Thorsten Rieck

Herpes zoster in Germany: Quantifying the burden of disease

BackgroundHerpes zoster (HZ) is caused by a reactivation of the varicella-zoster-virus (VZV) and mainly affects individuals aged ≥ 50 years. Vaccines have been licensed or are under development that can protect against HZ and its main complication postherpetic neuralgia (PHN). In Germany, the burden of disease caused by HZ is not well known. To support the decision making process related to a potential vaccination recommendation, we estimated annual HZ disease burden in people aged ≥ 50 years in Germany by utilizing various data sources.MethodsWe assessed for 2007 and 2008 HZ-outpatient incidence (number of cases per 1,000 person-years, PY) by utilizing the Association of Statutory Health Insurance Physicians (ASHIP) database, which contains nationwide routine outpatient data. For the same time period annual number of HZ-inpatients and HZ-associated deaths were identified by using the Federal Health Monitoring System (FHM). PHN-incidence and loss of quality-adjusted life years (QALYs) caused by HZ were calculated by multiplying number of identified HZ-patients with upper and lower limit estimates for proportion of HZ-cases developing PHN and HZ-related QALY, respectively.ResultsFor the study period we identified an annual average of 306,511 HZ-outpatients aged 50+, resulting in a HZ-incidence of 9.6/1,000 PY. A total 14,249 HZ-associated inpatients and 66 deaths were reported in both years on average. HZ-incidence increased by age from 6.21 in people 50-54 years to 13.19 per 1,000 PY in people aged ≥ 90 years. Females were significantly more frequently affected than males in terms of outpatient HZ-incidence (11.12 vs. 7.8 per 1,000 PY), inpatient HZ-incidence (0.51 vs. 0.38 per 1,000 PY) and mortality (0.29 vs. 0.10 per 100,000 PY). PHN-incidence was estimated to range between 0.43 and 1.33 per 1,000 PY. Based on these figures, there were between 3,065 to 24,094 QALYs lost due to HZ in persons aged ≥ 50 years in Germany per annum.ConclusionOur study provides important baseline estimates for HZ-related disease burden in Germany. HZ poses a considerable burden on the health care system in Germany both in terms of outpatient and inpatient services. Follow-up assessments of HZ disease burden are needed to monitor the impact of VZV-vaccinations in Germany.

Vaccination coverage among children in Germany estimated by analysis of health insurance claims data

In Germany, the national routine childhood immunization schedule comprises 12 vaccinations. Primary immunizations should be completed by 24 mo of age. However, nationwide monitoring of vaccination coverage (VC) is performed only at school entry. We utilized health insurance claims data covering ~85% of the total population with the objectives to (1) assess VC of all recommended childhood vaccinations in birth-cohorts 2004–2009, (2) analyze cross-sectional (at 24 and 36 mo) and longitudinal trends, and (3) validate the method internally and externally. Counting vaccine doses in a retrospective cohort fashion, we assembled individual vaccination histories and summarized VC to nationwide figures. For most long-established vaccinations, VC at 24 mo was at moderate levels (~73–80%) and increased slightly across birth-cohorts. One dose measles VC was high (94%), but low (69%) for the second dose. VC with a full course of recently introduced varicella, pneumococcal, and meningococcal C vaccines increased across birth-cohorts from below 10% above 60%, 70%, and 80%, respectively. At 36 mo, VC had increased further by up to 15 percentage points depending on vaccination. Longitudinal analysis suggested a continued VC increase until school entry. Validation of VC figures with primary data showed an overall good agreement. In conclusion, analysis of health insurance claims data allows for the estimation of VC among children in Germany considering completeness and timeliness of vaccination series. This approach provides valid nationwide VC figures for all currently recommended pediatric vaccinations and fills the information gap between early infancy and late assessment at school entry.

Mumps epidemiology in Germany 2007-11

In Germany, mumps has been notifiable until 2013 only in the five Eastern federal states (EFS) of former East Germany. Due to different immunisation policies until 1990 and varying vaccination coverages thereafter, mumps incidences cannot be extrapolated to the 11 Western federal states (WFS). We studied mumps-related International Classification of Diseases (ICD-10) code diagnoses claimed through statutory health insurances between 2007 and 2011 to estimate countrywide mumps incidences in the outpatient sector, and compared them with case numbers from ambulatory notification data. Overall, 32,330 outpatient mumps cases were claimed. Annual incidence ranged between 9.3/100,000 and 11.8/100,000 and showed a significant decreasing trend. Compared with EFS, mumps incidence in WFS was higher and indicated a shift towards older age groups. Notified outpatient case numbers in EFS were 13-fold lower and from voluntary surveillance during an outbreak in the WFS Bavaria 8-fold lower than from insurance data (n=316 versus n=4,217 and n=238 versus 1,995, respectively). Of all notified cases with available information, 75.4% (EFS) and 57.6% (Bavaria) were unvaccinated; 6.8% (EFS) and 19.3% (Bavaria) required hospitalisation. In Germany, mumps is still endemic despite decades of vaccination, with considerable underreporting in the established notification systems.

Measles incidence and reporting trends in Germany, 2007-2011.

Abstract Objective We aimed to quantify progress towards measles elimination in Germany from 2007 to 2011 and to estimate any potential underreporting over this period. Methods We determined the annual incidence of notified cases of measles – for each year – in northern, western, eastern and southern Germany and across the whole country. We then used measles-related health insurance claims to estimate the corresponding incidence. Findings In each year between 2007 and 2011, there were 6.9–19.6 (mean: 10.8) notified cases of measles per million population. Incidence decreased with age and showed geographical variation, with highest mean incidence – 20.3 cases per million – in southern Germany. Over the study period, incidence decreased by 10% (incidence rate ratio, IRR: 0.90; 95% confidence interval, CI: 0.85–0.95) per year in western Germany but increased by 77% (IRR: 1.77; 95% CI: 1.62–1.93) per year in eastern Germany. Although the estimated incidence of measles based on insurance claims showed similar trends, these estimates were 2.0- to 4.8-fold higher than the incidence of notified cases. Comparisons between the data sets indicated that the underreporting increased with age and was generally less in years when measles incidence was high than in low-incidence years. Conclusion Germany is still far from achieving measles elimination. There is substantial regional variation in measles epidemiology and, therefore, a need for region-specific interventions. Our analysis indicates underreporting in the routine surveillance system between 2007 and 2011, especially among adults.

Effectiveness of routine and booster pertussis vaccination in children and adolescents, federal state of Brandenburg, Germany, 2002-2012.

Background: In Germany, whole-cell pertussis vaccines were rapidly replaced by high-concentration acellular pertussis-containing vaccines (3+1 doses from 2 months of age) starting in 1995. Boosters were recommended for 9- to 17-year-olds (2000) and for 5- to 6-year-olds (2006). Pertussis incidence remains high despite rising vaccination coverage (VC). Therefore, we analyzed VC and vaccine effectiveness (VE) in the federal state of Brandenburg. Methods: In a stratified case–cohort analysis, we compared VC of reported pertussis cases with VC assessed in schools and kindergartens in the following strata: Children aged 2–3 years born 2005–2009 (toddlers), 5–7 years born 1995–2006 (pre-schoolers) and 15–16 years born 1995–1996 (adolescents). We calculated VE for primary and booster vaccination using Poisson regression. Results: Four-dose VE decreased from 96.9% in toddlers [95% confidence interval (CI): 72.2–99.3] to 87.8% in pre-schoolers (95% CI: 79.7–92.7) to 81.7% in adolescents (95% CI: 40.6–92.8). Four-dose VE was lower in pre-schoolers born after 1996 (75.4%) than in those born 1995–1996, ~1% and ~21% of whom had received ≥1 dose of whole-cell pertussis vaccines, respectively. VE was higher in pre-schoolers and adolescents who received a booster (92.8%and 96.5%, respectively). However, overall booster VC was only 19% and 76% in these age groups, respectively. Conclusions: We observed high VE of routine pertussis vaccination, with evidence of waning over time and improved VE after booster vaccination. Increased uptake and monitoring of recommended pertussis boosters is urgently recommended to decrease high pertussis morbidity particularly in older children and adolescents.

Application of the screening method to monitor influenza vaccine effectiveness among the elderly in Germany

BackgroundElderly people are at increased risk for severe influenza illness and constitute therefore a major target-group for seasonal influenza vaccination in most industrialized countries. The aim of this study was to estimate influenza vaccine effectiveness (VE) among individuals aged 60+ years over three seasons and to assess if the screening method is a suitable tool to monitor influenza VE in this particular target-group in Germany.MethodsWe identified laboratory-confirmed influenza cases aged 60+ years through the national communicable disease reporting system for seasons 2010/11, 2011/12 and 2012/13. Vaccination coverage (VC) data were retrieved from a database of health insurance claims representing ~85% of the total German population. We applied the screening method to calculate influenza subtype-specific VE and compared our results with VE estimates from other observational studies in Europe.ResultsIn total, 7,156 laboratory-confirmed influenza cases were included. VE against all influenza types ranged between 49% (95% confidence interval [CI]: 39–56) in 2011/12 and 80% (95% CI: 76-83%) in 2010/11. In 2010/11 subtype-specific VE against influenza A(H1N1)pdm and B was 76% and 84%, respectively. In the following seasons, VE against influenza A(H1N1)pdm, A(H3N2) and B was 87%, -9% , 74% (2011/12), and 74%, 39%, 73% (2012/13). VE was higher among hospitalized compared to non-hospitalized influenza A cases. Seventeen observational studies from Europe reporting subtype-specific VE among the elderly were identified for the respective seasons (all applying the test-negative design) and showed comparable subtype-specific VE estimates.ConclusionsAccording to our study, influenza vaccination provided moderate protection against laboratory-confirmed influenza A(H1N1)pdm and B in individuals aged 60+ but no or only little protection against A(H3N2). Higher VE among hospitalized cases might indicate higher protection against severe influenza disease. Based on the available data, the screening method allowed us to assess subtype-specific VE in hospitalized and non-hospitalized elderly persons. Since controlling for several important confounders was not possible, the applied method only provided crude VE estimates. However, given the precise VC-data and the large number of cases, the screening method provided results being in line with VE estimates from other observational studies in Europe that applied a different study design.

Anaphylaxis After Immunization of Children and Adolescents in Germany.

Background: Anaphylaxis is a life-threatening event. The aim of this study was to estimate the annual frequency of anaphylaxis after immunization in individuals younger than 18 years in Germany leading to hospitalization. Methods: All suspected cases of postvaccination anaphylaxis involving individuals aged 0−17 years reported to the German surveillance unit for rare pediatric diseases (Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland) from June 2008 through May 2010, and all suspected cases of anaphylaxis as an adverse event following immunization in the same age group reported to the Paul-Ehrlich-Institut during the observational period were classified according to the Brighton collaboration case definition. Only hospitalized cases of anaphylaxis fulfilling Brighton collaboration case definition level 1–3 criteria were eligible. Estimates for the annual frequency were calculated by using capture–recapture methods. Results: A total of 22 reports were eligible. Median age of the affected individuals (13 males, 9 females) was 7.0 years (range: 2 months to 17 years). Anaphylaxis occurred most frequently after administration of AS03 adjuvanted A/H1N1 pandemic influenza vaccine (n = 8). The annual frequency of anaphylaxis after vaccination (excluding pandemic influenza vaccine as well as monovalent measles and rubella vaccines) was estimated to be 6.8 (95% confidence interval: 6.1–10.9). The estimated incidence of anaphylaxis after administration of specific vaccines ranged from 0.4 to 127.6 cases per 1,000,000 doses administered. Conclusions: This study confirms that anaphylaxis after immunization in children and adolescents is a rare event. AS03 adjuvanted A/H1N1 pandemic influenza vaccine seems to be associated with a higher risk of anaphylaxis when compared with other vaccines.

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.

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.

Impfprävention in Deutschland: Ein Überblick zu den Entwicklungen der letzten 25 Jahren

Zusammenfassung Das Impfsystem in Deutschland hat sich in den letzten 25 Jahren wesentlich weiterentwickelt. Essentiell war die Schaffung gesetzlicher Rahmenbedingungen sowohl für die Entwicklung einheitlicher Impfempfehlungen, deren Finanzierung und Umsetzung als auch für deren Evaluation. Mit der Zulassung neuer Impfstoffe und Einführung neuer Konzepte haben die Empfehlungen der Ständigen Impfkommission (STIKO) ein deutlich größeres Spektrum und tragen zu einem effektiven Schutz vor übertragbaren Erkrankungen in der Allgemeinbevölkerung und auch in speziellen Risikogruppen bei. Im Vergleich zu 1993 stehen heute Daten zur Verfügung, die es besser ermöglichen, die Inanspruchnahme von Impfungen auf regionaler Ebene und in einzelnen Altersgruppen zu analysieren oder die Effekte der Impfungen zu belegen.