Supplementary Information for - Evolution of pneumococcal serotype 19A in Bangladesh: insights from genomic analysis

AbstractBackground Invasive pneumococcal disease (IPD), caused by Streptococcus pneumoniae, remains a major global health concern, particularly for children. Among more than 100 pneumococcal serotypes, 19A is known for its multidrug resistance and increased incidence following PCV7/PCV10 introduction in many countries. Bangladesh introduced PCV10 nationwide in 2015 considering the low burden of 19A, and hence, continuous monitoring of the serotype is required.

Methods
Utilizing the IPD surveillance data from 2004 to 2023 in Bangladesh, we investigated the incidence of serotype 19A before and after PCV10 introduction. Whole-genome sequencing was performed on 153 pneumococcal 19A isolates from IPD, otitis media, nasopharyngeal carriage, and urine samples. Using phylogenetic and BEAST analyses, we evaluated the population structure of 19A in Bangladesh, including circulating subtypes, global pneumococcal sequence clusters (GPSCs), sequence types (STs), and antimicrobial resistance (AMR) genes, and compared these findings with 19A genomes available from other countries.

Results
Our findings indicate no significant increase in hospital IPD incidence due to serotype 19A following the introduction of PCV10. The MDR 19A-ST320 lineage (GPSC1) remains absent in Bangladesh. ST12888 (GPSC84) appear to have become dominant after PCV10 introduction, rising from 15% (8/53) to 70% (70/100) in the post-PCV10 era. GPSC84 possesses a capsular locus of 19A subtype I (19A-I), which emerged independently from the standard 19A locus. Macrolide resistance within the 19A-I/GPSC84 lineage was also observed and is estimated to have originated between 2007-2011. The diverse distribution of GPSCs and STs detected in Bangladesh is distinct from other countries.

Conclusion
This study presents the first comprehensive genomic analysis of the serotype 19A population in Bangladesh, supporting the decision to introduce PCV10 in Bangladesh based on local pneumococcal serotype burden data. However, the rapid evolution within the local 19A population highlights the need for continuous epidemiological and genomic surveillance to support effective vaccination programs.