Alphavirus and Flavivirus Laboratory Case Definition (LCD)

The Public Health Laboratory Network have developed a standard case definition for the diagnosis of diseases which are notifiable in Australia. This page contains the laboratory case definition for alphavirus and flavivirus infections.

Page last updated: 22 December 2004

A PDF version of this alphavirus and flavivirus infections case definitions (PDF file 28Kb) is available

Authorisation: PHLN

Consensus Date: 7 February 2001



Preamble

The PHLN Summary Laboratory Definitions are derived from parent documents which provide more details about laboratory testing for these conditions and should be consulted as necessary [web address to be provided shortly, inquiries and comments to PHLN@health.gov.au ].  Reference laboratories should be consulted regarding which isolates or specimens should be considered for reference testing.

These laboratory case definitions are valid only if certain criteria apply namely:
The test has been done in the context of an appropriate clinical setting and/or illness;
  • The utility of the test should be known in the population from which the test sample is derived;
  • Appropriate tests are conducted in NATA/RCPA accredited facilities with appropriate quality control and external proficiency program performance; and
  • Tests, particularly, but not only nucleic acid tests, have appropriate documented validation.

Serology

Terms used in the serological criteria include:
  • Seroconversion:  Change from IgG negative to IgG positive between acute and convalescent samples.  This may be used for confirming recent infection using tests that do not quantify the antibody levels.  That includes most enzyme immunoassay, particle agglutination, immunofluorescent antibody and latex agglutination tests as performed routinely.
  • Significant increase in antibody level or titre:  This is generally confined to tests which use titrations in two-fold dilutions, in which a four-fold increase is regarded as significant.  For enzyme immunoassay tests that are not titred, it may be possible to establish changes in absorbance that may be regarded as significant.  This has to be determined and validated for individual tests, and should be approached with caution.
  • Single high titre:  Generally the level constituting a single high titre is not stated.  That is because it may vary between tests and laboratories.  In those cases it needs to be established from local experience and evaluation.
  • Detection of IgM:  This is usually sufficient to indicate recent infection.  However following some infections - such as those due to the alphaviruses and flaviviruses - IgM persists for months to years, and may only be used as presumptive evidence of recent infection.  Readers should be aware that cross-reacting IgM can occur, particularly with flavivirus infections.  False positive IgM reactions are a recognised problem in serological diagnosis, and laboratories should have ensured that their methods and protocols take this in to account.

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Acronyms, abbreviations and symbols


µm
AIDS
BFV
CDC
CF
CSF
CWA
DEN
DFA
DNA
EIA
FTA-ABS
gp
HAV
HBsAg
HBV
HCV
HDV
HEV
HIV
HUS
IFA
Ig
IHA
JE
kDa
KUN
LA
LPS
MAT
MIF
MVE
NAT
NATA
NLV
PCR
RCPA
RNA
RPR
RRL
RRV
RSV
SIN
TPHA
TPPA
VDRL
YF
micrometre
acquired immunodeficiency syndrome
Barmah Forest virus
Centres for Disease Control and Prevention
complement fixation
cerebrospinal fluid
cardiolipin wasserman reaction
dengue fever
direct fluorescence assay
deoxyribonucleic acid
enzyme immunoassay
ABS fluorescent treponemal antibody absorbed
glycoprotein
hepatitis A virus
hepatitis B surface antigen
hepatitis B virus
hepatitis C virus
hepatitis D virus
hepatitis E virus
human immunodeficiency virus
haemolytic uraemic syndrome
indirect fluorescent antibody
immunoglobulin
indirect haemagglutination
Japanese encephalitis
kilo dalton
Kunjin
latex agglutination
lipopolysaccharide
microscopic agglutination test
microimmunofluorescence
Murray Valley encephalitis
nucleic acid test
National Association of Testing Authorities, Australia
Norwalk-like virus
polymerase chain reaction
Royal College of Pathologists of Australasia
ribonucleic acid
rapid plasma reagin
WHO Western Pacific Regional Poliovirus Reference Laboratory
Ross River virus
respiratory syncytial virus
Sindbis
Treponema pallidum haemagglutination assay
Treponema pallidum particle agglutination
Venereal Diseases Research Laboratory
yellow fever

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Condition
PHLN Parent Document Number
Definitive Criteria
Suggestive Criteria
Alphavirus infection

(Ross River virus [RRV], Barmah Forest virus [BFV] and Sindbis virus [SIN])
0013
Alphavirus other than Sindbis
  1. Isolation of alphavirus from clinical material; OR
  2. Detection of specific alphavirus by NAT; OR
  3. IgG seroconversion to specific alphavirus; OR
  4. Significant increase in IgG level or titre to specific alphavirus.
Alphavirus other than Sindbis
  1. Detection of IgM to specific alphavirus.

Sindbis
  1. Isolation of SIN from clinical material; OR
  2. Detection of SIN by NAT; OR
  3. Seroconversion or significant increase in IgG level or titre to SIN confirmed by neutralisation titres or other specific serology; OR
  4. IgG seroconversion to SIN but not RRV or BFV; OR
  5. Significant increase in IgG level or titre to SIN but not RRV or BFV.
Sindbis
  1. Detection of IgM to SIN but not RRV or BFV.
Flavivirus infection

(Dengue [DEN], Murray Valley encephalitis [MVE], Japanese encephalitis [JE], Kunjin [KUN] and yellow fever [YF])
(yet to be written)
  1. Isolation of flavivirus from clinical material; OR
  2. Detection of viral RNA in clinical material; OR
  3. Seroconversion or significant increase in IgG level or titre to a flavivirus
  • Specific virus can be assigned if the IgG is shown to be specific to a single virus, by neutralisation or other specific tests
  • Unspecified flavivirus infection if the IgG cannot be shown to be specific to a single virus.
  1. Detection of IgM to a single flavivirus

Dengue
  • Specific virus can be assigned based on detection of DEN IgM alone.

Other flaviviruses
  • Specific virus can be assigned if the IgM to a single flavivirus is detected in the absence of IgM to other likely flaviviruses provided that there is a suitable clinical and exposure history.  Where MVE, KUN or JE is suspected, IgM tests should be done for antibody to DEN, MVE, KUN and JE as a minimum.  Where YF is suspected IgM tests should be done for YF, KUN, DEN and JE as a minimum.
  • Unspecified flavivirus infection if IgM is detected against more than one virus or the full range of flavivurses has not been tested, provided that there is a suitable clinical and exposure history.

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