Elsevier

Vaccine

Volume 27, Issue 31, 24 June 2009, Pages 4136-4141
Vaccine

Reduction in the incidence of invasive pneumococcal disease after general vaccination with 7-valent pneumococcal conjugate vaccine in Germany

https://doi.org/10.1016/j.vaccine.2009.04.057Get rights and content

Abstract

General vaccination with the 7-valent pneumococcal conjugate vaccine was recommended in Germany in July 2006 for all children <2 years. The proportion of reported invasive pneumococcal disease (IPD) caused by vaccine serotypes before vaccine introduction was considerably lower than in the US.

We report data from nationwide surveillance of IPD in children with two reporting sources, pediatric hospitals and microbiological laboratories in Germany. Incidence rates with regard to age groups and pneumococcal serotypes are based on capture recapture estimates combining the two reporting sources.

Between July 1, 1997 and June 30, 2003, 2680 cases (an average 447 yearly cases) of IPD were observed in children <16 years in Germany compared to 223 cases between July 1, 2007 and June 30, 2008. A significant reduction in overall incidence (4/100,000–3.2/100,000) was attributed to significant reductions in children younger than 2 years (20.0/100,000–11.0/100,000). While the incidence of all serotypes included in the vaccine was reduced in the age group <2 years, the incidence of non-vaccine serotypes remained stable.

These data show a first success of the pneumococcal vaccination program in Germany. Further changes in incidence and serotype distribution of IPD are subject to future surveillance.

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).

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    These authors contributed equally to this study.

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