Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

Quick Takes

  • In a randomized, controlled trial among children and adolescents with echocardiographic evidence of latent rheumatic heart disease, the use of intramuscular penicillin G benzathine every 4 weeks for 2 years was associated with a substantial reduction in the risk of echocardiographic progression of rheumatic heart disease.
  • The number needed to receive prophylaxis to prevent one case of latent rheumatic heart disease progression was 13 (95% CI, 10-21).
  • Among those with disease progression, there was a high prevalence of moderate or severe disease at 2 years, underscoring the potential clinical impact of screening.

Study Questions:

Is secondary antibiotic prophylaxis effective in preventing progression of latent rheumatic heart disease?

Methods:

In a randomized, controlled trial, children and adolescents aged 5-17 years in primary and secondary schools in Gulu, Uganda, were invited to participate in echocardiographic screening for latent rheumatic heart disease; participants with abnormal screening echocardiograms were referred for clinical evaluation and detailed echocardiography. Those with a new diagnosis of latent rheumatic heart disease were randomly assigned to receive either intramuscular injections of penicillin G benzathine every 4 weeks for 2 years or no prophylaxis. All 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 underwent screening echocardiograms, 3,327 initially were assessed as having latent rheumatic heart disease, of whom 926 subsequently received a definitive diagnosis based on confirmatory echocardiography. Of these, consent for participation was provided for 916, all of whom underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of three participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years (3 of 3 [100%] progressing to moderate or severe rheumatic heart disease), compared with 33 (8.2%) in the control group (16 of 33 [48%] progressing to moderate or severe disease; risk difference, −7.5 percentage points; 95% confidence interval [CI], −10.2 to −4.7; p < 0.001). The number needed to receive prophylaxis to prevent one case of latent rheumatic heart disease progression was 13 (95% CI, 10-21). 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 5-17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. The authors concluded that further research is needed before the implementation of population-level screening can be recommended.

Perspective:

Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening can detect rheumatic heart disease at an early, latent stage. This prospective, randomized study from Uganda found that antibiotic prophylaxis with intramuscular penicillin G benzathine every 4 weeks for 2 years was associated with a substantial reduction compared to placebo in the risk of echocardiographic progression of latent rheumatic heart disease (risk difference, −7.5 percentage points; 95% CI, −10.2 to −4.7; p < 0.001), with the need to treat 13 children or adolescents to prevent disease progression in one. The high prevalence of moderate or severe disease at 2 years among those with progression underscores the potential clinical impact of pursuing broad efforts at screening and, if validated in additional studies, the use of secondary antibiotic prophylaxis for latent rheumatic heart disease.

Keywords: AHA Annual Scientific Sessions, AHA21, Anaphylaxis, Anti-Bacterial Agents, Antibiotic Prophylaxis, Diagnostic Imaging, Disease Progression, Echocardiography, Heart Valve Diseases, Pediatrics, Penicillin G Benzathine, Rheumatic Heart Disease, Secondary Prevention


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