Optimising Intervention Strategies To Reduce The Burden Of Group A Streptococcus In Aboriginal Communities
Funder
National Health and Medical Research Council
Funding Amount
$856,896.00
Summary
Skin sores are highly prevalent in remote Australian Indigenous communities and can lead to invasive infections and rheumatic heart disease. We will develop mathematical models to understand the transmission of skin sores, allowing us to define the optimal extent (household, community, region), timing and triggers for interventions to interrupt transmission. This will guide public health policy in reducing the prevalence of skin sores and scabies, and their accompanying disease burden.
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.
The END RHD CRE: Developing An Endgame For Rheumatic Heart Disease In Australia
Funder
National Health and Medical Research Council
Funding Amount
$2,601,147.00
Summary
Rheumatic heart disease (RHD) is caused by an abnormal immune reaction to some bacterial infections. Although RHD is rare in developed countries, Indigenous Australians still live with the burden of RHD. The END RHD CRE will explore risk factors for RHD, prevention with antibiotics, management of RHD and the potential for vaccine development. Individuals and communities experiencing RHD are integral partners to this work. The CRE will establish a strategy for ending RHD in Australia.
Can Skin Infection With Group A Streptococcus Cause Acute Rheumatic Fever?
Funder
National Health and Medical Research Council
Funding Amount
$459,450.00
Summary
It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of ....It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of the cause of ARF, and have important implications for prevention of ARF around the world. Presently, these approaches focus on diagnosing and treating sore throat, but no country has proven that such a program can be successful in substantially reducing new cases of ARF. If it was known that skin infection could lead to ARF, then countries (including Australia) could emphasise the importance of skin health programs. A further benefit of this knowledge would be to influence GAS vaccine development, which presently is largely focused on the prevention of sore throat. A different possibility has recently been raised - that the cause of ARF may not always be GAS, but instead that the related bacteria GCS and GGS may have the potential to cause this disease. Proof of this hypothesis would even more dramatically alter our understanding of disease causation, prevention, and vaccine development. We propose to determine the cause of ARF in Aboriginal communities by regularly swabbing families of people with a history of ARF, and using genetic fingerprinting of the bacteria from the skin and throat swabs. When cases of ARF occur, we will be able to determine the site and type of infection that precipitated the attack. We will conduct a related study in more communities, in which we will swab family members of people with ARF and of control families (without ARF) to determine the bacteria most commonly isolated from ARF families.Read moreRead less
Population-level Epidemiological Trends In Hepatocellular Carcinoma In Queensland 1996 - 2010.
Funder
National Health and Medical Research Council
Funding Amount
$251,695.00
Summary
Incidence and mortality of hepatocellular carcinoma (HCC, the most common form of liver cancer) is increasing in Australia, driven by viral hepatitis infections. Disease burden is not defined in Queensland, particularly for Indigenous, migrant and regional and remote communities. Such factors may influence risk of viral hepatitis, access to treatment, and incidence and survival of HCC. Defining disease burdens will enable clinical programs targeted at groups most at risk in order to impact HCC t ....Incidence and mortality of hepatocellular carcinoma (HCC, the most common form of liver cancer) is increasing in Australia, driven by viral hepatitis infections. Disease burden is not defined in Queensland, particularly for Indigenous, migrant and regional and remote communities. Such factors may influence risk of viral hepatitis, access to treatment, and incidence and survival of HCC. Defining disease burdens will enable clinical programs targeted at groups most at risk in order to impact HCC trends.Read moreRead less
Regulation Of Secretion Of The Fungal Virulence Determinant, Phospholipase B
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted ....Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted by the disease-causing fungus, Cryptococcus neoformans, and that it is important in enabling the fungus to invade the host's cells and spread around the body from the lungs to the brain, where it can cause meningoencephalitis. PLB is also produced by other disease-causing fungi. The mechanism of PLB secretion is completely unknown. In this project we aim to determine the pathways involved in PLB secretion with the intention of exploiting steps unique to pathogenic fungi, for the future design of new anti-fungal drugs.Read moreRead less
Invasive fungal infections are a serious, escalating health issue. They cause severe disease with high death rates and are very costly to the health system. Current drugs often have suboptimal efficacy and cause side effects. New drugs are needed urgently. Many fungi, including the AIDS-related pathogen, Cryptococcus neoformans, secrete phospholipase B (Plbp) to facilitate infection. We will identify and investigate the Plbp secretion pathway as a novel anti-fungal drug target.