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.
Recently Acquired Hepatitis C Infection: Insights From Virological, Therapeutic And Epidemiological Studies
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Every year around 10,000 new cases of hepatitis C (HCV) infection occur within Australia, most of which are undiagnosed. Reasons for this include a lack of public awareness about the benefits of treatment at this stage. As new antiviral agents become available it is likely that therapy for recent HCV will become even easier and more successful. The aim of this research is to explore HCV transmission patterns, treatment strategies and long term health outcomes in people with recent HCV.
The HITS Study: Modes Of Transmission, Natural History And Determinants Of Outcome From Primary Hepatitis C Infection
Funder
National Health and Medical Research Council
Funding Amount
$948,250.00
Summary
Hepatitis C (HCV) affects approximately 200,000 Australians, of whom a significant minority develop long term complications, including cirrhosis, liver failure and liver cancer. The dominant mode of transmission of this virus is via blood-to-blood contact, particularly via injecting drug use. Prisons appear to be a key focus of transmission of hepatitis C in the community as the majority of inmates are incarcerated for drug-related crimes, and injecting drug use remains prevalent whilst in priso ....Hepatitis C (HCV) affects approximately 200,000 Australians, of whom a significant minority develop long term complications, including cirrhosis, liver failure and liver cancer. The dominant mode of transmission of this virus is via blood-to-blood contact, particularly via injecting drug use. Prisons appear to be a key focus of transmission of hepatitis C in the community as the majority of inmates are incarcerated for drug-related crimes, and injecting drug use remains prevalent whilst in prison. In addition, as almost one in two inmates are already infected at the time of incarceration, those who are uninfected appear to be at significant risk of becoming infected through other (non-injecting) routes such as tattooing, fights and other coincidental blood exposures. This application seeks support for the HITS study (Hepatitis C Incidence and Transmission in Prisons study) - a prospective cohort study of inmates of NSW prisons. Following a successful pilot in which the substantial bureaucratic and logistical hurdles were resolved, the main cohort has been enroling since late 2000. The initial data have confirmed a high rate of at risk behaviour amongst inmates and three primary HCV infections acquired in prison have been documented featuring an unusual antibody negative pattern which would typically pass undetected in screening assays for HCV infection. After exposure to HCV and the development of primary infection, approximately one in five individuals successfully resolves the infection and clears the virus, presumably via an efficient immune response or a non-virulent virus, or a combination of these factors. Therefore, in addition to the public health aspects of the HITS study, the research also aims to define the immunological and virological factors which allow clearance of HCV. These studies will provide key information to guide treatment and immunisation strategies against hepatitis C.Read moreRead less
Models Of Care For Hepatitis C In The Era Of Directly Acting Antivirals
Funder
National Health and Medical Research Council
Funding Amount
$124,608.00
Summary
This project aims to evaluate how service delivery can enhance the impact of directly acting antivirals (DAA) on hepatitis C treatment uptake in three parts: i) To assess the impact of ten integrated hepatology nurses on treatment uptake in Victoria ii) To assess the feasibility of patient driven contact tracing to treat hepatitis C with DAA in a study of people who inject drugs iii) To assess the impact of offering DAA therapy in primary health care compared with a hospital.
The Epidemiology And Treatment Of Infections Due To Multiresistant Gram Negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$274,946.00
Summary
This fellowship application deals with the treatment of infections due to antibiotic resistant bacteria. The World Economic Forum recently discussed threats to our modern way of life. The highest ranked threats were climate change, terrorism and antibiotic resistance. During this Fellowship, two large clinical trials of treatment strategies for antibiotic resistant bacteria will be supervised by Professor Paterson.
Evaluation Of Naturally Occurring Resistance To Direct Acting Antiviral Drugs (DAAs) In Individuals With Acute Hepatitis C Infection
Funder
National Health and Medical Research Council
Funding Amount
$333,778.00
Summary
Hepatitis C therapy in the future is likely to involve the use of Directly Acting Antivirals, which offer a better chance of treatment success and shorter treatment courses. The downside to these new agents is the possible development of drug resistance. Studies suggest that drug resistant strains may already exist in some individuals prior to treatment. This study plans to use sensitive methods to examine how common drug resistant strains are in untreated individuals with acute hepatitis C.
Antibiotics have different effects on our own bacterial ecology, with sometimes unexpected detrimental effects. In this project, we will study this in detail and particularly address the question of 'good' and 'bad' antibiotics and how to identify them. National antibiotic policy and the deployment of 'decontamination' strategies in the critically ill are directly related issues and we expect to inform these important policy debates.
Molecular Mechanisms Of Ivermectin Resistance In The Ectoparasitic Mite, Sarcoptes Scabiei
Funder
National Health and Medical Research Council
Funding Amount
$289,561.00
Summary
A largely neglected parasitic disease, scabies is a significant disease of children, particularly in remote Aboriginal communities in northern Australia. The recent emergence of ivermectin resistance threatens future control of scabies. This research explores the genetic basis of ivermectin resistance in the scabies mite, developing molecular markers to identify the emergence of resistance in the community, leading to improved tools for resistance management and sustainable treatment strategies.
RECOMBINANT MALARIAL PYRIMIDINE ENZYMES AS DRUG TARGETS
Funder
National Health and Medical Research Council
Funding Amount
$229,750.00
Summary
Malarial parasites have now developed resistance to most of the available drugs and there is an urgent need for drugs with new mechanisms of action. Institutions collaborating on the Malarial Genome Project have sequenced the majority of DNA in the 14 chromosomes. The nucleotide sequence available on the internet contains thousands of open reading frames (ORFs) which encode proteins essential for survival of the parasite. Many of these proteins are enzymes which are suitable targets for drug dev ....Malarial parasites have now developed resistance to most of the available drugs and there is an urgent need for drugs with new mechanisms of action. Institutions collaborating on the Malarial Genome Project have sequenced the majority of DNA in the 14 chromosomes. The nucleotide sequence available on the internet contains thousands of open reading frames (ORFs) which encode proteins essential for survival of the parasite. Many of these proteins are enzymes which are suitable targets for drug development. A knowledge of the molecular architecture of the active site of such enzymes provides a template for drug design. The malarial parasite, Plasmodium falciparum, can only synthesise pyrimidine nucleotides for DNA via the de novo pyrimidine pathway. We have cloned the genes encoding three of the enzymes of the de novo pathway using sequence information from the Malarial Genome Project. Dihydroorotase, orotate phosphoribosyltransferase, and OMP decarboxylase, catalyse reactions 3, 5 and 6 of the pathway. We have expressed these enzymes in the bacterium Escherichia coli enabling large-scale production of these drug targets. We propose to characterise the catalytic and inhibitory properties of these enzymes, and grow protein crystals for determination of atomic structures by x-ray diffraction. The structures will provide templates for rational design of new antimalarial drugs. In a second approach for develoment of new drugs, the 3 malarial enzymes will be screened against chemical libraries for inhibition of catalytic activity. The initial screen will utilise a high throughput Biacore 3000 instrument which detects strong interactions between a target enzyme and candidate inhibitors. A thorough knowledge of the catalytic mechanisms, the three-dimensional structures and novel first generation inhibitors of these 3 malarial target enzymes, will provide a strong basis for development of new antimalarial drugs.Read moreRead less