Table 1. Clinical Manifestations and Type of Infection*
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Type of First Episode Genital Infection |
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Primary HSV-1 N = 20 |
Primary HSV-2 N=189 |
NonPrimary HSV-2† n=76 |
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Percent with systemic symptoms |
58 |
62 |
16 |
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Mean duration local pain, days |
12.5 |
11.8 |
8.7 |
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Mean number of lesions |
24.3 |
15.5 |
9.5 |
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Percent with bilateral lesions |
100 |
82 |
55 |
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Percent forming new lesions during course of disease |
68 |
75 |
45 |
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Mean duration viral shedding from genital lesions, days |
11.1 |
11.4 |
6.8 |
|
Mean duration lesions, days |
22.7 |
18.6 |
15.5
|
* Adapted from Reference (45).
† P<0.05 for each comparison between nonprimary and primary HSV-2 infection.
Table 2. Clinical Manifestations of Primary HSV-2 Genital Herpes*
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Men |
Women |
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Percent with constitutional symptoms |
39 |
68 |
P<0.05 |
|
Percent with meningitis symptoms |
11 |
36 |
P<0.05 |
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Percent with local pain |
95 |
99 |
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|
Mean duration of local pain, days (range) |
10.9 (1-40) |
11.9 (1-37 |
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|
Percent with dysuria |
44 |
83 |
P<0.05 |
|
Mean duration of dysuria, days (range) |
7.2 (2-20) |
11.9 (1-26) |
P<0.05 |
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Percent with urethral/vaginal discharge |
27 |
85 |
P<0.05 |
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Mean duration of discharge, days |
5.6 |
12.9 |
P<0.05 |
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Percent with tender adenopathy |
80 |
81 |
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Mean duration adenopathy, days |
8.6 |
14.2 |
P<0.05 |
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Mean area of lesions, mm2 (range) |
427 (6-1671) |
550 (8-3908) |
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Mean duration of viral shedding from lesions, days |
10.5 |
11.8 |
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Percent with HSV isolated from urethra |
28 |
76 |
P<0.05 |
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Percent with HSV isolated from cervix |
-- |
88 |
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Mean duration viral shedding from cervix, days |
-- |
11.4 |
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|
Mean duration of lesions, days |
16.5 |
19.7
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Adapted from Reference (45).
Table 3. Clinical Manifestations of Recurrent Genital Herpes*
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Men N = 218 |
Women N = 144 |
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Percent experiencing prodromal symptoms |
53 |
43 |
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Percent with pain Mean duration pain, days (range) Mean duration itching, days (range) |
67 3.9 (1-14) 4.6 (1-16) |
88 5.9 5.2 (1-15) |
P<0.01 P<0.01
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Percent with dysuria |
9 |
27 |
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Percent with tender lymph nodes Mean duration tender nodes, days (range) |
23 9.2 (1-25) |
31 5.9 (1-15) |
P<0.01 |
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Percent with bilateral lesions |
15 |
4 |
P<0.05 |
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Percent forming new lesions during episode |
43 |
28 |
P<0.05 |
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Mean number of lesions at onset of episode, days (range) |
7.5 (1-25) |
4.8 (1-15) |
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Mean time to crusting, days (range) |
4.1 (1-15) |
4.7 (2-13) |
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Mean time to healing, days (range) |
10.6 (5-25) |
9.3 (4-29) |
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Mean duration of viral shedding from lesions, days (range)
|
4.4 (1-20) |
4.1 (2-14) |
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* Adapted from Reference (52).
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Table 4. Diagnostic Tests for HSV Infection and Disease Download PDF
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Diagnostic modality |
Description |
Sensitivity and/or specificity |
Utility in clinical practice |
Source(s) of specimen |
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Cytology |
Cytologic examination of cells from skin or mucous membrane |
Sensitivity of 60-70% |
May be useful for presumptive diagnosis |
Maternal cervix
Genital lesion(s)
Infant skin, mouth, conjunctivae, or corneal lesion |
|
Serology |
Detection of antibody
Two type-specific antibody assays manufactured by Focus Technologies, Inc., have received FDA approval: the HerpeSelectÒ HSV-1 and HSV-2 ELISA and the HSV-1 and HSV-2 Immunoblot tests.
Several additional tests which claim to distinguish between HSV-1 and HSV-2 antibody are commercially available, but high cross-reactivity rates due to their use of crude antigen preparations significantly limit their utility |
HerpeSelectÒ HSV-2 ELISA: Sensitivity of 96-100%, specificity of 97-98%
HerpeSelectÒ HSV-2 Immunoblot: Sensitivity of 97–100%, specificity of 98%
Type-specific tests for HSV-1 tend to be 5–10% less sensitive than their HSV-2 counterparts
|
Beyond the infantile period, establishes prior infection with HSV-1 and/or HSV-2. Does not distinguish site of infection.
Could be considered in patients with symptomatic genital disease with lesions in an advanced stage of healing, and patients with risk factors for HSV but no history of genital herpetic lesions
Not useful for diagnosis of neonatal HSV disease. |
Blood |
|
Viral culture |
Specimen collected, transferred in appropriate viral transport media on ice to a diagnostic virology laboratory, and inoculated into cell culture systems, which are then monitored for cytopathic effects characteristic of HSV replication. |
~ 95% of vesicular genital lesions will grow HSV, compared with 70% of ulcerative lesions and 30% of crusted lesions |
The definitive diagnostic method of establishing HSV disease outside of the CNS |
Skin vesicles, oropharynx, CSF, urine, blood, stool or rectum, oropharynx, and conjunctivae. |
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Polymerase chain reaction |
Detection of viral DNA by molecular amplification |
Neonatal HSV CNS disease: Sensitivity 75-100%; specificity 71-100%
HSE beyond the neonatal period: Sensitivity 95-100%; specificity 94% |
The gold standard for documenting CNS HSV disease |
CSF
Cutaneous or mucous membrane lesions |
Table 5. Herpes Blood Tests Quick Reference Guide (from http://www.ashastd.org/pdfs/blood_test.pdf, accessed February 3, 2005) Download PDF
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|
biokit HSV-2 Rapid Test† |
HerpeSelectÒ |
CAPTIAÔ HSV IgG Type Specific ELISA |
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ELISA |
Immunoblot |
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Supplier |
biokit USA (formerly Diagnology with POCkitÒ test) |
Focus Diagnostics, Inc. (formerly Focus Technologies) |
Trinity Biotech USA |
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FDA Approved |
Yes (August 1999) |
Yes (February 2000) |
Yes (April 2000) |
Yes (July 2004) |
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Antibodies Detected |
HSV-2 only |
HSV-1 or HSV-2 |
HSV-1 and HSV-2 |
HSV-1 or HSV-2 |
|
Sensitivity (no false negatives) |
93-96% accurate* |
96-100% accurate* |
97-100% accurate* |
90-100% accurate** |
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Specificity (no false positives) |
95-98% accurate* |
97-100% accurate* |
98% accurate* |
90-99% accurate** |
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HRC Recommended Window Period |
12 to 16 weeks after exposure |
12 to 16 weeks after exposure |
12 to 16 weeks after exposure |
12 to 16 weeks after exposure |
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Collection Method |
Finger prick/blood |
Blood draw (sent to local lab) |
Blood draw (sent to local lab) |
Blood draw (sent to local lab) |
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Test Location |
In provider office |
Various labs |
Various labs |
Various labs |
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Result Time |
Less than 10 minutes |
~ 1 to 2 weeks |
~ 1 to 2 weeks |
~ 1 to 2 weeks |
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Can Be Used During Pregnancy |
Not FDA approved |
Yes |
Yes |
Yes |
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Manufacturer’s List Price Per Test (does not include provider or lab fees) |
~ $20 |
~ $4 |
~ $19 |
~ $4 |
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Phone Number |
Toll-free (800) 926-3353 |
Toll-free (800) 505-0536 (to find a specific lab) |
Toll-free (800) 325-3424 (to find a specific lab) |
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Web site |
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* Adapted from Reference (8).
** Adapted from Reference (8), and from FDA Summary of Safety and Effectiveness Information CAPTIA™ HSV-2 IgG Type Specific Test Kit, July 2004.
† Also available from Fisher HealthCare as Sure-Vue™ HSV-2 Rapid Test. For more information, call toll-free (800) 766-7000 or log on to www.fisherhealthcare.com.
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Table 6. Recommended uses of HSV type-specific serologic testing*
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Indication |
HSV type-specific testing |
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Confirm diagnosis of genital herpes |
Clinical diagnosis is not sensitive or specific; therefore, laboratory confirmation of HSV-1 or -2 is recommended |
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Establish diagnosis of genital herpes |
Atypical genital lesions often represent genital herpes; therefore, HSV type-specific serology for HSV-1 and -2 is recommended |
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Testing of high-risk populations |
Serologic testing for HSV-2 should be offered as part of standard sexually transmitted disease screening |
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Testing partners of HSV-infected people |
Discordance in HSV infection can only be established by laboratory testing; therefore, to counsel patients about the risk of transmission, HSV-1 and -2 serology should be offered |
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Testing of HIV-infected individuals |
Given the epidemiologic synergy between HIV and HSV, testing for HSV-2 should be offered routinely to HIV seropositive people |
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Testing in pregnancy |
Serologic testing for HSV-1 and -2 should be offered to pregnant women to identify those susceptible to HSV acquisition in late pregnancy |
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General screening |
Currently not recommended
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* From Reference (222).
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Table 7. Therapeutic management of nongenital HSV infections Download PDF |
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Primary Oropharyngeal HSV Infections (Gingivostomatitis; HSV-1) |
Recurrent Oropharyngeal HSV Infections (Herpes labialis; HSV-1) |
Other Primary HSV Skin Infections (HSV-1) |
HSV keratitis or keratoconjunctivitis (HSV-1) |
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|
Acyclovir |
600 mg/m2/dose po QID x 10 d (adult maximum 200 mg/dose po 5X/d) |
15 mg/kg/day ¸ q 8h until able to switch to po
200 mg/dose po 5X/day x 7-10 d |
Eczema herpeticum: 10 mg/kg/dose po 3-5X/d x 5-7 d (adult maximum 200 mg/dose po 5X/d)
Whitlow: 200 mg/dose po 5X/day x 10 d |
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Valaciclovir |
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2 grams orally twice a day for 1 day |
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Famciclovir |
|
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Whitlow: 125 mg/dose po BID |
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Penciclovir (DenavirÒ) |
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Apply topically q 2 h during waking hours x 4 d |
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Trifluridine |
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1 drop q 2h (maximum 9 drops/d) until cornea is re-epithelialized, then q 4h for an additional 7d (maximum 21 d) |
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Vidarabine |
|
|
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Thick strip of ointment (1.25 cm) q 3h until cornea is completely re-epithelialized, then BID for an additional 7 d |
|
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Table 8. Therapeutic management of genital HSV infections (HSV-2 or HSV-1)* Download PDF
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First Clinical Episode (treat orally for 7-10 days†) |
Episodic Recurrent Infection¶ (treat orally for 5 days) |
Oral Suppressive therapy |
Episodic recurrent infection in HIV-infected persons (treat orally for 5-10 days) |
Oral Suppressive therapy in HIV-infected persons |
Advantages |
Disadvantages |
|
Acyclovir |
200 mg 5X/day OR 400 mg 3X/day |
200 mg 5X/day OR 800 mg 2X/day |
400 mg 2X/day |
200 mg 5X/day OR 400 mg 3X/day |
400-800 mg 2X/day or 3X/day |
Less expensive
Smaller tablets
Liquid formulation available |
Less convenient dosing regimens |
|
Valaciclovir |
1000 mg/ 2X/day |
500 mg 2X/day‡ OR 1000 mg 1X/day |
500 mg 1X/day§ OR 1000 mg 1X/day |
1000 mg 2X/day |
500 mg 2X/day |
More convenient dosing regimens |
More expensive
Larger caplet |
|
Famciclovir |
250 mg 3X/day |
125 mg 2X/day |
250 mg 2X/day |
500 mg 2X/day |
500 mg 2X/day |
More convenient dosing regimens
Smaller tablet
|
More expensive |
* Modified from Reference (5).
† The range of duration of therapy relates to differences in treatment durations in the original clinical studies. If the shorter course of therapy is initially prescribed, the patient should be reevaluated toward the end of treatment and therapy should be continued if new lesions continue to form, if complications develop, or if systemic signs and symptoms have not abated.
‡ Three-day course of therapy also acceptable
§ For patients with ≤ 9 recurrences/year
¶ When started within 24 hours of the recurrence
Table 9. Telephone and Online Resources for Herpes Information
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Organization |
Telephone Information |
Website |
|
American Social Health Association (ASHA) |
800-230-6039 (Resource Center) 919-361-8488 (Patient Herpes Hotline)
|
www.ashastd.org (ASHA website) www.ashastd.org/hrc (Herpes Resource Center website) www.ashasdt.org/hrc/helpgrp1.html (HELP support groups for people in the U.S., Canada, and Australia with genital herpes) |
|
The Centers for Disease Control and Prevention (CDC) |
800-227-8922 National STD Hotline |
www.cdc.gov (CDC website) www.cdc.gov/nchstp/dstd/dstdp.html (CDC fact sheet on STDs) |
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Planned Parenthood |
800-230-7526 |
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GlaxoSmithKline |
|
www.harduherpes.nu (in Swedish) |
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Novartis |
|
www.herpes.com.au (Australia) |
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National Institutes of Health |
|
www.nih.gov (NIH website) www.niaid.nih.gov/dmid/stds (NIAID fact sheet on STDs) |
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American Herpes Foundation |
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International Herpes Management Forum |
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DAC Consultants |
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International Herpes Alliance |
|
|
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Association Herpès |
|
www.herpes.asso.fr (in French) |