Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female mosquitoes. About 3.2 billion people – almost half of the world’s population – are at risk of malaria.
Researchers from The University of Sydney in collaboration with the Australian Synchrotron, the Australian Nuclear Science and Technology Organisation (ANSTO) and researchers in the United States, have revealed how a dangerous form of malaria can lead to brain damage and death, developing a new multi-modal imaging approach that could also shed light on neurodegenerative diseases including Parkinson’s and Alzheimer’s.
In the research, funded by the Australian Research Council and published overnight in Science Advances, the team used a suite of imaging techniques to solve decades-old controversies on how ‘friendly fire’ of the immune system causes deadly cerebral malaria, a disease mostly affecting children under five in Africa and adults in South East Asia, paving the way for new anti-inflammatory and anti-oxidant treatments.
Dr Mark Hackett from The University of Sydney, says the research produced complementary information from five forms of imaging – including the spread of metals, density of haemoglobins and distribution of other biomolecules – providing conclusive evidence of how malaria-infected red blood cells can induce brain damage.
‘To avoid being cleansed from the body by the spleen, malaria-infected red blood cells are forced by the parasite to display sticky proteins on their surface, allowing them to anchor to the walls of small blood vessels elsewhere in the body; when this occurs in the brain it can result in cerebral malaria.
‘Using cutting-edge imaging techniques we showed, in cerebral malaria, the biochemical damage caused when the immune system attacks to kill the infected, anchored blood cells, breaches the highly sensitive blood-brain barrier, allowing the mingling of blood and inflammatory molecules in brain tissue, leading to its destruction.’
Dr Hackett says the combined imaging approach drew on the best attributes of microscopy resources at the Australian partner organisations, and high spatial resolution X-Ray fluorescence microscopy at Argonne National Laboratory in the United States, to gather information without chemically interfering with brain tissue samples, enabling a more accurate reflection of the disease environment.
Professor Peter Lay, Director of the Vibrational Spectroscopy Core Facility at The University of Sydney says the new clarity around the mechanisms of deadly cerebral malaria – which claims the lives of 750,000 people globally each year – will inform new interventions for people at risk of the disease and opens up avenues of research into other brain diseases.
‘Previously we did not clearly understand processes involved in the disease, but our new evidence that the immune system is to blame for the initial damage, with subsequent oxidative stress inducing the death of brain tissues, means we can develop anti-inflammatory and anti-oxidant interventions that subdue the immune attack and reduce subsequent brain damage.
‘We believe our chemical-free multi-modal approach to imaging the brain can be applied to research across all chronic neurodegenerative disease and we plan to replicate this successful experimental approach to shed new light into the molecular processes that drive multiple sclerosis, motor neurone disease and Parkinson’s and Alzheimer’s diseases.’