rheumatic fever Archives

Penicillin slows impacts of rheumatic heart disease in Ugandan children

November 15, 2021

“We know from previous studies that though it is not always well-documented, sub-Saharan Africa continues to have some of the highest numbers of people with rheumatic heart disease and the highest numbers of people dying from it,” said Craig Sable, M.D., associate chief of Cardiology at Children’s National Hospital and co-senior author of the study. “This study is the first large-scale clinical trial to show that early detection coupled with prophylactic treatment of penicillin is feasible and can prevent rheumatic heart disease from progressing and causing further damage to a child’s heart.”

Penicillin, a widely available and affordable antibiotic, may be one key to turning the tide on the deadly impacts of rheumatic heart disease (RHD) for children in developing nations. This according to the new findings of a large-scale, randomized controlled trial completed in Uganda and published in the New England Journal of Medicine.

The most devastating feature of RHD is severe heart valve damage that is caused by rheumatic fever — a condition that results from the body’s immune system trying to fight poorly treated, repeat infections from streptococcus bacteria, also known as strep throat. Though widely eradicated in nations such as the United States due to the swift detection and treatment of strep throat, rheumatic fever remains prevalent in developing countries including those in sub-Saharan Africa. Current estimates are that 40.5 million people worldwide live with rheumatic heart disease, and that it kills 306,000 people every year. Most of those affected are children, adolescents and young adults under age 25.

“We know from previous studies that though it is not always well-documented, sub-Saharan Africa continues to have some of the highest numbers of people with rheumatic heart disease and the highest numbers of people dying from it,” said Craig Sable, M.D., associate chief of Cardiology at Children’s National Hospital and co-senior author of the study. “This study is the first large-scale clinical trial to show that early detection coupled with prophylactic treatment of penicillin is feasible and can prevent rheumatic heart disease from progressing and causing further damage to a child’s heart.”

The study was led by an international panel of pediatric cardiac experts from institutions including Children’s National, Cincinnati Children’s Medical Center, the Uganda Heart Institute and Murdoch Children’s Research Institute in Melbourne, Australia.

“Our study found a cheap and easily available penicillin can prevent progression of latent rheumatic heart disease into more severe, irreversible valve damage that is commonly seen in our hospitals with little or no access to valve surgery,” said co-lead author Emmy Okello, M.D., chief of Cardiology at the Uganda Heart Institute.

To Andrea Beaton, M.D., associate professor of Cardiology at Cincinnati Children’s and co-lead author, this is the first contemporary randomized controlled trial in rheumatic heart disease. “The results are incredibly important on their own, but also demonstrate that high-quality clinical trials are feasible to address this neglected cardiovascular disease,” she said.

Beaton et al. named the trial Gwoko Adunu pa Lutino (GOAL), which means “protect the heart of a child.” The study enrolled 818 Ugandan children and adolescents ages 5 to 17 years old who were diagnosed with latent rheumatic heart disease to see if an injection of penicillin was effective at preventing their heart condition from worsening.

“There are many challenges with recruitment and retention of trial participants in areas like our study region in Uganda,” said Dr. Sable. “But it is critical to work together and overcome barriers, because we must study these treatments in the people most affected by the condition to understand how they, and others like them, may benefit from the findings.”

Of the 799 participants who completed the trial, the group receiving a prophylactic injection of penicillin (399 volunteers) had three participants show evidence of worsened rheumatic heart disease on repeat echocardiogram after two years. In contrast, 33 of the 400 volunteers in the control group, who received no treatment, showed similar progression on echocardiogram results.

Professor Andrew Steer, who is theme director of Infection and Immunity at Murdoch Children’s Research Institute in Melbourne and who served as senior author of the study, said screening for latent rheumatic heart disease was critical to stop progression because heart valve damage was largely untreatable. “Most patients are diagnosed when the disease is advanced and complications have already developed. If patients can be identified early, there is an opportunity for intervention and improved health outcomes.”

The results were shared in a special presentation at the American Heart Association’s Scientific Sessions on the same day that the findings were published in the New England Journal of Medicine.

The trial was supported by the Thrasher Pediatric Research Fund, Gift of Life International, Children’s National Hospital Foundation: Zachary Blumenfeld Fund, Children’s National Hospital Race for Every Child: Team Jocelyn, the Elias/Ginsburg Family, Wiley-Rein LLP, Phillips Foundation, AT&T Foundation, Heart Healers International, the Karp Family Foundation, Huron Philanthropies and the Cincinnati Children’s Hospital Heart Institute Research Core.

Learn more about the challenges of rheumatic heart disease in sub-Saharan Africa and other developing parts of the world through the Rheumatic Heart Disease microdocumentary series:

Acute rheumatic fever often goes undiagnosed in sub-Saharan Africa

August 20, 2021

Despite low numbers of documented acute rheumatic fever cases in sub-Saharan Africa, the region continues to show some of the highest numbers of people with, and dying from, rheumatic heart disease, the serious heart damage caused by repeat instances of rheumatic fever.

Despite low numbers of documented acute rheumatic fever cases in sub-Saharan Africa, the region continues to show some of the highest numbers of people with, and dying from, rheumatic heart disease, the serious heart damage caused by repeat instances of rheumatic fever. A population-based study in the Lancet Global Health collected evidence of acute rheumatic fever in two areas of Uganda, providing the first quantifiable evidence in decades that the disease continues to take a deadly toll on the region’s people.

“These findings matter. Access to life-saving heart surgery is only available to a very small fraction of the hundreds of thousands of patients in Africa who have irreversible heart damage from rheumatic heart disease,” says Craig Sable, M.D., associate chief of Cardiology at Children’s National Hospital and one of the senior authors of the study. “It’s time to focus upstream on capturing these conditions sooner, even in low-resource settings, so we can implement life-sustaining and cost-saving preventive treatments that can prevent further heart damage.”

The authors, who hail from Uganda and several institutions around the United States, including Children’s National and Cincinnati Children’s Hospital Medical Center, note this is the first study to use an active case-finding strategy for diagnosing acute rheumatic fever. They also note that raising awareness in the community and among its healthcare workers while also finding new ways to overcome some of the diagnostic challenges in these low-resource settings greatly improved diagnosis and treatment of the condition.

The study also described clinical characteristics of children ages 5 to 14 presenting with both definitive and possible acute rheumatic fever, providing further clinical data points to help healthcare workers in these communities differentiate between this common infection and some of the other frequently diagnosed conditions in the region.

“With this study, we can now confidently dismiss the myth that acute rheumatic fever is rare in Africa,” the authors write. “It exists at elevated rates in low-resource settings such as Uganda, even though routine diagnosis remains uncommon. While these incidence data have likely underestimated the cases of acute rheumatic fever in two districts in Uganda, they show that opportunity exists to improve community sensitization and healthcare worker training to increase awareness of acute rheumatic fever. Ultimately this leads to diagnosing more children with the condition before they develop rheumatic heart disease, so that they can be offered secondary prophylaxis with penicillin.”

Children with suspected acute rheumatic fever participated in this population-based study. Data was collected over 12 months in Lira district (January 2018 to December 2018) and over nine months (June 2019 to February 2020) in Mbarara district.

Follow-up of children diagnosed in this study will provide more data on the outcomes of acute rheumatic fever, including a better understanding of the risk for a child to develop rheumatic heart disease.

This work was funded by the American Heart Association Children’s Strategically Focused Research Network Grant #17SFRN33670607 and by DEL‐15‐011 to THRiVE‐2 and General Electric.

Learn more about the challenges of rheumatic heart disease in sub-Saharan Africa and other developing parts of the world through the Rheumatic Heart Disease microdocumentary series:

AHA doubles down on global support, prevention and research in rheumatic heart disease

December 8, 2020

Dr. Craig Sable and pediatric cardiology colleagues led the creation of a scientific statement and advocacy statement focused on eradicating RHD.

A pair of articles appearing in the American Heart Association’s (AHA) journal Circulation lays out a call to action for advocacy and scientific priorities crucial to the global eradication of rheumatic heart disease (RHD).

Cardiologists from Children’s National Hospital, and others who completed their pediatric cardiology fellowships at Children’s National before moving on to careers at other institutions, have been active proponents and advocates for these efforts for many years and led key research and clinical care efforts related to RHD in other countries of the world.

These cardiologists, including the associate chief of cardiology at Children’s National, Craig Sable, M.D., who previously served as chair of the AHA Council on Lifelong Congenital Heart Disease and Heart Health in the Young, also helped lead the creation of these new published statements.

Contemporary diagnosis and management of rheumatic heart disease: Implications for closing the gap

This clinical and research statement “seeks to examine the current state of-the-art recommendations and to identify gaps in diagnosis and treatment globally that can inform strategies for reducing disease burden.”

Key recommendations and related challenges were mapped out, including:

The need for echocardiography screening based on World Heart Federation echocardiographic criteria for identifying patients earlier, when prophylaxis is more likely to be effective. However, the authors note that several important questions need to be answered before this can translate into public policy.
The creation of population-based registries to effectively enable optimal care and secondary penicillin prophylaxis within available resources, though the team acknowledges that challenges with penicillin procurement and concern with adverse reactions in patients with advanced disease remain important issues.
Heart failure management, prevention, early diagnosis and treatment of endocarditis, oral anticoagulation for atrial fibrillation and prosthetic valves used as vital therapeutic adjuncts.
Multidisciplinary team management of health of women with unoperated and operated rheumatic heart disease before, during and after pregnancy is the best approach, though it is a significant challenge.
Percutaneous balloon mitral valvuloplasty should be considered for patients with isolated mitral stenosis.
Timely heart valve surgery, especially valve repair for rheumatic mitral regurgitation, can mitigate the progression to heart failure, disability and death. However, some of these procedures are not available to the vast majority of patients in endemic regions.

The recommendations made in the scientific statement form the foundation for the advocacy companion document.

The AHA’s call to action for reducing the global burden of rheumatic heart disease: a policy statement from the AHA

The advocacy statement outlines five key areas of support:

Professional healthcare worker education and training.
Technical support for the implementation of evidence-based strategies for rheumatic fever/RHD prevention.
Access to essential medications and technologies.
Research.
Advocacy to increase global awareness, resources and capacity for RHD control.

The authors write, “In bolstering the efforts of the American Heart Association to combat RHD, we hope to inspire others to collaborate, communicate and contribute.”

Speaking of the two statements as a whole, the authors of the scientific statement conclude that, “Ultimately, the combination of expanded treatment options, research and advocacy built on existing knowledge and science provides the best opportunity to address the burden of rheumatic heart disease.”

Read more about Children’s National Heart Institute’s research, education and clinical care in rheumatic heart disease.

Craig Sable, M.D., Associate Chief of the Division of Cardiology and Director of Echocardiography at Children’s National Health System, is working with hundreds of doctors to create a scalable solution to reduce the global burden of rheumatic heart disease (RHD). Dr. Sable received a lifetime achievement award — the 2018 Cardiovascular Disease in the Young (CVDY) Meritorious Achievement Award — from the American Heart Association for his work in Uganda.

Lifesaving heart surgeries for RHD complications in Uganda go on despite COVID-19

April 29, 2020

Patients and staff at the Uganda Heart Institute for RHD-related heart surgeries in Uganda, March 2020. These patients were originally scheduled as part of the cancelled medical mission, but UHI cardiovascular surgeon successfully managed these cases without the support of the mission doctors from the U.S.

In early March as countries around the globe began to wrestle with how best to tackle the spread of COVID-19, a group of doctors, nurses, researchers and other medical staff from Children’s National Hospital were wrestling with a distinct set of challenges: What to do about the 10 Ugandan children and adults who were currently scheduled for lifesaving heart surgery (and the countless others who would benefit from the continued training of the local heart surgery team) to correct complications of rheumatic heart disease (RHD) during an impending medical mission in the country.

Rheumatic heart disease impacts over 39 million people globally and causes nearly 300,000 deaths per year. RHD is the result of frequent, untreated streptococcal throat infections in childhood that ultimately cause the body’s immune system to repeatedly damage heart valves. It is completely preventable, yet the majority of the world’s children still live in impoverished and overcrowded conditions that predispose them to RHD. Most patients present with advanced valvular heart disease. For example, in Uganda, an RHD registry includes over 600 children with clinical RHD, of which nearly 40% die within four years and the median survival time from enrollment in the registry is only nine months. For these patients, heart surgery is the only viable solution for long-term survival and normal quality of life.

Patricia: 9-year-old from Gulu (northern Uganda), had mitral valve replacement and was doing well on a recent follow-up visit at her home.

The scheduled trip from Washington was part of a nearly 20-year partnership** between doctors, nurses, researchers and other medical staff in the United States, including Craig Sable, M.D., associate chief of cardiology, and and Pranava Sinha, M.D.,pediatric cardiovascular surgeon, at Children’s National Hospital in Washington, D.C., and the Uganda Heart Institute in Kampala, Uganda. The partnership aims to tackle RHD head-on. It provides surgical skill transfer, allows for treatment of more complex patients, and increases sustainable surgical capacity for Uganda’s RHD patients over time. As a result, over the last 15 years more than 1,000 children have received lifesaving heart surgery in Uganda, with the Uganda Heart Institute (UHI) performing one to two heart valve surgeries every two weeks over the last few years.

Jackline: 12-year-old from Gulu, had mitral valve repair and aortic valve replacement. Jackline and Patricia were diagnosed through one of our research programs and benefit from our novel telehealth program, which helps connect patients from remote parts of Uganda to specialists at UHI.

COVID-19 was changing the current plan, however. Travel between countries was limited, and the team from the U.S. wouldn’t have been permitted to leave the U.S. and return according to schedule. The trip, and the support teams who were scheduled to arrive to help with the surgeries, were cancelled. The U.S. team members who had already arrived in Uganda were sent home after helping their UHI colleagues set up and prepare for the surgeries as much as possible. Knowing that patients and families were counting on the surgery mission to go forward after waiting for months or years to have surgery for heart valve disease, UHI decided not to cancel the majority of the surgeries. Instead, for the first time, they planned and successfully completed five valve-related cases in a single week – several of them quite complex. The cardiologists and cardiac surgeons from Children’s National who were supposed to be in-country for these procedures were forced to limit their in person assistance to the set-up activities the week prior to surgery and telehealth consult during the procedures.

“It was hard not to be able to stay and work with the UHI team to help these families,” says Dr. Sable. “But we are so proud of the UHI team for meeting this challenge on their own. We knew they had the skills to perform at this volume and complexity. It’s a proud moment to see the team accomplish this major milestone, and to see the patients they cared for thrive.”

The patients are the most important outcome: The five who had successful open-heart surgery are all doing well, either on their way to recovery or already discharged to their communities, where they will, for the first time in memory, be able to play, exercise and go to school or work.

Longer term, this success demonstrates the UHI medical team’s ability to manage greater surgical capacity even when surgical missions from the U.S. resume. The partnership’s goal is to complete at least 1,000 annual operations (both pediatric and adult), with the majority being performed by the local team. Having this capacity available will mean the difference between life and death for many children and adults who have RHD in Uganda and the surrounding countries.

**This work is supported by the Edwards Life Sciences/Thoracic Surgery Foundation, the Emirates Airline Foundation, Samaritan’s Purse Children’s Heart Project and Gift of Life International.

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