Role Of P2X7 In Innate And Adaptive Immunity To Mycobacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Tuberculosis remains an enormous global health problem. Some 32% of the world s population are infected, with over 2 million persons dying each year. It is not well understood why some infected individuals develop clinical disease yet others remain healthy, but many cases are due to reactivation of dormant organisms lying within a specialized white cell, the macrophage. We know that declining socio-economic conditions, HIV co-infection, and some genetic risk factors such as HLA type contribute t ....Tuberculosis remains an enormous global health problem. Some 32% of the world s population are infected, with over 2 million persons dying each year. It is not well understood why some infected individuals develop clinical disease yet others remain healthy, but many cases are due to reactivation of dormant organisms lying within a specialized white cell, the macrophage. We know that declining socio-economic conditions, HIV co-infection, and some genetic risk factors such as HLA type contribute to the likelihood of an individual developing disease, but current known factors are insufficient to fully account for the risk of an infected individual developing disease. We have recently shown that the tuberculosis bacteria can be killed by the addition of a natural compound, ATP, to infected macrophages. This process occurs when ATP activates the P2X7 receptor leading to mycobacterial killing. We have identified several polymorphisms (mutations) in the P2X7 receptor. In individuals with one particular polymorphism, designated A1513C, these people do not respond to ATP and do not kill tuberculosis using this pathway. TB patients who are heterozygous for the A1513C polymorphism show approximately a 50% reduction in mycobacterial killing. We have preliminary evidence that this A1513C polymorphism is expressed at an over represented frequency in TB patients we have tested, suggesting that having this polymorphism may increase your risk of developing tuberculosis. The aim of this project is two fold. One, we will investigate the functioning of this receptor, determining how the P2X7 receptor is activated and how it interacts with other molecules in the immune system to kill tuberculosis. Secondly we shall determine if polymorphisms in the P2X7 receptor are a risk factor for the development of tuberculosis and leprosy disease.Read moreRead less
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.
Modelling The Effects Of Immunity On Influenza Transmission - Implications For Prevention And Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$275,767.00
Summary
There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our proj ....There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our project will use data from historic and contemporary outbreaks of influenza and build mathematical models to explain the rate of growth of an influenza outbreak in terms of: 1. The proportion of people exposed to influenza who do not become ill (although there can be evidence of infection if careful studies are made). This proportion is about 33%. 2. The proportion of people who are protected from influenza by immunity, whether induced by vaccination or by past exposure to natural influenza infection (this can vary from 0% in isolated populations which have not seen influenza for many years up to 80 or 90% in urbanised populations that are exposed to influenza almost every season). 3. Different rates of contact between different people and groups of people - some may be exposed so often that their immunity is boosted regularly without them becoming severely ill; others, living in more isolated circumstances, may be rarely exposed, but when they are, they are more likely to become severely ill. 4. The effects of influenza vaccine in inducing protective immunity - it is well known that there is good protection if the vaccine is well matched to the circulating virus. 5. The effects of live virus infection in inducing (short-lived) protection against a wider range of influenza viruses. Our model results will be used to guide vaccine design and pandemic planning.Read moreRead less
Next Generation Sequencing Of Hepatitis C Virus To Detect Drug Resistance Mutations
Funder
National Health and Medical Research Council
Funding Amount
$39,497.00
Summary
Hepatitis C is the leading cause of liver cancer and liver failure requiring transplantation in Australia. New antiviral drugs set to revolutionise hepatitis C treatment by substantially improving cure rates could be challenged by the development of resistance mutations, which would make these drugs less effective. We aim to develop a practical test to be used routinely to guide clinicians in choosing appropriate anti-viral drugs for their patients.
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
The Molecular Basis Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$16,230,996.00
Summary
Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as ....Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as novel drugs. These are urgently needed to reduce death and illness due to bacterial infectious diseases in the 21st century. 11Read moreRead less
Risk Factors, Mechanisms, And Treatment Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$265,138.00
Summary
The monkey parasite P. knowlesi is an increasing cause of human malaria in SE Asia. My studies on the clinical epidemiology, diagnosis and treatment of non-severe and severe malaria in Malaysia have changed policy. I will further define the clinical epidemiology of malaria patients in this area over time, assess risk factors for knowlesi malaria, and evaluate the role of human and parasite factors in disease severity, and treatment for reducing acute kidney injury in knowlesi malaria.
HIV Risks And Points Of Intervention For Chinas Internal Migrants In The Export Processing Zones Of Guangdong.
Funder
National Health and Medical Research Council
Funding Amount
$367,239.00
Summary
The project seeks to explore the HIV risks of internal migrants working in the Zhu Jiang Delta, China’s most significant ‘export processing zone’. As China’s economic boom is built upon the backbones of internal migrants, HIV-AIDS has the potential to cause a public health crisis with a devastating economic impact. Using a multi-method approach the risks and approaches to mitigating the risks will be explored in this vulnerable population.
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.