https://orcid.org/0009-0005-8865-3085
ABSTRACT
Despite widespread use of pneumococcal vaccines throughout Europe, the burden of pneumococcal disease (PD) in adults is considerable. To mitigate this burden, National Immunization Technical Advisory Groups (NITAGs) and Health Technology Assessment (HTA) agencies assess the value of different vaccine schedules for protecting against PD. The aim of this review was to assess the evidence and rationales used by NITAGs/HTA agencies, when considering recent changes to National Immunization Programs (NIPs) for adults, and how identified changes affected vaccine coverage rates (VCRs). A systematic review was conducted of published literature from PubMed® and Embase®, and gray literature from HTA/NITAG websites from the last 5 y, covering 31 European countries. Evidence related to NIP recommendations, epidemiology (invasive PD, pneumonia), health economic assessments and VCRs were collected and synthesized. Eighty-four records providing data for 26 countries were identified. Of these, eight described explicit changes to NIPs for adults in seven countries. Despite data gaps, some trends were observed; first, there appears to be a convergence of NIP recommendations in many countries toward sequential vaccination, with a pneumococcal conjugate vaccine (PCV), followed by pneumococcal polysaccharide vaccine 23. Second, reducing economic or healthcare burden were common rationales for implementing changes. Third, most health economic analyses assessing higher-valency PCVs for adults found its inclusion in NIPs cost-effective. Finally, higher coverage rates were seen in most cases where countries had expanded their NIPs to cover at-risk populations. The findings can encourage agencies to improve surveillance systems and work to reach the NIP’s target populations more effectively.
Introduction
Pneumococcal disease (PD) includes a set of symptomatic infections caused by the bacteria Streptococcus Pneumoniae (S. Pneumoniae) and is a major cause of morbidity and mortality in both children and adults worldwide. PD can be divided into noninvasive and invasive forms of the disease. The most burdensome manifestations of invasive pneumococcal disease (IPD) are pneumococcal meningitis, bacteremic pneumonia, and pneumococcal bacteremia.Citation1 Though anyone can contract PD, children under 5 y of age, the elderly, and immunocompromised people are at the greatest risk.Citation2,Citation3 In adults, noninvasive pneumococcal community-acquired pneumonia (CAP) is the most common expression of pneumococcal diseaseCitation4 and it is the leading cause of mortality in adults and children around the world.Citation5
For European countries, the burden of PD in adults has been explored previously in the literature.Citation3,Citation4,Citation6,Citation7 Worldwide, the most common cause of CAP is S. Pneumoniae.Citation8 Though the microbiologic diagnostic data is limited, and their estimates vary, CAP is often used as a surrogate for pneumococcal pneumonia. A 2013 estimate for annual incidence of all-cause CAP in European adults ranged between 1.07 and 1.2 per 1000 person-years and increased with age (14 per 1000 person-years in adults aged 65 y). A separate study estimated that all-cause CAP in adults costs the European economy about €10.1 billion (2012 Euros) annually, with €3.6 billion of that value related to productivity loss.Citation9
A large part of the burden associated with PD can be mitigated through pneumococcal vaccination. S. pneumoniae produces a polysaccharide capsule essential for its pathogenicity, serving as a virulence factor that hampers host immune clearance mechanisms.Citation3,Citation10 Currently, there are more than 100 recognized polysaccharide serotypes.Citation11,Citation12 Pneumococcal conjugate vaccines (PCVs) and pneumococcal polysaccharide vaccines (PPVs) have successfully targeted several of them, thus reducing the risk of infection by conferring protection against the specific serotypes selected for those vaccines. All the available pneumococcal vaccines were designed to elicit antibodies against the capsule polysaccharides of the pneumococcal isolates commonly causing disease at the time of development. Therefore, the antibodies only provide protection against the pneumococcus expressing the vaccine-targeted capsules (i.e., against the serotypes chosen for the vaccine), and are not intended to provide protection against non-vaccine serotypes.Citation12 Pneumococcal vaccines provide protection from IPD as well as noninvasive pneumococcal infection, and decrease vaccine-type nasopharyngeal colonization, thus reducing transmission to unvaccinated individuals.Citation4
In 1983, the first PPV developed, PPV23, was approved for use on children aged two or older and adults,Citation13 and is still in circulation today. Following the introduction of PCV7, the first pneumococcal conjugate vaccine, widespread inoculation of children throughout Europe substantially decreased most vaccine-type disease, and reduced the overall prevalence of the seven most common serotypes of S. Pneumoniae Citation14 and provided additional protection for adults by mitigating the spread across the population.Citation15 However, the residual burden associated with the increased prevalence of non-vaccine serotypesCitation16 encouraged the development of higher-valency PCVs.Citation15 The European Medicines Agency approved PCV10 and PCV13 in 2009, which improved overall serotype coverage.Citation17 As a result, these higher valency pneumococcal vaccinations have been introduced into NIPs for children, adults, or both, in certain European countries at varying timepoints over the past 13 y. The continued partial coverage of the newer PCVs have further encouraged the development and introduction of two PCVs with higher valency: PCV15 and PCV20.Citation18 In addition, recent studies in Europe have encouraged the use of sequential vaccination in adults and elderly, to improve coverage for at-risk individuals.Citation19,Citation20
provides the European Centre for Disease Prevention and Control’s (ECDC) overview of the current recommendations for pneumococcal vaccination in adults, by European country.
Figure 1. Recommended pneumococcal vaccinations for adults in 2022, by country (ECDC)Citation21.
Variations in vaccine introduction and use stem from recommendations made by Health Technology Assessment (HTAs) or by National Immunization Technical Advisory Groups (NITAGs). These multidisciplinary expert panels are appointed by each country to assess the value of adding different vaccines to their NIPs. They do so by reviewing epidemiological evidence (incidence, prevalence, unmet need, etc.), as well as health-economic evidence (cost-effectiveness, budget impact, etc.), among other aspects. A study from 10 y ago determined that 85% of the 27 European countries who responded to their survey had formed a NITAG to help determine NIP policy,Citation22 a number which has grown since then.
The recent emergence of the COVID-19 pandemic has sparked further interest in vaccination for PD in adults.Citation23 New studies assessing the relationship between SARS-CoV-2 and S. Pneumoniae have posited increased lethality of coinfection with both pathogens,Citation24 as well as reduced antibiotic susceptibility in non-vaccine serotypes coinciding with the emergence of COVID-19.Citation25 Given that PD is an issue in both the young and the old, different factors need to be considered by NITAGs for these separate populations. The use of pneumococcal vaccines in NIPs for children is well documented, and previous literature has assessed the epidemiological and health economic evidence reviewed by NITAGs in their decision-making processes.Citation26 However, to our knowledge, there is a lack of literature assessing the decisions European NITAGs make about including adult pneumococcal vaccines in their NIPs, particularly in recent years.
Understanding more about how NITAGs make these recommendations can provide academic, public, and private stakeholders with more information on why certain countries choose to include adult pneumococcal vaccines in their NIPs. Furthermore, it highlights how the decisions can potentially impact access for the population and the disease burden within that country. Despite widespread use of pneumococcal vaccines in children and adults, the burden of PD persists,Citation27,Citation28 meaning that these decisions can affect the lives of thousands of people.
The present study aimed to systematically review and collect information on the consideration of changes to NIPs for adults by European HTAs or NITAGs, in 27 EU countries, as well as Iceland, Norway, Switzerland, and the United Kingdom (UK). If changes had been considered by a particular agency, associated records from gray and published literature were reviewed and the available epidemiological and health economic evidence on burden of IPD and CAP, used by those agencies in their decision-making processes was collected. Finally, an attempt was made to map any changes in NIPs for adults to the vaccine coverage rates (VCRs) in the respective country, after that NIP change.
Methods
This systematic literature review (SLR) involved a structured and pragmatic process for finding, collecting, synthesizing, and reporting the relevant content from records identified within the pre-specified project parameters. The SLR was carried out in line with the Centre for Reviews and Dissemination’s (CRD) guidance for undertaking reviews in health care,Citation29 which included using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and a four-phase flow diagram.Citation30 All methods implemented in this review were pre-specified in the study protocol.
The eligibility criteria are provided in detail in supplementary Table S1. In brief, published articles and gray literature containing information for the chosen countries about pneumococcal NIP recommendations for adults, epidemiological evidence for IPD/pneumonia in adults, and health economic evidence related to pneumococcal vaccines for adults were included. Relevant record types included technology appraisal guidance, appraisal reports, recommendation extensions, NITAG reports with relevant data, and published literature reporting on pneumococcal vaccine recommendations for adults. The countries included in the review were as follows: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Netherlands, Norway, Poland, Portugal, Republic of Malta, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, the UK.
The following literature sources were used:
Grey literature (HTA and NITAG websites)
PubMed®, PubMed® in-process from January 1st, 2017 – May 20th, 2022
EMBASE® from January 1st, 2017 – May 20th 2022
The HTA agencies and NITAG websites outlined in supplementary Table S2 were searched for relevant evidence. The agency website list was developed and merged based on information from several sources including the Global NITAG Network website,Citation31 and the publicly available lists of HTA and advisory agencies from the International Network of Agencies for Health Technology Assessment (INAHTA)Citation32 and European Network for Health Technology Assessment (EUNetHTA).Citation33 All identified recommendation and/or vaccine coverage reports, and other relevant outcomes that fulfilled the criteria in supplementary Table S1 were included in the review. English websites and records were considered as a first choice, however, in case the website and/or subsequent relevant material was not available in English, that text was translated to English using Google Translate and included in the review with this limitation.
In addition to the agency website search, PubMed® and Embase® were searched to identify additional relevant HTA and advisory reports. Search strings can be found in supplementary Table S3 and Table S4, respectively.
The methods for selecting records mimic the recommendations found in the PRISMA guidelines for conducting systematic reviews.Citation30 Study selection followed a two-step process; in step one, identified literature were screened by title and abstract (or equivalent text) and categorized as ‘include,’ ‘unsure’ and ‘exclude,’ by two independent reviewers based on eligibility criteria. In step two, two reviewers independently reviewed the full texts of the records in the ‘included’ and ‘unsure’ categories against the eligibility criteria. Reasons for rejections and exclusions of studies were recorded for all records reviewed at the full-text stage. All relevant data from the included full text reports were extracted into a prespecified data extraction grid, developed during the protocol phase. Two reviewers extracted data independently. At all stages, discrepancies between reviewers were resolved by consensus and unresolved discrepancies were referred to a third arbitrator who was a senior advisor, and a consensus was reached.
The data extraction grid contained the following outcome categories:
Metadata: Author, year, title, country, etc.
General information: HTA/NITAG agency(s), population, recommendation, considered changes
Epidemiological evidence: Context, incidence, prevalence, mortality, etc.
Serotype data: Distribution, antibiotic resistance/susceptibility
Economic evidence: HE models used, major assumptions, major inputs, outcomes, conclusion
For the synthesis process, information related to recommendation decisions and evidence used did not require the use of effect measures. VCRs were recorded as percentages, with confidence intervals included, where reported. As the majority of records were expected to be gray literature, and the expected study types would vary considerably, it was deemed impractical at the protocol stage to conduct a risk of bias assessment that would allow the quality of records to be assessed and compared.
This study employed a narrative synthesis of the results; no meta-analysis of the extracted data was performed. No methods were used to assess reporting bias. The potential reporting bias from missing results in the synthesis is examined in the discussion section. It was deemed unnecessary to assess certainty and/or confidence beyond the methods reported in the individual studies. However, the limitations of the body of evidence are considered in the discussion section.
Results
is a PRISMA flow chart, visualizing the record selection process. A total of 460 unique records were identified across the bibliographic database (PubMed® and Embase®) and gray literature searches. The records were then screened and assessed for eligibility according to the methods described above, with the reasons for exclusion recorded at the full text review stage (provided in ). In total, 84 (52 + 32) records were included for the final data extraction.Citation34–118
Figure 2. PRIMSA flow chart depicting the record selection process.
The 84 records included evidence for 26 of the 31 chosen countries, with no data identified for Bulgaria, Cyprus, Czech Republic, Latvia, and Malta. Some of the included studies provided data for multiple countries and/or multiple outcome categories (recommendation data, coverage rates, etc.). The countries with the greatest number of records containing relevant data were Netherlands (10 records), Italy, Germany, France, and Denmark (8 records each). A total of 42 records provided data related to adult, pneumococcal NIP recommendations, 41 records contained data on VCR, 22 records contained economic evidence and 22 records included epidemiological evidence for IPD or pneumonia. However, the authors were only able to identify data in all four outcome categories for seven of the included countries (Belgium, Denmark, France, Germany, Italy, Portugal, and Netherlands), meaning that for the other chosen countries, the included records did not include data for one or more of the outcome categories.
The supplementary material contains the results of the individual studies, organized into tables for each of the outcome categories: recommendation data (Table S5), epidemiology data (Table S7), health economic data (Table S8), and vaccine coverage (Table S9).
Pneumococcal NIP recommendations for adults
There were 42 records containing information on pneumococcal NIP recommendations. Of those, 32 (76%) were identified through NITAG/HTA websites, while 10 (24%) were from PubMed® and Embase®. Most of these records focused on describing existing recommendations, with 40 of the 42 records expressing positive decisions. The remaining two records just discussed the recommendations for adults. provides a breakdown of the number of records recommending each pneumococcal vaccination, by country. The most common pneumococcal recommendations for adults were sequential vaccination with PCV13 and then PPV23 (21 records, across 12 countries) and PPV23 alone (17 records, across 10 countries). Eleven records established that 10 countries recommended use of PCV13 alone. Two records each were identified with recommendations for the use of PCV20 (Belgium and Denmark) and PCV10 (Greece and Ireland), while one record in Belgium recommended the alternative use of PCV15 in tandem with PPV23 for adults. For further details about the recommendation information, see Table S5.
Figure 3. Number of records per country providing a recommendation, per pneumococcal vaccination (as of 2022).
Eight of the records with recommendation information explicitly expressed interest in changing their pneumococcal NIP recommendations. Table S6 provides an overview of the discussions in these records. There are differences in the considerations and evidence that NITAGs employ when assessing the value of including adult pneumococcal vaccinations in their NIPs. A recommendation record for the UK described a panel discussion where the participants considered a change to their NIP.Citation65 The topics included in this discussion were the introduction of new conjugate vaccines, PCV15 and PCV20, the relationship between COVID-19 and PD, trends in the incidence of PD, the relative effectiveness of PCV13 and PPV23 for adults, indirect protection from childhood immunization programs, and other. The committee concluded that it would be useful to have a model assessing the impact of introducing the newer high-valency PCVs into NIPs for adults.
A recommendation document for Portugal described a change in their NIP for adults to include PPV23 in addition to PCV13.Citation51 They also extended coverage to provide free PPV23 for select at-risk groups (in addition to PCV13) and expanded the risk groups included in the recommendation. The justifications for this change focused mainly on the shift in residual burden of serotypes not covered by the currently recommended vaccinations as well as the responsibility of the state to bear this cost to reduce societal burden.
Despite these variations in evidence and recommendations, the evidence collected appears to show a convergence in NIP recommendations among the included European countries, toward similar strategies for vaccination. The predominant update to recommendations was a change from single vaccine (e.g., PPV23, PCV13) to sequential vaccination with a higher-valency PCV (PCV13, PCV15, or PCV20), followed by PPV23 for older and/or immunocompromised adults, with the intention of improving both effectiveness and serotype coverage. There are a few other trends present as well; many of the recommendations involve an expansion of coverage to additional risk groups in adults. The available rationales for these changes commonly focus on reducing either healthcare or economic burden, with some even mentioning the COVID-19 pandemic and the subsequent risk of co-infection. The available rationales are provided in more detail in Table S6. Some of the included records also discuss partial or total reimbursement for vaccination, to reduce economic burden for at-risk individuals.
However, there are some countries, such as Netherlands, who continue to maintain, or have reverted to individual PPV23 vaccination, citing cost benefit, or herd immunity achieved from childhood vaccination as a rationale.
Epidemiological evidence
There were 22 records with epidemiologic evidence provided in the context of PV use for adults. Fourteen records (63.6%) were from PubMed® and Embase®, and eight (36.4%) were from HTA/NITAG reports. The types of data examined by countries, where data were identified are summarized in , color coded by the source of data. Supplementary Table S7 provides the details of the data available in the identified records. The most common types of evidence assessed across countries were incidence and serotype distribution data for IPD, and incidence and mortality data for pneumonia. Incidence data can provide decision makers with a clear picture of the annual burden of pneumococcal disease in adults. Serotype distribution data can aid in discussions of the extent of coverage that different pneumococcal vaccines can provide (i.e., whether the common serotypes expressed in the public are covered by certain pneumococcal vaccines). The interest in mortality data for pneumonia is also understandable, given that all-cause CAP is the leading cause of pneumonia mortality in the world.Citation5
Table 1. Summary of epidemiology data types included in records for each country.
Of the 22 identified records, 11 (50%) expressed positive recommendations for their NIPs, e.g., with either a new recommendation or simply by retaining or amending the existing dosing scheme at that time. The remaining 11 records did not discuss recommendations. Some countries furthermore referenced European-level data, and/or data sourced at the national and subnational level, though the majority of data were identified from published literature. It was also interesting to note that most of the records (21/22, 95%) were either economic assessments or recommendation records, which also reported epidemiological data in the background for their assessments.
Many of the records provided data stratified by age groups above 50, suggesting the importance of agespecific data for determining which groups to include in the recommendations. The only record which provided time-trend data was from Finland, which indicated an increase in the incidence of hospital-treated primary pneumonia for all adult age groups except the oldest (ages 75+ y).
Health economic evidence
Of the 22 identified records reporting health economic evidence, 20 (91%) were published papers from PubMed® and Embase®, while two (9%) were HTA/NITAG reports. The summary of the available data in the records can be found in supplementary Table S8. Sixteen of the 22 records performed cost-effectiveness analyses (CEA), and 12 of those CEAs were cost-utility analyses (CUA). Four studies performed budget impact models (BIM) and three performed cost analyses (CA). A summary of the key study features is provided in . Of the health economic analyses identified, the majority (17/22, 77.2%) assessed the impact of including PCV13 for adults in the NIP for their respective country. Ten records assessed the impact of introducing PCV13 versus the following comparators: PPV23 or no vaccine (4/10, 40% each), PCV13+PPV23 sequentially or just PPV23 (1/10, 10%), and remaining record did not report the comparator (1/10, 10%). In three records, sequential vaccination with PCV13 and PPV23 (both) was compared to either PPV23 alone (2/3, 66.7%) or in separate dosing schemes for different subgroups (1/3, 33.3%).
Table 2. Key features of the health economic assessment records.
For CEAs or CUAs assessing the inclusion of PCV13 (either alone or in combination with PPV23), the studies found PCV13 to be cost-effective in 76.9% (10/13) of assessments. Two studies in Netherlands found PCV13, not to be cost-effective; one study compared PCV13 alone to PPV23 alone, determining that the higher cost of PCV13 yielded too high of an incremental cost-effectiveness ratio (ICER) for people aged 70+ y.Citation105 The other study assessed the impact of including vaccinated adults’ future costs on the cost-effectiveness of PCV13 versus no NIP for adults. The authors argued that extending the lifespan of those with comorbidities incurs higher future costs, thus reducing the cost-effectiveness of PCV13.Citation50
The major point of concern in assessments comparing PCV13 to PPV23 was that of the relatively high price of PCV13.Citation105,Citation113 However, adding a single dose of PCV13 for those with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) was shown to be highly cost-effective compared to vaccination with PPV23 alone (different records from Germany, Netherlands, and France).Citation59,Citation67,Citation90 A record from Spain also concluded that sequential vaccination of immunocompetent adults aged 60+ y with PCV13-PPV23 would improve the health outcomes, but at a higher cost, exceeding typical cost-effective benchmarks, compared to PPV23 alone,Citation55 indicating that these cost-effectiveness comparisons were dependent on other factors in addition to price.
Vaccine coverage rates
There were 41 records that included data on VCR, most of which (38, 92.6%) came from PubMed® and Embase®. The countries with the highest number of records reporting coverage rate data were France (n = 7), Germany (n = 6) and Belgium (n = 4). The most commonly reported rates were vaccine-specific; either for PPV23 alone (17 studies) or PCV13 alone (14 studies). Nine studies reported VCRs for adults vaccinated with PPV23 and/or PCV13, and five studies reported VCRs for adults vaccinated sequentially with both. Fourteen studies did not specify a vaccine type for their coverage rates. There were 13 studies that stratified estimates into sub-groups, based on age, risk group (e.g., comorbidity) or geography. Furthermore, five (12.2%) of these studies estimated coverage rates for the protection that a specific vaccine provides against the S. pneumoniae serotypes prevalent in that population (hereafter referred to as ‘serotype coverage rates’), while remaining 36 (87.8%) studies estimated the shares of the population that has received one or more pneumococcal vaccines (VCRs). The details of the coverage rate data included in the identified records is presented by country in supplementary Table S9.
The estimates, target populations assessed, and reporting methods varied for all included records. However, some associations can be drawn between the VCR and the changes in recommendation presented above. Before the latest expansion of the German NIP in 2016 to include more coverage for elderly and at-risk individuals, two records estimated low overall VCRs with PCV13 in immunocompromised adults (4.4%)Citation94 and elderly people (3.2%).Citation100 However, after the change in NIP, more recent studies estimated a higher coverage rate for both sequential vaccination (9.9% who received PCV13+PPV23) as well as for PPV23 vaccination (35.1%) in the at-risk population.Citation76 Similarly higher VCRs were estimated in older populations after the German change in NIP (PPV23: 39%,Citation76 50% [Citation74; PCV13: 38%;Citation74 overall: 30.3%Citation111]. High PPV23 coverage rates were also reported in Dutch adults [(73%Citation87] after the 2018 change to their NIP. In these cases, the VCR evidence confirms the impact of the NIP change.
Only three studies provided trends in VCRs over time, the details of which are provided in . An Austrian study estimated an increase in VCR over the past 5 y from 15% to 20%, in the population aged 50+ y, and at-risk with chronic disease.Citation110 A French study estimated about a 9% point increase in VCR in immunocompromised adults from 2014 to 2018, but about an 8% point decrease in the overall coverage rate of at-risk adults.Citation114 A separate French study estimated a small decrease in the number vaccinated patients diagnosed with chronic diseases between their control and study periods.Citation66
Table 3. Included VCR studies with data across time.
Studies comparing PPV23 uptake in adults, ages 50+ y in BelgiumCitation112 and SpainCitation109 estimated very different VCRs (Belgium, ages 65–74 in 2015: 2.48%; Spain, ages 65–79 in 2017: 63.1%). The differences between the two samples (e.g., ages included, year of estimation) likely does not explain all the variation in these rates; other influencing factors could include access to supplies, the date of introduction of NIP, differences in vaccine delivery infrastructure, the cost to the individual and more.
There were four records estimating serotype coverage rates for specific vaccines, with one study each providing estimates for DenmarkCitation41 Poland,Citation75 Greece,Citation70 and Croatia.Citation43 Across the timeframes for the different estimates, there was more variation in the serotype coverage of PCV13 than PPV23. For PCV13, estimates ranges from 37.8% in Greece between 2009 and 2016, to 80.2% in Croatia between 2005 and 2019. Meanwhile, estimates for PPV23 ranged from 73% in Denmark in 2017 to 93.6% in Croatia between 2005 and 2019. The smaller variation in serotypes covered may in part be indicative of the additional serotypes included in PPV23 but variations in estimates for both imply changes to the composition of serotypes across European countries.
Discussion
This study sought to assess the recent changes and trends in adult pneumococcal vaccination programs across Europe, and to tie those decisions to both the evidence used and their impact on VCRs. Across the literature describing recommendations by NITAGs, there were several general trends that could be gleaned from the available data. In recent years, there appears to be a convergence of NIP recommendations toward sequential vaccination with a higher-valency PCV, followed by PPV23, for optimal coverage across serotypes. Also, most countries with new recommendations have expanded their NIPs to cover additional risk groups in adults, sometimes subsidizing the cost for vaccines for these groups as well. The rationales provided in the available data revealed common goals to reduce economic or healthcare burden, or both, as well as minimizing risk of co-infection. It was also evident from the data gathered that agencies reviewing epidemiological evidence found value in collecting estimates stratified by age.
This convergence of recommended vaccine schedules and the prevailing rationales in the data suggested that the majority of the countries where data were identified found that sequential vaccination with a high-valency PCV, followed by vaccination with PPV23 provided optimal protection and a minimization of economic burden, for their country’s circumstances. The strategy of a high-valency PCV combined with PPV23 is also the current recommendation in both the USACitation119 and Australia,Citation120 for adults with underlying risks. However, the recommendations for elderly populations differ; in the US, either PCV20 alone or a high-valency PCV combined with PPV23 is recommended for those age 65 or older, while in Australia, PCV13 alone is recommended for those age 70 or older. Meanwhile, Japan currently recommends the use of PPV23 alone for older people.Citation121 These differences imply that a multitude of factors (e.g., vaccine availability, vaccine recommendations for the pediatric population, age-specific considerations, risk of pneumococcal infection, costs, etc.) may influence policy maker’s recommendations.
Health economic analyses predominantly studying the introduction of PCV13 to target adult populations were overwhelmingly positive, with the majority (76.9%) of studies determined that inclusion of PCV13 would be cost-effective at the chosen willingness-to-pay threshold. However, a few studies and/or recommendation records expressed concerns about the high cost associated with PCV13, ruling that the herd immunity granted by inoculating children combined with use of PPV23 provided adequate protection without the inclusion of PCV13. In addition, where VCR could be associated with changes in recommendations, higher coverage rates were seen in most cases where countries had expanded their NIPs to cover additional risk groups and include additional vaccines.
Changes to NIPs for adults in large European countries affect both access to treatment and PD burden for millions of people. For example, the Austrian record detailed in involved a budget impact analysis of the current NIP for adults, which consists of sequential vaccination with PCV13 and PPV23 for all adults ages 50+ y.Citation110 A 2022 population pyramid of Austria showed that almost 42% of their population are 50+ y (about 3.7 million adults).Citation122 The record estimated that the VCR for this population increased by 5% points over the past 5 y, which suggests that the policy impacted the lives about 186,000 newly vaccinated people in Austria during that period.Citation110
The included evidence was not without limitations. The density and format of the available information in the chosen countries was inconsistent despite reviewing both published and gray literature. For example, it was difficult to compare either VCRs or recent epidemiology data with the decisions made in the countries with available information. This made assessments of the impact of these decisions difficult to conduct. Data inconsistencies could be minimized by the implementation of surveillance systems and standardized methods for reporting. However, some patterns were identified; age-stratified epidemiological data indicated an interest in identifying the target age groups where vaccination would be beneficial. This age-specific interest was also expressed in health economic assessments like the CUA in Netherlands, which found too high of an ICER for people aged 70+ y.Citation105 A recent CUA in Belgium, assessing the impact of sequential vaccination with PCV13 and PPV23,Citation112 was succeeded by a change in the Belgian NIP for adults to include sequential vaccination with a high-valency PCV and PPV23.Citation47 Many of the included records discussed expansions of the risk groups included in the existing recommendations, providing further coverage for immunocompromised groups, which was then evident within reported data from Austria and France.Citation66,Citation110,Citation114 However, inconsistent trends in coverage implied that factors other than the implementation of new NIPs impact coverage.
There were also limitations of the review process, biggest of which was the issue of language and translation. The inability for the review team to review all records in their native languages, combined with the inconsistent accuracy of Google Translate made it more difficult to determine whether certain records were relevant, or whether they described a change in policy or continuation of existing policy. Furthermore, the review team chose not to include published literature in other languages than English, as there was a worry that Google Translate would be insufficient to translate peer-reviewed academic writing. Additionally, the project did not have the scope to contact each of the individual agencies to get direct guidance on their NIPs for pneumococcal disease, meaning that the grey literature search process was in part dependent on the navigability of government websites in each country.
Despite these limitations, it is clear throughout all records that despite widespread recommendation of high-valency pneumococcal vaccinations in both adults and children, the burden of PD is still high. This residual burden persists in-part through non-vaccine serotypesCitation123,Citation124 and through vaccine serotypes, such as 19A and 3, which continue to be prevalent in populations where pneumococcal vaccines are available.Citation125 This shift has encouraged the development of vaccines covering additional serotypes.Citation27,Citation126 However, other research points toward concerns over the waning benefits associated with the expansion of serotype coverage.Citation127,Citation128 Additionally, despite improved NIP recommendations for adults, differences in reimbursement policy, availability, public awareness, and other factors mean that not all at-risk individuals follow these recommendations.
For these reasons it is important that HTAs, NITAGs, and policy makers understand the importance of collecting, reporting, and then considering all the available information, being transparent about their decision-making processes, and communicating those decisions to their target populations so that the maximum benefit of these inoculations can be realized. These actions can better be achieved through consistent reporting of the relevant information by academia and relevant agencies, to provide a solid foundation upon which to make these decisions.
Author’s contributions
AB and ET conceptualized the project and developed the design together with NN, PK, and SA. SA reviewed all publications, and together with NN extracted all data. NN and SA synthesized the results and wrote the manuscript, with support from PK and high-level input from both AB and ET. AB was chief advisor on the project. All authors discussed the results and contributed to the final manuscript.
Consent for publication
All authors approved the final version of the article, including the authorship list.
Supplemental Material
Download PDF (1.6 MB)Acknowledgments
We would like to recognize Naveen Sharma’s contribution to the processes of protocol development and data extraction during this study. While he was not able to contribute to the synthesis and reporting of the content, his help was much appreciated.
Disclosure statement
AB and ET are employees of MSD. SA, NN, and PK are current employees of Quantify Research, which received consulting fees from MSD to support the preparation and development of the study and manuscript. The authors report no other conflicts of interest in this work.
Data availability statement
All data generated or analyzed during this study are included in this published article (and its supplementary information files).
Supplementary data
Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2023.2279394.
Additional information
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References
- Drijkoningen JJ, Rohde GG. Pneumococcal infection in adults: burden of disease. Clin Microbiol Infect. 2014;20(Suppl 5):45–13. doi:10.1111/1469-0691.12461.
- Chalmers JD, Campling J, Dicker A, Woodhead M, Madhava H. A systematic review of the burden of vaccine preventable pneumococcal disease in UK adults. BMC Pulm Med. 2016;16(1):77. doi:10.1186/s12890-016-0242-0.
- Navarro-Torné A, Montuori EA, Kossyvaki V, Méndez C. Burden of pneumococcal disease among adults in Southern Europe (Spain, Portugal, Italy, and Greece): a systematic review and meta-analysis. Hum Vaccin Immunother. 2021;17(10):3670–86. doi:10.1080/21645515.2021.1923348.
- Ceyhan M, Dagan R, Sayiner A, Chernyshova L, Dinleyici E, Hryniewicz W, Kulcsár A, Mad’arová L, Pazdiora P, Sidorenko S, et al. Surveillance of pneumococcal diseases in central and Eastern Europe. Hum Vaccin Immunother. 2016;12(8):2124–34. doi:10.1080/21645515.2016.1159363.
- Center for Disease Control and Prevention (CDC). Global Pneumococcal Disease & Vaccine. 2022. https://www.cdc.gov/pneumococcal/global.html#:~:text=The%20World%20Health%20Organization%20(WHO,cause%20of%20pneumonia%20mortality%20globally.
- Blasi F, Mantero M, Santus P, Tarsia P. Understanding the burden of pneumococcal disease in adults. Clin Microbiol Infect. 2012;18(Suppl 5):7–14. doi:10.1111/j.1469-0691.2012.03937.x.
- Torres A, Cillóniz C, Blasi F, Chalmers JD, Gaillat J, Dartois N, Schmitt HJ, Welte T. Burden of pneumococcal community-acquired pneumonia in adults across Europe: a literature review. Respir Med. 2018;137:6–13. doi:10.1016/j.rmed.2018.02.007.
- Shoar S, Musher DM. Etiology of community-acquired pneumonia in adults: a systematic review. Pneumonia (Nathan). 2020;12(1):11. doi:10.1186/s41479-020-00074-3.
- Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012;67(1):71–9. doi:10.1136/thx.2009.129502.
- Paton JC, Trappetti C, Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA, Braunstein M, Rood JI. Streptococcus pneumoniae Capsular Polysaccharide. Microbiol Spectr. 2019;7(2). doi:10.1128/microbiolspec.GPP3-0019-2018.
- Ganaie F, Maruhn K, Li C, Porambo RJ, Elverdal PL, Abeygunwardana C, van der Linden M, Duus JØ, Sheppard CL, Nahm MH, et al. Structural, genetic, and serological elucidation of Streptococcus pneumoniae serogroup 24 serotypes: discovery of a New serotype, 24C, with a variable capsule structure. J Clin Microbiol. 2021;59(7):e0054021. doi:10.1128/JCM.00540-21.
- Ganaie F, Saad JS, McGee L, van Tonder AJ, Bentley SD, Lo SW, Gladstone RA, Turner P, Keenan JD, Breiman RF, et al. A New pneumococcal capsule type, 10D, is the 100th serotype and has a large cps fragment from an oral Streptococcus. mBio. 2020;11(3). doi:10.1128/mBio.00937-20.
- Musher DM, Anderson R, Feldman C. The remarkable history of pneumococcal vaccination: an ongoing challenge. Pneumonia (Nathan). 2022;14(1):5. doi:10.1186/s41479-022-00097-y.
- Izurieta P, Bahety P, Adegbola R, Clarke C, Hoet B. Public health impact of pneumococcal conjugate vaccine infant immunization programs: assessment of invasive pneumococcal disease burden and serotype distribution. Expert Rev Vaccines. 2018;17(6):479–93. doi:10.1080/14760584.2018.1413354.
- Westerink MA, Schroeder HW Jr., Nahm MH. Immune responses to pneumococcal vaccines in children and adults: rationale for age-specific vaccination. Aging Dis. 2012;3:51–67.
- Weil-Olivier C, van der Linden M, de Schutter I, Dagan R, Mantovani L. Prevention of pneumococcal diseases in the post-seven valent vaccine era: a European perspective. BMC Infect Dis. 2012;12(1):207. doi:10.1186/1471-2334-12-207.
- European Center for Disease Control (ECDC). Annual epidemiological report for 2016: invasive pneumococcal disease. Belgium: ECDC; 2016.
- Kobayashi M, Farrar JL, Gierke R, Britton A, Childs L, Leidner AJ, Campos-Outcalt D, Morgan RL, Long SS, Talbot HK, et al. Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. Adults: updated recommendations of the advisory committee on immunization practices — United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(4):109–17. doi:10.15585/mmwr.mm7104a1.
- Azuma M, Oishi K, Akeda Y, Morino S, Motoki Y, Hanibuchi M, Nishioka Y. Safety and immunogenicity of sequential administration of PCV13 followed by PPSV23 in pneumococcal vaccine-naïve adults aged ≥ 65 years: comparison of booster effects based on intervals of 0.5 and 1.0 year. Vaccine. 2023;41(5):1042–9. doi:10.1016/j.vaccine.2022.12.060.
- Cripps AW, Folaranmi T, Johnson KD, Musey L, Niederman MS, Buchwald UK. Immunogenicity following revaccination or sequential vaccination with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in older adults and those at increased risk of pneumococcal disease: a review of the literature. Expert Rev Vaccines. 2021;20(3):257–67. doi:10.1080/14760584.2021.1889374.
- ECDC. Pneumococcal Disease: recommended vaccinations. 2022. https://vaccine-schedule.ecdc.europa.eu/Scheduler/ByDisease?SelectedDiseaseId=25&SelectedCountryIdByDisease=-1.
- Nohynek H, Wichmann O, DA F. National advisory groups and their role in immunization policy-making processes in European countries. Clin Microbiol Infect. 2013;19(12):1096–105. doi:10.1111/1469-0691.12315.
- Córcoles ÁV. Pneumococcal vaccination in times of COVID-19. Med Clin (Engl Ed). 2022;158(8):366–8. doi:10.1016/j.medcle.2022.01.004.
- Barman TK, Singh AK, Bonin JL, Nafiz TN, Salmon SL, Metzger DW. Lethal synergy between SARS-CoV-2 and Streptococcus pneumoniae in hACE2 mice and protective efficacy of vaccination. JCI Insight. 2022;7(11). doi:10.1172/jci.insight.159422.
- Sempere J, Llamosí M, López Ruiz B, Del Río I, Pérez-García C, Lago D, Gimeno M, Coronel P, González-Camacho F, Domenech M, et al. Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004–20: a national surveillance study. Lancet Microbe. 2022;3(10):e744–e52. doi:10.1016/S2666-5247(22)00127-6.
- Bencina G, Fues Wahl H, Tsoumani E, Salomonsson S. Recommendations and Health Technology Assessment (HTA) landscape evaluation for pediatric pneumococcal conjugate vaccines (PCV) in Europe: A systematic literature review. Hum Vaccin Immunother. 2022;18(5):2060017. doi:10.1080/21645515.2022.2060017.
- Hu T, Weiss T, Bencina G, Owusu-Edusei K, Petigara T. Health and economic burden of invasive pneumococcal disease associated with 15-valent pneumococcal conjugate vaccine serotypes in children across eight European countries. J Med Econ. 2021;24(1):1098–107. doi:10.1080/13696998.2021.1970975.
- Huang L, Wasserman M, Grant L, Farkouh R, Snow V, Arguedas A, Chilson E, Sato R, Perdrizet J. Burden of pneumococcal disease due to serotypes covered by the 13-valent and new higher-valent pneumococcal conjugate vaccines in the United States. Vaccine. 2022;40(33):4700–8. doi:10.1016/j.vaccine.2022.06.024.
- CRD CfRaD. Systematic Reviews - CRD’s guidance for undertaking reviews in health care. 2009.
- Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj. 2021;372:n71. doi:10.1136/bmj.n71.
- National Immunization Technical Advisory Groups. 2020. https://www.nitag-resource.org/.
- International Network of Agencies for Health Technology Assessment (INAHTA). Members List. http://www.inahta.org/members/members_list/.
- European Network for Health Technology Assessment EUnetHTA Network. https://eunethta.eu/about-eunethta/eunethtanetwork/.
- AEMPS. Consejo interterritorial del sistema nacional de salud vacunación específica en personas adultas (≥18 años) con condiciones de riesgo. 2022.
- AIFA. L’uso dei Farmaci in Italia Rapporto Nazionale Anno. 2020.
- Alexander Kuhlmann J-MGVDS. Serotype dynamics in pneumococcal diseases and the performance of vaccination strategies for older adults in Germany. 2020.
- Agencji Oceny Technologii Medycznych i Taryfikacji (AOTMiT). Opinia Prezesa Agencji Oceny Technologii Medycznych i Taryfikacji nr 25/2021 z dnia 30 kwietnia 2021 r. o projekcie programu polityki zdrowotnej „Program profilaktyki zakażeń pneumokokowych u osób powyżej 65 roku życia”. 2021.
- Agencji Oceny Technologii Medycznych i Taryfikacji (AOTMiT). Protokół nr 15/2022 z posiedzenia Rady Przejrzystości. 2022.
- Bauer A, Tiefengraber D, Wiedermann U. Towards understanding vaccine hesitancy and vaccination refusal in Austria. Wien Klin Wochenschr. 2021;133(13):703–13. doi:10.1007/s00508-020-01777-9.
- Bhavsar AB, Olbrecht J, Izurieta P. Pin33 cost-effectiveness of current pneumococcal vaccines in older adults in european settings: a systematic literature review. Value Health. 2019;22:S645. doi:10.1016/j.jval.2019.09.1277.
- Birck AM, Nordin Christensen L, Pedersen MH, Olsen J, Johnson KD, Bencina G, Clausen TH, Larsen CS. Health economic evaluation of introducing a PPSV23-based vaccination programme to adults aged 65 and above, and an extension to the 60-64 age group in Denmark. Expert Rev Vaccines. 2021;20(10):1327–37. doi:10.1080/14760584.2021.1977627.
- Boccalini S, Bechini A, Gasparini R, Panatto D, Amicizia D, Bonanni P. Economic studies applied to vaccines against invasive diseases: an updated budget impact analysis of age-based pneumococcal vaccination strategies in the elderly in Italy. Hum Vaccin Immunother. 2017;13(2):417–22. doi:10.1080/21645515.2017.1264827.
- Butić I, Gužvinec M, Jelić M, Groš I, Lucić S, Bošnjak M, Tambić Andrašević A. Serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates among Croatian adults during a fifteen year period (2005-2019). Croat Med J. 2022;63(2):156–65. doi:10.3325/cmj.2022.63.156.
- CFV. Eidgenössische Kommission für Impffragen Protokoll der 88. Plenarsitzung. 2022.
- Constantinou CA, Ziogas DC, Venetsanopoulou A, Gamaletsou MN, Koutsogeorgopoulou L, Barbouni A, Tzioufas AG, Sipsas NV. A clinical audit of pneumococcal vaccination among patients with autoimmune rheumatic diseases living in Greece: the power of awareness. Vaccine. 2021;39(11):1593–7. doi:10.1016/j.vaccine.2021.02.009.
- Contou D, Coudroy R, Colin G, Tadié J-M, Cour M, Sonneville R, Mekontso Dessap A, de Prost N. Pneumococcal purpura fulminans in asplenic or hyposplenic patients: a French multicenter exposed-unexposed retrospective cohort study. Crit Care. 2020;24(1):1–8. doi:10.1186/s13054-020-2769-y.
- Council SH. Avis 9674 - Vaccination antipneumococcique (adultes). 2022.
- CSMI. Infections invasives à Pneumocoques. 2022.
- De Burghgraeve T, Henrard S, Verboven B, Van Pottelbergh G, Vaes B, Mathei C. The incidence of lower respiratory tract infections and pneumococcal vaccination status in adults in Flemish primary care. Acta Clin Belg. 2021;76(5):335–45. doi:10.1080/17843286.2020.1735113.
- de Vries L, Kellerborg K, Brouwer W, van Baal P. Don’t forget about the future: The impact of including future costs on the cost-effectiveness of adult pneumococcal conjugate vaccination with PCV13 in the Netherlands. Vaccine. 2021;39(29):3834–43. doi:10.1016/j.vaccine.2021.05.091.
- DGS. Programa nacional de vacinação. 2022.
- Esposito S, Franco E, Gavazzi G, de Miguel AG, Hardt R, Kassianos G, Bertrand I, Levant M-C, Soubeyrand B, López Trigo JA, et al. The public health value of vaccination for seniors in Europe. Vaccine. 2018;36(19):2523–8. doi:10.1016/j.vaccine.2018.03.053.
- Garcia Garrido HM, Mak AM, Wit FW, Wong GW, Knol MJ, Vollaard A, Tanck MWT, Van Der Ende A, Grobusch MP, Goorhuis A, et al. Incidence and risk factors for invasive pneumococcal disease and community-acquired pneumonia in human immunodeficiency virus–infected individuals in a high-income setting. Clin Infect Dis. 2020;71(1):41–50. doi:10.1093/cid/ciz728.
- Giuffrida S. Calabria: a successful experience implementing herpes zoster vaccination strategies. Aging Clin Exp Res. 2019;31(3):421–3. doi:10.1007/s40520-019-01145-2.
- Gomez SC, Jiang Y, Lu X, Pulfer GN, Boix PR. Pin44-economic evaluation of 60+ years adult vaccination strategy using pneumococcal polysaccharide vaccine in Spain. Value Health. 2018;21:S228. doi:10.1016/j.jval.2018.09.1363.
- Gouveia M, Jesus G, Inês M, Costa J, Borges M. Cost-effectiveness of the 13-valent pneumococcal conjugate vaccine in adults in Portugal versus “no vaccination” and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine. Hum Vaccin Immunother. 2019;15(4):850–8. doi:10.1080/21645515.2018.1560769.
- Guerrini G, Franzetti F, Giacomelli R, Meroni L, Riva A, Scirè CA, Scrivo R, Tavio M, Agostinone A, Airò P, et al. Italian recommendations for influenza and pneumococcal vaccination in adult patients with autoimmune rheumatic diseases. Clin Exp Rheumatol. 2019;38(2):245–56. doi:10.55563/clinexprheumatol/hj69ne.
- HAS. Vaccination contre les infections à pneumocoque en contexte de pénurie de vaccin pneumococcique non conjugué 23-valent. 2017.
- HCSP. Infections à pneumocoque : recommandations vaccinales pour les adultes. 2017.
- Folkehelseinstituttet. Pneumokokkvaksine til risikogrupper. 2020.
- Health M. Farmako-ekonomický rozbor lieku. 2017.
- Horvat M, Robnik B, Bizjak K, Vuzem S, Miksić NG. Audit of post-splenectomy prophylaxis in a single tertiary center in Slovenia: where are we and what should be done? Surg Infect (Larchmt). 2021;22(3):292–8. doi:10.1089/sur.2020.038.
- INSP. Luna Națională a informării despre VACCINARE aprilie 2022. 2022.
- ISS. Guida alla controindicazioni. 2018.
- JCVI. Minute of the JCVI pneumococcal sub-committee meeting 2022.
- Kopp A, Mangin O, Gantzer L, Lekens B, Simoneau G, Ravelomanantsoa M, Evans J, Bergmann JF, Sellier P. Pneumococcal vaccination coverage in France by general practitioners in adults with a high risk of pneumococcal disease. Hum Vaccin Immunother. 2021;17(1):162–9. doi:10.1080/21645515.2020.1756669.
- Kuchenbecker U, Chase D, Reichert A, Schiffner-Rohe J, Atwood M, Ortiz JR. Estimating the cost-effectiveness of a sequential pneumococcal vaccination program for adults in Germany. PloS One. 2018;13(5):e0197905. doi:10.1371/journal.pone.0197905.
- Landlaeknir DoHE. Pneumokokkasýking, ífarandi. 2019.
- Larsen L, Bistrup C, Sørensen SS, Boesby L, Nguyen MTT, Johansen IS. The coverage of influenza and pneumococcal vaccination among kidney transplant recipients and waiting list patients: a cross‐sectional survey in Denmark. Transpl Infect Dis. 2021;23(3):e13537. doi:10.1111/tid.13537.
- Maraki S, Mavromanolaki VE, Stafylaki D, Hamilos G, Samonis G. The evolving epidemiology of serotype distribution and antimicrobial resistance of streptococcus pneumoniae strains isolated from adults in Crete, Greece, 2009–2016. Infect Chemother. 2018;50(4):328–39. doi:10.3947/ic.2018.50.4.328.
- Marbaix S, Peetermans WE, Verhaegen J, Annemans L, Sato R, Mignon A, Atwood M, Weycker D. Cost-effectiveness of PCV13 vaccination in Belgian adults aged 65-84 years at elevated risk of pneumococcal infection. PloS One. 2018;13(7):e0199427. doi:10.1371/journal.pone.0199427.
- Matthews I, Lu X, Xia Q, Black W, Nozad B. Pneumococcal vaccine coverage among individuals aged 18 to 64 years old with underlying medical conditions in the UK: a retrospective database analysis. BMC Public Health. 2020;20(1):1–0. doi:10.1186/s12889-020-09613-5.
- McCarthy H, Jackson M, Corcoran M, McElligott M, MacHale E, Sulaiman I, Cushen B, Costello RW, Humpreys H. Colonisation of Irish patients with chronic obstructive pulmonary disease by Streptococcus pneumoniae and analysis of the pneumococcal vaccine coverage: a non-interventional, observational, prospective cohort study. BMJ Open. 2017;7(7):e013944. doi:10.1136/bmjopen-2016-013944.
- Mertsch P, Rademacher J, de Roux A, Barten G, Diel R, Gert E, Naim J, Zurawski A, Welte T, Ringshausen FC. PROGNOSIS-the German bronchiectasis registry: first results. Eur Respiratory Soc. 2017;50(61):PA4059.
- Wróbel I, Kuch A, Waśko I, Gołębiewska A, Ronkiewicz P, Kiedrowska M, et al. Postępy Mikrobiologii - Invasive pneumococcal disease among patiens above 65 years old. Polskie towarzystwo mikrobiologów. 2017;56(3):42.
- Mohr A, Plentz A, Sieroslawski A, Pezenburg F, Koch M, Bauernfeind S, Pfeifer M, Salzberger B, Hitzenbichler F. Adherence to STIKO recommendations in patients with pulmonary disease in southeast Germany. Infection. 2021;49(6):1319–23. doi:10.1007/s15010-021-01708-4.
- Monier A, Puyade M, Hernanz MG, Bouchaert P, Leleu X, Tourani J, Roblot F, Rammaert B. Observational study of vaccination in cancer patients: how can vaccine coverage be improved? Médecine et Maladies Infectieuses. 2020;50(3):263–8. doi:10.1016/j.medmal.2019.11.006.
- Ng WL, Anjum A, Sebastian A, Devlin J, Fraser A. P04 A quality improvement initiative to improve influenza and pneumococcal vaccination rates in patients receiving biological DMARDS (bDMARDs) in the mid-west of Ireland. Rheumatology. 2020;59(Supplement_2):keaa111. 003. doi:10.1093/rheumatology/keaa111.003.
- Office NI. Pneumococcal infection. 2018:1–12.
- Papagiannis D, Rachiotis G, Mariolis A, Zafiriou E, Gourgoulianis KI. Vaccination coverage of the elderly in Greece: a cross-sectional nationwide study. Can J Infect Dis Med Microbiol. 2020;2020. doi:10.1155/2020/5459793.
- Paparoupa M. Pneumokokken-Impfung im Erwachsenenalter. Praevention und Rehab. 2017;29:106.
- Piotrowska A, Paradowska-Stankiewicz I, Skarżyński H. Rates of vaccination against Streptococcus pneumoniae in cochlear implant patients. Med Sci Monit. 2017;23:4567. doi:10.12659/MSM.903188.
- Popova A, Shipulina O, Dmitryukova M, Deulina M, Pokrovsky V. Results of HPV testing for anal screening in men who have sex with men. J Int AIDS Soc. 2018;21:180–.
- PSC. Priporočila za cepljenje odraslih in otrok, starih 5 let in več, proti pnevmokoknim okužbam. 2019.
- PSC. Povzetek glavnih značilnosti zdravila. 2021.
- Ratera. Vaccination of adults.
- RIVM. Monitor Vaccinatiegraad Nationaal Programma Pneumokokkenvaccinatie Volwassenen (NPPV). 2020.
- RIVM. Pneumokokkenvaccinatie Factsheet. 2022.
- RIVM. Pneumokokkenziekte Richtlijn. 2022.
- Rozenbaum M, editor. 1434. Cost-effectiveness of sequencial vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by the 23 valent polysaccharide vaccine (PPV23) in the Netherlands. Open Forum Infectious diseases. USA: Oxford University Press; 2018. p. S443–S444.
- Rozenbaum M, editor. 1439. The cost-effectiveness of vaccinating adults at increased risk of pneumococcal disease against pneumococcal disease in the Netherlands. Open Forum Infectious diseases. USA: Oxford University Press; 2018. p. S445.
- Runyo F, Matignon M, Audureau E, Vindrios W, Boueilh A, Gomart C, Grimbert P, Gallien S, Melica G. Infectious disease consultation is effective in boosting vaccine coverage in patients awaiting kidney transplantation: a French prospective study. Transpl Infect Dis. 2021;23(4):e13607. doi:10.1111/tid.13607.
- Sanduzzi A, Canora A, Belfiore P, Bocchino M, Liguori R, Liguori G. Impact of 13Valent vaccine for Prevention of pneumococcal diseases in children and adults at risk: possible scenarios in Campania region. Infectious disorders-drug targets (formerly Current drug targets-Infectious disorders). Infect Disord Drug Targets. 2019;19(4):403–8. doi:10.2174/1871526518666180820161630.
- Schmedt N, Schiffner-Rohe J, Sprenger R, Walker J, von Eiff C, Häckl D, Gopichandran V. Pneumococcal vaccination rates in immunocompromised patients—a cohort study based on claims data from more than 200,000 patients in Germany. PloS One. 2019;14(8):e0220848. doi:10.1371/journal.pone.0220848.
- Sevilla J, Stawasz A, Burnes D, Poulsen P, Sato R, Bloom D. Calculating the indirect costs of adult pneumococcal disease and the rate of return to the 13-valent pneumococcal conjugate vaccine (PCV13) in older adults, with an application to Denmark. Value Health. 2017;20(9):A787. doi:10.1016/j.jval.2017.08.2302.
- SSI. Pneumokokvaccine 23-valent (Pneumovax). 2022.
- SST. Tilbud om pneumokokvaccination til særlige risikogrupper. 2020.
- SST. Tilskud til vacciner til visse persongrupper. 2022.
- Sticchi L, Taramasso L, Di Biagio A, Olobardi D, Icardi G, Bassetti M. Will vaccine hesitancy compromise our efforts to face the next SARS-CoV-2 epidemic wave? Hum Vaccin Immunother. 2021;17(6):1664–5. doi:10.1080/21645515.2020.1829413.
- Storch J, Fleischmann-Struzek C, Rose N, Lehmann T, Mikolajetz A, Maddela S, Pletz MW, Forstner C, Wichmann O, Neufeind J, et al. The effect of influenza and pneumococcal vaccination in the elderly on health service utilisation and costs: a claims data-based cohort study. Eur J Health Econ. 2022;23(1):67–80. doi:10.1007/s10198-021-01343-8.
- Suitner C, Salvador Casara BG, Maggi S, Baldo V. An independent study to compare compliance, attitudes, knowledge, and sources of knowledge about pneumococcal vaccinations among an Italian sample of older adults. Vaccines. 2022;10(4):490. doi:10.3390/vaccines10040490.
- Tavares J, Cruz AR, Nogueira R. Chronic obstructive pulmonary disease–are we vaccinating the patients? Eur Respiratory Soc; 2017.
- THL (Finnish Institute for Health and Welfare). Pneumokokkirokotusstrategiat. 2018; 1–52.
- THL (Finnish Institute for Health and Welfare). Riskiryhmien pneumokokkirokotukset. 2022.
- Thorrington D, Van Rossum L, Knol M, De Melker H, Rümke H, Hak E, Van Hoek AJ. Impact and cost-effectiveness of different vaccination strategies to reduce the burden of pneumococcal disease among elderly in the Netherlands. PloS One. 2018;13(2):e0192640. doi:10.1371/journal.pone.0192640.
- Tubiana S, Labarere J, Levraut J, Michelet P, de Vaux FJ, Doumenc B, Hausfater P, Choquet C, Plaisance P, Schmidt J, et al. Effectiveness of a multifaceted informational-based and text message reminders on pneumococcal and influenza vaccinations in hospital emergency departments: a cluster-randomized controlled trial. Vaccines. 2021;9(9):962. doi:10.3390/vaccines9090962.
- ULAC. The number of people vaccinated against pneumococcal infection has increased. 2021.
- VACSATC. FELNŐTTEKNEK AJÁNLOTT VÉDŐOLTÁSOK. 2017.
- Vila-Córcoles A, Ochoa-Gondar O, de Diego C, Satué E, Vila-Rovira A, Aragón M. Pneumococcal vaccination coverages by age, sex and specific underlying risk conditions among middle-aged and older adults in Catalonia, Spain, 2017. Eurosurveillance. 2019;24(29):1800446. doi:10.2807/1560-7917.ES.2019.24.29.1800446.
- Walter E, Eichhober G, Voit M. Pin32 - a public health and budget impact analysis (BIA) of vaccinating adults against pneumococcal-diseases in austria. Value Health. 2019;22:S645. doi:10.1016/j.jval.2019.09.1276.
- Weinmayr L-M, Steinhäuser J, Gehring SC, Goetz K. Vaccination management for elderly patients in primary care settings–documentation and responsibilities during a vaccination campaign. Patient Prefer Adherence. 2019;13:1295. doi:10.2147/PPA.S212507.
- Willem L, Blommaert A, Hanquet G, Thiry N, Bilcke J, Theeten H, Verhaegen J, Goossens H, Beutels P. Economic evaluation of pneumococcal vaccines for adults aged over 50 years in Belgium. Hum Vaccin Immunother. 2018;14(5):1218–29. doi:10.1080/21645515.2018.1428507.
- Wolff E, Storsaeter J, Örtqvist Å, Naucler P, Larsson S, Lepp T, Roth A. Cost-effectiveness of pneumococcal vaccination for elderly in Sweden. Vaccine. 2020;38(32):4988–95. doi:10.1016/j.vaccine.2020.05.072.
- Wyplosz B, Fernandes J, Sultan A, Roche N, Roubille F, Loubet P, Fougère B, Moulin B, Duhot D, Vainchtock A, et al. Pneumococcal and influenza vaccination coverage among at-risk adults: A 5-year French national observational study. Vaccine. 2022;40(33):4911–21. doi:10.1016/j.vaccine.2022.06.071.
- Zeevat F, Boersma W, van der Schans J, Boersma C, Postma M. Pin65 cost-effectiveness analysis on elderly pneumococcal vaccination in the netherlands: challenging the dutch health council’s advice. Value Health. 2019;22:S650. doi:10.1016/j.jval.2019.09.1306.
- Zeevat F, van der Schans J, Boersma W, Boersma C, Postma MJ. Cost-effectiveness analysis on elderly pneumococcal vaccination in the Netherlands: challenging the Dutch health Council’s advice. Vaccine. 2019;37(43):6282–4. doi:10.1016/j.vaccine.2019.08.051.
- Zorginstituut. Vaccinatie pneumokokken 60-plussers buiten Zorgverzekeringswet om financieren. 2018.
- Zorginstituut. Verslag van de vergadering van de Wetenschappelijke Adviesraad (WAR) over 13-valente pneumokokken-polysacharidenconjugaatvaccin (Prevenar®). 2021.
- (CDC) CfDCaP. Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. Adults: updated recommendations of the advisory committee on immunization practices — United States, 2022. USA: CDC; 2022. 2022 Jan 28; 71(4):109–17. doi:10.15585/mmwr.mm7104a1.
- Department of Health and Aged Care (Australia). Pneumococcal vaccination for all Australians Australia. 2023. https://immunisationhandbook.health.gov.au/resources/publications/pneumococcal-vaccination-for-all-australians#:~:text=Children%20over%2012%20months%2C%20adolescents,at%20least%205%20years%20later.
- Ministry of Health LaW厚. Pneumococcal infection (elderly) Japan. 2023. https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/kenkou/kekkaku-kansenshou/haienkyukin/index_1.html.
- Populationpyramid.net. Population pyramids of the world from 1950 to 2100: Austria. 2022. https://www.populationpyramid.net/austria/2022/.
- Wasserman MD, Perdrizet J, Grant L, Hayford K, Singh S, Saharia P, Horn, EK, Farkouh, RA. Clinical and economic burden of pneumococcal disease due to serotypes contained in Current and investigational pneumococcal conjugate vaccines in children under five years of age. Infect Dis Ther. 2021;10(4):2701–20. doi:10.1007/s40121-021-00544-1.
- Kwambana-Adams B, Hanson B, Worwui A, Agbla S, Foster-Nyarko E, Ceesay F, Ebruke C, Egere U, Zhou Y, Ndukum M, Sodergren E. Rapid replacement by non-vaccine pneumococcal serotypes may mitigate the impact of the pneumococcal conjugate vaccine on nasopharyngeal bacterial ecology. Sci Rep. 2017;7(1):8127. doi:10.1038/s41598-017-08717-0.
- Yoon JG, Jang AY, Kim MJ, Seo YB, Lee J, Choi YH, Kim YK, Jeong EJ, Kim HS, Kwon KT, et al. Persistent serotype 3 and 19A invasive pneumococcal diseases in adults in vaccine era: Serotype-dependent difference in ceftriaxone susceptibility. Vaccine. 2022;40(15):2258–65. doi:10.1016/j.vaccine.2022.03.004.
- Janssens E, Flamaing J, Vandermeulen C, Peetermans WE, Desmet S, De Munter P. The 20-valent pneumococcal conjugate vaccine (PCV20): expected added value. Acta Clin Belg. 2023;78(1):78–86. doi:10.1080/17843286.2022.2039865.
- Løchen A, Croucher NJ, Anderson RM. Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency. Sci Rep. 2020;10(1):18977. doi:10.1038/s41598-020-75691-5.
- Mungall BA, Hoet B, Nieto Guevara J, Soumahoro L. A systematic review of invasive pneumococcal disease vaccine failures and breakthrough with higher-valency pneumococcal conjugate vaccines in children. Expert Rev Vaccines. 2022;21(2):201–14. doi:10.1080/14760584.2022.2012455.