The jAGuar study: Understanding the clinical and molecular epidemiology of superficial group A streptococcal infections in Uganda.

Streptococcus pyogenes or group A Streptococcus (GAS) is ranked as the 4th deadliest bacterium in the world, causing more than 500,000 deaths per year. GAS causes disease ranging from uncomplicated pharyngitis and impetigo to life-threatening sepsis. GAS is also responsible for a large burden of post-streptococcal sequalae, including rheumatic fever (RF) and rheumatic heart disease (RHD), with over 40 million current prevalent cases. Ultimately, the most effective global approach to RHD control is prevention of superficial GAS infections, including with a GAS vaccine. Establishing robust data on the prevalence and incidence of superficial GAS infections, with a longer-term objective of obtaining critical data and establishing infrastructure needed for GAS vaccine trials, is an essential global priority, endorsed by World Health Organization7 and the Strep A Vaccine Global Consortium (SAVAC, LOS). In light of this challenge, the jAGuar study (Amabwa G’omumiro, sore throat in Luganda), will expand our understanding of superficial GAS infections (pharyngitis and impetigo) in Uganda through prospective epidemiological surveillance, novel GAS transmission studies, and molecular characterization of circulating GAS strains. The study will also build local capacity for GAS surveillance and sample processing, establishing a well-characterized GAS biobank for future studies, and will be the global leader in surveillance of superficial GAS infections.   The jAGuar study is designed as a school-based GAS surveillance program in 2 districts comprising: (1) school-wide screening visits 3 times/year, and (2) active weekly surveillance clinics for symptomatic sore throats and skin infection. At least 800 children, aged 3-15 years, will be enrolled and prospectively followed for 12 months. Prevalence (cross-sectional screening) and incidence (symptomatic infection) data on GAS pharyngitis and impetigo (Aim 1) will be supplemented by targeted intensive household and classroom surveillance triggered by sets of children who are GAS positive (symptomatic and asymptomatic) (Aim 2). These data will be supplemented by 3 geographically diverse “snapshot” cohorts (each with 1 school and ~200 children) with a single school-wide screening and 3-month clinic to fully capture the GAS epidemiological and molecular profile in Uganda. The expected outcomes of jAGuar are (i) a comprehensive understanding of the clinical and molecular epidemiology and transmission of superficial GAS infection in Uganda, (ii) establishment of state-of-the-art GAS surveillance sites in Uganda, including capacity building for handling clinical, microbiological, and immunological data and (iii) establishment of a robust GAS biobank for future investigations. Combined, this research will provide an unprecedented depth to GAS disease epidemiology in an RHD endemic setting that will inform the establishment of vaccine trial sites in sub-Saharan Africa for the first generation of GAS vaccines currently under development.