How The Placental Protein Syncytin Impairs Maternal Immune Responses To Influenza
Funder
National Health and Medical Research Council
Funding Amount
$609,862.00
Summary
Pregnant women are known to be highly susceptible to certain viral infections, especially influenza, which results in severe illness and even death. The reason for this transitory susceptibility are unknown. We have found that a protein, Syncytin, has the ability to impair maternal immune responses to influenza We now will determine how it does this and discover potential interventions to reverse these effects.
Assessment Of Interventions For Controlling Pandemic Influenza And Determining Data Needs To Inform These Assessments
Funder
National Health and Medical Research Council
Funding Amount
$183,040.00
Summary
The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at ri ....The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at risk of being infected. We will compare these control measures by taking due account of the ability and resources available for these interventions, and with regard to the need to maintain essential services. The comparisons will be made using mathematical models that describe the transmission of the infection. All available data and advice from experts will be used to ensure that realistic models are used for the comparisons. We will also use the models to determine the best use of the limited antiviral drugs available, until a vaccine becomes available. We will consider how the control strategy should be changed if a strain develops that is resistant to the antiviral drugs. In addition, we will determine what data need to be collected during the early stages of a pandemic to help us to determine the best use of the antiviral drugs, the best use of a new vaccine and to check on the development of resistance to the antiviral drugs.Read moreRead less
Identifying The Microbiological Risk Factors For Acute Lower Respiratory Infection In Indigenous Children To Inform Future Intervention Strategies
Funder
National Health and Medical Research Council
Funding Amount
$495,745.00
Summary
Lung infections such as pneumonia are common in Indigenous children, and can lead to repeated hospitalisation and permanent lung damage. They are also an important cause of preventable death in children. This study will look at the role of bacteria and viruses in lung infections, and will inform interventions to reduce the burden and consequences of lung infections in Indigenous children.
Molecular Basis For The Emergence Of Community Acquired Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$427,518.00
Summary
Golden Staph is a major problem in our hospitals but serious Golden Staph infections are increasingly common in the community, among otherwise healthy people who have had no contact with hospitals. This project will find out how Golden Staph is evolving to become more likely to cause disease in the community. This knowledge can then be used to design new strategies for early detection, prevention and treatment.
Mathematical Modelling Of Bacterial Carriage In Children
Funder
National Health and Medical Research Council
Funding Amount
$421,746.00
Summary
Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, child ....Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, children attending group child care are at high risk of ear infections. As many bacteria are resistant, antibiotics are now much less effective than when they were first introduced. Furthermore, there is a continuing load of infection for children in Aboriginal communities, in PNG and other developing countries, causing hearing loss, chronic respiratory problems, and heart disease and renal disease in later life. Using data previously collected from other studies in Indigenous communities and children in child care, mathematical models allow us to ask what if?, and answer important public health questions: 1. What environmental and public health measures can reduce the cycle of cross-infection in child-care and high-risk populations? 2. What coverage rates with pneumococcal vaccine will eliminate the vaccine-specific bacteria from child care centres, from the wider community, and from high risk populations? 3. Will infections with bacteria not covered by vaccine then increase? 4. Will the resistant bacteria tend to disappear if antibiotic use is restricted? 5. Under what circumstances will antibiotics help to control infection? The modelling will promote understanding of the social and health costs of bacterial infection in Aboriginal communities and child care and use educational scenarios to promote uptake of the most cost-effective and socially acceptable interventions.Read moreRead less
A Study To Investigate Alternative Regimens For Pneumococcal Vaccination Of Infants In A Developing Country
Funder
National Health and Medical Research Council
Funding Amount
$1,622,210.00
Summary
Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccine is very expensive (approximately USD $200-infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver thi ....Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccine is very expensive (approximately USD $200-infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver this vaccine, which are safe and effective. A recent WHO-GAVI meeting to address impediments to the introduction of these vaccines in developing countries recognized the need to evaluate other regimens of Pnc conjugate vaccine as an important research priority. This study has been deliberately formulated with that need in mind. The site for this research is Fiji. Although health services are good, Pnc disease, particularly pneumonia, remains the commonest cause of childhood morbidity and mortality. Fiji has good vaccine coverage and was the first Pacific country to introduce Hib vaccine. The arrival of the new, expensive Pnc conjugate vaccine presents a dilemma for Fiji and many similar countries. The expense of this vaccine would consume a large portion of the health budget. This study has two components: 1. A Phase 2 immunogenicity study (involving 750 infants) to evaluate regimens using reduced numbers of doses of Pnc conjugate vaccine, and using timing of dosing and combinations with the Pnc polysaccharide (PS) vaccine that may be more suited to the epidemiology of Pnc disease in developing countries. 2. An epidemiological study will measure the burden of invasive Pnc disease and pneumonia in Fiji. This will be part of a global effort to address these issues, and will be used to develop rapid assessment tools for these diseases in developing countries. We will seek cofounding for this component.Read moreRead less
Analysis Of Viral And Cellular Gene Expression During Human Cytomegalovirus Latent Infection Of Hematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
Summary
Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body a ....Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. This project has three major components. Firstly, we aim to continue studies which are defining what viral genes are active (ie expressed) during latent infection. Identification of these genes and determination of how they function may have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during latency and reactivation. The study of viral and cellular gene expression during latency may contribute to the development of drugs which interfere with the viruses ability to become latent or reactivate. Thirdly, we have preliminary results which suggest that latent HCMV may actively avoid detection by the immune system. In this project we also aim to determine the mechanism by which the virus interferes with the expression of molecules which are an essential component of our immune system.Read moreRead less
Viral And Host Cell Gene Expression During The Establishment And Maintenance Phases Of Human Cytomegalovirus Latency
Funder
National Health and Medical Research Council
Funding Amount
$149,250.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. The overall aim of these studies is to provide a much better understanding of how CMV latency is established and maintained, with the ultimate goal of making advances for the design of anti-viral therapies to disrupt these processes. This project has three major components: Firstly, we aim to identify and characterise viral gene expression during the establishment of latency and these findings will have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during the establishment and maintenance phases of latency. Thirdly, we will apply microarray technologies to determine how human cell genes are altered in response to the expression of individual viral genes that are active during the latent phase of infection.Read moreRead less