In a randomized controlled trial of close to 1,000 Ugandan children and youth with latent rheumatic heart disease (RHD), those who received monthly injections of penicillin G benzathine for 2 years had less disease progression than those who did not.
RHD, a valvular heart disease caused by rheumatic fever that develops after untreated Streptococcus pyogenes infection, is the most common acquired cardiovascular disease among children and young adults.
“It is clear that secondary antibiotic prophylaxis can improve outcomes for children with echo-detected rheumatic RHD,” co–lead author of the study, Andrea Z. Beaton, MD, said in an interview.
“There is huge potential here, but we are not quite ready to advocate for this strategy as a broad public health approach,” said Dr. Beaton, a pediatric cardiologist at Cincinnati Children’s Hospital Medical Center.
“We need to understand more the practical translation of this strategy to a low-resourced public health system at scale, improve [penicillin G benzathine] supply, and improve community and health care worker knowledge of this disease.”
Dr. Beaton presented the findings at the American Heart Association scientific sessions, and the study was simultaneously published in the New England Journal of Medicine on Nov. 13, 2021.
The GOAL trial – or the Gwoko Adunu pa Lutino trial, meaning “protect the heart of a child” – screened 102,200 children and adolescents aged 5-17. Of these kids and teenagers, 926 (0.9%) were diagnosed with latent RHD based on a confirmatory electrocardiogram.
“For now, I would say, if you are screening, then kids found to have latent RHD should be put on prophylaxis,” Dr. Beaton said.
“I think this is also a powerful call for more research [severely lacking in RHD],” to improve risk stratification, determine how to implement screening and prophylaxis programs, and develop new and better approaches for RHD prevention and care.
“This essential trial partially addresses the clinical equipoise that has developed regarding penicillin administration in latent RHD,” said Gabriele Rossi, MD, MPH, who was not involved with this research.
It showed that, out of the final 818 participants included in the modified intention-to-treat analysis, a total of 3 (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, compared with 33 participants (8.2%) in the control group (risk difference, −7.5 percentage points; 95% confidence interval, −10.2 to −4.7; P < .001).
“This is a significant difference,” Dr. Rossi, from Médecins Sans Frontières (Doctors Without Borders), Brussels, said in an interview, noting that, however, it is not known what happens after 2 years.
The authors estimated that 13 children or adolescents with latent rheumatic heart disease would need to be treated to prevent disease progression in one person at 2 years, which is “acceptable,” he continued.
However, “screening, diagnosis, clinical follow-up, treatment, and program management [would] require substantial strengthening of health systems and the workforce, which is still far from being realizable in many African and low-income country settings,” Dr. Rossi noted.
Related study in Italy
Previously, Dr. Rossi and colleagues conducted a trial, published in 2019, that showed it was feasible to screen for asymptomatic RHD among refugee/migrant children and youths in Rome.
From February 2016 to January 2018, they screened more than 650 refugee/migrant children and adolescents who were younger than 18. They came largely from Egypt (65%) but also from 22 other countries and were often unaccompanied or with just one parent.
The number needed to screen was 5 to identify a child/youth with borderline RHD and around 40 to identify a child/youth with definite RHD.
Dr. Rossi noted that local resurgences of RHD have also been also documented in high-income countries such as Europe, Australia, New Zealand, Canada, and the United States, often among disadvantaged indigenous people, as described in a 2018 Letter to the Editor in the New England Journal of Medicine.
Dr. Beaton noted that a review of 10-year data (2008-2018) from 22 U.S. pediatric institutions showed that in the United States the prevalence of RHD “is higher in immigrant children from RHD endemic areas, but because of total numbers, more RHD cases than not are domestic.” Children living in more deprived communities are at risk for more severe disease, and the burden in U.S. territories is also quite high.