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.

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.

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.

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.