This study presents the first long-term epidemiological and genomic analysis of invasive Streptococcus agalactiae (GBS) infections in the Faroe Islands. Despite the limited population size, our findings indicate an overall trend toward increasing GBS incidence over the 15-year period (2009–2024), consistent with trends reported across Northern and Western Europe (Fig. 1). This rising burden is likely associated with aging populations and increasing prevalence of comorbidities, as observed in comparable high-income settings2,4,21.
The potential influence of the COVID-19 pandemic on GBS incidence remains uncertain. While restrictive measures during the pandemic led to reduced transmission of respiratory pathogens such as Streptococcus pneumoniae, no similar reduction in GBS infections was observed (Fig. 1).
This pattern is consistent with the view that invasive GBS may be less influenced by short-term changes in respiratory transmission dynamics and may therefore function as a relatively stable comparator organism in surveillance analyses22. Following the easing of pandemic restrictions, increases in invasive bacterial infections have been reported in several settings, and a similar post-pandemic increase in GBS incidence is plausible23,24.
Given the suggested increase in incidence, vaccination represents a promising strategy. The hexavalent polysaccharide conjugate vaccine (GBS6) targets the six most prevalent serotypes globally (Ia, Ib, II–V) and would have covered 16 of the 18 serotyped isolates in this study. However, serotype VIII and IX were also detected—highlighting the risk of serotype replacement, as seen in pneumococcal disease following PCV introduction25. The protein-based GBS-NN/NN2 vaccine candidate targets conserved N-terminal domains of the Alp-family proteins (AlphaC, Rib, Alp1, Alp2/Alp3). All sequenced isolates expressed at least one Alp-family protein, suggesting that, based on the circulating serotypes and Alp-family genes identified, the strains observed in this study would likely be largely covered by current candidate GBS vaccines, even in older adults.
The absence of the rib gene in our dataset is noteworthy, as rib is uniformly present among serotype III/CC17 (ST17) strains, which are disproportionately associated with neonatal meningitis and sepsis16. Consistent with this, no CC17/serotype III isolates were identified in the present study, and the dominance of AlphaC supports findings from other high-income settings16. Cross-protection among Alp variants remains under investigation, particularly for Alp1 and Alp2/Alp3 26.
Our MLST data revealed a predominance of CC12 among recent invasive GBS isolates in the Faroe Islands, followed by CC452, CC1, CC23, and CC456 (Table 1). Notably, no isolates from the hypervirulent CC17 lineage were detected. Along with the near absence of serotype III, this suggests that most infections likely occurred in adults rather than neonates. However, because age data were not available, it is not possible to determine which age groups constitute the dominant burden of invasive GBS infections in this study. This interpretation is therefore based on established strain disease associations rather than patient level metadata. In other studies, CC17 and serotype III are consistently associated with neonatal disease, particularly late-onset meningitis27,28. These findings reflect a moderate degree of genetic diversity among circulating strains. This pattern is consistent with broader GBS population studies, which typically identify CC1, CC10, CC17, CC19, and CC23 as the most common human-associated clonal complexes29,30. CC10 and CC12 represent the same broader lineage, as ST10 and ST12 are single-locus variants. In the current PubMLST database (https://pubmlst.org/organisms), both ST10 and ST12 are assigned to CC12, which is now considered the predominant founder type of this clonal cluster. Accordingly, only CC12 and not CC10 was detected in our dataset.
At the molecular level, all sequenced isolates carried the cfb and sodA genes (Table 1). These conserved genes are widely used as molecular markers for species confirmation and identification of S. agalactiae in both diagnostic and genomic analyses18,31. The srr1 gene was present in nearly all isolates, reflecting its widespread distribution across GBS lineages6,16.
The detection of the hypervirulence-associated hvgA gene in the isolate (serotype Ia, CC452) (Table 1) is rare, as it is typically associated with serotype III and the CC17 lineage, although it has also been linked to other serotypes and to CC452.16. The hvgA gene is classically associated with the hypervirulent CC17 lineage and has been strongly linked to neonatal meningitis16.
PI-1, PI-2a, PI-2b are GBS surface structures involved in colonization and invasiveness, with PI-1 linked to innate immune evasion, PI-2a to adherence/biofilm formation, and PI-2b to enhanced invasiveness and intracellular survival, including blood–brain barrier penetration6. Genes for the Pilus islands (PI) proteins were detected in all isolates in this study (Table 1), with PI-1 and PI-2a found to be the dominant Pilus, while PI-2b was identified in only one isolate.
Phenotypic and genotypic antimicrobial susceptibility testing confirmed universal susceptibility to penicillin among the tested isolates. This finding is consistent with surveillance data from Denmark, where beta-hemolytic streptococci have remained susceptible to penicillin since national monitoring began in the DANMAP reports (https://www.danmap.org/, accessed 25-06-2025). Although sporadic cases of penicillin non-susceptibility have been reported in Europe32, GBS is generally considered penicillin-susceptible16,33.
The observation that four GBS isolates exhibited resistance to both erythromycin and clindamycin, with two carrying the erm(A) gene (Table 1), aligns with global trends. While resistance to first-line therapy remains uncommon, increasing resistance to second-line agents such as macrolides and lincosamides is a growing concern worldwide33. In Denmark, erythromycin and clindamycin resistance levels are reported at approximately 20–25%, as documented in recent DANMAP reports (accessed 25-06-2025).
This study is limited by the small population size and relatively low number of cases, which constrain its statistical power. The exclusion of patient-level demographic data, such as age, sex, comorbidities, and education level of the patients, due to both the small population and General Data Protection Regulation (GDPR) restrictions, further limits the ability to perform stratified analyses. Additionally, not all isolates underwent whole-genome sequencing or complete phenotypic testing, which may introduce selection bias. In particular, isolates available for genomic analysis were primarily from later years, potentially underrepresenting earlier cases or specific clinical presentations.