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.
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.
A Safety, Tolerability, Pharmacokinetic And Efficacy Study Of Azithromycin Plus Piperaquine As Intermittent Presumptive Treatment In Pregnant Papua New Guinean Women
Funder
National Health and Medical Research Council
Funding Amount
$345,684.00
Summary
The purpose of this research is to investigate a new antimalarial combination therapy, azithromycin (AZI) plus piperaquine (PQ), for the prevention of malaria infection in pregnant Papua New Guinean women. It is anticipated that these studies will provide sufficient data to determine if AZI-PQ is a suitable alternative treatment option in PNG, and other countries which have similar malaria epidemiology including the presence of drug resistant parasites.
Molecular Mechanisms Of Ivermectin Resistance In The Ectoparasitic Mite, Sarcoptes Scabiei
Funder
National Health and Medical Research Council
Funding Amount
$289,561.00
Summary
A largely neglected parasitic disease, scabies is a significant disease of children, particularly in remote Aboriginal communities in northern Australia. The recent emergence of ivermectin resistance threatens future control of scabies. This research explores the genetic basis of ivermectin resistance in the scabies mite, developing molecular markers to identify the emergence of resistance in the community, leading to improved tools for resistance management and sustainable treatment strategies.
RECOMBINANT MALARIAL PYRIMIDINE ENZYMES AS DRUG TARGETS
Funder
National Health and Medical Research Council
Funding Amount
$229,750.00
Summary
Malarial parasites have now developed resistance to most of the available drugs and there is an urgent need for drugs with new mechanisms of action. Institutions collaborating on the Malarial Genome Project have sequenced the majority of DNA in the 14 chromosomes. The nucleotide sequence available on the internet contains thousands of open reading frames (ORFs) which encode proteins essential for survival of the parasite. Many of these proteins are enzymes which are suitable targets for drug dev ....Malarial parasites have now developed resistance to most of the available drugs and there is an urgent need for drugs with new mechanisms of action. Institutions collaborating on the Malarial Genome Project have sequenced the majority of DNA in the 14 chromosomes. The nucleotide sequence available on the internet contains thousands of open reading frames (ORFs) which encode proteins essential for survival of the parasite. Many of these proteins are enzymes which are suitable targets for drug development. A knowledge of the molecular architecture of the active site of such enzymes provides a template for drug design. The malarial parasite, Plasmodium falciparum, can only synthesise pyrimidine nucleotides for DNA via the de novo pyrimidine pathway. We have cloned the genes encoding three of the enzymes of the de novo pathway using sequence information from the Malarial Genome Project. Dihydroorotase, orotate phosphoribosyltransferase, and OMP decarboxylase, catalyse reactions 3, 5 and 6 of the pathway. We have expressed these enzymes in the bacterium Escherichia coli enabling large-scale production of these drug targets. We propose to characterise the catalytic and inhibitory properties of these enzymes, and grow protein crystals for determination of atomic structures by x-ray diffraction. The structures will provide templates for rational design of new antimalarial drugs. In a second approach for develoment of new drugs, the 3 malarial enzymes will be screened against chemical libraries for inhibition of catalytic activity. The initial screen will utilise a high throughput Biacore 3000 instrument which detects strong interactions between a target enzyme and candidate inhibitors. A thorough knowledge of the catalytic mechanisms, the three-dimensional structures and novel first generation inhibitors of these 3 malarial target enzymes, will provide a strong basis for development of new antimalarial drugs.Read moreRead less