Annicka Reuss

Influenza vaccine effectiveness estimates in Europe in a season with three influenza type/subtypes circulating: the I-MOVE multicentre case–control study, influenza season 2012/13

In the fifth season of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE), we undertook a multicentre case-control study (MCCS) in seven European Union (EU) Member States to measure 2012/13 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory confirmed as influenza. The season was characterised by substantial co-circulation of influenza B, A(H1N1)pdm09 and A(H3N2) viruses. Practitioners systematically selected ILI patients to swab ≤7 days of symptom onset. We compared influenza-positive by type/subtype to influenza-negative patients among those who met the EU ILI case definition. We conducted a complete case analysis using logistic regression with study as fixed effect and calculated adjusted vaccine effectiveness (AVE), controlling for potential confounders (age, sex, symptom onset week and presence of chronic conditions). We calculated AVE by type/subtype. Study sites sent 7,954 ILI/acute respiratory infection records for analysis. After applying exclusion criteria, we included 4,627 ILI patients in the analysis of VE against influenza B (1,937 cases), 3,516 for A(H1N1)pdm09 (1,068 cases) and 3,340 for influenza A(H3N2) (730 cases). AVE was 49.3% (95% confidence interval (CI): 32.4 to 62.0) against influenza B, 50.4% (95% CI: 28.4 to 65.6) against A(H1N1)pdm09 and 42.2% (95% CI: 14.9 to 60.7) against A(H3N2). Our results suggest an overall low to moderate AVE against influenza B, A(H1N1)pdm09 and A(H3N2), between 42 and 50%. In this season with many co-circulating viruses, the high sample size enabled stratified AVE by type/subtype. The low estimates indicate seasonal influenza vaccines should be improved to achieve acceptable protection levels.

The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2)

BACKGROUND In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season. METHODS Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochranes Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model. RESULTS We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). CONCLUSIONS The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses.

I-MOVE multicentre case–control study 2010/11 to 2014/15 : is there within-season waning of influenza type/subtype vaccine effectiveness with increasing time since vaccination?

Since the 2008/9 influenza season, the I-MOVE multicentre case-control study measures influenza vaccine effectiveness (VE) against medically-attended influenza-like-illness (ILI) laboratory confirmed as influenza. In 2011/12, European studies reported a decline in VE against influenza A(H3N2) within the season. Using combined I-MOVE data from 2010/11 to 2014/15 we studied the effects of time since vaccination on influenza type/subtype-specific VE. We modelled influenza type/subtype-specific VE by time since vaccination using a restricted cubic spline, controlling for potential confounders (age, sex, time of onset, chronic conditions). Over 10,000 ILI cases were included in each analysis of influenza A(H3N2), A(H1N1)pdm09 and B; with 4,759, 3,152 and 3,617 influenza positive cases respectively. VE against influenza A(H3N2) reached 50.6% (95% CI: 30.0-65.1) 38 days after vaccination, declined to 0% (95% CI: -18.1-15.2) from 111 days onwards. At day 54 VE against influenza A(H1N1)pdm09 reached 55.3% (95% CI: 37.9-67.9) and remained between this value and 50.3% (95% CI: 34.8-62.1) until season end. VE against influenza B declined from 70.7% (95% CI: 51.3-82.4) 44 days after vaccination to 21.4% (95% CI: -57.4-60.8) at season end. To assess if vaccination campaign strategies need revising more evidence on VE by time since vaccination is urgently needed.

INCIDENCE RATE OF NONTUBERCULOUS MYCOBACTERIAL DISEASE IN IMMUNOCOMPETENT CHILDREN: A PROSPECTIVE NATIONWIDE SURVEILLANCE STUDY IN GERMANY

An increasing incidence in disease caused by nontuberculous mycobacteria is being reported. We investigated the burden of disease in immunocompetent German children in a prospective nationwide study from April 2003 to September 2005. Ninety-seven percent of children presented with lymphadenitis; median age was 2.5 years. Using the capture-recapture method, we estimated a cumulative incidence rate of 3.1/100000 children.

Varicella vaccination coverage of children under two years of age in Germany.

BackgroundSince July 2004, routine varicella vaccination is recommended by the German Standing Vaccination Committee in Germany. Health Insurance Funds started to cover vaccination costs at different time points between 2004 and 2006 in the Federal States. Nationwide representative data on vaccination coverage against varicella of children under two years of age are not available. We aimed to determine varicella vaccination coverage in statutory health insured children under two years of age in twelve German Federal States using data from associations of statutory health insurance physicians (ASHIPs), in order to investigate the acceptance of the recommended routine varicella vaccination programme.MethodsWe analysed data on varicella vaccination from 13 of 17 ASHIPs of the years 2004 to 2007. The study population consisted of all statutory health insured children under two years of age born in 2004 (cohort 2004) or 2005 (cohort 2005) in one of the studied regions. Vaccination coverage was determined by the number of children vaccinated under 2 years of age within the study population.ResultsVaricella vaccination coverage of children under two years of age with either one dose of the monovalent varicella vaccine or two doses of the measles, mumps, rubella, and varicella vaccine increased from 34% (cohort 2004) to 51% (cohort 2005) in the studied regions (p < 0.001). More than half of the vaccinated children of cohort 2004 and two third of cohort 2005 were immunised at the recommended age 11 to 14 months. The level of vaccination coverage of cohort 2004 was significantly associated with the delay in introduction of cost coverage since the recommendation of varicella vaccination (p < 0.001).ConclusionsOur study shows increasing varicella vaccination coverage of young children, indicating a growing acceptance of the routine varicella vaccination programme by the parents and physicians. We recommend further monitoring of vaccination coverage using data from ASHIPs to investigate acceptance of the routine vaccination programmes over time.

Contact Investigation for Imported Case of Middle East Respiratory Syndrome, Germany

No evidence was found for nosocomial transmission of this coronavirus.

Influenza vaccination coverage in the 2004/05, 2005/06, and 2006/07 seasons: a secondary data analysis based on billing data of the German Associations of Statutory Health Insurance Physicians

BACKGROUND The German Standing Committee on Vaccination recommends annual vaccination for persons in high-risk groups in order to lower the disease burden associated with seasonal influenza. The stated target is 75% vaccination coverage of people over age 60 by the year 2010. We present statistics based on billing data of the German associations of statutory health insurance physicians regarding vaccination coverage for influenza in the three seasons from 2004/05 to 2006/07. METHODS We analyzed anonymous data from 14 of the 17 associations of statutory health insurance physicians in Germany. The study population consisted of all persons covered by statutory health insurance in the geographical areas under study (61.5 million persons, or 86% of the total population of these areas). Vaccination coverage was calculated as the number of vaccinated persons divided by the number of persons covered by statutory health insurance. RESULTS The influenza vaccination coverage of the overall study population was 19% in 2004/05, 22% in 2005/06, and 21% in 2006/07. The coverage of persons over age 60 was 45% in 2004/05, 50% in 2005/06, and 49% in 2006/07 and was higher in areas that were formerly part of East Germany than in the rest of the country. More than a third of all vaccinated persons were vaccinated in all three seasons, as were almost half of the vaccinated persons over age 60. CONCLUSION There was no secular increase in influenza vaccination coverage over the period 2005/06 to 2006/07. The stated target of 75% vaccination coverage for persons over age 60 by the year 2010 would thus seem to represent a major challenge for all persons involved. The analysis of data of the associations of statutory health insurance physicians enables continuous monitoring of influenza vaccination coverage.

Bestimmung von Impfquoten und Inzidenzen von Erkrankungen anhand von Daten der Kassenärztlichen Vereinigungen

BACKGROUND The KV-Sentinel, established in 2004, is a joint project of the Robert Koch Institute and the 17 associations of statutory health insurance physicians (ASHIPs) in Germany. The ASHIPs provide anonymous physicians billing data to the Robert Koch Institute. The aim of this article is to describe methodological approaches for processing these routine data to determine vaccination coverage and incidence of vaccine preventable diseases. Furthermore, we discuss limitations in interpreting these data. METHODS The ASHIPs perform a data query of all vaccinations and of ICD-10 codes for pertussis, measles, mumps, varicella and herpes zoster and send anonymous data to the Robert Koch Institute. We perform routine tests to ensure data quality. Study population is the statutory health insured population (85.5% of the German population). Vaccination coverage is determined by the number of vaccinated persons and the number of statutory health insured persons. Incidence is calculated by the number of diseased persons per 100 000 statutory health insured persons. RESULTS All 17 ASHIPs participate in the project. In total, 95 905 605 data records for vaccinations and 4 570 919 data records for pertussis, measles, mumps, varicella and herpes zoster were provided from 2004 to 2007. After performing routine tests with regard to structure and content of data, more than 99% of the data records can be analysed. In 2007, the majority of given vaccinations were monovalent vaccinations against influenza (39%) and tick-borne encephalitis (17%). In 2006 and 2007, 1 893 790 data records for diagnoses were provided. Of these, 75% were acute diagnoses and of these 70% were confirmed diagnoses. Most often, ICD-10 codes for herpes zoster (57%) and varicella (35%) were reported. CONCLUSION Nationwide vaccination coverage of statutory health insured persons by age group can be determined by using billing data. It is possible to validate billing data of vaccinations with available data from other studies. Interpretation of billing data of acute vaccine preventable diseases remains challenging because it is difficult to assess potential under- or overestimation without the possibility of external validation. Therefore, further research is needed.

Under-reporting of measles: an evaluation based on data from north rhine-westphalia.

BACKGROUND Eliminating measles in Europe by 2015 is a WHO health goal. In Germany, physicians are legally required to report measles cases, yet it seems likely that reporting is less than universal. The goal of this study is to compare the number of measles cases that are reflected by data from the statutory health insurance (SHI) carriers with the number of physician-reported cases during and after a recent outbreak in the German state of North Rhine-Westphalia (NRW). METHODS We analyzed the billing data of SHI carriers relating to measles in 2006 and 2007, as well as the measles cases that were reported in NRW over this period as required by law. We calculated the incidence of measles as the number of measles cases per 100 000 insurees (SHI carrier data) or per 100 000 persons in the overall population (reporting data). RESULTS The measles outbreak in the first half of 2006 comprised 1713 measles cases according to the SHI data and 1665 cases that were reported as required by law (ratio, 1.02:1). From mid-2006 to the end of 2007, the SHI data reflected 821 cases, but only 349 cases were reported (ratio, 2.35:1). Younger patients were more commonly found among the cases reflected in the SHI data than among the reported cases. CONCLUSION Our study confirms that the system of legally mandated reporting underestimates the true number of measles cases, particularly in times when most cases are sporadic, and particularly in children who are less than 5 years old.

[Overview and assessment of available data sources to determine incidence of vaccine preventable diseases, vaccination coverage, and immune status in Germany].

ZusammenfassungDie Surveillance von impfpräventablen Erkrankungen und durchgeführten Impfungen ist notwendig, um entsprechend den Impfempfehlungen und den verfolgten gesundheitspolitischen Zielen epidemiologische Daten zu liefern. Die verfügbaren Datenquellen für die Erfassung von Neuerkrankungen an impfpräventablen Krankheiten, zum Durchimpfungsgrad und zum Immunstatus der Bevölkerung sind lückenhaft und liefern kein vollständiges Bild der epidemiologischen Situation. Für die Mehrheit der impfpräventablen Krankheiten gibt es durch die Meldepflicht und zusätzliche Sentinels bundesweite Daten über ihr Vorkommen. Einige, für die Regelimpfungen empfohlen sind, stehen jedoch nicht unter einer Surveillance. Die Erhebung von Daten zu durchgeführten Impfungen erfolgt in Deutschland dezentral und regional. Bundesweit kontinuierlich erhobene Daten zu Impfquoten liegen ausschließlich für Schulanfänger vor. Die Analyse von Versorgungsdaten, wie zum Beispiel von Daten der Krankenkassen oder Kassenärztlichen Vereinigungen, kann eine Möglichkeit sein, diese Datenlücken zu schließen.AbstractThe surveillance of vaccine preventable diseases and vaccination coverage is necessary in order to deliver epidemiological data with respect to national vaccination recommendations and control targets. The data available on the incidence of vaccine preventable diseases, vaccination coverage, and immune status of the population are fragmentary and do not allow the epidemiological situation to be fully assessed. Although the majority of vaccine preventable diseases are under surveillance nationwide (by statutory reporting or sentinel surveillance), data are not available for some diseases. In addition, data on vaccination coverage are not collected centrally. Nationwide data on vaccination coverage are only available for children at school entry. Use of secondary data such as data from health insurance companies or associations of statutory health insurance physicians provides an opportunity to close gaps in knowledge and to improve the surveillance of vaccine preventable diseases.The surveillance of vaccine preventable diseases and vaccination coverage is necessary in order to deliver epidemiological data with respect to national vaccination recommendations and control targets. The data available on the incidence of vaccine preventable diseases, vaccination coverage, and immune status of the population are fragmentary and do not allow the epidemiological situation to be fully assessed. Although the majority of vaccine preventable diseases are under surveillance nationwide (by statutory reporting or sentinel surveillance), data are not available for some diseases. In addition, data on vaccination coverage are not collected centrally. Nationwide data on vaccination coverage are only available for children at school entry. Use of secondary data such as data from health insurance companies or associations of statutory health insurance physicians provides an opportunity to close gaps in knowledge and to improve the surveillance of vaccine preventable diseases.