Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are a major problem for Australian Indigenous people. Accurate diagnosis of ARF allows for early preventive therapy with long acting penicillin, which can prevent RHD from developing or worsening. The aim of this study is to recruit a cohort of children and young people with ARF and apply the latest technologies to their blood samples, with the aim of developing a diagnostic test and open leads for potential new treatments.