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Penicillin reduces pediatric rheumatic heart disease progression

Written by | 21 Dec 2021 | Paediatrics

Treatment with penicillin significantly reduces the risk of underlying rheumatic heart disease progression in children and adolescents, researchers reported on Nov. 12, 2021 in the NEJM/New England Journal of Medicine.

“This randomized trial investigated the effectiveness of secondary antibiotic prophylaxis in modifying the natural history of latent rheumatic heart disease. We observed a significant reduction in the risk of disease progression in the prophylaxis group,” the authors said.

As background the authors noted that rheumatic heart disease affects more than 40.5 million people globally and results in 306,000 deaths annually. Echocardiographic screening can detect rheumatic heart disease at an early, latent stage.

The investigators conducted a randomized trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years-old who had been diagnosed with latent rheumatic heart disease.

The subjects were randomized to receive either injections of penicillin G benzathine every 4 weeks for 2 years or no prophylaxis.

All subjects underwent echocardiography at baseline and at 2 years after randomization.

The primary endpoint was echocardiographic progression of latent rheumatic heart disease at 2 years.

Of the 102,200 children and adolescents who received screening echocardiograms, 3,327 were initially assessed as having latent rheumatic heart disease. Subsequently, 926 of these children and adolescents received a definitive diagnosis based on confirmatory echocardiography. They were determined to be eligible for the trial.

Consent or assent for participation was provided for 916 of these subjects.

Secondary review of the confirmatory echocardiograms obtained at enrollment led to the exclusion of 98 subjects (10.7%) owing to reclassification (77 as normal, 15 as alternative diagnosis, and 6 as moderate or severe disease).

The remaining 818 subjects (409 in each group) were included in the intention-to-treat analysis, and 799 (97.7%) completed the trial.

The researchers reported that 3 (0.8 per cent) subjects who received penicillin showed latent rheumatic heart disease progression, compared to 33 (8.3 per cent) who didn’t receive penicillin, a statistically significant difference (P<0.001).

Investigator Daniel Engelman, MD, Clinician Scientist Fellow at the Murdoch Children’s Research Institute (MCRI),Melbourne, Australia, said the results showed a significant reduction in disease development and was larger than what had been predicated. “The results suggest that for every 13 children with latent disease who receive treatment for two years, one child will be prevented from developing more severe disease. As a preventative strategy for a severe, chronic disease, this is a very important finding,”

Author and MCRI Professor Andrew Steer added, “Currently, most patients are diagnosed when the disease is advanced, and complications have already developed. This late diagnosis is associated with a high death rate at a young age, in part due to the missed opportunity to benefit from preventative antibiotic treatment. If patients can be identified early, there is an opportunity for intervention and improved health outcomes.”

The authors concluded, “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.”

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