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
Alcoholic Chronic Pancreatitis: Induction, Progression And Reversal
Funder
National Health and Medical Research Council
Funding Amount
$632,211.00
Summary
Pancreatitis (inflammation of the pancreas) is a serious complication of alcohol abuse. Patients suffer from severe and often intractable abdominal pain, maldigestion and diabetes, We have recently shown that gut toxins (endotoxins) may act as a trigger factor for pancreatitis in alcoholics. The proposed project aims to characterise the effects of gut toxins on the pancreas during alcohol abuse so as to identify pathways that may be therapeutically targeted to prevent or retard the disease.
A Randomised Trial To Control Sexually Transmitted Infections In Remote Aboriginal Communities.
Funder
National Health and Medical Research Council
Funding Amount
$1,847,403.00
Summary
This project will trial strategies for attaining clinical best practice in sexual health with an overall objective of reducing the high rates of sexually transmitted infection in remote Aboriginal communities in central and northern Australia. The trial will take place in 21 communities of which seven will be randomly assigned in each of the three years of the trial. This trial will determine whether strengthening primary health services can reduce the level of these infections.