A New Model For The Pathogenesis Of Rheumatic Fever: Superantigen Priming Of The Immune Response To Group A Streptococci
Funder
National Health and Medical Research Council
Funding Amount
$248,820.00
Summary
Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, c ....Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, control of this ARF will partly depend on new and better treatment and prevention strategies. To achieve these goals a deeper understanding of the immune mechanisms underlying this disease is urgently needed. It is known that ARF is caused by an abnormal immune response following streptococcal infection. This leads to the production of cells called T cells that attack the body s own tissues rather than the bacteria itself. This autoimmune disease is responsible for the heart damage that underlies ARF. It is believed that this proces only occurs when susceptible individuals are infected with specific rheumatogenic strains of streptococci. However there are a number of deficiencies in this model and it is proposed that there is an additional factor responsible for the abnormal immune response in ARF. This project will explore the possibility that bacterial toxins called superantigens are the critical missing factor , by studying the immune response in ARF. Superantigens are produced by certain streptococci and staphylococci, and are potent in minute quantities causing widespread activation of the immune system. They have been found to play an important role in a number of autoimmune diseases and the type of immune response found in ARF fits well with that expected if superantigens were involved. If superantigens play an important role in causing the abnormal immune response in ARF then a number of new avenues would open for the treatment and prevention of this disease.Read moreRead less
Mathematical Modelling Of Bacterial Carriage In Children
Funder
National Health and Medical Research Council
Funding Amount
$421,746.00
Summary
Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, child ....Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, children attending group child care are at high risk of ear infections. As many bacteria are resistant, antibiotics are now much less effective than when they were first introduced. Furthermore, there is a continuing load of infection for children in Aboriginal communities, in PNG and other developing countries, causing hearing loss, chronic respiratory problems, and heart disease and renal disease in later life. Using data previously collected from other studies in Indigenous communities and children in child care, mathematical models allow us to ask what if?, and answer important public health questions: 1. What environmental and public health measures can reduce the cycle of cross-infection in child-care and high-risk populations? 2. What coverage rates with pneumococcal vaccine will eliminate the vaccine-specific bacteria from child care centres, from the wider community, and from high risk populations? 3. Will infections with bacteria not covered by vaccine then increase? 4. Will the resistant bacteria tend to disappear if antibiotic use is restricted? 5. Under what circumstances will antibiotics help to control infection? The modelling will promote understanding of the social and health costs of bacterial infection in Aboriginal communities and child care and use educational scenarios to promote uptake of the most cost-effective and socially acceptable interventions.Read moreRead less
Estimating The Burden Of Group A Streptococcal Diseases In Victoria
Funder
National Health and Medical Research Council
Funding Amount
$386,760.00
Summary
Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal pop ....Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal population (e.g. rheumatic fever, kidney disease). Streptococcal sore throat remains one of the most common childhood infections, and severe group A streptococcal diseases are thought to be increasing in incidence in Australia. Yet, there are no accurate data on the incidence and costs of these or other GAS diseases in non-Aboriginal Australians, or in most other populations around the world. It is becoming more urgent to collect this data as numerous vaccine candidates are entering human trials, new approaches to the treatment of sore throat are emerging, and new strategies to treat and control the spread of severe disease are being developed. We propose a comprehensive strategy to measure the incidence, prevalence and costs of each group of GAS diseases. We will follow a group of families for 12 months to detect cases of GAS sore throat and skin sores and measure the impact on the family. We will survey children in schools to estimate the prevalence of skin sores. We will check hospital records to calculate the number of cases of rheumatic fever and kidney disease. And we will maintain surveillance for severe diseases by checking hospital and laboratory records. We will also check to see if family members of people with severe disease have the GAS bacterium in their throats. We will then compile these data into a comprehensive estimate of the burden of disease in Victoria, and estimate the cost-effectiveness of different treatment and prevention strategies.Read moreRead less
AusDiab 3: Emerging Risk Factors For And Long-term Incidence Of Cardio-metabolic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$2,616,397.00
Summary
This study will track 11,000 Australian adults over 12 years to determine how many develop diabetes, obesity, kidney and heart disease. The study will develop ways to best predict those who are going to develop these conditions before they have arisen, and will explore a range of novel risk factors to better understand these conditions.
CENTRE OF RESEARCH EXCELLENCE TO REDUCE INEQUALITY IN HEART DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$2,607,253.00
Summary
There is increasing recognition of a societal responsibility to provide effective and sustainable health care to the entire population and not just to selected parts. Indigenous and regional Australians are most affected by Australia's biggest killer - heart disease. In response, the CRE to Reduce Inequality in Heart Disease, is a national collaboration of researchers from a range of health disciplines. Together they aim to address this problem by developing sustainable and cost-effective health ....There is increasing recognition of a societal responsibility to provide effective and sustainable health care to the entire population and not just to selected parts. Indigenous and regional Australians are most affected by Australia's biggest killer - heart disease. In response, the CRE to Reduce Inequality in Heart Disease, is a national collaboration of researchers from a range of health disciplines. Together they aim to address this problem by developing sustainable and cost-effective health care services.Read moreRead less
A National Population-based Study Of Rheumatic Heart Disease In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$877,826.00
Summary
Whilst overall a rare disease, Indigenous peoples have disproportionately high rates of rheumatic heart disease (RHD). This study explores the prevalence and distribution of RHD in pregnancy in Australia and New Zealand. It details current management, diagnostic and referral process and risk factors. Key attributes of culturally safe models of care for RHD in pregnancy are explored, particularly as they relate to Indigenous women. Findings will inform policy, guidelines and education resources.
Chronic Kidney Disease In Indigenous Australians: Using Existing Data To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$303,014.00
Summary
Indigenous Australians not only suffer from a high burden of kidney disease, but also have poorer disease outcomes compared to non-Indigenous Australians. My research program is focused on improving outcomes for Indigenous Australians with kidney disease by using existing health care data to work out where and why their outcomes are poor within the health care system. It will enable us to identify ways to improve health care systems for Indigenous Australians.
The Management To Optimise Diabetes And MEtabolic Syndrome Risk Reduction Via Nurse-led Intervention (MODERN) Study
Funder
National Health and Medical Research Council
Funding Amount
$1,445,861.00
Summary
There is increasing recognition of society’s responsibility to provide effective and sustainable health care to the entire population and not just selected parts. This practical study will test the impact of a nurse-led, multidisciplinary prevention program to reduce the risk of future cardiovascular events in middle-aged individuals at a high risk of developing cardiovascular disease (CVD) living in regional Australia.
Improving Delivery Of Secondary Prophylaxis For Rheumatic Heart Disease: A Stepped-wedge, Community-randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,913,074.00
Summary
Rheumatic heart disease (RHD) is a major health problem in Indigenous communities. Continued progress in controlling RHD requires an understanding of how to improve delivery of regular injections of penicillin - secondary prophylaxis (SP). We will evaluate a systems-based approach to improving delivery of SP, using a stepped-wedge trial in 12 communities in NT and Qld. If successful, this model will provide a practical and transferable model.