Virulence Strategies Of LEE-negative Shiga Toxigenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$230,246.00
Summary
Shiga toxigenic Escherichia coli (STEC) are a diverse group of pathogens that cause serious gastrointestinal disease in humans, which can lead to life-threatening complications. This project is aimed at understanding how these bacteria cause disease, and is focused on a subset of STEC strains that are highly virulent and produce a novel cytotoxin. A better understanding of the pathogenic mechanisms of STEC is essential for development of improved therapeutic and preventative strategies.
Pathogenesis And Prevention Of Shiga Toxigenic Escherichia Coli Infections
Funder
National Health and Medical Research Council
Funding Amount
$341,320.00
Summary
Shiga toxin (Stx)-producing strains of Escherichia coli (STEC) are known to cause diarrhoea and haemorrhagic colitis in humans. In a proportion of cases, this leads to potentially fatal systemic complications, such as haemolytic uraemic syndrome (HUS), which is the commonest cause of acute renal failure in children. HUS has a high mortality rate in spite of intensive supportive therapy. Morbidity is also substantial, as permanent renal damage and neurological sequelae occur in a significant prop ....Shiga toxin (Stx)-producing strains of Escherichia coli (STEC) are known to cause diarrhoea and haemorrhagic colitis in humans. In a proportion of cases, this leads to potentially fatal systemic complications, such as haemolytic uraemic syndrome (HUS), which is the commonest cause of acute renal failure in children. HUS has a high mortality rate in spite of intensive supportive therapy. Morbidity is also substantial, as permanent renal damage and neurological sequelae occur in a significant proportion of survivors. Large outbreaks of STEC infection are becoming increasingly common, and highlight the threat to public health posed by these bacteria. The serious systemic complications of STEC disease, as well as much of the intestinal pathology, are directly attributable to Stx. However, pathogenesis is multifactorial and capacity of the bacteria to colonize the gut is a crucial virulence trait. STEC infections can now be diagnosed very early in the course of disease, but currently no effective therapeutic intervention is possible. We are addressing this deficiency by developing a novel therapy for STEC infections based on a genetically modified harmless bacterium capable of binding toxin in the gut. Vaccines capable of preventing transmission of STEC disease in the community are also needed, but development of these demands a full understanding of the mechanisms whereby diverse STEC strains adhere to intestinal epithelium and colonize the human gut. We are therefore also examining the interaction between STEC and gut epithelial cells at the cellular and molecular level, with a view to identifying and assessing the vaccine potential of key determinants of adherence.Read moreRead less
An RCT To Determine The Optimum Frequency Of Botulinum Toxin Injections To The Calf In Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$286,358.00
Summary
Cerebral Palsy (CP) is the most common cause of disability amongst children across the developed world. There are about 1800 children with CP in Victoria alone. It is caused by damage to the brain in early childhood. Children with CP have difficulty controlling how their muscles work. Muscles are often spastic, which means that they are switched on all the time, and this makes walking and performing other tasks difficult. As the child grows the spastic muscles can become too short and this occur ....Cerebral Palsy (CP) is the most common cause of disability amongst children across the developed world. There are about 1800 children with CP in Victoria alone. It is caused by damage to the brain in early childhood. Children with CP have difficulty controlling how their muscles work. Muscles are often spastic, which means that they are switched on all the time, and this makes walking and performing other tasks difficult. As the child grows the spastic muscles can become too short and this occurs can only be corrected by orthopaedic surgery. The spasticity in particular muscles can be reduced by injecting them with Botulinum Toxin (commonly known as Botox and used cosmetically to remove wrinkles). The effects of a single injection have been closely studied and we know that the effect of the toxin wears off. Children are thus offered repeat injections but there have been no studies to investigate what is the most appropriate interval between injections. The aim of this study is to determine this. In routine clinical practice children tend to get injections approximately once a year. A consideration of what we know about how the toxin acts, however, suggests that injections every 4 months might be expected to be more effective. This study will thus randomly allocate children to receive injections either every twelve months or every four months over a two year period. During the study both groups will be monitored to see if there are differences in how easily they can walk and perform other functions and in their overall quality of life. After the study the children will also be assessed to see whether there is any difference in the length of the spastic muscles. There have been no other studies to investigate the most appropriate interval between injections. This study will thus be the first anywhere and will be the foundation for guidelines for the ongoing use of botulinum toxin in children with cerebral palsy in Australia and throughout the world.Read moreRead less