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
Tropical Infectious Diseases - Pathogenisis And Vaccine Research
Funder
National Health and Medical Research Council
Funding Amount
$7,311,989.00
Summary
The diseases on which three themes of the work proposed centre, malaria, streptococcal diseases and scabies are infectious diseases largely affecting indigenous people in various parts of the world on a massive scale, for which there are no vaccines. The aim of the work is to develop vaccines or other biological prevention measures against each of these diseases and the problems that need to be solved are similar. The team includes senior experts on thebiology of infectious diseases with long hi ....The diseases on which three themes of the work proposed centre, malaria, streptococcal diseases and scabies are infectious diseases largely affecting indigenous people in various parts of the world on a massive scale, for which there are no vaccines. The aim of the work is to develop vaccines or other biological prevention measures against each of these diseases and the problems that need to be solved are similar. The team includes senior experts on thebiology of infectious diseases with long histories of collaboration as well as younger members with impressive credentials that are new to the collaboration. The fourth theme of the work proposed is concerned with inventive new ways of making such vaccines by novelchemical methods. It has already been the subject of published collaborative work onstreptococcal disease and is equally applicable to the other themes.Read moreRead less
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
Translating Bacterial Molecular Epidemiology Into Information To Improve Infectious Disease Risk Assessment And Control
Funder
National Health and Medical Research Council
Funding Amount
$494,500.00
Summary
Streptococcus pneumoniae (pneumococcus) and group B streptococcus (GBS) are important pathogenic bacteria, which cause septicaemia and meningitis in young infants, the elderly and people with certain chronic diseases. Both consist of a number of different types, some of which are more likely to cause disease than others. Pneumococcal vaccines that protect against the commonest pathogenic types are used in Australia in people most at risk.Antibiotic resistance is an increasing problem, which shou ....Streptococcus pneumoniae (pneumococcus) and group B streptococcus (GBS) are important pathogenic bacteria, which cause septicaemia and meningitis in young infants, the elderly and people with certain chronic diseases. Both consist of a number of different types, some of which are more likely to cause disease than others. Pneumococcal vaccines that protect against the commonest pathogenic types are used in Australia in people most at risk.Antibiotic resistance is an increasing problem, which should be partly off-set by immunisation. Giving antibiotics during labour, to women colonised with GBS, can reduce infection rates in newborns, but there are many disadvantages of this approach, including the risk of increased antibiotic resistance. Vaccines against GBS are mpt yet available. We have developed methods to identify detailed fingerprints of these bacteria which allow us to identify types, antibiotic resistance and, for GBS, other characteristics which can distinguish highly pathogenic strains from the majority that are carried harmlessly and unlikely to cause disease. The methods are still quite slow and expensive and produce complex patterns,which are difficult to interpret rapidly. We plan to develop a new, rapid and relatively inexpensive, fingerprinting system for these bacteria and computer programs to analyse and interpret the results. They will allow us to check the strains of pneumococci that cause disease to make sure that new ones, not covered by the vaccine, do not become more common and reduce the effectiveness of vaccine and that antibiotic resistance does not increase further. The methods will also allow us to study differences between the small proportion of GBS strains that cause neonatal infection and the majority that are carried harmlessly by pregnant women and are of little risk to their babies. Eventually this should allow doctors to identify women whose babies are most at risk, reduce unnecessary antibiotic use.Read moreRead less
Immunity And Pathogenesis In Tropical And Infectious Diseases: Implications For Vaccines And
Funder
National Health and Medical Research Council
Funding Amount
$15,794,553.00
Summary
Malaria, streptococcal diseases, helminthiases and scabies are diseases of indigenous people on a massive scale, which lack vaccines. We aim to understand the pathogenesis of these diseases and develop vaccines and other treatments to combat them. Team includes senior experts on infectious diseases with long collaborative histories and younger members with impressive credentials. The work proposed also concerns inventive new ways of making such vaccines by novel chemical methods and aspects of d ....Malaria, streptococcal diseases, helminthiases and scabies are diseases of indigenous people on a massive scale, which lack vaccines. We aim to understand the pathogenesis of these diseases and develop vaccines and other treatments to combat them. Team includes senior experts on infectious diseases with long collaborative histories and younger members with impressive credentials. The work proposed also concerns inventive new ways of making such vaccines by novel chemical methods and aspects of delivery.Read moreRead less