Molecular epidemiology of Streptococcus pneumoniae serotypes 6A and 6B: A systematic review of circulating clones and clonal clusters

BACKGROUND: Pneumococcal serotypes 6A and 6B are members of Streptococcus pneumoniae serogroup 6 and are among the most prevalent serotypes causing invasive pneumococcal diseases (IPD). These serotypes are associated with unique clonal lineages, with some exhibiting antibiotic resistance and high virulence properties. OBJECTIVE: To explore the global spread of serotypes 6A and 6B clones, detailing their circulating patterns across regions. METHODS: Following the PRISMA guide, four databases were searched for peer-reviewed articles using molecular genotyping to determine sequence types (STs) of serotypes 6A and 6B. RESULTS: Thirty-seven studies from 23 countries reporting 138 STs for serotype 6A and 106 for serotype 6B were included in the systematic review. Both serotypes were strongly associated with IPD. For serotype 6A, clonal complexes (CCs) 473 and 3173 were predominant. CC473, comprising ST473, ST1876, and ST471, exhibited widespread distribution across Europe, Asia, the Americas, and Oceania, while CC3173 (ST3173, ST361) was mainly reported in Africa and Asia. For serotype 6B, CC90 (ST90, ST273) and CC176 were the dominant lineages, with isolates recovered from all continents. Notably, ST395, ST1692, and ST3173 were identified in both serotypes. For example, ST395 was reported as 6A in Portugal, the United States, and Australia, and as 6B in Portugal; ST1692 was detected as 6B in Portugal and 6A in Australia; and ST3173 was observed as both 6A and 6B in China. CONCLUSIONS: Serotypes 6A and 6B exhibit complex genetic variation and intercontinental widespread, with some lineages spanning both serotypes. This highlights their epidemiological significance and potential role in the spread of invasive pneumococcal diseases and antibiotic resistance globally.