Characterisation Of Immune Responses To Sarcoptes Scabiei Cysteine Proteases, Group 1 Allergen Homologues, In Scabies
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Scabies, a parasitic skin infestation by the 'itch' mite Sarcoptes scabiei, causes significant health problems for children and adults in many remote Aboriginal communities in Australia. Scabies is often the underlying cause of streptococcal skin infections which can cause serious complications such as kidney and heart disease. Although diagnosed scabies cases can be successfully treated, individuals have often already transmitted the disease to others prior to receiving therapy. A particularly ....Scabies, a parasitic skin infestation by the 'itch' mite Sarcoptes scabiei, causes significant health problems for children and adults in many remote Aboriginal communities in Australia. Scabies is often the underlying cause of streptococcal skin infections which can cause serious complications such as kidney and heart disease. Although diagnosed scabies cases can be successfully treated, individuals have often already transmitted the disease to others prior to receiving therapy. A particularly dreadful form of scabies, known as crusted scabies, can develop in a minority of people, in which mites multiply in their millions and the affected person develops severe crusting of the skin. This has resulted in death within 5 years for up to 50% of people with this form of scabies. Scabies mites are scientifically very similar to house dust mites, and they produce cross reactive proteins. Molecular studies in our laboratory have enabled the identification and cloning of a number of scabies molecules with considerable similarity to known house dust mite proteins that cause allergic disease. In this study we propose to focus on a group of scabies proteins with significant identity to the extensively studied Group 1 house dust mite allergens, reported to cause an immune response in 90% of mite allergic people. We propose to use these scabies mite molecules to characterise the immune response in ordinary scabies and compare it to the more severe and debilitating crusted form of the disease. Characterisation of the immune response in scabies will ultimately aid in the development of new treatment for crusted scabies based on immunotherapy. Studies will also investigate for any cross reactivity with the house dust mite group 1 molecules and enable the design of specific immunodiagnositics to distinguish house dust mite allergy from scabies infestation and thus facilitate early diagnosis of scabies carriers and better control of the infestation in endemic communities.Read moreRead less
Investigating The Molecular Basis Of Emerging Drug Resistance In Scabies Mites
Funder
National Health and Medical Research Council
Funding Amount
$516,000.00
Summary
Scabies is a disease of the skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. In remote Aboriginal communities in northern and central Australia up to 60% of children can be infected. Scabies causes intense itching of the skin, resulting in skin damage through scratching, and serious secondary bacterial infections leading to kidney and heart disease. Some remote communities in the NT are documented to have the highest rates of kidney and heart disease in the world. The location ....Scabies is a disease of the skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. In remote Aboriginal communities in northern and central Australia up to 60% of children can be infected. Scabies causes intense itching of the skin, resulting in skin damage through scratching, and serious secondary bacterial infections leading to kidney and heart disease. Some remote communities in the NT are documented to have the highest rates of kidney and heart disease in the world. The location of the Menzies School of Health Research in this region where scabies is endemic has enabled us to undertake a number of studies on the disease. Our world first molecular study using microsatellite markers demonstrated that scabies mites on people were genetically distinct from those on dogs. This had important implications in control programs in the communities. Additional work has focused on laboratory studies to monitor the sensitivity of mites to current treatments used in community control programs and for the treatment of crusted scabies, a very severe and debilitating form of the disease. We have reported evidence of increasing resistance of scabies mites to topical 5%permethrin and documented both in vitro and clinical evidence of resistance to oral ivermectin. We now seek support to extend this work to identify at the molecular level the mechanisms of resistance and use this knowledge to design a diagnostic test. This work has both local and global implications. Scabies is a significant disease of children primarily in many indigenous and third world communities, as well as associated with nursing homes and HIV infection. The tools developed in this project will enable the assessment of drug treatment failures and assist in the development of more sensitive methods for monitoring resistance in the community, including the potential for reversing it. This will avoid the current global problems of resistance observed in other organisms such as headlice.Read moreRead less
Scabies is a significant disease of children particularly in indigenous communities. This project is aimed at working out how scabies mites resist medications used to treat them and to design a test for drug resistance. The tools developed in this project will enable the assessment of treatment failures and assist in the development of more sensitive methods for monitoring resistance in the community, including the potential for reversing it.
A vaccine against the bacteria Group A streptococcus (‘strep’) could prevent common minor infections like sore throat and school sores as well as deadly ones like necrotising fasciitis (‘flesh eating disease’). It would also reduce long-term heart (rheumatic heart disease) and kidney problems. We are going to try and deliberately give a sore throat to adult volunteers under very close medical supervision so that we can learn more about immunity to strep and to help make and test new vaccines.
A New Model For The Pathogenesis Of Rheumatic Fever: Superantigen Priming Of The Immune Response To Group A Streptococci
Funder
National Health and Medical Research Council
Funding Amount
$248,820.00
Summary
Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, c ....Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, control of this ARF will partly depend on new and better treatment and prevention strategies. To achieve these goals a deeper understanding of the immune mechanisms underlying this disease is urgently needed. It is known that ARF is caused by an abnormal immune response following streptococcal infection. This leads to the production of cells called T cells that attack the body s own tissues rather than the bacteria itself. This autoimmune disease is responsible for the heart damage that underlies ARF. It is believed that this proces only occurs when susceptible individuals are infected with specific rheumatogenic strains of streptococci. However there are a number of deficiencies in this model and it is proposed that there is an additional factor responsible for the abnormal immune response in ARF. This project will explore the possibility that bacterial toxins called superantigens are the critical missing factor , by studying the immune response in ARF. Superantigens are produced by certain streptococci and staphylococci, and are potent in minute quantities causing widespread activation of the immune system. They have been found to play an important role in a number of autoimmune diseases and the type of immune response found in ARF fits well with that expected if superantigens were involved. If superantigens play an important role in causing the abnormal immune response in ARF then a number of new avenues would open for the treatment and prevention of this disease.Read moreRead less
Targeting The Human Immune Response To Bacterial Superantigens.
Funder
National Health and Medical Research Council
Funding Amount
$165,424.00
Summary
This research investigates the human immune response to infection with toxin producing bacteria. Toxins activate the human immune system which can lead to serious illness or the development of disease that can progress rapidly and be associated with high rates of morbidity and mortality. Investigating the harmful effects of infection with toxin producing bacteria in humans and the damage caused by their toxins is essential for the development of effective therapeutic strategies.
Group A Streptococcal Human Challenge Study: Accelerating Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$2,018,741.00
Summary
Infection with group A streptococcus (GAS) is a major cause of morbidity and mortality worldwide, including in the Aboriginal population of Australia. Concerted efforts for vaccine development have been hampered by the absence of a suitable animal model. To address this critical knowledge gap we propose to develop a controlled human infection model of GAS infection. This model will provide a direct pathway for the future appraisal of novel GAS vaccines.
Evidence-driven Strategies To Reduce The Burden Of Infections Among Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$267,859.00
Summary
Dr Asha Bowen will be building the evidence to reduce the burden of infectious diseases in Australia's Indigenous children during her early career fellowship. This will include a randomised controlled trial on the treatment of acute gastroenteritis in the Northern Territory and developing new strategies to reduce the burden of skin infections in children living in remote communities.
PrtFII, A Streptococcus Pyogenes Fibronectin Binding Protein, And Invasive Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$296,540.00
Summary
Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin bind ....Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin binding protein, than those from uncomplicated skin sores. In this application we propose to extend this observation and compare biochemical properties of PrtFII from strains belonging to the above two sets of collections. We hypothesise that PrtFII from invasive strains bind to fibronectin more tightly than the proteins from strains that cause uncomplicated infection. We also will test whether sera from invasive disease cases have lower titre of antibodies to the conserved region of PrtFII than sera from uncomplicated cases. A streptococcal vaccine by necessity has to be a multi-component vaccine to cover a wide spectrum of diseases and epidemiological differences. The study proposed here may provide a basis to argue whether or not to include PrtFII in such a multi-component vaccine.Read moreRead less