Molecular epidemiological and pathogenesis studies of Streptococcus pneumoniae serotype 1 strains from West Africa

In West Africa, Streptococcus pneumoniae remains a leading cause of deaths in young children and serotype 1 strains are particularly important in causing invasive pneumococcal disease (IPD) despite being rare in nasopharyngeal carriage. The S. pneumoniae ST217 clonal complex, consisting of ST217 and the various locus variants has been shown to be the predominant pneumococcal serotype 1 clone in the sub-region. It is unclear how the recent introduction of pneumococcal conjugate vaccine (PCV) in countries in the sub-region could affect patterns of pneumococcal disease. Improving our understanding of the unique nature of pneumococcal serotype 1 strains within the context of other pneumococcal serotypes circulating in West Africa prior to introduction of PCV would be critical in interpreting any subsequent changes in patterns of disease in this region. This forms the basis for my research studies for this PhD thesis. Epidemiological studies on S. pneumoniae strains in The Gambia revealed that a new dominant clone of serotype 1, ST3081, a single locus variant of ST217, emerged and appeared to have spread across the whole country. ST3081 appeared to have replaced ST618, a triple locus variant of ST217 and the previously dominant pneumococcal serotype 1 lineage circulating in The Gambia for over a decade earlier. This thesis, which also evaluated antimicrobial resistance patterns, showed that ST3081 isolates were more resistant to co-trimoxazole than ST618 isolates. In addition, comparative genomic analysis highlighted the role of recombination in driving the evolution of serotype 1 STs in The Gambia. It also revealed important genetic differences between these two predominant STs in The Gambia, ST3081 and ST618, in antimicrobial genes such as tetM and virulence genes such as exist within the fucose metabolism operon. These findings would be useful in informing strategies to improve the monitoring and control of pneumococcal serotype 1 disease.