Submitted:
21 August 2025
Posted:
25 August 2025
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Abstract
Background/Objectives: This study analyzes the epidemiology of invasive pneumococcal disease (IPD) and the dynamics of Streptococcus pneumoniae serotypes in the Comunidad Valenciana (CV), Spain, over a 10-year period (2014–2024), with particular focus on vaccine coverage and effectiveness of PCV13 compared to the newer PCV20 and PCV21 formulations. Methods: A total of 2,014 isolates were collected from sterile clinical samples and characterized by serotype, patient demographics, and vaccination status. Results: Overall vaccination coverage was low (22.6%), with the highest rates observed in children under 10 years (78%) compared to only 16% in those aged 10–64 years and 22% in those over 64. Serotype distribution revealed 120 distinct serotypes, with serotype 8 (17.6%) and serotype 3 (14.7%) being the most frequent. Serotype 8 predominated among unvaccinated individuals, while serotype 3 remained highly prevalent despite inclusion in PCV13, reflecting limited vaccine effectiveness. Other relevant serotypes included 22F, 9N, 19A, 6C, and 23A. Temporal analysis showed increases in serotypes 8, 3, and 23A in recent years, while 9N, 19A, 15A, and 11A significantly declined. Among serotypes with <2% incidence, some such as 4, 12F, 16F, and 24F showed upward trends. Conclusions: The findings suggest that PCV20 currently provides broad coverage of dominant serotypes, but PCV21 may offer advantages should serotypes like 23A, 9N, or 15A increase further due to serotype replacement. Continuous epidemiological surveillance is essential to guide evidence-based vaccine policy and anticipate future vaccine reformulations.
Keywords:
1. Introduction
2. Materials and Methods
2.1. Study Design and Data Collection
2.2. Sociodemographic and Clinical Data
2.3. Statistical Analysis
- 0.00–0.09: negligible
- 0.10–0.29: small
- 0.30–0.49: medium
- ≥0.50: large
3. Results
3.1. Vaccination Status Overview
| Age | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Total | <10 | 10-64 | >64 | ||||||
| Count | N % | Count | N % | Count | N % | Count | N % | ||
| Total | 1993 | 100.0% | 112 | 100.0% | 819 | 100.0% | 1062 | 100.0% | |
| Not vaccinated/Unknown status | 1542 | 77.4% | 25 | 22.3% | 689 | 84.1% | 828 | 78.0% | |
| Vaccinated with PPV23 | 226 | 11.3% | 3 | 2.7% | 45 | 5.5% | 178 | 16.8% | |
| Vaccinated with PCV13 | 125 | 6.2% | 53 | 47.4% | 51 | 6.3% | 21 | 2.0% | |
| Vaccinated, but vaccine type unknown | 73 | 3.7% | 30 | 27% | 26 | 3.2% | 17 | 1.5% | |
| Vaccinated with both PCV13 and PPV23 | 27 | 1.4% | 1 | 0.9% | 8 | 1.0% | 18 | 1.7% | |
3.2. Pneumococcal Serotypes

- Serotype 8 was more common in individuals over 10 years of age, particularly those aged 10–64 years.
- Serotype 3 was more frequent in individuals over 64 years than in those aged 10–64 years.
- Serotypes 10A and 23B were more frequent in children under 10 years of age (small effect size, Cramer’s V = 0.186).
3.3. Serotypes and Vaccination
| Vaccination status | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total | Not vaccinated/Unknown | Vaccinated PCV13 | Vaccinated PPV23 | Vaccinated with PCV13 and PPV23 | Vaccinated, but vaccine type unknown | ||||||||
| Count | N % | Count | N % | Count | N % | Count | N % | Count | N % | Count | N % | ||
| Serotypes (>2% incidence) | Total | 2014 | 100.0% | 1563 | 100.0% | 125 | 100.0% | 226 | 100.0% | 27 | 100.0% | 73 | 100.0% |
| Others | 669 | 33.2% | 472 | 30.2% | 61 | 48.8% | 87 | 38.5% | 14 | 51.9% | 35 | 47.9% | |
| 8 | 354 | 17.6% | 308 | 19.7% | 11 | 8.8% | 23 | 10.2% | 5 | 18.5% | 7 | 9.6% | |
| 3 | 297 | 14.7% | 243 | 15.5% | 12 | 9.6% | 32 | 14.2% | 3 | 11.1% | 7 | 9.6% | |
| 22F | 101 | 5.0% | 86 | 5.5% | 5 | 4.0% | 8 | 3.5% | 2 | 7.4% | 0 | 0.0% | |
| 9N | 80 | 4.0% | 71 | 4.5% | 0 | 0.0% | 8 | 3.5% | 0 | 0.0% | 1 | 1.4% | |
| 14 | 71 | 3.5% | 60 | 3.8% | 3 | 2.4% | 7 | 3.1% | 0 | 0.0% | 1 | 1.4% | |
| 19A | 70 | 3.5% | 54 | 3.5% | 5 | 4.0% | 6 | 2.7% | 0 | 0.0% | 5 | 6.8% | |
| 6C | 66 | 3.3% | 51 | 3.3% | 2 | 1.6% | 13 | 5.8% | 0 | 0.0% | 0 | 0.0% | |
| 23A | 61 | 3.0% | 46 | 2.9% | 1 | 0.8% | 9 | 4.0% | 1 | 3.7% | 4 | 5.5% | |
| 10A | 56 | 2.8% | 35 | 2.2% | 12 | 9.6% | 5 | 2.2% | 1 | 3.7% | 3 | 4.1% | |
| 15A | 46 | 2.3% | 29 | 1.9% | 6 | 4.8% | 6 | 2.7% | 0 | 0.0% | 5 | 6.8% | |
| 31 | 45 | 2.2% | 36 | 2.3% | 0 | 0.0% | 7 | 3.1% | 0 | 0.0% | 2 | 2.7% | |
| 11A | 43 | 2.1% | 28 | 1.8% | 4 | 3.2% | 9 | 4.0% | 0 | 0.0% | 2 | 2.7% | |
| 23B | 40 | 2.0% | 31 | 2.0% | 3 | 2.4% | 5 | 2.2% | 0 | 0.0% | 1 | 1.4% | |
| Invalidated | 15 | 0.7% | 13 | 0.8% | 0 | 0.0% | 1 | 0.4% | 1 | 3.7% | 0 | 0.0% | |
3.4. Serotype Trends Over Time
| Year | |||||||||
| Total | 2014-2019 | 2020-2022 | 2023-2024 | ||||||
| Count | N % | Count | N % | Count | N % | Count | N % | ||
| Serotype | Total | 1330 | 100.0% | 810 | 100.0% | 111 | 100.0% | 409 | 100.0% |
| 8 | 354 | 26.6% | 185 | 22.8% | 43 | 38.7% | 126 | 30.8% | |
| 3 | 297 | 22.3% | 164 | 20.2% | 28 | 25.2% | 105 | 25.7% | |
| 22F | 101 | 7.6% | 66 | 8.1% | 4 | 3.6% | 31 | 7.6% | |
| 9N | 80 | 6.0% | 60 | 7.4% | 2 | 1.8% | 18 | 4.4% | |
| 14 | 71 | 5.3% | 46 | 5.7% | 1 | 0.9% | 24 | 5.9% | |
| 19A | 70 | 5.3% | 53 | 6.5% | 9 | 8.1% | 8 | 2.0% | |
| 6C | 66 | 5.0% | 43 | 5.3% | 1 | 0.9% | 22 | 5.4% | |
| 23A | 61 | 4.6% | 30 | 3.7% | 5 | 4.5% | 26 | 6.4% | |
| 10A | 56 | 4.2% | 28 | 3.5% | 9 | 8.1% | 19 | 4.6% | |
| 15A | 46 | 3.5% | 37 | 4.6% | 2 | 1.8% | 7 | 1.7% | |
| 31 | 45 | 3.4% | 32 | 4.0% | 3 | 2.7% | 10 | 2.4% | |
| 11A | 43 | 3.2% | 37 | 4.6% | 2 | 1.8% | 4 | 1.0% | |
| 23B | 40 | 3.0% | 29 | 3.6% | 2 | 1.8% | 9 | 2.2% | |
| Year | |||||||
| Total | 2014-2021 | 2022-2024 | |||||
| Count | N % | Count | N % | Count | N % | ||
| Serotype | Total | 1330 | 100.0% | 856 | 100.0% | 474 | 100.0% |
| 8 | 354 | 26.6% | 205 | 23.9% | 149 | 31.4% | |
| 3 | 297 | 22.3% | 171 | 20.0% | 126 | 26.6% | |
| 22F | 101 | 7.6% | 69 | 8.1% | 32 | 6.8% | |
| 9N | 80 | 6.0% | 62 | 7.2% | 18 | 3.8% | |
| 14 | 71 | 5.3% | 47 | 5.5% | 24 | 5.1% | |
| 19A | 70 | 5.3% | 56 | 6.5% | 14 | 3.0% | |
| 6C | 66 | 5.0% | 43 | 5.0% | 23 | 4.9% | |
| 23A | 61 | 4.6% | 31 | 3.6% | 30 | 6.3% | |
| 10A | 56 | 4.2% | 31 | 3.6% | 25 | 5.3% | |
| 15A | 46 | 3.5% | 39 | 4.6% | 7 | 1.5% | |
| 31 | 45 | 3.4% | 33 | 3.9% | 12 | 2.5% | |
| 11A | 43 | 3.2% | 39 | 4.6% | 4 | 0.8% | |
| 23B | 40 | 3.0% | 30 | 3.5% | 10 | 2.1% | |
4. Discussion
5. Conclusions
- PCV20 covers the main circulating serotypes currently, including 8, 3, 22F, 14, 19A, 11A, and 10A.
- PCV21 could be superior if serotypes such as 9N, 23A/B, 15A, and 31 increase in incidence as a consequence of serotype replacement following the introduction of PCV20. This study provides preliminary data that must be confirmed with further follow-up. At present, the rise in serotypes not included in PCV20 appears residual. It remains to be seen what collateral impact PCV20 inclusion in vaccination programs may have.
- Future research should assess immune responses to PCV20, especially against serotype 3, one of the most lethal and evasive serotypes not well controlled by PCV13.
- It is essential to select vaccines based on local epidemiological data.
- This study underscores the importance of ongoing epidemiological surveillance of IPD to evaluate the evolution of vaccine and non-vaccine serotypes, analyze vaccine effectiveness, and guide future evidence-based vaccine reformulation.
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
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| Age | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Total | <10 | 10-64 | >64 | ||||||
| Count | N % | Count | N % | Count | N % | Count | N % | ||
| Serotype | Total | 1319 | 100.0% | 60 | 100.0% | 532 | 100.0% | 727 | 100.0% |
| 8 | 353 | 26.8% | 5 | 8.3% | 188 | 35.3% | 160 | 22.0% | |
| 3 | 293 | 22.2% | 15 | 25.0% | 99 | 18.6% | 179 | 24.6% | |
| 22F | 99 | 7.5% | 5 | 8.3% | 40 | 7.5% | 54 | 7.4% | |
| 9N | 79 | 6.0% | 0 | 0.0% | 35 | 6.6% | 44 | 6.1% | |
| 14 | 71 | 5.4% | 5 | 8.3% | 21 | 3.9% | 45 | 6.2% | |
| 19A | 70 | 5.3% | 5 | 8.3% | 22 | 4.1% | 43 | 5.9% | |
| 6C | 64 | 4.9% | 1 | 1.7% | 21 | 3.9% | 42 | 5.8% | |
| 23A | 61 | 4.6% | 3 | 5.0% | 19 | 3.6% | 39 | 5.4% | |
| 10A | 56 | 4.2% | 10 | 16.7% | 24 | 4.5% | 22 | 3.0% | |
| 15A | 46 | 3.5% | 3 | 5.0% | 18 | 3.4% | 25 | 3.4% | |
| 31 | 44 | 3.3% | 0 | 0.0% | 15 | 2.8% | 29 | 4.0% | |
| 11A | 43 | 3.3% | 2 | 3.3% | 13 | 2.4% | 28 | 3.9% | |
| 23B | 40 | 3.0% | 6 | 10.0% | 17 | 3.2% | 17 | 2.3% | |
| Year | |||||||
| Total | 2014-2021 | 2022-2024 | |||||
| Count | N % | Count | N % | Count | N % | ||
| Serotype | Total | 2014 | 100.0% | 1252 | 100.0% | 762 | 100.0% |
| 4 | 29 | 1.4% | 12 | 1.0% | 17 | 2.2% | |
| 38 | 23 | 1.1% | 9 | 0.7% | 14 | 1.8% | |
| 12F | 22 | 1.1% | 5 | 0.4% | 17 | 2.2% | |
| 16F | 16 | 0.8% | 3 | 0.2% | 13 | 1.7% | |
| 24 | 11 | 0.5% | 1 | 0.1% | 10 | 1.3% | |
| 17F | 11 | 0.5% | 1 | 0.1% | 10 | 1.3% | |
| 15B/C | 10 | 0.5% | 1 | 0.1% | 9 | 1.2% | |
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