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The Clinical Value Of Serology And Molecular Tests For Diagnosing Invasive Aspergillosis In At-risk Hematology Patients
Funder
National Health and Medical Research Council
Funding Amount
$1,095,500.00
Summary
Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic t ....Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic tests are not good at detecting infection or often only detect the infection at advanced stages when treatment is ineffective. Because of the limitations of current diagnostic tests the current practice is to give empiric antifungal therapy (EAFT) early to treat Invasive Aspergillosis. However studies have demonstrated that this therapy has only resulted in a minor reduction in the mortality rates and it causes significant drug toxicity. It is a suboptimal treatment modality. New tests have been developed to diagnose Invasive Aspergillosis. These tests are for the detection of an Aspergillus protein in blood and for the detection of Aspergillus DNA in the blood. Available data suggests that these new tests are sensitive in the detection of Invasive Aspergillosis. Also other studies suggest that these new tests make an early diagnosis and seem to be able to monitor responses to treatment. However no study has been performed to date which demonstrates that the use of these tests can impact on important patient outcomes. This trial is designed to determine whether the use of the new tests to guide therapy will help improve treatment of Invasive Aspergillosis, reduce drug toxicity and reduce the death rate in the high-risk patients as compared with the current standard method of diagnosis and treatment with EAFT. If the trial is successful then this represents a significant advancement in the treatment and survival of leukaemic and bone marrow transplantation patients.Read moreRead less
An In Depth Analysis Of Clinical And Virological Outcomes Of 2 Strategies For The Antiretroviral Salvage Of First-line Regimen Virological Failure For HIV-1 Infection Tested In An Australian-led Randomised, International, Multi-centre Clinical Trial
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
The recently completed Australian-led SECOND-LINE trial is the first high quality study to provide reliable evidence for policy recommendations for the composition of anti-HIV drug cocktails after standard initial treatment has failed. This award will support the researcher in further refining our understanding of how to manage second-line therapy including proposals to test the use of low-cost technologies for application in resource-limited settings where the majority of people with HIV live.
Early Diagnosis And Prognosis Of Severe Dengue In Vietnamese Children
Funder
National Health and Medical Research Council
Funding Amount
$689,323.00
Summary
Dengue is a mosquito-borne viral infection. Tropical Australia has experienced multiple outbreaks of dengue in the last decade. This project, conducted in Ho Chi Minh City, Viet Nam, will define the accuracy of a rapid diagnostic test for the early diagnosis of severe dengue. In doing so, we will also derive an algorithm using simple laboratory and clinical findings that can help identify those patients at greatest risk of severe complications, with benefits for both patients and hospitals.
A Functional And Structural Approach To Understanding Leptospiral Host-pathogen Interactions
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Leptospirosis is a zoonosis of worldwide distribution caused by infection with pathogenic Leptospira. Infection occurs due to contact with water contaminated by urine of domestic animals. It occurs infrequently in Australia, but recent local surveillance data indicate hospitalisation rate of 56% with an average duration of 5.3 days. Through the combined approach of structural biology and functional microbiology we hope to understand how leptospira interacts with the human host.
Factors That Influence Disease Severity In Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$149,076.00
Summary
Tuberculosis (TB) is a major global health problem and is one of the leading causes of death from an infectious disease worldwide. The severity of disease that occurs with TB is dependent on many complex factors including the infected person’s immune system and factors related to the TB organism itself. This research will determine the key factors that cause severe disease in TB which will translate into improved care of TB patients and enhance further research in this field.
Integrons, Mobile Gene Cassettes And Pathogencity In Vibrio Cholerae
Funder
National Health and Medical Research Council
Funding Amount
$550,285.00
Summary
Bacteria are remarkably adaptive and evolve in ways that plants and animals do not. One of these ways is Lateral Gene Transfer or LGT, which is a process allowing bacterial cells to share genes. Such mobile genes can greatly influence the extent to which pathogenic bacteria can cause disease. One notable example is Vibrio cholerae where many strains can be benign but some can give rise to cholera pandemics. Here, we will investigate this phenomenon in this important bacterium.
Dissecting The Role Of The Adipokine Leptin In Control Of The Inflammatory Response To Helicobacter Pylori
Funder
National Health and Medical Research Council
Funding Amount
$569,063.00
Summary
Helicobacter pylori is a bacterium that causes chronic gastric inflammation (gastritis), which may lead to cancer. Approximately 20% of Australians are infected. As part of the search for a human vaccine, we are attempting to understand the immune response against this bacterium. This study will investigate a novel observation that adipokines-small proteins produced by fat cells can regulate the actions of immune cells in the stomach and in this way determine whether vaccination works.
Targeting The Mannose Activation Pathway In Leishmania - Novel Drug Targets And Vaccines.
Funder
National Health and Medical Research Council
Funding Amount
$338,661.00
Summary
Leishmaniasis is a parasitic disease ranging in severity from skin lesions to fatal systemic infection. It is a serious public health problem throughout many regions of the world. Co-infection with HIV has emerged as a serious problem in Africa, South America and southern Europe. Recently, leishmaniasis has been identified in East Timor and in kangaroos in Australia. Treatment of leishmaniasis is based on chemotherapy, but currently used drugs are expensive, have high toxicity and unwanted side ....Leishmaniasis is a parasitic disease ranging in severity from skin lesions to fatal systemic infection. It is a serious public health problem throughout many regions of the world. Co-infection with HIV has emerged as a serious problem in Africa, South America and southern Europe. Recently, leishmaniasis has been identified in East Timor and in kangaroos in Australia. Treatment of leishmaniasis is based on chemotherapy, but currently used drugs are expensive, have high toxicity and unwanted side effects. They have also been compromised by the emergence of resistance in the parasite. Leishmania synthesises a range of surface molecules, which are needed for virulence and parasite survival in the host. The biosynthesis process of these molecules requires activated mannose. We have identified two novel parasite genes encoding for enzymes, which are essential for the biosynthesis of surface virulence factors. When either of these genes is deleted the parasite can no longer cause disease. This suggests that drugs targeting the two enzymes will be able to control the infection. We will produce crystals of these enzymes and solve their 3D structure using state of the art technology to screen libraries of synthetic chemicals to find candidate inhibitors of enzyme activity. When these compounds are identified we will use computer modelling to design compounds based on these inhibitors and crystal structure, which will lead to a new generation of anti-Leishmania drugs. We will also determine whether the avirulent parasites can be used as an attenuated vaccine. Recovery from infection leads to a solid immunity and protection from subsequent infection indicating that vaccination is feasible, but despite of a huge amount of research there is no antileishmanial vaccine currently available. This study will lead to potential novel antileishmanial drugs and vaccines. It will also provide fundametal new knowledge of the structure of enzymes critical for parasite virulence.Read moreRead less
Trafficking And Expression Of PfEMP1 On The Surface Of P.falciparum-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
Malaria causes over 2 million deaths each year. The parasite infects human red blood cells and expresses a virulence protein on the erythrocyte surface allowing it to adhere to the microcapillaries preventing clearance through the spleen. We aim to understand how the parasite is able to express this virulence protein on the parasite-infected red blood cell surface. Identification of the proteins involved will provide potential drug targets to develop novel antimalarial compounds and strategies.