Determining the Impact of Penicillin on Latent Rheumatic Heart Disease
BACKGROUND: Rheumatic heart disease (RHD) is a cumulative heart valve disease that results from Group A streptococcal infection, triggering the systemic inflammatory condition acute rheumatic fever (ARF), mainly in children, and leading to chronic cardiac valve disease. GAP: Echocardiography can “see” latent RHD before symptoms develop, allowing for early disease detection and initiation of benzathine penicillin G (BPG) prophylaxis. While BPG prophylaxis is known to stop disease progression and cause disease regression among patients with ARF, its effect on latent RHD is not known. HYPOTHESIS: Hypothesis 1: Prophylaxis with BPG will result in fewer children with latent RHD showing progression of echocardiographic valve changes at 2 years compared to children with latent RHD not receiving BPG prophylaxis. (We expect at least a 50% relative reduction in progression in the BPG arm: range 15%-25% control arm vs. 7.5-12.5% BPG-arm.); Hypothesis 2: Prophylaxis with BPG will result in more children with latent RHD showing regression of echocardiographic valve changes by 2 years compared to children with latent RHD not receiving BPG prophylaxis. (We expect at least a 50% relative increase in regression in the BPG arm: range 10-20% control arm vs. 20-40% BPG arm.) METHODS: We will conduct a randomized controlled trial of penicillin prophylaxis in children (5-17 years) with latent RHD according to the 2012 World Heart Federation (WHF) criteria. RESULTS: A total of 916 children were enrolled between July and November 2018, meeting the enrollment target within the planned time frame. Follow-up is expected to continue until December 2020, with final outcomes assessment between July and November 2020. IMPACT: Results of our study will immediately inform the standard of care for children diagnosed with latent RHD, and could help shape, over 2-3 years, practical and scalable screening programs that could substantially decrease the burden of RHD in our lifetime.