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

Authorisation: PHLN

Consensus Date: 7 February 2001

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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 Isolation of alphavirus from clinical material; OR Detection of specific alphavirus by NAT; OR IgG seroconversion to specific alphavirus; OR Significant increase in IgG level or titre to specific alphavirus.	Alphavirus other than Sindbis Detection of IgM to specific alphavirus.
		Sindbis Isolation of SIN from clinical material; OR Detection of SIN by NAT; OR Seroconversion or significant increase in IgG level or titre to SIN confirmed by neutralisation titres or other specific serology; OR IgG seroconversion to SIN but not RRV or BFV; OR Significant increase in IgG level or titre to SIN but not RRV or BFV.	Sindbis 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)	Isolation of flavivirus from clinical material; OR Detection of viral RNA in clinical material; OR 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.	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.