Viral infections of the central nervous system (CNS) have been emerging and re-emerging worldwide, and the Australasia region has not been spared. Enterovirus A71 and enterovirus D68, both human enteroviruses, are likely to replace the soon-to-be eradicated poliovirus to cause global outbreaks associated with neurological disease. Although prevalent elsewhere, the newly emergent orthoflavivirus, Japanese encephalitis virus (genotype IV), caused human infections in Australia in 2021, and almost certainly will continue to do so because of spillovers from the natural animal host-vector life cycle endemic in the country. Another orthoflavivirus, Murray Valley encephalitis virus, has re-emerged in Australia. The Hendra henipavirus together with Nipah henipavirus are listed as high-risk pathogens by the World Health Organization because both can cause lethal encephalitis. The former remains a health threat in Australasia because bats may still be able to spread the infection to unvaccinated Australian horses and other animals acting as intermediate hosts, and thence to humans. The global COVID-19 pandemic, caused by the emerging severe acute respiratory syndrome coronavirus-2, a virus transmitted from animals to humans that was first described and first arose in China, is associated with acute and long-lasting CNS pathology. Fortunately, the pathology and pathogenesis of these important neurotropic viruses are now better understood, leading to better management protocols and prevention strategies. Pathologists are in a unique position to contribute to the diagnosis and advancement in our knowledge of infectious diseases. This review summarises some of the current knowledge about a few important emerging and re-emerging CNS infections in Australasia and beyond.
Matched MeSH terms: Central Nervous System Viral Diseases/diagnosis; Central Nervous System Viral Diseases/epidemiology; Central Nervous System Viral Diseases/virology
In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virus infection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease.
Matched MeSH terms: Central Nervous System Viral Diseases/diagnosis; Central Nervous System Viral Diseases/epidemiology; Central Nervous System Viral Diseases/pathology; Central Nervous System Viral Diseases/virology
Enterovirus-D68 (EV-D68) was first identified in 1962 in pediatric patients with acute respiratory conditions in California, USA (US). From the 1970s to 2005, EV-D68 was underestimated due to limited data and serotyping methods. In 2014, the United States experienced outbreaks of acute flaccid myelitis (AFM) in children EV-D68 positive. WIN-like compounds (pleconaril, pocapavir, and vapendavir) bind to the virus capsid and have been tested against various enteroviruses (EVs) in clinical trials. However, these compounds encountered issues with resistance and adverse effects, which impeded their approval by the Food and Drug Administration (FDA). Presently, the medical field lacks FDA-approved antiviral treatments or vaccines for EV-D68. Ongoing research efforts are dedicated to identifying viable therapeutics to address EV-D68 infections. This review explores the current advancements in antiviral therapies and potential therapeutics to mitigate the significant impact of EV-D68 infection control.
Matched MeSH terms: Central Nervous System Viral Diseases