The Clinical Value Of Serology And Molecular Tests For Diagnosing Invasive Aspergillosis In At-risk Hematology Patients
Funder
National Health and Medical Research Council
Funding Amount
$1,095,500.00
Summary
Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic t ....Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic tests are not good at detecting infection or often only detect the infection at advanced stages when treatment is ineffective. Because of the limitations of current diagnostic tests the current practice is to give empiric antifungal therapy (EAFT) early to treat Invasive Aspergillosis. However studies have demonstrated that this therapy has only resulted in a minor reduction in the mortality rates and it causes significant drug toxicity. It is a suboptimal treatment modality. New tests have been developed to diagnose Invasive Aspergillosis. These tests are for the detection of an Aspergillus protein in blood and for the detection of Aspergillus DNA in the blood. Available data suggests that these new tests are sensitive in the detection of Invasive Aspergillosis. Also other studies suggest that these new tests make an early diagnosis and seem to be able to monitor responses to treatment. However no study has been performed to date which demonstrates that the use of these tests can impact on important patient outcomes. This trial is designed to determine whether the use of the new tests to guide therapy will help improve treatment of Invasive Aspergillosis, reduce drug toxicity and reduce the death rate in the high-risk patients as compared with the current standard method of diagnosis and treatment with EAFT. If the trial is successful then this represents a significant advancement in the treatment and survival of leukaemic and bone marrow transplantation patients.Read moreRead less
Economic, social and cross cultural issues in non-pharmaceutical protection of front line responders to pandemic influenza and emerging infections. The protection of front line responders in a pandemic is essential to underpin an effective response. This research is the only work internationally which will address a key gap in evidence. This research has major implications for the national stockpile and for management of front line responders in a pandemic. These data are urgently needed, not ju ....Economic, social and cross cultural issues in non-pharmaceutical protection of front line responders to pandemic influenza and emerging infections. The protection of front line responders in a pandemic is essential to underpin an effective response. This research is the only work internationally which will address a key gap in evidence. This research has major implications for the national stockpile and for management of front line responders in a pandemic. These data are urgently needed, not just in Australia, but globally to inform pandemic planning and disease control policy around emerging infections and bioterrorism.Read moreRead less
Comparative Pathophysiology And Clinical Epidemiology Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$267,172.00
Summary
The simian parasite P. knowlesi is the most common cause of malaria in Malaysia and can cause severe and fatal disease. We are currently conducting a study of all malaria patients admitted to a tertiary referral hospital in Sabah, Malaysia. This will allow us to describe the epidemiological and clinical features of the hospitalised patients, including changes over time. We are also conducting novel pathophysiological studies which will allow us to understand how P. knowlesi causes sever disease.
This Fellowship will provide support for the Marshall Centre which is providing research and research training in the fields of bacteriology, epidemiology and vaccinology. It has significant regional collaborative links. Molecular epidemiology and pathogenesis of Helicobacter pylori, the stomach bacteria which causes ulcers and for which Warren and Marshall won the 2005 Nobel Prize in Medicine. Development of animal models to study the immune response so that the new bacterium can be used as a v ....This Fellowship will provide support for the Marshall Centre which is providing research and research training in the fields of bacteriology, epidemiology and vaccinology. It has significant regional collaborative links. Molecular epidemiology and pathogenesis of Helicobacter pylori, the stomach bacteria which causes ulcers and for which Warren and Marshall won the 2005 Nobel Prize in Medicine. Development of animal models to study the immune response so that the new bacterium can be used as a vaccine delivery agent.Read moreRead less
Platform FoR European Preparedness Against (Re-)emerging Epidemics- Australia
Funder
National Health and Medical Research Council
Funding Amount
$386,463.00
Summary
Infectious diseases rank high among the threats to human wellbeing and prosperity- globalisation, migration, tourism, intensive farming and changing climate enhance the likelihood of emergence of outbreaks of infectious disease. The optimal response to an emerging infectious disease requires the rapid acquisition of new knowledge. This project ensures that Australia can contribute to globally coordinated research that will meet the research challenge associated with any new pandemic infection.
PrtFII, A Streptococcus Pyogenes Fibronectin Binding Protein, And Invasive Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$296,540.00
Summary
Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin bind ....Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin binding protein, than those from uncomplicated skin sores. In this application we propose to extend this observation and compare biochemical properties of PrtFII from strains belonging to the above two sets of collections. We hypothesise that PrtFII from invasive strains bind to fibronectin more tightly than the proteins from strains that cause uncomplicated infection. We also will test whether sera from invasive disease cases have lower titre of antibodies to the conserved region of PrtFII than sera from uncomplicated cases. A streptococcal vaccine by necessity has to be a multi-component vaccine to cover a wide spectrum of diseases and epidemiological differences. The study proposed here may provide a basis to argue whether or not to include PrtFII in such a multi-component vaccine.Read moreRead less
A Comparative Study Of The Pathophysiology Of Severe Knowlesi And Falciparum Malaria
Funder
National Health and Medical Research Council
Funding Amount
$660,293.00
Summary
Plasmodium knowlesi causes monkey malaria, but has recently been found to infect humans resulting in severe disease and death similar to Plasmodium falciparum. Clinical features of severe P. knowlesi and how it causes complications are poorly described and understanding this could improve treatment and outcomes. In patients with P. knowlesi, we want to describe the clinical features, the ability to cause severe disease, and measure 1) markers of platelet activation and 2) capillary obstruction a ....Plasmodium knowlesi causes monkey malaria, but has recently been found to infect humans resulting in severe disease and death similar to Plasmodium falciparum. Clinical features of severe P. knowlesi and how it causes complications are poorly described and understanding this could improve treatment and outcomes. In patients with P. knowlesi, we want to describe the clinical features, the ability to cause severe disease, and measure 1) markers of platelet activation and 2) capillary obstruction and red cell deformability,Read moreRead less
The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manip ....The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manipulation of the pathogen. Other than providing fundamental information on host-pathogen interactions, this work may lead to novel disease interventions by inhibition of bacterial virulence factor activity and/or enhancement of host inflammatory and immune responses.Read moreRead less
Rhinovirus impairs physiological and immunological lung development and causes exacerbation of allergic airways disease. Rhinovirus (RV) infections account for around 90 per cent of asthma exacerbations, yet the mechanisms behind this are unknown. This project will use mouse models to study the effects of early life RV infection and allergic sensitisation on respiratory and immunological development, with the expectation that early life RV infection disrupts anitgen presenting cell function.