Rheumatic Heart Disease Prophylaxis

 ORIGINAL ARTICLEFREE PREVIEW

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

List of authors.

• Andrea Beaton, M.D., 
• Emmy Okello, Ph.D., 
• Joselyn Rwebembera, M.Med., 
• Anneke Grobler, Ph.D., 
• Daniel Engelman, Ph.D., 
• Juliet Alepere, B.A., 
• Lesley Canales, B.A., 
• Jonathan Carapetis, Ph.D., 
• Alyssa DeWyer, B.S., 
• Peter Lwabi, M.Med., 
• Mariana Mirabel, Ph.D., 
• Ana O. Mocumbi, Ph.D., 

Abstract

BACKGROUND

Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown.

METHODS

We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years.

RESULTS

Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, −7.5 percentage points; 95% confidence interval, −10.2 to −4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis).

CONCLUSIONS

Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525. opens in new tab.)

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Supported by the Thrasher Research Fund, Gift of Life International, Children’s National Hospital Foundation (Zachary Blumenfeld Fund and Race for Every Child [Team Jocelyn]), the Elias–Ginsburg Family, Wiley Rein, Philips Foundation, AT&T Foundation, Heart Healers International, the Karp Family Foundation, Huron Philanthropies, and the Cincinnati Children’s Hospital Heart Institute Research Core.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Drs. Beaton and Okello contributed equally to this article.

This article was published on November 13, 2021, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

This article is dedicated to the late Professor Bongani Mayosi, an original investigator of the GOAL trial. Professor Mayosi was a mentor, colleague, and friend who inspired and guided rheumatic heart disease research as part of his life’s work toward a more equitable future for Africa and the world.

Author Affiliations

From Cincinnati Children’s Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati School of Medicine — both in Cincinnati (A.B.); Uganda Heart Institute (E.O., J.R., J.A., P.L., M.N., E.N., I.O.O.), and the Department of Medicine, Makerere University (E.O.) — both in Kampala, Uganda; Children’s National Hospital, Washington, DC (L.C., M. Murali, R.S., C.A.S.); Murdoch Children’s Research Institute (A.G., D.E., A.C.S.), and Melbourne Children’s Global Health, Royal Children’s Hospital (D.E., A.C.S.), Melbourne, and Telethon Kids Institute, Perth Children’s Hospital, University of Western Australia, Perth (J.C.) — all in Australia; Virginia Tech Carilion School of Medicine, Roanoke, VA (A.D.W.); Assistance Publique–Hôpitaux de Paris, Université de Paris, and Cardio-Oncologie, Hôpital Européen Georges-Pompidou — both in Paris (M. Mirabel); Instituto Nacional de Saúde, Maputo, Mozambique (A.O.M.); Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (M.C.P.N.); Emory University School of Medicine, Atlanta (A.S.); Green Lane Paediatric and Congenital Cardiac Service, Starship Children’s Hospital, Auckland, New Zealand (N.W.); Geisel School of Medicine, Dartmouth–Hitchcock Medical Center, Lebanon, NH (M.Z.); the Division of Paediatric Cardiology, Department of Paediatrics, Red Cross War Memorial Children’s Hospital, and the Division of Cardiology, Department of Medicine, Groote Schuur Hospital — both in Cape Town, South Africa (L.Z.); and All India Institute of Medical Sciences, New Delhi, India (G.K.).

Dr. Beaton can be contacted at andrea.beaton@cchmc.org or at Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229.