An entirely preventable condition leaving Indigenous children with severe and irreversible heart damage may be spread due to a reservoir of bacteria in the throat that causes no symptoms in the host, Australian researchers have found.
It is a discovery that will likely have implications for rheumatic heart disease (RHD) prevention and vaccine development, infectious diseases physicians say.
RHD is a chronic and severe disease affecting disadvantaged areas of low- and middle-income countries. Australia has one of the highest reported rates of RHD in the world, where it is only found in remote Indigenous communities plagued by social disadvantage.
In those communities, RHD overwhelmingly affects children, many of whom have endured open-heart surgery.
RHD is caused by infection with the highly contagious group A streptococcus bacterium, which causes the common “strep throat” and can also cause skin infections. Most people experience strep throat as children and receive fast treatment with antibiotics.
Yet Indigenous children living in remote communities may experience repeated, chronic infections with strep A due to overcrowding, poverty and difficulty accessing healthcare. These repeated, untreated infections can cause acute rheumatic fever, an inflammatory disease.
This fever can lead to the irreversible heart damage known as RHD. Without open-heart surgery to repair or replace the damaged heart valves, clots can form and sufferers may die from stroke or heart failure.
In a bid to understand why Australia has struggled to reduce rates of RHD, researchers led by the Doherty Institute in Melbourne analysed the genetic makeup of hundreds of strep A bacterial samples in a freezer, collected between 2003 and 2005 by Dr Malcolm MacDonald.
MacDonald visited Aboriginal households across three remote Northern Territory communities every four weeks, looking for strep A by taking swabs from the skin and throats of householders, including those with no symptoms.
“But what wasn’t available at that time was whole genome sequencing, which is what we’ve now done,” said Prof Steven Tong, an infectious diseases physician at the Doherty Institute.
“We’ve gone back to the freezers, pulled out all the isolates of the bacteria that Malcolm collected decades ago and looked at the whole DNA sequence of each of these germs.”
Researchers believe skin-to-skin transmission of strep A is an important factor in disease spread in Aboriginal communities, with overcrowded living conditions exacerbating this spread, so treating skin disease is a focus of prevention along with treating anyone with a sore throat.
But the genome sequencing revealed the strep A bacteria found in the throats of those who reported no symptoms was the same isolate as that found in people with skin infections and symptomatic disease.
Dr Michael Marks, an associate professor in infectious diseases at the London School of Hygiene & Tropical Medicine, said a “key question” with RHD has “been the extent to which transmission occurs between infections in the throat and the skin, and what is driving transmission overall in communities where this infection is a serious problem”.
He said the study by Tong and his peers revealed “both skin and throat infections appeared to lead to onward spread of the bacteria, but there were about twice as many infections seeming to be linked to a throat infection suggesting that these infections are playing a key role”.
“Importantly, these throat infections were asymptomatic, which suggests that if we only target individuals with symptoms of strep throat, then we will miss a lot of people who have infection and who can spread the bacteria to others,” Marks said.
In 2015–19, there were 1,325 new RHD diagnoses among Indigenous Australians, the Australian Institute of Health and Welfare reported, with more than half of those in people aged under 25. The disease killed 400 people in the same period.
Prof Andrew Steer, a paediatric infectious diseases physician at the Royal Children’s hospital in Melbourne, is working on a vaccine for strep A and said the findings “tell us that we need to measure asymptomatic throat colonisation of strep A in the vaccine trials”.
“As time has gone by, and as living conditions and access to medicine improved, the disease has shifted from being a global disease to being a disease in disadvantaged populations in low- and middle-income countries,” Steer said.
“And as the disease in the US, Europe and the eastern seaboard of Australia began to disappear, so did efforts around vaccine development,” he said.
“It’s only really now, I think partly thanks to efforts led by Australians, that there’s been a revived, renewed, rejuvenated effort to develop a vaccine for rheumatic heart disease.”
