Genetic Modulation Of The Host Response To Pulmonary TB
Funder
National Health and Medical Research Council
Funding Amount
$540,273.00
Summary
Tuberculosis (TB) is an enormous global health problem. The World Health Organisation estimates that TB, which is caused by infection with the bacteria Mycobacterium tuberculosis, infects 2 billion individuals, leading to 2 million deaths and 8 million new cases of disease per year. Most TB disease is not manifest at the time of infection, but is a reactivation of latent disease in people who do not completely eradicate the primary infection. In a latent infection an effective chronic host respo ....Tuberculosis (TB) is an enormous global health problem. The World Health Organisation estimates that TB, which is caused by infection with the bacteria Mycobacterium tuberculosis, infects 2 billion individuals, leading to 2 million deaths and 8 million new cases of disease per year. Most TB disease is not manifest at the time of infection, but is a reactivation of latent disease in people who do not completely eradicate the primary infection. In a latent infection an effective chronic host response contains dormant TB organisms inside activated macrophages. Cells are recruited to wall off infected macrophages and specific T cells continually induce the activate state with minimal tissue damage (immunopathology). Although currently available antibiotics can kill TB organisms, the treatment is prolonged, expensive, difficult to administer in poorly resourced regions and not effective against multi-drug resistant organisms. New therapies to treat both active disease and prevent reactivation in individuals who are latently infected are urgently required. This proposal will address this problem using a novel approach, namely gene manipulation to augment host immunity to TB and limit concurrent immunopathology. We will construct vectors to increase expression of the key immune molecules, the T lymphocyte activating cytokines IL-12 and IL-23, and the macrophage effector molecules LRG-47 and Indoleamine 2,3-Dioxygenase (IDO). These molecules are known to be involved in TB killing. We will determine if increasing their expression increases the killing capacity of TB-infected macrophages and we will examine how these molecules interact to aid clearance of the TB bacilli. This internationally competitive grant will further our detailed understanding of the complex immune response to TB organisms and lead to the development of novel therapies to treat TB infection and prevent reactivation of latent disease.Read moreRead less
Improving Protection Against Childhood Tuberculosis: The Influence Of BCG Vaccine Strain And Age On Protective Immunity
Funder
National Health and Medical Research Council
Funding Amount
$473,739.00
Summary
BCG vaccine is of vital importance in the fight against the increasing problem of TB worldwide, particularly in children. This project will compare the 3 most commonly used different strains of BCG vaccine to determine which produces the best protective immunity in newborns. It will also determine whether BCG at birth or at 2 months of age provides better protection. Optimising the timing and strain used for BCG immunisation would prevent large numbers of cases and deaths from TB at low cost.
This fellowship aims to develop evidence-based clinical and public health approaches to the control of multi-drug resistant tuberculosis. Projects include identifying optimal treatment approaches to drug resistant tuberculosis by using meta-analyses; analysing the cost-effectiveness of strategies to prevent drug resistant tuberculosis; understanding transmission of drug resistance within households and implementing a major clinical trial of antibiotic therapy to prevent the disease.
Development And Validation Of A Latent Tuberculosis Diagnostic
Funder
National Health and Medical Research Council
Funding Amount
$534,865.00
Summary
Globally, tuberculosis is a leading cause of death with 9.6 million new diagnoses in 2014. The diagnosis of latent TB infection is important, but is difficult to make because current assays are suboptimal. We have developed a very simple assay which detects responses to TB antigens by co-expression of two surface markers expressed by CD4+ T cells. We propose to develop this into a highly standardised kit for the diagnosis of TB with our commercial partner Cytognos.
Towards The Elimination Of Tuberculosis And Rheumatic Heart Disease In Northern Australia And Our Region
Funder
National Health and Medical Research Council
Funding Amount
$258,600.00
Summary
My research program addresses tuberculosis and rheumatic heart disease, which are leading challenges for Northern Australia and our region. Both are diseases caused by infections with long-term complications. They cause illness and death in young Aboriginal people and neighbouring Southeast Asian populations. There are many gaps in our ability to effectively detect and prevent these diseases. My research targets these gaps, from cutting-edge science to translation of guidelines into practice.
Functional And Structural Studies Of A Glycosyltransferase Essential For Complex Glycolipid Biosynthesis In Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$508,838.00
Summary
Tuberculosis (TB) kills more than three million people each year while the causative bacterial species, Mycobacterium tuberculosis, infects one-third of the entire human population. An alarmingly high rate of TB exists in Australia's indigenous population. This proposal aims to identify and characterise essential processes involved in synthesis of the outer coat of the bacterium which are potential targets for new drugs for the treatment of this devastating disease.
Pathophysiology And Treatment Of Malaria And Other Tropical Infectious Diseases Prevalent In Our Region
Funder
National Health and Medical Research Council
Funding Amount
$560,284.00
Summary
Nick Anstey is internationally recognised for his discoveries in malaria and other tropical infectious diseases. He leads a major tropical infectious disease research program in Darwin and SouthEast Asia that attracts some of the brightest researchers and students from Australia and beyond to understand disease mechanisms and work on new ways to treat illness and prevent death. He uses results to change policy and practice not only in Australia but around the world.