From Maps To Efficient Multi-parasite Control In The Philippines
Funder
National Health and Medical Research Council
Funding Amount
$358,121.00
Summary
Schistosomiasis and soil-transmitted helminths are major parasitic infections in Asia, causing anaemia, poor growth and poor school performance and death in some chronic schistosomiasis cases. We will use maps to demonstrate the geographic distribution of these parasites in the Philippines. We will estimate the impact and costs and benefits of parasite control programmes. This research will help plan more efficient parasite control and reduce the impact of these infections in the Philippines.
Transport Pathways Of Host-derived Iron In Schistosomes Parasites
Funder
National Health and Medical Research Council
Funding Amount
$322,091.00
Summary
This project will identify the diversity and biological roles of receptors for metabolic iron expressed on the body surface of the parasitic blood flukes (schistosomes) of humans. Schistosomes are a major health problem in many tropical countries and are responsible for significant human morbidity and lost productivity. Adult worms feed on human blood, from which derive amino acids for the production of many hundreds of eggs released per day into the human blood stream. The intense cellular resp ....This project will identify the diversity and biological roles of receptors for metabolic iron expressed on the body surface of the parasitic blood flukes (schistosomes) of humans. Schistosomes are a major health problem in many tropical countries and are responsible for significant human morbidity and lost productivity. Adult worms feed on human blood, from which derive amino acids for the production of many hundreds of eggs released per day into the human blood stream. The intense cellular response induced by parasite eggs trapped in body organs is the major cause of chronic human disease. We have discovered two intriguing phenomena of iron metabolism in schistosomes. Firstly, schistosomes have a greater reliance on iron than many other organisms, storing a surfeit in cells that produce the protein-rich egg shell. Secondly, a major transmembrane iron transporter of the parasites, thought to be involved in the uptake of iron, is found on the parasite external body surface and not in the parasite intestine. The extensive nutritional dependence of these worms on iron and the surface location of mediators of iron uptake raise the exciting possibility that we have uncovered a novel system that might be exploited for vaccine or drug-mediated control of these significant human parasites. If we can dissect the pathways schistosomes use to derive iron from their hosts, we may be able to generate vaccines to block this nutritional pathway, or use drugs to block embryogenesis. This project is a fact-finding mission that asks if the host-interactive tegument of these parasites is a major source of metabolic iron. Molecules we demonstrate to be present on the surface will be tested as vaccine candidates in mouse vaccine trialsRead moreRead less
Fitness Versus Fatness: Disentangling Their Effects On Disease Outcomes And Estimating The Population Burden Of Disease
Funder
National Health and Medical Research Council
Funding Amount
$188,537.00
Summary
Overweight and physical inactivity are two of the major risk factors for cardiovascular disease and diabetes. With increasing population levels of overweight, governments are increasingly advocating public health measures aimed at increasing physical activity levels or otherwise decreasing weight. There has been much research concerning which of these factors is the key prognostic factor for adverse health outcomes, but an ongoing lack of clarity of research findings has led to uncertainty as to ....Overweight and physical inactivity are two of the major risk factors for cardiovascular disease and diabetes. With increasing population levels of overweight, governments are increasingly advocating public health measures aimed at increasing physical activity levels or otherwise decreasing weight. There has been much research concerning which of these factors is the key prognostic factor for adverse health outcomes, but an ongoing lack of clarity of research findings has led to uncertainty as to the direction of recommendations for preventive health strategies and population lifestyle changes. In addition, the risks of overweight, in particular, have been accused of being exaggerated in both the scientific and lay literature. This is often due to the difficulty of dealing appropriately with time varying confounders which are also intermediate factors (such as hypertension). To date, no studies have performed careful longitudinal modelling of the joint effects of physical inactivity and overweight on cardiovascular events and diabetes while taking into account the effects of factors, such as hypertension or atherosclerosis, that influence both physical activity and overweight as well as disease, and simultaneously are consequences of these risk factors. Standard statistical methods are known to produce biased estimates in these situations but we will apply more recently developed statistical techniques to provide much improved estimation of these effects. After the statistical modelling stage, we will model the burden of diabetes, cardiovascular disease and mortality associated with given levels of overweight and physical inactivity. These will be combined with population levels of overweight and inactivity to identify the fraction of the current and future burden of disease attributable to these risk factors.Read moreRead less
ROLE OF PROTEASE ACTIVATED RECEPTORS IN CYSTIC FIBROSIS LUNG PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$176,521.00
Summary
Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the ....Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the respiratory epithelium. These, in turn, stimulate the movement of neutrophils from the blood to the lung where damage then ensues. How these proteases stimulate release is unclear but studies suggest other proteases involved in inflammation induce release through their interaction with a novel group of protease activated receptors (PAR). In this study, we wish to determine whether PAR are activated or inactivated by host and bacterial proteases commonly seen in the lungs of CF patients. If PAR are activated, it may be possible to develop antagonists which target specific PARS to modulate respiratory epithelial cell function. If inactivated, preservation by adjunct protease inhibitor treatment may be highly beneficial. We will use in vitro technology and cells derived from non-CF and CF patients. This study has great potential in the development of adjunct anti-inflammatory therapy for the treatment of both CF and other inflammatory lung diseases.Read moreRead less
Development And Application Of Theoretical Models Of Plasmodium Transmission To Guide Malaria Elimination Efforts
Funder
National Health and Medical Research Council
Funding Amount
$315,401.00
Summary
There is currently a worldwide endeavour to eliminate malaria but there are few tools available to evaluate the impact of intervention strategies in the Asia-Pacific region. This project aims to address this deficiency by developing simulation models of Plasmodium vivax and mixed species infections, and using these new tools to investigate the likely impact of a variety of intervention strategies including bed nets, improved access to treatment and mass drug administration.