Serological Tests for HSV Sensitivity and Specificity

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Serological Tests for HSVSensitivity and
Specificity
R L Ashley (USA)
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Role of serology symptomatic

• To supplement or confirm virus detection efforts
  (culture, antigen detection, PCR)
• when lesions are negative for virus
• when lesions cannot be sampled for virus
• when lesions are healed or not present

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Role of serology subclinical

• To establish a diagnosis in high-risk patients
• partner has genital herpes
• sexual history suggests risk
• subclinical or atypical infection is suspected
• To identify infection in patients not in
  high-risk groups

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Why are clinical judgement and patient history
insufficient to diagnose genital herpes?

• Symptoms of herpes may be misinterpreted
• Other agents or syndromes may cause lesions
  typical of herpes

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Most patients have not been diagnosed
Per cent of HSV-2 persons reporting a history
of genital herpes NHANES study 9 UK blood
donors 17 USA (Seattle) family
practice 26 USA (Seattle) STD women 34 UK STD
clinic 32
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Clinical judgement fallible

• Prospective HSV-discordant couples trial
• clinical diagnosis made in 47/54 new HSV-2 cases
  presenting with symptoms
• true positive false positive diagnosis made at a
  41 ratio (60 true 14 false positive).
• Directed history study
• 50 of those considered highly likely to have
  genital herpes were HSV-2 seronegative

Langenberg et al. N Engl J Med 199934114321438
Brown et al. Am J Obstet Gynecol
199517212991303
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University of Washington Westernblot profiles
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Commercial type specific testsbased on gG
Company Name of Test Status Gull/Meridian Premie
r Type Specific HSV-1 IgG FDA Approved
1999 Premier Type Specific HSV-2 IgG FDA
Approved 1999 Diagnology POCkit HSV-1 Rapid
Test FDA Approved 1999 MRL HSV-1 ELISA
IgG Pending FDA approval 1999 Diagnostics HSV-
2 ELISA IgG Pending FDA approval 1999 HSV-1
and HSV-2 Differentiation Pending
FDA Immunoblot approval 1999 Roche Cobas Core
IgG EIA Not tested for FDA Sorin ETI-HSVK-G Not
tested for FDA
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CDC Panel test results
Test Sensitivity Specificity Meridian
HSV-1 93 93 MRL HSV-1 100 93 Merdian
HSV-2 86 100 POCkit HSV-2 100 97 MRL
HSV-2 100 100
CDC panel results are presented as a means to
convey further information of the performance of
these assays with a masked, characterized serum
panel. This does not imply an endorsement of the
assays by the CDC
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Comparison of HSV-2 tests1
Test Sensitivity Sensitivity Specificity Cost Easy
lt1M UW WB2 85 99 99 High No Gull
Merdian 8 8199 9799 Low Yes POCkit
HSV-2 80 96100 98 Mod. Yes MRL Immunoblot ND 97
100 9498 Mod. Yes ELISA ND 96100 9697 Low Yes
1. Against UW WB 2. Against cultureUW WB
University of Washington Western blot
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Comparison of HSV-2 tests
Test Sensitivity Specificity Gold
standard Sorin 96 97 Culture, Behring
Roche 96 95 Culture, Behring
Seronegative status determined by non-typing
serology for specificity calculation
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When does sensitivity matter?

• Test cut-offs sacrifice sensitivity for
  specificity
• Soon after infection (tests vary markedly for
  their time to detect seroconversion)
• In all testing situations
• When a test is used as a gold standard to define
  performance of a new test
• low sensitivity of the gold standard will yield
  apparent false positive results for the new test

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When does specificity matter?
Prevalence affects positive predictive value
(PPV) PPV False /1000
tests Specificity 96 99 96 99 Prevalence
15 81 95 34 9 20 86 96 32 8 50 96 99 20
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Diagnosing unrecognizedgenital herpes
(Consider test specificity)
History c/w
Low risk
High risk
Type-specific serology
Type-specific serology
Positive
Negative
Positive
Negative
Confirm with different serology
Negative predictive value high
Diagnosis made
Repeat test on later serum
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Diagnosing symptomaticgenital herpes
(Consider test sensitivity)
History c/w recent acquisition
Yes
No
Other type-specific tests
Negative or Equivocal
Positive
POCKit orWestern blot
Pair with 1216 week serum
Negative or Equivocal
Positive
Repeat test in 6 weeks Consider HSV-1
Diagnosis made
Repeat test
Repeat in 6 weeks Consider HSV-1
Diagnosis made