Annette Siedler

Association of serotype of Streptococcus pneumoniae with risk of severe and fatal outcome.

Background: Invasive pneumococcal disease (IPD) in children may manifest as bacteremia/sepsis, bacteremic pneumonia, or meningitis, with serious outcomes that include hospitalization, neurologic sequelae, or death. The risk of severe or fatal outcome of disease is associated with host-related factors, such as age or comorbid conditions. Furthermore, there is an ongoing discussion about organism-related factors, such as the pneumococcal serotype. Methods: Data on 494 children aged <16 years hospitalized for IPD between 1997 and 2003 in pediatric hospitals in Germany were analyzed. Serotype specific case-fatality rates and rates of severe outcome were compared using standardized mortality ratios (SMR). The risk of severe or fatal outcome for the serotype with the highest case-fatality rate was further analyzed using multivariate logistic regression adjusting for age younger than 1 year, meningitis, sex, and immunocompromised status as potential confounders. Results: The overall case-fatality rate was 5.3% and the rate of severe outcome was 17.0%. Serotype 7F had the highest case-fatality rate (14.8%, SMR 3.1), followed by serotypes 23F (8.3%, SMR 1.7) and 3 (8.3%, SMR 1.7). The highest rate of severe outcome was also observed for 7F (40.7%, SMR 2.4). Multivariate analysis showed an odds ratio of 4.3 (1.3–14.7) for fatal outcome and 4.0 (1.6–10.4) for severe outcome comparing 7F to all other serotypes. Conclusions: In this study population, serotype 7F accounted for a higher risk of severe and fatal outcome than other serotypes of Streptococcus pneumoniae. In describing the epidemiology of IPD, the serotype-specific risk for severe or fatal outcome is an important complement to other serotype-specific aspects like incidence and antibiotic resistance pattern.

Comparative varicella vaccine effectiveness during outbreaks in day-care centres

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.

Towards elimination : measles susceptibility in Australia and 17 European countries

OBJECTIVE To evaluate age-specific measles susceptibility in Australia and 17 European countries. METHODS As part of the European Sero-Epidemiology Network 2 (ESEN2), 18 countries collected large national serum banks between 1996 and 2004. These banks were tested for measles IgG and the results converted to a common unitage to enable valid intercountry comparisons. Historical vaccination and disease incidence data were also collected. Age-stratified population susceptibility levels were compared to WHO European Region targets for measles elimination of < 15% in those aged 2-4 years, < 10% in 5-9-year-olds and < 5% in older age groups. FINDINGS Seven countries (Czech Republic, Hungary, Luxembourg, Spain, Slovakia, Slovenia and Sweden) met or came very close to the elimination targets. Four countries (Australia, Israel, Lithuania and Malta) had susceptibility levels above WHO targets in some older age groups indicating possible gaps in protection. Seven countries (Belgium, Bulgaria, Cyprus, England and Wales, Ireland, Latvia and Romania) were deemed to be at risk of epidemics as a result of high susceptibility in children and also, in some cases, adults. CONCLUSION Although all countries now implement a two-dose measles vaccination schedule, if the WHO European Region target of measles elimination by 2010 is to be achieved higher routine coverage as well as vaccination campaigns in some older age cohorts are needed in some countries. Without these improvements, continued measles transmission and outbreaks are expected in Europe.

Four years of universal pneumococcal conjugate infant vaccination in Germany: Impact on incidence of invasive pneumococcal disease and serotype distribution in children

INTRODUCTION Vaccination with pneumococcal conjugate vaccine (PCV) for all children <2 years was recommended in Germany in July 2006. Initially PCV7 was exclusively used; PCV10 became available from April 2009 and PCV7 was replaced by PCV13 in December 2009. OBJECTIVE To compare the incidence and serotype distribution of invasive pneumococcal disease (IPD) for pneumococcal meningitis and non-meningitis IPD in children from 2007 to 2010 with reference to the pre-vaccination period from 1997 to 2001. METHODS Nationwide surveillance of IPD for children <16 years in Germany was based on two independent reporting sources: active surveillance in paediatric hospitals and passive web-based surveillance through microbiological laboratories. Serotyping was performed using the Neufeld Quellung reaction. CASE DEFINITION isolation of Streptococcus pneumoniae from a normally sterile body site. IPD incidence was estimated by capture-recapture analysis. Rate ratios comparing post- to pre-vaccination incidence were calculated as well as PCV7 and non-PCV7 serotype specific incidences. RESULTS While PCV7 incidence decreased by 88% (95%CI: 83 to 91) in children <16 years both in pneumococcal meningitis and non-meningitis IPD, an increase in Non-PCV7 serotypes was observed which was more pronounced in non-meningitis cases (168%; 95%CI: 140-257) than in pneumoccocal meningitis (65%; 95%CI: 23-123). The changes in incidence after four years were: <16 years: -35% (95%CI: -49 to -19), <2 years: -46% (95%CI: -61 to -27) for pneumococcal meningitis and+11% (95%CI: -4 to +29) and -26% (95%CI: -41 to -7) for non-meningitis IPD respectively. CONCLUSION Infant PCV7 vaccination in Germany prompted a decrease in the incidence of pneumococcal meningitis similar to that observed in England/Wales. In non-meningitis IPD the decrease was smaller and confined to the age group <2 years with no change or an increase in incidence in other age groups pointing to potential ascertainment bias due to increased blood-culturing.

Childhood invasive pneumococcal disease in Germany between 1997 and 2003: Variability in incidence and serotype distribution in absence of general pneumococcal conjugate vaccination

Based on active prospective surveillance, we report the incidence and serotype distribution for invasive pneumococcal disease in German children between 1997 and 2003. While incidence of meningitis cases was stable over time, there was an increase in non-meningitis cases. In absence of a general pneumococcal conjugate vaccination program, there were considerable and significant changes in serotype distribution over time. These should be considered when discussing the effect of vaccination programs and related changes in serotype distribution.

Epidemiology of pneumococcal disease in children in Germany.

Recently published and as yet unpublished data allow a reasonable estimate of the annual burden of pneumococcal disease in Germany. At least 277000 episodes of otitis media and at least 2000 episodes of sinusitis occur in children under the age of 5 y. Pneumococcal meningitis was found in 200 children under the age of 16 y; the estimate for all age groups ranges from 450 to 1100 cases. Of approximately 150000 cases of ambulatory pneumococcal pneumonia, at least 63 000–105000 patients are hospitalized each year.

REGIONAL DIFFERENCES IN THE EPIDEMIOLOGY OF INVASIVE PNEUMOCOCCAL DISEASE IN TODDLERS IN GERMANY

In a population-based study, regional differences in incidence, serotype distribution and resistance rates in invasive pneumococcal disease in 1-2-year-old children were related to different day care attendance rates. Day-care attendance appears to be a relevant risk factor in some German states and should be considered for inclusion in the recommendations for pneumococcal vaccination of children at risk.

Potential benefits from currently available three pneumococcal vaccines for children--population-based evaluation.

BACKGROUND Currently there are 3 pneumococcal vaccines available in Germany. The aim of this study is to evaluate the potential of the three currently available pneumococcal vaccines to reduce the burden of invasive pneumococcal disease in children. SUBJECTS Children younger than 16 years who have been hospitalized because of IPD between July 2007 and June 2009 in a German pediatric hospitals. METHOD Surveillance of IPD in German pediatric hospitals and laboratories serving these hospitals. The case definition is isolation of Streptococcus pneumoniae from any normally sterile body site. The actual number of IPD cases is based on the capture recapture method combining information from both reporting systems. RESULTS In the study period an estimated yearly number of 164 IPD cases occurred among children younger than 2 years compared to 144 and 116 cases among children aged 2-4 years and 5-15 years. Among children under 2 years of age, 69 cases were caused by serotypes covered by PCV10 compared to 103 cases potentially preventable by PCV13. Among children aged 2-4 years 94 IPD cases were caused by serotypes covered by PCV13 compared to 108 cases covered by PPV23. CONCLUSION The newly available pneumococcal conjugate vaccines with better serotype coverage have the potential to further reduce IPD burden in Germany. The additional benefit of vaccination of children aged 2-4 years at high risk for pneumococcal infections with PPV23 is questionable.

Background paper to the decision not to recommend a standard vaccination with the live attenuated herpes zoster vaccine for the elderly in Germany

A live attenuated vaccine (Zostavax (R)) against herpes zoster (HZ) and posther-petic neuralgia (PHN) was licensed for persons 50 years of age and older in 2006 and became available in Germany in September 2013. Based on the conclusion, that an effective and sustainable reduction of the HZ disease burden cannot be achieved with this vaccine, the STIKO decided against issuing a recommendation for routine HZ vaccination at this time. This decision is based on a systematic review of available data on the efficacy, duration of protection, and safety of the vaccine, and is supported by the results of health economic modelling. Both, the risk of developing HZ and the severity of the illness increase markedly with age. The efficacy of the vaccine, however, decreases with advancing age, from 70% for persons in their 50s to 41% for persons in their 70s to less than 20% for persons 80 years of age and older. The duration of vaccine related protection is limited to only a few years. The modelling results show only a slight, age-dependent reduction in the total number of HZ cases through vaccination with the live attenuated vaccine. The reduction ranged from 2.6% for persons vaccinated at the age of 50 to 0.6% for those vaccinated at the age of 80, based on assumed vaccine coverage of 35.5%. In addition to the vaccines poor efficacy and duration of protection, HZ vaccination does not offer any added value in terms of herd immunity, since HZ is a disease of an endogenously reactivated pathogen with low transmission potential. Finally, the live attenuated vaccine is often contraindicated in persons who are at greatest risk of HZ and its complications. Thus, in the overall appraisal, the epidemiological benefit-risk assessment of the HZ vaccination did not lead to a recommendation for routine vaccination with the live attenuated vaccine. An individual benefit-risk assessment may, however, lead to a different decision in individual patients.

Hacia la eliminación: vulnerabilidad al sarampión en Australia y en 17 países europeos

Introduction Live attenuated measles vaccines have been available since the early 1960s and are now in use worldwide. They have the potential to achieve highly effective measles control and elimination, as observed in the Americas. (1) In 1998, the WHO European Region agreed to eliminate measles in Europe by 2007. (2) By 2002, the incidence of measles in Europe was estimated to be below 5 per 100 000 and a strategic plan was developed which outlined an approach for achieving elimination by the revised year of 2010. (3-5) The approach focused on each member state delivering two doses of measles vaccine through the routine programme at very high (> 95%) coverage, undertaking catch-up campaigns to address older susceptible cohorts, strengthening surveillance through case-based reporting and laboratory confirmation of suspect cases, and improving communication about the benefits and risks of vaccination. To measure progress towards elimination and to identify populations for vaccination campaigns, age-group specific susceptibility targets were established that corresponded to an effective reproduction number less than one, and hence elimination. (6,7) These age-specific susceptibility levels could be estimated from high-quality historical vaccine coverage data (but only in populations with no measles transmission) or from population serological surveillance data. (8) Progress towards elimination can also be assessed from age-specific incidence data, but this is less useful when dose to elimination because it is possible for susceptible age cohorts to go unnoticed for many years. Outbreaks in older susceptible cohorts have occurred in Europe in recent years and are serious because of the greater morbidity caused by the disease in older individuals. (9,10) The size of outbreaks generated by imported measles cases can also be used to determine the effective reproductive number if cases are confirmed and extensive investigation to identify all cases in a cluster is performed. (7) In many countries, high-quality historical vaccine coverage and disease incidence data are not available so serological surveillance is an essential part of assessing population immunity. Even in countries with good vaccine coverage and disease incidence, data serological surveillance can help identify older susceptible cohorts and also problems with vaccine effectiveness. Although serological surveillance has clear potential, in the past it has been difficult to compare countries because they have used different methods for testing serum antibody levels. To obtain standardized serological data, countries participated in the measles work-package of the European Sero-Epidemiology Network 2 (ESEN2). (11) The ESEN2 project was a continuation of the original ESEN project with the same purpose of coordinating and harmonizing serological surveillance in Europe. (8,12,13) The measles component of the original project included seven countries, and identified four with a low risk of outbreaks (England and Wales, Finland, France and the Netherlands) and three with an intermediate/high risk of measles outbreaks (Denmark, Germany and Italy). Germany and Italy have since experienced outbreaks, highlighting the importance of seroepidemiological surveys and the need for targeted action based on the results. (14,15) In this paper, the results from measles serological surveillance in participating countries, as well as data on measles vaccine coverage and disease incidence, are presented and compared to the WHO European Region elimination targets. The results are used to identify susceptible cohorts to help inform future vaccination strategies as well as to identify discordance with routine coverage estimates suggesting possible problems with vaccine effectiveness or coverage data. Methods Serum bank collection Each participating country was required to test a serum bank representative of the general population in their country using their usual measles assay for measuring antimeasles IgG antibody. …