Patricia Izurieta*
Dorota Borys- Vaccines R&D/Infectious Disease, GSK, Wavre, Belgium
Introduction: Despite the widespread implementation of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in infant national immunization programs and anticipated herd effects, pneumococcal disease incidence remains relatively high among older adults. In this vulnerable population, this includes not only invasive pneumococcal disease (IPD), but, more notably, non-invasive community-acquired pneumonia (CAP). A comprehensive understanding of adult pneumococcal epidemiology, particularly that of non-invasive CAP, is essential to guide future vaccination strategies for this population.
Methods: We systematically reviewed observational studies (2006–2020) on pneumococcal serotype distribution in IPD and non-invasive CAP among adults aged ≥65 years after PCV implementation in children, focusing on the period post-implementation of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and 13-valent PCV (PCV13). Serotype-specific pooled percentage averages were calculated to determine the contribution of each serotype to a certain clinical manifestation.
Results: Our analysis of 17 IPD and 17 CAP studies indicates the persistence of several vaccine serotypes, particularly serotypes 3 and 19A, in both clinical manifestations. Also serotype 7F remained frequently reported. The predominant non-PCV13 serotypes identified in both manifestations were serotypes 8, 12F, 15A, and 22F.
Conclusion: The persistence of certain PCV13-serotypes in pneumococcal disease among adults aged ≥65 years suggests that herd immunity by infant PCV immunization may be insufficient to provide optimal protection in this population. This, coupled with emerging non-PCV13 serotypes due to serotype replacement and other limitations of current vaccines, supports the need for new vaccination technologies and strategies to improve protection of older adults.
1 Introduction
Streptococcus pneumoniae (Spn) causes significant morbidity and mortality globally, particularly among young children (aged ≤5 years), older adults (aged ≥65 years), and those with underlying medical conditions (1–4). The clinical spectrum of pneumococcal infections ranges from mild conditions such as acute otitis media (AOM) (among children) or sinusitis, to severe conditions like non-invasive community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) (3, 5). At least 100 Spn serotypes are known (6), but only a subset of these is responsible for most infections (7).
Pneumococcal conjugate vaccines (PCVs) targeting particular serotypes have been widely used in infant national immunization programs (NIPs) for nearly 2 decades. Starting from 2009, the 7-valent PCV (PCV7, Prevenar/Prevnar, Pfizer Inc.) was replaced in infant NIPs by the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix, GSK) or the 13-valent PCV (PCV13, Prevenar 13/Prevnar 13, Pfizer Inc.) (7). Since 2015, PCV uptake in infants has been high in high-income countries, with uptake levels exceeding 80%, while uptake has generally been lower in low- and middle-income countries, ranging between 28 and 60% (8). With the recent authorization of new PCVs for infant use, targeting 15 (PCV15, Vaxneuvance, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. [MSD]) or 20 (PCV20, Prevenar 20/Prevnar 20, Pfizer Inc.) serotypes, health authorities are currently re-evaluating their recommendations (9).
For adults, guidelines on pneumococcal vaccination vary among countries. Since the 1980s, the pneumococcal polysaccharide vaccine covering 23 serotypes (PPSV23, Pneumovax 23, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. [MSD]) has been widely recommended for high-risk individuals aged ≥2 years (10), and many countries also recommend the vaccine for adults aged ≥65 years (11–14). However, PPSV23 has been shown to elicit an immune response that is neither long lasting nor anamnestic upon subsequent challenge (15), and its effectiveness has been estimated at 45–59% against IPD, and 48–53% against pneumococcal pneumonia by cohort and case–control studies (16). Since 2014, some countries recommend PCV13 for use in vulnerable adult populations (9) and are currently considering PCV15, PCV20 or the recently approved 21-valent PCV (PCV21, Capvaxive, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. [MSD]) (9, 17).
Although PCV use has significantly reduced pneumococcal disease incidence in children (18–20), and despite the potential benefits of both direct adult vaccination and herd protection in adults from infant PCV programs, the burden of pneumococcal diseases remains high among older adults (21–26). One reason may be that the pneumococcal vaccine uptake among older adults has remained suboptimal, even in high-income countries, with average rates of 68% in the United States (US) (2019–2020), 58% in Canada (2018–2019), 33.6% in Japan (2014–2020), and just 18% in Europe (2015–2016) (27–30). Besides, the remaining burden may be explained by inadequate (herd) protection of current vaccines against certain serotypes, and differences in serotype distribution between age groups. Moreover, serotype replacement, a phenomenon where the reduction in PCV-targeted serotypes leads to increased circulation and disease caused by non-PCV serotypes (23, 31), may amplify the burden. Therefore, understanding adult pneumococcal disease epidemiology after PHiD-CV/PCV13 implementation in infant NIPs is essential to guide future vaccination strategies.
Pneumococcal epidemiological data are primarily available on IPD because serotyping is a routine component of most mandatory IPD surveillance programs (7). However, the serotype distribution may vary by clinical manifestation of Spn (7, 32–35). Understanding the epidemiology of non-invasive pneumococcal CAP is thus at least equally important, given its higher incidence among older adults compared to IPD and the substantial associated healthcare costs (24, 36). Still, serotype data for this clinical manifestation remain relatively scarce (7), largely due to limitations in available microbiological methods, such as the low sensitivity of sputum cultures and sputum PCR due to poor sample quality and prior antibiotic use (37), and the incomplete serotype coverage of urinary antigen detection tests and immunoassays (38–40). Additionally, no dedicated surveillance mechanisms exist for non-invasive CAP (7, 24).
In this systematic literature review (SLR), our objective was to synthesize worldwide published data of observational studies on pneumococcal serotype distribution in both IPD and non-invasive CAP in adults aged ≥65 years after the widespread uptake of PHiD-CV/PCV13 in infants, compared to the post-PCV7 era. Ultimately, this review aimed to enhance our understanding of the dynamic interplay between PHiD-CV/PCV13 implementation in infant NIPs, herd protection, serotype replacement, and the pneumococcal epidemiology in older adults.
2 Methods
The present analysis is part of a larger SLR that aimed to evaluate the impact of infant PHiD-CV/PCV13 uptake on the serotype distribution in remaining invasive and non-invasive pneumococcal disease in both children aged ≤5 years and adults aged ≥65 years. The pneumococcal diseases of interest were AOM (among children only), CAP, and IPD. This manuscript summarizes the findings for adults. The findings for children are discussed in a separate manuscript (41). The review was performed according to a predefined protocol and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (42).
2.1 Systematic search strategy
PubMed and Embase were systematically searched to retrieve articles on pneumococcal serotype distribution in IPD and CAP among adults aged ≥65 years after the implementation of PCV7, PHiD-CV, or PCV13 in infant NIPs. Search strings consisted of a combination of terms for Spn serotypes, PCVs, and pneumococcal diseases. A limitation was set on the date of publication from 1 January 2006 to 31 December 2020, considering the widespread utilization of PCV7 in infant NIPs in many Western countries in 2006, while also limiting the extraction of data that was obtained during and after the coronavirus disease 2019 (COVID-19) pandemic (COVID-19 was declared a pandemic by the WHO in March 2020). Post-PHiD-CV/PCV13 serotyping data were of primary interest to our study. Studies conducted after PCV7 implementation were included to assess changes in serotype distribution before and after PHiD-CV/PCV13 uptake. Additional details can be found in the Supplementary methods.
2.2 Eligibility criteria and study selection
All predefined eligibility criteria for study inclusion were applied at 2 stages: at screening and at the data extraction phase. For this manuscript, studies including data on adults ≥65 years were retained.
Eligible studies related to CAP were observational studies. CAP was defined as pneumonia acquired outside of the hospital (43), and serotyping was done on samples obtained from non-sterile sites (sputum, urine, bronchial aspirates, biopsy samples, etc.). Studies on invasive CAP were not eligible given that this condition is typically classified under IPD. To minimize the potential impact of incidental small findings or limited cohort observations, only CAP studies reporting on a predefined minimum of 20 serotyped isolates were included.
Given that many published observational studies on IPD were expected, eligible IPD studies were in the first instance limited to SLRs/meta-analyses. Since no SLRs were identified, as predefined in the protocol, the eligibility criteria for IPD were expanded to include the most recent pre-COVID-19 observational studies published between 2018 and 2020. Serotyping was done on samples obtained from sterile sites (blood, cerebrospinal fluid, pleural effusion, joint fluid, pericardial fluid, etc.) (44). Only studies reporting on at least 30 serotyped isolates were included, as many publications were expected for IPD allowing for more stringent criteria compared to CAP.
A detailed description of inclusion/exclusion criteria and study selection workflow is outlined in the Supplementary methods.
2.3 Data extraction and analysis
To determine the contribution of each serotype to a certain clinical manifestation, pooled percentage averages were calculated for each serotype using the following formula:
where the “sum” corresponds to the total number of samples across studies included in the corresponding analysis. The serotype-specific pooled percentage average thus determines the average proportion of a given serotype, relative to all serotyped samples of the studies included in the corresponding analysis. This method ensures the weighted representation of the distribution of serotypes in pneumococcal disease (either IPD or CAP) by accounting for variations in sample sizes across the included studies. Since percentages are calculated for each serotype separately, rather than as proportions of a whole, the sum of all pooled percentage averages may exceed 100% for a certain clinical manifestation.
For each clinical manifestation, the included studies were categorized into 2 vaccine periods based on information provided in the publications: post-PCV7 or post-PHiD-CV/PCV13 (pooled), referring to the use of these vaccines in infants.
The primary analysis for each clinical manifestation included only data originating from studies conducted in countries where the PCV was implemented through infant NIPs. Studies conducted in countries where the PCV was only available in private markets, and not included in the infant NIP, were excluded. Such exclusions were based on the premise that these settings might lack the effects of herd protection due to low infant PCV uptake. Additionally, a more comprehensive sensitivity analysis was conducted for each clinical manifestation, based on data from all eligible studies, including those in countries that implemented PCVs in the private market only. Furthermore, subgroup analyses were conducted by classifying each eligible study based on the PCV product (PHiD-CV or PCV13).
Serotype-specific pooled percentage averages were reported only if data from at least 5 studies were available for that serotype. This threshold was established to limit the potential for data skewing resulting from a limited number of studies, focusing on the serotypes supported by stronger evidence. This criterion could not be applied to all subgroup analyses per PCV product and the post-PCV7 analyses due to the limited number of eligible studies for some subgroups.
The analyses were performed using R studio. All analyses were descriptive, and no formal statistical testing was performed. More details on the data extraction procedure and study categorization can be found in the Supplementary methods.
3 Results
3.1 Study selection
Of the 3,822 screened publications, 126 studies were selected for data extraction, of which 109 studies were included in the quantitative analysis. The main reason for study exclusion was the lack of sufficient details for further analysis. In total, 33 studies covered serotype distribution data in adults aged ≥65 years. Of these, 17 reported data on IPD (45–61), and 17 on non-invasive CAP (49, 62–77); [one study reported on both disease manifestations (49)] (Figure 1). Of the 33 studies considered, most were conducted in Europe (n = 18), followed by Asia (n = 10), North America (n = 4), and South America (n = 1).
Figure 1. PRISMA flow chart of the systematic literature search. # All records excluded during data extraction relate to children aged ≤5 years. *Some of the records included in this review also contain data on children aged ≤5 years (n = 11), but these datapoints were not included in the analysis on adults aged ≥65 years. One study on adults aged ≥65 years reported on both IPD and CAP. **Records included in this review containing only data on children aged ≤5 years were excluded for the purpose of this publication. n, number of records; SLR, systematic literature review; IPD, invasive pneumococcal disease; CAP, community-acquired pneumonia.
3.2 IPD
3.2.1 IPD study characteristics
Across all included studies on IPD, 4/17 studies reported data obtained post-PCV7 infant implementation (51, 54, 57, 58), and 14/17 post-PHiD-CV/PCV13 uptake (45–50, 53–56, 58–61). There were 2 studies that reported stratified data following both PCV7 and PHiD-CV or PCV13 (54, 58). One study reported data obtained post-PCV7 and post-PCV13 implementation without differentiating which period the data corresponded to, and could thus not be used for further analysis (52). The majority of the post-PHiD-CV/PCV13 studies were conducted in infant NIP settings (12/14 studies), and most exclusively used PCV13 (12/14 studies). Most of these PCV13 studies (8/12 studies) included data that were collected up to 4 to 8 years following its introduction in infant NIPs. One study was in a setting of exclusive PHiD-CV use [Austria (59)], and 1 in a setting of mixed PHiD-CV and PCV13 use [South Korea (53)]. In total, serotyping data from 27,757 adult IPD isolates were extracted post-PHiD-CV/PCV13 uptake in infants. Study-specific details, including study type, age range, sample type, total number of isolates, PCV product, inclusion in the infant NIP, and the range of years of PCV use, are provided in Table 1.
Table 1. Characteristics of the included IPD studies post-PHiD-CV/PCV13 uptake in infants.
3.2.2 Serotype distribution in adult IPD post-PHiD-CV/PCV13 uptake in infants
Post-PHiD-CV/PCV13 implementation through infant NIPs (primary analysis comprising data of 12 studies), the 10 most reported serotypes in older adults with IPD were serotype 3, with a pooled percentage average of 11.6% across studies, 8 (10.0%), 22F (8.2%), 19A (7.1%), 12F (5.9%), 9 N (5.1%), 15A (5.0%), 7F (4.4%), 6C (4.3%), and 23A (3.9%) (Figure 2A; Supplementary Table S3). A nearly identical serotype distribution pattern was obtained by the sensitivity analysis including 2 additional IPD-related studies where PCV13 was introduced via the private market only (Supplementary Figure S1).
Figure 2. Serotype distribution in invasive pneumococcal disease among adults aged ≥65 years (A) post-PHiD-CV/PCV13 implementation through infant national immunization programs (n = 12), and (B) post-PCV13 uptake in infants (either through infant national immunization programs or private markets) (n = 12). The top 20 serotypes are shown. Serotypes are represented by colors corresponding to the lowest valency PCV product in which they are included. In the PCV legend, the additional serotypes included in the product are relative to the next lower valency product. Pooled percentage averages were calculated for each serotype individually, thus the sum of all serotypes may exceed 100%. For panel A, serotype-specific pooled percentage averages were calculated only if 5 or more studies reported on the respective serotype. For panel B, the pooled percentage averages were calculated irrespective of the number of studies reporting on it. IPD, invasive pneumococcal disease; n, number of studies that were included in the analysis; NIP, national immunization program; PCV, pneumococcal conjugate vaccine; PCV7, 7-valent PCV; PCV13, 13-valent PCV; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine.
A stratified analysis on data obtained from the 12 PCV13-related studies yielded a highly comparable serotype distribution pattern and corresponding pooled percentage averages (Figure 2B). A single study in PHiD-CV setting (59) reported serotype 3 (28.6%) as the leading serotype, followed by serotypes 19A (7.4%), and 22F (6.1%) (Supplementary Figure S2).
In the post-PCV7 period (3 studies in infant NIP context), serotype 3 (16.6%) was the leading serotype (Supplementary Figure S3). When comparing the reporting of PCV13 serotypes post-PHiD-CV/PCV13 uptake with the post-PCV7 period, the pooled percentage averages in the primary analysis for serotype 3 were 16.6% post-PCV7 vs. 11.6% post-PHiD-CV/PCV13, and 8.6% vs. 7.1% for serotype 19A. An important decrease in the reporting of several other PCV13 serotypes was observed.
3.3 Non-invasive CAP
3.3.1 CAP study characteristics
Among the 17 included CAP studies, 3 reported discernible data obtained post-PCV7 infant uptake (67, 72, 76), and 11 post-PHiD-CV/PCV13 uptake (49, 62–64, 66, 68–71, 73, 76). There was one study that reported stratified data from both PCV periods (76). Four studies reported indistinguishable data from both PCV periods and could thus not be used for further analysis (65, 74, 75, 77). All of the studies with data from the post-PHiD-CV/-PCV13 period (11 studies) were in a setting of PCV13 use, and most of these (8/11 studies) were conducted in countries with PCV13 implementation through infant NIPs. Six of these 8 PCV13 studies included data that were collected up to 4 to 8 years following its introduction in infant NIPs. Overall, serotyping data from a total of 3,247 adult CAP isolates were extracted post-PCV13 uptake in infants. Study-specific details, including study type, age range, sample type, total number of isolates, PCV product, inclusion in the infant NIP, and the range of years of PCV use, are provided in Table 2.
Table 2. Characteristics of the included non-invasive CAP studies post-PHiD-CV/PCV13 uptake in infants.
3.3.2 Serotype distribution in adult non-invasive CAP post-PCV13 uptake in infants
Post-PCV13 implementation through infant NIPs (primary analysis comprising data of 8 studies), the 10 most often reported serotypes in older adults with CAP were 3 (16.6%), 8 (8.9%), 19A (8.4%), 7F (4.9%), 15A (4.8%), 5 (4.8%) 11A (4.2%), 6A (3.9%), 12F (3.5%), and 22F (3.3%) (Figure 3; Supplementary Table S4). The sensitivity analysis, which included data of 3 additional studies where PCV13 was marketed only, showed that serotypes 3 (15.2%), 19A (8.4%), and 8 (7.4%) remained top-ranked (Supplementary Figure S4).
Figure 3. Serotype distribution in non-invasive community-acquired pneumonia among adults ≥65 years post-PCV13 implementation through infant national immunization programs (n = 8). The top 20 serotypes are shown. Serotypes are represented by colors corresponding to the lowest valency PCV product in which they are included. In the PCV legend, the additional serotypes included in the product are relative to the next lower valency product. Pooled percentage averages were calculated for each serotype individually, thus the sum of all serotypes may exceed 100%. Serotype-specific pooled percentage averages were calculated only if 5 or more studies reported on the respective serotype. CAP, community-acquired pneumonia; n, number of studies that were included in the analysis; NIP, national immunization program, PCV, pneumococcal conjugate vaccine; PCV7, 7-valent PCV; PCV13, 13-valent PCV; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine.
In the post-PCV7 era (3 studies, all in infant NIP context), serotype 3 was the leading serotype (16.0%) (Supplementary Figure S5). When comparing the reporting of PCV13 serotypes between both PCV periods, pooled percentage averages were 16.0% post-PCV7 vs. 16.6% post-PHiD-CV/PCV13 for serotype 3, 7.4% vs. 8.4% for 19A, and 3.4% vs. 4.9% for 7F. The reporting of other PCV13 serotypes was low and comparable between both periods (Supplementary Figure S5).
4 Discussion
Our analyses show a low reporting rate of most PCV13 serotypes in both IPD and non-invasive CAP among older adults after the implementation of PHiD-CV/PCV13 in infant NIPs. Yet, PCV13-unique serotypes 3 and 19A remained prominent in both manifestations, with pooled percentage averages ranging from 7.1 to 16.6%. Also serotype 7F remained frequently reported (4.4% in IPD and 4.9% in non-invasive CAP). Since most of the included studies were conducted in countries without routine pneumococcal vaccine recommendations for older adults at the time of study conduct [e.g., France (78)] or with low uptake levels among this population [e.g., in many countries in Europe (29) and in Japan (30)], the trends we observed are likely attributed to herd protection by infant PCV use. Because of the limited number of studies in PHiD-CV context, our data primarily show the impact of infant PCV13 use on adult pneumococcal epidemiology.
In line with several other literature reviews/multi-country surveillance studies focusing on pneumococcal epidemiology in adult IPD (18, 21, 79–84) or CAP (85) after infant PHiD-CV/PCV13 implementation, our analyses therefore suggest that herd immunity via infant immunization may not provide sufficient protection in older adults against some serotypes, such as 3 and 19A.
In addition, our analysis identified several frequently reported non-PCV13 serotypes in older adults. Serotype 8 was identified as the second leading serotype in both disease manifestations, with pooled percentage averages of 10.0% (IPD) and 8.9% (CAP). Serotype 22F was another highly ranked non-PCV13 serotype in IPD (8.2%). The identification of these serotypes aligns with the initial results of the Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project collected between 2015 and 2018 (81, 86), an important ongoing, global IPD epidemiology study that uses “raw” surveillance data that may more accurately reflect the current epidemiology and may thus be less prone to bias compared to our study on published observational studies. Other common non-PCV13 serotypes identified in our analyses were 12F and 15A, contributing to both IPD and CAP with a pooled percentage averages ranging from 3.5 to 5.9%. Beyond these shared serotypes, disparities in serotype distribution between IPD and CAP were observed, likely reflecting differences in invasiveness potential of serotypes (87). Several factors may influence the invasiveness potential of serotypes and thus contribute to these differences, including phylogenetic relatedness between serotypes, potential cross-protection between related serotypes, vaccine pressure that is currently mostly focused on IPD-associated serotypes, and antibiotic-selective pressure (88–91). Comprehensive surveillance of both clinical manifestations, ideally incorporating genomic analysis (92), will be crucial to track serotype dynamics and assess the impact of serotype-specific pneumococcal vaccines.
Both serotypes 8 and 22F are included in at least one of the newly licensed vaccines for infants (PCV15/PCV20) (93, 94), thus their anticipated widespread uptake via infant NIPs could lead to a further reduction in pneumococcal disease burden among older adults. Regardless, since herd immunity by infant vaccination may not provide sufficient protection for certain serotypes in adults and the serotype distribution differs between children and adults (86), direct immunization of adults with a vaccine tailored to this population may be a more effective strategy. PCV21, designed based on adult IPD epidemiology, is a prime example of this approach (95). Yet, as our findings indicate that the serotype distribution differs between IPD and non-invasive CAP and given that replacement disease is likely to occur with the use of PCV21, similar to PHiD-CV/PCV13 implementation in infant NIPs (80), the benefit of this vaccine could be temporary (80). In addition, the current PCV technology has been shown to exert carrier-induced epitope suppression, a phenomenon where the immune response to certain serotypes is suppressed due to the presence of carrier proteins (96). As this phenomenon is particularly evident with increasing valency and thus a higher dosage of carrier proteins, the addition of more serotypes to existing PCV formulations may compromise vaccine effectiveness. New vaccine technologies and strategies that can mitigate this phenomenon and thereby broaden and improve protection are therefore essential, targeting serotypes for which current pneumococcal vaccines have been less effective and addressing emerging serotypes across all disease manifestations tailored to older adults.
Our SLR has some limitations. The pooling of data obtained from different settings may have introduced heterogeneity into our findings, which precluded formal statistical comparisons among the different PCV periods and PCV products, such as a meta-analysis. Instead, we calculated a pooled percentage average for each serotype in each analysis, which accounts for the relative importance of values based on the sample size of the corresponding study. The pooled percentage average is grounded in the number of cases for each serotype reported by each study, and thus enhances the robustness and reliability of our findings. However, this may also skew the serotype distribution toward those serotypes with higher reporting rates. Moreover, for our primary analyses, we only included serotypes that were reported by at least 5 studies, aiming to focus on the serotypes with high reporting rates. However, this may have obscured an important emerging serotype reported by a limited number of studies.
In addition, we did not analyze the impact of direct adult vaccination with PPSV23 and/or PCV13 on the serotype distribution, as vaccination rates in older adults were relatively low and uptake data were not consistently available for all the included study periods. Some of the included studies were conducted in settings where pneumococcal vaccination of older adults was recommended (78), although uptake rates were generally low in these regions (29, 30). This limits the differentiation between indirect and direct vaccination effects on the serotype distribution in older adults.
Although a formal risk of bias assessment was not performed, we believe that the rigorous inclusion criteria and critical appraisal of data quality ensured that the included data were adequate for descriptive analyses. However, these strict criteria may have contributed to the inclusion of data that mostly originated from high-income countries, which may limit the generalizability of our findings.
Lastly, our analysis was restricted to data up to 2020 to avoid potential effects of the COVID-19 pandemic on pneumococcal disease epidemiology, including the worldwide decline in pneumococcal disease burden, and disruptions in vaccination programs and surveillance systems (97–100). Consequently, our findings may not fully reflect the current serotype distribution in pneumococcal disease among older adults. However, despite the increased awareness of respiratory infections and the importance of vaccination of older adults due to the COVID-19 pandemic (101, 102), pneumococcal vaccine uptake among older adults has not increased in many countries post-pandemic (103–107). Notably, recent studies indicate that pneumococcal disease due to PCV13 serotypes 3 and 19A has persisted among adults in multiple countries during and following the COVID-19 pandemic, including several European countries, the UK, the US, and Brazil (108–113), supporting the continued relevance of our findings.
In conclusion, the persistent prevalence of specific PCV13 serotypes alongside the concurrent emergence of non-PCV13 serotypes, as well as the differences in epidemiology across the diverse clinical pneumococcal manifestations, present dynamic challenges for optimizing vaccine strategies in older adults. In addition to increasing efforts to improve uptake in this susceptible population, the development of more effective vaccines using improved technologies and broad serotype coverage, will be crucial to enhance the impact on the disease burden in older adults and to address the evolving pneumococcal epidemiology.
Trademark statement
Synflorix is a trademark licensed to or owned by GSK. Prevenar/Prevnar, Prevenar 13/Prevnar 13 and Prevenar 20/Prevnar 20 are trademarks of Pfizer Inc. Pneumovax 23, Vaxneuvance, and Capvaxive are trademarks of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (MSD).
Author contributions
PI: Conceptualization, Data curation, Formal analysis, Writing – review & editing. DB: Conceptualization, Data curation, Formal analysis, Writing – review & editing.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by GSK, which was involved in all stages of the conduct of this review and covered the costs associated with the development and publication of this manuscript.
Acknowledgments
The authors would like to thank P95 for performing the systematic literature review search and analyses, Rakesh Ojha (GSK) for data verification, and Naveen Karkada (GSK) for providing statistical support. The authors would also like to thank the Akkodis Belgium platform for writing and editorial assistance (by Elisabeth Rossaert), manuscript coordination, and design support, on behalf of GSK.
Conflict of interest
PI and DB are employed by and hold financial equities in GSK.
Generative AI statement
The authors declare that no Gen AI was used in the creation of this manuscript.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2025.1544331/full#supplementary-material
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Keywords: invasive pneumococcal disease, non-invasive community-acquired pneumonia, older adults, pneumococcal conjugate vaccine, serotype distribution, Streptococcus pneumoniae
Citation: Izurieta P and Borys D (2025) Serotype distribution of invasive and non-invasive pneumococcal disease in adults ≥65 years of age following the introduction of 10- and 13-valent pneumococcal conjugate vaccines in infant national immunization programs: a systematic literature review. Front. Public Health. 13:1544331. doi: 10.3389/fpubh.2025.1544331
Edited by:
Sathyabaarathi Ravichandran, Jackson Laboratory for Genomic Medicine, United StatesReviewed by:
Eustachio Cuscianna, University of Bari Aldo Moro, ItalyPramod Shinde, La Jolla Institute for Immunology (LJI), United States
Lansong Huang, Shandong University, China
Copyright © 2025 Izurieta and Borys. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Patricia Izurieta, cGF0cmljaWEucy5penVyaWV0YUBnc2suY29t