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.

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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