The current epidemiological situation of invasive pneumococcal disease in Spain

Table of Contents

• 0.1 Introduction
• 0.2 Most common serotypes causing IPD in Spain
• 0.3 Reasons for succession of vaccine serotypes
• 0.4 Most prominent non-vaccine serotypes causing IPD
• 0.5 In conclusion
• 0.6 Literature
• 1 What are the implications ‌of emerging serotypes and antibiotic-resistant⁢ strains of Streptococcus pneumoniae for public health policies and vaccination strategies ⁤in Spain?

-yeah-

Introduction

Recently, two articles have appeared, the first of National Center of Epidemiology (CNE) and both National Pneumococcus Reference Laboratorywhich will update the epidemiology situation of invasive pneumococcal disease (IPD) in our country. Although the methodology is different, both studies, with some differences, produce similar results.

One finding, already expected, is that after the end of the COVID-19 pandemic, pneumococcal infections (and other respiratory transmitted bacterial infections) decreased – largely due to the lack of distribution of respiratory viruses due to preventive measures – the occurrence and the number of pre-pandemic cases have been reached and even exceeded, especially in children under 4 years of age (1), as happened in other countries.

Also, and as expected, both studies show that up to 60-70% of current IPD cases are caused by serotypes that are not in the 13-valent pneumococcal conjugate vaccine (non-vaccine serotypes or SNV), which is common with most countries where this vaccine has been used. However, a relevant finding is that a significant proportion of IPD is caused by vaccine serotypes (VS) that are included in PCV13: 3, 19A, 19F, 14 and 4 (1,2). This persistence of VS has been confirmed in many European countries with high vaccination coverage (3-5).

Most common serotypes causing IPD in Spain

Figure 1 shows the 10 most frequent serotypes causing IPD in both studies and at each age with similar results: the first three are 8, 3 and 22F. The dramatic increase in serotype 3 after the pandemic has also occurred in other countries, until it became the first cause of IPD (4,5).

Figure 1. The 10 most frequent serotypes that cause invasive pneumococcal disease in Spaina.

In children under 5 years of age, the distribution of serotypes causing IPD is different (Figure 2). In both studies, the most common serotype is 3, followed by serotypes 24F and 22F. Serotype 8 is much more common in children than in adults, and it mainly affects older children (1).

Figure 2. Distribution of serotypes causing Invasive Pneumococcal Disease in Spain in children under 5 years of age.

The 24F serotype, mainly pediatric, has been stable over the past 3 years and mainly affects children under 4 years of age. It tends to cause meningitis and often associates with antibiotic resistance (4,6). In France, it rapidly increased after the introduction of PCV13, which counteracted the decrease in meningitis cases due to other serotypes (6).

In people over 65 years of age, serotype 3 is the most common. Given the high prevalence of pneumococcal infections in this age group (1,7,8), it is not surprising that in 2023, 75% of deaths from IPD were due to this serotype in our country ( 1). In Portugal, after the pandemic, serotype 3 has also been the most frequent cause of IPD followed by serotypes 8, 10A and 24 F (4).

Reasons for succession of vaccine serotypes

The reasons for the persistence of SVs are not fully known. VNC13 is effective against IPD due to serotype 3 (9), although its efficacy is less than that against other serotypes. This may be the reason why serotype 3, along with 19A and 19F, are the most frequent in vaccine failures (1,10). It is a proven fact that protection against IPD with these three serotypes requires higher levels of antipolysaccharide antibodies (11), which is probably related to the faster loss of effectiveness of PCV13 against serotypes 3 and 19A (3 ).

Perhaps the fact that best explains the adverse effect of PCV13 on IPD caused by serotype 3 is its little or no effect on nasopharyngeal colonization by this serotype. In England, after 10 years of vaccination with PCV13, 3 and 19A (12) are the only SVs that persist in the nasopharynx. The same thing happens in a country as close to ours as Portugal, where the most common vaccine serotypes are 19F, 3 and 19A (13). In this same country, the most frequent SNVs in the nasopharynx are: 15B/C, 11A, 23A, and 23B (13).

Most prominent non-vaccine serotypes causing IPD

Among the non-vaccinal serotypes (SNV), serotypes 4, 10A and 11A deserve some consideration.

Serotype 4 affects almost exclusively adults (1) and its increase has been observed in other countries, such as England (5). Serotype 10A, whose presence seems to be increasing, mainly affects children under 4 years of age, has a high invasive potential and tends to cause meningitis (4). Serotype 11A is associated with resistance to penicillin and amoxicillin (14,15) and is, of all pneumococcal serotypes, the most lethal (1,7).

In conclusion

Data from both studies provide detailed estimates of the potential coverage of PCV15 and PCV20 vaccines in different age groups. Thus, although the percentage of coverage for VNC15 and VNC20 in adults is around 40% and 75%, respectively, in children under 5 years of age this difference is smaller (around 45- 50% for VNC15 and 60-70% for NCV20).

50% of the serotypes that cause IPD are not covered by VNC15 or VNC20, so it will be necessary to monitor IPD to assess the possible effect of the extended valence VNCs which will arrive in the coming years.

-yeah-

Literature

1. Soler-Soneira M, Del-Águila-Mejía J, Acosta-Gutiérrez M, Sastre-García M, Amillategui-Dos-Santos R, Cano Portero R. Invasive Pneumococcal Disease in Spain in 2023. Weekly Epidemiological Journal. 2024; 32(2):74-93.

2. Pérez-García C, Sempere J, de Miguel S, Hita S, Úbeda A, Vidal EJ, et al. A study of invasive pneumococcal disease in Spain investigating the impact of the COVID-19 pandemic (2019-2023). J Infect [Internet]. 2024; 89(2): 106204.
3. Savulescu C, Krizova P, Valentiner-branth P, Ladhani S, Rinta-kokko H, Levy C, et al. Efficacy of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: the SpIDnet multicenter observational study. vaccination [Internet]. 2023; 40(29):3963–74.
4. Silva-costa C, Gomes-silva J, Pinho M, Friães A, Subtil-limpo F. Recurrence of pediatric invasive pneumococcal disease in Portugal after the COVID-19 pandemic was not associated with changes major serotype. J Infect. 2024; 89: 106242.
5. Bertran M, D’Aeth JC, Abdullahi F, Eletu S, Andrews NJ, Ramsay ME, et al. Invasive pneumococcal disease 3 years after introduction of a reduced 13-valent pneumococcal conjugate vaccine schedule in England: a prospective national observational study. Lancet Infect Dis. 2024; 24(5): 546–56.
6. Ouldali N, Levy J, Varon E, Bonacorsi S, Bechet S, Cohen R, et al. Incidence of pediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey. Lancet Infect Dis. 2018; 18(9):983–91.
7. De Miguel S, Latasa P, Yuste J, García L, Ordobás M, Ramos B, et al. Age-related serotype-related case fatality rate in invasive pneumococcal disease in the autonomous community of Madrid between 2007 and 2020. Microorganisms. 2021; 9(11):7–17.
8. Calvo-Silvera S, et al. Development of invasive pneumococcal disease with serotype 3 in adults: a three-year Spanish retrospective study. Lancet Reg Health Eur 2024 May 3:41:100913.
9. Singing HL, De Wals P, Gessner BD, Isturiz R, Laferriere C, Mclaughlin JM, et al. Efficacy of 13-valent pneumococcal conjugate vaccine against invasive disease caused by Serotype 3 in Children: A Systematic Review and Meta-analysis of Observational Studies. Clin Infect Dis. 2019; 68(12): 2135–43.
10. Mungall BA, Hoet B, Nieto Guevara J, Soumahoro L. Systematic review of invasive pneumococcal disease vaccine failure and breakthrough with enhanced pneumococcal conjugate vaccines in children. Vaccines Rev expert. 2022; 21(2): 201–14.
11. Andrews NJ, Waight PA, Burbidge P, Pearce E, Roalfe L, Zancolli M, et al. Serotype-specific efficacy and correlates of protection for the 13-valent pneumococcal conjugate vaccine: An indirect postlicensure cohort study. Lancet Infect Dis. 2014; 14(9):839–46.
12. Tiley KS, Ratcliffe H, Voysey M, Jefferies K, Sinclair G, Carr M, et al. Behavior of Nasopharyngeal Pneumococcus in Children in England up to 10 years after 13-Valent pneumococcal conjugate vaccine Introduction: Persistence of Serotypes 3 and 19A and Emergence 7C. J Infect Dis. 2023; 227(5):610–21.
13. Candeias C, et al. Streptococcus pneumoniae carriage, serotypes, genotypes, and antimicrobial resistance trends among children in Portugal, after introduction of PCV13 in the National Immunization Program: A cross-sectional study. vaccine 2024; Volume 42, Issue 22, 17 September 2024, 126219.
14. Sempere J, et al. Impact of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and emergence of less resistant Streptococcus pneumoniae serotypes in Spain, 2004-20: a national surveillance study. The Lancet Microbe. 2022; 3(10): e744–52.
15. Gonzalez-Díaz A, et al. Two multiple fragment recombination events led to the spread of the β-lactam-resistant serotype 11A-ST6521 associated with pneumococcal clone Spain9V-ST156 in Southwestern Europe, 2008 to 2016. Euro Surveillance. 2020; 25(16): pii = 1900457.

More information on this website

— CAV-AEP. Pneumococcusin AEP’s Online Immunization Manual.
— CAV-AEP. Other news about pneumococcus and its vaccine.