Community-based Surveillance Of Bacterial Respiratory Pathogens In The NT And WA
Funder
National Health and Medical Research Council
Funding Amount
$782,905.00
Summary
This surveillance project is a continuation of previous work that describes the strains of respiratory bacterial pathogens in the various community groups - Indigenous and non-Indigenous - across the NT and in WA (urban and remote areas). New vaccines are complex and whilst overall benefits are considerable, there are potential influences on microbiology that may be unwanted. Detailed knowledge of these effects will assist in selection of the best vaccines for use in Australia.
The pneumococcus is a major cause of bacterial pneumonia, sepsis and meningitis especially in children and the elderly. Antibiotic-resistant pneumococci are becoming more prevalent, and available vaccines have major shortcomings. We propose to identify and characterise the factors produced by this organism during infection that enable it to cause invasive disease. Such factors could be incorporated into protein-based pneumococcal vaccines currently under development.
Development Of Improved Preventative Therapeutic Strategies For The Control Of Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bact ....A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bacterial infections are responsible for >10 million deaths p.a., and the economic impact is inestimable. For most major pathogens, vaccines are either unavailable or have serious shortcomings. Resistance to commonly used antimicrobials is increasing at an alarming rate, and modern travel has assisted the rapid global dissemination of highly resistant and virulent clones. Morbidity and mortality are also predicted to increase as a consequence of human-induced environmental changes and the growing proportion of the population with increased susceptibility to infection. Effective management of bacterial infectious diseases in the 21st century will require a two-pronged approach involving the development of cheaper and more effective vaccines, as well as novel anti-infectives refractory to known resistance mechanisms. However, formulation of optimal therapeutic and preventative strategies demands a thorough understanding of the biology of disease, particularly the complex interactions between bacterial pathogens and their human hosts. I have also played a leadership role in establishing the Pneumococcal Vaccine Consortium, which has just submitted a co-ordinated suite of multicentre proposals to PATH Vaccine Solutions to fund final preclinical testing, GMP scale-up and Phase I-II-III trials of protein-based pneumococcal vaccines that we have developed. The PATH accelerated pneumococcal vaccine development program is of enormous potential significance, because there is now a very real probability of pneumococcal protein vaccines being fast-tracked into human trials. Our aim is to create a direct pipeline from antigen discovery in the collaborators’ laboratories into the clinic. If successful, these vaccines could save millions of lives. This will be of enormous satisfaction to me personally, as it was I who originally proposed and demonstrated “proof of principle” for the vaccine potential of pneumococcal proteins, and I have been advocating assessment of their protective efficacy in humans for over 20 years. Thus, receipt of an Australia Fellowship will undoubtedly further support the internationalisation of Australian medical research.Read moreRead less
GENETIC ANALYSIS OF POLYSACCHARIDE CAPSULE BIOSYNTHESIS AND REGULATION IN STREPTOCOCCUS PNEUMONIAE
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until r ....Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until recently, very little was known of the pneumococcal genes involved in production of this antigen. This project aims to continue characterization of these genes, and examination of the factors which regulate their expression. This regulatory mechanism may be very important, because production of increased levels of the polysaccharide capsule is believed to be an crucial step in the transition from carriage to invasion. An understanding of the molecular events involved in biosynthesis and regulation of capsule production will improve our understanding of the disease process and identify alternative targets for antimicrobial therapy.Read moreRead less
Optimising Prevention And Vaccination Policy For Pneumococcal Disease, Influenza And RSV In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$174,933.00
Summary
Despite recommending pneumococcal vaccine in the Northern Territory since 2000 for Indigenous Australians from 15 years of age, and increasing vaccination coverage, a corresponding reduction in disease has not been observed. This study will provide an evidence base for future vaccination policy by examining whether there is an adequate immune response to pneumococcal vaccination in Indigenous Australians, and whether prior vaccination could reduce the immune response to revaccination.
A Serotype-independent, Broad Spectrum Pneumococcal Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$955,585.00
Summary
Streptococcus pneumoniae (the pneumococcus) is the world’s most formidable bacterial pathogen, causing 1-2 million deaths each year. Existing vaccines provide protection against only a limited proportion of strains and their widespread use is increasing the prevalence of strains against which the vaccines provide no protection. This project aims to translate a novel broadly protective pneumococcal vaccine into the commercial development pipeline.
Reducing The Community Burden Of Respiratory Infections In Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Lower respiratory infections are the leading cause of preventable mortality among Indigenous children in the Northern Territory. Streptococcus pneumoniae remain one of the major paediatric respiratory pathogens. In this proposal I will describe the impact of past and present pneumococcal vaccination strategies on the burden of infant respiratory infections in this region.
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
A Preliminary Assessment Of The Genetic Population Structure Of Asterias Amurensis In Tasmania
Funder
Fisheries Research and Development Corporation
Funding Amount
$38,343.00
Summary
Objectives: 1. Determine whether the introduced seastar is the southern sub-species, Japanese and Russian populations of Asterias amurensis versicolor or a northern sub-species 2. Determine whether the Tasmanian populations are derived from one or several introductions 3. Determine whether the invasion of Tasmanian waters has been accompanied by a loss of genetic variation with respect to native populations
NCCP: Defining Best Practice For Viral Susceptibility Testing Of Non-target Species To Cyprinid Herpesvirus 3 -a Discussion Paper Based On Systematic Quantitative Literature Reviews
Funder
Fisheries Research and Development Corporation
Funding Amount
$124,626.00
Summary
The National Carp Control Plan (NCCP), an initiative of the Australian government, aims to reduce common carp numbers in Australian waters. A key aspect of this plan is to use a biological control agent to kill common carp in waters of the Murray-Darling basin. Since 2008 CSIRO researchers have been investigating the potential for Cyprinid herpesvirus 3 (CyHV-3) to control common carp numbers in this region as well as exploring potential negative outcomes arising from the introduction of this ex ....The National Carp Control Plan (NCCP), an initiative of the Australian government, aims to reduce common carp numbers in Australian waters. A key aspect of this plan is to use a biological control agent to kill common carp in waters of the Murray-Darling basin. Since 2008 CSIRO researchers have been investigating the potential for Cyprinid herpesvirus 3 (CyHV-3) to control common carp numbers in this region as well as exploring potential negative outcomes arising from the introduction of this exotic virus. One critical issue is the potential for non-target species (NTS) to be infected and negatively affected by CyHV-3. Susceptibility studies performed in vitro and in vivo were undertaken and used to predict in situ outcomes. These studies indicated that NTS tested were not susceptible to CyHV-3. However, since the publication of these results, stakeholder groups have raised several concerns. These concerns must be resolved to mitigate against the infection of NTS by CyHV-3 and to ensure continued stakeholder engagement. Six areas of concern have been raised by stakeholders. 1. Immune-competency status of fish was not considered in susceptibility studies 2. Techniques used to determine viral infection were perceived to be unreliable 3. Undiagnosed mortalities of NTS were not adequately addressed 4. Positive PCR test results observed in NTS were not adequately explained 5. Only mature or advanced juvenile fish were assessed for susceptibility to CyHV-3 6. The range of NTS investigated for susceptibility was limited and did not include a number of species that may be exposed to CyHV-3 It is proposed that a discussion paper be prepared to examine these issues. This paper would determine if previous susceptibility testing for CyHV-3 in the NCCP adequately addressed those issues detailed above. Using the information collected, recommendations for susceptibility testing of NTS to CyHV-3 in the context of the NCCP would be presented. The current understanding of what constitutes best practice for viral susceptibility testing at the time of the review would also be discussed. This would include a commentary on the predictive capacity of in vitro and in vivo studies when translated to the in situ environment.
Objectives: 1. The overarching objective of this project is to investigate potential problems, limitations and concerns related to viral susceptibility testing of NTS to CyHV-3 in the context of the NCCP and to define what constitutes best practice in viral susceptibility testing. 2. Review and discuss the implications of immune-competency status in pathogen susceptibility testing of aquatic organisms. 3. Review the range of techniques for assessing viral infection in aquatic animals and evaluate their accuracy and reliability. 4. Discuss the occurrence and implications of undiagnosed mortalities and ‘false positives’ in pathogen susceptibility studies. 5. Determine, based on existing literature, potential differences in the susceptibility of larval, juvenile and mature fish to viruses. 6. Investigate, based on existing literature, the potential for fish and other aquatic organisms beyond those previously investigated by the NCCP to become infected by CyHV-3 as a result of actions of the NCCP. Read moreRead less