By Dr Timothy Barnett, Senior Research Fellow, Telethon Kids Institute

Acute rheumatic fever (ARF) is an autoimmune disease triggered by group A Streptococcus (GAS) infection, with adolescents and young people most at risk. Recurrent episodes of ARF lead to cumulative heart valve damage and the development of rheumatic heart disease (RHD).

Despite often being referred to as a Third World disease, Australia’s Indigenous communities have some of the highest rates of ARF and RHD in the world. Children from these areas also experience a high burden of GAS skin infections, with an average of 45% of young people having impetigo, commonly known as school sores, at any given time.

GAS infection of the throat (strep throat) initiates the development of ARF, but it is not clear whether GAS skin infections can also cause it. Also, the exact mechanism that causes the autoimmunity of ARF is very poorly understood. This has meant that we still don’t have a diagnostic test for ARF, and no targeted treatments that improve long-term outcomes.

There is a need to better control rampant skin infections in remote communities, but the spectre of antibiotic resistance hangs over these programs. Environmental and social factors contributing to the disease also need to be addressed.

As part of the Improving Health Outcomes in the Tropical North: a multidisciplinary collaboration (HOT NORTH) being undertaken at the Telethon Kids Institute under the leadership of Prof Jonathan Carapetis, work is being done to improve methods for monitoring GAS antibiotic susceptibility.

Of particular focus is cotrimoxazole, increasingly used to treat GAS and Staphylococcus aureus skin infections in Northern Australia, and the subject of a clinical trial (led by Dr Asha Bowen, Telethon Kids Institute). This work includes the identification of cotrimoxazole-resistance genes, developing improved laboratory testing methods, and systems that will allow genetic testing for impetigo pathogens and antibiotic-resistance genes directly from clinical samples.

Unravelling immune system derangements that lead a GAS infection to become ARF is another collaborative project being undertaken. We are working to identify immune signatures of ARF that will then be used to develop a diagnostic test and/or possibly new immune-based therapies. By understanding the types of immune cells and GAS antigens that contribute to ARF, we may also be able to shed light on the significance of GAS skin disease as a trigger for ARF.

Hopefully the work will ultimately reduce the incidence of primary GAS infection, and subsequent development of ARF and RHD in children at risk. Improved molecular understanding of the link between GAS infection and ARF should also lead to better treatments and diagnostic tools, thereby reducing the health burden of ARF and RHD.

 

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