Trends in age-specific varicella incidences following the introduction of the general recommendation for varicella immunization in Germany, 2006-2022.

BACKGROUND: In Germany, general childhood varicella vaccination has been recommended since 2004. A feared effect of low vaccination coverage is a possible shift in incidence from children to teenagers and young adults who are at higher risk of severe outcomes. If true, this shift would possibly necessitate changes to the national immunization strategy. We aimed to evaluate the effects of the general vaccination recommendation on age-specific varicella incidences in Germany in general and examine specifically whether a shift from children to teenagers (15 to 19 years) has occurred. METHODS: Trends in age-specific incidences were evaluated using triangulation with the following datasets: national mandatory notification data (N) (2014-2022), billing data of the statutory health insurance associations (I) (2009-2017) and data from a doctor's sentinel system (S) (2006-2017). Similar clinical case definitions were used in N and S, while I used ICD-10-codes. Age groups were stratified as available in all three systems. Incidences per year were calculated based on the total population (N), the number of statutory health insured (I), and extrapolated from S to the total population. RESULTS: During all years of observation, age-specific incidences have dropped significantly across all age-groups for S und I. The age groups (under 10 years) with initially highest incidences were the ones with the strongest reductions (under 1 year: -90%, 1-4 years: -95.5%, 5-9 years: -89.2% for S; -67.7%, -78%, -79.3% for I). A single 53.1% increase in the low incidence in S among 15-19-year olds observed in 2017 compared to 2016 could not be confirmed in N or I. Increases in incidences during the first two years of N are probably due to improved notification behaviour over these years. In 2019, all age-specific incidences increased (N), with 15 to 19-year olds showing the highest relative increase (28.2%). CONCLUSIONS: Since the introduction of the general vaccine recommendation against varicella, incidences across all age-groups have declined significantly. Available data indicate no evidence for a shift in disease incidence to older age groups. Every incidence increase beyond childhood age should however be followed up closely. So far, children and adolescents have both benefitted from the current vaccination strategy.

[Evaluation of the COVID-19 vaccination after broad implementation-an interim conclusion for Germany in July 2022]. / Evaluation der COVID-19-Impfung nach breiter Anwendung ­ ein Zwischenfazit für Deutschland im Juli 2022.

Vaccines against COVID-19 have been available in Germany since December 2020. At the Robert Koch Institute (RKI), the Immunization Unit is responsible for monitoring vaccination coverage and assessment of vaccine effectiveness. This article provides an overview of the respective reporting structures, vaccination databases, and epidemiological studies established by the Immunization Unit during the COVID-19 pandemic. We describe the COVID-19 Digital Vaccination Coverage Monitoring (DIM), which provides daily updates on vaccination coverage by age group. We next describe how, based on the DIM data and COVID-19 case data, the assessment of vaccine effectiveness against different clinical endpoints (hospitalization, intensive care, death) is performed. While this method is used for a preliminary estimate of vaccine efficacy, population-based nonrandomized studies are able to provide more precise and detailed estimates under "real-world" conditions. In this context, we describe the hospital-based case-control study COViK, which is being conducted in collaboration with the Paul Ehrlich Institute (PEI). We discuss strengths and limitations of the abovementioned structures and tools. Finally, we provide an outlook on future challenges that may arise during the ongoing pandemic and during the transition phase into an endemic situation.

Impact of COVID-19 immunisation on COVID-19 incidence, hospitalisations, and deaths by age group in Germany from December 2020 to October 2021.

BACKGROUND: Utilising national surveillance data, we investigated the impact of the COVID-19 immunisation campaign on COVID-19 morbidity and mortality between December/2020 and October/2021 in Germany. METHODS: We compared patterns in immunisation coverage, incidence, hospitalisations, and deaths among 12-17, 18-59, and 60+ year-olds and examined these patterns within the context of anti-pandemic measures. RESULTS: COVID-19 incidence increased in all age groups following the end of lockdown restrictions in March/2021, but as Germany experienced successive peaks in incidence, age groups with higher immunisation coverage experienced successively smaller peaks. Notwithstanding corresponding increases during periods of higher incidence, among those aged 60+ years, COVID-19 related hospitalisations and deaths declined considerably as immunisation coverage increased, despite circulation of virus variants known to cause more severe illness. CONCLUSION: Although ecological in nature, this study allows us to demonstrate clear patterns of decline in COVID-19 morbidity and mortality in Germany during the course of the immunisation campaign.

A 5-year look-back at the notification and management of vaccine supply shortages in Germany.

BackgroundUnavailability of vaccines endangers the overall goal to protect individuals and whole populations against infections.MethodsThe German notification system includes the publication of vaccine supply shortages reported by marketing authorisation holders (MAH), information on the availability of alternative vaccine products, guidance for physicians providing vaccinations and an unavailability reporting tool to monitor regional distribution issues.AimThis study provides a retrospective analysis of supply issues and measures in the context of European and global vaccine supply constraints.Resultsbetween October 2015 and December 2020, the 250 notifications concerned all types of vaccines (54 products). Most shortages were caused by increased demand associated with immigration in Germany in 2015 and 2016, new or extended vaccine recommendations, increased awareness, or changes in global immunisation programmes. Shortages of a duration up to 30 days were mitigated using existing storage capacities. Longer shortages, triggered by high demand on a national level, were mitigated using alternative products and re-allocation; in a few cases, vaccines were imported. However, for long lasting supply shortages associated with increased global demand, often occurring in combination with manufacturing issues, few compensatory mechanisms were available. Nevertheless, only few critical incidents were identified: (i) shortage of hexavalent vaccines endangering neonatal immunisation programmes in 2015;(ii) distribution issues with influenza vaccines in 2018; and (iii) unmet demand for pneumococcal and influenza vaccines during the coronavirus disease (COVID)-19 pandemic.ConclusionVaccine product shortages in Germany resemble those present in neighbouring EU states and often reflect increased global demand not matched by manufacturing capacities.

Monitoring of Influenza Vaccination Coverage among Pregnant Women in Germany Based on Nationwide Outpatient Claims Data: Findings for Seasons 2014/15 to 2019/20.

Pregnant women and their infants are at increased risk for severe influenza-related complications. A decade has passed since influenza vaccination was first recommended for pregnant women in Germany in 2010; however, monitoring of vaccination coverage (VC) has not yet been implemented for this target group. Using nationwide outpatient claims data, we here provide results on influenza VC among pregnant women in Germany for seasons 2014/15 to 2019/20. For any given season, pregnant women were defined as women who had undergone prenatal health care in at least two consecutive quarters within a season. VC increased from 9.0% in season 2014/15 to 16.6% in 2019/20 (+84%), while most of the increase occurred from season 2016/17 (VC: 9.9%) onwards (+68%). Consistently across seasons, women in east Germany were 40 to 60% more likely to be vaccinated compared to women residing in west Germany. According to age, the highest VC was observed among women aged 35 to <40 years (2019/20: 18.2%). Despite noticeable increases in influenza VC during recent years, overall coverage remains low among pregnant women. Starting with this analysis, VC among pregnant women in Germany will be monitored on a yearly basis in order to detect trends and identify immunization gaps.

Cancelled routine vaccination appointments due to COVID-19 pandemic in Germany.

Pandemic measures to mitigate the outbreak of SARS-CoV-2 in Germany led to cancellations of routine vaccination appointments for both adults and children. Survey data indicate that, with easing pandemic restrictions, many cancelled appointments were rescheduled or caught up. Nevertheless, 40% of cancelled appointments were still not rescheduled and were primarily cancelled by patients. Therefore, doctors should regularly remind patients of vaccinations and use every visit to improve their vaccination statuses.

[The global measles crisis-a diversity of causes from armed conflicts to vaccination skepticism]. / Die globale Masernkrise ­ Ursachenvielfalt von bewaffneten Konflikten bis Impfskepsis.

BACKGROUND AND AIM: Despite a safe and effective vaccine being available for many years, the number of measles cases has been increasing again worldwide since 2018. Our report aims to identify putative reasons for this development. METHODS: We conducted a selective literature search. Further, current reports and data from the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and the World Bank were evaluated. RESULTS: According to the WHO, Madagascar, the Ukraine, and Israel had the highest incidences of measles worldwide between 1 July 2018 and 30 June 2019. Measles outbreaks are a sign of inadequate vaccination rates caused by multiple structural and psychological barriers. Structural barriers to measles vaccination, such as a lack of routine vaccination programs, have been identified as the main cause of low measles vaccination rates, particularly in fragile countries e.g. due to armed conflicts, but also in some subpopulations of higher-income countries e.g. due to lacking resources for vaccination services. Psychological barriers leading to vaccination skepticism were prevalent mainly in developed countries with well-functioning health systems and a high standard of living. CONCLUSION: The reasons for the global measles crisis are manifold and in some cases have existed for decades. However, the consequences appear to be accumulating and have had a dramatic impact on case numbers since 2018. The goal of measles elimination and maintenance of the necessary vaccination programs is a constant challenge that requires strict and permanent compliance with WHO recommendations. The number of measles cases reported in Germany is still at a level above the key target for measles elimination specified in the national immunization plan. Timely and/or locally restricted as well as nationwide outbreaks continue to occur. Since infectious agents can be transmitted across borders, the international perspective is an essential component of national health policy in Germany.

Non-specific effects of MMR vaccines on infectious disease related hospitalizations during the second year of life in high-income countries: a systematic review and meta-analysis.

Children who had received MMR as the most recent vaccine had a pooled 35% (95%CI: 12-53%) lower risk for hospitalization due to any infectious disease, compared to children who had received DTaP as the most recent vaccine (three studies, 1,919,192 children). The effect was stronger for respiratory tract infections than for gastrointestinal infections. Two studies investigated MMR alone, compared to concurrent administration of MMR and DTaP vaccines. Here, the pooled estimate for reduction in risk of hospitalization for any infectious disease was smaller and not significant (15%; 95%CI: -9% to 34%). Risk of bias was serious to critical in all studies. Moreover, two of the five studies demonstrated a significantly reduced risk for a control outcome (hospitalization for injuries), strongly indicating healthy vaccinee bias or residual confounding. The available evidence is insufficient to support a change in current vaccination schedules.

[Vaccination coverage of children and adolescents in Germany: New data from KiGGS Wave 2 and trends from the KiGGS study]. / Durchimpfung von Kindern und Jugendlichen in Deutschland: Aktuelle Daten aus KiGGS Welle 2 und Trends aus der KiGGS-Studie.

Since the baseline study of the "German Health Interview and Examination Survey for Children and Adolescents (KiGGS)" in 2003-2006, vaccination conditions in Germany have changed and additional vaccinations have been included in the immunization schedule. The current KiGGS data can be used to assess the current vaccination status of 3­ to 17-year-olds and trends in the 1985-2013 birth cohorts.Of the 15,023 total participants in KiGGS Wave 2, 3238 aged 3-17 years participated in the KiGGS Wave 2 examinations and submitted the complete vaccination certificate or were, according to their parents, unvaccinated. In this group, vaccination coverage was high for the majority of vaccinations for both girls and boys. Vaccination coverage has increased in children and adolescents in the last 10 years. This is especially true for vaccines for which there were strong deficiencies in the KiGGS baseline study, such as the hepatitis B and second measles vaccinations in all age groups, the booster dose against pertussis (11- to 17-year olds), as well as the booster dose against tetanus in the 7­ to 10-year-olds.Sociodemographic factors are still determinants of vaccination status. Less than one child in two is vaccinated against hepatitis B (45.9%) when parents state fear of side effects or indicate vaccine skepticism as reasons against vaccinations. Despite significant increases, vaccination coverage at the end of the second year of life is still far below 95% for all vaccinations (measles: 1st dose: 88.6%; 2nd dose: 64.4%) even in the most recent birth cohorts.The results show where further efforts are needed to increase vaccination coverage by the remaining last percentage points, achieve the timely delivery of all vaccinations listed in the immunization schedule, as well as meet the defined elimination goals.

[Compliance with adult measles and pertussis vaccination recommendations : Analysis of data from the national monitoring system KV-Impfsurveillance]. / Umsetzung der Masern- und Pertussisimpfempfehlungen für Erwachsene : Analyse von Daten des bundesweiten Monitorings der KV-Impfsurveillance.

The Standing Committee on Vaccination recommends adult measles and pertussis vaccination. The measles vaccine has been recommended since 2010 to adults born after 1970 with less than two doses in childhood, and an acellular pertussis vaccine (ap) since 2009 to be administered to all adults, with the next recommended decennial tetanus (T) and diphtheria (d) booster as a Tdap combination vaccine.We aim to determine the annual uptake of the measles vaccine (vaccination incidence) and its proportion in pediatric and gynecological practices as interdisciplinary services (2009-2016). We further aim to calculate the 10-year ap vaccination coverage and missed vaccination opportunities as the proportion vaccinated with Td only among all Td and Tdap vaccinees (2007-2016).Within the national vaccination monitoring system KV-Impfsurveillance of the Robert Koch Institute and all Associations of Statutory Health Insurance Physicians, all persons receiving the relevant vaccinations were identified in nationwide statutory health insurance claims and related to the numbers of insured persons.The measles vaccination incidence in 2009 was 0.4%, increasing to ≥1.0% annually since 2013. It was higher in western than eastern federal states and higher among women than men. Of all measles vaccinations, 6.8% were given by pediatricians. Men received 2.6% of their vaccinations by gynecologists. The ap vaccination coverage was 32.4%. The proportion of exclusively Td vaccinated adults fell from 84% (2007) to 24% (from 2013 onwards).Since their recommendation, the KV-Impfsurveillance system shows increased uptake of measles and pertussis vaccines with regional and sex differences and is thus instrumental in their evaluation. Analyses of interdisciplinary vaccinations and missed vaccination opportunities provide insight into the potential for increasing uptake.

Systematic Review and Meta-analysis of Chickenpox Vaccination and Risk of Herpes Zoster: A Quantitative View on the "Exogenous Boosting Hypothesis".

BACKGROUND: The "exogenous boosting hypothesis" postulates that reexposure to circulating varicella zoster virus (VZV) over the life span inhibits reactivation of VZV. Consequently, if circulation of VZV is suppressed by introduction of chickenpox vaccination, incidences of herpes zoster may rise. METHODS: We performed a systematic review and metaanalysis on impact of chickenpox vaccination on herpes zoster incidence and time trend, focusing on population-level effects by analyzing interrupted time-series (ITS) studies. We searched Medline and Embase for ITS reporting incidences of chickenpox and herpes zoster before and after implementation of chickenpox vaccination. Autoregressive integrated moving average models were calculated. Change in trend and incidence from studies were pooled. RESULTS: Twelve studies were included, of which 6 were eligible for metaanalysis. Metaanalysis revealed a significant increase in chickenpox cases prior to implementation of chickenpox vaccination and a reversed trend thereafter, particularly in individuals aged 1-4 years. The increase in age-adjusted herpes zoster incidence before implementation of chickenpox vaccination did not change thereafter. However, separate analysis of age groups revealed a net increase of hospitalized herpes zoster cases in individuals aged 10-49 years after implementation of chickenpox vaccination. This very small effect (fewer than 2 additional cases per 100 000 persons) did not occur in other age groups. CONCLUSIONS: To date, no conclusive evidence exists that chickenpox vaccination has a substantial population-level impact on herpes zoster in nonvaccinated age groups. While exogenous boosting may exist, the effect size generated by chickenpox vaccination might be rather small on the population level.

Trends in herpes zoster epidemiology in Germany based on primary care sentinel surveillance data, 2005-2016.

Herpes zoster (HZ) is caused by reactivation of the varicella-zoster-virus (VZV). Childhood varicella vaccination, as recommended in Germany in 2004, may reduce the risk of HZ in vaccinated children but also virus circulation and thus the booster possibility of latent infected persons. In this context we analyzed age-specific trends in HZ epidemiology in Germany using data on HZ-associated outpatient consultations in participating sentinel sites and HZ-associated cases in all hospitals since 2005. We analyzed two separate time periods that differed in sentinel management and data integrity. For the period 2005-2010, we found a decrease in HZ-associated outpatient consultations in 1- to 4-year-olds (IRR = 0.72, 95%CI 0.63-0.81, p<0.001). For the period 2013-2016, we observed a decrease in HZ-associated outpatient consultations in 10- to 14-year-olds (IRR = 0.85, 95%CI 0.78-0.93, p<0.01). Moreover, we detected an increase in the age groups 20 years and older except for the group 30-39 years. HZ-associated hospitalizations showed similar trends for the second time period (here 2012-2015). The decrease in HZ-associated outpatient consultations and hospitalizations in children started and continued over cohorts eligible for varicella vaccination and could be a result of their reduced HZ-risk. Whether the observed steady increasing HZ incidences for adults are associated with the varicella vaccination in children remains unclear and could not be investigated with our data.

Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany - a mathematical modelling study.

BACKGROUND: Epidemiological studies suggest that reduced exposure to varicella might lead to an increased risk for herpes zoster (HZ). Reduction of exposure to varicella is a consequence of varicella vaccination but also of demographic changes. We analyzed how the combination of vaccination programs and demographic dynamics will affect the epidemiology of varicella and HZ in Germany over the next 50 years. METHODS: We used a deterministic dynamic compartmental model to assess the impact of different varicella and HZ vaccination strategies on varicella and HZ epidemiology in three demographic scenarios, namely the projected population for Germany, the projected population additionally accounting for increased immigration as observed in 2015/2016, and a stationary population. RESULTS: Projected demographic changes alone result in an increase of annual HZ cases by 18.3% and a decrease of varicella cases by 45.7% between 1990 and 2060. Independently of the demographic scenario, varicella vaccination reduces the cumulative number of varicella cases until 2060 by approximately 70%, but also increases HZ cases by 10%. Unlike the currently licensed live attenuated HZ vaccine, the new subunit vaccine candidate might completely counteract this effect. Relative vaccine effects were consistent across all demographic scenarios. CONCLUSION: Demographic dynamics will be a major determinant of HZ epidemiology in the next 50 years. While stationary population models are appropriate for assessing vaccination impact, models incorporating realistic population structures allow a direct comparison to surveillance data and can thus provide additional input for immunization decision-making and resource planning.

Invasive pneumococcal disease in children under 16 years of age: Incomplete rebound in incidence after the maximum effect of PCV13 in 2012/13 in Germany.

OBJECTIVE: To identify a potential nadir of the impact of pneumococcal conjugate vaccination (PCV) in infancy on invasive pneumococcal diseases (IPD) in children under 16 in Germany. METHODS: Active surveillance on IPD based on two independent data sources with capture-recapture correction for underreporting. Annual incidence rates by age group, serotypes, site of infection, and relative incidence reduction compared to pre-vaccination period (1997-2001) at nadir and for the most recent season are reported. We calculated vaccine coverage at the age of 24 months using health insurance claims data. RESULTS: 96-97% of children had received at least two doses of PCV since 2009. The maximum impact on overall IPD incidence was achieved in 2012/13 (-48% [95% CI: -55%; -39%]) with a rebound to -26% [95% CI: -36%; -16%] in 2015/16. Non-PCV13 serotypes accounted for 84.1% of the IPD cases in 2015/16. The most frequent non-PCV serotypes in IPD in 2014/15 and 2015/16 were 10A, 24F, 15C, 12F, 38, 22F, 23B, and 15B. The impact at nadir was highest in children 0-1 years of age both in meningitis and non-meningitis cases, whereas the impact for other age groups was higher for meningitis cases. The rebound mainly pertained to non-meningitis cases. CONCLUSION: The maximum impact of pneumococcal conjugate vaccination has been attained and signs of a rebound are apparent. Sustained surveillance for IPD in children is warranted to assess whether these trends will continue. There may be a need for vaccines using antigens common to all serotypes.

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

BACKGROUND: In 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. METHODS: Serum 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. RESULTS: The 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). CONCLUSION: In 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.

Assessing varicella vaccine effectiveness and its influencing factors using health insurance claims data, Germany, 2006 to 2015.

In Germany, routine childhood varicella vaccination was implemented in 2004 with two doses recommended since 2009. We used an immunisation information system based on countrywide health insurance claims data to analyse vaccine effectiveness (VE) and factors influencing VE. We applied proportional hazard models to estimate VE under various conditions and compared the risk of acquiring varicella among unvaccinated children in regions with high vs low vaccination coverage (VC). Among 1.4 million children we identified 29,404 varicella cases over a maximum follow-up of 8 years post-vaccination. One-dose VE was 81.9% (95% confidence interval (CI): 81.4-82.5), two-dose VE 94.4% (95% CI: 94.2-94.6). With dose one given 1-27 days after measles-containing vaccine (MCV), one-dose VE was 32.2% (95% CI: 10.4-48.6), two-dose VE 92.8% (95% CI: 84.8-96.6). VE was not associated with age at vaccination (11-14 vs ≥ 15 months), time since vaccination, or vaccine type. Unvaccinated children had a twofold higher risk of acquiring varicella in low VC regions. Our system generated valuable data, showing that two-dose varicella vaccination provides good protection for at least 8 years. Unvaccinated children benefit from herd effects. When the first varicella vaccine dose is given shortly after MCV, a second dose is essential.

[The epidemiology of varicella disease in Germany after introduction of a vaccination recommendation : Analysis of mandatory and sentinel data between 2002 and 2014]. / Die Epidemiologie der Varizellen in Deutschland unter Einfluss der Varizellen-Impfempfehlung : Auswertung der Sentinel- und Meldepflichtdaten 2002­2014.

BACKGROUND: Since 2004 a single varicella vaccination for all infants aged 11-14 months has been recommended in Germany and since 2009 a second dose at the age of 15-23 months is recommended. Vaccination coverage after 24 months rose from 43% in 2006 to 87.5% in 2012. A mandatory notification system was introduced in the New Federal States (NFS) between 2002 and 2009 and nationwide in 2013. A national sentinel system has been in place since 2005. OBJECTIVE AND METHOD: We analyzed both data sources to describe the varicella epidemiology related to vaccination coverage after initiation of routine childhood varicella vaccination and to evaluate both notification systems regarding informative value and data quality. We looked at trends, age distribution and incidences using Microsoft Excel and Stata12. Vaccination coverage data were available from health insurance claims data. RESULTS: By 2013 a decrease of cases/medical practice/month from 3.47 to 0.43 was observed. The incidence in the NFS declined from 32 to 12 out of 100,000. Sentinel and mandatory notification data showed the largest decrease among the 1-4 year-olds (-94 and -90% resp.). In 2014, varicella incidences increased in all age groups, but not the cases/medical-practice/month by age in the sentinel. DISCUSSION: Increasing vaccination coverage and decreasing varicella cases demonstrate the success of routine childhood varicella vaccination. Mandatory notification data allow incidence calculation; The sentinel system has been providing more detailed information about vaccination status, better data quality and continuous national data since 2005, irrespective of the Infectious disease protection act. Trends and age distribution can be continuously calculated, whereas the nationwide mandatory data collected in the short period since April 2013 can only be evaluated to a limited extent.

Strong Additional Effect of a Second Varicella Vaccine Dose in Children in Germany, 2009-2014.

OBJECTIVES: Vaccine effectiveness (VE) of 1 and 2 varicella vaccine doses in children aged 1-4 years in Germany was evaluated to determine the additional effect of a second dose recommended at least 4 weeks after the first dose and before the second birthday. STUDY DESIGN: To estimate the VE, the proportion of cases vaccinated was compared with the proportion of the population vaccinated using nationwide sentinel surveillance data from 2009-2014 and health insurance claims data covering the period January 2009-March 2014, respectively. A general linear model was used to estimate the OR of vaccination in the cases and the population and the corresponding CIs to observe the stability of the VE estimates over time, and to assess the incremental effectiveness of a second dose. RESULTS: The overall VE after 1 dose was 86.6% (95% CI: 85.2-87.9), ranging between 94.6% (95% CI: 87.9-97.6) in the first quarter of 2011 and 50.3% (95% CI: 7.3-73.4) in the third quarter of 2013. The overall VE after 2 doses was 97.3% (95% CI: 97.0-97.6), ranging between 99.5% (95% CI: 97.8-99.9) in the second quarter of 2009 and 91.3% (95% CI: 85.7-94.8) in the third quarter of 2013. The incremental VE of 2 doses was 84.6% (95% CI: 81.7-86.9). CONCLUSIONS: The substantially higher VE of 2 varicella vaccine doses compared with 1 dose in young children and the strong additional effect of the second dose support the public health relevance of a 2-dose schedule and the success of the early second vaccine dose.