Modelling Streptococcal Urogenital Tract Infection To Study Mechanisms Of Bacterial Colonization And Persistence
Funder
National Health and Medical Research Council
Funding Amount
$412,085.00
Summary
Colonization of the urogenital tract with bacterial pathogens is one of the most common infections in humans. In Australia millions of people are colonized in their urogenital tracts at any given time, often asymptomatically, and many such individuals require medical intervention for the treatment of consequent infections that result from persistent colonization. Bacterial colonization of the urogenital tract is associated with a variety of disease presentations including urinary tract infection ....Colonization of the urogenital tract with bacterial pathogens is one of the most common infections in humans. In Australia millions of people are colonized in their urogenital tracts at any given time, often asymptomatically, and many such individuals require medical intervention for the treatment of consequent infections that result from persistent colonization. Bacterial colonization of the urogenital tract is associated with a variety of disease presentations including urinary tract infections and neonatal infections resulting from vertical transmission of colonizing bacteria from mothers to newborns. Aside from sexually-transmitted diseases the most prominent bacterial pathogens that colonize the urogenital tract are Group B Streptococcus (GBS) and Escherichia coli. GBS in particular exist in the female urogenital tract as a persistent microbial reservoir in up to 40% of pregnant women and are transmitted to newborns in up to 72% of live births. Colonization of newborns leads to invasive disease including pneumonia, sepsis, and meningitis. While the disease presentations resulting from colonization of the urogenital tract vary the underlying basis that leads to disease is antecedent bacterial persistence in the urogenital tract despite immune system activation. The mechanisms whereby GBS evade immune responses in the urogenital tract to allow their survival are unknown. I will define the immune-evasion mechanisms and virulence traits used by GBS, as a model urogenital pathogen, to successfully colonize the urogenital tract in the face of mounting immune responses. These studies will provide a better understanding of the pathogenesis of urogenital disease in terms of bacterial colonization and immune-evasion strategies. This will shed light onto new approaches for the prevention and treatment of urogenital disease in humans such as improved vaccination, locally acting cytokines, and deliberate colonization with non-invasive strains for the prevention of disease.Read moreRead less
Improving Reproductive Health Through Infectious Diseases Research
Funder
National Health and Medical Research Council
Funding Amount
$1,957,108.00
Summary
Infectious diseases that impact upon reproductive health remain a major problem worldwide. This proposal will examine human papillomavirus infection, the role of the human microbiota in a number of conditions (necrotising enterocolitis, bacterial vaginosis, and human papillomavirus infection), and antibiotic resistance in sexually transmitted infections. The knowledge generated will be used to improve diagnostics.
International Neonatal Immunotherapy Study (INIS): A Randomised Trial Of Intravenous Immunoglobulin For Neonatal Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$1,151,250.00
Summary
There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routi ....There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routine treatment for serious infection in the newborn. The International Neonatal Immunotherapy Study (INIS) is a randomised trial to study the potential benefits of IVIG in 5,000 newborn babies in 150 centres world wide. 26 centres are in Australia and New Zealand, whose expected contribution of 1,500 babies will be vital to the success of the study. INIS is supported by the Commonwealth Government and Australian Red Cross Blood Service, who will oversee the supply and distribution of IVIG, and the NHMRC Clinical Trials Centre, who will coordinate the study. Infants will have a detailed specialist assessment at 2 years of age and a parent questionnaire will be completed, to assess their development. An economic evaluation will be performed to estimate the long-term savings to Australian Health Services and families associated with the IVIG therapy. The IVIG product to be used in Australia is Intragam P, manufactured by CSL, who have an unrivalled safety record. CSL has been making IVIG since 1989 and no transmission of HIV or hepatitis viruses has ever been reported. CSL estimate the risk of transmission of these viruses by IVIG is under 1 in 10 million treatments. INIS will provide reliable evidence about IVIG, a treatment with minimum known risk that may benefit thousands of Australian children and millions more worldwide.Read moreRead less
Is There Cytomegalovirus In Mothers Breastmilk And Does It Cause Infection In Very Premature Babies?
Funder
National Health and Medical Research Council
Funding Amount
$235,970.00
Summary
The hypothesis behind this study is that some very premature infants become infected with cytomegalovirus (CMV) from their mother's breast milk. This proposal is for a study of 200 CMV antibody positive mothers who are expressing breast milk for their very premature infants. We believe this is likely to be about 50% of all mothers. It has been well established that some full term infants are infected with CMV from their mother's breastmilk. The question now is do very premature infants with poor ....The hypothesis behind this study is that some very premature infants become infected with cytomegalovirus (CMV) from their mother's breast milk. This proposal is for a study of 200 CMV antibody positive mothers who are expressing breast milk for their very premature infants. We believe this is likely to be about 50% of all mothers. It has been well established that some full term infants are infected with CMV from their mother's breastmilk. The question now is do very premature infants with poor immunity develop serious infections from cytomegalovirus. This project has the overall aim of determining what proportion of very premature infants become ill with CMV excreted in their mother's breast milk, and then determining the nature and severity of those illnesses. It will also define how many mothers of premature infants are excreting CMV in their breast milk, the time this starts after birth, the viral load transmitted to the infant, the age after birth when the infants first become infected, the proportion who become ill with the infection, the details of the diseases and whether freezing breast milk kills the CMV.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
Inter-hospital Variations In Outcomes Of Very Preterm Infants Admitted To Neonatal Intensive Care Units
Funder
National Health and Medical Research Council
Funding Amount
$130,440.00
Summary
Most babies who are born very preterm (less than 32 weeks' gestation; ie more than 2 months early) are admitted to a neonatal intensive care unit (NICU). These babies stay in hospital for 2 to 4 months and need lots of care (using vast amounts of the available health resources). When compared to babies born at term, these very preterm babies are much more likely to die or to suffer from a range of poor outcomes that impact on their long-term development and quality of life. The Australian and Ne ....Most babies who are born very preterm (less than 32 weeks' gestation; ie more than 2 months early) are admitted to a neonatal intensive care unit (NICU). These babies stay in hospital for 2 to 4 months and need lots of care (using vast amounts of the available health resources). When compared to babies born at term, these very preterm babies are much more likely to die or to suffer from a range of poor outcomes that impact on their long-term development and quality of life. The Australian and New Zealand Neonatal Network (ANZNN) is a collaboration of clinical staff in all 29 NICUs in the region, whose aim is to improve the care of high-risk newborn infants and their families in Australia and New Zealand through collaborative audit and research. This audit has reported considerable differences in the rates of death and poor outcomes between NICUs. Other networks have reported similar variations. Variations in outcomes could be due to 1) differences in the way the diagnosis is made in each unit, 2) differences in how small or ill the babies are when admitted, or 3) different quality of care in each NICU. We need to take account of the first two possibilities before we can compare NICUs fairly and allow them to work towards achieving the best outcomes for very premature babies. To do this, our project will use advanced statistical techniques to look at the risk factors associated with death and poor outcome in very preterm babies. We will then be able to 'predict' outcomes and see if the differences between NICUs are real or not. If the variation between units is explained by differences in clinical practices, then this has enormous potential for quality improvement within the NICUs and through the development of new policy guidelines for clinical practice. The statistical models developed during this project will be useful for clinicians in other health areas and in other countries.Read moreRead less
Generating And Applying Clinical Research To Improve The Outcomes Of Neonatal Intensive Care
Funder
National Health and Medical Research Council
Funding Amount
$568,892.00
Summary
Birth is a complex process and sometimes babies require help to make the transition to independent life. Professor Peter Davis is conducting research into how best to support this transition. This involves helping the lungs to work efficiently and supporting the changes in circulation of the blood to the brain and to the rest of the body. His work aims to quickly identify babies who need help and then provide better treatments to make sure they have the best chance of a healthy life.
Optimising Early Respiratory Support For Preterm Infants: The HIPSTER Trial
Funder
National Health and Medical Research Council
Funding Amount
$696,791.00
Summary
Premature babies who need breathing support are often given ‘nasal continuous positive airway pressure’ (NCPAP) via large nasal prongs. It works well but is uncomfortable. A newer, popular support is ‘high flow’ (HF) which uses smaller nose prongs and may be more comfortable, but HF has not been well studied. The HIPSTER trial will compare these systems in 750 premature babies, at random half will have NCPAP, half will have HF. We will assess whether babies do equally well with each system.
Respiratory failure at birth is a major cause of death and disease in newborn infants. At birth the airways must be cleared of liquid to allow the inhalation of air, but, little is known about the process of lung aeration, because it has not been possible to observe or measure it. We have developed imaging and analytical techniques to observed and measure lung aeration. We will determine ventilation procedures that promote uniform lung aeration and minimise lung injury in ventilated infants.
Sensory Exposure Of Neonates In Single-room Environments (SENSE)
Funder
National Health and Medical Research Council
Funding Amount
$108,902.00
Summary
Preterm babies are often slower to reach developmental milestones than term babies. Extremely preterm babies spend a long time developing in the neonatal unit, which is suboptimal to the womb. Evidence suggests that open neonatal units are bright and loud and single rooms may be better for neonatal development. However, a recent study found poorer neurodevelopment with single rooms. This study aims to improve outcomes in single rooms through the application of a sound and language intervention.