Molecular Typing And Epidemiology Of Bordetella Pertussis In Australia
Funder
National Health and Medical Research Council
Funding Amount
$552,662.00
Summary
Pertussis, commonly known as whooping cough, is an acute respiratory disease caused by Bordetella pertussis. Despite more than half a century of vaccination, pertussis has remained endemic in Australia, causing epidemic outbreaks every 3 to 4 years. Indeed the incidence has been increasing in recent years with over 11,000 cases notified in 2005.Pertussis is the commonest of all vaccine preventable diseases targeted by the Australian standard vaccination schedule. To control pertussis, appropriat ....Pertussis, commonly known as whooping cough, is an acute respiratory disease caused by Bordetella pertussis. Despite more than half a century of vaccination, pertussis has remained endemic in Australia, causing epidemic outbreaks every 3 to 4 years. Indeed the incidence has been increasing in recent years with over 11,000 cases notified in 2005.Pertussis is the commonest of all vaccine preventable diseases targeted by the Australian standard vaccination schedule. To control pertussis, appropriate epidemiological surveillance must be implemented to monitor the circulating B. pertussis strains and emergence of any new strains, in particular those that escape the protection by vaccines. This project will use a novel genomic comparison approach to find variation known as single nucleotide polymorphisms (SNP) present around the genome. We will use these SNPs to analyse a large collection of Australian and worldwide isolates to identify those SNPs most suitable for typing and determine the optimal number of SNPs needed for discrimination. A standardized, consistent and reliable typing method for strain identification will be established. We will further develop an integrated method for detecting known variation in the genes encoding the five acellular vaccine antigens. A combined method for strain identification and detection of antigenic variation will then be developed for culture-independent typing, enabling identification of the strain infecting an individual directly from a clinical sample without the need for culture. This study will establish molecular methods for surveillance of pertussis in Australia, essential for further improvement of acellular pertussis vaccines and public health control measures.Read moreRead less
Beta-lactamase Mediated Antibiotic Resistance In Gram-negative Pathogens: How Does Genotype Relate To Phenotype?
Funder
National Health and Medical Research Council
Funding Amount
$397,869.00
Summary
Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expressio ....Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expression of an enzyme called a beta-lactamase. This enzyme breaks down the penicillin. Beta-lactamase enzymes come in many different varieties, and new varieties appear quite frequently. Remarkably, when new kinds of penicillin are invented to circumvent resistance, the appearance of new beta-lactamases that can break down these new penicillins follows shortly thereafter. The objectives of our research are twofold. Firstly, it is now clear that the relationship between the beta-lactamase genes in a bacterium and the resulting pattern of resistance can be very complex. It can involve both the broad nature of the genes, the numbers of duplicates of the genes inside the cell, and very minor changes to the gene sequences. We will probe the relationship between the gene and resistance so as to understand it at a deeper level. Secondly, we will use this information to develop very efficient and cost affective methods for keeping track of the spread of the different varieties of beta-lactamase genes. These methods will be designed to be carried out on real-time PCR machines. These high-tech devices are general purpose gene analyzers that can carry out many different kinds of genetic assay. They are rapidly becoming ubiquitous in clinical microbiology laboratories. The use of these methods will provide much hard information that will be used to minimise the dissemination of antibiotic resistance.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