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.
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 .
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 . 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 . 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 . 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 , 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 .