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
Long-term Implications And Outcomes Of Anti Hepatitis B Virus (HBV) Treatment In HIV-HBV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$293,931.00
Summary
Chronic hepatitis B (HBV) infection may cause serious liver disease in some people, including liver failure or liver cancer. Being infected with both HBV and HIV increases the chances of these complications occurring and the rate they develop. The optimal long term management of HIV-HBV co-infection remains unclear; and the effects of antiretroviral therapy on liver disease progression outcome is unknown in the setting of HIV-HBV co-infection.
A Prospective, Randomised, Double-blind Trial Of Extended- Versus Bolus-infusion ?-lactam Therapy In Infective Exacerbations Of Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$148,431.00
Summary
I am an infectious diseases physician focused on the most effective way to use antibiotics to treat infections. People with cystic fibrosis often get lung infections and the bacteria that causes this, Pseudomonas aeruginosa, can be difficult to treat. I will be investigating whether infusing antibiotics over a prolonged period of time is more effective than standard therapy in treatment of Pseudomonas aeruginosa lung infections in patients with cystic fibrosis.
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.
Understanding And Preventing Airborne Transmission Of Infectious Respiratory Aerosols
Funder
National Health and Medical Research Council
Funding Amount
$393,894.00
Summary
This project aims to significantly advance our understanding of how infectious bacteria are transmitted through the air, and what basic control measures are most effective at preventing this. This research is focused on persons with cystic fibrosis (CF), as they may be particularly susceptible to such transmission, but our results will also help us better understand how other infections are spread through the air. This is especially important given the recent global influenza pandemic.
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
Genetic Dissection Of Biofilm Development By Non-typeable Haemophilus Influenzae
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
The bacterial pathogen non-typeable Haemophilus influenzae (NTHi) is a common cause of chronic infections of the middle ear and of the airways of patients suffering cystic fibrosis, or chronic obstructive pulmonary disease (COPD). These infections are associated with bacterial biofilms that are significantly resistant to both antibiotics and immune defences. This project aims to characterise the process of NTHi biofilm development so that novel diagnostic tools and therapeutics can be developed.
Characterisation Of Extracellular DNases Of Pseudomonas Aeruginosa And Their Contribution To Disease
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
The bacterium Pseudomonas aeruginosa causes a number of serious diseases of humans particularly of immunocompromised patients. We have found that this bacterium secretes enzymes that have the ability to digest DNA. This proposal aims to work out how this bacterium uses these enzymes to infect human tissues and escape killing by immune cells. The results from this study will help to determine if these proteins may be used as targets for the development of new anti-infective drugs.
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