New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
Mechanisms Of Infection Triggered Renal Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$413,900.00
Summary
Kidney disease, including glomerulonephritis, is an important cause of ill-health in Australia. Some forms of kidney inflammation are linked to infection, but we don�t understand why. This project explores products from bacteria, particularly S.aureus, to work out how bacterial infection affects a form of kidney inflammation - ANCA-associated glomerulonephritis. It will establish how infection related signals activate local and immune cells, and define links between infection and the disease.
Advancement Of A Personalised Approach To Minimising Infective Complications In Cancer Care
Funder
National Health and Medical Research Council
Funding Amount
$265,138.00
Summary
Managing infections in patients with cancer have become more difficult and unpredictable because of new generation cancer therapies. Measuring the response of the immune system (immune profiling) will allow us to predict which patients will develop infection so that action such as vaccination can be taken to reduce their risk. This program will refine immune profiling to personalise infection care for cancer patients and to introduce it into hospital practice.
A Randomised Placebo-controlled Trial Of Antibiotics To Prevent Urinary Tract Infection In Children
Funder
National Health and Medical Research Council
Funding Amount
$735,000.00
Summary
This study is needed to determine whether a common clinical practice long-term antibiotic treatment for children following urinary tract infection (UTI) - is safe and effective in preventing further UTI and if so, whether all appropriate children are being treated. UTI will affect about 10% of Australian children by high school age (88,000 children per year). Because UTI may damage the kidneys, the management priority for children with UTI has been prevention of further infection. Currently this ....This study is needed to determine whether a common clinical practice long-term antibiotic treatment for children following urinary tract infection (UTI) - is safe and effective in preventing further UTI and if so, whether all appropriate children are being treated. UTI will affect about 10% of Australian children by high school age (88,000 children per year). Because UTI may damage the kidneys, the management priority for children with UTI has been prevention of further infection. Currently this means the identification of children thought to be most at risk of recurrent UTI by renal tract imaging. Those found to have reflux of urine from the bladder to the kidney (present in about 30% of those with UTI) are then placed on antibiotics fro 2-5 years. Unfortunately there has never been a properly designed trial to test whether antibiotics do really prevent UTI and if so, whether children with reflux are the appropriate and only group requiring treatment. Long term antibiotics may in fact do more harm than good because of side effects like skin, bowel and blood problems and because resistant bacteria may develop. The design of this study involves the random allocation of placebo or antibiotic (cotrimoxazole, the usual antibiotic given in this case) to about 800 children after their first symptomatic UTI. These children are treated and followed for one year to determine the rate of futher UTI in both groups. Any difference in outcome between the two groups of children will be because of the antibiotic treatment. This study may prove long-term antibiotics are ineffective and therefore should not be routinely used. In this case investigation of children to detect vesicoureteric reflux would serve little purpose and should be abandoned. Alternatively antibiotic treatment may be shown as effective treatment for preventing further UTI and in this case the study will clearly identify those children who will benefit.Read moreRead less
The Molecular Basis Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$16,230,996.00
Summary
Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as ....Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as novel drugs. These are urgently needed to reduce death and illness due to bacterial infectious diseases in the 21st century. 11Read moreRead less
This Centre of Research Excellence will translate the best available evidence to improve cancer outcomes through better management of infections in cancer patients, a rapidly growing group. We will establish new research networks to detect emerging multi resistant infections, develop guidelines on how to manage them, implement locally successful programs that have been shown to save lives nationally and validate new practice changing immune, bioinformatics and diagnostic technologies.
THE IMMUNOLOGICAL LEGACY OF OBESITY ON VIRAL PATHOGENESIS
Funder
National Health and Medical Research Council
Funding Amount
$652,275.00
Summary
Obesity is a key risk factor for severe viral infections. Our preliminary data suggest that in mice this susceptibility is not reduced by weight loss. In this grant we will investigate a) the mechanisms driving the legacy effect of obesity on antiviral immunity b) whether or not we can reverse this legacy effect by treatment with the drug MCC950 and c) the antiviral response of overweight children and adults who have and haven't recently lost weight.
Attenuating Severe Infections In Chronic Inflammatory Diseases Through Modulation Of Transforming Growth Factor-β Activity
Funder
National Health and Medical Research Council
Funding Amount
$611,793.00
Summary
Asthma and chronic obstructive pulmonary disease (COPD) are characterised by enhanced TGF? expression, which is accompanied by susceptibility to recurrent viral and bacterial infections. Such infections exacerbate lung inflammation in these patients, generally requiring emergency department treatment. This project proposes to clarify the therapeutic potential of TGF? inhibitors to reduce the impact of viral infections in patients with COPD and asthma.
Activation And Inhibition Of The Plasminogen/Plasmin System
Funder
National Health and Medical Research Council
Funding Amount
$800,663.00
Summary
Plasmin is crucial enzyme present in blood plasma that functions in clot dissolution, inflammation, tissue remodeling, and wound healing. We aim to study how this enzyme system is controlled, by studying its interaction with receptors, co-factors and inhibitors. The information we gain will help drive the development of new generation therapeutics for the fine control of plasmin function in clotting disease, bleeding and inflammation.