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
Multi-Targeted Inhibition Of An Essential Tetrameric Enzyme From Drug -Resistant Streptococcus Pneumonie.
Funder
National Health and Medical Research Council
Funding Amount
$534,313.00
Summary
Streptococcus pneumoniae is an significant human pathogen which causes several diseases including pneumonia and meningitis. Treatment of infection involves the use of antibiotics such as penecillin, however, resistant strains are now emerging. This project will address the real need to develop new antibiotics targeting this organism. This is essentially a drug discovery project which exploits a novel means to target Streptococcus pneumoniae.
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.
Optimising Heart Disease Prevention And Management
Funder
National Health and Medical Research Council
Funding Amount
$4,647,175.00
Summary
As we become older and risk factors such as obesity become more common, our biggest contributor to death and disability, cardiovascular disease (including heart disease), will continue to exert an enormous burden on our health care system and society. We will extend our ground-breaking research on multidisciplinary teams to create new and innovative health care programs to optimise the prevention and management of new heart disease and chronic forms of heart disease.
Periodontal Disease And Chronic Kidney Disease Among Aboriginal Adults; An RCT
Funder
National Health and Medical Research Council
Funding Amount
$1,035,550.00
Summary
Chronic Kidney Disease is a growing public health concern in Australia, especially among Aboriginal populations. It is associated with progression to end stage kidney disease requiring dialysis, cardiovascular disease burden and high mortality. This study will use a randomised controlled trial design to determine if comprehensive periodontal therapy reduces progression of kidney disease among Aboriginal adults with chronic kidney disease residing in Central Australia.
The Burden And Risk Factors Of Depressive Disorders In Indigenous Australians: Implications For Early Detection And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
This Fellowship addresses the high rates of depression amongst Indigenous Australians. The proposed work will quantify the extent to which two major risk factors contribute to the burden of depression in this population and the burden avertable from interventions to modify these risk factors. Findings would inform resource allocation and health service delivery, and in doing so, present opportunities for improvements in the health of Indigenous Australians.
Regulation Of NOD Signalling By IAPs And RIP Kinases
Funder
National Health and Medical Research Council
Funding Amount
$643,172.00
Summary
Alterations in NOD signalling have been implicated in various human inflammatory diseases, particularly in Crohn’s disease and asthma. In this project we will identify new molecules that regulate NOD signalling and test the effect of drugs that inhibit known components of these pathways to determine their utility in treating inflammatory diseases.
Defining Epigenetic Predictors Of Long-term Outcomes Of Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$409,408.00
Summary
On average, those born premature do worse health-wise than those born at term. However, some do worse than others. Our aim is to identify these people at birth to better help doctors and parents to closely monitor their health. For this, we will be “reading the diary of pregnancy” in the molecules added to chromosomes in blood during pregnancy in young adults with will characterised states of health. We will analyse DNA from blood that we will extract from stored heel prick spots.
Restoration Of The Nigrostriatal Pathway In The Parkinsonian Brain
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Many obstacles exist for cell transplantation in Parkinson's disease; namely poor restoration of the host brain circuitry due to incorrect graft placement. This results in incomplete motor function and unwanted side effects. Through iterative studies we endeavor to restore this circuitry by placing grafts in the appropriate location and promoting their survival and growth-integrations. This will require: optimizing the donor tissue and exposure of the graft to growth stimulating factors.