Seeking progress in global diagnosis of rheumatic fever, researchers see 'full circle moment' for MUSC

It’s been 75 years since a pioneering MUSC surgeon performed a first-of-its-kind procedure on a patient suffering from heart disease caused by acute rhematic fever, the same condition that would tragically take his own life just months later.

Now, decades later, a team of MUSC researchers are working to improve the diagnosis of the same deadly condition in the hopes of saving countless lives around the world.

MUSC faculty, Russell Norris, Ph.D., and Richard Drake, Ph.D., are part of the Preventing Rheumatic Injury Biomarker Alliance, a five-year $8 million grant initiative to study patients with acute rheumatic fever (ARF), a potential complication found in individuals with untreated cases of Group A strep infections.

Funded by the Leducq Foundation, the grant supports sample collection from patients ages 5 to 18 in Brazil, India, Tanzania and Uganda. ARF is found most often in lower-to-middle-income countries where there is a lack of access to antibiotics that treat a strep infection.

Once collected overseas, the samples will be sent to researchers in Charleston, Boston and San Francisco to complete analyses in search of a biomarker to help to determine how the underlying strep bacterial infection generates an immune attack on the heart and other organs.

“When you get strep in the U.S., or other similar countries, you receive an antibiotic, and that’s it – you usually don’t have any further ramifications,” said Norris, a professor in the MUSC Department of Regenerative Medicine and Cell Biology. “We are all going to be infected with strep at some point, and, typically, you first get it as a kid. That’s why we focus our attention on the 5-to-18-year-old patients who can benefit the most because that’s an early, critical stage of the disease.”

The end goal of the initiative will be to use new diagnostic technology developed at MUSC to generate a point-of-care tool that can be used to improve diagnosis of patients with acute rheumatic fever. The purpose of the tool will be to help individuals to avoid progression to rheumatic heart disease, which is a thickening and stiffening of heart valves that can cause heart failure, stroke, pulmonary hypertension and mortality.

A deadly disease from a common infection

According to the U.S. Centers for Disease Control and Prevention (CDC), more than 470,000 new cases of ARF are diagnosed around the world each year. While ARF is caused by untreated cases of strep infection, not all cases progress to the condition. More than 300,000 deaths occur from rheumatic heart disease, or its complications, around the world each year, with the highest incidences of ARF occurring in children between the ages of 5 and 15, according to the CDC.

Waldrez Dutra, Ph.D., a professor in the Department of Morphology at the Federal University of Minas Gerais in Brazil, stressed just how critical this project could be in saving the lives of thousands of children in her home country and abroad.

“There is no test available to identify patients with early stages of this disease, which means treatment can be delayed and people may not get the help they need in time,” Dutra said. “A diagnostic test that can identify early stages of rheumatic heart disease would allow for early treatment and potentially save millions of lives while also improving the quality of life for those affected.”

The Smithy legacy at MUSC

As MUSC researchers try to improve detection of ARF to help patients to avoid progression to rheumatic heart disease, they are doing so on the same campus where one surgeon’s work led to one of the most significant advancements in the treatment of the same condition.

On Jan. 30, 1948, Horace Smithy Jr., M.D., an associate professor at the Medical College of South Carolina, completed the first successful mitral valve operation. The procedure featured the use of a valvulotome (click here to view a photo of the device), an instrument he’d designed that allowed him to cut away scar tissue from within heart valves, caused by ARF.

Smithy had been driven for years toward his research discovery, as he’d suffered his own childhood bout with ARF.

The invention of the valvulotome was significant to the field and cemented his legacy not only on campus but within the greater field of cardiovascular surgery, said Marc Katz, M.D., MUSC professor and chief of the Division of Cardiothoracic Surgery.

“The valvulotome is a device that you could insert into the heart, and it’s like a hole punch,” Katz said. “You’d punch through some of the leaflets to make the opening wider. He had good success with it.”

An illustration of a heart procedure using the valvulotome is shown.

News of the successful surgery made it into The New York Times on Feb. 10, 1948. According to the report, the patient, a 21-year-old woman from Canton, Ohio, had suffered two severe heart attacks in the three years since an initial bout with ARF. Hearing of Smithy’s research on animals in Charleston, the woman convinced him to conduct the procedure on her.

According to the article, “The patient had a scar in the heart valve which interfered with the flow of blood from one main heart chamber to the other. Dr. Smithy, thrusting into the heart a slender rod through which he manipulated a movable blade, cut the scarred valve. The surgeon could not see the valve and had to work the rod by feel.”

The article reported that Smithy completed the surgery in 90 minutes.

Tragically, Smithy was unable to find a surgeon to perform a similar procedure on him before his health quickly began to deteriorate. The 34-year-old pioneering physician passed away on Oct. 28, 1948.

Collaboration crossing continents

Now, decades later, Norris said it feels special to work with his colleagues to achieve scientific progress on the same disease Smithy was similarly devoted to.

“It’s an amazing full circle moment,” he said. “It makes you feel like there’s a reason why we’re a part of this program. It’s a very odd coincidence, but I think Horace would be pretty pleased if he knew what we were doing, and he’d be pretty proud of MUSC.”

While MUSC researchers will play substantial roles in the grant work, collaboration with colleagues around the world will be crucial in the overall success of the project.

Robert Levine, M.D., a professor of medicine at Harvard Medical School and lead project investigator, said the strength of the alliance, and what makes success possible, is built on the relationships between institutions.

“This network builds on global health relations between MUSC and Muhimbili National Hospital in Tanzania, between academic institutions in Boston and Brazil and between MUSC and Massachusetts General Hospital,” he said.

The project, Norris said, will also create outstanding opportunities for students to learn and contribute to the project – work that should have a lasting impact on all involved.

“This is my second Leducq grant I’ve been a part of, and it’s an opportunity unlike any other that establishes outstanding training, education and great patient interaction,” he said. “My grant was from 15 to 20 years ago, and I’m still working with those colleagues. It really provides a fertile ground to grow, and it’ll help accelerate discovery and leadership from students, fellows and faculty here at MUSC.”