Murray Valley encephalitis virus: Infectious substances pathogen safety data sheet

Section I - Infectious agent

Name

Murray Valley encephalitis virus

Agent type

Virus

Taxonomy

Family

Flaviviridae

Genus

Orthoflavivirus

Species

murrayense^{Footnote 1}

Synonym or cross-reference

Causative agent of Murray Valley encephalitis (MVE), formally known as Australian X disease or Australian encephalitis^{Footnote 2}.

Characteristics

Brief description

Murray Valley encephalitis virus (MVEV) is part of the Japanese encephalitis (JE) serological complex and is an enveloped and spherical virus that measures between 40-60 nm in diameter, as other viruses of the family Flaviviridae^{Footnote 2Footnote 3Footnote 4}. It contains a non-segmented single-stranded positive-sense RNA genome, approximately 9.2-13 kb in length^{Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 9Footnote 10}. Within the bilayered lipid envelope, the genome is surrounded by an icosahedral nucleocapsid^{Footnote 4Footnote 6Footnote 9}.

Properties

MVEV is a mosquito-borne arbovirus with four recognized genotypes (G1-G4), with G1 being the most prevalent^{Footnote 2Footnote 11}. The genome encodes three structural proteins (capsid protein C, the membrane protein prM, and the envelope protein E) and seven non-structural proteins (NS1, NS2A, NS2B, the helicase/protease NS3, NS4A, NS4B, and the viral RNA polymerase NS5)^{Footnote 2Footnote 3Footnote 4}.

Virion binding and uptake is facilitated via receptor-mediated endocytosis^{Footnote 10}. Once infected, host cells replicate the viral RNA genome and assemble the virion particle by budding through the membranes of the endoplasmic reticulum^{Footnote 2Footnote 10}.

Section II - Hazard identification

Pathogenicity and toxicity

Most cases of human MVEV infection are asymptomatic or present as a mild, non-specific febrile illness usually accompanied by headache, myalgia, and occasionally a rash^{Footnote 2Footnote 12Footnote 13}. Clinically overt disease is estimated to occur in 1 of 150 to 1,000 infections^{Footnote 2Footnote 12Footnote 13}.

Lasting usually 2 weeks, clinical disease associated with MVEV infection is characterized by a rapid onset of 2-5 days of fever, headache, myalgia, malaise, anorexia, and nausea before neurological complications occur^{Footnote 2Footnote 7Footnote 14}. Signs of neurological involvement occur within approximately 5 days of onset and include drowsiness, irritability, confusion, speech disturbances, photophobia, numbness, stiff neck, encephalitis, paralysis (including respiratory paralysis), meningismus, and spastic quadriplegia, and seizures^{Footnote 2Footnote 6Footnote 7Footnote 9Footnote 14Footnote 15Footnote 16}. In severe cases, disease may progress to respiratory failure, coma, and death^{Footnote 2}. MVE is more severe and common in children, in whom convulsions occur frequently, and Aboriginal populations^{Footnote 2Footnote 9}. The case fatality rate ranges from 15-32%, whereas long-term neurological sequelae occur in 30-50% of survivors, such as cerebellar and extrapyramidal movement disorders, and cranial palsies, and only 40% recover completely^{Footnote 2Footnote 6Footnote 7Footnote 12Footnote 13Footnote 14Footnote 15Footnote 16}.

Notably, four clinical patterns of disease have been observed, including relentless progression to death, prominent spinal cord involvement, cranial nerve/brainstem involvement and tremor, and encephalitis with complete recovery^{Footnote 2}. Overall, cases involving flaccid paralysis with rapid progression to respiratory failure is a predictor of poor neurological outcome and death^{Footnote 2}.

MVEV infection has additionally been reported in horses, with more severe cases commonly being reported^{Footnote 13Footnote 17}. The majority of equine cases show clinical symptoms consistent with encephalitis, including both neurological and muscular signs^{Footnote 17}. Viral encephalitis in horses, including MVEV, is characterized by ataxia, depression, altered mental state, muscle fasciculations, hypermetria, hyperaesthesia, circling, recumbency, facial paralysis, weight loss, and pyrexia^{Footnote 17}. Severe cases may also present with lameness and blindness^{Footnote 17}.

Epidemiology

MVEV circulates in Australia and Papua New Guinea, and most likely in the Indonesian archipelago^{Footnote 2Footnote 12Footnote 13Footnote 14Footnote 15}. The virus is endemic in northern Australia and Papua New Guinea and is occasionally epizootic in southeastern and southwestern Australia^{Footnote 2Footnote 11Footnote 15}. In Australia, MVEV is endemic in the Kimberley region of Western Australia (WA), the north of the Northern Territory (NT), and in northern Queensland^{Footnote 2Footnote 12}. G1 is the predominantly circulating genotype in mainland Australia, whereas the G2 genotype is more restricted and consists of mosquito isolates from the Kimberley region of WA^{Footnote 11Footnote 18}. Genotypes G3 and G4 have been identified in Papua New Guinea^{Footnote 11Footnote 18}. MVE usually occurs from February to June^{Footnote 7Footnote 19}.

MVEV was suspected to be the causative agent of several large epidemics of encephalitis, designated Australian X disease, in 1917, 1918, 1922, and 1925 on the east coast of Australia, which ranged from 21 to 114 cases^{Footnote 2Footnote 13}. In 1951, a confirmed epidemic of MVEV occurred in southeastern Australia and resulted in 45 cases; however, all but two cases originated from the Murray Valley^{Footnote 2Footnote 13}. Another outbreak occurred in Australia in 1974, comprising 58 cases, including 13 deaths^{Footnote 13Footnote 14}. The last major outbreak occurred in Australia in 2011 and resulted in 17 confirmed cases, including 3 deaths, one of which was acquired in Australia but became symptomatic in Canada^{Footnote 13Footnote 20}.

Predisposing factors for MVEV infection are situational, including geographical location, occupational, and human behaviour^{Footnote 13Footnote 21}. Human behaviours that could result in an increased risk for infection include being outdoors, especially in a generally wet environment, such as going fishing or camping^{Footnote 13}. On the other hand, in occupational settings, an increased risk of infection could be a result of working with organisms, specifically mosquitos, infected with MVEV^{Footnote 22}.

Host range

Natural host(s)

Waterfowl of the order Ciconiiformes, particularly the Nankeen (or rufous) night heron (Nycticorax caledonicus), and other herons and egrets are primary (definitive) hosts^{Footnote 2Footnote 11Footnote 13}. Mosquitoes are secondary (intermediate) hosts^{Footnote 2Footnote 7}. Dead-end hosts include humans, horses, cattle, feral pigs, chickens, rabbits, canids (dogs and dingoes), rats, camels, and western grey kangaroos^{Footnote 2Footnote 12Footnote 13Footnote 23}.

Other host(s)

Experimentally infected hosts include hamsters and mice^{Footnote 2Footnote 24Footnote 25}.

Infectious dose

The infectious dose for humans is unknown. However, in experimental settings, a mean 50% tissue culture infectious dose (TCID₅₀) of 5.74 ± 0.24 log IU/mL was determined for MVEV following titration on Vero cells and incubation for 5days^{Footnote 26}.

Incubation period

The incubation period is between 5 and 28 days^{Footnote 3Footnote 14}.

Communicability

In both human and animals, the preferred mode of transmission is by injection via the bite of a mosquito that has been infected by feeding on MVEV-infected waterfowl^{Footnote 7Footnote 8Footnote 27}. In experimental settings, inoculation by the oral, subcutaneous, and intranasal routes has been shown to induce infection and/or disease in animal models, suggesting that ingestion, contact with mucous membranes or damaged skin, and inhalation are possible routes of transmission in humans^{Footnote 28Footnote 29}.

Direct or indirect human-to-human transmission is unlikely as humans are considered dead-end hosts, although there is evidence that orthoflaviviruses can be transmitted vertically^{Footnote 6Footnote 21Footnote 22Footnote 30Footnote 31}. Indirect animal-to-animal transmission occurs between waterfowl as MVEV is maintained in a transmission cycle involving mosquito vectors and waterfowl amplifying hosts^{Footnote 11Footnote 15}.

Section III - Dissemination

Reservoir

Waterfowl of the order Ciconiiformes, particularly the Nankeen (or rufous) night heron (Nycticorax caledonicus), and other herons and egrets are the main reservoir hosts of MVEV; however, cattle, horses, and feral pigs may also act as reservoirs^{Footnote 2Footnote 7Footnote 9Footnote 12Footnote 14Footnote 21}.

Zoonosis

MVEV is transmitted from infected animals (particularly waterfowl) to humans via indirect zoonosis, specifically via MVEV-infected mosquitoes^{Footnote 2Footnote 3Footnote 12}. Humans are considered dead-end hosts for MVEV; as such, reverse zoonosis or zooanthroponosis is unlikely to occur^{Footnote 2Footnote 21}.

Vectors

Culex mosquitoes, particularly Culex annulirostris, are the main vectors, although Aedes mosquitoes, particularly Aedes normanensis, are also believed to play a role in MVEV transmission^{Footnote 2Footnote 7Footnote 12Footnote 19}.

It is important to note that vertical transmission between arthropod vectors and their offsprings is possible for orthoflaviviruses and has been reported for Japanese encephalitis virus (JEV)^{Footnote 22Footnote 27}.

Section IV - Stability and viability

Drug susceptibility/resistance

None known^{Footnote 2Footnote 16}.

Susceptibility to disinfectants

MVEV is rapidly inactivated by common laboratory disinfectants, including 70% ethanol, 1% sodium hypochlorite, 2% glutaraldehyde, and quaternary ammonium compounds^{Footnote 32}. In addition, similar to all lipid-enveloped viruses, MVEV is likely susceptible to phenolics, iodophors, formaldehyde (paraformaldehyde and formalin), and peracetic acid^{Footnote 33}.

Physical inactivation

The thermal inactivation point of orthoflaviviruses, including MVEV, is 40°C, and virus present in serum or culture media can be inactivated by heating at 56°C for 30 minutes^{Footnote 34}. Additionally, a study involving arboviruses, including MVEV, showed an approximate 98% reduction in arboviral infectivity in buffy coat-derived platelets using the Mirasol pathogen reduction technology (PRT) system, which is a UV light procedure^{Footnote 26}.

Survival outside host

Unknown.

Section V - First aid/medical

Surveillance

As most cases present as asymptomatic or mild, monitor for worsening or new symptoms to provide proper clinical care if required^{Footnote 2}. MVEV infection can be confirmed by detection of MVEV, MVEV RNA, or MVEV-specific IgM by reverse transcriptase followed by PCR (RT-PCR), the enzyme-linked immunosorbent assay (ELISA), or microsphere immunoassays^{Footnote 2Footnote 6Footnote 7Footnote 16}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

No specific treatment is available; however, intensive supportive care may be required to treat symptoms^{Footnote 2Footnote 7Footnote 9Footnote 16}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

There is no vaccine currently available for MVEV^{Footnote 2Footnote 7Footnote 9}. However, there is mixed evidence of cross-protection from the JE vaccine as both JEV and MVEV are part of the JE serocomplex^{Footnote 2Footnote 3Footnote 21}. In experimental settings, the JE vaccine induced cross-protective immunity in animal models, although a study using mice showed that vaccination enhanced MVE and caused a more severe clinical course^{Footnote 2Footnote 3Footnote 21}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

No known post-exposure prophylaxis.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI - Laboratory hazard

Laboratory-acquired infections

No reported cases of laboratory-acquired infection with MVEV.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

MVEV can be found in blood (plasma and serum), urine, and cerebrospinal fluid^{Footnote 15Footnote 16}.

Primary hazards

Autoinoculation with infectious material is the primary hazard associated with exposure to MVEV^{Footnote 7Footnote 31}.

Special hazards

Work with experimentally infected mosquitoes may present a special hazard.

Section VII - Exposure controls/personal protection

Risk group classification

MVEV is a Risk Group 3 Human Pathogen and Risk Group 3 Animal Pathogen, and is a Security Sensitive Biological Agent (SSBA)^{Footnote 35Footnote 36}.

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures.

Section VIII - Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with the disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and SSBA toxins in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX - Regulatory and other information

Canadian regulatory information

Controlled activities with MVEV require a Pathogen and Toxin licence issued by the Public Health Agency of Canada (PHAC). MVEV is a terrestrial animal pathogen; therefore, importation of MVEV requires an import permit under the authority of the Health of Animals Regulations (HAR), issued by the PHAC. The PHAC issues a Pathogen and Toxin Licence, which includes an HAR importation permit.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations

Last file update

June 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright ^© Public Health Agency of Canada, 2024, Canada

References