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In January 2023, an outbreak of Murray Valley Encephalitits (MVE) was reported on January 16, 2023. Cases have subsequently been detected in Victoria (VIC)1, Northern Territory (NT)4, New South Wales (NSW)5, and Western Australia (WA), Australia. with 9 confirmed cases and 3 deaths as of April 6, 2023. This marks the first human case of MVE in Victoria since the last outbreak in 1974 and the first ever reported cases in NSW. Significant weather patterns throughout 2022 are thought to have contributed to the resurgance of MVEV. People of all ages are affected by MVE and those frequenting inland riverine regions, extending up towards the Murray River may be at increased risk of infection. This watching brief serves to inform on the increased transmission of MVE across Australia in 2023.

We report the case of a 62-year-old male who presented to the Emergency Department (ED) with altered mental status following a motor vehicle accident. He was transferred to the Intensive Care Unit (ICU) with worsening of his neurological status and subsequently diagnosed with Murray Valley encephalitis: a serious but rare condition caused by infection with Murray Valley encephalitis virus (MVEV). He continued to deteriorate despite treatment with antivirals, glucocorticoids, and therapeutic plasma exchange (TPE) in addition to supportive care and eventually succumbed to his illness. In this report, we review the clinical course, pathophysiology, diagnosis, and characteristic radiological features of Murray Valley encephalitis and highlight the challenges in treating this potentially devastating disease., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Derrick et al.)

Murray Valley encephalitis virus (MVEV), a flavivirus belonging to the Japanese encephalitis serogroup, can cause severe clinical manifestations in humans. We report a fatal case of MVEV infection in a young woman who returned from Australia to Canada. The differential diagnosis for travel-associated encephalitis should include MVEV, particularly during outbreak years.

Alfred Walter Campbell (1868–1937) established the basic cytoarchitectonic structure of the human brain while he was working as a pathologist at the Rainhill Lunatic Asylum near Liverpool in the United Kingdom. He returned to Australia in 1905 and continued doing research while establishing a neurological practice. His research over the next 17 years focused on four topics: (a) localisation in the cerebellum, (b) the neuroses and psychoses in war, (c) localisation in the cerebral cortex of the gorilla, and (d) the causes and pathology of the mysterious Australian “X” Disease (later known as Murray Valley encephalitis). In this article, I elaborate on his research in these areas, which provided evidence (a) against Louis Bolk’s thesis that variation in the size of the cerebellar cortex reflected variation in the amount of cortex controlling various groups of muscle, (b) against the view that the neuroses and psychoses in war were different from those in civilian life, (c) for a parcelation of the cortex of the gorilla brain that supported his earlier findings in the higher apes, and (d) on the cause and pathophysiology of Australian “X” disease. Much of this research was overlooked, but it remains of considerable value and historical significance. [ABSTRACT FROM PUBLISHER]

Abstract Objective: To assess evidence of recent and past exposure to Murray Valley encephalitis virus (MVEV) and West Nile clade Kunjin virus (KUNV) in residents of the Murray Valley, Victoria, during a period of demonstrated activity of both viruses in early 2011. Methods: A cross‐sectional serosurvey using two convenience samples: stored serum specimens from a diagnostic laboratory in Mildura and blood donors from the Murray Valley region. Specimens were collected between April and July 2011. The main outcome measure was total antibody (IgM and IgG) reactivity against MVEV and KUNV measured using an enzyme immunoassay and defined as inhibiting binding of monoclonal antibodies by >50%, when compared to negative controls. Evidence of recent exposure was measured by the presence of MVEV and KUNV IgM detected by immunofluorescence. Results: Of 1,115 specimens, 24 (2.2%, 95% CI 1.3–3.0%) were positive for MVEV total antibody, and all were negative for MVEV IgM. Of 1,116 specimens, 34 (3.1%, 95% CI 2.0–4.0%) were positive for KUNV total antibody, and 3 (0.27%) were KUNV IgM positive. Total antibody seroprevalence for both viruses was higher in residents born before 1974. Conclusions: Despite widespread MVEV and KUNV activity in early 2011, this study found that seroprevalence of antibodies to both viruses was low (

Murray Valley Encephalitis virus (MVEV) is a mosquito-borne Flavivirus. Clinical presentation is rare but severe, with a case fatality rate of 15–30%. Here we report a case of MVEV from the cerebrospinal fluid (CSF) of a patient in the Northern Territory in Australia. Initial diagnosis was performed using both MVEV-specific real-time, and Pan-Flavivirus conventional, Polymerase Chain Reaction (PCR), with confirmation by Sanger sequencing. Subsequent isolation, the first from CSF, was conducted in Vero cells and the observed cytopathic effect was confirmed by increasing viral titre in the real-time PCR. Isolation allowed for full genome sequencing using the Scriptseq V2 RNASeq library preparation kit. A consensus genome for VIDRL-MVE was generated and phylogenetic analysis identified it as Genotype 2. This is the first reported isolation, and full genome sequencing of MVEV from CSF. It is also the first time Genotype 2 has been identified in humans. As such, this case has significant implications for public health surveillance, epidemiology, and the understanding of MVEV evolution.

Background Murray Valley encephalitis virus (MVEV) is a flavivirus that occurs in Australia and New Guinea. While clinical cases are uncommon, MVEV can cause severe encephalitis with high mortality. Sentinel chicken surveillance is used at many sites around Australia to provide an early warning system for risk of human infection in areas that have low population density and geographical remoteness. MVEV in Western Australia occurs in areas of low population density and geographical remoteness, resulting in logistical challenges with surveillance systems and few human cases. While epidemiological data has suggested an association between rainfall and MVEV activity in outbreak years, it has not been quantified, and the association between rainfall and sporadic cases is less clear. In this study we analysed 22 years of sentinel chicken and human case data from Western Australia in order to evaluate the effectiveness of sentinel chicken surveillance for MVEV and assess the association between rainfall and MVEV activity. Methods Sentinel chicken seroconversion, human case and rainfall data from the Kimberley and Pilbara regions of Western Australia from 1990 to 2011 were analysed using negative binomial regression. Sentinel chicken seroconversion and human cases were used as dependent variables in the model. The model was then tested against sentinel chicken and rainfall data from 2012 and 2013. Results Sentinel chicken seroconversion preceded all human cases except two in March 1993. Rainfall in the prior three months was significantly associated with both sentinel chicken seroconversion and human cases across the regions of interest. Sentinel chicken seroconversion was also predictive of human cases in the models. The model predicted sentinel chicken seroconversion in the Kimberley but not in the Pilbara, where seroconversions early in 2012 were not predicted. The latter may be due to localised MVEV activity in isolated foci at dams, which do not reflect broader virus activity in the region. Conclusions We showed that rainfall and sentinel chickens provide a useful early warning of MVEV risk to humans across endemic and epidemic areas, and that a combination of the two indicators improves the ability to assess MVEV risk and inform risk management measures. [ABSTRACT FROM AUTHOR]

Highlights: [•] A microsphere array assay was developed specific for JEV serocomplex viruses. [•] The assay detected viral RNA equally sensitive to reference PCR assays. [•] The assay differentiated closely related viruses WNV, Kunjin, MVEV and JEV. [•] The assay identified mixed virus populations of exotic WNV and endemic Kunjin. [•] The multiplex assay format is suitable for diagnostics and surveillance programs. [ABSTRACT FROM AUTHOR]

Abstract: Murray Valley encephalitis is an infectious disease spread by a mosquito-borne virus endemic in Papua New Guinea and northern Australia. In the past decade, it has spread to various regions of Australia and there is currently no therapeutic treatment against this disease. An attractive drug target is the viral serine protease NS2B/NS3, a critical enzyme involved in viral replication. Herein, we report the inhibitory activities of 37 C-terminal agmatine peptidomimetic inhibitors which led to the design of a novel structurally-constrained competitive inhibitor 38 possessing a K i of 2.5 ± 0.5 μM. We believe our data provides crucial insights into the viral protease active site specificity which could be used to facilitate drug design against Murray Valley encephalitis viral infections. [Copyright &y& Elsevier]

Abstract: Murray Valley encephalitis virus (MVEV) is a member of the flavivirus group, a large family of single stranded RNA viruses, which cause serious disease in all regions of the world. Its genome encodes a large polyprotein which is processed by both host proteinases and a virally encoded serine proteinase, non-structural protein 3 (NS3). NS3, an essential viral enzyme, requires another virally encoded protein cofactor, NS2B, for proteolytic activity. The cloning, expression and biochemical characterisation of a stable MVEV NS2B–NS3 fusion protein is described. [Copyright &y& Elsevier]

Our paper presents an assessment of research and operational development in relation to medically important mosquito-borne disease, mainly the arboviruses Ross River, Barmah Forest, Murray Valley encephalitis, Japanese encephalitis, Kunjin and dengue, but also with respect to malaria. Since 1972, there have been considerable gains in research output, organisational structure, communication, surveillance including quarantine inspection and operational control. This has been due to the 1974 epidemic of Murray Valley encephalitis virus extending into temperate Australia, increasing occurrence of Ross River and the dengue viruses, the discovery of Barmah Forest virus as a disease entity in 1988, and the introduction of Japanese encephalitis in 1995. Because many of the outputs involve methodologies of global import, this has resulted in an unprecedented upsurge in publications of international standard. [ABSTRACT FROM AUTHOR]

A 5-year-old Thoroughbred mare presented with signs of severe pain and was taken to exploratory laparotomy based on suspicion of an acute abdominal lesion. A mild gastrointestinal lesion was discovered, but was considered disproportional to the severity of signs displayed. The mare was later euthanased because of intractable pain. Comprehensive postmortem examination, including polymerase chain reaction testing of central nervous system tissue samples, allowed a definitive diagnosis of Murray Valley encephalomyelitis to be made. This case demonstrates the variability of clinical presentations in horses infected with Murray Valley encephalitis virus. [ABSTRACT FROM AUTHOR]

Summary: We describe a patient with serologically proven Murray Valley encephalitis (MVE), whose presentation was clinically and radiologically characteristic of Herpes simplex encephalitis (HSE). The reports of MRI abnormalities in MVE, and the closely related Japanese Encephalitis and West Nile virusii are mostly of bilateral thalamic or grey matter involvement. The MRI scan findings in this case instead showed the typical temporal lobe changes of HSE. Our case report highlights that MVE can mimic HSE, both clinically and radiologically. Therefore it is important to collect an accurate and detailed travel history from patients where there is a risk of exposure to MVE virus. If suspected, antibody testing of serum and CSF, and CSF for MVE-RNA if available, should be undertaken. This case also highlights the potential under-diagnosis of Murray Valley encephalitis. [Copyright &y& Elsevier]

Murray Valley Encephalitis virus (MVEV) is a mosquito-borne Flavivirus. Clinical presentation is rare but severe, with a case fatality rate of 15–30%. Here we report a case of MVEV from the cerebrospinal fluid (CSF) of a patient in the Northern Territory in Australia. Initial diagnosis was performed using both MVEV-specific real-time, and Pan-Flavivirus conventional, Polymerase Chain Reaction (PCR), with confirmation by Sanger sequencing. Subsequent isolation, the first from CSF, was conducted in Vero cells and the observed cytopathic effect was confirmed by increasing viral titre in the real-time PCR. Isolation allowed for full genome sequencing using the Scriptseq V2 RNASeq library preparation kit. A consensus genome for VIDRL-MVE was generated and phylogenetic analysis identified it as Genotype 2. This is the first reported isolation, and full genome sequencing of MVEV from CSF. It is also the first time Genotype 2 has been identified in humans. As such, this case has significant implications for public health surveillance, epidemiology, and the understanding of MVEV evolution. [ABSTRACT FROM AUTHOR]

Background Waterbirds are the major hosts of various arboviruses. Murray Valley encephalitis virus (MVEV) is an arbovirus native to northern Australia, the major hosts of which are Phalacrocoraciformes (cormorants), Ciconiiformes (herons) and other waterbirds. MVEV is transmitted to humans by mosquitoes and can cause acute encephalomyelitis. In Victoria, MVEV is restricted to the northern side of the Great Dividing Range (GDR), suggesting that waterbirds cannot cross the high country. Methods and results We tested this hypothesis by analysing data on waterbird banding and recovery and discovered that 12 species can cross the GDR. Conclusion Waterbirds have the potential to carry arboviruses, including MVEV, into southern Victoria. [ABSTRACT FROM AUTHOR]

Murray Valley encephalitis virus (MVEV), a flavivirus belonging to the Japanese encephalitis serogroup, can cause severe clinical manifestations in humans. We report a fatal case of MVEV infection in a young woman who returned from Australia to Canada. The differential diagnosis for travel-associated encephalitis should include MVEV, particularly during outbreak years.

The objective of this chapter is to provide an updated and concise systematic review on taxonomy, history, arthropod vectors, vertebrate hosts, animal disease, and geographic distribution of all arboviruses known to date to cause disease in homeotherm (endotherm) vertebrates, except those affecting exclusively man. Fifty arboviruses pathogenic for animals have been documented worldwide, belonging to seven families: Togaviridae (mosquito-borne Eastern, Western, and Venezuelan equine encephalilitis viruses; Sindbis, Middelburg, Getah, and Semliki Forest viruses), Flaviviridae (mosquito-borne yellow fever, Japanese encephalitis, Murray Valley encephalitis, West Nile, Usutu, Israel turkey meningoencephalitis, Tembusu and Wesselsbron viruses; tick-borne encephalitis, louping ill, Omsk hemorrhagic fever, Kyasanur Forest disease, and Tyuleniy viruses), Bunyaviridae (tick-borne Nairobi sheep disease, Soldado, and Bhanja viruses; mosquito-borne Rift Valley fever, La Crosse, Snowshoe hare, and Cache Valley viruses; biting midges-borne Main Drain, Akabane, Aino, Shuni, and Schmallenberg viruses), Reoviridae (biting midges-borne African horse sickness, Kasba, bluetongue, epizootic hemorrhagic disease of deer, Ibaraki, equine encephalosis, Peruvian horse sickness, and Yunnan viruses), Rhabdoviridae (sandfly/mosquito-borne bovine ephemeral fever, vesicular stomatitis-Indiana, vesicular stomatitis-New Jersey, vesicular stomatitis-Alagoas, and Coccal viruses), Orthomyxoviridae (tick-borne Thogoto virus), and Asfarviridae (tick-borne African swine fever virus). They are transmitted to animals by five groups of hematophagous arthropods of the subphyllum Chelicerata (order Acarina, families Ixodidae and Argasidae-ticks) or members of the class Insecta: mosquitoes (family Culicidae); biting midges (family Ceratopogonidae); sandflies (subfamily Phlebotominae); and cimicid bugs (family Cimicidae). Arboviral diseases in endotherm animals may therefore be classified as: tick-borne (louping ill and tick-borne encephalitis, Omsk hemorrhagic fever, Kyasanur Forest disease, Tyuleniy fever, Nairobi sheep disease, Soldado fever, Bhanja fever, Thogoto fever, African swine fever), mosquito-borne (Eastern, Western, and Venezuelan equine encephalomyelitides, Highlands J disease, Getah disease, Semliki Forest disease, yellow fever, Japanese encephalitis, Murray Valley encephalitis, West Nile encephalitis, Usutu disease, Israel turkey meningoencephalitis, Tembusu disease/duck egg-drop syndrome, Wesselsbron disease, La Crosse encephalitis, Snowshoe hare encephalitis, Cache Valley disease, Main Drain disease, Rift Valley fever, Peruvian horse sickness, Yunnan disease), sandfly-borne (vesicular stomatitis-Indiana, New Jersey, and Alagoas, Cocal disease), midge-borne (Akabane disease, Aino disease, Schmallenberg disease, Shuni disease, African horse sickness, Kasba disease, bluetongue, epizootic hemorrhagic disease of deer, Ibaraki disease, equine encephalosis, bovine ephemeral fever, Kotonkan disease), and cimicid-borne (Buggy Creek disease). Animals infected with these arboviruses regularly develop a febrile disease accompanied by various nonspecific symptoms; however, additional severe syndromes may occur: neurological diseases (meningitis, encephalitis, encephalomyelitis); hemorrhagic symptoms; abortions and congenital disorders; or vesicular stomatitis. Certain arboviral diseases cause significant economic losses in domestic animals-for example, Eastern, Western and Venezuelan equine encephalitides, West Nile encephalitis, Nairobi sheep disease, Rift Valley fever, Akabane fever, Schmallenberg disease (emerged recently in Europe), African horse sickness, bluetongue, vesicular stomatitis, and African swine fever; all of these (except for Akabane and Schmallenberg diseases) are notifiable to the World Organisation for Animal Health (OIE, 2012)., (© 2014 Elsevier Inc. All rights reserved.)

Objective: To assess evidence of recent and past exposure to Murray Valley encephalitis virus (MVEV) and West Nile clade Kunjin virus (KUNV) in residents of the Murray Valley, Victoria, during a period of demonstrated activity of both viruses in early 2011., Methods: A cross-sectional serosurvey using two convenience samples: stored serum specimens from a diagnostic laboratory in Mildura and blood donors from the Murray Valley region. Specimens were collected between April and July 2011. The main outcome measure was total antibody (IgM and IgG) reactivity against MVEV and KUNV measured using an enzyme immunoassay and defined as inhibiting binding of monoclonal antibodies by >50%, when compared to negative controls. Evidence of recent exposure was measured by the presence of MVEV and KUNV IgM detected by immunofluorescence., Results: Of 1,115 specimens, 24 (2.2%, 95% CI 1.3-3.0%) were positive for MVEV total antibody, and all were negative for MVEV IgM. Of 1,116 specimens, 34 (3.1%, 95% CI 2.0-4.0%) were positive for KUNV total antibody, and 3 (0.27%) were KUNV IgM positive. Total antibody seroprevalence for both viruses was higher in residents born before 1974., Conclusions: Despite widespread MVEV and KUNV activity in early 2011, this study found that seroprevalence of antibodies to both viruses was low (<5%) and little evidence of recent exposure., Implications: Our findings suggest both viruses remain epizootic in the region and local residents remain potentially susceptible to future outbreaks., (© 2013 Victorian Government Department of Health. ANZJPH © 2013 Public Health Association of Australia.)