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
Estimating The Burden Of Group A Streptococcal Diseases In Victoria
Funder
National Health and Medical Research Council
Funding Amount
$386,760.00
Summary
Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal pop ....Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal population (e.g. rheumatic fever, kidney disease). Streptococcal sore throat remains one of the most common childhood infections, and severe group A streptococcal diseases are thought to be increasing in incidence in Australia. Yet, there are no accurate data on the incidence and costs of these or other GAS diseases in non-Aboriginal Australians, or in most other populations around the world. It is becoming more urgent to collect this data as numerous vaccine candidates are entering human trials, new approaches to the treatment of sore throat are emerging, and new strategies to treat and control the spread of severe disease are being developed. We propose a comprehensive strategy to measure the incidence, prevalence and costs of each group of GAS diseases. We will follow a group of families for 12 months to detect cases of GAS sore throat and skin sores and measure the impact on the family. We will survey children in schools to estimate the prevalence of skin sores. We will check hospital records to calculate the number of cases of rheumatic fever and kidney disease. And we will maintain surveillance for severe diseases by checking hospital and laboratory records. We will also check to see if family members of people with severe disease have the GAS bacterium in their throats. We will then compile these data into a comprehensive estimate of the burden of disease in Victoria, and estimate the cost-effectiveness of different treatment and prevention strategies.Read moreRead less
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less