Mechanism/s Of Disease Caused By Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$479,517.00
Summary
A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract ill ....A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract illness similar to RSV, but with an unknown etiology, suggests that HMPV may mediate similar clinical pathology. Nothing is currently known about the immune response to HMPV, or the association of these responses with lung disease. The objectives of this proposal are to elucidate the mechanisms of immunity and disease pathogenesis associated with human metapneumovirus (HMPV) and to investigate the use of a novel vaccine to protect against HMPV infection. Once this data is obtained, the study will provide the foundation for further research in the development of vaccines or therapeutic protocols to treat HMPV. It will also provide valuable information for understanding the disease in humans. Also,it is likely that HMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less
RNAi Therapeutic Intervention Of Human Viral Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$584,117.00
Summary
Human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. HMPV is emerging as a major cause of morbidity and life-threatening respiratory tract disease in infants, young children and the elderly worldwide. No treatment is currently available. The objectives of this proposal are to develop novel antiviral drugs that silence the expression of viral genes and to examine protection against the disease.
Otitis Media In Indigenous And Non-Indigenous Children: Microbiological And Immunological Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$534,400.00
Summary
Otitis media (middle ear infections) is a major health problem in children. Many children suffer repeated attacks requiring frequent courses of antibiotics, some need surgery and some suffer serious consequences, particularly hearing loss. This can affect performance at school, hence employment and social circumstances in adulthood. Indigenous children suffer much higher rates of disease with more complications than non-Indigenous children. Many factors predispose to the heavy burden of disease. ....Otitis media (middle ear infections) is a major health problem in children. Many children suffer repeated attacks requiring frequent courses of antibiotics, some need surgery and some suffer serious consequences, particularly hearing loss. This can affect performance at school, hence employment and social circumstances in adulthood. Indigenous children suffer much higher rates of disease with more complications than non-Indigenous children. Many factors predispose to the heavy burden of disease. In the Kalgoorlie-Boulder area we are following Indigenous and non-Indigenous children from birth to 24 months to look at a broad range of factors in order to proceed as soon as possible to appropriate intervention programs. Samples from the back of the nose are collected to find out the relationship between carriage of a range of bacteria or viruses and risk of getting otitis media. Information on antibiotic resistance of the bacteria we isolate will assist in ensuring appropriate treatment of otitis media. We also collect a sample of breast milk from mothers and several samples of saliva to find out about the immune system of babies and how this relates to disease to assist in an ongoing program of vaccine development for prevention of otitis media. We will find out how environmental factors such as crowding or passive smoking relate to carriage of bacteria and whether a combination of different factors increase risk of disease. A new vaccine called pneumococcal conjugate vaccine, recently licensed in Australia, is highly effective in preventing severe diseases such as pneumonia and meningitis and affords some protection against ear infections. It is likely to be offered first to Indigenous children because they suffer very high rates of pneumococcal disease. The vaccine may alter the types of bacteria in the nose. This needs to be monitored carefully which will be possible during this study.Read moreRead less
How Anti-inflammatory Drugs Differentially Affect The Bronchoprotective Signalling Of Protease-Activated Receptor-2
Funder
National Health and Medical Research Council
Funding Amount
$421,690.00
Summary
Asthma contributes significantly to the burden of ill health and impaired quality of life in Australian communities, and for many measures of asthma, Australia has amongst the highest prevalence when compared with other countries. Furthermore, there is evidence that the prevalence of asthma has increased during the latter part of the 20th century. There is currently no cure for asthma, and the need for better asthma therapies through the discovery of novel targets for drug development has never ....Asthma contributes significantly to the burden of ill health and impaired quality of life in Australian communities, and for many measures of asthma, Australia has amongst the highest prevalence when compared with other countries. Furthermore, there is evidence that the prevalence of asthma has increased during the latter part of the 20th century. There is currently no cure for asthma, and the need for better asthma therapies through the discovery of novel targets for drug development has never been more acute. PAR2 is a receptor that is located on the surface of many cell types in the respiratory tract, including the epithelial cells that line the airway tubes. When PAR2 is stimulated it causes the epithelial cells to produce and release large amounts of PGE2 (prostaglandin E2). PGE2 released from epithelial cells then binds to other proteins such as the prostanoid EP2 receptor located on smooth muscle cells. This causes the airway smooth muscle cells to relax. Drugs that cause airway smooth muscle cells to relax - called bronchodilators - make breathing easier, and are often used during an asthma attack to relieve bronchoconstriction. It also appears that activation of the PPP axis inhibits airway wall swelling (that is, has anti-inflammatory actions). Thus, drugs that activate the PPP axis may be beneficial in the treatment of asthma by reducing airway sweeling and producing smooth muscle relaxation. Thus, we we are investigating ways of optimally stimulating the PAR2-PGE2-prostanoid EP2 receptor axis (the PPP axis), as a means of develeping novel treatments for asthma.Read moreRead less
Evolution Of Airway Function And Inflammation In Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,447.00
Summary
Our goal is to evaluate if lung function can identify the onset of early lung disease in infants with cystic fibrosis (CF). We aim to evaluate: - Changes in lung function in infants with CF. - Associations between lung function and lung inflammation and infection. - Links between infant lung function and disease severity at 2 years of age. The long term aims are to determine how useful lung function will be in trials of novel treatments for the early treatment of CF.
CHARACTERISATION OF NOVEL PICORNAVIRUS-LIKE VIRUSES IDENTIFIED FROM PATIENTS WITH ACUTE RESPIRATORY INFECTIONS.
Funder
National Health and Medical Research Council
Funding Amount
$366,998.00
Summary
The common cold and serious chest colds are usually due to viral infections, and mostly occur in children. Unfortunately we can only be certain of the virus causing this illness in as little as 15% of cases. We intend to address this lack of research by examining, in detail, a new virus we recently identified in a child with serious respiratory illness that required admission to hospital. Testing by our laboratory suggests that the new virus is related to picornaviruses (which cause some common ....The common cold and serious chest colds are usually due to viral infections, and mostly occur in children. Unfortunately we can only be certain of the virus causing this illness in as little as 15% of cases. We intend to address this lack of research by examining, in detail, a new virus we recently identified in a child with serious respiratory illness that required admission to hospital. Testing by our laboratory suggests that the new virus is related to picornaviruses (which cause some common colds) but seems to be present in children with far more serious illness. Our study plans to more completely identify the new picornavirus-like virus (PLV) using the tools of molecular biology and the expertise of a senior team of Australian scientists and clinicians who have recently made several virus discoveries in Australia, demonstrating that Australian virus research is capable of achieving highly competitive results that benefit our hospitals and especially their young patients. Our studies will develop extremely sensitive tests which rely on the detection of very small amounts of the viral genome. We can use these tests to determine what the whole virus looks like, when it might occur during the year and whether the PLV are found worldwide. Our studies will also produce viral proteins in the laboratory and use these to make new tests for stored blood samples. If a blood sample comes from a patient who has previously been infected by PLV, their blood will contain specific antibodies which we will then be able to detect. We also intend to determine whether some strains of PLV are more or less likely to cause serious illness than others. Improved understanding of these and other viruses minimises the chance of illness spreading within a hospital, helps scientists to decide against which viruses to design vaccines and drugs and aids medical doctors to better identify what once went undiagnosed.Read moreRead less
Burden Of Respiratory Infection In The First 2 Years Of Life: A Birth Cohort Study Of Emerging Respiratory Pathogens.
Funder
National Health and Medical Research Council
Funding Amount
$1,168,963.00
Summary
Respiratory illnesses are extremely common, but there is little information about patterns of infection in the community using modern diagnostic tests. Children have the highest rates of infection and transmit to all other age groups. We intend to recruit 138 newborns to monitor respiratory symptoms and collect specimens for testing in the first two years of life. This will allow us to document illnesses due to known and newly identified respiratory pathogens.
The Early Inflammatory Response To Virulent And Avirulent Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells s ....Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells such as macrophages. By avoiding this route of uptake and destruction, the virus is free to infect and replicate in other cells of the respiratory tract. Furthermore, by evading macrophage entry, the virus avoids triggering the release of early inflammatory mediators from these cells and this may affect both the speed and the magnitude of the subsequent inflammatory response. This study will contribute to a greater understanding of factors involved in initiating and regulating inflammation in the respiratory tract following viral infection. Furthermore, the findings may provide new insights into mechanisms of virulence of influenza and other enveloped viruses.Read moreRead less
The Significance Of Human Metapneumovirus In The Australian Paediatric Population
Funder
National Health and Medical Research Council
Funding Amount
$457,625.00
Summary
A newly discovered paramyxovirus, human metapneumovirus (hMPV), shows clinical and virological charcteristics very similar to those of human respiratory syncytial virus (hRSV). Human RSV is the major cause of acute lower respiratory illness in infants and accounts for more than 1 million deaths world wide annually. Most infants are infected in their first year of life, and re-infection is common. Genetic variation of the virus is thought to play a critical role in its ability to escape the immun ....A newly discovered paramyxovirus, human metapneumovirus (hMPV), shows clinical and virological charcteristics very similar to those of human respiratory syncytial virus (hRSV). Human RSV is the major cause of acute lower respiratory illness in infants and accounts for more than 1 million deaths world wide annually. Most infants are infected in their first year of life, and re-infection is common. Genetic variation of the virus is thought to play a critical role in its ability to escape the immune response and establish multiple sequential infections in the same host. Currently, we have no knowledge of the extent that hMPV exists in the Australian population, nor do we know if hMPV is a significant respiratory pathogen in paediatric patients. This research aims to determine the importance of hMPV as a respiratory agent, and will establish the rate, age of exposure, and incidence of hMPV infection in Australian children. In addition, we will identify the hMPV strains (genotypes) that infect local children, and the difference, if any, between these and virus strains detected in children from other community groups, and from overseas. Such data is invaluable in devising a future vaccine strategy for hMPV, and the study of the genetic variability among Australian strains will have profound implications for public health. This research project is a preliminary study into the clinical and virological significance of hMPV, in children, and will form a basis for future research projects. Once this preliminary data is obtained, further studies are possible to determine the cellular immune response to hMPV infection and its role in long-term protection. Also,it is likely that hMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less