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Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis

PMCID: PMC11947070

PMID: 39706205

Abstract

Summary Background Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. Methods IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5–17 years, 18–49 years, and ≥50 years). Findings The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3–12·9) of IPD cases in children younger than 5 years and 15·5% (13·4–19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2–65·4) and 45·6% (40·0–50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3–30·0) of IPD cases in children younger than 5 years and 29·5% (27·5–33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2–43·1]) and adults aged 50 years or older (14·8% [11·9–17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1–9·7% for PCV15, 13·5–36·0% for PCV20, 29·9–53·8% for PCV21, 15·6–42·0% for PCV24, and 31·5–50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. Interpretation The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. Funding Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

Full Text

A ten-valent PCV (PCV10; Synflorix, GSK, Coleford, UK) and a 13-valent PCV (PCV13; Prevenar 13, Pfizer) have been available since 2010 and are widely used. Questions remain regarding whether one prevents more disease than the other and the potential impact of new higher-valency vaccines on remaining disease. Several new PCVs have been recently licensed for use in infants (appendix 2 p 10): another ten-valent PCV (Pneumosil, Serum Institute of India, Pune, India), which received WHO prequalification in 2019 and differs slightly from Synflorix in the serotypes covered; a 15-valent PCV (PCV15; VAXNEUVANCE, Merck, Darmstadt, Germany), licensed for children in 2022, which includes PCV13 serotypes and two additional serotypes; and a 20-valent PCV (PCV20; Prevenar 20, Pfizer), licensed for children in 2023–24, which also includes PCV13 serotypes and seven additional serotypes. PCV15 and PCV20 are also licensed for adults, as is a 21-valent PCV (PCV21; V116 and CAPVAXIVE, Merck), which excludes PCV10 serotypes except serotype 7F. A 23-valent pneumococcal polysaccharide vaccine (PPV23; Pneumovax23, Merck) is licensed for individuals aged 2 years or older and is recommended in many countries for older adults, but is not an infant vaccine. Other higher-valency PCVs in the pipeline include multiple 24-valent PCVs (GSK, Vaxcyte, and Merck), which include all PCV13 types and target the same serotypes as PPV23 plus 6A, and a 25-valent PCV (IVT PCV-25, Inventprise, Redmond, WA, USA), which includes all PCV13 types except serotype 6A (appendix 2 p 10).
The datasets provided by the institutions conducting the surveillance underwent extensive quality checks by PSERENADE analysts to identify potential biases that could affect the serotype distribution, including selective serotyping of cases or incomplete serotyping methods that might result in a non-representative serotype distribution of all IPD. These evaluations and resulting decisions on whether to include the data were discussed with site investigators. Site characteristics and serotyping methods are described in appendix 2 (p 11).
Analyses were performed using R version 4.3.3, and for modelling the VGAM package was used (appendix 2 p 2).
Of 76 sites that contributed IPD data to the PSERENADE project, 54 (71%) were eligible for analysis (63 362 cases from 42 PCV13 sites and 6806 cases from 12 PCV10 sites; figure 1; appendix 2 p 11). Six sites were excluded due to concurrent PCV10 and PCV13 use, and 16 were excluded because they had no serotyped IPD cases in the defined mature PCV10 or PCV13 period. 28 (52%) eligible sites were from Europe or North America. Of the 18 (33%) sites from low-income and middle-income countries, only five had more than 20 eligible cases for children and seven had more than 20 eligible cases for adults. All eligible sites had eligible data for the analysis of children younger than 5 years (7318 cases from PCV13 sites and 1109 cases from PCV10 sites; table). For adults aged 50 years or older, 31 PCV13 sites (43 774 cases) and 11 PCV10 sites (3978 cases) had data eligible for analysis; seven did not report data for adults and five did not have data in the mature PCV10 or PCV13 period as defined for adults (figure 1). Ten sites did not use a booster dose schedule (3 + 0), of which only five had eligible data for adults, and most of these had fewer than 20 eligible cases (eight of ten for children and three of five for adults; table). Specific years of included data varied by site and age group, but primarily represented the years 2015–18. Additional site details and characteristics are described in appendix 2 (p 11) and elsewhere.
At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3–12·9) of IPD cases among children younger than 5 years and 15·4% (13·4–19·3) among adults aged 50 years and older (figure 2, appendix 2 p 14). PCV10-type IPD was primarily due to serotype 14 in children (4·4%, ranked fifth among all serotypes in children in PCV10 sites) and serotypes 7F and 4 in adults (2·9% each, ranked ninth and tenth; figure 3, appendix 2 p 15). Serotype 1, which is known to cause outbreaks, was rarely seen at any age or product stratum (0·3–1·6%). For PCV13 sites, 26·4% (21·3–30·0) of IPD cases were caused by PCV13 serotypes among children and 29·5% (27·5–33·0) among adults (figure 2). The main PCV13 serotype causing IPD, and the top serotype overall, was serotype 3 for both children (9·6% [6·8–12·4]) and adults (14·5% [12·4–16·7]), followed by 19A (6·5% [ranked third] for children and 5·2% [ranked fifth] for adults; figure 3). The proportion of PCV13-type IPD was greater at PCV10 sites than at PCV13 sites in both children (52·1% vs 26·4%) and adults (45·6% vs 29·5%; figure 2), largely due to serotype 19A, which caused 30·6% (18·2–43·1) of IPD in children at PCV10 sites and 14·8% (11·9–17·8) in adults (figure 3). The contribution of serotype 6C, potentially covered by serotype 6A in PCV13 but not PCV10, was also higher at PCV10 sites than PCV13 sites (6·3% vs 0·8% in children and 6·0% vs 2·5% in adults). Similar to PCV13 sites, serotype 3 caused 8·4% (5·8–11·0) of IPD in children and 14·3% (11·3–17·3) in adults at PCV10 sites.
In aggregate, IPD serotype coverage across both age groups and PCV-use groups was 36·0–56·3% for PCV15, 62·4–65·6% for PCV20, 66·2–72·1% for PCV24, 76·5–83·6% for PCV25, and 65·4–70·9% for PPV23 (figure 2, appendix 2 p 14). The five additional serotypes in PCV15 caused 46·3% of IPD beyond PCV10 among children and 35·5% among adults at PCV10 sites, and 9·6% beyond PCV13 among children and adults at PCV13 sites. The additional serotypes in PCV20 beyond PCV15 caused 9·3–14·7% of IPD in PCV10 sites and 23·4–26·4% in PCV13 sites. These proportions were more similar between PCV10 and PCV13 sites when PCV13 serotypes and serotype 6C were excluded from the denominator (appendix 2 p 24). Serotypes included in PCV21, which only include one PCV10 type (7F), caused 77·5–83·3% of IPD across all age and product strata; serotype coverage of PCV21 and PCV10 (or PCV13) combined was 86·0–91·4% (appendix 2 p 14). Across age groups, 74·5–80·7% of IPD cases at PCV10 sites were caused by the serotypes in PCV21 beyond PCV10 types (ie, all but 7F, which is included in PCV10), and 60·6–61·7% of IPD cases at PCV13 sites were caused by the serotypes in PCV21 beyond PCV13 types (ie, all but 3, 6A, 7F, and 19A, which are included in PCV13; appendix 2 p 15).
At least 13 of the most common serotypes for each age group and PCV setting are included in at least one higher-valency PCV (figure 4, appendix 2 p 26). Among children, serotype 24F was the most common non-PCV13 type at PCV10 sites (4·6% [95% CI 1·8–7·4]) and 15BC at PCV13 sites (9·5% [8·4–10·5]). Among adults, serotypes 8, 9N, and 22F were the most common non-PCV13 serotypes, together causing 15·3% of cases at PCV10 sites and 22·6% at PCV13 sites.
At PCV13 sites, children aged 0–23 months had a lower proportion of PCV13-type IPD (22·5% [95% CI 18·3–26·0]) than children aged 24–59 months (33·4% [25·5–37·1]; appendix 2 p 16), due primarily to serotypes 1, 3, and 19A (appendix 2 pp 17, 29). Serotypes in PCV15 (33·1% vs 40·7%), PCV20 (61·2% vs 64·9%), PCV24 (65·9% vs 67·7%), and PCV25 (75·9% vs 77·8%) were more similar between age groups (appendix 2 p 16). Non-PCV13 serotypes 10A and 33F were more common among younger children, whereas 12F and 23B were more common among older children. Data at PCV10 sites were insufficient for further age stratification (appendix 2 p 27).
When stratifying adults in PCV13 sites by finer age groups, serotypes covered by PCV10 (range across age groups 7·5% to 9·7%), PCV13 (26·9% to 27·8%), PCV15 (37·0% to 37·9%), and PCV21 (83·8% to 85·4%) caused generally similar proportions of disease among groups, whereas serotype coverage appeared to decline with age for PCV20 (65·8% for age 50–64 years to 58·1% for age ≥85 years), PCV24 (76·2% to 66·4%), PCV25 (79·5% to 75·3%), and PPV23 (75·8% to 65·8%; appendix 2 p 16). Declines by age in serotype coverage by higher-valency vaccines were largely due to serotypes 8 (from 12·6% of cases in adults aged 50–64 years to 7·3% for age ≥85 years), 9N (6·7% to 5·3%), and 12F (6·4% to 3·7%), but CIs were wide. Non-PPV23 serotypes generally increased with age (appendix 2 pp 17, 29).
Data were insufficient to further stratify serotype distributions already stratified by product and age by UN region. However, heterogeneity in the proportion of IPD covered by the different products across sites within the same region was generally wide, in part due to small sample sizes, and overlapped across sites from other regions (figure 4, appendix 2 p 18). No clear regional patterns were apparent in the proportion of vaccine-type IPD (or other PCV valency) across sites according to their region, except that a greater number of PCV13 sites in Latin America had more PCV13-type IPD than North American or European sites for children younger than 5 years. At PCV10 sites, the proportion of IPD among adults due to PCV20, PCV24, and PCV25 types and PPV23 types was lower in Latin American than European sites (figure 4).
Heterogeneity across sites in serotype-specific ranking and proportions was also observed, both within and across regions (appendix 2 p 30). Heterogeneity was unlikely to be due to differences in the age distributions of IPD cases, which were generally similar across sites (appendix 2 p 27).
When estimating PCV serotype coverage using median instead of the modelled weighted mean, estimates were generally within 5% (figure 4). Sensitivity analyses that excluded small sites (<20 cases), excluded large sites (eg, England and Wales) individually, or restricted the mature period to 7 years or more after introduction of PCV10 or PCV13 did not meaningfully influence results (data not shown).
PCV21 (CAPVAXIVE), targeted at adults, predominantly covers serotypes not included in PCV10 or PCV13 and includes seven serotypes not in PPV23, several of which were in the top-ten non-PCV13 types in both adults and children. We estimated that PCV21 targets approximately 62% of all adult IPD beyond PCV13 types in mature PCV13 settings and 46% in mature PCV10 settings (and in children aged <5 years, 61% in mature PCV13 settings and 38% in mature PCV10 settings), and 20–27% of adult IPD beyond that targeted by PCV20 (appendix 2 pp 14–15). Thus, a PCV21 adult immunisation programme in conjunction with infant vaccination using a different PCV has the potential to substantially reduce disease in adults if the vaccine-type effect from PCV21 is similar to that seen with PCV10 and PCV13 for children. Although we see herd protection in adults by immunising children with PCVs, it is unclear whether children can be similarly protected by immunising adults with PCVs.

Sections

"[{\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"SD2\", \"SD2\"], \"section\": \"Introduction\", \"text\": \"A ten-valent PCV (PCV10; Synflorix, GSK, Coleford, UK) and a 13-valent PCV (PCV13; Prevenar 13, Pfizer) have been available since 2010 and are widely used. Questions remain regarding whether one prevents more disease than the other and the potential impact of new higher-valency vaccines on remaining disease. Several new PCVs have been recently licensed for use in infants (appendix 2 p 10): another ten-valent PCV (Pneumosil, Serum Institute of India, Pune, India), which received WHO prequalification in 2019 and differs slightly from Synflorix in the serotypes covered; a 15-valent PCV (PCV15; VAXNEUVANCE, Merck, Darmstadt, Germany), licensed for children in 2022, which includes PCV13 serotypes and two additional serotypes; and a 20-valent PCV (PCV20; Prevenar 20, Pfizer), licensed for children in 2023\\u201324, which also includes PCV13 serotypes and seven additional serotypes. PCV15 and PCV20 are also licensed for adults, as is a 21-valent PCV (PCV21; V116 and CAPVAXIVE, Merck), which excludes PCV10 serotypes except serotype 7F. A 23-valent pneumococcal polysaccharide vaccine (PPV23; Pneumovax23, Merck) is licensed for individuals aged 2 years or older and is recommended in many countries for older adults, but is not an infant vaccine. Other higher-valency PCVs in the pipeline include multiple 24-valent PCVs (GSK, Vaxcyte, and Merck), which include all PCV13 types and target the same serotypes as PPV23 plus 6A, and a 25-valent PCV (IVT PCV-25, Inventprise, Redmond, WA, USA), which includes all PCV13 types except serotype 6A (appendix 2 p 10).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"SD2\"], \"section\": \"Site identification\", \"text\": \"The datasets provided by the institutions conducting the surveillance underwent extensive quality checks by PSERENADE analysts to identify potential biases that could affect the serotype distribution, including selective serotyping of cases or incomplete serotyping methods that might result in a non-representative serotype distribution of all IPD. These evaluations and resulting decisions on whether to include the data were discussed with site investigators. Site characteristics and serotyping methods are described in appendix 2 (p 11).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"SD2\"], \"section\": \"Analytical model\", \"text\": \"Analyses were performed using R version 4.3.3, and for modelling the VGAM package was used (appendix 2 p 2).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"F1\", \"SD2\", \"T1\", \"F1\", \"T1\", \"SD2\"], \"section\": \"Results\", \"text\": \"Of 76 sites that contributed IPD data to the PSERENADE project, 54 (71%) were eligible for analysis (63 362 cases from 42 PCV13 sites and 6806 cases from 12 PCV10 sites; figure 1; appendix 2 p 11). Six sites were excluded due to concurrent PCV10 and PCV13 use, and 16 were excluded because they had no serotyped IPD cases in the defined mature PCV10 or PCV13 period. 28 (52%) eligible sites were from Europe or North America. Of the 18 (33%) sites from low-income and middle-income countries, only five had more than 20 eligible cases for children and seven had more than 20 eligible cases for adults. All eligible sites had eligible data for the analysis of children younger than 5 years (7318 cases from PCV13 sites and 1109 cases from PCV10 sites; table). For adults aged 50 years or older, 31 PCV13 sites (43 774 cases) and 11 PCV10 sites (3978 cases) had data eligible for analysis; seven did not report data for adults and five did not have data in the mature PCV10 or PCV13 period as defined for adults (figure 1). Ten sites did not use a booster dose schedule (3 + 0), of which only five had eligible data for adults, and most of these had fewer than 20 eligible cases (eight of ten for children and three of five for adults; table). Specific years of included data varied by site and age group, but primarily represented the years 2015\\u201318. Additional site details and characteristics are described in appendix 2 (p 11) and elsewhere.\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"F2\", \"SD2\", \"F3\", \"SD2\", \"F2\", \"F3\", \"F2\", \"F3\"], \"section\": \"Results\", \"text\": \"At PCV10 sites, PCV10 serotypes caused 10\\u00b70% (95% CI 6\\u00b73\\u201312\\u00b79) of IPD cases among children younger than 5 years and 15\\u00b74% (13\\u00b74\\u201319\\u00b73) among adults aged 50 years and older (figure 2, appendix 2 p 14). PCV10-type IPD was primarily due to serotype 14 in children (4\\u00b74%, ranked fifth among all serotypes in children in PCV10 sites) and serotypes 7F and 4 in adults (2\\u00b79% each, ranked ninth and tenth; figure 3, appendix 2 p 15). Serotype 1, which is known to cause outbreaks, was rarely seen at any age or product stratum (0\\u00b73\\u20131\\u00b76%). For PCV13 sites, 26\\u00b74% (21\\u00b73\\u201330\\u00b70) of IPD cases were caused by PCV13 serotypes among children and 29\\u00b75% (27\\u00b75\\u201333\\u00b70) among adults (figure 2). The main PCV13 serotype causing IPD, and the top serotype overall, was serotype 3 for both children (9\\u00b76% [6\\u00b78\\u201312\\u00b74]) and adults (14\\u00b75% [12\\u00b74\\u201316\\u00b77]), followed by 19A (6\\u00b75% [ranked third] for children and 5\\u00b72% [ranked fifth] for adults; figure 3). The proportion of PCV13-type IPD was greater at PCV10 sites than at PCV13 sites in both children (52\\u00b71% vs 26\\u00b74%) and adults (45\\u00b76% vs 29\\u00b75%; figure 2), largely due to serotype 19A, which caused 30\\u00b76% (18\\u00b72\\u201343\\u00b71) of IPD in children at PCV10 sites and 14\\u00b78% (11\\u00b79\\u201317\\u00b78) in adults (figure 3). The contribution of serotype 6C, potentially covered by serotype 6A in PCV13 but not PCV10, was also higher at PCV10 sites than PCV13 sites (6\\u00b73% vs 0\\u00b78% in children and 6\\u00b70% vs 2\\u00b75% in adults). Similar to PCV13 sites, serotype 3 caused 8\\u00b74% (5\\u00b78\\u201311\\u00b70) of IPD in children and 14\\u00b73% (11\\u00b73\\u201317\\u00b73) in adults at PCV10 sites.\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"F2\", \"SD2\", \"SD2\", \"SD2\", \"SD2\"], \"section\": \"Results\", \"text\": \"In aggregate, IPD serotype coverage across both age groups and PCV-use groups was 36\\u00b70\\u201356\\u00b73% for PCV15, 62\\u00b74\\u201365\\u00b76% for PCV20, 66\\u00b72\\u201372\\u00b71% for PCV24, 76\\u00b75\\u201383\\u00b76% for PCV25, and 65\\u00b74\\u201370\\u00b79% for PPV23 (figure 2, appendix 2 p 14). The five additional serotypes in PCV15 caused 46\\u00b73% of IPD beyond PCV10 among children and 35\\u00b75% among adults at PCV10 sites, and 9\\u00b76% beyond PCV13 among children and adults at PCV13 sites. The additional serotypes in PCV20 beyond PCV15 caused 9\\u00b73\\u201314\\u00b77% of IPD in PCV10 sites and 23\\u00b74\\u201326\\u00b74% in PCV13 sites. These proportions were more similar between PCV10 and PCV13 sites when PCV13 serotypes and serotype 6C were excluded from the denominator (appendix 2 p 24). Serotypes included in PCV21, which only include one PCV10 type (7F), caused 77\\u00b75\\u201383\\u00b73% of IPD across all age and product strata; serotype coverage of PCV21 and PCV10 (or PCV13) combined was 86\\u00b70\\u201391\\u00b74% (appendix 2 p 14). Across age groups, 74\\u00b75\\u201380\\u00b77% of IPD cases at PCV10 sites were caused by the serotypes in PCV21 beyond PCV10 types (ie, all but 7F, which is included in PCV10), and 60\\u00b76\\u201361\\u00b77% of IPD cases at PCV13 sites were caused by the serotypes in PCV21 beyond PCV13 types (ie, all but 3, 6A, 7F, and 19A, which are included in PCV13; appendix 2 p 15).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"F4\", \"SD2\"], \"section\": \"Results\", \"text\": \"At least 13 of the most common serotypes for each age group and PCV setting are included in at least one higher-valency PCV (figure 4, appendix 2 p 26). Among children, serotype 24F was the most common non-PCV13 type at PCV10 sites (4\\u00b76% [95% CI 1\\u00b78\\u20137\\u00b74]) and 15BC at PCV13 sites (9\\u00b75% [8\\u00b74\\u201310\\u00b75]). Among adults, serotypes 8, 9N, and 22F were the most common non-PCV13 serotypes, together causing 15\\u00b73% of cases at PCV10 sites and 22\\u00b76% at PCV13 sites.\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"SD2\", \"SD2\", \"SD2\", \"SD2\"], \"section\": \"Results\", \"text\": \"At PCV13 sites, children aged 0\\u201323 months had a lower proportion of PCV13-type IPD (22\\u00b75% [95% CI 18\\u00b73\\u201326\\u00b70]) than children aged 24\\u201359 months (33\\u00b74% [25\\u00b75\\u201337\\u00b71]; appendix 2 p 16), due primarily to serotypes 1, 3, and 19A (appendix 2 pp 17, 29). Serotypes in PCV15 (33\\u00b71% vs 40\\u00b77%), PCV20 (61\\u00b72% vs 64\\u00b79%), PCV24 (65\\u00b79% vs 67\\u00b77%), and PCV25 (75\\u00b79% vs 77\\u00b78%) were more similar between age groups (appendix 2 p 16). Non-PCV13 serotypes 10A and 33F were more common among younger children, whereas 12F and 23B were more common among older children. Data at PCV10 sites were insufficient for further age stratification (appendix 2 p 27).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"SD2\", \"SD2\"], \"section\": \"Results\", \"text\": \"When stratifying adults in PCV13 sites by finer age groups, serotypes covered by PCV10 (range across age groups 7\\u00b75% to 9\\u00b77%), PCV13 (26\\u00b79% to 27\\u00b78%), PCV15 (37\\u00b70% to 37\\u00b79%), and PCV21 (83\\u00b78% to 85\\u00b74%) caused generally similar proportions of disease among groups, whereas serotype coverage appeared to decline with age for PCV20 (65\\u00b78% for age 50\\u201364 years to 58\\u00b71% for age \\u226585 years), PCV24 (76\\u00b72% to 66\\u00b74%), PCV25 (79\\u00b75% to 75\\u00b73%), and PPV23 (75\\u00b78% to 65\\u00b78%; appendix 2 p 16). Declines by age in serotype coverage by higher-valency vaccines were largely due to serotypes 8 (from 12\\u00b76% of cases in adults aged 50\\u201364 years to 7\\u00b73% for age \\u226585 years), 9N (6\\u00b77% to 5\\u00b73%), and 12F (6\\u00b74% to 3\\u00b77%), but CIs were wide. Non-PPV23 serotypes generally increased with age (appendix 2 pp 17, 29).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"F4\", \"SD2\", \"F4\"], \"section\": \"Results\", \"text\": \"Data were insufficient to further stratify serotype distributions already stratified by product and age by UN region. However, heterogeneity in the proportion of IPD covered by the different products across sites within the same region was generally wide, in part due to small sample sizes, and overlapped across sites from other regions (figure 4, appendix 2 p 18). No clear regional patterns were apparent in the proportion of vaccine-type IPD (or other PCV valency) across sites according to their region, except that a greater number of PCV13 sites in Latin America had more PCV13-type IPD than North American or European sites for children younger than 5 years. At PCV10 sites, the proportion of IPD among adults due to PCV20, PCV24, and PCV25 types and PPV23 types was lower in Latin American than European sites (figure 4).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"SD2\", \"SD2\"], \"section\": \"Results\", \"text\": \"Heterogeneity across sites in serotype-specific ranking and proportions was also observed, both within and across regions (appendix 2 p 30). Heterogeneity was unlikely to be due to differences in the age distributions of IPD cases, which were generally similar across sites (appendix 2 p 27).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"F4\"], \"section\": \"Results\", \"text\": \"When estimating PCV serotype coverage using median instead of the modelled weighted mean, estimates were generally within 5% (figure 4). Sensitivity analyses that excluded small sites (<20 cases), excluded large sites (eg, England and Wales) individually, or restricted the mature period to 7 years or more after introduction of PCV10 or PCV13 did not meaningfully influence results (data not shown).\"}, {\"pmc\": \"PMC11947070\", \"pmid\": \"39706205\", \"reference_ids\": [\"SD2\"], \"section\": \"Discussion\", \"text\": \"PCV21 (CAPVAXIVE), targeted at adults, predominantly covers serotypes not included in PCV10 or PCV13 and includes seven serotypes not in PPV23, several of which were in the top-ten non-PCV13 types in both adults and children. We estimated that PCV21 targets approximately 62% of all adult IPD beyond PCV13 types in mature PCV13 settings and 46% in mature PCV10 settings (and in children aged <5 years, 61% in mature PCV13 settings and 38% in mature PCV10 settings), and 20\\u201327% of adult IPD beyond that targeted by PCV20 (appendix 2 pp 14\\u201315). Thus, a PCV21 adult immunisation programme in conjunction with infant vaccination using a different PCV has the potential to substantially reduce disease in adults if the vaccine-type effect from PCV21 is similar to that seen with PCV10 and PCV13 for children. Although we see herd protection in adults by immunising children with PCVs, it is unclear whether children can be similarly protected by immunising adults with PCVs.\"}]"

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