Should Very Premature Babies Receive A Placental Transfusion At Birth? A Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$2,875,774.00
Summary
Premature babies under 30 weeks gestation are up to a hundred times more likely than full term babies to die or survive with major disability, often from brain damage due to poor blood flow after birth. This randomised study will find out if giving them more placental blood at birth, by means of a delay in clamping the umbilical cord, then milking it, reduces anemia, blood transfusions, brain damage, infection, death and disability. The results may benefit millions of premature babies worldwide.
Developing A Vaccine To Protect Against Hypervirulent Strains Of Group A Streptococcus
Funder
National Health and Medical Research Council
Funding Amount
$536,850.00
Summary
Epidemic invasive GAS disease is associated with the emergence of the globally disseminated M1T1 clone and is linked to the mutation in the CovR/S regulator. This mutation leads to over- expression of SpyCEP and inhibits recruitment of neutrophils to the site of infection. Inclusion of an immunogenic fragment of SpyCEP into our current vaccine would enhance its efficacy and lead to the development of a vaccine with a wider coverage and better protective efficacy against hypervirulent GAS strains
Investigation Of The Localisation, Transport And Vaccine Potential Of Group A Streptococcal Cell Surface Proteins.
Funder
National Health and Medical Research Council
Funding Amount
$505,523.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represe ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represent candidate vaccine antigens capable of conferring protective immunity. We therefore propose to examine these surface proteins as components of experimental vaccines against GAS.Read moreRead less
Utilisation Of The Human Plasminogen Activation System By Group A Streptococci: Contribution To Virulence And Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Streptococcus pyogenes (group A streptococci; GAS) is a bacterium which causes human skin and throat infections as well as highly invasive diseases including the flesh eating disease necrotising fasciitis. Additionally, serious sequelae, including rheumatic fever and acute glomeulonephritis, may result following infection. Such diseases cause high morbidity and mortality in Aboriginal populations and are a continual significant drain on the national health fund. An important mode of invasion by ....Streptococcus pyogenes (group A streptococci; GAS) is a bacterium which causes human skin and throat infections as well as highly invasive diseases including the flesh eating disease necrotising fasciitis. Additionally, serious sequelae, including rheumatic fever and acute glomeulonephritis, may result following infection. Such diseases cause high morbidity and mortality in Aboriginal populations and are a continual significant drain on the national health fund. An important mode of invasion by GAS may be related to their ability to capture and activate host plasminogen via surface-associated or secreted plasminogen binding proteins (receptors). Plasminogen can be activated by host activators or secreted GAS streptokinase to the potent enzyme plasmin which is responsible for the degradation of tissue barriers. Thus, GAS may utilise plasmin to destroy tissue barriers and invade host tissues. The characterisation of the interaction between GAS and the plasminogen activation system would clarify the role of this system in invasive disease and provide potential targets for therapeutic intervention.Read moreRead less
Unified Model For Group A Streptococcal Invasive Disease Initiation.
Funder
National Health and Medical Research Council
Funding Amount
$605,221.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis and streptococcal toxic shock-like syndrome. We have recently discovered the trigger mechanism for GAS invasive disease. We hypothesise that the initial host response at the site of infection selects for a GAS invasive phenotype. We propose to examine the chain of events which result in tissue invasion in order to unde ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis and streptococcal toxic shock-like syndrome. We have recently discovered the trigger mechanism for GAS invasive disease. We hypothesise that the initial host response at the site of infection selects for a GAS invasive phenotype. We propose to examine the chain of events which result in tissue invasion in order to understand these disease processes and allow the development of future therapeutic interventions.Read moreRead less
Role Of Bacteriophage-encoded Streptodornase In Invasive Disease Caused By Diverse Group A Streptococcal M Serotypes.
Funder
National Health and Medical Research Council
Funding Amount
$832,544.00
Summary
Streptococcus pyogenes (group A streptococcus, GAS) is estimated to cause ~700 million cases of self-limited throat or skin infection each year worldwide. Invasive GAS disease occurs in approximately 1-1000 cases, with associated mortality of 25%. We have recently discovered that a viral infection can reprogram GAS for invasive disease propensity. We will investigate whether this phenomenon is widespread, in order to understand this process and develop future therapeutics.
Estimating The Burden Of Group A Streptococcal Diseases In Victoria
Funder
National Health and Medical Research Council
Funding Amount
$386,760.00
Summary
Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal pop ....Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal population (e.g. rheumatic fever, kidney disease). Streptococcal sore throat remains one of the most common childhood infections, and severe group A streptococcal diseases are thought to be increasing in incidence in Australia. Yet, there are no accurate data on the incidence and costs of these or other GAS diseases in non-Aboriginal Australians, or in most other populations around the world. It is becoming more urgent to collect this data as numerous vaccine candidates are entering human trials, new approaches to the treatment of sore throat are emerging, and new strategies to treat and control the spread of severe disease are being developed. We propose a comprehensive strategy to measure the incidence, prevalence and costs of each group of GAS diseases. We will follow a group of families for 12 months to detect cases of GAS sore throat and skin sores and measure the impact on the family. We will survey children in schools to estimate the prevalence of skin sores. We will check hospital records to calculate the number of cases of rheumatic fever and kidney disease. And we will maintain surveillance for severe diseases by checking hospital and laboratory records. We will also check to see if family members of people with severe disease have the GAS bacterium in their throats. We will then compile these data into a comprehensive estimate of the burden of disease in Victoria, and estimate the cost-effectiveness of different treatment and prevention strategies.Read moreRead less
Defining The Role Of Plasminogen Activation In Group A Streptococcal Invasive Disease
Funder
National Health and Medical Research Council
Funding Amount
$425,763.00
Summary
The "flesh-eating" bacteria group A streptococcus (GAS) causes life threatening invasive diseases such as necrotizing fasciitis and toxic shock syndrome (>600,000 cases and 163,000 deaths per year). For some types of GAS, plasminogen binding is essential for virulence.The aim of this work is to determine the extent to which plasminogen binding contributes to disease caused by highly virulent GAS. These studies will allow the development of new therapeutics and treatments.