Clinical Impact Of Clonal Pseudomonas Aeruginosa In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$547,238.00
Summary
In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on ....In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on the major bacterial problem, Pseudomonas aeruginosa. Several studies from Australia and the UK, including our own have shown that about 30% to 45% of patients share the same strain of Pseudomonas aeruginosa within a centre. We know that two dominant strains of Pseudomonas aeruginosa are found in CF centres on the eastern board of Australia. This is unexpected as this bacterium is usually acquired from the environment. The emergence of these clonal strains is causing increasing anxiety in the CF community. This study is designed to provide vitally needed information on the clinical implications of being infected by an clonal strain of Pseudomonas aeruginosa and the risk factors for the acquisition of an clonal strain. This new information will provide a rationale basis for the need for changes to infection control policies (including patient segregation), better outcome predictors for patients infected with clonal strain of Pseudomonas aeruginosa.Read moreRead less
Confirming The Burden Of Disease Associated With Dementia Using New Empirically Driven Australian Based Disability Rati
Funder
National Health and Medical Research Council
Funding Amount
$138,084.00
Summary
The amount of burden the population experiences as a result of individual diseases influences health policy. The Australian Burden of Disease project quantifies the relative burden associated with each disease. New estimates are to be released this year will outline the magnitude of burden associated with dementia now and estimate that for the year 2023. Although the projections use the best data available, three improvements to the methodology would improve the accuracy of the dementia burden e ....The amount of burden the population experiences as a result of individual diseases influences health policy. The Australian Burden of Disease project quantifies the relative burden associated with each disease. New estimates are to be released this year will outline the magnitude of burden associated with dementia now and estimate that for the year 2023. Although the projections use the best data available, three improvements to the methodology would improve the accuracy of the dementia burden estimates. First, the dementia calculations currently use a “disability weight” metric derived from a Dutch study. This is problematic in that the weights do not reflect an Australian experience of dementia, nor do they reflect the preferences of people closely affected by the disease (e.g. carers). Second, the dementia estimates do not include cases of mild cognitive impairment (considered a precursor state of dementia). Hence the dementia estimates may not estimate the full impact of dementia in Australia. Finally, there is no evidence that the method used by the Burden of Disease study to account for the impact of disease comorbidity adequately deals with the comorbidity associated with dementia. Consequently, there is need to develop a new and comprehensive set of disability weights for dementia that are Australian-based, include all stages of dementia severity and account for comorbidity. The proposed project aims to develop a new set of empirically derived Australian-based disability weights for dementia. The project will entail three studies. The first study will generate empirically based case vignettes that describe a range of dementia case scenarios. These descriptions will then be used in rating exercises (Study 2) to develop new disability weights. The second study involves Australian health practitioners, carers and lay persons reading case vignettes and completing health valuation rating exercises to generate new disability weights for dementia. The third study uses the new disability weights to re-calculate the burden of disease estimates for dementia. The new estimates will be compared to those reported by the 2007 Australian Burden of Disease project. In knowing the accuracy of the estimates, policy makers can use the burden data for dementia with confidence when engaging in service planning for the future.Read moreRead less
Novel Compounds For Use As Inhibitors Of Virulence Of Human Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interferin ....There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interfering with the way many pathogens regulate the production of virulence traits. Some bacteria are able to signal members of their population by the specific uptake and recognition, through a receptor protein, of chemical cues they secrete into the environment. Accumulation of these cues or signals triggers expression of the genes that code for the virulence traits. Moreover, one particular class of these signal response proteins has been identified in many pathogens and has been shown to regulate protease production and production of a protective extracellular slime layer called a capsule. If one or more of these traits can be blocked, then the virulence of the bacterium can be reduced. We have preliminary data which demonstrates that the algal compounds do in fact prevent the expression of virulence traits and thus should be useful as new agents for the treatment of disease. The causative agents of cholera and severe gatroenteritis, Vibrio cholerae and V. parahaemolyticus respectively, have one or the other of these virulence traits, but the pathogen Vibrio vulnificus has all three and therefore is an excellent model pathogen. We propose to explore the ability of the algal compounds to specifically shut down expression of virulence factors with a long term aim for the development of these compounds as novel antimicrobial therapies for the post-antibiotic era.Read moreRead less
Aerobic Exercise To Improve Cardiovascular And Neurological Health Outcomes In The Chronic Stroke Population
Funder
National Health and Medical Research Council
Funding Amount
$147,274.00
Summary
Physical activity is beneficial to people of all ages, to maintain heart health and brain function in relation to things like memory and complex thinking. Exercise is particularly important as we get older, especially after health problems such as heart attack or stroke, but it can be difficult to exercise safely at this time. This research project will develop an exercise program for individuals following stroke that is likely to improve fitness, heart and brain health and well-being.
Gender As A Determinant Of Health – Consolidating The Evidence Base. An Analysis Of Gender Equity And Health Outcomes In Lower Income Countries, With A Focus On Maternal And Neonatal Mortality
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Gender has been cited as a powerful influence on the extent and distribution of adverse health outcomes, especially maternal and neonatal mortality. It has been suggested that global health and development targets cannot be reached without adequate attention to gender equity. A strong evidence base is vital if gender is to be meaningfully considered in the post-2015 agenda. This thesis aims to extend this evidence base.
I conduct epidemiological research on illicit drug use and harm, with a particular focus upon surveillance of drug use disorders and morbidity in sentinel populations. My epidemiological research has focused particularly on the comorbidity between drug de
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
Fungi are increasingly causing life-threatening infections. Little is known about the mechanisms underlying these infections. We will compare the genomes of high and low virulent fungal strains to gain insides into the basis of these differences by using C. gattii as model of a globally highly pathogenic fungus. The findings will be generalized by comparing the obtained results with the genomes of other important pathogenic fungi to develop a scientific basis for better treatment strategies.
The fungal pathogen Cryptococcus neoformans is responsible for up to a million deaths annually, necessitating the development of novel antifungals. We have characterised the GTP biosynthesis enzyme IMP dehydrogenase, revealing it is critical for infection, and structural and functional analysis reveals routes to inhibitor specificity. In the proposed work will develop novel antifungal compounds that target this enzyme, as well as investigate related enzymes as potential future drug targets.