An evaluation of Staphylococcus aureus colonisation: epidemiology, risk factors, and transmission in diverse settings

Staphylococcus aureus is a human pathobiont that typically colonises the anterior nares.
Whilst colonisation is often asymptomatic, it also increases the risk of invasive, potentially life-threatening infection. S. aureus is the leading cause of death from bacterial infection
worldwide, with treatment frequently complicated by antimicrobial resistance. This thesis
presents three complementary projects investigating the epidemiology, transmission, and
host-pathogen interactions of S. aureus colonisation across diverse geographical and
socioeconomic settings.

The first project used a longitudinal cohort design in Sri Lanka, a country with a high burden of antimicrobial resistance, to investigate colonisation and transmission of infecting S. aureus strains at the community and healthcare interface. The second project, a systematic review and meta-analysis of S. aureus colonisation in healthy individuals from low- and middle-income countries was performed to estimate the pooled prevalence of colonisation and associated host and bacterial characteristics. The third project was a longitudinal, multi-faceted investigation of S. aureus colonisation in a UK cohort, integrating bacterial, host, and socio-environmental factors to characterise colonisation phenotypes.

Key findings include the consistent prevalence of S. aureus colonisation across healthy
populations despite diverse geographical and socioeconomic contexts. Strain-level analyses highlighted the dominance of region-specific clones with differing virulence potential, emphasising the need for molecular surveillance to inform localised infection prevention strategies. Traditional binary definitions of S. aureus colonisation fail to capture the dynamic continuum of bacterial density, with periods of low-density colonisation often missed by culture methods. At the individual level, strain turnover was infrequent, suggesting stable host-pathogen interactions in the short term. However, few consistent exogenous risk factors for colonisation were identified, indicating the likely role of unmeasured biological or behavioural influences.

Together, these projects contribute to a more nuanced understanding of S. aureus colonisation and its drivers, with implications for surveillance programs and infection prevention strategies such as vaccination.