Viral And Host Cell Gene Expression During The Establishment And Maintenance Phases Of Human Cytomegalovirus Latency
Funder
National Health and Medical Research Council
Funding Amount
$149,250.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. The overall aim of these studies is to provide a much better understanding of how CMV latency is established and maintained, with the ultimate goal of making advances for the design of anti-viral therapies to disrupt these processes. This project has three major components: Firstly, we aim to identify and characterise viral gene expression during the establishment of latency and these findings will have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during the establishment and maintenance phases of latency. Thirdly, we will apply microarray technologies to determine how human cell genes are altered in response to the expression of individual viral genes that are active during the latent phase of infection.Read moreRead less
Prevention Of Multi-drug Resistant Tuberculosis In A High Prevalence Setting: ‘Connecting The DOTS’ In Vietnam
Funder
National Health and Medical Research Council
Funding Amount
$3,382,020.00
Summary
The close contacts of people with multi-drug resistant tuberculosis (MDR-TB) have a high risk of developing the disease. The V-QUIN MDR-TB Trial will evaluate the effectiveness of an oral antibiotic (levofloxacin) in preventing drug resistant TB among infected household contacts of TB patients. Household contacts from 10 Provinces in Vietnam will be randomly allocated to receive six-months of either levofloxacin or a placebo, and then followed for two years to see if they develop tuberculosis.
Community-wide Active Case Finding For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$3,422,325.00
Summary
During 2010, 8.8 million people developed TB and 1.45 million people died due to the disease. In this project, which will be conducted in Vietnam, one of the countries in our region with a particularly high prevalence of TB, we will test a new form of an old intervention: community-wide screening for TB, not with x-rays but by testing sputum. If the project is successful it has the potential to lead to a giant leap forward towards the elimination of TB as a global health problem.
Development And Validation Of A Latent Tuberculosis Diagnostic
Funder
National Health and Medical Research Council
Funding Amount
$534,865.00
Summary
Globally, tuberculosis is a leading cause of death with 9.6 million new diagnoses in 2014. The diagnosis of latent TB infection is important, but is difficult to make because current assays are suboptimal. We have developed a very simple assay which detects responses to TB antigens by co-expression of two surface markers expressed by CD4+ T cells. We propose to develop this into a highly standardised kit for the diagnosis of TB with our commercial partner Cytognos.
A New Direction For TB Control In Highly Endemic Countries: A RCT Of Active Case Finding
Funder
National Health and Medical Research Council
Funding Amount
$1,362,910.00
Summary
Tuberculosis is the number 1 health problem in Vietnam . Many people with TB do not know they have the disease but are infectious to others. Hence, the disease continues to spread. This project will investigate the role of x-ray screening to detect and treat more people with TB, particularly those who do not have symptoms. This may be an important element of future TB control programs in Vietnam and elsewhere in our region.
Improving Global Tuberculosis Control With The AuTuMN Platform
Funder
National Health and Medical Research Council
Funding Amount
$655,059.00
Summary
Tuberculosis (TB) is the world’s leading infectious killer, with the failure of global control responsible for the vast majority of Australia’s cases. Using our robustly developed software platform, we have performed several country-level studies to predict the future burden of disease and compare the impact of alternative responses to controlling the epidemic. In this project, we will extend our platform to perform simulations at the global level and answer key questions in TB control.
A Randomized Clinical Trial Comparing Effectiveness Of 4RIF And 9INH For Treatment Of Latent TB Infection
Funder
National Health and Medical Research Council
Funding Amount
$496,875.00
Summary
Treatment of latent tuberculosis infection (LTBI) is one intervention that is known to prevent the occurrence of active TB. Current treatment is based on a six to nine month course of isoniazid. The treatment has side effects in some people and many people do not complete the treatment. The present study is to test an alternative treatment regimen (4 months of rifampicin) which has fewer side-effects and is more likely to be completed.
Analysis Of Viral And Cellular Gene Expression During Human Cytomegalovirus Latent Infection Of Hematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
Summary
Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body a ....Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. This project has three major components. Firstly, we aim to continue studies which are defining what viral genes are active (ie expressed) during latent infection. Identification of these genes and determination of how they function may have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during latency and reactivation. The study of viral and cellular gene expression during latency may contribute to the development of drugs which interfere with the viruses ability to become latent or reactivate. Thirdly, we have preliminary results which suggest that latent HCMV may actively avoid detection by the immune system. In this project we also aim to determine the mechanism by which the virus interferes with the expression of molecules which are an essential component of our immune system.Read moreRead less
Interactions Between HIV And Mycobacterial Infections Of Macrophages Mediated By Changes In Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$119,625.00
Summary
HIV-AIDS and tuberculosis are two of the worlds most important diseases. HIV-AIDS is the fourth leading killing disease worldwide and tuberculosis is the leading opportunistic infection in patients with AIDS particularly in the developing world. Both microbes infect the same cell type, the macrophage, which is widely distributed throughout the body, particularly in lymph nodes and lung. Recent studies in humans have shown that HIV and TB like organisms stimulate each others growth. This study us ....HIV-AIDS and tuberculosis are two of the worlds most important diseases. HIV-AIDS is the fourth leading killing disease worldwide and tuberculosis is the leading opportunistic infection in patients with AIDS particularly in the developing world. Both microbes infect the same cell type, the macrophage, which is widely distributed throughout the body, particularly in lymph nodes and lung. Recent studies in humans have shown that HIV and TB like organisms stimulate each others growth. This study uses the immense power of DNA microarrays, based on the identification of almost all genes by the human genome project, to decipher the interactions between the two microbes. By following up new leads indicated by the microarrays, the way in which the microbes manipulate the macrophage to enhance their own growth and that of the other can be eventually deciphered. This will provide new strategies for future interventions. New drugs are urgently needed for both microbes.Read moreRead less