I am a clinician-scientist in infectious and tropical diseases, working towards the better understanding of the pathophysiology of malaria and other tropical diseases of public health importance in our region, and new ways of prevention and treatment.
Targeting Microvascular Dysfunction In Severe Malaria
Funder
National Health and Medical Research Council
Funding Amount
$871,923.00
Summary
In severe malaria blood vessels cannot make enough protective nitric oxide (NO). The gel-like lining of blood vessels (glycocalyx) is needed to produce NO, but this is damaged in some severe infections. We will test whether glycocalyx is lost in malaria and how it affects blood vessel NO and function in human volunteer infections and in patients with and without severe malaria. We will test whether a salt nitrite, can be used to safely increase NO and blood vessel function in severe malaria.
Pathophysiology And Treatment Of Malaria And Other Tropical Infectious Diseases Prevalent In Our Region
Funder
National Health and Medical Research Council
Funding Amount
$560,284.00
Summary
Nick Anstey is internationally recognised for his discoveries in malaria and other tropical infectious diseases. He leads a major tropical infectious disease research program in Darwin and SouthEast Asia that attracts some of the brightest researchers and students from Australia and beyond to understand disease mechanisms and work on new ways to treat illness and prevent death. He uses results to change policy and practice not only in Australia but around the world.
A Randomised Controlled Trial Of L-arginine And-or Vitamin D To Improve Outcomes In Pulmonary Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$942,297.00
Summary
Two nutrients, arginine and vitamin D, are used by defence cells in our lungs to kill the tuberculosis bacteria. We will test whether giving arginine and-or vitamin D to people with TB (in addition to their usual TB medications) will help them recover faster and cause less long-term lung damage. We will also check whether these nutrients make them less infectious to other people.
Interaction Of Anti-viral IDO And NOS2 In Vivo In A Novel Murine STD Model.
Funder
National Health and Medical Research Council
Funding Amount
$573,629.00
Summary
Sexually transmitted viral diseases (STD) are increasing globally, but we know little of how virus is controlled early in infection. We have shown for the first time in vivo, in our STD model, that during an antiviral immune response, soluble factors turn on an enzyme, indoleamine 2,3-dioxygenase (IDO), to break down and deplete the amino acid, L-tryptophan, starving virus to reduce growth early in STDs. Our project will further define the action and control of IDO in STD.
Endothelial Dysfunction As A Therapeutic Target In Severe Malaria
Funder
National Health and Medical Research Council
Funding Amount
$842,329.00
Summary
Even with very best drugs to kill malaria parasites, over 15% of patients with severe malaria still die. Their blood vessels are clogged up by malaria parasites. We have shown that the cells lining their blood vessels can't make enough nitric oxide to keep them non-sticky and allow blood through. We want to test whether giving arginine can 1) increase nitric oxide, 2) open up the clogged blood vessels and 3) dampen down other processes that clog up blood vessels in severe malaria.
We plan to continue our work that to date is consistent with the idea that excessive induction of the enzyme iNOS, and thus production of nitric oxide in key locations, is a central event in how falciparum malaria kills people who become infected with this parasite. This will largely be based on detecting iNOS and nitrotyrosine in tissues from autopsies collected as part of a malaria research programme conducted in Malawi. Laboratory experiments will also be performed. In particular, there is a ....We plan to continue our work that to date is consistent with the idea that excessive induction of the enzyme iNOS, and thus production of nitric oxide in key locations, is a central event in how falciparum malaria kills people who become infected with this parasite. This will largely be based on detecting iNOS and nitrotyrosine in tissues from autopsies collected as part of a malaria research programme conducted in Malawi. Laboratory experiments will also be performed. In particular, there is a body of evidence that suggests the following interactions between inflammatory cytokines and salicylate, with important practical ramifications, in children. 1. Salicylate toxicity, like the acute multi-organ form of childhood malaria it mimics, is probably caused by excess systemic iNOS induction. This plausibly includes the metabolic acidosis, hypoglycaemia, seizures, coma and cerebral oedema seen in both conditions. Both are thus logically susceptible to treatment with specific iNOS inhibitors. 2. The same picture would arise in children when smaller doses of salicylate synergise with IFN-g, IL-1b, and perhaps other cytokines induced by malaria as well as by viruses. This gives the first proposed explanation for Reye's syndrome, defining the circumstances in which it occurs, and predicting a rationale for its treatment. Through the parallels seen in different age groups in malaria and aspirin toxicity, it also rationalises the difference in childhood vs adult malaria syndromes. 3. The overall severity and mortality of childhood malaria in East Africa may be worsened, through this cytokine-salicylate synergy, by home treatment with aspirin when children first become ill. 4. A relative absence of salicylate intake by children in various malarial Pacific Islands may contribute to falciparum malaria being a less severe disease there than in East Africa.Read moreRead less