Reduction in the incidence of invasive pneumococcal disease after general vaccination with 7-valent pneumococcal conjugate vaccine in Germany
Introduction
Streptococcus pneumoniae is a major source of morbidity and mortality worldwide. It is estimated that at least one million children under the age of 5 years die of pneumococcal disease every year, mostly in developing countries [1]. Invasive pneumococcal disease (IPD) in children is associated with considerable case-fatality rates and rates of sequelae, even in industrialized countries [2], [3], [4], [5], [6]. In the eighties of the last century, a 23-valent polysaccharide vaccine (PPV23) was licensed that covers 23 of the 91 pneumococcal serotypes. Since polysaccharides do not elicit an immune response in children under the age of 2, this vaccine was only licensed for children of 2 years and older. However, it is particularly the age group of children from 0 to 1 year of age that shows the highest incidence of IPD.
In February 2000, a 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in the US. This vaccine was shown to elicit a good immune response, also in children under 2 years of age, and was licensed for children of 2 months and older, offering the possibility for a general vaccination program in infants and toddlers. Starting from 2001, a strong decrease of IPD incidence in children has been reported from the US [7], [8], [9], [10], [11]. Comparing 1998–1999 with 2005, the annual rate of invasive pneumococcal disease in children younger than 5 years has dropped from 98.7 to 23.4 per 100,000 population in eight states of the US [8]. While the annual rate of IPD per 100,000 population caused by vaccine serotypes has decreased dramatically (81.9 in 1997–1998 compared to 1.7 in 2005), the rate of IPD caused by non-vaccine serotypes was slightly increased (16.8 in 1997–1998 compared to 21.7 in 2005) [8]. Recent data have shown a strong decrease in both pneumonia and otitis media among children in the US [12], [13].
In Europe, vaccination with PCV7 has to this day been implemented in 17 countries [14]: Luxembourg (2005), UK, Norway, France, Germany, Greece, Switzerland and The Netherlands (all 2006), Belgium (2007), Denmark, Cyprus, Hungary, Ireland, Slovakia and Sweden (all 2008). In Spain only the region of Madrid has a vaccination program. In the rest of the country vaccination is only done for high-risk children. In Italy PCV7 has been introduced in different provinces between 2003 and 2005, including more than 75% of the birth cohort.
Surveillance data from the pre-vaccination period in Germany show that about 60% of IPD cases in children of 16 years and younger were caused by serotypes included in PCV7 [15]. Among children younger than 5 years, this proportion was higher with around 70% [16]. PCV7 vaccination was recommended for high-risk children in July 2001. The definition of high-risk included children with acquired or congenital immunodeficiency, chronic diseases of e.g. heart or lung, preterm birth, low birth weight, failure to thrive, and severe neurological conditions. An estimated 8% of the children born between July 2000 and June 2003 had received pneumococcal vaccination according to those guidelines between July 2001 and June 2003 until the age of 24 months [17]. In July 2006, vaccination of all children was recommended by the German Standing Vaccination Committee (STIKO) [18]. A 3+1 schedule with doses at 2, 3, and 4 months and a booster dose at 11–14 months was recommended. A catch up for all children up to 23 months of age and identified risk groups up to 59 months of age was recommended.
In this paper we report data from a nationwide surveillance of IPD in children younger than 16 years in Germany. We compare data from July 2007 to June 2008 with data collected between July 1997 and June 2003. Incident cases are estimated from capture recapture analyses based on two reporting sources.
Section snippets
Study background
Nationwide surveillance of invasive pneumococcal disease in children younger than 16 years in Germany was based on two reporting sources. Cases were identified through two independent surveillance systems, a hospital-based surveillance system and a laboratory based surveillance system [19]. In January 2007 the laboratory based surveillance system was changed to the web-based sentinel Pneumoweb (URL: https://www3.rki.de/pneumoweb/), which included a convenient sample of participating labs [20].
Changes in incidence
Between July 1, 1997 and June 30, 2003, 2680 cases of IPD were observed in children of 15 years and younger in Germany, yielding an average number of about 447 cases per pneumococcal season (July 1–June 30 of subsequent year). Between July 1, 2007 and June 30, 2008, 223 cases were observed. This corresponds to a reduction in annual incidence per 100,000 population from 3.3 (95% confidence interval: 3.1–3.4) to 1.8 (95% CI: 1.6–2.1). The reduction was most pronounced among children younger than
Discussion
The incidence of IPD in German children younger than 2 years was significantly reduced approximately 1 year after the introduction of general vaccination with PCV7. This reduction was attributed to marked decreases in frequency of the serotypes included in PCV7, while the incidence of IPD caused by non-PCV7 types remained stable in this age group.
The change from an active surveillance based on monthly postcards to a web-based passive sentinel of the laboratory based surveillance system and the
Acknowledgments
We thank all pediatricians and microbiologists who reported cases and sent strains for serotyping. The hospital surveillance system was supported by a grant from Wyeth. R.R.R. has been an employee of Wyeth since 9/2007. Parts of this work result from the Ph.D. Thesis of S.R. at the medical faculty of the University of Munich (in preparation).
References (33)
- et al.
Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis
Lancet
(2007) - et al.
Childhood invasive pneumococcal disease in Germany between 1997 and 2003: variability in incidence and serotype distribution in absence of general pneumococcal conjugate vaccination
Vaccine
(2008) Prevenar vaccination: review of the global data, 2006
Vaccine
(2007)- et al.
Invasive pneumococcal disease among children in a health district of Barcelona: early impact of pneumococcal conjugate vaccine
Clin Microbiol Infect
(2006) - et al.
Changes in Streptococcus pneumoniae serotypes causing invasive disease with non-universal vaccination coverage of the seven-valent conjugate vaccine
Clin Microbiol Infect
(2008) - et al.
Effectiveness of a 2+1 dose schedule pneumococcal conjugate vaccination programme on invasive pneumococcal disease among children in Norway
Vaccine
(2008) - et al.
The pneumococcal problem
BMJ
(1996) - et al.
Meningitis in infancy in England and Wales: follow up at age 5 years
BMJ
(2001) - et al.
Invasive pneumococcal disease in an Alaska native population, 1980 through 1986
JAMA
(1989) - et al.
Comparison of incidence of invasive Streptococcus pneumoniae disease among children before and after introduction of conjugated pneumococcal vaccine
Pediatr Infect Dis J
(2005)
Prospective surveillance of incidence, serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae among hospitalized children in Austria
J Antimicrob Chemother
Epidemiology of invasive childhood pneumococcal infections in Greece
Acta Paediatr Suppl
Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease—United States, 1998–2003
MMWR Morb Mortal Wkly Rep
Invasive pneumococcal disease in children 5 years after conjugate vaccine introduction—eight states, 1998–2005
MMWR Morb Mortal Wkly Rep
Surveillance for invasive pneumococcal disease during 2000–2005 in a population of children who received 7-valent pneumococcal conjugate vaccine
Pediatr Infect Dis J
Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae
N Engl J Med
Cited by (99)
Vaccines Against Central Nervous System Infections: Past Achievements and Future Challenges
2018, The Microbiology of Central Nervous System InfectionsPublic health microbiology in Germany: 20 years of national reference centers and consultant laboratories
2015, International Journal of Medical MicrobiologyCitation Excerpt :The NRC and the RKI for meningococcal diseases and H. influenzae examined a cluster of invasive meningococcal disease in young men who have sex with men in Berlin (Marcus et al., 2013). NRCs and CLs are also involved in evaluating implemented vaccination recommendations and analyzing the effectiveness of the vaccines (Kalies et al., 2009; Ruckinger et al., 2009). For which pathogen a reference laboratory is to be established is decided based on the public health relevance of the pathogen as appraised by the RKI and on the needs expressed by the national public health services (“Öffentlicher Gesundheitsdienst,” ÖGD) (Gilsdorf and Krause, 2011).
Pneumococcal Vaccination and Consequences
2015, Streptococcus Pneumoniae: Molecular Mechanisms of Host-Pathogen InteractionsNational surveillance of invasive pneumococcal diseases in Taiwan, 2008-2012: Differential temporal emergence of serotype 19A
2014, VaccineCitation Excerpt :Although pneumococcal vaccination has not been implemented nationwide in Taiwan, partial vaccination coverage has contributed, at least in part, to the observed decline in IPD due to serotypes included in PCV7. The highest incidence was among children aged 2–4 years, consistent with an earlier report from Taiwan [15], but in contrast to many reports from other countries, where the highest incidence was recorded among children <2 years [5,6,10]. This discrepancy may be attributable to many factors, including attendance at day care centers, which was reported to be strongly associated with IPD [18,19] and pneumococcal carriage [17] in children.
- 1
These authors contributed equally to this study.