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
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
Bringing back Australia's lost woodland biodiversity: towards strategic multi-species reintroductions. Australia has the highest rate of mammal extinction of any continent on the planet. This has reduced biodiversity and compromised many important ecological processes. What is the best way to re-build depauperate mammal communities with multi-species reintroductions? What effects do multi-species reintroductions have on recipient ecosystems? This project aims to explore these questions by reintr ....Bringing back Australia's lost woodland biodiversity: towards strategic multi-species reintroductions. Australia has the highest rate of mammal extinction of any continent on the planet. This has reduced biodiversity and compromised many important ecological processes. What is the best way to re-build depauperate mammal communities with multi-species reintroductions? What effects do multi-species reintroductions have on recipient ecosystems? This project aims to explore these questions by reintroducing three mammal species to a critically endangered temperate woodland: a carnivore (the eastern quoll), an insectivore (yellow-footed antechinus), and a herbivore (the eastern chestnut mouse). Results from this sequenced multi-species reintroduction experiment will have broad applicability to ecosystem restoration in Australia and overseas.Read moreRead less
Integrating fire and predator management to conserve threatened species. This project aims to empower land managers to better conserve Australia’s threatened native animals by developing decision-support approaches that facilitate integrated management of threatening processes. The project will use a combination of novel predictive models, field experiments and data syntheses to assist land managers to better conserve Australia’s threatened native fauna. This project will benefit biodiversity co ....Integrating fire and predator management to conserve threatened species. This project aims to empower land managers to better conserve Australia’s threatened native animals by developing decision-support approaches that facilitate integrated management of threatening processes. The project will use a combination of novel predictive models, field experiments and data syntheses to assist land managers to better conserve Australia’s threatened native fauna. This project will benefit biodiversity conservation by enabling more effective allocation of limited conservation resources.Read moreRead less
Improving the Governance of Species Lists. The aim of this project is to develop a system of governance for the creation of taxonomic lists. This project expects to apply knowledge of how other science organizations govern themselves to the governance of taxonomic lists, estimate the costs of current inefficiencies and identify impediments to improvement. Expected outcomes of this project include a process for validating global lists of species. This should provide significant benefits, such as ....Improving the Governance of Species Lists. The aim of this project is to develop a system of governance for the creation of taxonomic lists. This project expects to apply knowledge of how other science organizations govern themselves to the governance of taxonomic lists, estimate the costs of current inefficiencies and identify impediments to improvement. Expected outcomes of this project include a process for validating global lists of species. This should provide significant benefits, such as single lists of species that can be adopted at any scale and are readily comparable across countries and applications. A single list will ensure threatened species and those of quarantine or health concern don’t fall through the cracks and cause problems.Read moreRead less
A landscape-scale experimental test of factors driving mammal declines in northern Australia. Australia has suffered the highest rate of modern mammal extinctions in the world. Foxes have been largely responsible for this extinction in southern Australia and probably also Central Australia. However the decline in mammals in northern Australia has occurred later than that in the south, and in the absence of foxes. We will adopt an experimental approach to determine the mechanisms driving mammal d ....A landscape-scale experimental test of factors driving mammal declines in northern Australia. Australia has suffered the highest rate of modern mammal extinctions in the world. Foxes have been largely responsible for this extinction in southern Australia and probably also Central Australia. However the decline in mammals in northern Australia has occurred later than that in the south, and in the absence of foxes. We will adopt an experimental approach to determine the mechanisms driving mammal declines and extinctions in northern Australia. Populations of brush-tail tree rats (Conilurus penicillatus) will be translocated to suitable habitat on mainland sites that experience different fire regimes and predation pressures.Read moreRead less
Reconnecting Warlpiri communities with cultural heritage materials. The projects aims to reconnect Warlpiri communities with past documentation and recordings of their cultural heritage. Centred in Yuendumu, the project expects to unpack the significance of past documentation of cultural heritage for present day Warlpiri people who live in vastly different social worlds from their forebears. Through collaborations with Warlpiri families, and Partner Organisation, Pintupi Anmatyerr Warlpiri (PAW) ....Reconnecting Warlpiri communities with cultural heritage materials. The projects aims to reconnect Warlpiri communities with past documentation and recordings of their cultural heritage. Centred in Yuendumu, the project expects to unpack the significance of past documentation of cultural heritage for present day Warlpiri people who live in vastly different social worlds from their forebears. Through collaborations with Warlpiri families, and Partner Organisation, Pintupi Anmatyerr Warlpiri (PAW) Media and Communications, the project will see the set up of activities to engage with these materials and the production of resources for use by future generations.Read moreRead less
Arresting declines of arboreal mammals in the tropical savannas. This project aims to evaluate the hypothesis that arboreal species are limited by the abundance of tree hollows, and that historical increases in the frequency of intense fires may be reducing hollow abundance. Northern Australia’s mammals are in severe decline, and arboreal species are among those that have fared worst. There is abundant anecdotal evidence that a decline in hollow abundance is the cause. Working with the Western A ....Arresting declines of arboreal mammals in the tropical savannas. This project aims to evaluate the hypothesis that arboreal species are limited by the abundance of tree hollows, and that historical increases in the frequency of intense fires may be reducing hollow abundance. Northern Australia’s mammals are in severe decline, and arboreal species are among those that have fared worst. There is abundant anecdotal evidence that a decline in hollow abundance is the cause. Working with the Western Australian Department of Parks and Wildlife in the Kimberley, the last region on the Australian mainland with an intact mammal fauna, the project aims to explore management options for increasing the availability of hollow denning sites for arboreal mammals (e.g. fire management, artificial nest boxes), and evaluate the likely impact of such actions on mammal populations across northern Australia.Read moreRead less
Conservation management of seed-eating birds in the tropical savannas. Biodiversity loss in the savannas indicates unsustainable management. This research will enhance our abilities to effectively manage Australia's tropical savannas, as well as contributing to several State and Territory, Commonwealth and international obligations to maintain biodiversity. Understanding the processes underlying current declines will also make the effects of future management or environment changes easier to pre ....Conservation management of seed-eating birds in the tropical savannas. Biodiversity loss in the savannas indicates unsustainable management. This research will enhance our abilities to effectively manage Australia's tropical savannas, as well as contributing to several State and Territory, Commonwealth and international obligations to maintain biodiversity. Understanding the processes underlying current declines will also make the effects of future management or environment changes easier to predict. Retaining threatened species can benefit remote and regional communities through tourism, and also through the extra employment required to implement the management prescriptions that will be developed from this research.Read moreRead less