Defining Targets For Antifungal Stewardship In Immunocompromised Patients: Optimising Care And Safety
Funder
National Health and Medical Research Council
Funding Amount
$108,902.00
Summary
Patients with impaired immune systems are at risk of serious fungal infections. Antifungal medicines used to prevent and treat these infections can be toxic and costly. This project aims to review current antifungal use and improvement activities in place in health services, assess prescriber knowledge, and to evaluate current doses of echinocandin antifungals used in liver failure patients. This project will identify ways to improve antifungal use needed for effective and safe prescribing.
Towards The Elimination Of Tuberculosis And Rheumatic Heart Disease In Northern Australia And Our Region
Funder
National Health and Medical Research Council
Funding Amount
$258,600.00
Summary
My research program addresses tuberculosis and rheumatic heart disease, which are leading challenges for Northern Australia and our region. Both are diseases caused by infections with long-term complications. They cause illness and death in young Aboriginal people and neighbouring Southeast Asian populations. There are many gaps in our ability to effectively detect and prevent these diseases. My research targets these gaps, from cutting-edge science to translation of guidelines into practice.
Determination Of Disease Specific Epitopes In Rheumatic Heart Disease In Australia
Funder
National Health and Medical Research Council
Funding Amount
$374,817.00
Summary
Rheumatic Fever and Rheumatic Heart Disease (RF-RHD) remain a significant cause of illness in Aboriginal communities in Australia. RF-RHD is a complication which follows infection with a specific bacterium. The purpose of this study is to compare the body's response and find out the patterns of antibody and immune cell reactivity to the bacterium and body proteins in RF-RHD patients and controls. It will also enable us to study the mechanisms that initiate the disease process.
Patient Tailored Immunity Transplant For The Prevention Of Viral Infections Post Haemopoietic Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$567,967.00
Summary
Blood or bone marrow transplantation can cure leukaemia and related blood disorders, but patients are susceptible to infections in the period early after transplant. Infectious complications remain a leading cause of death among allogeneic transplant recipients. Our research aims to prevent the onset of infection using novel cell therapies to rapidly restore the immune system thus preventing the problems associated with the transplant process.
There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this proj ....There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this project is to investigate the liver disease caused by HBV in co-infected patients and the development of antiviral resistance due to the long-term treatment with lamivudine. We will develop a data base to monitor virological, biochemical and histological parameters for each of these co-infected patients. We will collate all information on these patients that are attending these various centres. This data base will be essential for monitoring the disease in patients with a poor immune system versus patients with a normal immune system. The HBV virus isolated from these patients will be characterised by sequence analysis. The sequence analysis of these viruses will be compared before and after treatment to determine any resistance markers that have developed. These resistant markers will be copied into an infectious clone using specialised molecular techniques. Clones containing these resistant markers will be analysed in the laboratory to determine the antiviral sensitivity to lamivudine and a number of new drugs against hepatitis B virus. This information will be important in treating patients that are co-infected with HBV and HIV and have already developed resistance to lamivudine.Read moreRead less
Establishment Of A Bank Of Third Party T Cells To Treat Virus Infections (that Are Resistant Or Unsuitable For Other Forms Of Antibiotic Therapy) In Immunocompromised And Transplant Patients Across Australia
Funder
National Health and Medical Research Council
Funding Amount
$811,530.00
Summary
Bone marrow transplantation can cure cancers of the blood but patients are susceptible to viral infections due to ongoing immune deficiency. We have shown you can grow immune cells in the laboratory and transfer this immunity to transplant recipients. While effective, this has not been widely adopted due to the time, complexity and costs of the process. We aim to address these issues by providing a treatment option for patients with life threatening infections using immediately available “off th ....Bone marrow transplantation can cure cancers of the blood but patients are susceptible to viral infections due to ongoing immune deficiency. We have shown you can grow immune cells in the laboratory and transfer this immunity to transplant recipients. While effective, this has not been widely adopted due to the time, complexity and costs of the process. We aim to address these issues by providing a treatment option for patients with life threatening infections using immediately available “off the shelf” immune cells.Read moreRead less
Characterisation Of Immune Responses To Sarcoptes Scabiei Cysteine Proteases, Group 1 Allergen Homologues, In Scabies
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Scabies, a parasitic skin infestation by the 'itch' mite Sarcoptes scabiei, causes significant health problems for children and adults in many remote Aboriginal communities in Australia. Scabies is often the underlying cause of streptococcal skin infections which can cause serious complications such as kidney and heart disease. Although diagnosed scabies cases can be successfully treated, individuals have often already transmitted the disease to others prior to receiving therapy. A particularly ....Scabies, a parasitic skin infestation by the 'itch' mite Sarcoptes scabiei, causes significant health problems for children and adults in many remote Aboriginal communities in Australia. Scabies is often the underlying cause of streptococcal skin infections which can cause serious complications such as kidney and heart disease. Although diagnosed scabies cases can be successfully treated, individuals have often already transmitted the disease to others prior to receiving therapy. A particularly dreadful form of scabies, known as crusted scabies, can develop in a minority of people, in which mites multiply in their millions and the affected person develops severe crusting of the skin. This has resulted in death within 5 years for up to 50% of people with this form of scabies. Scabies mites are scientifically very similar to house dust mites, and they produce cross reactive proteins. Molecular studies in our laboratory have enabled the identification and cloning of a number of scabies molecules with considerable similarity to known house dust mite proteins that cause allergic disease. In this study we propose to focus on a group of scabies proteins with significant identity to the extensively studied Group 1 house dust mite allergens, reported to cause an immune response in 90% of mite allergic people. We propose to use these scabies mite molecules to characterise the immune response in ordinary scabies and compare it to the more severe and debilitating crusted form of the disease. Characterisation of the immune response in scabies will ultimately aid in the development of new treatment for crusted scabies based on immunotherapy. Studies will also investigate for any cross reactivity with the house dust mite group 1 molecules and enable the design of specific immunodiagnositics to distinguish house dust mite allergy from scabies infestation and thus facilitate early diagnosis of scabies carriers and better control of the infestation in endemic communities.Read moreRead less
The Clinical Value Of Serology And Molecular Tests For Diagnosing Invasive Aspergillosis In At-risk Hematology Patients
Funder
National Health and Medical Research Council
Funding Amount
$1,095,500.00
Summary
Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic t ....Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic tests are not good at detecting infection or often only detect the infection at advanced stages when treatment is ineffective. Because of the limitations of current diagnostic tests the current practice is to give empiric antifungal therapy (EAFT) early to treat Invasive Aspergillosis. However studies have demonstrated that this therapy has only resulted in a minor reduction in the mortality rates and it causes significant drug toxicity. It is a suboptimal treatment modality. New tests have been developed to diagnose Invasive Aspergillosis. These tests are for the detection of an Aspergillus protein in blood and for the detection of Aspergillus DNA in the blood. Available data suggests that these new tests are sensitive in the detection of Invasive Aspergillosis. Also other studies suggest that these new tests make an early diagnosis and seem to be able to monitor responses to treatment. However no study has been performed to date which demonstrates that the use of these tests can impact on important patient outcomes. This trial is designed to determine whether the use of the new tests to guide therapy will help improve treatment of Invasive Aspergillosis, reduce drug toxicity and reduce the death rate in the high-risk patients as compared with the current standard method of diagnosis and treatment with EAFT. If the trial is successful then this represents a significant advancement in the treatment and survival of leukaemic and bone marrow transplantation patients.Read moreRead less
Investigating The Molecular Basis Of Emerging Drug Resistance In Scabies Mites
Funder
National Health and Medical Research Council
Funding Amount
$516,000.00
Summary
Scabies is a disease of the skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. In remote Aboriginal communities in northern and central Australia up to 60% of children can be infected. Scabies causes intense itching of the skin, resulting in skin damage through scratching, and serious secondary bacterial infections leading to kidney and heart disease. Some remote communities in the NT are documented to have the highest rates of kidney and heart disease in the world. The location ....Scabies is a disease of the skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. In remote Aboriginal communities in northern and central Australia up to 60% of children can be infected. Scabies causes intense itching of the skin, resulting in skin damage through scratching, and serious secondary bacterial infections leading to kidney and heart disease. Some remote communities in the NT are documented to have the highest rates of kidney and heart disease in the world. The location of the Menzies School of Health Research in this region where scabies is endemic has enabled us to undertake a number of studies on the disease. Our world first molecular study using microsatellite markers demonstrated that scabies mites on people were genetically distinct from those on dogs. This had important implications in control programs in the communities. Additional work has focused on laboratory studies to monitor the sensitivity of mites to current treatments used in community control programs and for the treatment of crusted scabies, a very severe and debilitating form of the disease. We have reported evidence of increasing resistance of scabies mites to topical 5%permethrin and documented both in vitro and clinical evidence of resistance to oral ivermectin. We now seek support to extend this work to identify at the molecular level the mechanisms of resistance and use this knowledge to design a diagnostic test. This work has both local and global implications. Scabies is a significant disease of children primarily in many indigenous and third world communities, as well as associated with nursing homes and HIV infection. The tools developed in this project will enable the assessment of drug treatment failures and assist in the development of more sensitive methods for monitoring resistance in the community, including the potential for reversing it. This will avoid the current global problems of resistance observed in other organisms such as headlice.Read moreRead less