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
Approaches to combat AIDS and its causative agent, the human immunodeficiency virus HIV-1, have thus far proved ineffective. The proposed research program intends to investigate the nuclear import of two HIV-1 proteins which have central roles in HIV infection. We will apply our expertise in the area of the regulation of nuclear import of viral proteins, and build on our observations with respect to these proteins to attempt to establish the mechanistic basis of their nuclear import, and how thi ....Approaches to combat AIDS and its causative agent, the human immunodeficiency virus HIV-1, have thus far proved ineffective. The proposed research program intends to investigate the nuclear import of two HIV-1 proteins which have central roles in HIV infection. We will apply our expertise in the area of the regulation of nuclear import of viral proteins, and build on our observations with respect to these proteins to attempt to establish the mechanistic basis of their nuclear import, and how this differs from the conventional nuclear import pathways used by normal cellular proteins. We already have evidence that nuclear import of HIV-Tat is regulated in novel fashion by cellular factors, and intend, through determining its mechanistic basis, to be able to form the basis of a strategy to block this import pathway specifically, and thereby inhibit HIV replication. This may form the basis in the future of a new pharmaceutical approach to combat HIV-AIDS.Read moreRead less
Research & Training To Reduce Morbidity & Mortality From Malaria In Papua ( Indonesia)& Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$1,649,828.00
Summary
Malaria kills many thousands of people each year in Indonesia and PNG. This project will look at better ways to treat and prevent malaria. The team will examine whether using new combinations of drugs in clinics can reduce the amount of severe malaria seen in Papua. The team will examine whether giving people with severe malaria arginine, a naturally occurring amino acid, can increase molecules that may protect against severe malaria. Finally it will examine how lung damage occurs in people with ....Malaria kills many thousands of people each year in Indonesia and PNG. This project will look at better ways to treat and prevent malaria. The team will examine whether using new combinations of drugs in clinics can reduce the amount of severe malaria seen in Papua. The team will examine whether giving people with severe malaria arginine, a naturally occurring amino acid, can increase molecules that may protect against severe malaria. Finally it will examine how lung damage occurs in people with severe malaria and whether this can be predicted.Read moreRead less
PASSPORTS TO ADVANTAGE: Health And Capacity Building As A Basis For Social Integration
Funder
National Health and Medical Research Council
Funding Amount
$1,894,012.00
Summary
This project will conduct a randomised controlled trial of a post-release intervention for adult prisoners in Queensland. The findings of the study will inform the development of an evidence-based post-release intervention for prisoners in Australia and elsewhere, as well as providing an unprecedented insight into the post-release experiences of prisoners in Queensland.