Severe Malaria In Children In Papua New Guinea: A Longitudinal Study Of Pathophysiology, Management And Outcome
Funder
National Health and Medical Research Council
Funding Amount
$484,808.00
Summary
The features of severe infection in children living in tropical countries may not allow differentiation between malaria and bacterial-viral causes. This can create significant problems with deciding on appropriate management. In addition, the main complications of malaria such as coma, increased acid levels in the blood and anaemia are not well understood. We plan to characterise infections in Papua New Guinean children in detail and explore mechanisms behind important malarial complications.
The Clag Gene Family Of P. Falciparum; Examining Roles In Cytoadherence, Rheological Properties Or Tissue Trophism.
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
There are approximately 500 million of cases of malaria per year worldwide and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by the sticking of red blood cells which contain malaria parasites to the lining of microscopic veins and blocking them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the ....There are approximately 500 million of cases of malaria per year worldwide and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by the sticking of red blood cells which contain malaria parasites to the lining of microscopic veins and blocking them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the acronym clag, for cytoadherence-linked asexual gene. Most Australians know of clag as a glue, and our data provides evidence that it sticks the parasitised red cells to veins via a protein called CD36 on the internal surface of veins. Our evidence for this has been published in two prestigious international journals. We propose here to examine the same gene in a mouse malaria model as it should be highly informative to see what effect destoying clag has on the disease in a living animal. Obviously this cannot be tested in people. It has now become clear that there are a number of slightly different clag genes and we do not know what the others do. We propose here that they may enable the parasitised red cells to stick to targets other than CD36 on the surfaces of veins, or affect blood flow of infected cells, or direct the parasitised red cells to other organs. The experiments that we propose should reveal whether these ideas are true.Read moreRead less
Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by ....Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the acronym clag, for cytoadherence-linked asexual gene; most Australians know of Clag as a glue. Our evidence for this has been accepted for publication by the prestigious USA journal Proceedings of the National Academy of Sciences of the USA. Recent work overseas aimed at determining the entire DNA sequence of the malaria parasite has shown that clag is not alone; there are at least 9 slightly different clag genes in the malaria parasite. What do the others do? We propose two possibilities. The first is that all of them act in cytoadherence but that different clags enable the parasitised cells to stick to different things on the lining of veins. The second is that they enable the parasitised cells, or perhaps the parasites alone, to stick to other things at different stages of the complex life cycle of the parasite. The experiments that we propose should show whether either of these proposals is true.Read moreRead less
Dysregulation Of Cytokine Networks: A Key Determinant Of The Pathogenesis Of Cerebral Malaria.
Funder
National Health and Medical Research Council
Funding Amount
$480,989.00
Summary
Malaria is a parasitic disease that kills some 2 million people each year. It affects the Australian region, e.g. PNG and SE Asia. One of the most serious complications is cerebral malaria (CM). It affects the brain and is often fatal. This project will show whether the early meeting of the malaria parasite with the host's immune system determines if the infection will be a mild, resolving one or a severe, possibly lethal one causing CM. This is highly relevant to vaccine development strategies.
Investigation Of A Virulence Locus On Chromosome 9 Of Plasmodium Falciparum Utilising Improved Transfection Technology
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Worldwide, there are approximately 500 million cases of malaria per year with over 1 million deaths, predominately in children under 5 years of age in Africa. We have identified a region of the malaria parasites' genome that we believe is responsible for two aspects of the parasites life cycle. Firstly, there is a gene responsible for the development of the sexual stage of the parasite that allows transmission from humans to mosquitoes and secondly there are two other genes that allow the parasi ....Worldwide, there are approximately 500 million cases of malaria per year with over 1 million deaths, predominately in children under 5 years of age in Africa. We have identified a region of the malaria parasites' genome that we believe is responsible for two aspects of the parasites life cycle. Firstly, there is a gene responsible for the development of the sexual stage of the parasite that allows transmission from humans to mosquitoes and secondly there are two other genes that allow the parasite to evade the human hosts immune system. We intend to investigate these genes using newly developed genetic engineering tools with the ultimate aim of finding agents or vaccines that can block their action, thus preventing either transmission of the parasite or the severe effects of infection.Read moreRead less
Age-and Species-related Regulation Of Host Inflammatory Responses In Falciparum And Vivax Malaria
Funder
National Health and Medical Research Council
Funding Amount
$323,640.00
Summary
Malaria kills 1 million people every year, mostly children. The cause of death from malaria differs between children and adults, yet the reason for these differences is unknown. We have shown that in adults regulatory immune cells contribute to malaria disease complications. We want to test if these cells also worsen malaria disease in children. Understanding age-related differences in immune cell regulation will help to improve malaria treatment and aid development of effective malaria vaccines ....Malaria kills 1 million people every year, mostly children. The cause of death from malaria differs between children and adults, yet the reason for these differences is unknown. We have shown that in adults regulatory immune cells contribute to malaria disease complications. We want to test if these cells also worsen malaria disease in children. Understanding age-related differences in immune cell regulation will help to improve malaria treatment and aid development of effective malaria vaccines for adults and children.Read moreRead less
Pathophysiology Of Malaria-associated Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$422,517.00
Summary
About 2 million people die each year from complications of malaria infection. A frequent, life-threatening complication of severe malaria is lung oedema. There is no specific treatment for the lung complications, which are poorly understood. There has been until now no good model system to study malaria lung complications. We have developed in mice an experimental model of malaria specifically to determine the mechanisms that cause lung pathology, which has never been done before. Such experimen ....About 2 million people die each year from complications of malaria infection. A frequent, life-threatening complication of severe malaria is lung oedema. There is no specific treatment for the lung complications, which are poorly understood. There has been until now no good model system to study malaria lung complications. We have developed in mice an experimental model of malaria specifically to determine the mechanisms that cause lung pathology, which has never been done before. Such experiments cannot be performed in humans for ethical and logistical reasons. We believe that pulmonary oedema is caused by products of the immune system and we will rigorously test this idea in our study. The aim is to learn more about the processes occurring in this disease so as to devise new treatment strategies.Read moreRead less
A Randomised Control Trial Of Medical Treatment Versus The Placement Of The Lap Band In Severely Obese Adolescents.
Funder
National Health and Medical Research Council
Funding Amount
$481,905.00
Summary
There has been a substantial rise in the number of overweight and obese adolescents in our community. While prevention of obesity is the ultimate goal, effective stratagies for the management of obese adolescents must be sought. Unfortunately there are few studies that have focused on this problem in adolescents and success has been very limited. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in severely obese (body mass index > 35 kg-m2) adul ....There has been a substantial rise in the number of overweight and obese adolescents in our community. While prevention of obesity is the ultimate goal, effective stratagies for the management of obese adolescents must be sought. Unfortunately there are few studies that have focused on this problem in adolescents and success has been very limited. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in severely obese (body mass index > 35 kg-m2) adults and there are now several small studies that demonstrate its effectiveness in adolescents. Modern obesity surgery involving the keyhole placement of an adjustable band around the very upper part of the stomach has proven to be safe and effective and requires one 24 hr stay in hospital. In this collaborative study, involving the Monash University Centre for Obesity Research and Education and the Royal Children's Hospital, we propose to formally test, for the first time, the effectiveness of a weight loss program that includes adjustable band surgery, and compare this with a comprehensive best care behavioral program, over a period of 2-years in severely obese adolescents. We estimate that suitable subjects will come from the top 1% for body mass index in our community. After thorough assessment 50 suitable candidates with ages ranging from 14 to 18 years will be randomly allocated to one of the two treatment programs. The intensity of each program will be similar. A broad range of measues including: weight, health status, physical disability, psychological status, body image and quality of life, will be performed before and at completion of the 2-year programs. In addition we will compare the complications, compliance and cost of the two programs. This study will help us assess and compare the effectiveness of the 2 programs and provide vital information regarding the role of modern keyhole obesity surgery for the management of severely obese adolescents.Read moreRead less