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
The measurement of primary traits in second language oral proficiency in second language acquisition research. The proposed research will help to inform high-quality learning outcomes for international ESL (English as a Second Language) students and students who study Japanese or Spanish as a second language in Australian universities. Improved effectiveness in current second language teaching pedagogy will result from a deeper understanding of the role that the key language traits (syntactic co ....The measurement of primary traits in second language oral proficiency in second language acquisition research. The proposed research will help to inform high-quality learning outcomes for international ESL (English as a Second Language) students and students who study Japanese or Spanish as a second language in Australian universities. Improved effectiveness in current second language teaching pedagogy will result from a deeper understanding of the role that the key language traits (syntactic complexity, lexical range, accuracy and fluency) play in the attainment of advanced proficiency. Read moreRead less
Mechanisms Underlying Generation Of Febrile Seizures In Mouse Models Of Human Familial Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$304,559.00
Summary
Febrile Seizures (FS) affect 3% of children aged 0.5 - 6 yrs and have been proposed as an indicator of severe forms of adult generalized epilepsy. Mechanisms underlying FS generation are unknown although studies of Australian families suffering from epilepsy have linked 2 genes to FS. We have generated mice expressing these 2 genes. Aims and Outcomes: to investigate events triggering FS which will provide important insights into why FS occurs in children. (NB: CIA 2 yr career interruption)
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
Detecting language disorder in children with a language background other than English: the role of the Dynamic Assessment. 17.6% of Australia's culturally diverse population are born in non-English speaking countries. Recently, reports of unprecedented growth in the diagnosis of children with language disorders have emerged. There are difficulties in accurately identifying children at risk of language disorder. We hypothesize that some children with language backgrounds other than English (LBOTE ....Detecting language disorder in children with a language background other than English: the role of the Dynamic Assessment. 17.6% of Australia's culturally diverse population are born in non-English speaking countries. Recently, reports of unprecedented growth in the diagnosis of children with language disorders have emerged. There are difficulties in accurately identifying children at risk of language disorder. We hypothesize that some children with language backgrounds other than English (LBOTE) are mis-identified. If true, then scarce resources are being misdirected and inappropriately allocated, depriving children with true language disorder of support and intervention. The aim of this project is to determine the utility of the Dynamic Assessment to discriminate normal language learning from language learning difficulties in LBOTE children.
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Aboriginal-English speaking students' (mis)understanding of school literacy materials in Australian English. Aboriginal students have a right to quality education that gives them skills for full participation in Australian society. However, in the past the education system in Australia has largely failed to improve educational outcomes for Aboriginal students and has to a large extent failed to equip teachers of Aboriginal children with the relevant professional development that they need. This ....Aboriginal-English speaking students' (mis)understanding of school literacy materials in Australian English. Aboriginal students have a right to quality education that gives them skills for full participation in Australian society. However, in the past the education system in Australia has largely failed to improve educational outcomes for Aboriginal students and has to a large extent failed to equip teachers of Aboriginal children with the relevant professional development that they need. This project will directly focus on this issue of highest national priority and will make an attempt to explore Aboriginal-English speaking students' understanding of school materials. The results will be used in Aboriginal teacher education.Read moreRead less