Penicillin for the heart

A new study has found that regular, affordable antibiotic treatment significantly reduced the risk of underlying rheumatic heart disease progression in children and adolescents.

Based in Uganda and undertaken by a multinational team that includes the Murdoch Children’s Research Institute (MCRI), in Melbourne, the research also shows that early screening is critical in preventing serious rheumatic heart disease progression and death in young children.

“Internationally it’s estimated that there are around 42 million people affected by rheumatic heart disease, and anywhere between 300,000 and 350,000 deaths a year,” says Professor Andrew Steer, director of MCRI’s infection and immunity research team. “The majority of those deaths are premature deaths, very often people in their 20s, and women more than men.

“So the terrible kind of thing we see is women who become pregnant, whose heart has to work for themselves and their baby, and they can become very sick. Premature mortality of women is a real characteristic of this disease.”

Steer says the disease starts as a strep throat. The patient’s immune system successfully fights the bacteria in the throat, but then it “gets a bit confused”.

“We think that this is what we call cross-reactive response – the immune system, which has made the bacteria go away, starts fighting different parts of the body, which causes rheumatic fever. That’s characterised by fever, sore joints, maybe a rash and it attacks the heart – the saying is that it licks the joints but bites the heart.

“The effect on the heart is that the heart valves can then develop into rheumatic heart disease, which can become a devastating, long-standing chronic illness.”

Rheumatic heart disease is considered a disease of poverty and disadvantage, yet Australia has some of the highest rates in the world, where the disease disproportionately affects Indigenous Australians, and children aged between five and 14 years most likely to get rheumatic fever.

“It’s a little bit hard to put an absolute figure on [incidence in Indigenous Australia],” says Steer. “But some of the figures that I’ve seen suggest up to 1% of Indigenous children being affected by rheumatic heart disease.”

Research highlights:

• An international study has found a regular antibiotic treatment significantly reduced the risk of underlying rheumatic heart disease progression in Ugandan children and adolescents
• The trial showed 0.8 per cent of participants who received regular injections of penicillin for two years progressed to serious rheumatic heart disease, compared to 8.3 per cent who received no treatment  
• It is estimated that 13 children with latent rheumatic heart disease would need to be treated with antibiotics to prevent one case of disease progression two years later
• The researchers stated the findings showed early screening would help to prevent serious rheumatic heart disease progression and death in young children

The trial involved 818 Ugandan children aged 5–17 years with latent rheumatic heart disease. All underwent echocardiography screening, where ultrasound waves produce images of the heart, at the start and again at the end of the trial. The participants either received four-weekly injections of penicillin for two years, or no treatment.

Study co-author Associate Professor Andrea Beaton, a paediatric cardiologist at Cincinnati Children’s Hospital Medical Center, US, says that until this study it was unknown if antibiotics were effective at preventing the progression of latent rheumatic heart disease.

“We know that from some old studies that penicillin prophylaxis – so you get an injection of long-lasting penicillin every 28 days, which is usually given in the bum – is the standard treatment to prevent progression in rheumatic heart disease,” Steer says. “The idea is you’ve then got penicillin in the body, which prevents you getting another sore throat due to strep A, which prevents you getting another bout of rheumatic fever, which can make your rheumatic heart disease progress.

“So we know that works for more moderate to severe rheumatic heart disease, but we didn’t know if it works for this echocardiogram-detected mild rheumatic heart disease. That was the really big, pivotal question to answer.”

The findings from the screenings, published in the New England Journal of Medicine, reported just three (0.8 per cent) participants who received penicillin experienced latent rheumatic heart disease progression, compared to 33 (8.3 per cent) who didn’t receive the treatment.

Steer’s co-author and MCRI colleague Dr Daniel Engelman says the results showed a significant reduction in disease development and was more substantial than what was 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,” he says. “As a preventative strategy for a severe, chronic disease, this is a very important finding.”

Steer says the study and results are “highly relevant to Australia”.

“Rheumatic heart disease is a real sign of the gap in health and health outcomes for Indigenous people in Australia,” he says. “You know, we really shouldn’t have rheumatic heart disease in our Indigenous population. So it’s important to look at all the different ways that we could mitigate the disease. And one of them would be through a screening program.”

Steer describes the incidence of rheumatic heart disease in the general Australian population as “very uncommon”.

The study team now have funding from the Thrasher Foundation – which part-funded the Uganda trial – for a project they’ve named Goalpost, which will follow up on the Ugandan children over the next 2–5 years to see if their heart disease normalises or progresses.

“And we’re [also] designing a study, which we’re calling Goalie, where we hope to compare oral penicillin with the intramuscular penicillin,” says Steer. “In [the Uganda] study, we used injections of penicillin every 28 days, which worked well – that’s what the trials show. But getting injections is painful. There are side effects. There are issues also for the healthcare system and for families travelling into the health care centres. So we want to know if it could be just daily oral penicillin.”

The study leader in Uganda, cardiologist Dr Emmy Okello of the Uganda Heart Institute, says the Ugandan government should strengthen programs that promote screening of rheumatic heart disease and the availability of penicillin.

“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,” Okello says.