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
Centre For Research Excellence In Malaria Elimination
Funder
National Health and Medical Research Council
Funding Amount
$2,470,291.00
Summary
The CRE will work to accelerate progress towards malaria elimination in our region, through Surveillance, to develop better ways to monitor malaria transmission and discover who is infected, and to track movement of malaria parasites and spread of drug resistance. Diagnosis, to develop and test new, more sensitive ways of detecting malaria. Treatment, to fast track development of new antimalarials, and improve access to ensure all infected people get highly effective drugs.
Surviving in a toad-colonised landscape: manipulating predator behaviour to reduce the impact of the cane toad invasion. Invasive species pose a major threat to biodiversity; and within Australia, cane toads are widely viewed as one of the biggest such problems. Vigorous attempts at toad control have failed to slow the invasion front, and toads are now entering the Kimberley region. If we can’t stop the toads, are there other ways to reduce the numbers of native predators killed by eating thes ....Surviving in a toad-colonised landscape: manipulating predator behaviour to reduce the impact of the cane toad invasion. Invasive species pose a major threat to biodiversity; and within Australia, cane toads are widely viewed as one of the biggest such problems. Vigorous attempts at toad control have failed to slow the invasion front, and toads are now entering the Kimberley region. If we can’t stop the toads, are there other ways to reduce the numbers of native predators killed by eating these poisonous invaders? Predators given nausea-inducing chemicals with their first toad meal rapidly learn to avoid cane toads as prey, enabling them to survive even where toads are present. The study will develop those methods for several vulnerable native species, including techniques for deployment of aversion-inducing baits in advance of the toad invasion.Read moreRead less
TELEPHONE COUNSELLING FOR MAINTENANCE OF PHYSICAL ACTIVITY, WEIGHT LOSS And GLYCAEMIC CONTROL IN TYPE 2 DIABETES
Funder
National Health and Medical Research Council
Funding Amount
$1,285,894.00
Summary
Regular exercise, a healthy diet and weight loss are key to managing type 2 diabetes, yet these are major challenges for most people with diabetes. This study will evaluate the impact of a telephone counselling program to assist people with type 2 diabetes to exercise, eat a healthy diet and lose weight, with the goal of helping them to sustain these changes over the long-term. It is expected that these lifestyle changes will also result in improved blood glucose control and quality of life.
A multispecies approach to managing feral animals in tropical savanna landscapes. Controlling invasive species is important for maintaining healthy landscapes. Often, multiple invasive species occupy a landscape and simultaneous management of them is required. Our innovative management tool will allow land managers to develop and implement control strategies for environmentally invasive species in Northern Australia and globally.
Cane toads in southern Australia: invasion dynamics and options for control. This project aims to investigate the spread of cane toads through southern Australia, an invasion front that has attracted far less research than the same species’ expansion through tropical regions, even though toads severely impact native wildlife in both areas. This project expects to generate new knowledge to determine why the rate of toad invasion is so much slower in New South Wales than in the tropics, and how be ....Cane toads in southern Australia: invasion dynamics and options for control. This project aims to investigate the spread of cane toads through southern Australia, an invasion front that has attracted far less research than the same species’ expansion through tropical regions, even though toads severely impact native wildlife in both areas. This project expects to generate new knowledge to determine why the rate of toad invasion is so much slower in New South Wales than in the tropics, and how best to modify newly-developed approaches to toad control to the conditions in southern Australia. Expected outcomes include predicting future trajectories of expansion, and identifying optimal approaches to toad control and impact mitigation. This should provide significant benefits for biodiversity conservation.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
Modelling and control of mosquito-borne diseases in Darwin using long-term monitoring. Management of mosquito populations is a high public health priority because these insects can spread diseases such as malaria, dengue, Ross River virus, Barmah Forest virus, Murray Valley encephalitis, Japanese encephalitis and Kunjin/West Nile virus. Our research into the effectiveness of mosquito control programs in Darwin is of immediate national relevance and priority given the need to Safeguard Australia ....Modelling and control of mosquito-borne diseases in Darwin using long-term monitoring. Management of mosquito populations is a high public health priority because these insects can spread diseases such as malaria, dengue, Ross River virus, Barmah Forest virus, Murray Valley encephalitis, Japanese encephalitis and Kunjin/West Nile virus. Our research into the effectiveness of mosquito control programs in Darwin is of immediate national relevance and priority given the need to Safeguard Australia from invasive diseases. There is an urgency to undertake our research because global environmental change and increasing movements of people (particularly military personnel) from overseas regions where these diseases are endemic is increasing the vulnerability of northern Australia to the (re)establishment of mosquito borne diseases.Read moreRead less