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Enterovirus 71 In The Asia-Pacific Region: Reverse Genetic Approaches To Virus Surveillance And Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$690,833.00
Summary
In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop ....In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop a genetically defined, live attenuated vaccine strain. Candidate vaccine strains will be tested for their effectiveness in both cell culture-based and animal models.Read moreRead less
Sensitive, Rapid And Accurate Detection Of The Emergence Of Neuraminidase Inhibitor Resistance By Real-time PCR, LCR And
Funder
National Health and Medical Research Council
Funding Amount
$118,875.00
Summary
An influenza pandemic causing by highly pathogenic H5N1 virus may occur in the near future. As a vaccine for H5N1 will not be available in the foreseeable months, antiviral drugs are the only possible choice for prophylaxis and treatment. Currently only two drugs have been clinically proven to be effective against H5N1 strain and the emergence of drug resistant in H5N1 influenza virus has been reported which may significantly hamper the treatment. Understanding and monitoring the emergence of th ....An influenza pandemic causing by highly pathogenic H5N1 virus may occur in the near future. As a vaccine for H5N1 will not be available in the foreseeable months, antiviral drugs are the only possible choice for prophylaxis and treatment. Currently only two drugs have been clinically proven to be effective against H5N1 strain and the emergence of drug resistant in H5N1 influenza virus has been reported which may significantly hamper the treatment. Understanding and monitoring the emergence of these drug resistant strains during local spreading will be critical in managing an H5N1 influenza pandemic in Australia. In the proposed project, we will develop important diagnostic tools using our world leading Rolling Circle Amplification (RCA) technology for the monitoring of the development and possible transmission of drug resistant influenza strains. Upon finishing the project, at lease three sensitive diagnostic methods will be developed for the detection of the emergence of drug resistance at the very early stage.Read moreRead less
Assessment Of Development Of Resistance To Neuraminidase Inhibitors In A (H5N1) Influenza Viruses Using A Ferret Model
Funder
National Health and Medical Research Council
Funding Amount
$165,546.00
Summary
The neuraminidase (NA) inhibitors are considered the most effective anti-influenza drugs available for both prevention and treatment of influenza virus infection including A(H5N1) viruses. The drugs are effective against all subtypes of influenza A, making them ideal for use in the early months of a pandemic prior to an appropriate vaccine being produced. As a result many countries around the world, including Australia, have stockpiled these drugs (mainly Tamiflu) as part of their pandemic prepa ....The neuraminidase (NA) inhibitors are considered the most effective anti-influenza drugs available for both prevention and treatment of influenza virus infection including A(H5N1) viruses. The drugs are effective against all subtypes of influenza A, making them ideal for use in the early months of a pandemic prior to an appropriate vaccine being produced. As a result many countries around the world, including Australia, have stockpiled these drugs (mainly Tamiflu) as part of their pandemic preparedness plans. However, of concern is the increasing number of recent reports of a higher than expected level of resistance in epidemic influenza being generated against these drugs. A recent isolation of an H5N1 virus from a Vietnamese girl highlights that these viruses can also be resistant to Tamiflu. Within Australia, Tamiflu will be a critical weapon against the initial wave of an influenza pandemic, therefore it is vital that more is known about the propensity of the H5N1 virus to generate resistance, and possibly make these drugs clinically less effective. The aim of the project is to determine the levels, mode and type of resistance that may occur when ferrets are experimentally infected with HP A(H5N1) virus and then treated with NA inhibitors drugs such as Tamiflu. In the event of resistant viruses being isolated following drug pressure from Tamiflu, the strains will then be tested for their sensitivity to the other NA inhibitor drugs Relenza (zanamivir) or the peramivir (a third currently unlicensed NA inhibitor). The results from this cross resistance work will allow strategies to be put into place regarding the administration of an alternative NA inhibitor in the event of a pandemic virus acquiring particular NA mutations which may for example result in Tamiflu resistance. To determine the relative human risk of a NA inhibitor resistant A(H5N1) virus, studies to determine how infectious or transmissible the viruses are would be performed on all resistant strains isolated. NA inhibitor resistant strains demonstrate varying degrees of transmissibility and fitness, therefore it would be beneficial to classify this for any strains generated from this study so as to be in a better position to understand the public health implications if a particular resistant strain was to arise.Read moreRead less
Screening Agents Active Against The Late-stage Inflammatory Cytokines For Activity Against Influenza Disease
Funder
National Health and Medical Research Council
Funding Amount
$241,409.00
Summary
Infection with a virulent influenza virus that the body has never encountered before, particularly H5N1, sends the immune system into overdrive, and causes a massive release of proteins (inflammatory cytokines), known as a cytokine storm, that in and of itself leads to death. The object of this research is to screen, in a mouse influenza model, agents known to prevent this occurring and antagonise it once it has occurred. This will be done with and without Tamiflu, a standard anti-influenza drug ....Infection with a virulent influenza virus that the body has never encountered before, particularly H5N1, sends the immune system into overdrive, and causes a massive release of proteins (inflammatory cytokines), known as a cytokine storm, that in and of itself leads to death. The object of this research is to screen, in a mouse influenza model, agents known to prevent this occurring and antagonise it once it has occurred. This will be done with and without Tamiflu, a standard anti-influenza drug.Read moreRead less
Optimising Current Therapeutic Approaches To Schizophrenia: The OPTiMiSE Consortium
Funder
National Health and Medical Research Council
Funding Amount
$1,016,659.00
Summary
Despite modern treatments advances (medications and psychological treatments), the prognosis of schizophrenia has only improved marginally and is individually variable. The OPTiMiSE Consortium, consisting of leading experts in schizophrenia research across Europe and a group in Australia, will commence a 5-year research program world-first in scale and scope. We will investigate the biological markers related to treatment response in over 1000 individuals with recent-onset schizophrenia. Schizop ....Despite modern treatments advances (medications and psychological treatments), the prognosis of schizophrenia has only improved marginally and is individually variable. The OPTiMiSE Consortium, consisting of leading experts in schizophrenia research across Europe and a group in Australia, will commence a 5-year research program world-first in scale and scope. We will investigate the biological markers related to treatment response in over 1000 individuals with recent-onset schizophrenia. Schizophrenia is a chronic disease and despite modern medication and psychological treatments the outcome is highly variable and often poor. The Melbourne Neuropsychiatry Centre is part of the European based OPTiMiSE Consortium, the largest ever research program evaluating why individuals with schizophrenia vary in response to different medications. We will examine what characteristics predict which drugs are most helpful to 120 individuals with first episode schizophreniaRead moreRead less
Injecting Drug Users: Social Networks And Molecular Epidemiology Of The Hepatitis C Virus
Funder
National Health and Medical Research Council
Funding Amount
$543,868.00
Summary
The hepatitis C virus (HCV) continues to spread among injecting drug users (IDUs) in Australia at a very high rate, despite success in preventing the spread of HIV in the same groups; the complete reasons for this remain unclear. There is an urgent need for the HCV epidemic among IDUs to be contained. To do so, we must better understand the ways in which it is spreading among IDUs. Much is known about risk behaviours of individual IDUs and how they contribute to HCV transmission; much less is kn ....The hepatitis C virus (HCV) continues to spread among injecting drug users (IDUs) in Australia at a very high rate, despite success in preventing the spread of HIV in the same groups; the complete reasons for this remain unclear. There is an urgent need for the HCV epidemic among IDUs to be contained. To do so, we must better understand the ways in which it is spreading among IDUs. Much is known about risk behaviours of individual IDUs and how they contribute to HCV transmission; much less is known about how these behaviours are modified by the influence of the IDUs peer group, especially their immediate and intimate social networks. Despite its importance in influencing attitudes and behaviours, and therefore HCV transmission, this has never been studied in Australia, nor, in relation to HCV, in the world. We hope that by studying social and risk networks of IDUs we shall discover new ways in which control of the HCV epidemic can be achieved in Australia. We intend to do this among two groups of young IDUs, one of Vietnamese ethnicity, located in the one suburb of Melbourne. By using field techniques for gathering information (ethnography), and sophisticated analytic techniques to understand how these networks are formed and influence behaviours, we hope to be able to identify interventions which work at the level of the social group rather than the individual in bringing about the behaviour change necessary to prevent HCV transmission. To ensure that the risk networks we describe are as influential as they appear, and to discover more about the variability of HCV, we will also be investigating the relationship between the various strains of HCV in members of the IDU networks, particularly as another measure of the connectedness of networks and network members. This will be done using sophisticated genetic analysis of the HCV obtained from network members by blood test.Read moreRead less
Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment an ....Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment and assessment of a cohort of 1500 postmenopausal women with either low or high bone mineral density from pre-existing population cohorts in Australia. A genomewide association study will then be performed on these cases. Associated genes in different datasets will then be investigated further in our cohort, and high-density SNP mapping performed to identify true associated variants. These studies should identify most genetic variants associated with BMD variation and low trauma fracture in the general community, allowing development of diagnostic-disease predictive genetic tests, and informing development of novel therapeutic agents for osteoporosis.Read moreRead less
Molecular Epidemiology Of Infection In Aboriginal Communities
Funder
National Health and Medical Research Council
Funding Amount
$149,103.00
Summary
Destructive diseases of the gum tissue are known to be profoundly affected by modifying factors including systemic diseases such as diabetes, socio-economic conditions and the lack of effective control of microbial accumulation at the gum margin. This investigation will examine the hypothesis that a limited number of pathogenic bacterial strains, defined by quantitative molecular probe analysis, persist in or re-infect individuals to maintain a high disease burden in the presence of adverse modi ....Destructive diseases of the gum tissue are known to be profoundly affected by modifying factors including systemic diseases such as diabetes, socio-economic conditions and the lack of effective control of microbial accumulation at the gum margin. This investigation will examine the hypothesis that a limited number of pathogenic bacterial strains, defined by quantitative molecular probe analysis, persist in or re-infect individuals to maintain a high disease burden in the presence of adverse modifying factors that prevail in isolated, disadvantaged Aboriginal communities.Read moreRead less
Novel, High-throutyput Platform For Rapid Identification, Quantintation, Differential Diagnosis, And Resistance Testing
Funder
National Health and Medical Research Council
Funding Amount
$333,362.00
Summary
This proposal utilizes a newly invented process (multiplex tandem polymerase chain reaction, MT-PCR) to measure multiple (up to 100) genetic targets (eg RNA or DNA) in one sample. A range of different virus and bacterial genes can be detected, including those which make the influenza virus different (eg H1N1 or H5N1) and allow it to bypass vaccine immunity or resist drug therapy (due to neuraminidase inhibitor resistance). We will simultaneously target infections which are influenza-like (ILI) o ....This proposal utilizes a newly invented process (multiplex tandem polymerase chain reaction, MT-PCR) to measure multiple (up to 100) genetic targets (eg RNA or DNA) in one sample. A range of different virus and bacterial genes can be detected, including those which make the influenza virus different (eg H1N1 or H5N1) and allow it to bypass vaccine immunity or resist drug therapy (due to neuraminidase inhibitor resistance). We will simultaneously target infections which are influenza-like (ILI) or which might make influenza infection worse (eg staphylococcal pneumonia) as well as their resistance genes (eg MRSA). The test is rapid and automated and includes a specimen processing (DNA and RNA extraction) function that is being developed in parallel. We expect to be able to conduct high-throughput screening of multiple samples for a limited number of targets or conduct multiple tests on fewer specimens, simply by adjusting assay configuration. Measurement of the rise and fall in concentrations of influenza virus in infected persons will allow us to understand when they are no longer infectious to others, to predict when they are getting better or worse, and allow us to better understand the pattern of illness in people who are immunized against influenza or on drug therapy, or are in some other special category (eg immune compromise due to organ transplantation). While this will be able to be rolled out by our industry partners in the event of an influenza pandemic, it does not require an outbreak for successful development, and has value well beyond influenza diagnosis.Read moreRead less