vaccination has been introduced in several countries, but is controversial in Europe. In Denmark, varicella is not part of the national immunization program and there is no national surveillance of varicella. The primary aim of the study was to describe the epidemiology and clinical characteristics of children hospitalized with varicella in Denmark. The secondary aim was to validate the sensitivity and completeness of the Danish National Patient Register. Active surveillance of children hospitalized with varicella was carried out at 4 pediatric departments. In the Danish National Patient Register, we identified all children discharged with an International Classification of Diseases, 10th revision code of varicella from the 4 departments. We used a capture-recapture analysis to estimate the "true" number of hospitalized children with varicella. By active surveillance, we identified 86 children eligible for clinical description. In 87% of cases, the children were 0-4 years of age. Complications were identified in 69% of patients, including 1 child with postvaricella cerebral angiopathy. In the National Patient register (NPR), we identified 125 children with a discharge diagnosis of varicella. By capture-recapture analysis, the sensitivity of the NPR was estimated to be 74%. Varicella can cause serious complications including cerebral angiopathy in children in Denmark. The NPR will be a useful tool for estimating hospitalization incidence, but will underestimate the true number of hospitalizations.

Current and future effects of varicella and herpes zoster vaccination in Germany – Insights from a mathematical model in a country with universal varicella vaccination

ABSTRACTVaricella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age-classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the model's results provide valuable insights that support decision-making regarding national VZV vaccination strategies.

Low varicella-related consultation rate in the Netherlands in primary care data

BackgroundIn the Netherlands, a relatively low varicella disease burden compared to other European countries is observed within routine surveillance. To validate this, we estimated the varicella-related consultation rate using The Integrated Primary Care Information database. MethodsIn this retrospective cohort study, varicella patients in 2006–2008 were identified by the International Classification of Primary Care (A72) and free text in the electronic medical records, and manually reviewed to be categorised as ‘varicella’ or ‘probable varicella’. The incidence of GP-consultation, specialist referral, emergency department contact and hospitalisation due to varicella was calculated, standardised to the Dutch population. ResultsWe identified 1881 varicella cases (2348 including probable cases), 14 patients were hospitalised. The overall incidence of GP-consultation due to varicella per 100,000 person-years was at least 281 (95%CI 268–294) and when probable cases were also included at maximum 354 (95%CI 340–369). The overall incidence of specialist referral, emergency department contact and hospitalisation per 100,000 person-years was 3.9 (95%CI 2.7–5.6), 2.5 (95%CI 1.5–4.0) and 2.0 (95%CI 1.2–3.4) respectively. ConclusionsThis study confirms the relatively low disease burden due to varicella in the Netherlands. In this study, using primary care data, similar incidences of GP consultation and referral to secondary care due to varicella were found as in routine surveillance. The lower varicella-related consultation rate might be linked to more conservative GP consultation behaviour in the Netherlands, and the relatively young age of infection. This is highly relevant for the decision-making process whether or not to introduce universal childhood varicella vaccination in the Netherlands.

Universal varicella vaccination in the Sicilian paediatric population: rapid uptake of the vaccination programme and morbidity trends over five years

Following the licensure of the Oka/Merck varicella vaccine in Italy in January 2003, the Sicilian health authorities launched a universal vaccination programme in all nine Local Health Units. A two-cohort vaccination strategy was adopted to minimise the shift of the mean age of varicella occurrence to older age groups, with the goal of vaccinating with one dose at least 80% of children in their second year of life and 50% of susceptible adolescents in their 12th year of life. Two studies were implemented in parallel to closely monitor vaccination coverage as well as varicella incidence.

Varicella vaccination in HIV-positive individuals – a time to act

Purpose of the study Primary varicella infection in the HIV population can have serious sequelae. The HIV non-VZV immune population is at risk of attack rates of up to 90% from infected household contacts, who are predominantly children. Universal childhood varicella vaccination is currently under review in Ireland. New recommendations of the Advisory Committee on Immunisation Practices (MMWR) 2007 include expanding the use of varicella vaccine for HIV-infected adults and adolescents with CD4 >200, with vaccination of household contacts of those with CD4<200. These guidelines prompted us to review our HIV patient cohort, 30% of whom are from sub-Saharan Africa (SSA), reflecting the changing demographics of the Irish population. VZV non-immunity is known to be higher in the SSA population.

Varicella Vaccine, Cost-effectiveness Analyses, and Vaccination Policy

HAS VARICELLA VACCINATION BEEN AS COSTeffective as anticipated when it was universally recommended for children 10 years ago? The answer is complicated and illuminates an evolving controversy regarding the role of cost-effectiveness analyses in deliberations over national vaccine recommendations. In 1994, Lieu and colleagues estimated the costeffectiveness of a universal childhood varicella vaccination program. Projecting a national vaccination rate of 97% by the sixth year of the program, they estimated a 94% reduction in varicella incidence, accompanied by an 89% reduction in direct medical costs. Accounting as well for reductions in the quantity of parents’ and other adults’ lost work time attributable to varicella (ie, the “indirect” benefits of vaccination), Lieu et al projected that a varicella vaccination program would save more than $5 for every $1 spent. These projections of reduced varicella disease burden and direct medical costs with varicella vaccination appear prescient, even though they were based on optimistic vaccination rates. In this issue of JAMA, Zhou and colleagues present data from a national group of privately insured individuals in 1994-2002 that indicate reductions of nearly 90% in hospitalization rates for varicella, nearly 60% in ambulatory visit rates, and 74% in costs borne by health care payers— accomplished in an era when slightly more than 80% of US toddlers had been vaccinated against chickenpox. Cost reductions might have been even more substantial if Zhou et al had sufficient data to analyze pharmaceutical expenditures for antiviral agents that Lieu et al considered. Although the study by Zhou et al is based solely on trends among insured individuals, the magnitude of their findings corresponds well to patterns of varicella incidence and mortality collected without regard to payer and to varicellarelated hospitalization trends and associated charges collected on insured and uninsured children and adults. In addition, these data support the strong evidence of herd immunity against varicella in the vaccination era, with adults experiencing the benefits of children’s vaccination, and infants—who are not eligible for vaccination—showing the greatest reductions of all child age groups. Nonetheless, these findings do not conclusively confirm that childhood varicella vaccination is as cost-effective as originally anticipated, for several reasons. First, the cost of the vaccine has increased more than $10 per dose in inflationadjusted terms since 1995 (the current public sector price per dose is $52.25), although an increase of this magnitude was not anticipated to change the cost-effectiveness dramatically. Second, the national varicella vaccine recommendation prompted states to measure and react to varicella as a reportable vaccine-preventable illness. The costs of such monitoring and of responding to outbreaks of varicella (eg, in day care or school settings) may be substantial and were not included in the original analysis by Lieu et al. Third, and perhaps most important, there is great uncertainty about the extent to which parents and other adults experienced reductions in lost work time attributable to varicella. As with other childhood and adolescent vaccines that have recently been recommended (eg, pneumococcal and meningococcal conjugate vaccines), indirect cost savings with varicella vaccine were expected to be larger than savings in direct medical costs. With varicella vaccine, the ratio of indirect cost savings to direct cost savings was expected to be nearly 5:1. Despite the importance of indirect cost quantification to the evaluation of vaccination programs, there are no established mechanisms to measure such effects. Therefore, it is possible that the increasing value of work time over the past decade may have increased savings beyond what Lieu et al anticipated. Conversely, increasing unemployment may have allowed more parents to care for their ill children at home without missing work, effectively reducing savings attributable to the program. Both of these changes may have occurred disproportionately in specific sectors of the economy (eg, wage increases in the software industry and unemployment increases in the manufacturing industry) that may have different likelihoods of having young children in the household. These changes are plausible, but their magnitude remains unknown. Pointing out current limitations in measuring indirect benefits of vaccination programs may seem methodologically nitpicky, but it is more than an academic exercise. The contem-

Decline in Mortality with Varicella Vaccination

To the Editor: Nguyen et al. (Feb. 3 issue)1 report on the effect of the U.S. varicella vaccination program on disease-related mortality. The effectiveness of such programs also includes reducing severe varicella-associated complications. In Italy, from 1995 to 2003, when no universal childhood varicella vaccination program was in effect, we documented 303 admissions (median age of patients, 4.2 years; range, 0 to 15) to a children's research hospital for varicella for a total of 2420 days of hospitalization. Thirty-nine patients (13 percent) had varicella-associated complications (1.2 percent of admissions for varicella), including 13 with central nervous system involvement and 7 . . .

Varicella Vaccine Leads to Decline in Mortality

Introduction of the universal childhood varicella vaccination program in the U.S. in 1995 was controversial, because many clinicians and parents did

The Impact of Varicella Vaccine

The introduction of the universal childhood varicella vaccination program in 1995 was controversial because many clinicians and parents did not believe in the need to immunize for a benign disease. CDC investigators have tallied the annual deaths, from 1990 through 2001, in which varicella …

The seroepidemiology of primary varicella-zoster virus infection in Flanders (Belgium).

The age-specific seroprevalence of varicella-zoster virus (VZV) antibodies was assessed in a sample of the Flemish (Belgian) population. ELISA tests were used to analyse 1673 sera from subjects aged 1 to 44 years (October 1999-April 2000). Chickenpox infections in Flanders appear to affect children at a younger age than in other European countries since 47.37% (95% CI: 37.33-57.41) is already immune at 2 years of age. For older age-groups, the prevalence is similar to that of most European countries: 80.19% (95% CI: 72.60-87.78) at 5 years, 92.52% (95% CI: 87.54-97.51) at 9 years and 100%> or =40 years. The accuracy of non-positive recollections of varicella histories among Flemish 10 to 17-year olds was examined on the basis of a second (residual) serum bank. In this group, VZV seroprevalence was almost always 100% (or nearly 100%), irrespective of age, degree of reliability (negative or uncertain answers) or level of ascertainment (child personally or parents). The limited size of this second data set did not allow for an accurate assessment of the negative predictive value of such recollections. since varicella-zoster virus predominantly affects very small children and is generally perceived as benign, the required high coverage rate of a universal childhood varicella vaccination programme may be hard to attain. Adolescent strategies can minimise the population risks involved but the accuracy of non positive antecedents of chickenpox needs to be documented to assess the efficiency of such strategies.