Epidemiology of Streptococcus pyogenes in The Gambia: investigating carriage and disease burden, transmission dynamics and diagnostic accuracy

Streptococcus pyogenes (S. pyogenes; StrepA; Group A Streptococcus; GAS) causes a substantial burden of disease globally ranging from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year globally, disproportionately in low- and middle-income countries (LMIC). StrepA-positive pharyngitis can lead to acute rheumatic fever and rheumatic heart disease in some patients, which causes most StrepA-associated mortality. The importance of StrepA skin infections has been recognised in high-RHD settings, but data is lacking. As well as pyoderma, asymptomatic carriage of StrepA in the pharynx and on skin may be important for transmission. The overarching aim of this thesis is to investigate the epidemiology of StrepA carriage and infection in The Gambia, the pathways by which it spreads within households, and how transmission and disease risk are shaped by individual, household, and environmental factors, while also evaluating the accuracy and utility of clinical decision rules and rapid diagnostic tests for StrepA pharyngitis in this setting. In Sukuta, an urban area of The Gambia, two observational studies were conducted to better understand these aspects of StrepA epidemiology. The first recruited children presenting to primary healthcare with acute pharyngitis to assess the prevalence of StrepA pharyngitis, and to assess the diagnostic accuracy of clinical decision rules and rapid diagnostic tests for the diagnosis of StrepA pharyngitis in this setting. The second, a longitudinal household cohort study conducted over one year, sought to understand the temporal relationship between StrepA carriage and disease, how it is spread from person to person, via skin or pharynx, acquired inside or outside households, and what risk factors for carriage and disease exist. The study utilised frequent microbiological swabbing visits with same-day culturing for StrepA isolates to provide robust measures of disease burden. Detailed information on socio-demographics, social-mixing behaviour, water access and sanitation, was combined with emm-typing of isolates to investigate risk factors for StrepA disease and for transmission. Utilising approaches never used before in Africa, this PhD thesis addresses several key gaps in relation to StrepA epidemiology in LMICs, providing vital data to inform surveillance strategies, optimise diagnostic pathways and guide the development of targeted interventions to reduce the burden of StrepA disease.