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Flavivirus (unspecified) Infection

Queensland Health Guidelines for Public Health Units

Revision History

Version Date Changes
1.0 August 2017 Full revision of guideline. 

Infectious Agent

Flaviviruses in this category include Alfuy, Kokobera, Edge Hill, Stratford, New Mapoon and other non-individually listed flaviviruses for the purpose of notification.

Notification Criteria

Note

1. It is recognised that some cases of human infection cannot be attributed to a single flavivirus. This may either be because the serology shows specific antibody to more than one virus, specific antibody cannot be assigned based on the tests available in Australian reference laboratories, or a flavivirus is detected that cannot be identified.

2. Confirmation by a second arbovirus reference laboratory is required if the case cannot be attributed to known flaviviruses.

3. Occasional human infections occur due to other known flaviviruses, such as Kokobera, Alfuy, Edge Hill and Stratford viruses.

Laboratory definitive evidence

1. Isolation of a flavivirus that cannot be identified in Australian reference laboratories or which is identified as one of the flaviviruses not individually listed.

Individually listed flaviviruses:

  • Dengue
  • Yellow fever
  • West Nile virus (kunjn)
  • Japanese encephalitis
  • Murray Valley encephalitis
  • Zika

OR

2. Detection of a flavivirus, by nucleic acid testing, that cannot be identified in Australian reference laboratories or which is identified as one of the flaviviruses not individually listed.

OR

3. IgG seroconversion or a significant increase in antibody level of flavivirus specific IgG that cannot be identified or which is identified as being specific for one of the flaviviruses not individual listed. There must be no history of recent Japanese encephalitis or yellow fever vaccination.

OR

4. Detection of flavivirus IgM in cerebrospinal fluid, with reactivity to more than one flavivirus antigen (Murray Valley encephalitis, West Nile kunjin, Japanese Encephalitis and/or dengue) or with reactivity only to one or more of the flaviviruses not individually listed.

OR

5. Detection of flavivirus IgM in the serum, with reactivity to more than one flavivirus antigen (Murray Valley encephalitis, West Nile kunjin, Japanese Encephalitis and/or dengue) or with reactivity only to one or more of the flaviviruses not  individually listed. This is only accepted as laboratory evidence for encephalitic illnesses. There must be no history of recent Japanese encephalitis or yellow fever vaccination.

Laboratory suggestive evidence

Detection of flavivirus IgM in the serum, with reactivity to more than one flavivirus antigen (Murray Valley encephalitis, West Nile kunjin, Japanese Encephalitis and/or dengue) or with reactivity to any of the flaviviruses not individually listed. There must be no history of Japanese encephalitis or yellow fever vaccination in the previous three months. This applies to non-encephalitic disease only.

Clinical evidence

1. Non-encephalitic disease: acute febrile illness with headache, myalgia and/or rash

OR

2. Encephalitic disease: acute febrile meningoencephalitis characterised by one or more of the following:

  • focal neurological disease or clearly impaired level of consciousness
  • an abnormal computerised tomograph or magnetic resonance image or electroencephalogram  presence of pleocytosis.

Notification Procedure

Pathology Laboratories:

Notify all confirmed and probable cases by facsimile, email or other electronic means.

Reporting to NOCS

Report confirmed and probable cases.

Confirmed case
A confirmed case requires laboratory definitive evidence AND clinical evidence.

Probable Case
A probable case requires laboratory suggestive evidence AND clinical evidence.

Notes on laboratory diagnosis

  • PCR is available through FSS, however FSS has not reported a positive PCR for these viruses (ALFV, KOKV, STRV) in human samples. This could be due to low viral load at time of testing or genetic variation.
  • Viral culture:  available but not routine.
  • IgG: Flavivirus IgG ELISA contains a pool of antigens including all four DENV serotypes, JEV, MVEV, KUNV, ALFV, KOKV and STRV, YFV and ZIKV. The test appears to be insensitive for detecting IgG to ALFV, KOKV and STRV. By special request, testing can be performed using standalone IgG and IgM assays for specific viruses in order to detect seroconversion. These tests are not validated and not reported on Auslab.
  • IgM: Flavivirus IgM ELISA contains a pool of antigens including all four DENV serotypes, JEV, MVEV, KUNV, ALFV, KOKV and STRV, YFV and ZIKV. IgM reactives are tested using the panel of viruses by microsphere immunoassay. In many patients the specificity of the IgM can be determined i.e. specificity to one flavivirus in the panel over all others. In other cases the IgM may be cross-reactive across the board and are reported as “flavivirus unspecified” . Some patient specimens demonstrate IgM specific for either Kokobera or Stratford viruses, while others show cross-reactivity between the two. Paired sera are required to demonstrate a significant rise in antibody to confirm recent infection.
  • Note that the specific IgM may not reflect the current infecting virus in cases of secondary flavivirus infection (i.e. previous infection with a different flavivirus) or if there is a history of vaccination with e.g. YFV or JEV.

Public health significance and occurrence

Human cases of these flavivirus are uncommonly reported in Queensland. Kokobera, Stratford, Edge Hill, and New Mapoon viruses are closely related and usually present as acute polyarticular disease however, some viruses in this group have been found to be neuro-invasive during animal studies.

Clinical Features

Usually presents as a self-limiting febrile illness characterised by headache, arthralgia, myalgia and lethargy, and sometimes accompanied by rash. Full recovery however can take several months.

Reservoir

Serological evidence suggests kangaroos, other macropods and horses are reservoirs.

Mode of Transmission

Thought to be vectored by a variety of mosquitoes most likely Culex annulirostris and  Aedes vigilax in Queensland.

Incubation Period

Uncertain, possibly 3 -11 days.

Period of communicability

No evidence of human to human transmission.

Susceptibility and resistance

Antibodies to the Kokobera group of viruses are thought to be common in people from north Queensland.

Management

Cases

Public health investigation of individual cases is usually not warranted however can be considered if clusters of cases are notified.

Contacts

Contact tracing

No

Community outbreaks/epidemics

  • Identify vector species involved and their breeding places and promote control.
  • Advise the use of personal protective measures.

Preventive measures

  • Mosquito control where appropriate for known vectors e.g. Culex annulirostris.
  • Personal protective measures (long sleeved clothes, mosquito repellents, and screened tents/bed nets if camping).
  • Promote mosquito avoidance.
  • Notification is usually not timely. Therefore surveillance and control of mosquitoes rather than surveillance of cases is a preferable public health measure.

References

May F J et al, Genetic divergence among members of the Kokobera group of flaviviruses supports their separation into distinct species, Journal of General Virology, 2013, 94, 1462-7.

Mackenzie J S et al, The Zoonotic Flaviviruses of Southern, South-Eastern and eastern Asia, and Australia: The Potential for Emergent Viruses, Zoonosis and Public Health, 2009, 56, 338-356.

Nisbet D J et al, Identification of new flaviviruses in the Kokobera Virus complex, Journal of General Virology, 2005, 86, 121-124.

Boughton C R et al, Illness caused by a Kokobera-like virus in south-eastern Australia, Medical Journal of Australia, 1986, 145, 90-91.

Last updated: 2 August 2017