Secondary Antibiotic Prophylaxis Reduces Rheumatic Heart Disease Progression

Researchers sought to determine whether secondary antibiotic prophylaxis could help prevent progression of latent rheumatic heart disease.

Secondary antibiotic prophylaxis was observed to reduce the risk for disease progression at 2 years among children and adolescents with latent rheumatic heart disease, according to a study published in The New England Journal of Medicine.

For the study, researchers conducted a randomized, controlled trial ( Identifier: NCT03346525) in children and adolescents (N=102,200) aged 5 to 17 years. All study participants were screened for latent rheumatic heart disease by echocardiogram at primary and secondary schools in Uganda between 2018 and 2020. Children with abnormal results (n=916) were randomly assigned to receive intramuscular penicillin G benzathine every 4 weeks for 2 years (n=458) or no intervention (n=458). Participants were assessed by echocardiogram at 2 years for evidence of disease progression.

The prophylaxis and control cohorts comprised children with a mean age of 12.6±2.8 and 12.5±2.9 years; 57.0% and 54.0% were girls; 80.2% and 82.9% had borderline rheumatic heart disease; 81.4% and 77.0% were in semipermanent housing; and the average number of persons living in their households was 7.9±3.5 and 7.9±3.2, respectively.

A total of 399 in the prophylaxis and 400 in the control cohort completed the trial. Among those who completed the trial, 99.1% of injections were administered and 98.8% were given in the acceptable window of time.

At 2 years, echocardiographic progression of latent rheumatic heart disease was observed among 0.8% of the prophylaxis and 8.2% of the control cohorts (risk difference, -7.5%; 95% CI, -10.2% to -4.7%; P <.001). Among those with progression, 100% of the prophylaxis and 48.5% of the control groups had progression to moderate or severe rheumatic heart disease.

Echocardiographic regression of latent rheumatic heart disease was observed among a similar proportion of the prophylaxis and control groups (48.9% vs 47.8%). Among those with regression, 94.0% had a normal echocardiogram at the 2-year follow-up.

Among the prophylaxis recipients, 64.6% had any adverse event including pain, limp, or swelling (51.5%); skin rash or hives (14.8%); redness, bruising, or bleeding (3.1%); or other (20.7%). A total of 6 events were grade 3 or 4.

This study found that secondary antibiotic prophylaxis significantly reduced the progression of latent rheumatic heart disease among children and adolescents.

“Although further research is needed to assess real-world implementation, population-based screening and initiation of prophylaxis may eventually prove to be integral components of the National Rheumatic Heart Disease action plans envisioned by the World Health Assembly in 2017 in a resolution on rheumatic heart disease,” the study authors noted.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Beaton A, Okello E, Rwebembera J, et al. Secondary antibiotic prophylaxis for latent rheumatic heart disease N Engl J Med. Published online November 13, 2021. doi:10.1056/NEJMoa2102074