Abstract

Introduction: Rheumatic heart disease (RHD) is the largest contributor to cardiac mortality in children worldwide. Little contemporary data exist on its antecedent illness, acute rheumatic fever (ARF). There is an urgent need to understand outcomes following ARF in RHD-endemic settings. We aimed to describe medium-term mortality, disease recurrence, and change in carditis among Ugandan children following ARF diagnosis, and to identify correlates of mortality. Methods: We conducted a prospective cohort study of children diagnosed with definite ARF in 2017-2020 during a community-based incidence study. Patients were enrolled in a national registry and followed with annual review, most recently in August 2022. Kaplan-Meier (KM) survival analysis was used to describe all-cause mortality and individual Cox proportional hazards regression models were used to identify correlates of death. Descriptive statistics were used to characterize changes in carditis. Results: Among 135 children with definite ARF, 22/135 (16.3%) experienced death, 19/135 (14.1%) cardiac death, 5/135 (3.7%) ARF recurrence, and 5/135 (3.7%) surgery over a median (interquartile range) of 4.25 (3.4, 5.1) years. KM analysis saw 14/22 (63.6%) of deaths occur by one year, 16/22 (72.7%) by two years, and 20/22 (90.9%) by three years. The presence of moderate/severe carditis (HR 14.1, 95% CI 4.2, 47.7) and PR prolongation (HR 3.9, 95% CI 1.5, 9.9) at diagnosis was associated with increased cardiac mortality. Among 107 survivors included in echocardiographic sub-analysis, 27/107 (25.2%) had improvement in carditis, 70/107 (65.4%) no change, and 10/107 (9.4%) progression. Conclusions: These are the first contemporary data from sub-Saharan Africa reviewing medium-term outcomes following ARF. Adverse outcome rates exceeded those reported elsewhere. Most decedents already had advanced cardiac involvement upon first ARF diagnosis, as evidenced by PR prolongation and high-grade carditis, suggesting a history of prior undiagnosed ARF recurrences that had already compounded into RHD. These data indicate that a high burden of ARF exists in the community that is undetected by current methods, emphasizing the need for better point-of-care diagnostics to improve early ARF detection.

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