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Antibiotic prophylaxis for screen-detected latent rheumatic heart disease reduced progression of disease in children, the GOAL trial showed.

Echocardiographic progression was reduced to 0.8% at 2 years compared with 8.2% with no prophylaxis (P<0.001), reported Andrea Beaton, MD, of Cincinnati Children's Hospital Medical Center, at the American Heart Association virtual meeting. The findings were simultaneously published online in the .

"These are actually very exciting findings from global cardiovascular standpoint," commented Michael Honigberg MD, MPP, of Massachusetts General Hospital in Boston. "The magnitude of difference in the outcome is pretty striking."

The number needed to treat was 13 at 2 years, although the number needed to screen to find one person eligible for treatment was more than 100. More than 100,000 children, ages 5 to 17 years, were screened with echocardiography to find the 926 in the trial.

Screening for latent rheumatic heart disease under developed by the World Health Organization and the Council of Europe has been .

"However, these trial data alone are not sufficient justification for adoption of a screening policy," Beaton's group wrote.

Serious adverse events from prophylaxis with penicillin G benzathine (Bicillin L-A) every 4 weeks for 2 years occurred in one in 200 participants (two cases), including mild anaphylaxis with one in 10,000 injections (one case).

"Further study is needed to determine the efficacy, outcomes, and cost-effectiveness of alternative approaches, including secondary prophylaxis with oral penicillin and regular echocardiographic follow-up to monitor for progression in persons not receiving prophylaxis," Beaton's group concluded.

Among the practical challenges to a screening and prophylaxis program are the requirement for highly specialized echocardiographic interpretation and skilled staff to administer injections, they noted.

"Does this work in real life outside of the context of a very well-done clinical trial is another unanswered question," noted Honigberg, who was not involved with the trial. "Making sure you have basic equipment and training to perform screening echocardiography in resource-limited setting is not a trivial undertaking."

The trial screened students at primary and secondary schools in Gulu, Uganda, and surrounding districts from July 2018 through October 2020. Abnormal screening echocardiograms led to referral for clinical evaluation and detailed echocardiography for 3,327. Of those, 926 were confirmed to have latent rheumatic heart disease, which was not yet moderate or severe, and were eligible for the trial. After consensus panel review of the echo findings, 818 randomized participants comprised the modified intention-to-treat population.

"At scale, it is likely that health care personnel with less training would implement screening activities and prophylaxis administration, which could increase the likelihood of misdiagnosis and related adverse events, respectively," the researchers noted.

"Furthermore, retention in care of patients with rheumatic heart disease is critical to achieving adequate treatment adherence, and the highly successful strategies used in our trial (e.g., the use of peer groups and case managers, as well as reimbursement of travel expenses) would be challenging and expensive to implement at scale," they added. "Both of these issues could be compounded by the longer duration of clinical follow-up required (typically at least 5 years as compared with our 2-year research end point)."

Notably, echocardiographic regression was common, occurring in about half of both treatment groups without a significant difference between them. Fully 94.0% of these children had a normal echocardiogram at the end of the trial.

"Initial regression may not imply lifelong protection," Beaton's group wrote. "However, the high incidence of regression seen in this trial arouses the concern that if screening in children and adolescents were adopted, a proportion of those treated would not be expected to benefit."

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