eCase - Pneumococcal Disease EU

CME

Pneumococcal Disease: Current Concepts for At-Risk Adults

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit™

Released: August 22, 2024

Expiration: August 21, 2025

Elisabeth Botelho-Nevers, MD, PhD, HDR

CME/CE Information

Activity

Progress

1 2

Course Completed

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Introduction Burden of Pneumococcal Disease Spotlight on S. pneumoniae Adult Pneumococcal Vaccines Pneumococcal Vaccination Rates Pneumococcal Vaccines in Development References

Evolution of IPD Incidence Rate by Age and Vaccination Coverage at the Age of 24 Months in Metropolitan France

The graph depicts data from the French National Reference Center for Pneumococci, showing curves of IPD. It illustrates a notable decline in incidence rates among children younger than 2 years old following the introduction of conjugate vaccines. In addition, it highlights a decrease in invasive pneumococcal infections among individuals older than age 65, even before adult vaccinations were introduced. The study showed that in 2021, the overall incidence of IPD decreased by 9% compared to 2020.

These data underscore the concept of herd immunity and emphasize the importance of vaccinating children, not only to protect them but also to have a positive impact on adult populations.⁹

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Representation of Vaccine Serotypes (PCV13) in IPD By Age

Recently, there has been a resurgence in pneumococcal infections among both children and adults, even after the introduction of adult vaccination in France in 2017. This resurgence is attributed to serotype escape. Following the introduction of these vaccines in children, there was a significant reduction in PCV13 serotypes.

Before the introduction of PCV13, children had a high proportion of IPD caused by PCV serotypes now included in PCV13. Similar trends were observed in adults, showing a decrease in IPD due to PCV13 serotypes.

However, there are still cases of IPD caused by PCV13 serotypes, alongside nonvaccine serotypes. The incidence of invasive pneumococcal infections associated with vaccine serotypes varies by age group, indicating ongoing challenges despite vaccination efforts.¹⁰

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Proportion of Acute CAP With Serotypes Included in PCV20 in Europe

This graph shows the proportion of CAP cases due to serotypes included in PCV20, the latest conjugate vaccine available in Europe. Examining the serotypes associated with CAP in different countries, it is evident that the serotypes are less covered by PCV13 compared to PCV15 and PCV20. This trend is consistent across all countries presented (Sweden, Germany, Spain, UK, Greece, and Italy).^11-16

In France, an epidemiologic study analyzing the serotype distribution in antigen testing among patients with CAP confirmed that the serotypes covered by PCV13 are fewer than those covered by PCV20.¹⁷

Specifically, serotypes covered by PCV20 account for 7.5% to 23.8% of all CAP cases in adults across various European countries.^11-16

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Incidence of IPD Among People Aged ≥65 Years

When examining the incidence of IPD and the distribution of serotypes among adults, we observe trends over the years represented by different colors on this graph. There is a decrease in some PCV13-included serotypes. With increased vaccination efforts, invasive infections associated with PCV13 serotypes have generally declined, with the exception of serotype 3, which remains prevalent despite being included in PCV13.

We see the emergence of nonvaccine serotypes, including a notable increase in serotype 8 over the years. Serotypes 22F and 9N show stability. No single nonvaccine serotype predominates among adults.¹⁰

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Serotype Coverage in IPD in Adults in France

When comparing PCV20 to PCV13 for the coverage of IPD, we observe an increased capability of PCV20 to cover and protect against a greater number of pathogens. This trend applies to individuals younger than age 65 as well as those aged 65 years or older.

Pneumococcal polysaccharide vaccine (PPSV) 23 may offer better coverage in terms of number of serotypes covered, but polysaccharide vaccines generally do not induce robust immune responses. Conjugate vaccines, on the other hand, elicit stronger immune responses. Since the development of conjugate vaccines, there has been a higher percentage of serotype coverage against invasive infections.

The National Reference Center for Pneumococci (CNRP) 2023 report indicates that in France, nearly 65% of IPD cases in adults are caused by serotypes covered by PCV20.¹⁰

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Meningitis in Adults and Sensitivity to Cefotaxime

A key objective of pneumococcal vaccines is to protect against and reduce infections caused by serotypes that exhibit resistance, as some pneumococcal serotypes are associated with antibiotic resistance.

According to the CNRP 2023 report, some pneumococcal strains show reduced sensitivity to cefotaxime, a critical antibiotic used in treating meningitis. Over time, certain pneumococcal strains associated with invasive infections such as bacteremia and meningitis have emerged that are not covered by PCV13. For example, serotype 8 alone accounts for more than 15% of pneumococcal bacteremia cases and over 10% of meningitis cases. This trend extends to other serotypes as well.¹⁰

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Most Frequently Isolated Serotypes in French Adults Aged ≥65 Years With IPD, 2019 and 2020

Certain serotypes responsible for a significant number of infections are not currently covered by vaccines. Even though the polysaccharide vaccine PPSV23 offers broad coverage, including serotype 8, it generally induces a weaker immune response than conjugate vaccines. Therefore, enhancing immunogenicity and immune response across various serotypes is crucial, and can be achieved more effectively with conjugate vaccines. This highlights the need to expand the range of serotypes targeted by conjugate vaccines.⁹

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IPD Trends in Spain in Adults Aged 18-64 Years

Similar trends are seen in other European countries, such as in Spain. A study examining data from national laboratories in Spain showed that there has been a decline in the incidence of invasive diseases caused by PCV13 serotypes over time, confirming the presence of herd immunity originating from pediatric vaccination efforts with the administration of PCV13. In addition, serotype 3 remains consistently the most prevalent among PCV serotypes in people 18 to 64 years of age.¹⁸

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IPD Trends in Spain in Adults Aged ≥65 Years

In the same study conducted in Spain, the administration of PCV13 showed a clear impact in pneumococcal disease epidemiology and reduced the burden of IPD in patients aged 65 years or older by herd immunity. This trend is consistent across all countries, showing a decrease in PCV13-covered serotypes concurrent with the introduction of childhood vaccinations. However, in some countries, including in France, there has been a resurgence in invasive pneumococcal infections due to serotype escape.¹⁸

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**Most Common S. pneumoniae Serotypes in Europe by Year**

Serotype 8 continues to show increasing prevalence in Europe, alongside serotype 3. This trend persists even though PCV13 and most other available vaccines cover these serotypes. This likely illustrates both undervaccination and serotype escape.⁴

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Which pneumococcal serotypes most commonly cause disease in adults in Europe?

A.
Serotypes 15A and 35F, despite inclusion in most pneumococcal vaccines
B.
Serotypes 15A and 35F, but neither are included in available pneumococcal vaccines
C.
Serotypes 3 and 8, despite inclusion in most pneumococcal vaccines
D.
Serotypes 3 and 8, but neither are included in available pneumococcal vaccines

Pneumococcal Serotype Evolution in European Adults

Despite children being vaccinated with pneumococcal conjugate vaccines in Europe, pneumococcal infections are still a major cause of morbidity and mortality in adults with risk factors. Vaccinating these adults is an important prevention strategy.

Findings from a 2023 systematic review on serotype evolution in Europe have shown that there has been a notable increase in serotype 8 and other serotypes, including those with antimicrobial resistance. This underscores the necessity to expand vaccine coverage, particularly with PCV20, which may enhance protection against pneumococcal disease and can broaden coverage for these serotypes.¹⁹

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