Article

Health and Economic Impact of the United States Varicella Vaccination Program, 1996-2020

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Background: The aim of this study was to evaluate the health and economic impact of the varicella vaccination program on varicella disease in the United States (US), 1996-2020. Methods: Analysis was conducted using the Centers for Disease Control and Prevention or published annual population-based varicella incidence, and varicella-associated hospitalization, outpatient visit, and mortality rates in the US population aged 0-49 years during 1996-2020 (range, 199.5-214.2 million persons) compared to before vaccination (1990-1994). Disease costs were estimated using the societal perspective. Vaccination program costs included costs of vaccine, administration, postvaccination adverse events, and travel and work time lost to obtain vaccination. All costs were adjusted to 2020 US dollars using a 3% annual discount rate. The main outcome measures were the number of varicella-associated cases, hospitalizations, hospitalization days, and premature deaths prevented; life-years saved; and net societal savings from the US varicella vaccination program. Results: Among US persons aged 0-49 years, during 1996-2020, it is estimated that more than 91 million varicella cases, 238 000 hospitalizations, 1.1 million hospitalization days, and almost 2000 deaths were prevented and 118 000 life-years were saved by the varicella vaccination program, at net societal savings of $23.4 billion. Conclusions: Varicella vaccination has resulted in substantial disease prevention and societal savings for the US over 25 years of program implementation.

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... The annual incidence of varicella in the general population in Asia Pacific in the absence of universal varicella vaccination (UVV) programs varies depending on the quality of a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 surveillance and other factors, with the highest estimated pre-UVV annual incidence (2,530 per 100,000 persons) reported in Taiwan, which has a robust national surveillance system [3]. The implementation of UVV has led to a substantial decrease in varicella incidence, healthcare resource utilization (HCRU), and costs associated with varicella in various countries [1,[4][5][6][7][8]. ...
... The implementation of UVV has led to significant reductions in varicella cases, hospitalizations, and costs in the Asia-Pacific region and globally [1,[4][5][6][7][40][41][42]. For example, the introduction of UVV led to a 2.9-to 3.8-fold reduction in varicella disease burden in Taiwan [3,43]. ...
... For example, the introduction of UVV led to a 2.9-to 3.8-fold reduction in varicella disease burden in Taiwan [3,43]. Similarly, the implementation of a UVV program in the US over 25 years led to a 97% decrease in varicella disease, with net societal savings of $23.4 billion [7]. UVV could be considered a possible strategy to reduce the clinical and economic burden of varicella in Thailand. ...
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Our multicenter, medical chart review, cost-of-illness study used a micro-costing approach to evaluate the economic burden associated with varicella in Bangkok, Thailand, from a societal perspective. We reviewed medical charts of adults and children with a primary diagnosis of varicella (2014–2018) from 4 hospitals in Bangkok. Reported healthcare resource utilization and missed school or workdays were extracted from medical charts. Mean direct, indirect, and total costs per patient were estimated for overall, adult, and pediatric patients (2020 USD). Of the 200 children and 60 adults, 99.6%, 5.4%, and 5.4% had a varicella-related outpatient visit, emergency department visit, and hospitalization, respectively. The mean direct medical cost was 33 USD for pediatric and adult patients. The mean cost of outpatient visits (8 vs 13 USD, P<0.001) and medications (7 vs 9 USD, P<0.001) was significantly lower among pediatric patients. Forty-eight children reported a mean of 5.8 school days lost, and 32 adult patients reported a mean of 7.4 workdays lost. The mean total cost per varicella patient was 89 USD, with the mean total cost higher for adult than pediatric patients (145 vs 72 USD, P<0.001). Indirect cost accounted for 63% of the total cost per patient (54% for pediatric patients and 77% for adult patients). There is a substantial economic burden associated with patients seeking varicella-related healthcare in Thailand, including considerable indirect costs.
... It is particularly emphasized that college students, healthcare workers, and school staff, who are at higher risk of VZV exposure or transmission, should be vaccinated if they lack evidence of immunity to chickenpox [37]. Moreover, global application experience has demonstrated that VarV vaccination markedly diminishes the incidence and severity of chickenpox [38][39][40], making it the most cost-effective strategy for preventing and controlling the disease [41][42][43]. For instance, following the implementation of the VarV vaccination strategy across the United States, the two-dose vaccine coverage rate among adolescents aged 13-17 exceeded 90%, while hospitalization and mortality rates for chickenpox in the 20-49 age group declined by 85% and 94%, respectively [44]. ...
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Background Adolescents and adults who contract chickenpox are at a higher risk of severe complications. Vaccination with the varicella vaccine (VarV) effectively prevents chickenpox. Research design and methods In this phase III, single-center, randomized, double-blind, active-controlled trial, 1,200 healthy participants were randomly assigned in a 1:1 ratio to receive two doses of either the test vaccine or the active control vaccine. Varicella-zoster virus (VZV) antibody was detected before vaccination and 42 days after the two doses of vaccination. Results The lower limits of the 95% CI for the differences in seroconversion rates and geometric mean titer (GMT) ratios between the two groups were greater than their respective pre-set non-inferiority margins. The overall incidence of Adverse events (AEs) and adverse reactions (ARs) in the test group was significantly lower than those in the control group. Additionally, the incidence rates of swelling and fatigue were lower in the test group compared to the control group after vaccination. Conclusions The test freeze-dried live attenuated VarV demonstrated good immunogenicity and higher safety compared to the active control vaccine in healthy participants aged 13–55 years. Clinical trials registration www.clinicaltrials.gov identifier: NCT06592456.
... Children with varicella play a significant role in the transmission of VZV. In the United States, varicella outbreaks are monitored through a combination of active and passive surveillance, which has shown a noteworthy decline in outbreaks since the implementation of a routine two-dose varicella vaccination schedule in 2007 (11). Therefore, extensive vaccination of eligible-age children is essential to effectively prevent the spread of varicella and reduce the attack rate. ...
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Introduction Varicella outbreaks significantly disrupt schools and other child-centered institutions. This study aimed to identify patterns and epidemiological features of varicella outbreaks in China from 2006 to 2022. Methods Data were extracted from outbreak reports submitted to the Public Health Emergency Reporting Management Information System within the specified timeframe. Analytical methods included Spearman correlation tests and the Mann-Kendall trend tests, conducted using R software to analyze and summarize reported data. Additionally, statistical analyses of trends and epidemiological characteristics were performed using SPSS software. Results Between 2006 and 2022, a total of 11,990 varicella outbreaks were reported in China, resulting in 354,082 cases. The attack rates showed a decreasing trend over the years (Z=−4.49, P<0.05). These outbreaks occurred in two peaks annually. The eastern region accounted for the highest number of outbreaks (31.53%), followed by the southwestern (24.22%) and southern (17.93%) regions. Varicella outbreaks were most common in elementary schools. Most of the outbreaks (60.43%) were classified as Grade IV (general) severity, with 86.41% of the outbreaks having 10–49 cases. The median and inter-quartile ranges (IQR) of the duration of outbreaks, response time, and case counts were 21 (10, 39) days, 4 (0, 12) days, and 23 (16, 35) cases, respectively. These variables showed a positive correlation (P<0.001). Conclusions Varicella outbreaks exhibited fluctuating trends, initially decreasing until 2012, followed by an increase, reaching the highest peak in 2018–2019. Continual monitoring of varicella epidemiology is necessary to assess the burden of the disease and formulate evidence-based strategies and policies for its prevention and control.
... According to the World Health Organization (WHO), VPDs accounted for approximately 1.5 million deaths each year, with children under the age of five years being the most vulnerable (DESA, 2019). Zhou et al. in 2022 estimated that the United States of America's (USA) varicella vaccination programme generated a return on investment of $1.70 for every $1 spent during the first 25 years, with benefits continuing beyond 2020 (Zhou et al., 2022). The WHO also acknowledged and concurred that investing in immunisation programmes led to substantial savings in healthcare costs and increased economic productivity. ...
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To cite: Mohamad Hafiz Abd Rahim, Siti Hajar Mahamad Dom, Mohd Shah Rezan Hamzah, Siti Hawa Azman, Zahirah Zaharuddin & Mathumalar Loganathan Fahrni (2024) Impact of pharmacist interventions on immunisation uptake: a systematic review and meta-analysis, Journal of Pharmaceutical Policy and Practice, 17:1, DOI: 10.1080/20523211.2023.2285955 Background: Under-utilisation of immunisation services remains a public health challenge. Pharmacists act as facilitators and increasingly as immunisers, yet relatively little robust evidence exists of the impact elicited on patient health outcome and vaccination uptake. Objective: To evaluate the influence of pharmacist interventions on public vaccination rate. Methods: SCOPUS, PubMed, and Web of Science were searched from inception to April 2023 to retrieve non-and randomised controlled clinical trials (RCTs). Studies were excluded if no comparator group to pharmacist involvement was reported. Data extraction, risk of bias assessments, and meta-analyses using random-effect models, were performed. Results: Four RCTs and 15 non-RCTs, encompassing influenza, pneumococcal, herpes zoster, and tetanus-diphtheria and pertussis vaccine types, and administered in diverse settings including community pharmacies, were included. Pooled effect sizes revealed that, as compared to usual care, pharmacists, regardless of their intervention, improved the overall immunisation uptake by up to 51% [RR 1.51 (1.28, 1.77)] while immunisation frequency doubled when pharmacists acted specifically as advocators [RR 2.09 (1.42, 3.07)]. Conclusion: While the evidence for pharmacist immunisers was mixed, their contribution to immunisation programmes boosted public vaccination rate. Pharmacists demonstrated leadership and acquired indispensable advocator roles in the community and hospital settings. Future research could explore the depth of engagement and hence the extent of influence on immunisation uptake.
... UVV resulted in higher overall costs but better clinical outcomes (quality-adjusted life-years), with incremental cost-effectiveness ratios from the payer perspective ranging from £6809-£16 698, depending on strategy, compared with no UVV [46]. A UVV program in the United States resulted in net societal savings of $23.4 billion in its first 25 years [47]. Furthermore, the introduction of a UVV program in the United States was associated with 97% reduction in varicella cases [5] with an estimated $259 million reduction in antibiotic and antiviral prescription costs per year [48]. ...
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Background Varicella is a highly infectious disease, particularly affecting children, that can lead to complications requiring antibiotics or hospitalization. Antibiotic use for varicella management is poorly documented. This study assessed antibiotic use for varicella and its complications in a pediatric population in England. Methods Data were drawn from medical records in the Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Patients <18 years old diagnosed with varicella during 2014–2018 with 3-month follow-up available were included. We described varicella-related complications, medication use, healthcare resource utilization, and costs from diagnosis until 3-month post-diagnosis. Results We identified 114,578 children with a primary varicella diagnosis. 7.7% (n = 8,814) had a varicella-related complication, the most common being ear, nose, and throat related (37.1%, n = 3,271). In all, 25.9% (n = 29,706/114,578) were prescribed antibiotics. A higher proportion of patients with complications than those without complications were prescribed antibiotics (64.3%, n = 5,668/8,814 vs. 22.7%, n = 24,038/105,764). Mean annualized varicella-related costs were £2,231,481 for the study cohort. Overall, antibiotic prescriptions cost ∼£262,007. Conclusions This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs.
... Of interest, the increase in the vaccination rates appeared to reduce not only vari-cella incidence, but also relevant healthcare costs, antiviral agent use, and the number of office visits. Although the healthcare seeking behavior may have influenced by COVID-19 pandemic [30][31][32], the findings of healthcare utilization are consistent with the costeffectiveness and cost-saving of universal varicella vaccination programs observed in other resource-rich countries [33][34][35]. ...
Article
Purpose: To determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan. Materials and methods: We conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005-2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization. Results: After the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9-56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1-53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2-57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5-67.1]), antiviral use (65.7 % reduction [59.7-70.8]), and healthcare costs (49.1 % [95 %CI, 32.7-61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014. Conclusions: Varicella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices.
... Ongoing tracking of varicella and HZ, especially severe outcomes, and duration of immunity will be essential as the program continues, as well as developing more sensitive laboratory assays to measure vaccine-induced immunity and improve diagnosis of the mild, modified breakthrough disease. Since 1995, the United States varicella vaccination program has led to prevention of more than 91 million varicella cases, 238 000 hospitalizations, and almost 2000 deaths, with an impressive return on investment with net societal savings of more than $23 billion [52]. It is a public health achievement made possible by the efforts of thousands of nurses, physicians, pharmacists, and public health staff who implemented this immunization program. ...
... The vaccination program dramatically decreased virus circulation and increased community protection. Each year, approximately 3.8 million varicella cases are now prevented in the United States, with ensuing reduction in severe presentations and cost savings [30]. Continued and improved surveillance for varicella cases (eg, establishing varicella case-based surveillance in all states, increase in laboratory testing of cases with clinical presentation suggestive of varicella, enhanced completeness of reporting of variables critical for varicella surveillance, use of syndromic surveillance to supplement case identification) is needed to accurately describe trends and epidemiology of disease and further guide prevention efforts. ...
Article
Surveillance is critical for monitoring vaccine impact. Varicella surveillance challenges predated varicella vaccine US licensure in 1995. Several interim steps were needed before case-based surveillance could be established in most states, and both active and passive surveillance was needed to document the vaccination program's impact on varicella incidence. By the end of the 1-dose program in 2005, incidence had declined 90% in the active surveillance areas, with significant declines occurring in all age groups within 5 years of program implementation. Additional declines occurred during the 2-dose program leading to >97% decline in incidence over the 25 years of program implementation through 2019, based on data from 4 states with continuous passive reporting. Surveillance showed that declines were highest among children and adolescents covered by the routine vaccination recommendations but occurred in all age groups. Although surveillance systems changed and were adapted to reflect evolving epidemiology, data consistently demonstrated decreasing varicella incidence following the vaccination program implementation. The vaccination program dramatically decreased virus circulation and increased community protection. Continued and improved varicella surveillance is needed to accurately monitor disease epidemiology and further guide prevention efforts.
Article
Background Varicella is a common infectious disease and a growing public health concern in China, with increasing outbreaks in Wuxi. Analyzing the correlation between climate factors and varicella incidence in Wuxi is crucial for guiding public health prevention efforts. Objective This study examines the impact of meteorological variables on varicella incidence in Wuxi, eastern China, from 2010 to 2019, offering insights for public health interventions. Methods We collected daily meteorological data and varicella case records from January 1, 2010, to December 31, 2019, in Wuxi, China. Generalized cross-validation identified optimal lag days by selecting those with the lowest score. The relationship between meteorological factors and varicella incidence was analyzed using Poisson generalized additive models and segmented linear regression. Subgroup analyses were conducted by gender and age. Results The study encompassed 64,086 varicella cases. Varicella incidence in Wuxi city displayed a bimodal annual pattern, with peak occurrences from November to January of the following year and lower peaks from May to June. Several meteorological factors influencing varicella risk were identified. A decrease of 1°C when temperatures were ≤20°C corresponded to a 1.99% increase in varicella risk (95% CI 1.57-2.42, P<.001). Additionally, a decrease of 1°C below 22.38°C in ground temperature was associated with a 1.36% increase in varicella risk (95% CI 0.96-1.75, P<.001). Each 1 mm increase in precipitation above 4.88 mm was associated with a 1.62% increase in varicella incidence (95% CI 0.93-2.30, P<.001). A 1% rise in relative humidity above 57.18% increased varicella risk by 2.05% (95% CI 1.26-2.84, P<.001). An increase in air pressure of 1 hPa below 1011.277 hPa was associated with a 1.75% rise in varicella risk (95% CI 0.75-2.77, P<.001). As wind speed and evaporation increased, varicella risk decreased linearly with a 16-day lag. Varicella risk was higher with sunshine durations exceeding 1.825 hours, with a 14-day lag, increasing by 1.30% for each additional hour of sunshine (95% CI 0.62-2.00, P=.006). Subgroup analyses revealed that teenagers and children under 17 years of age faced higher varicella risks associated with temperature, average ground temperature, precipitation, relative humidity, and air pressure. Adults aged 18-64 years experienced increased risk with longer sunshine durations. Additionally, males showed higher varicella risks related to ground temperature and air pressure compared with females. However, no significant gender differences were observed regarding varicella risks associated with temperature (male: P<.001; female P<.001), precipitation (male: P=.001; female: P=.06), and sunshine duration (male: P=.53; female: P=.04). Conclusions Our preliminary findings highlight the interplay between varicella outbreaks in Wuxi city and meteorological factors. These insights provide valuable support for developing policies aimed at reducing varicella risks through informed public health measures.
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Background Varicella, a contagious infectious disease caused by varicella zoster virus (VZV), can result in hospitalization and, occasionally, death. Varicella virus vaccine live (VVVL [VARIVAX]) was introduced in the United States in 1995. Methods This comprehensive review of the VVVL safety profile is based on 22 years of postmarketing adverse event (AE) data received through spontaneous and noninterventional study reports submitted by health care providers and on a review of the published literature (cumulatively from March 17, 1995, through March 16, 2017, during which period >212 million doses were distributed globally). Results The VVVL safety profile was consistent with previous publications, with common AEs including varicella, rash, and pyrexia. AE reports have decreased over time, from ~500 per million doses in 1995 to ~40 per million doses in 2016; serious AEs comprise 0.8 reports per million doses. Secondary transmission was rare (8 confirmed cases); polymerase chain reaction analysis indicated that 38 of the 66 reported potential secondary transmission cases of varicella were attributable to wild-type VZV. The prevalence of major birth defects in the Pregnancy Registry was similar to that in the general US population. In total, 86 cases of death were reported after vaccination with VVVL; immunocompromised individuals appeared to be most at risk for a fatal varicella- or herpes zoster–related outcome. Conclusions This comprehensive 22-year review confirms the overall safety profile for VVVL, with no new safety concerns identified. Since VVVL’s introduction in 1995, notable declines in varicella cases and in varicella-related deaths have occurred compared with the prevaccination period.
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Background. Human-capital based lifetime productivity estimates are frequently used in cost-of-illness (COI) analyses and, less commonly, in cost-effectiveness analyses (CEAs). Previous US estimates assumed that labor productivity and real earnings both grow by 1% per year. Objectives. We present estimates of annual and lifetime productivity for 2016 using data from the American Community Survey, the American Time Use Survey, and the Current Population Survey and with varying assumptions about real earnings growth. Methods. We estimated the sum of market productivity (gross annual personal labor earnings adjusted for employer-paid benefits) and the imputed value of non-market time spent in household, caring, and volunteer services. The present value of lifetime productivity at various ages was calculated for synthetic cohorts using annual productivity estimates, life tables, discount rates, and assumptions about future earnings growth rates. Results. Mean annual productivity was 57,324forUSadultsin2016,including57,324 for US adults in 2016, including 36,935 in market and 20,389innonmarketproductivity.Lifetimeproductivityatbirth,usinga320,389 in non-market productivity. Lifetime productivity at birth, using a 3% discount rate, is roughly 1.5 million if earnings grow by 1% per year and $1.2 million if future earnings growth averages 0.5% per year. Conclusions. Inclusion of avoidable productivity losses in societal-perspective CEAs of health interventions is recommended in new US cost-effectiveness guidelines. However, estimates vary depending on whether analysts choose to estimate total productivity or just market productivity and on assumptions made about growth in future productivity and earnings.
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When the US varicella vaccination program was introduced in 1995, its impacts on the epidemiology of herpes zoster (HZ) were not precisely known. We used a large claims database to examine HZ incidence in the US during 1998-2019 among persons aged ≥30 years (the prevaccine cohort, born before 1990), and aged 1-29 years (includes the postvaccine cohort, born since 1990). We defined incident HZ as the first instance of an outpatient or emergency department (ED) claim with an HZ diagnostic code. Additionally, we examined the proportion of HZ visits among all ED visits as a complementary method to assess for healthcare-seeking artifacts in the findings. In persons aged ≥30 years (prevaccine cohort), we observed age-specific increases in HZ incidence during the earlier study years, with decelerations in later years, starting in 2007 with oldest age groups. Similar patterns were seen when we examined HZ visits as a proportion of all ED visits. For persons aged 1-29 years, age-specific HZ incidence increased early in the study period for the oldest age groups who were born prevaccine, but later declined in a stepwise pattern once each age group was comprised of persons born in the postvaccine period. Our results, corroborated with previously published studies, do not support prior modeling predictions that the varicella vaccination program would increase HZ incidence among adult cohorts who previously experienced varicella. Our findings also suggest that continued declines in age-specific HZ incidence as varicella-vaccinated cohorts age are likely.
Article
Surveillance is critical for monitoring vaccine impact. Varicella surveillance challenges predated varicella vaccine US licensure in 1995. Several interim steps were needed before case-based surveillance could be established in most states, and both active and passive surveillance was needed to document the vaccination program's impact on varicella incidence. By the end of the 1-dose program in 2005, incidence had declined 90% in the active surveillance areas, with significant declines occurring in all age groups within 5 years of program implementation. Additional declines occurred during the 2-dose program leading to >97% decline in incidence over the 25 years of program implementation through 2019, based on data from 4 states with continuous passive reporting. Surveillance showed that declines were highest among children and adolescents covered by the routine vaccination recommendations but occurred in all age groups. Although surveillance systems changed and were adapted to reflect evolving epidemiology, data consistently demonstrated decreasing varicella incidence following the vaccination program implementation. The vaccination program dramatically decreased virus circulation and increased community protection. Continued and improved varicella surveillance is needed to accurately monitor disease epidemiology and further guide prevention efforts.
Article
Background: . The Vaccine Adverse Event Reporting System (VAERS) is the United States national passive vaccine safety surveillance system. We updated the data on the safety of single-antigen varicella vaccine (VAR) and assessed the safety of combination measles, mumps, rubella, and varicella vaccine (MMRV) licensed in the United States using VAERS data. Methods: US VAERS reports received after administration of VAR and MMRV during 2006-2020 were identified. Reports were analyzed by vaccine type, age, seriousness, most common adverse events (AEs), and concomitant vaccines. We reviewed medical records of selected reports of AEs of special interest and conducted empirical Bayesian data mining to identify disproportionally reported AEs. Results: During 2006-2020, approximately 132.8 million VAR doses were distributed; 40 684 reports were received in VAERS (30.6/100 000 doses distributed), with 4.1% classified as serious (1.3/100 000 doses distributed). Approximately 35.5 million MMRV doses were distributed; 13 325 reports were received (37.6/100 000 doses distributed) with 3.3% classified as serious (1.3/100 000 doses distributed). The most common adverse health events after both VAR and MMRV were injection site reactions (31% and 27%), rash (28% and 20%), and fever (12% and 14%), respectively. Vaccination errors accounted for 23% of reports after VAR administration and 41% after MMRV administration, but ≥95% of them did not describe an adverse health event. AEs associated with evidence of vaccine strain varicella-zoster virus (vVZV) infection included meningitis, encephalitis, herpes zoster, and 6 deaths (all in immunocompromised persons with contraindications for vaccination). No new or unexpected AE was disproportionally reported. Conclusions: No new or unexpected safety findings were detected for VAR and MMRV given as recommended, reinforcing the favorable safety profiles of these vaccines. Providers should obtain specimens for viral testing and strain-typing for serious AEs if they consider vVZV as the possible causative agent.
Article
Tracking vaccination coverage is a critical component of monitoring a vaccine program. Three different surveillance systems were used to examine trends in varicella vaccination coverage during the United States vaccination program: National Immunization Survey-Child, National Immunization Survey-Teen, and immunization information systems (IISs). The relationship of these trends to school requirements and disease decline was also examined. Among children aged 19-35 months, ≥1 dose of varicella vaccine increased from 16.0% in 1996 to 89.2% by the end of the 1-dose program in 2006, stabilizing around at least 90.0% thereafter. The uptake of the second dose was rapid after the 2007 recommendation. Two-dose coverage among children aged 7 years at 6 high-performing IIS sites increased from 2.6%-5.5% in 2006 to 86.0%-100.0% in 2020. Among adolescents aged 13-17 years, ≥2-dose coverage increased from 4.1% in 2006 to 91.9% in 2020. The proportion of adolescents with history of varicella disease declined from 69.9% in 2006 to 8.4% in 2020. In 2006, 92% of states and the District of Columbia (DC) had 1-dose daycare or school entry requirements; 88% of states and DC had 2-dose school entry requirements in the 2020-2021 school year. The successes in attaining and maintaining high vaccine coverage were paramount in the dramatic reduction of the varicella burden in the United States over the 25 years of the vaccination program, but opportunities remain to further increase coverage and decrease varicella morbidity and mortality.
Article
We describe the changing epidemiology of varicella outbreaks informed by past and current active and passive surveillance in the United States by reviewing data published during 1995-2015 and analyzing new data from 2016 to 2019. Varicella outbreaks were defined as ≥5 varicella cases within 1 setting and ≥1 incubation period. During the 1-dose varicella vaccination program (1995‒2006), the number of varicella outbreaks declined by 80% (2003-2006 vs 1995-1998) in 1 active surveillance area where vaccination coverage reached 90.5% in 2006. During the 2-dose program, in 7 states with consistent reporting to the Centers for Disease Control and Prevention, the number of outbreaks declined by 82% (2016-2019 vs 2005-2006). Over the entire program (1995-2019), outbreak size and duration declined from a median of 15 cases/outbreak and 45 days duration to 7 cases and 30 days duration. The proportion of outbreaks with <10 cases increased from 28% to 73%. During 2016‒2019, most (79%) outbreak cases occurred among unvaccinated or partially vaccinated persons eligible for second-dose vaccination, highlighting the potential for further varicella control.
Article
To describe the impact of the US varicella vaccination program on severe varicella outcomes, we analyzed varicella hospitalizations using the National Inpatient Sample 1993-2019 and varicella deaths using the National Center for Health Statistics data 1990-2019. Over 25 years of vaccination program (1995-2019), varicella hospitalizations, and deaths declined 94% and 97%, respectively, among persons aged <50 years. Most of the decline (∼90%) occurred during the 1-dose period (through 2006/2007) by attaining and maintaining high vaccination coverage; additional declines occurred during the 2-dose period, especially in the age groups covered by the 2-dose recommendation. The greatest decline for both hospitalizations and deaths (97% and >99%, respectively) was among persons aged <20 years, born during the varicella vaccination program. In the <20 age group, varicella hospitalization has become a rare event, and varicella deaths have been practically eliminated in the United States. A total of >10 500 varicella hospitalizations and 100 varicella deaths are now prevented annually in the United States as a direct result of vaccination and reduction in varicella-zoster virus circulation.
Article
Introduction Children may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration. Methods In six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003–2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR. Results Among 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups. Conclusions HZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.
Article
Introduction: Policy-makers in many countries have been wary of introducing varicella vaccination programs because of concerns that reduced exposures to varicella zoster virus could increase incidence herpes zoster (HZ) incidence. The U.S. introduced varicella vaccination in 1996 and has empiric evidence regarding this concern. Areas covered: This comprehensive review provides background emphasizing the epidemiology of varicella and of HZ in the U.S. before and after introduction of their respective vaccines. The epidemiology is complex, and interpretation is complicated by methodologic challenges, by unexplained increases in age-specific HZ incidence that preceded varicella vaccination, and by introduction of vaccines for prevention of HZ. Nonetheless, observations from studies using different platforms and designs have yielded consistent findings, suggesting they are robust. Expert opinion: There has been no evidence that the U.S. varicella vaccination program increased HZ incidence in the general adult population over baseline trends. Furthermore, HZ incidence in children is declining. The U.S. experience can inform development of new generations of models to predict HZ trends. More importantly, it provides reassurance for countries considering varicella vaccination that an effective program can reduce varicella morbidity and mortality while reducing the likelihood of HZ among children, and potentially, over time, across the entire population.
Article
Background and objectives: After the 1996 introduction of routine varicella vaccination in the United States, most studies evaluating pediatric herpes zoster (HZ) incidence reported lower incidence over time, with varying degrees of decline. Using the combined databases of 6 integrated health care organizations, we examined HZ incidence in children over a 12-year period in the varicella vaccine era. Methods: This study included children aged 0 through 17 years from 2003 through 2014. Using electronic medical records, we identified HZ cases through International Classification of Diseases, Ninth Revision diagnosis code 053. We calculated HZ incidence rates per 100 000 person years of health plan membership for all children and among children who were vaccinated versus unvaccinated. We calculated rates for the 12-year period and examined temporal trends. Among children who were vaccinated, we compared HZ rates by month and year of age at vaccination. Results: The study included 6 372 067 children with ≥1 month of health plan membership. For the 12-year period, the crude HZ incidence rate for all subjects was 74 per 100 000 person years, and the rate among children who were vaccinated was 38 per 100 000 person years, which was 78% lower than that among children who were unvaccinated (170 per 100 000 person years; P < .0001). Overall HZ incidence declined by 72% (P < .0001) from 2003 through 2014. Annual rates in children who were vaccinated were consistently lower than in children who were unvaccinated. Conclusions: With this population-based study, we confirm the decline in pediatric HZ incidence and the significantly lower incidence among children who are vaccinated, reinforcing the benefit of routine varicella vaccination to prevent pediatric HZ.
Article
Background: Although the 1-dose varicella vaccination program, introduced in 1996, has led to significant declines in varicella disease, outbreaks continued to occur, which led to the adoption of a 2-dose vaccination program in 2007. We previously reported an 88% decline in varicella-related hospitalizations and a 59% decline in outpatient visits during 1994-2002. We now update data on varicella healthcare utilization with 10 years of additional data, during a period of stabilizing first-dose coverage and rapidly increasing second-dose coverage. Methods: We performed a retrospective cohort study using claims data from 1994-2012 Truven Health MarketScan databases. We examined trends in rates of varicella-related outpatient visits and hospitalizations for MarketScan enrollees aged 0-49 years, including outpatient laboratory testing, outpatient antiviral use, and pediatric strokes, with 1994-1995 as the prevaccination period and 2006-2012 as the 2-dose varicella vaccination period. Results: Varicella outpatient visits declined 84% in 2012 versus the prevaccination period, with a 60% decline during the 2-dose period. Varicella hospitalizations declined 93% in 2012 versus the prevaccination period, with a 38% decline during the 2-dose period. The proportion of those with a varicella outpatient visit having varicella laboratory testing increased from 6% in 2003 to 17% in 2012. There were 21 445 (17%) with a claim for antivirals, which was relatively stable over time. There was no reduction in pediatric strokes during 1994-2012. Conclusions: We document from our large study population that the varicella vaccination program has led to significant declines in outpatient visits and hospitalizations from the prevaccination period through 2012, with additional declines during the 2-dose varicella vaccination period.
Article
Objective. —To evaluate the economic consequences of a routine varicella vaccination program that targets healthy children.Methods. —Decision analysis was used to compare the costs, outcomes, and cost-effectiveness of a routine vaccination program with no intervention. Clinical outcomes were based on a mathematical model of vaccine efficacy that relied on published and unpublished data and on expert opinion. Medical utilization rates and costs were collected from multiple sources, including the Kaiser Permanente Medical Care Program and the California Hospital Discharge Database.Results. —A routine varicella vaccination program for healthy children would prevent 94% of all potential cases of chickenpox, provided the vaccination coverage rate is 97% at school entry. It would cost approximately 162millionannuallyifonedoseofvaccineperchildwererecommendedatacostof162 million annually if one dose of vaccine per child were recommended at a cost of 35 per dose. From the societal perspective, which includes work-loss costs as well as medical costs, the program would save more than 5foreverydollarinvestedinvaccination.However,fromthehealthcarepayersperspective(medicalcostsonly),theprogramwouldcostapproximately5 for every dollar invested in vaccination. However, from the health care payer's perspective (medical costs only), the program would cost approximately 2 per chickenpox case prevented, or $2500 per life-year saved. The medical cost of disease prevention was sensitive to the vaccination coverage rate and vaccine price but was relatively insensitive to assumptions about vaccine efficacy within plausible ranges. An additional program for catch-up vaccination of 12-year-olds would have high incremental costs if the vaccination coverage rate of children of preschool age were 97%, but would result in net savings at a coverage rate of 50%.Conclusions. —A routine varicella vaccination program for healthy children would result in net savings from the societal perspective, which includes work-loss costs as well as medical costs. Compared with other prevention programs, it would also be relatively cost-effective from the health care payer's perspective.(JAMA. 1994;271:375-381)
Article
The Philadelphia Department of Public Health (PDPH) conducts active surveillance for varicella in West Philadelphia. For its approximately 300 active surveillance sites, PDPH mandates biweekly reports of varicella (including zero cases) and performs intensive case investigations. Elsewhere in Philadelphia, surveillance sites passively report varicella cases, and abbreviated investigations are conducted. We used active varicella surveillance program data to inform the transition to nationwide passive varicella surveillance. We compared classification of reported cases, varicella disease incidence, and reporting completeness for active and passive surveillance areas for 2005-2010. We assessed reporting completeness using capture-recapture analysis of 2- to 18-year-old cases reported by schools/daycare centers and health-care providers. From 2005 to 2010, PDPH received 3,280 passive and 969 active surveillance varicella case reports. Most passive surveillance reports were classified as probable cases (18% confirmed, 56% probable, and 26% excluded), whereas nearly all of the active surveillance reports were either confirmed or excluded (36% confirmed, 11% probable, and 53% excluded). Overall incidence rates calculated using confirmed/probable cases were similar in the active and passive surveillance areas. Detection of laboratory-confirmed, breakthrough, and moderate-to-severe cases was equivalent for both surveillance areas. Although active surveillance for varicella results in better classified cases, passive surveillance provides comparable data for monitoring disease trends in breakthrough and moderate-to-severe varicella. To further improve passive surveillance in the two-dose-varicella vaccine era, jurisdictions should consider conducting periodic enhanced surveillance, encouraging laboratory testing, and collecting additional varicella-specific variables for passive surveillance.
Article
The development of a varicella vaccine has raised questions about the cost effectiveness of vaccination, but little information on the costs of chickenpox exists. The purpose of this study was to evaluate medical costs and the value of work loss among families whose children had chickenpox. Interviews were conducted with 179 families who made advice nurse calls or urgent care clinic visits to three clinics in the Northern California Kaiser Permanente Medical Care Plan. Two-thirds of working mothers and one-third of working fathers missed work to care for children with chickenpox. The mean value of the work lost because of chickenpox was 293/familyor293/family or 183/chickenpox case. The estimated costs of nonprescription medications were 20/familyor20/family or 12.50/chickenpox case. Children were sick enough to need to stay home for only one-third as many days as chicken actually stayed home because of school exclusion policies. These empiric results differ from previous estimates of the medical and work loss costs of varicella and should be included in analyses of the cost effectiveness of proposed vaccination programs.
Article
We present data to confirm that exposure to varicella boosts immunity to herpes-zoster. We show that exposure to varicella is greater in adults living with children and that this exposure is highly protective against zoster (Incidence ratio=0.75, 95% CI, 0.63-0.89). The data is used to parameterise a mathematical model of varicella zoster virus (VZV) transmission that captures differences in exposure to varicella in adults living with and without children. Under the 'best-fit' model, exposure to varicella is estimated to boost cell-mediated immunity for an average of 20 years (95% CI, 7-41years). Mass varicella vaccination is expected to cause a major epidemic of herpes-zoster, affecting more than 50% of those aged 10-44 years at the introduction of vaccination.
Article
Since varicella vaccine was first recommended for routine immunization in the United States in 1995, the incidence of disease has dropped substantially. However, national surveillance data are incomplete, and comprehensive data regarding outpatient as well as hospital utilization have not been reported. To examine the impact of the varicella vaccination program on medical visits and associated expenditures. Retrospective population-based study examining the trends in varicella health care utilization, based on data from the MarketScan databases, which include enrollees (children and adults) of more than 100 health insurance plans of approximately 40 large US employers, from 1994 to 2002. Trends in rates of varicella-related hospitalizations and ambulatory visits and direct medical expenditures for hospitalizations and ambulatory visits, analyzed using 1994 and 1995 as the prevaccination baseline. From the prevaccination period to 2002, hospitalizations due to varicella declined by 88% (from 2.3 to 0.3 per 100,000 population) and ambulatory visits declined by 59% (from 215 to 89 per 100,000 population). Hospitalizations and ambulatory visits declined in all age groups, with the greatest declines among infants younger than 1 year. Total estimated direct medical expenditures for varicella hospitalizations and ambulatory visits declined by 74%, from an average of 84.9 million dollars in 1994 and 1995 to 22.1 million dollars in 2002. Since the introduction of the varicella vaccination program, varicella hospitalizations, ambulatory visits, and their associated expenditures have declined dramatically among all age groups in the United States.
Article
Two live, attenuated varicella zoster virus-containing vaccines are available in the United States for prevention of varicella: 1) a single-antigen varicella vaccine (VARIVAX, Merck & Co., Inc., Whitehouse Station, New Jersey), which was licensed in the United States in 1995 for use among healthy children aged > or = 12 months, adolescents, and adults; and 2) a combination measles, mumps, rubella, and varicella vaccine (ProQuad, Merck & Co., Inc., Whitehouse Station, New Jersey), which was licensed in the United States in 2005 for use among healthy children aged 12 months-12 years. Initial Advisory Committee on Immunization Practices (ACIP) recommendations for prevention of varicella issued in 1995 (CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1996;45 [No. RR-11]) included routine vaccination of children aged 12-18 months, catch-up vaccination of susceptible children aged 19 months-12 years, and vaccination of susceptible persons who have close contact with persons at high risk for serious complications (e.g., health-care personnel and family contacts of immunocompromised persons). One dose of vaccine was recommended for children aged 12 months-12 years and 2 doses, 4-8 weeks apart, for persons aged > or = 13 years. In 1999, ACIP updated the recommendations (CDC. Prevention of varicella: updated recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1999;48 [No. RR-6]) to include establishing child care and school entry requirements, use of the vaccine following exposure and for outbreak control, use of the vaccine for certain children infected with human immunodeficiency virus, and vaccination of adolescents and adults at high risk for exposure or transmission. In June 2005 and June 2006, ACIP adopted new recommendations regarding the use of live, attenuated varicella vaccines for prevention of varicella. This report revises, updates, and replaces the 1996 and 1999 ACIP statements for prevention of varicella. The new recommendations include 1) implementation of a routine 2-dose varicella vaccination program for children, with the first dose administered at age 12-15 months and the second dose at age 4-6 years; 2) a second dose catch-up varicella vaccination for children, adolescents, and adults who previously had received 1 dose; 3) routine vaccination of all healthy persons aged > or = 13 years without evidence of immunity; 4) prenatal assessment and postpartum vaccination; 5) expanding the use of the varicella vaccine for HIV-infected children with age-specific CD4+ T lymphocyte percentages of 15%-24% and adolescents and adults with CD4+ T lymphocyte counts > or = 200 cells/microL; and 6) establishing middle school, high school, and college entry vaccination requirements. ACIP also approved criteria for evidence of immunity to varicella.
Article
Frequent varicella outbreaks with sizable impact on the US public health system have continued to occur despite the success of the country's 1-dose varicella vaccination program. The Advisory Committee on Immunization Practices recently recommended adding a routine second dose of varicella vaccine and weighed economic projections as well as public health goals in their deliberations. This decision-tree—based analysis was conducted to evaluate the economic impact of the projected 2-dose varicella vaccination program as well as the existing 1-dose program. The analysis used population-based vaccination coverage and disease incidence data to make projections for a hypothetical US birth cohort of 4,100,000 infants born in 2006. Compared with no vaccination, both the 1-dose program (societal benefit-cost ratio [BCR], 4.37) and 2-dose program (BCR, 2.73) were estimated to be cost saving from the societal perspective. Compared with the 1-dose program, the incremental second dose was not cost saving (societal incremental BCR, 0.56). The incremental cost effectiveness ratio for the second dose was 343percaseprevented,or343 per case prevented, or ∼109,000 per quality-adjusted lifeyear saved, and these results were sensitive to assumptions about vaccine effectiveness and prices.
Article
Two national surveys were conducted to evaluate the status of varicella case-based surveillance and outbreak response. Although progress toward national surveillance has been significant, a large number of jurisdictions are still without case-based surveillance. For jurisdictions beginning case-based surveillance with limited resources, a staged approach is recommended. The national outbreak survey showed that a significant number of varicella outbreaks continue to occur. The majority of jurisdictions respond to these outbreaks, although the response varies considerably. Depending on the outbreak-response approach, costs per outbreak ranged from 3000foratypical,orpassive,responseto3000 for a typical, or passive, response to 6000 for a more active response. As varicella surveillance and outbreak control improves, jurisdictions may benefit from more-standardized outbreak-control practices. The recent recommendation by the Advisory Committee on Immunization Practices for a routine second dose of varicella vaccine should lead to better varicella disease control, making case-based surveillance and appropriate outbreak response even more feasible.
  • S Weinmann
  • A L Naleway
  • P Koppolu
Weinmann S, Naleway AL, Koppolu P, et al. Incidence of herpes zoster among children: 2003-2014. Pediatrics 2019; 144.