Serotype 3 invasive pneumococcal disease in Tuscany across the eras of conjugate vaccines (2005-2024) and anthropic-driven respiratory virus fluctuations

Abstract

Serotype 3 Streptococcus pneumoniae (ser3) has emerged as a leading cause of invasive pneumococcal disease (IPD) despite targeted vaccination efforts. Preliminary evidence reported a differential impact of anti-ser3-pneumococcal-conjugate-vaccines (PCVser3) on different clinical presentations of ser3-IPD. Recently, a temporal association between respiratory syncytial virus (RSV) and IPD was observed in children, supporting a role of RSV in driving IPD dynamics. Ser3 IPD cases occurred in Tuscany from November 2005 to March 2024 were included. Comparisons of different clinical presentations (bacteremic pneumonias and osteomyelitis versus sepsis and meningitis) were made between younger and older patients and between vaccinated and unvaccinated ones. The temporal correlation between ser3 IPD, RSV and influenza was qualitatively described from 2015/2016 to 2023/2024. Among 160 ser3 IPD recorded cases, fully-immunized patients showed a significantly lower proportion of sepsis and meningitis compared to non-immunized patients (all ages: 7.5% versus 58.5%, p < .0001; aged 14-years and younger: 0% versus 31.3%, p = .0019). Ser3 IPD showed a strong temporal association with influenza virus outbreak but not with isolated RSV outbreak. Nearly two decades of molecular surveillance of ser3 in Tuscany suggest that the most severe IPD presentations, such as sepsis and meningitis, are significantly lower in individuals who received PCVser3 immunization. Ser3 IPD incidence is temporally associated with influenza outbreaks but not with RSV.

Keywords: Invasive pneumococcal disease; PCV; children; immunization; meningitis; pneumococcal conjugate vaccine; sepsis; serotype 3.

Figure 1.

Number of cases of serotype 3 invasive pneumococcal disease recorded in Tuscany from November 2005 to March 2024 divided per epidemic season and age group (Upper panel: subjects aged 14 and younger; Lower panel: subjects older than 14 years of age).

Figure 2.

(a) The column chart depicts the number of cases of serotype 3 invasive pneumococcal disease (ser3 IPD) recorded in Tuscany from November 2005 to March 2024 divided per age groups and clinical presentation. The pie charts depict the percentage representation of the different clinical presentations of ser3 IPD in subjects aged 14 and younger and in subjects older than 14 years of age. (b) Percentage of full immunization with a pneumococcal conjugate vaccine containing the ser3 antigen (PCVser3) in subjects aged 14 and younger and in subjects older than 14 years of age. (c) Percentage representation of the different clinical presentations of ser3 IPD in PCVser3-immunized and non-immunized subjects of all ages. (d) Absolute numbers of cases of ser3 IPD dived per age and clinical presentation (column charts) and percentage representation of the different clinical presentation (pie charts) in PCVser3-immunized and non-immunized subjects aged 14 and younger. Color legend refers to all panels. P stands for p-value obtained with the Chi-squared or Fisher’s exact test, depending on the number of observations.

Figure 3.

Absolute number of cases of serotype 3 invasive pneumococcal disease (ser3 IPD, red line), influenza virus (influenza, blue line) and respiratory syncytial virus (RSV, light blue line) infection recorded per year from the 2015/2016 to the 2023/2024 epidemic season in subject aged 14 years and younger. Ser3 IPD cases were recorded all over Tuscany. RSV and influenza cases were recorded in the major pediatric hospital of Tuscany region. RSV and influenza virus recorded case scale is presented on the left side (blue) while ser3 IPD recorded case scale is presented on the right side (red).