Comparative varicella vaccine effectiveness during outbreaks in day-care centres

doi:10.1016/j.vaccine.2009.10.086

Vaccine

Volume 28, Issue 3, 8 January 2010, Pages 686-691

https://doi.org/10.1016/j.vaccine.2009.10.086 Get rights and content

Abstract

Background

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC).

Methods

Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age < 11 months, vaccinated at age < 11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC).

Findings

Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57–81, p < 0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix^® (RR = 2.8, 95%CI 1.0–7.8, p = 0.05) or Priorix-Tetra^® (RR = 2.4, 95%CI 0.7–8.3, p = 0.18) but lower for 2 doses of Priorix-Tetra^® (RR = 0.5, 95%CI 0.1–2.7, p = 0.41) than for 1 dose of Varivax^®.

Interpretation

Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.

Section snippets

Study design

Local health authorities throughout Germany were encouraged to report varicella outbreaks to the Robert Koch Institute (RKI) on a voluntary basis. Outbreaks were confirmed by public health professionals and an identification letter was sent to each DCC (A, B, C, D, E, F and G). At site visits of DCC we requested self-administered questionnaires including varicella history and demographic characteristics from the parents of all children. Furthermore we reviewed children's vaccination records,

Results

Characteristics of the outbreaks investigated in 7 DCC in Berlin and Potsdam in 2008 and 2009 are shown in Table 1. Altogether 1084 children were attending investigated DCC at the time of the outbreaks. Age was known in 1045 (96%) children; median and mean age was 4 years (interquartile range 2.9–5.2 years of age).

We received 749 (69%) questionnaires and varicella vaccination status was verified by the vaccination records of 631 (58%) individuals (Fig. 1). Compliance with return of

Discussion

To our knowledge, our study is the first to compare VE and risk factors for BV after varicella vaccination with different vaccine brands in the same population. Our results indicate that VE and the risk of BV is not only associated with the number of vaccine doses but also with the vaccine brand. The estimated VE for 1 dose of Varilrix^® or Priorix-Tetra^® was lower than for 1 dose of Varivax^®. Only few data exist regarding VE of different varicella vaccine brands. Seward et al. reported an

Conclusions

In order to achieve a maximum benefit of the varicella vaccination program and to reduce varicella morbidity in Germany, we strongly recommend enhanced efforts to increase the uptake of at least 1 dose of varicella vaccine.

Though, 1 dose vaccination schedule may not achieve program goals or adequate varicella control as 1 dose VE is significantly lower than 2 doses varicella VE. As VE after 1 dose of Varilrix^® is similar to that after 1 dose of Priorix-Tetra^®, the varicella vaccine component is

Acknowledgements

We would like to thank the following persons for their assistance with the outbreak investigation: DCCs staff, Sina Bärwolff, Sabine Ploeger, Sabine Klamka of Local Public Health Dept. in Marzahn-Hellersdorf of Berlin and staff of Local Public Health Dept. in Potsdam and in Märkisch-Oderland, Germany. We are very grateful to Marion Muehlen and other EPIET coordinators, Matthias an der Heiden, and Rüdiger von Kries for expert consultations and Jaska Schirmack for data entry. We would like to

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Effectiveness of the combined MMRV Priorix-Tetra™ vaccine against varicella in a large Italian region: A case-control study
2024, Vaccine
Priorix-Tetra™ (MMRV GlaxoSmithKline Biologicals’ vaccine) was developed based on the existing measles-mumps-rubella and varicella vaccines. In this study, we aimed to estimate the effectiveness of the combined measles-mumps-rubella-varicella Priorix-Tetra™ vaccine against varicella in real-world conditions.
We conducted a post-marketing retrospective case-control study in the Apulia region of Italy in children aged 1–9 years born between January 1, 2008 and December 31, 2016. We assessed the effectiveness against varicella of all grades of severity (including hospitalisation) and against hospitalisation for varicella of a single and two doses of Priorix-Tetra™. Moreover, we also assessed effectiveness of monovalent varicella (monovalent-V) vaccine and any varicella vaccines. Vaccine effectiveness was calculated as (1–OR) x 100. We introduced demographic variables in the model to adjust Vaccine effectiveness (aVE) by potential confounders (sex and year of birth).
We recorded 625 varicella cases and matched them with 1,875 controls. Among 625 cases, 198 had received a single MMRV dose, 10 two MMRV doses, 46 a single monovalent-V dose, none two monovalent-V doses; four a monovalent-V as first dose and MMRV as second dose, and one a MMRV as first dose and monovalent-V as second dose; 366 cases were not vaccinated.
The aVE against varicella of all grades of severity was 77.0% and 93.0% after a single dose and after two doses of MMRV, respectively. The aVE against varicella of all grades was 72.0% after a single dose of monovalent-V vaccine. The aVE against varicella of all grades of severity was 76.0% after a single dose and 94.0% after two doses of any varicella vaccine. The aVE against varicella hospitalisation was 96% after a single dose of any varicella vaccine.
Priorix-Tetra™ showed to be an effective vaccine and the two-dose schedule should be recommended to optimise immunisation programmes. A single dose was able to provide protection against varicella hospitalisation.
Comparison of performance of varicella vaccines via infectious disease modeling
2022, Vaccine
Citation Excerpt :
While the pooled estimates differ from the ones obtained in the current study and RCTs, the majority of studies included in Marin et al analysis were conducted in outbreak settings where vaccine efficacy is known to be underestimated. A real world observational study in Germany of 631 vaccinated children reported one dose effectiveness of V-MSD to be 86% (95% CI: 56–96%) compared to 56% for V-GSK (95% CI: 29–72%), estimates again lower than in our study as this study was conducted in an outbreak setting [24]. The World Health Organization recommends universal varicella vaccination in countries that can maintain vaccination coverage rates of ≥80% [25].
Population-level infectious disease models for varicella require vaccine parameters, namely 'take' and 'duration of protection' (defined here as vaccine performance), to quantify the impact of vaccination. Current published models for varicella use vaccine parameters derived from various methodologies which does not allow for the direct comparison of different vaccines.
We estimated take and duration of protection using deterministic compartmental models to simulate clinical trials of one- or two-dose varicella vaccination using Varivax® (V-MSD) and Varilrix® (V-GSK). We fit different models to clinical trial data on breakthrough infections and evaluated their respective goodness-of-fit using the Akaike Information Criterion (AIC).
Based upon the clinical trial data, we estimated that 90.3% (95% CI: 87.8–92.9%) of the cohort gained permanent protection from breakthrough varicella after the first dose of V-MSD compared to 61.7% (95% CI: 58.2–65.3%) with the first dose of V-GSK. We further estimated that a total of 97.0% (95% CI: 95.2–98.8%) and 93.8% (95% CI: 92.2–95.4%) of the cohort were permanently protected after two-doses of V-MSD and V-GSK, respectively. According to the AIC, our new model (V-MSD AIC = 92.7; V-GSK AIC = 170.3) provided a better fit than an existing model (V-MSD AIC = 108.9; V-GSK AIC = 216.1).
The model developed fits the long-term clinical trial data on breakthrough infections for both V-MSD and V-GSK, thus, allowing for the direct comparison of vaccine performance. We estimated that a single dose of V-MSD was more likely to provide permanent protection than a single dose of V-GSK, while the protection offered by two doses was similar for both vaccines.
Trend in varicella patients 4 years after implementation of universal two-dose varicella vaccination in Japan
2020, Vaccine
To elucidate the trend and clinical spectrum of virologically diagnosed varicella patients after implementation of universal vaccination as a national immunization program in Japan.
Study subjects were patients suspected of varicella, less than 15 years of age, who visited 14 pediatric clinics in the Nagoya VZV Study Group from September 2015 to August 2019. Practitioners collected patient samples and information such as backgrounds, clinical symptoms, and previous immunization status. All patients were confirmed as having varicella based on molecular diagnostic assays.
Varicella zoster virus (VZV) DNA was detected in swab samples from 506 (83.1%) of the 609 suspected patients. The 455 varicella patients for whom vaccination status was available were divided into two groups: 180 universal vaccination targets and 275 non-targets. Numbers of monthly varicella patients decreased gradually during the observation period. In the 2016/17 season, the seasonal epidemic of varicella became undetectable in the universal vaccination target group, and starting in the 2017/18 season, it was obscured even in the non-target group. The median age of patients was significantly lower in the universal vaccination target group (3 years) than the non-target group (7 years) (P < 0.001). Vaccination status differed significantly between the two groups (P < 0.001). Most varicella patients were in the non-target group, especially those who had been vaccinated once (60.4%). Frequency of fever (P < 0.001) and number of skin rashes at the time of the first hospital visit (P = 0.001) were significantly higher in the non-target group.
Although the number of childhood varicella patients declined after implementation of national immunization with two doses of varicella vaccination, sporadic outbreaks still occurred, mainly in the non–universal vaccination target group. Insufficient vaccination of members of this group is likely to be a major reason for small local outbreaks.
Varicella outbreak trends in school settings during the voluntary single-dose vaccine era from 2006 to 2017 in Shanghai, China
2019, International Journal of Infectious Diseases
Citation Excerpt :
In response to cases of BV, a two-dose VarV schedule has been implemented in several higher socio-economic status countries and regions since 2006 (Marin et al., 2007; Wutzler et al., 2017). The incidence of BV cases during outbreaks in daycare centers decreased significantly from 19% in regions with a single-dose VarV schedule to 3% in regions with a two-dose VarV schedule during outbreaks (Spackova et al., 2010). As geometric mean antibody concentrations increase roughly 10-fold following administration of the second dose of VarV in children, boosting may help students who have failed to respond to the priming immunization to mount a protective immune response (Bonanni et al., 2013).
To investigate varicella outbreak trends among schoolchildren during the voluntary single-dose varicella vaccine (VarV) era in Shanghai, China.
Trends in school varicella outbreaks from 2006 to 2017 were assessed using joinpoint regression models. The impacts of changes in single-dose VarV coverage among schoolchildren and implementation of post-exposure prophylaxis (PEP) strategies on outbreak trends were further analyzed.
In total, 265 varicella outbreaks involving 3263 cases were reported in Shanghai from 2006 to 2017. The number of outbreaks showed an increasing trend from 2006 to 2017 (t = 2.62, p = 0.026), especially in kindergartens. The proportion of breakthrough varicella cases among all outbreak-related cases showed an increasing trend from 30.4% in 2008 to 85.7% in 2017 (t = 7.45, p < 0.001). Single-dose VarV coverage among schoolchildren was 88.1%, and showed a significant increase from the 1996 to the 2008 birth cohorts, followed by a non-significant decline from the 2008 to the 2014 birth cohorts. During school outbreaks in which PEP campaigns were conducted, the varicella attack rate was significantly lower than those in outbreaks without PEP campaigns (1.2% vs. 1.4%; Chi-square = 23.35, p < 0.001).
Even with high coverage, single-dose VarV is insufficient to prevent school outbreaks. The administration of VarV as PEP is an appropriate intervention for varicella outbreak control prior to implementing a two-dose VarV schedule.
Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: 10-year follow-up of a phase 3 multicentre, observer-blind, randomised, controlled trial
2019, The Lancet Infectious Diseases
The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella.
This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12–22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3:3:1) to receive two doses of MMRV, one dose of MMR and one dose of varicella vaccine, or two doses of MMR, 42 days apart. Varicella cases were confirmed by detection of viral DNA, or epidemiological link and clinical assessment, by an independent data monitoring committee; disease severity was based on a modified Vázquez scale. Hazard ratios for MMRV and MMR + V versus MMR estimated in the per-protocol cohort using a Cox proportional hazards regression model were used to calculate vaccine efficacy and 95% CI. Serious adverse events were recorded throughout the study in all vaccinated children. Study objectives were secondary and descriptive. The trial is registered at ClinicalTrials.gov, number NCT00226499.
Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. The per-protocol cohort included 2279 children from the MMRV group, 2266 from the MMR + V group, and 744 from the MMR group. From baseline to a median follow-up of 9·8 years, 76 (3%) children in the MMRV group, 469 (21%) in the MMR + V group, and 352 (47%) in the MMR group had varicella. Vaccine efficacy against all varicella was 95·4% (95% CI 94·0–96·4) for MMRV and 67·2% (62·3–71·5) for MMR + V; vaccine efficacy against moderate or severe varicella was 99·1% (97·9–99·6) for MMRV and 89·5% (86·1–92·1) for MMR + V. During phase b, serious adverse events were reported by 290 (15%) of 1961 children in the MMRV group, 317 (16%) of 1978 in the MMR + V group, and 93 (15%) of 641 in the MMR group. There were no treatment-related deaths.
The 10-years vaccine efficacy observed, suggests that a two-dose schedule of varicella vaccine provided optimum long-term protection for the prevention of varicella by offering individual protection against all severities of disease and leading to a potential reduction in transmission, as observed in the US experience with universal mass vaccination.
GlaxoSmithKline Biologicals.
Varicella vaccine effectiveness over 10 years in Australia; moderate protection from 1-dose program
2019, Journal of Infection
Citation Excerpt :
Many studies did not specify or include both vaccines brands, although most were conducted in the US, where only Varivax® has been used. A study by Spackova et al.36 was able to perform a side by side comparison of VE for Varivax® and Varilrix®, with point estimates for 1-dose effectiveness of 86% (95% CI: 56–96%) and 56% (95% CI: 29–72%), respectively. In the meta-analysis by Marin et al.35 stratification by brand showed a higher 1-dose point estimate of 82% (95% CI: 79–85%) for Varivax® compared to 77% (95% CI: 62–85%) for Varilrix®, although confidence intervals were overlapping.
To examine the impact of Australia's single dose infant varicella vaccination program, we assessed single dose varicella vaccine effectiveness (VE) in preventing hospitalised disease using two methods.
Clinically confirmed varicella cases from the Paediatric Active Enhanced Disease Surveillance (PAEDS) sentinel network were age-matched to 20 controls obtained from the Australian Immunisation Register. Conditional logistic regression models were used to estimate VE and compared with estimates obtained using our second approach.
There were 78 hospitalised varicella cases during the post vaccine introduction period from January 2008 to December 2015, who were eligible for funded varicella vaccination. Median age at onset was 4.5 years and more than half (59%) were vaccinated. The majority of children received one vaccine brand (Varilrix, GSK). The estimated case-control VE for one dose of vaccine against hospitalised varicella was 64.7% (95% CI: 43.3–78.0%); estimates using the screening method were not significantly different. Exclusion of children who were immunocompromised did not significantly alter VE estimates.
Although Australia's program has impacted on the burden of varicella disease, single dose VE against varicella hospitalisation is only moderate. Greater reductions in varicella disease could potentially be achieved by incorporation of a second vaccine dose into the program to minimise breakthrough disease and interrupt virus circulation.

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Comparative varicella vaccine effectiveness during outbreaks in day-care centres

Abstract

Background

Methods

Findings

Interpretation

Section snippets

Study design

Results

Discussion

Conclusions

Acknowledgements

Infect Dis Clin North Am

Lancet

Lancet

Vaccine

Vaccine

Int J Infect Dis

Varicella vaccination in Japan, South Korea, and Europe

J Infect Dis

MWAOMaPAOM

Vaccine. 5th ed.

Epidemiologisches Bull

Assessing vaccine efficacy in the field. Further observations

Epidemiol Rev

Epidemiologic methods in immunization programs

Epidemiol Rev

Varicella vaccine effectiveness in the US vaccination program: a review

J Infect Dis

Vaccine effectiveness and severity of varicella among previously vaccinated children during outbreaks in day-care centers with low vaccination coverage

Pediatr Infect Dis J

Use of a computerized database to study the effectiveness of an attenuated varicella vaccine

Pediatr Infect Dis J

Effectiveness of the Oka/GSK attenuated varicella vaccine for the prevention of chickenpox in clinical practice in Israel

Pediatr Infect Dis J

Varicella vaccine effectiveness during an outbreak in a partially vaccinated population in Spain

Pediatr Infect Dis J