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Worldwide Molecular Analysis Of Streptococcus Pyogenes Scarlet Fever Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$544,041.00
Summary
The microorganism group A Streptococcus (also called GAS or Streptococcus pyogenes) ranks among the top 10 infectious disease killers of humans. Recently, outbreaks of scarlet fever have occurred in both Asia and the United Kingdom, placing a serious strain on health systems. The reasons underlying these outbreaks remain unknown. Our team will lead the global effort to characterise this rise in scarlet fever, and provide recommendations and solutions to health professionals.
Mobility, Mixing And Infectious Disease Transmission Among Remote-living Indigenous Australians: Addressing A Knowledge Gap To Identify Effective Strategies For Sustained Disease Control
Funder
National Health and Medical Research Council
Funding Amount
$340,891.00
Summary
Indigenous Australians in remote communities experience extremely high rates of infections such as skin sores. I will study the mobility and social interactions of Indigenous people in remote communities in the Northern Territory to better understand how infectious diseases spread throughout these communities. This information will be used in mathematical models to plan the most effective strategies to permanently reduce the burden of infectious diseases among Indigenous Australians.
Structure And Biophysical Analysis Aided Design Of Novel Toxoid Vaccines For A Major Class Of Bacterial Toxins.
Funder
National Health and Medical Research Council
Funding Amount
$608,425.00
Summary
Inactivated bacterial toxins (toxoids), such as the tetanus vaccine, are safe and effective vaccines. Cholesterol dependent cytolysins (CDCs) are bacterial toxins produced by many important human pathogens including Group A Streptococcus (GAS) and Pneumococcus. GAS has no available vaccine and Pneumococcus does not have a universal vaccine. We have developed a new way of inactivating CDCs based on new knowledge of how they target human cells and will use this knowledge to make new vaccines.
A vaccine against the bacteria Group A streptococcus (‘strep’) could prevent common minor infections like sore throat and school sores as well as deadly ones like necrotising fasciitis (‘flesh eating disease’). It would also reduce long-term heart (rheumatic heart disease) and kidney problems. We are going to try and deliberately give a sore throat to adult volunteers under very close medical supervision so that we can learn more about immunity to strep and to help make and test new vaccines.
Characterising The Molecular Pathogenesis Of Newly Emergent Invasive Group A Streptococcus M4 Serotypes In Australia
Funder
National Health and Medical Research Council
Funding Amount
$523,756.00
Summary
Group A Streptococcus (GAS) is a human pathogen of global significance, responsible for life-threatening invasive infections such as flesh-eating disease (>650,000 cases per year), with a mortality rate of 25%. A recent outbreak of serotype M4 GAS caused severe invasive infections in Queensland Australia. The aim of this work is to determine how M4 GAS causes invasive disease. Understanding this mechanism will allow the development of new generation therapeutics, treatments and improved healt ....Group A Streptococcus (GAS) is a human pathogen of global significance, responsible for life-threatening invasive infections such as flesh-eating disease (>650,000 cases per year), with a mortality rate of 25%. A recent outbreak of serotype M4 GAS caused severe invasive infections in Queensland Australia. The aim of this work is to determine how M4 GAS causes invasive disease. Understanding this mechanism will allow the development of new generation therapeutics, treatments and improved health outcomes.Read moreRead less
Interrogation Of Streptococcal Genomic Epidemiology Within Disease Endemic Regions
Funder
National Health and Medical Research Council
Funding Amount
$325,896.00
Summary
Group A streptococcal (GAS) bacterial infections within the Indigenous populations of Northern Australia are amongst the highest in the world. This project uses comparative bacterial genomics to examine current and historical outbreaks of GAS disease in Northern Australia relative to globally sourced GAS. This will be used to examine the spread of disease causing GAS between remote communities as well as investigating genetic markers of disease and informing therapeutic interventions.
A New Model For The Pathogenesis Of Rheumatic Fever: Superantigen Priming Of The Immune Response To Group A Streptococci
Funder
National Health and Medical Research Council
Funding Amount
$248,820.00
Summary
Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, c ....Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, control of this ARF will partly depend on new and better treatment and prevention strategies. To achieve these goals a deeper understanding of the immune mechanisms underlying this disease is urgently needed. It is known that ARF is caused by an abnormal immune response following streptococcal infection. This leads to the production of cells called T cells that attack the body s own tissues rather than the bacteria itself. This autoimmune disease is responsible for the heart damage that underlies ARF. It is believed that this proces only occurs when susceptible individuals are infected with specific rheumatogenic strains of streptococci. However there are a number of deficiencies in this model and it is proposed that there is an additional factor responsible for the abnormal immune response in ARF. This project will explore the possibility that bacterial toxins called superantigens are the critical missing factor , by studying the immune response in ARF. Superantigens are produced by certain streptococci and staphylococci, and are potent in minute quantities causing widespread activation of the immune system. They have been found to play an important role in a number of autoimmune diseases and the type of immune response found in ARF fits well with that expected if superantigens were involved. If superantigens play an important role in causing the abnormal immune response in ARF then a number of new avenues would open for the treatment and prevention of this disease.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.
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
MOLECULAR ANALYSIS OF VIRULENCE FACTORS OF GROUP B STREPTOCOCCI
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Streptococcus agalactiae, more commonly referred to as group B streptococcus (GBS), is the commonest cause of life-threatening infection (specifically bacteraemia, pneumonia and meningitis) in neonates. Mortality is high even in developed countries where antimicrobial therapy is readily available. In spite of the importance of GBS disease, the precise molecular mechanisms whereby the organism colonizes, invades and damages host tissues are poorly understood. The long term goal of this project is ....Streptococcus agalactiae, more commonly referred to as group B streptococcus (GBS), is the commonest cause of life-threatening infection (specifically bacteraemia, pneumonia and meningitis) in neonates. Mortality is high even in developed countries where antimicrobial therapy is readily available. In spite of the importance of GBS disease, the precise molecular mechanisms whereby the organism colonizes, invades and damages host tissues are poorly understood. The long term goal of this project is to gain a complete understanding of the pathogenesis of GBS disease and to apply this to development of improved preventative strategies. We propose to carry out a comprehensive molecular characterization of genes encoding putative GBS virulence determinants, with particular reference to those which encode the capacity to adhere to and invade host cells. GBS carrying defined mutations in these genes will be constructed and their virulence will be compared with that of the otherwise isogenic parental GBS. This will enable us to determine the precise contribution of each putative virulence factor to the pathogenesis of disease. Moreover, proteins shown to be important in this process will be tested for vaccine potential.Read moreRead less