Introduction

Pneumococcal infection causes a spectrum of diseases from mild presentations such as sinusitis and otitis media, to more serious diseases such as meningitis, bacteremia, and pneumonia [1]. The 23-valent pneumococcal polysaccharide vaccine (PPV) was introduced in 1983 and is available in Europe for immunization against pneumococcal diseases caused by the 23 serotypes contained in the vaccine (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F) in adults and children aged ≥2 years [2]. The first pneumococcal conjugate vaccine (PCV7) was licensed in 2000 for immunization against pneumococcal diseases, including sepsis, meningitis, pneumonia, bacteremia, and acute otitis media (AOM) caused by the seven serotypes contained in the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) in infants and children aged 2 months to 5 years [3]. PCV10 (serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) was approved in 2009 for protection against invasive pneumococcal disease (IPD), pneumonia, and AOM in infants and children aged from 6 weeks up to 5 years [4]. A higher-valent PCV, PCV13, comprising six additional serotypes to PCV7 (serotypes 1, 3, 5, 6A, 7F, and 19A) is now available in Europe for the prevention of IPD in adults aged ≥18 years, and for the prevention of IPD, pneumonia, and AOM in infants and children aged between 6 weeks and 17 years [5].

The global burden of pneumococcal diseases is high, with young children and adults ≥50 years of age at particular risk of infection. In the 1990s, the age groups with the highest incidence of IPD and highest case fatality rates were infants aged <2 years and adults aged >50 years [6]. Routine childhood pneumococcal immunization programs have helped to alleviate the burden of disease in children [7, 8]. Since 2006, the World Health Organization (WHO) has recommended that PCV be included in all routine childhood immunization programs [9]. Consequently, PCV use has increased from 1% of all WHO member states in 2000 to 44% in 2012, representing 31% of the global birth cohort [9]. Of the European region member states, 49% had introduced PCV by 2012 [9]. Over time the benefits of childhood vaccination with PCV in countries with high uptake have extended to unvaccinated children and adults as a result of the herd effect [10–13]. However, despite pneumococcal immunization programs covering adults and children, the burden in adults has remained high [14].

Recommendations for pneumococcal immunization across Europe are complex and are regularly updated. The objective of this review is to provide an overview of current government recommendations (not including scientific society recommendations), both national and regional where applicable, outside routine pneumococcal immunization programs for infants and children, in 16 individual countries across Western Europe (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, The Netherlands, Norway, Portugal, Spain, Sweden, and the United Kingdom [UK]), as of August 2014. A summary of the recommendations is provided in the text below, with more detailed information supplied for reference purposes in Table 1. To ensure the most up-to-date information for each country was included, Pfizer’s country Medical Affairs offices provided information regarding national and regional recommendations for pneumococcal vaccination. This article is based on pre-existing source material and does not include any studies with human or animal subjects performed by the author.

Table 1 Comparison of the recommendations and funding for pneumococcal immunization outside routine vaccination programs for children in Western European countries
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Recommendations Outside Routine Immunization Programs for Children for Pneumococcal Immunization in Western Europe

In addition to routine pneumococcal immunization programs in infants and children, most countries across Europe have further local or national recommendations (Table 1). Those without such recommendations may follow other guidelines, such as society guidelines or those from the Advisory Committee on Immunization Practices (ACIP; e.g., The Netherlands). Although generally falling within the prescribing information for the vaccines, pneumococcal immunization practices differ across Europe with regards to age groups and risk groups immunized, which vaccine (PPV versus PCV) is advised for which groups, and eligibility for reimbursement. The majority of the 16 Western European countries included in this article implement immunization programs with both age-based and risk-based elements. PPV23 is widely recommended across Western Europe; however, many countries have now included PCV in their pneumococcal immunization recommendations for certain groups of children and adults, either alone or in addition to PPV23. Figure 1 details the current adult national recommendations and reimbursement of PCV13.

Fig. 1
figure 1

European national recommendations and reimbursement of 13-valent pneumococcal conjugate vaccine (PCV13) in adults

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Age-Based Elements of Pneumococcal Immunization Programs

Age-based recommendations (usually for older adults) form part of the full immunization programs across most countries in Western Europe. However, the recommended vaccine and the age group eligible for vaccination vary between countries (Table 1). For example, immunization programs recommending PPV23 are implemented in Luxembourg (age >60 years), Finland, Ireland, Norway, Sweden, UK (all age ≥65 years), and most autonomous regions of Spain (age ≥60/≥65 years). Immunization programs recommending PCV exist in Greece (PCV13; >50 years), Germany (Saxony only; PCV; ≥60 years), Denmark (PCV13; ≥65 years), and some regions of Italy, including Tuscany (PCV13; ≥50 years), Basilicata, Bolzano, and Trento (all PCV13; >65 or ≥65 years), Liguria (PCV13; >70 years), Puglia (PCV13; cohorts 65, 70, 75 years), and Sicilia (PCV13; cohorts 65, 75 years). Additionally, age-based immunization programs recommending PCV and/or PPV23 exist in Austria, Belgium, and some regions of Italy.

Risk-Based Elements of Pneumococcal Immunization Programs

Some countries/regions across Western Europe advise pneumococcal immunization in individuals with specific co-morbidities that are considered to place them at an increased risk of pneumococcal diseases, regardless of age. Such purely risk-based elements are implemented in the pneumococcal immunization programs in Denmark, Norway, Sweden, UK, and some regions of Italy (Basilicata, Bolzano, Emilia Romagna, Lazio, Liguria, Marche, Trento, and Veneto; see Table 1 for specific risk groups and recommended vaccines).

Risk-based elements of pneumococcal immunizations programs across Europe can be very complex. For example, the risk groups eligible for vaccination can vary by age group (e.g., Belgium, Denmark, France, Germany, Ireland, Luxembourg, Spain [Murcia], and the UK), different vaccines may be advised for different risk groups (e.g., Finland, France, Ireland, Norway, and the UK) or different vaccines may be advised in different age groups considered to be at risk of pneumococcal diseases (e.g., France, Germany, Ireland, Luxembourg, and Portugal). Many European countries/regions advise vaccination with both PCV and PPV23 in individuals at risk of pneumococcal diseases (see the Additional information column in Table 1). However, PCV is preferred over PPV23 in individuals at risk of pneumococcal diseases in Finland (all high-risk individuals) and France (immunosuppressed and asplenic individuals).

Heterogeneity in the Definition of Individuals Considered to be at Risk of Pneumococcal Diseases

There is a marked variation between countries concerning which individuals are considered to be at risk of pneumococcal diseases and their eligibility for immunization, with some countries including many more medical conditions (e.g., Austria, Ireland, and Portugal) than others (e.g., Norway and national recommendations for Spain). Consistent with the ACIP recommendations for immunization of children and adults at risk of pneumococcal diseases [15, 16], common conditions considered to place individuals at an increased risk in Europe include underlying co-morbidities such as chronic kidney (risk category in adults only), heart, liver or respiratory disease, metabolic diseases (e.g., diabetes mellitus), central nervous system diseases (e.g., cerebrospinal fluid leak) and immunocompromised individuals, including human immunodeficiency virus (HIV)-positive individuals, primary immunodeficiency, organ transplantation, asplenia (functional or anatomical), and hematological cancer. Other risk factors less commonly included are previous IPD (Denmark, Ireland [children under the age of 5 years], Italy [Lombardia], Spain [Murcia and Basque Country], and Sweden) and lifestyle risk factors such as alcoholism (Belgium, Ireland, Italy [Bolzano and Emilia Romagna], Luxembourg, Spain [Madrid and all autonomous regions], and Sweden), smoking (Belgium and Ireland), and residing in a nursing home or permanent institution (Finland, Italy [Emilia Romagna, Trento, Tuscany, Umbria], Luxembourg, and Spain [all autonomous regions]). Most European countries recommend initial vaccination with PCV13 for individuals at risk of pneumococcal diseases, followed by PPV23 vaccination ≥8 weeks later. Although broadly in line with ACIP recommendations [15, 16], age groups and timing of vaccination vary between countries.

Funding of Pneumococcal Immunization Programs

Further differences between countries across Europe also relate to public reimbursement for pneumococcal immunization. It is not funded for any age or risk groups in Austria, Belgium, or Luxembourg. Partial funding is available in Denmark, Finland (stem cell transplantation patients), Ireland (all individuals receiving PCV <18 years of age and some patients receiving PPV23 at risk of pneumococcal disease required to pay an administration fee; no funding for those aged ≥18 years), Norway (asplenia, HIV and stem cell transplantation), and Sweden (PCV13 funded in Stockholm county in individuals at high risk of pneumococcal diseases; PPV23 varies regionally between local councils). In contrast, full public funding is provided in France, Germany, Greece, Portugal, Spain, and Italy (except Piemonte).

Impact of Recommendations and Pneumococcal Immunization on Disease

The impact of pneumococcal immunization is highly dependent on vaccine uptake. Differences in pneumococcal immunization recommendations can impact the rates of immunization between countries. Risk-based immunization programs require the identification of individuals with specific diseases, while targeting of vaccination is simpler for age-based programs and thus they are easier to implement. Countries with age-based recommendations and public reimbursement have demonstrated a higher uptake of PPV23 than countries immunizing only individuals at risk of pneumococcal diseases or countries without public reimbursement [17].

A meta-analysis of the efficacy of PPV in clinical trials demonstrated a high degree of heterogeneity between trials with little evidence of protection among elderly individuals or adults with chronic respiratory illness, for whom the vaccine was recommended [18]. Similarly, a meta-analysis of randomized controlled trials published up to June 2012 demonstrated the effectiveness of PPV in preventing IPD, but not all-cause pneumonia or mortality in the elderly [19]. However, data are conflicting. For example, in Japanese nursing home residents, PPV23 was shown to reduce the prevalence of pneumococcal pneumonia and all-cause pneumonia, as well as decrease mortality from pneumococcal pneumonia [20]. Although it is too early to assess the long-term impact of the inclusion of PCV in adult immunization programs, estimations can be made based on impact data from PCV7 childhood immunization programs, which have substantially reduced the burden of pneumococcal diseases in children [7, 8]. Emerging impact data in children show a decline in IPD due to serotypes contained in PCV13, following the introduction of PCV13 in Spain, England, and Norway [21–23]. Furthermore, it is anticipated that PCV13 will be cost-effective. Cost-effectiveness studies have predicted net savings of 102 million Euros over 5 years based on a model of a 65-year-old cohort immunization campaign in Spain [24], and between 7 million and 19 million Euros based on a model of an age-based PCV13 immunization program in adults aged ≥65 years in Italy [25].

Conclusion

Young children and adults aged ≥50 years are at particular risk of pneumococcal infection and despite childhood and adult immunization programs, burden of disease in adults remains high. Since the approval of PCV13 in adults aged ≥50 years in 2011, PCV13 is gradually being included in recommendations for adult pneumococcal immunization in addition to inclusion in childhood immunization programs within Western European countries. Ultimately, this should help to increase vaccine uptake and decrease the high burden of pneumococcal diseases in adults both through a direct effect of the vaccine and via a herd effect in unvaccinated individuals. Vaccine uptake and the effectiveness of pneumococcal immunization programs could be somewhat increased by raising awareness among healthcare professionals of the burden of pneumococcal diseases in adults, and improving the dissemination of recommendations for pneumococcal immunization. Moreover, the recommendations for pneumococcal immunization can be very complex and vary greatly between European countries in terms of age, risk, and which vaccine should be administered. When revising recommendations, public health officials should consider clarifying or simplifying recommendations, taking into account the merits of age-based versus risk-based recommendation for ease of implementation. This could help to increase vaccine uptake and thus reduce the burden of disease. Furthermore, the Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA; ClinicalTrials.gov #NCT00744263), a randomized placebo-control trial involving >84,000 pneumococcal vaccination-naïve, community-dwelling adults ≥65 years of age, will provide valid data on the role of adult PCV13 vaccination in preventing vaccine-type pneumococcal diseases, including pneumococcal community-acquired pneumonia and IPD, and thus has the potential to impact future pneumococcal vaccination recommendations [26, 27].