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Enhancing Treatment Of Hepatitis C In Opioid Substitution Settings II (ETHOS II): A Partnership Project To Enhance Hepatitis C Care In Drug And Alcohol Clinics
Funder
National Health and Medical Research Council
Funding Amount
$1,265,716.00
Summary
This Partnership Project will evaluate novel strategies to enhance care for hepatitis C infection in drug and alcohol clinics. Based on a foundation of strong, existing partnerships, this project has considerable potential to facilitate the translation of research outcomes into policy and practice and facilitate the scale-up of hepatitis C care in drug and alcohol clinics in NSW and nationally.
Long Term Persistence Of HIV In The Liver And The Clinical Impact On HIV-HBV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$1,393,245.00
Summary
This grant will address a major question in HIV cure research - the role of the liver as an HIV reservoir and the impact of HIV persistence in HIV-infected patients on suppressive antiretroviral therapy (ART) on liver disease, in the setting of HIV-HBV co-infection. We will trial a novel intervention to reduce HIV infection of the liver that could potentially reduce chronic liver disease in this setting.
Fine Positioning And Effector Function Of T Cells Recruited To The HCV Infected Liver
Funder
National Health and Medical Research Council
Funding Amount
$321,973.00
Summary
The majority of patients who become infected with hepatitis C virus (HCV) are unable to mount an effective immune response and clear the virus and therefore develop lifelong (chronic) infection. The persistence of virus in the liver of patients with chronic infection results in the recruitment of significant numbers of immune cells, notably T cells, from the bloodstream into the liver where they are involved in both viral control (but not viral clearance) and liver injury. The level of tissue in ....The majority of patients who become infected with hepatitis C virus (HCV) are unable to mount an effective immune response and clear the virus and therefore develop lifelong (chronic) infection. The persistence of virus in the liver of patients with chronic infection results in the recruitment of significant numbers of immune cells, notably T cells, from the bloodstream into the liver where they are involved in both viral control (but not viral clearance) and liver injury. The level of tissue injury observed and the speed of disease progression may be linked to the type of T cells recruited, their function, and their position in the liver. The aims of this project are to determine the factors involved in the fine positioning of T cells in the liver and establish a relationship between T cell recruitment, function, and progression of HCV disease in the liver.Read moreRead less
Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients ....Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients with chronic infection are expected to die prematurely due to chronic liver disease or primary liver cancer. Interestingly, exposure to HBV can lead to either acute resolving or chronic HBV infection. Like chronic infections, acute infections involve spread of virus to virtually every hepatocyte, followed by rapid clearance of the virus mediated by the host immune response. Our immediate aim is to study the resolution of acute HBV infections to determine how the stable intracellular viral genome, covalently closed circular DNA (cccDNA), is cleared from the nucleus of infected hepatocytes. Our broad long-term aim is to develop new and effective treatments for chronic HBV infection based on a better understanding of how acute HBV infections are resolved by the host. Based on our previous work we believe that clearance of cccDNA requires hepatocyte death, together with compensatory proliferation of other infected hepatocytes. We will perform detailed studies in duck hepatitis B virus (DHBV) infected ducks to determine if hepatocyte death and compensatory proliferation are essential to clear the infection, or if mechanisms exist for clearance that do not involve cell destruction.Read moreRead less
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
Early Diagnosis And Prognosis Of Severe Dengue In Vietnamese Children
Funder
National Health and Medical Research Council
Funding Amount
$689,323.00
Summary
Dengue is a mosquito-borne viral infection. Tropical Australia has experienced multiple outbreaks of dengue in the last decade. This project, conducted in Ho Chi Minh City, Viet Nam, will define the accuracy of a rapid diagnostic test for the early diagnosis of severe dengue. In doing so, we will also derive an algorithm using simple laboratory and clinical findings that can help identify those patients at greatest risk of severe complications, with benefits for both patients and hospitals.
A Functional And Structural Approach To Understanding Leptospiral Host-pathogen Interactions
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Leptospirosis is a zoonosis of worldwide distribution caused by infection with pathogenic Leptospira. Infection occurs due to contact with water contaminated by urine of domestic animals. It occurs infrequently in Australia, but recent local surveillance data indicate hospitalisation rate of 56% with an average duration of 5.3 days. Through the combined approach of structural biology and functional microbiology we hope to understand how leptospira interacts with the human host.
Factors That Influence Disease Severity In Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$149,076.00
Summary
Tuberculosis (TB) is a major global health problem and is one of the leading causes of death from an infectious disease worldwide. The severity of disease that occurs with TB is dependent on many complex factors including the infected person’s immune system and factors related to the TB organism itself. This research will determine the key factors that cause severe disease in TB which will translate into improved care of TB patients and enhance further research in this field.
Integrons, Mobile Gene Cassettes And Pathogencity In Vibrio Cholerae
Funder
National Health and Medical Research Council
Funding Amount
$550,285.00
Summary
Bacteria are remarkably adaptive and evolve in ways that plants and animals do not. One of these ways is Lateral Gene Transfer or LGT, which is a process allowing bacterial cells to share genes. Such mobile genes can greatly influence the extent to which pathogenic bacteria can cause disease. One notable example is Vibrio cholerae where many strains can be benign but some can give rise to cholera pandemics. Here, we will investigate this phenomenon in this important bacterium.