Transcript The Public Health Response to Genital Herpes: Where Do We Stand? H.

The Public Health Response to Genital
Herpes: Where Do We Stand?
H. Hunter Handsfield, M.D.
Connie L. Celum, M.D., M.P.H.
Lawrence Corey, M.D.
Gail Bolan, M.D., M.P.H.
Peter A. Leone, M.D., M.P.H.
The Public Health Response to Genital
Herpes: Where Do We Stand?
 Diagnosis: Test Performance and Practical Issues in
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Implementation (Handsfield; 20 min)
HIV/HSV-2 Interactions: Implications for Prevention
(Celum; 20 min)
Prevention: Effective Strategies Old and New (Corey;
20 min)
A Real-World Model (Straw Man?) for Genital Herpes
Clinical Care and Prevention in Public Health Settings
(Handsfield; 5 min)
Comment and Critique (Bolan, Leone, Panel; 10 min)
Discussion (Audience and Panel; 30 min)
The Public Health Response to Genital Herpes:
Where Do We Stand?
Diagnosis of Genital Herpes: Test
Performance and Practical Issues
in Implementation
H. Hunter Handsfield, M.D.
University of Washington
Public Health - Seattle & King County
Seattle, Washington
Public Health Issues in Genital Herpes
The Six Biggies
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Preventing sexual transmission of HSV
Relationship of HSV-2 infection to HIV
transmission and its prevention
Underdiagnosis of genital ulcer disease
The roles of type-specific serological testing
Under-treatment
Preventing neonatal herpes
Diagnosis of Genital
Ulcer Disease
Clinical Diagnosis of Genital
Ulcer Disease
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N = 446; microbiologic or virologic diagnosis made
in 220 (49%)
Sensitivity of classical clinical appearance was poor
(31-35%) for herpes, syphilis, and chancroid
Specificity was good for syphilis (98%), high PPV
Specificity only 94%for HSV and chancroid, low PPV
Conclusion: Classic chancre reliably indicates
syphilis, but is insensitive; otherwise, clinical
diagnosis is unreliable
lab tests essential
DiCarlo RP, Martin DH. CID 1997;25:299-300
Etiology of Genital Ulcer Disease
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516 GUD patients from STD Clinics in 10 of 11 U.S.
cities w/ highest syphilis rates
Excluded patients with typical herpes
PCR for HSV, T. pallidum, H. ducreyi
HSV
333 (64.5%)
Syphilis
64 (12.4%)
HSV + Syphilis
13 (2.5%)
Chancroid
16 (3.1%)
PCR negative
116 (22.4%)
Mertz K et al, JID 1998;178:1795-8
Diagnosis of Genital Herpes
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Test all genital ulcers for HSV
Also test all cases of classical genital herpes
- Clinical diagnosis insensitive and nonspecific
- Virus type determines clinical prognosis,
transmission, and counseling
Virologic tests
- PCR is test of choice; increasingly available
- Culture: The primary test in most settings
- Direct FA: Some don’t provide virus type
- Cytology (Tzanck prep): Insensitive, no virus
type, little or no use
Serological testing: Use only glycoprotein G (gG)
based assays
Serological Testing for
HSV Infection
Type-Specific HSV Serological Tests
Antibody to HSV-1 or -2 glycoprotein G (gG-1 or gG-2)
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Western blot
– The gold standard
Focus Technologies (formerly MRL)
HerpeSelectTM HSV-1 and HSV-2 ELISA
– Sensitivity for HSV-2 ~90, specificity ~98%
Focus Technologies HerpeSelectTM HSV-1 and
HSV-2 Differentiation Immunoblot
– Same antigen as ELISA, probably similar
performance
Proficiency Testing for HSV-1 and HSV-2
Antibody Tests
American College of Clinical Pathologists
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HSV-1 positive, HSV-2 negative (Western blot)
serum sent to 172 participating laboratories
- HSV-1 antibody detected
168 (98%)
- HSV-2 reported positive
• EIA (N = 153)
73 (48%)
• Non-EIA (N = 26)
23 (89%)
• gG based EIA (Focus) (N = 44) 0
Tests to be avoided: Wampole, Zeus, DiaSorin
Ashley-Morrow R, Friedrich R: Am J Clin Path December 2003
Barriers to HSV-2 Serological Testing
(And to Genital Herpes Prevention in General)
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Disbelief that HSV-2 infection matters
Test performance
Cost
Counseling barriers
Benefits vs Risks
Barriers to HSV-2 Serological Testing
(And to Genital Herpes Prevention in General)
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Disbelief that HSV-2 infection matters
Test performance
Cost
Counseling barriers
Benefits vs Risks
Persons at Risk Desire HSV Testing
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Leeds, UK, 200 consecutive STD patients: 92% for
themselves, 91% for their partners (Fairley & Monteiro,
Genitourin Med 1997;73:259-62)
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Seattle, Washington, USA, STD clinic patients
(Wald et al, unpublished)
- Cost-free testing: 756/1477 (51%)
- At $15.00: 558/3099 (18%)
Studies also indicate that many persons say they a
positive test result would be put to use to protect
partners from transmission (Stoner; Douglas; others)
Testing for Genital Herpes
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A decision to not even offer serological testing to
persons at risk for genital herpes is, at its core,
paternalistic:
- “I know what is best for you...
- ...and I’m not even going to give you the option”
A decision to not offer testing essentially prioritizes
provider issues over patient needs and prevention
- Counseling uncertainties
- Time
- Costs
Barriers to HSV-2 Serological Testing
(And to Genital Herpes Prevention in General)
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Disbelief that HSV-2 infection matters
Test performance
Cost
Counseling barriers
Benefits vs Risks
Positive Predictive Value
Sensitivity 90 %, Specificity 98%
Prevalence
PPV
FP Rate
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10%
83%
1 in 6
 25%
94%
1 in 20
 50%
98%
1 in 50
PPV of HSV-2 ELISA Based on HSV-1 Serostatus
and ELISA Optical Density Index
102 Men HSV-2 pos ELISA
Western blot done
44 HSV-1 neg by Western blot
44 HSV-2 pos by Western
blot (PPV=100%)
OD Index >3.0
33/34 HSV-2 pos by Western
blot (PPV=97%)
58 HSV-1 pos by Western blot
41 HSV-2 pos by Western
blot (PPV=71%)
OD Index <3.0
8/24 HSV-2 pos by Western
blot (PPV=33%)
HSV-2 ELISA Testing Algorithm
HSV-2 serology
HSV-2 OD
Index <3.0
HSV-2 OD
Index >3.0
Run HSV-1 serology
HSV-1 negative
HSV-2 true positive
HSV-1 positive
HSV-2 indeterminate
Repeat testing 3 months
or Western Blot
Options for Confirmatory Testing of
the Focus HSV-2 ELISA
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Western blot
HSV-1/OD index testing algorithm
Focus immunoblot?
Focus ELISA avidity assay?
Commercial confirmatory tests (rumors)
- Focus
- Others?
Repeat/convalescent testing
A Perspective on Confirmatory Testing
 Confirmation of Focus HSV-2 ELISA is an issue
only in populations at low or modest risk (e.g.,
prevalence <25%), not for diagnostic testing (prior
probability typically >50%)
- Clinical suspicion of herpes
- Sex partners of HSV-2-infected persons
- Most (all?) populations at risk for HIV
 In lower risk settings, follow the OD index/HSV-1
algorithm if/when confirmed in larger studies
 “Sell” HSV serological testing as test for diagnosis
and for other patently high-risk settings
- Screening in other settings will follow naturally
as providers gain comfort with high-risk testing
Barriers to HSV-2 Serological Testing
(And to Genital Herpes Prevention in General)
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Disbelief that HSV-2 infection matters
Test performance
Cost
Counseling barriers
Benefits vs Risks
Costs of HSV Serological Tests
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Cost
Medicaid
Lab Fee* Reimb
Focus ELISA
- HSV-2
- HSV-1
$5
$5
$15#
$10#
$22
$15
Focus immunoblot
$25
$40
$40
Western blot
$50
$120-150 Variable
* PHSKC Laboratory
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HSV-1 stand alone $15, HSV-1 & 2 $25; STD Clinic pays $5 each
Barriers to HSV-2 Serological Testing
(And to Genital Herpes Prevention in General)
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Disbelief that HSV-2 infection matters
Test performance
Cost
Counseling barriers
Benefits vs Risks
Elements of Herpes Education and
Counseling
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Natural course of disease
Subclinical shedding
Options to reduce transmission risk
- Symptom recognition abstinence
- Condoms
- Antiviral therapy
Increased risk of HIV conferred by HSV-2
Neonatal herpes risks and prevention
Minimal pre-test counseling: Counseling
should not be a barrier to testing
Barriers to HSV-2 Serological Testing
(And to Genital Herpes Prevention in General)
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Disbelief that HSV-2 infection matters
Test performance
Cost
Counseling barriers
Benefits vs Risks
Public Health Approaches to Genital
Herpes Prevention
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Test all genital ulcers for HSV
Liberal use of type-specific serologic tests
- Sex partners of infected persons
- Suggestive symptoms
- Patient request to R/O genital herpes
- Selected pregnant women and partners
- Persons with or at risk for HIV infection
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Assure that patients’ sex partners are evaluated
Public Health Approaches to Genital
Herpes Prevention
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Counsel infected persons and partners
- Subclinical shedding
- Symptom recognition
- Personal prevention strategies (condoms,
abstinence during symptoms)
Consider antiviral therapy to prevent Cesarean
section (may help prevent some cases of
neonatal herpes)
Antiviral therapy of selected infected persons
to prevent transmission
Biomedical Complications of HSV-2
Genital Infection
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Localized neuropathic manifestations
Meningitis (isolated, recurrent)
Erythema multiforme, Stevens Johnson syndrome
Perinatal and maternal morbidity
- Neonatal herpes
- Cesarean section
Nongenital autoinoculation syndromes
(conjunctivitis, keratitis, whitlow)
Chronic localized disease in immunodeficient
patients (especially HIV/AIDS)
Enhanced HIV transmission
Uses of Type-Specific HSV Serology
Definite Indications
 Diagnosis of GUD, recurrent Sx, etc
 Management of sex partners of persons with herpes
 Persons with or at risk for sexual acquisition of HIV
Other Uses
 Selected (all?) pregnant women and their partners
 Patient request
- Request to test for herpes
- Comprehensive STD evaluation
 Do not use routinely to screen all sexually active
persons (controversial)
Screening for Genital Herpes
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A decision to not even offer serological testing to
persons at risk for genital herpes is, at its core,
paternalistic:
- “I know what is best for you...
- ...and I’m not even going to give you the option”
A decision not to offer testing essentially prioritizes
provider issues over patient needs and prevention
- Counseling uncertainties
- Time
- Costs
Persons at Risk Desire HSV Testing

Leeds, UK, 200 consecutive STD patients: 92% for
themselves, 91% for their partners (Fairley & Monteiro,
Genitourin Med 1997;73:259-62)
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Seattle, Washington, USA, STD clinic patients
(Wald et al, unpublished)
- Cost-free testing: 756/1477 (51%)
- At $15.00: 558/3099 (18%)
Studies also indicate that many persons say they a
positive test result would be put to use to protect
partners from transmission (Stoner; Douglas; others)
Psychological Impact of Genital Herpes
Diagnosis
 Significant impact
(Carney et al, Genitourin Med 1994;70:40-5)
- Depression, isolation, fear of rejection: 55-82%of
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patients with initial GH
- Less frequent with repeat outbreaks (28-58%)
Or not so significant: No impairment on standard psych
testing of patients with RGH (median 6 yr) (Brookes et al,
Genitourin Med 1993;69:384-7)
 Responds to suppressive treatment (Patel et al, Sex Transm
Infect 1999;75:398)
 Anecdotal experience reassuring with frequent testing
- Public Health - Seattle King Co. STD Clinic
- Prenatal patients <5% (Brown et al)
Psychological Impact of Genital Herpes
Diagnosis
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So, the psychological impact is or isn’t very large;
variable results, undoubtedly related to differences
between populations and study design
Whatever impact there is appears to be largely
transient, likely responsive to counseling, and
reduced by antiviral therapy
Thus, either it is not a serious problem...
OR
It is a serious problem, making it all the more
important to prevent continued transmission which requires serologic diagnosis