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
Magnetic Resonance Methods For Automated, Non-invasive Diagnosis Of Focal Brain Infections
Funder
National Health and Medical Research Council
Funding Amount
$483,564.00
Summary
Brain lesions caused by infections, tumours and some other diseases, often cannot be distinguished from each other clinically or by neuro-radiology examinations. A brain biopsy is usually needed to make a definite diagnosis and may cause sequelae or not be possible if the lesion is in certain areas of the brain. Magnetic resonance imaging (MRI) has increased our ability to detect brain lesions but cannot unequivocally diagnose the disease process. Magnetic resonance spectroscopic (MRS) methods r ....Brain lesions caused by infections, tumours and some other diseases, often cannot be distinguished from each other clinically or by neuro-radiology examinations. A brain biopsy is usually needed to make a definite diagnosis and may cause sequelae or not be possible if the lesion is in certain areas of the brain. Magnetic resonance imaging (MRI) has increased our ability to detect brain lesions but cannot unequivocally diagnose the disease process. Magnetic resonance spectroscopic (MRS) methods report on the chemical composition of lesions and can provide a simultaneous picture of the location of the lesion and the pathology of the disease process. Brain biopsies may therefore be avoided in a significant number of cases where drainage or decompression of lesions are not needed as part of therapy. Identification of specific fingerprints for the different diseases will provide a rapid, robust, automated diagnosis, which will expedite management decisions and improve patient outcomes. It should also be possible to monitor the efficacy of drug treatments using MRS methods. Each of these outcomes would constitute a major medical advance.Read moreRead less
How Do Glycosaminoglycans Promote The Propagation Of Prions?
Funder
National Health and Medical Research Council
Funding Amount
$512,270.00
Summary
The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major c ....The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major component of purified prions is an abnormal disease associated form of the host encoded prion protein. Understanding how the disease associated form of the prion protein is generated and how host-derived cofactors contribute to its formation will help in our understanding of the infectious nature of these diseases and in the development of effective therapeutic and prophylactic strategies. Glycosaminoglycans are host-derived components of the extracellular matrix that are associated with prion protein plaques found in the brain tissue of patients with prion diseases. Glycosaminoglycans are believed to influence the transmission of prions and the ongoing propagation of infectivity. In this study the importance of glycosaminoglycans in the formation of the disease associated prion protein and the generation of infectivity will be investigated using both cell-free and cell-based models of prion propagation. The understanding gained from this study will be used to develop a high throughput assay that can be used to detect prion infection prior to the development of clinical disease and within a time frame whereby therapeutic intervention may be effective.Read moreRead less
Infrared Spectroscopic Imaging In The Diagnosis Of Cervical Cancer
Funder
National Health and Medical Research Council
Funding Amount
$291,600.00
Summary
In Victoria alone around 500000 Pap smears a year are examined for evidence of cancer of the cervix or conditions that may lead to cancer. This is a time consuming, labour intensive and costly process with a relatively high failure rate. A number of alternative techniques have been explored in the last decade with a view to providing a diagnostic technique that is free of human error, more reliable than the Pap method and easily used. An alternative technique based on using infrared light to pro ....In Victoria alone around 500000 Pap smears a year are examined for evidence of cancer of the cervix or conditions that may lead to cancer. This is a time consuming, labour intensive and costly process with a relatively high failure rate. A number of alternative techniques have been explored in the last decade with a view to providing a diagnostic technique that is free of human error, more reliable than the Pap method and easily used. An alternative technique based on using infrared light to probe smears shows promise in providing such an easily automated reliable method. We, and others have spent a number of years exploring this technique and have solved a number of the problems associated with it. Based on our work in the field and the work of others we now wish to develop a methodology using an infrared micro-imaging spectrometer combined with multivariate statistics that can be used to diagnose cervical cancer and the conditions that lead to cervical cancer.Read moreRead less
Detailed Investigation Of The Humoral Immune Response To HCV To Identify Diagnostic And Prognostic Serological Markers
Funder
National Health and Medical Research Council
Funding Amount
$387,466.00
Summary
The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the d ....The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the different stages of infection. The expected outcomes of this study include the identification of a marker of recent Hepatitis C infection. This will permit accurate epidemiological monitoring of Hepatitis C, better design of programs to control the spread, trace outbreaks and manage treatment programs. The identification of a marker capable of predicting the clinical outcome of infection would be invaluable to clinicians, because following acute infection with Hepatitis C, 20 to 30% of individuals will resolve their infection without the need for therapeutic intervention. The information obtained in this study will also lead to a better interpretation of diagnostic laboratory findings, improving our ability to provide clear and accurate reports to blood donors and consequently enhance the Australian blood supply in terms of safety and donor retention.Read moreRead less
Methods For Evaluating The Therapeutic Impact Of Diagnostic Tests - Development Of Guidelines
Funder
National Health and Medical Research Council
Funding Amount
$132,325.00
Summary
New diagnostic tests are frequently adopted in clinical practice without any evidence that they improve patient outcomes. This project will produce the first guidelines about the role and optimal design of studies assessing the impact of a new test on therapeutic decisions for conclusions about its clinical value. This work will inform researchers and clinicians to improve evidence-based diagnostic practice and promote the more efficient use of limited health care resources.
Improving Immunoassays For The Diagnosis Of Latent Tuberculosis Infection In Children
Funder
National Health and Medical Research Council
Funding Amount
$489,006.00
Summary
WHO highlights the urgent need for new tests for tuberculosis (TB). Diagnosis of latent TB infection (LTBI) is vital in children to prevent them developing active TB. A tuberculin skin test has long been used but is not always accurate. More accurate blood tests (immunoassays) have recently been developed which improve the diagnosis of LTBI in adults. However, we have shown that these assays do not work well in children. We aim to improve the performance of immunoassays for diagnosing LTBI in ch ....WHO highlights the urgent need for new tests for tuberculosis (TB). Diagnosis of latent TB infection (LTBI) is vital in children to prevent them developing active TB. A tuberculin skin test has long been used but is not always accurate. More accurate blood tests (immunoassays) have recently been developed which improve the diagnosis of LTBI in adults. However, we have shown that these assays do not work well in children. We aim to improve the performance of immunoassays for diagnosing LTBI in children.Read moreRead less
Identification Of Biomarkers For Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$607,489.00
Summary
Alzheimer's disease is the most common age-related neurodegenerative disease, and the most common cause of dementia. It is estimated that 212,000 Australians suffer from dementia and this will rise to approximately 730,000 by 2050. Currently there are no definitive diagnostic methods for AD. The research described in this application seeks to identify and validate a range of biomarkers identified in the blood of patients that would be suitable to use for diagnostic purposes.