Public health priority: Urgent.
PHU response time: Respond to confirmed cases within a day of notification Enter confirmed cases on NCIMS within one working day.
Case management: Determine possible exposures.
Contact management: Nil
Individual case management is the responsibility of the treating doctor. There is no specific treatment available for Murray Valley encephalitis virus (MVEV) infection. Patients who become unwell require supportive management by primary care or hospital services depending on the severity of illness.
Contacts of an infected person cannot be infected by person-to-person transmission, or through a mosquito transferring virus from one person to another as humans are not reservoirs. Information about co-exposed persons is included under the contact management section. Except in unique circumstances, tracing of co-exposed persons is not indicated.
Note: These guidelines form the public health response to a human case of MVEV infection and are part of the national Framework for the detection and management of MVEV infection in Australia.
MVEV is a flavivirus closely related genetically and antigenically to Japanese encephalitis virus, West Nile virus (including the Kunjin strain found in Australia) and several other flaviviruses. Alfuy virus (ALFV) which is classified as a subtype of MVEV, also occurs in Australia but it has not been associated with human disease.
The primary hosts of MVEV are thought to be water birds such as herons and egrets, which act as reservoirs or amplifiers for infection. In particular, the Rufus (or Nankeen) Night Heron (Nycticorax caledonicus) is considered important. The principal virus cycle exists between these birds and the mosquito vectors. Native placental mammals, marsupials such as macropods (kangaroos and related species), and domesticated animals such as fowl, horses, pigs and cattle may be infected, but their role in natural transmission cycles is uncertain.
MVEV is a mosquito-borne virus and transmission is via a bite from an infected mosquito. The primary vector is the fresh water breeding mosquito Culex annulirostris (the common banded mosquito). Other mosquito species, including other Culex species and some Aedes species may be involved in MVEV ecology. There is no evidence of person-to person transmission, either directly or via mosquitoes. Rare cases of intra-uterine transmission of flaviviruses have occurred as well as transmission by blood transfusion and needle stick injuries. 
The incubation period is usually 7 to 12 days, but occasionally can be as short as 5 days or as long as 28 days. Infection is believed to confer life-long immunity to MVEV.
Not applicable. There is no evidence of person-to person transmission.
MVEV commonly infects humans without producing apparent disease (subclinical infection). It may also cause a comparatively mild disease with features such as fever, headache, nausea and vomiting. In a small proportion of all people infected (estimated 1:200 – 1:1000) meningitis or encephalitis of variable severity develops. [2,3] In children, meningitis or encephalitis may occur in up to 1:20 cases of infection, depending on the geographical location. [4, 5, 6] Signs of brain dysfunction such as drowsiness, confusion, seizures, weakness, tremor, ataxia and/or cranial nerve palsies indicate the onset of encephalitis. Based on the 1974 outbreak(which occurred primarily in south-eastern Australia)and studies in Western Australia and Northern Territory, it is estimated that the case fatality rate of encephalitic cases is about 15%–30% [4, 6] with long-term neurological sequelae occurring in 30%–50% of survivors and only 40% recovering completely. [4, 5, 6, 7, 8]
The risk of infection with MVEV is dependent on the frequency and intensity of exposure to infected mosquitoes, and whether the person has been previously infected. People engaged in outdoor activities such as camping and fishing during periods of mosquito and virus activity may be at increased risk of infection. A four year longitudinal serologic study in an Indigenous community in Western Australia determined that the risk of infection among seronegative individuals was relatively constant regardless of age, although the numbers in the older groups were small.  The outcomes of encephalitis due to MVEV may be worse in the very young and those over 50 years-old, but severe disease and death may occur at any age. There is little information on MVEV infection in immunosuppressed persons but, based on overseas experience with similar flaviviruses, it is expected that they would be more susceptible to disease if infected.
MVEV was first isolated from patients who died from encephalitis during an outbreak of disease in the Murray Valley in Victoria and South Australia in 1951. The only Australia-wide outbreak of MVEV infection was in 1974, although most cases occurred in south-eastern Australia. Since then almost all cases have been infected in northern and central Australia, with regular MVEV activity and human cases in the Kimberley region of Western Australia and the northern two thirds of the Northern Territory. Infections have also occurred further south in the Pilbara, Gascoyne, Midwest, and Murchison areas of Western Australia (particularly in 2000 and 2011), in central Australia and in Queensland. There is also an occasional risk to south-eastern Australia, with cases reported in NSW in in 2008 and 2011, and in South Australia in 2011. MVEV has also been detected in horses from time-to-time; however, the implications for human health are unclear at this time. There was evidence of widespread MVEV activity in sentinel chickens and in horses in some areas of the southern states in 2011. 
MVEV activity in Australia may be broadly divided into two categories:
The risk of contracting MVEV infection is related to the presence of the principal vector, C. annulirostris, which is found throughout Australia (except for Tasmania). In northern Australia it is active year-round, with the number of mosquitoes greatest in the wet and post wet season. In southern regions, C. annulirostris tends to be a high-summer species associated with natural wetlands and irrigation waters, emerging during mid-to-late spring as the weather warms, peaking in abundance in mid-to late-summer, and disappearing before winter.
MVEV infection is a significant public health issue, with the potential for fatal cases and permanent disability. The potential severity elevates the level of public concern and media interest in MVEV infection. Economic impacts may also be significant, with direct costs of providing healthcare for persons with encephalitic disease and funding sentinel surveillance and mosquito control programs; and potentially indirect costs resulting from reduced tourism or labour shortages in mining or agricultural sectors in affected regions arising from public concern. National contingency plans are required for widespread outbreaks.
Evidence of increased virus activity, including sentinel chicken seroconversions, occurrence of a human case, or other evidence of increased activity such as animal (e.g. horse) infections should prompt consideration of a public awareness strategy to promote personal protective behaviours and a targeted alert to medical practitioners and emergency departments to promote a higher level of suspicion for MVEV infection when assessing patients. Public awareness strategies may be targeted at particular groups such as fishermen, or campers in a particular region or location and information about the disease may be provided to people with similar high risk exposures as a case where practicable.
Prevention activities include:
The objectives of human surveillance are:
Monitoring of vectors and viral activity are essential elements of MVEV surveillance in Australia. For further information on vector and host surveillance, refer to the framework for the detection and management of MVEV infection in Australia.
In some jurisdictions, MVEV (and Kunjin virus, KUNV) activity is monitored by detecting antibody seroconversion to the virus in samples from sentinel chickens. Dedicated sentinel chicken flocks are maintained all year round in Western Australia and the Northern Territory, and in the summer months in northern Victoria, along the Murray River in South Australia and in southern and western New South Wales. Sentinel chickens are generally bled monthly or fortnightly, and sometimes more frequently in higher risk periods. Currently, Queensland does not have dedicated sentinel chicken flocks. MVEV infection in horses may also provide a warning of MVEV activity, but the significance of MVEV detections in horses as it relates to human health risk is currently unknown.
Mosquito population surveillance is undertaken to monitor abundance of the principal vector species and to detect the presence of the virus in mosquitoes. Given adequate surveillance, virus activity can be expected to be seen in mosquito populations prior to any evidence of transmission to sentinel chickens (appearance of antibodies) or humans (clinical disease). The abundance of MVEV mosquito vectors is dictated principally by the abundance of water in the environment (rainfall patterns and irrigation) and temperature.
Monitoring of rainfall patterns, temperature, the Southern Oscillation Index via the Bureau of Meteorology and river flow data (e.g. Murray Darling Basin Commission) is also undertaken by some states.
Enter confirmed cases onto the notifiable diseases database within one working day of notification. Document the potential exposure location(s) in the notifiable diseases database.
On the day of notification, inform the communicable diseases control branch of the relevant state/territory Department of Health of the demographic and clinical aspects of the case and the likely place(s) of exposure. Where an exposure occurred outside the PHU area, also notify the relevant PHU as soon as possible. In the event of a cluster of cases, the state/territory communicable disease control branch should also notify the relevant details to the CDNA secretariat for dissemination to CDNA members, while individual cases should be included in the fortnightly jurisdictional reports.
Only confirmed cases of MVEV infection are notifiable. See the current national case definition for surveillance of MVEV infection for more information.
A diagnosis of MVEV infection should be considered amongst the differential diagnoses in any patient who presents with encephalitis and who has been in an enzootic or epizootic area within the incubation period of the disease (5-28 days prior to the onset of symptoms), especially during the wet and post-wet seasons in northern areas or mid-spring to mid-autumn in southern areas.
Samples should be sent to a PHLN laboratory, or an arbovirus reference laboratory that is National Association of Testing Authorities (NATA) accredited to perform relevant requested diagnostic testing on human samples (see Appendix 1). Where a case occurs in an area without known MVEV activity, positive results should be confirmed by a second arbovirus reference laboratory.
Virus can be detected by culture or by a nucleic acid test (NAT). The latter is more sensitive. Positive cultures are rare, and therefore culture is usually only performed where there is a positive NAT or where a suitable NAT is not available, and provided there is sufficient specimen volume. Tissue cultures are available in most arbovirus reference laboratories, but the availability of animal inoculation is very restricted.
Serological testing for flaviviruses is highly specialised due to the limited availability of the tests and difficulties in interpretation of results. Nearly all patients who have MVEV infection will have detectable IgM in the serum within a few days of onset of illness and it will persist for many months or years. Therefore detection of IgM in serum does not necessarily mean recent infection. Conversely, serum IgM may also be absent in some patients, especially those who have had previous flavivirus infections, such as MVEV infection in someone with past KUNV infection. IgM is present in the CSF in about 75% of encephalitis cases, and is indicative of intrathecal antibody production and central nervous system infection.
It is important that both acute and convalescent serum samples are collected in order to demonstrate a rise in IgG, as this confirms recent infection. However, both IgG and IgM are broadly cross-reactive among the flaviviruses. That is, a rise in IgG to MVEV with or without IgM, it could be due to infection with any flavivirus, depending on the patient’s travel and exposure history. In Australia we have to primarily consider KUNV, and possibly Japanese encephalitis virus (JEV), dengue virus (DENV) and Zika virus (ZIKV), but rarer flaviviruses such as Kokobera and Edge Hill viruses also occur. Returned travellers may have been exposed to other viruses such as West Nile virus, JEV, DENV and ZIKV.
Therefore, the following criteria have been developed to assist in distinguishing the specific virus responsible for a flavivirus infection:
Detection of IgM to more than one flavivirus should be classified as an unspecified flavivirus infection unless specific IgG has been confirmed and notified as arbovirus (not elsewhere classified or NEC)
The Public Health Laboratory Network of Australia (PHLN) has formulated a laboratory case definition for flavivirus infection available from the Australian Department of Health.
Investigation should commence within 24 hours of notification of a confirmed human case of MVEV infection. If any case is diagnosed outside the jurisdiction where the infection was likely to have been acquired, the communicable disease control branch in the state/territory where it was thought to have been acquired should be notified on the same day, in order to ensure appropriate preventive measures can be implemented promptly.
The extent of a response to a case or cases of MVEV infection should take into account recent and current preventive activities in the implicated area, any available information from local mosquito and sentinel chicken surveillance programs, the epidemiological significance of the reported cases, prevailing environmental conditions and expected outcomes of the outbreak response.
In areas of enzootic activity (see Disease occurrence and public health significance in Section 2. The Disease) with established surveillance and response programs there may be little need for detailed investigations and interventions beyond continuation of existing programs. Hence, the response may rely on pre-prepared public warnings and advice about mosquito avoidance measures, reminders to medical practitioners and targeted mosquito control measures near an affected population centre, as appropriate.
In epizootic areas, investigations, interventions and warnings may substantially reduce further risks and provide important information about factors contributing to the outbreak that will inform predictions of future outbreaks and management approaches.
All cases should be investigated to determine the likely place of acquisition of MVEV infection. An example MVEV investigation form is provided in Appendix 4.
PHU staff should ensure that action has been taken to:
Obtain a full travel history to determine whether they had visited an area with known (recent or previous) evidence of MVEV activity, during the exposure period (5-28 days prior to onset of symptoms) and whether the case had:
If a case has not travelled to an area of known MVEV activity in Australia (or the island of New Guinea, including Papua New Guinea, and the Indonesian Provinces of West Papua and Papua) within the incubation period of the disease, then the potential for infection to have occurred within a low-risk area of Australia exists. If this occurs, further investigation of potential reservoirs of infection and additional cases should be considered.
Interpretation of serological results may also require detailed questioning about past travel or residence within northern Australia or overseas where exposure to flaviviruses may have occurred.
No specific treatment is available for MVEV disease and care of symptomatic cases is largely supportive. Given the potential for neurological deterioration, patients with encephalitis should ideally be managed in hospitals with intensive care facilities and expertise in the management of complicated neurological disease. Management should be discussed with a physician with experience in the care of these patients.
A fact sheet on MVEV infection [PDF] should be made available to the case and family and other co-exposed individuals to provide information about the nature of the infection and the mode of transmission.
Case finding should be undertaken in response to all cases, but should be limited to the geographical location in which the case was most likely to have acquired their infection. Case finding should focus on human cases of acute febrile illness in the affected area with headache and other signs of encephalitis including seizures, confusion or depressed consciousness, with no other obvious cause. Most usually, active case finding would be limited to alerts to a small number of community and/or hospital-based medical practitioners serving a regional area and a state/territory public health laboratory, but in some circumstances wider alerts might be appropriate, and include metropolitan tertiary referral hospital emergency departments and intensive care units, and even monitoring of data from existing emergency department syndromic surveillance systems.
Additional activities to identify milder, non-encephalitic cases should be considered if resources allow. Where human cases are identified in unexpected areas, opportunistic serological testing of domestic animals (e.g. chicken flocks) may be useful to help define the range of MVEV activity. Similarly, opportunistic or systematic serosurveys of humans may be appropriate in defining infection rates and the area of risk.
MVEV is not transmitted between humans. Transmission of infection requires competent mosquito vectors and animal reservoirs of MVEV (see Section 2. The Disease).
Control of the spread of MVEV and prevention of human cases rests on the management of competent mosquito vectors and personal and community (e.g. location of human settlements relative to habitat) strategies of mosquito avoidance.
Environmental evaluation and implementation of control measures is the responsibility of local environmental health authorities and jurisdictional medical entomology units. The aim of this assessment is to identify risk periods and areas due to expected rainfall or flooding or other indicators from models to direct mosquito control activities, including identifying common breeding sites and control of both larval and adult populations of Culex vector mosquitoes.
Evaluation of environmental risks should include information from mosquito monitoring and sentinel chicken surveillance programs, if available, in the context of historical knowledge of MVEV activity relative to seasonal rainfall and flooding events. Local animal health authorities should also be consulted regarding animal surveillance.
A recent development has been the evaluation of a new surveillance tool involving testing for MVEV presence by a PCR method using honey baits in special mosquito traps. The sensitivity, cost-effectiveness and technical feasibility of honey bait traps are still being established, but these have the potential to be a very useful tool in the future. Where possible, honey bait trap mosquito virus surveillance could be set up in the area to monitor for MVEV activity, as an adjunct to other methods, and for the purposes of comparison and refinement of the method.
Contacts of an infected person cannot be infected by person-to-person transmission, or through a mosquito transferring virus from one person to another as humans are not reservoirs. Therefore, this section provides details on the public health response for co-exposed persons.
To date, MVEV disease has presented as sporadic cases, with no well documented instances of co-exposed persons developing disease. Similarly, time-place clusters of cases are rare, except over broad regions and extended time periods. Hence, except in unique circumstances, as described below, screening of co-exposed persons who do not have symptoms consistent with MVEV infection, is not indicated for public health purposes. Testing of these patients may be undertaken as part of their clinical management.
Special circumstances where tracing co-exposed persons might be appropriate include research projects aimed at determining infection rates in in small groups of co-exposed persons or within communities in which a case has occurred, or unusual instances where a case of MVEV disease was part of a small group (such as a fishing party camping in an isolated area) which experienced heavy mosquito-biting and information suggests that others in the group may have either non-encephalitic or encephalitic symptoms consistent with MVEV infection. In this instance the aim of identifying the co-exposed would be to facilitate laboratory testing and appropriate management for MVEV infection should any person from the co-exposed group have symptoms consistent with the disease.
See above - ordinarily, identification of co-exposed persons is not indicated. In unique circumstances, as described above, co-exposed might be defined as persons who had the same exposure(s) as the case, such as members of a small group who shared outdoor activities and heavy exposure to mosquito vectors with the case.
Nil. There is no vaccine available for MVEV.
The protective efficacy of JEV vaccines against NVEV infection have not been directly determined and may vary with the type of vaccine, with evidence to suggest that some may be protective while others may enhance infection.10 This should be considered should widespread JE vaccination be required in an area with known MVE enzootic transmission (e.g. following a hypothetical JE importation into FNQ, given that we have competent JE vectors).
See above - ordinarily co-exposed do not need to be identified and no education is required. In unique circumstances, as described under "Identification of contacts", an MVEV Infection Factsheet [PDF] could be made available for co-exposed.
Additional actions may be required where a cluster of cases in place or time is detected through analysis of case exposure history. The goal of the investigation is to identify the source of infection and potential risk factors for illness, thereby informing public health action. Stages and considerations may include:
The management and national co-ordination of an outbreak of MVEV infection in Australia is further detailed in the CDNA Framework for the Surveillance, Prevention and Control of Murray Valley Encephalitis.
Appendix 1 - List of Arbovirus Reference LaboratoriesAppendix 2 - MVEV Case Investigation FormAppendix 3 - PHU Checklist
Qld Health Forensic and Scientific Services39 Kessells RdCoopers PlainsPO Box 594 Archerfield Qld 4108Phone: (07) 3274 9151
Pathology West - Institute of Clinical Pathology and Medical Research (ICPMR)Westmead HospitalDarcy RoadWestmead NSW 2145Phone: (02) 9845 6255
Victorian Infectious Diseases Reference Laboratory (Human)10 Wrecklyn StNorth Melbourne Victoria 3051Phone: (03) 9342 2600
Department of Primary IndustriesAttwood Centre475 Mickleham RoadAttwood Victoria 3049Phone: (03) 9217 4200
CSIRO Livestock IndustriesAustralian Animal Health LaboratoryPrivate Bag 24 (5 Portarlington Road)Geelong Victoria 3220Switchboard: (03) 5227 5000
The Western Australian Centre for Pathology and Medical ResearchDivision of Microbiology and Infectious Diseases (Human)Hospital AvenueNedlands WA 6009Switchboard: (08) 9346 3122
Arbovirus Surveillance and Research LaboratoryDiscipline of Microbiology and Immunology (Animal/Vector)School of Pathology and Laboratory MedicineThe University of Western Australia35 Stirling HighwayCrawley WA 6009Phone: (08) 9346 2212