Increasing incidence of serotype 38 invasive pneumococcal disease driven by the ST393 clone among children, Denmark 2022-2024

Abstract

Non-vaccine-serotypes (non-VT) pose a challenge to reducing invasive pneumococcal disease (IPD). Since 2023, serotype 38 IPD has increased in Denmark promoting investigation of this serotype's characteristics. We included all non-VT IPD cases from 2014 to 2024 to calculate annual incidences per 100,000 individuals with 95% confidence intervals (CI). Clinical characteristics and outcomes of serotype 38 IPD were compared with other non-VT IPD in 2022 to 2024. Incidence of serotype 38 IPD increased mainly in children < 2 years, from 0.87 (95% CI 0.02-4.84) to 5.99 (95% CI 2.41-12.34) cases per 100,000 population, whereas the incidence for other non-VT remained stable. SNP analysis, conducted for serotype 38 isolates, revealed that the rise was driven by the ST393 clone with isolates not linked to a region or outbreak. Baseline characteristics and outcomes were similar between the 42 cases of serotype 38 IPD and the 412 other non-VT IPD cases, except for age distribution (p < 0.001) with serotype 38 IPD more frequent in children aged < 2 years (21.4% vs. 3.4%). In conclusion, serotype 38 IPD, driven by the ST393 clone, was the dominant serotype causing non-VT IPD in children < 2 years the last two years, however disease severity was similar to other non-VT IPD.

Keywords: Epidemiology; IPD; Incidence; Serotype 38; Streptococcus pneumoniae; Whole genome sequencing.

Fig. 1

Incidence of invasive pneumococcal disease (IPD) cases due to serotype 38 IPD and other non-vaccine serotypes (non-VT) IPD stratified by age group, Denmark 2014–2024. Incidence estimated as number of IPD per 100,000 population; non-VT defined as serotypes not included in the 13-valent pneumococcal conjugate vaccine (PCV13) or the 23-valent pneumococcal polysaccharide vaccine (PPV23). (A) Total population, (B) Age < 2 years, (C) Age ≥ 65 years, Denmark 2014–2024. The year 2024 is not complete and only includes samples until September.

Fig. 2

Phylogenetic tree of all ST393 isolates (39 isolates) collected from January 2022 to September 2024. The isolate PNC-2024-0448_Herlev_2024 was used as the reference strain in the Single Nucleotide Polymorphism (SNP) alignment. Labels indicate the sample number, year, and location (city in Denmark). The scale bar represents substitutions per site.