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I am an infectious diseases physician and basic scientist interested in the immunopathogenesis of HIV and hepatitis B virus. My work focuses on HIV viral reservoirs and immune reconstitution and the adaptive immune response to hepatitis B virus.
Screening Agents Active Against The Late-stage Inflammatory Cytokines For Activity Against Influenza Disease
Funder
National Health and Medical Research Council
Funding Amount
$241,409.00
Summary
Infection with a virulent influenza virus that the body has never encountered before, particularly H5N1, sends the immune system into overdrive, and causes a massive release of proteins (inflammatory cytokines), known as a cytokine storm, that in and of itself leads to death. The object of this research is to screen, in a mouse influenza model, agents known to prevent this occurring and antagonise it once it has occurred. This will be done with and without Tamiflu, a standard anti-influenza drug ....Infection with a virulent influenza virus that the body has never encountered before, particularly H5N1, sends the immune system into overdrive, and causes a massive release of proteins (inflammatory cytokines), known as a cytokine storm, that in and of itself leads to death. The object of this research is to screen, in a mouse influenza model, agents known to prevent this occurring and antagonise it once it has occurred. This will be done with and without Tamiflu, a standard anti-influenza drug.Read moreRead less
Processes Underlying Establishment And Maintenance Of The Latent HIV Resevoir And Potential Impact Of Integrase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$318,044.00
Summary
Therapy for HIV-infected individuals is currently able to control the growth of the virus, but cannot eradicate the viral infection. This is due to a pool of CD4+ T lymphocytes which contain HIV DNA in a latent state, ready to reactivate as soon as therapy is interrupted. This project aims to better understand how this pool of latently infected CD4+ T lymphocytes is established and maintained, particularly how it is linked to the essential T cell survival signal from interleukin 7.
Evaluation Of Naturally Occurring Resistance To Direct Acting Antiviral Drugs (DAAs) In Individuals With Acute Hepatitis C Infection
Funder
National Health and Medical Research Council
Funding Amount
$333,778.00
Summary
Hepatitis C therapy in the future is likely to involve the use of Directly Acting Antivirals, which offer a better chance of treatment success and shorter treatment courses. The downside to these new agents is the possible development of drug resistance. Studies suggest that drug resistant strains may already exist in some individuals prior to treatment. This study plans to use sensitive methods to examine how common drug resistant strains are in untreated individuals with acute hepatitis C.
Understanding The Side Effects Of HAART In HIV Patients
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Combination therapy has dramatically improved the life expectancy of people living with HIV. However, the long term side effects of these medications can be significant. Not everyone treated with the same drugs suffers similar side effects. This project seeks to unravel factors that lead a given individual to experience particular side effects. Understanding why medication side effects occur will be critical in finding safer ways to treat HIV.
HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional thro ....HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional throughout adult life. The role of the thymus in HIV-1 infection remains controversial. Studies of the role of the thymus in HIV-1-infected individuals has been limited by the lack of a marker of thymic function in vivo. We have recently developed a novel assay to quantify cells of recent thymic origin by taking advantage of certain molecular events that occur in the thymus during the production of new T lymphocytes. This molecular event creates a circular piece of DNA, called a T-cell receptor excision circles (TREC). TREC concentration in the periphery will increase with an increase in thymic output but will reduce in the presence of T cell proliferation or cell death. In order to determine the contribution of the thymus to immune reconstitution following HAART, we plan to study the dynamics of thymus function in HIV-1 infection by measuring TREC and T cell turnover in HIV-1 infection prior to and following HAART. In a subgroup of individuals, more commonly seen following treatment of HIV-1 infection in children, there is an increase in CD4+ T lymphocytes in the absence of a significant reduction in viral suppression. The role of the thymus in this unique subset of individuals will be studied.Read moreRead less
Disease Burden, Risk Factors And Treatment Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$95,564.00
Summary
Plasmodium knowlesi is a form of monkey malaria recently found to also cause increasing numbers of natural infections in humans in South-East Asia. This research will describe the burden of P. knowlesi malaria in an area of Malaysian Borneo. The risk factors for acquiring P. knowlesi malaria will be assessed. Finally the optimal treatment for non-severe cases of P. knowlesi and P. vivax malaria will also be evaluated by comparing the 2 currently recommended anti-malarial medications in Malaysia.
A Randomised Controlled Trial (RCT) Of Azithromycin Versus Doxycycline For The Treatment Of Rectal Chlamydia Infection In Men Who Have Sex With Men.
Funder
National Health and Medical Research Council
Funding Amount
$797,906.00
Summary
Rectal chlamydia is very common among gay men; it can exist for long periods without symptoms leading to ongoing transmission. Azithromycin (1 gram single dose) or 7 days doxycycline (100mg twice daily) are the two recommended treatments globally. But, there is concern about rectal chlamydia treatment with reports of up to 22% failure following azithromycin. We will conduct a randomised trial to compare these treatments for rectal chlamydia and determine which drug works better.
Malaria And Infectious Diseases In The Asia-Pacific: Drugs, Vaccines And Diagnostics
Funder
National Health and Medical Research Council
Funding Amount
$210,873.00
Summary
Dr Karunajeewa is an expert in the treatment of malaria and other infectious diseases that have a major impact on the health of people living in developing countries of the tropical zone of the Asia-Pacific region. His ongoing research aims to develop better ways of diagnosing these infections, defining their relative importance in terms of overall burden of disease, finding optimal drug treatments and testing the effectiveness of new vaccines for their prevention.