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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
Key indicators of development in adolescent writing. The project aims to identify significant indicators of development in the writing of adolescents at various stages of secondary education. There are a number of students who struggle with the demands of secondary schooling because they have not developed control over the more abstract, technical, and metaphorical language required in written assignments and examinations. This study will map the development of those linguistic resources critica ....Key indicators of development in adolescent writing. The project aims to identify significant indicators of development in the writing of adolescents at various stages of secondary education. There are a number of students who struggle with the demands of secondary schooling because they have not developed control over the more abstract, technical, and metaphorical language required in written assignments and examinations. This study will map the development of those linguistic resources critical to success in secondary learning, drawing on and extending Halliday's functional theory of language. An understanding of typical patterns of development will enable teachers to productively intervene in those cases where students' academic progress is impeded.
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Comprehensive Clinical Tests Of Vestibular Function To Track Vestibular Compensation And Meniere’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$390,625.00
Summary
This Project will apply new, fast, safe, comprehensive, balance tests we have developed to measure the function of the balance receptors of the inner ear. We will track changes in balance function during disease and recovery in the many, and increasing, number of Australian patients with balance disorders. These tests will give us insight into changes in the inner ear associated with severe attacks of vertigo and why some patients recover so poorly after damage to inner ear balance receptors.
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
Studies On The Effects Of Endogenous And Exogenous Opioids In Modulating Exercise-induced Dyspnoea In People With Moderate / Severe Chronic Obstructive Pulmonary Disease (COPD). Two Double-blind Randomised, Placebo Controlled Trials.
Funder
National Health and Medical Research Council
Funding Amount
$197,086.00
Summary
There is evidence that morphine-like chemicals made by the body itself help reduce breathlessness. It is not clear whether this response is because of the effects of these morphine-like chemicals on the brain, in the lung or both. This study will help understand where these chemicals act to reduce breathlessness in people with emphysema during exercise. Subsequently, it will also help to understand whether small, regular doses of morphine safely further reduce breathlessness during exercise.
Cracking the code of snails to elucidate parasite disease transmission. In Australia, a disease caused by liver flukes causes major economic losses to livestock production. The role of Australian pond snails as intermediate hosts for this parasite is poorly understood. This project aims to explore the phylogeography, biology and genomics of these snails. It expects to create novel molecular resources for important snail species and verify their roles as key vectors of flatworm parasites. The cur ....Cracking the code of snails to elucidate parasite disease transmission. In Australia, a disease caused by liver flukes causes major economic losses to livestock production. The role of Australian pond snails as intermediate hosts for this parasite is poorly understood. This project aims to explore the phylogeography, biology and genomics of these snails. It expects to create novel molecular resources for important snail species and verify their roles as key vectors of flatworm parasites. The curation of genomic and transcriptomic data sets, and elucidation of snail–parasite interactions will underpin the development of environmental diagnostic tests and deliver a new generation of intervention strategies to reduce the burden of liver fluke disease through the control of their snail intermediate hosts.Read moreRead less
Exploring The Role Of Respiratory Virus Infections In Childhood Asthma Exacerbations
Funder
National Health and Medical Research Council
Funding Amount
$596,649.00
Summary
The PEAK study will explore the reasons children get worse asthma symptoms when they get colds. These reasons examined include the asthma medications taken (or not taken), allergies and exposure to allergens and the type of virus involved. The study follows the children over the whole school term and uses a new way to sample virus by collecting it in the breath, this is more comfortable than old methods and can be done at home.
Invasive fungal infections are a serious, escalating health issue. They cause severe disease with high death rates and are very costly to the health system. Current drugs often have suboptimal efficacy and cause side effects. New drugs are needed urgently. Many fungi, including the AIDS-related pathogen, Cryptococcus neoformans, secrete phospholipase B (Plbp) to facilitate infection. We will identify and investigate the Plbp secretion pathway as a novel anti-fungal drug target.