Herpes simplex virus (HSV)

Suspected HSV infection without genital lesions/pregnant at risk for HSV infection

Antibodies to HSV are detected 2 weeks to 6 months after primary exposure1,2. A substantial proportion of newly-infected patients are positive for IgG and IgM, or IgG alone1,3,4. Despite the theory that IgM production ceases over time, levels of anti-HSV IgM can vary considerably after the primary infection and can be detected also due to recurrent episodes3,5. Approximately one-third of people infected with HSV-2 have detectable IgM with a recurrent infection. In addition, IgM tests cannot accurately distinguish between HSV-1 and HSV-2 antibodies and sometimes cross-react with other viruses in the same family6. For these reasons IgM testing is not recommended in routine clinical practice6-10.

Adapted from:

  1. American Sexual Health Association. Diagnosing Herpes. [Internet; updated 2024; cited 2024 Mar 5]. Available from: https://www.ashasexualhealth.org/herpes-testing/.
  2. Workowski, KA, et al. Sexually Transmitted Diseases Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70:29-36. [Internet; updated 2022 Sep 21; cited 2024 Mar 5]. Available from: https://www.cdc.gov/std/treatment-guidelines/herpes.htm.
  3. Sénat MV, et al. Prevention and management of genital herpes simplex infection during pregnancy and delivery: Guidelines from the French College of Gynaecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Repr Biol. 2018;224:93-101.
  4. Patel R, et al. European guideline for the management of genital herpes. Int J STD AIDS. 2017;28:1-14.
  5. Groves MJ. Genital Herpes: A Review. Am Fam Physician. 2016;93:928-934.
  6. Riedel A, et al. P5.071 Evaluation of Elecsys Immunoassay System for Determination of Type-Specific IgG Antibodies to HSV-1 and HSV-2. Sex Transm Infect. 2013;89(Suppl 1):A1-A428.
  7. Gardella C and Brown ZA. Managing genital herpes infections in pregnancy. Cleve Clin J Med. 2007;74:217-224.
  8. Morrow R and Friedrich D. Performance of a novel test for IgM and IgG antibodies in subjects with culture-documented genital herpes simplex virus-1 or -2 infection. Clin Microbiol Infect. 2006;12:463-469.
  9. Whitley RJ and Miller RL. Immunologic approach to herpes simplex virus. Viral Immunol. 2001;14:111-118.
Product Description Tests Product page
Elecsys® HSV-1 IgG a) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of IgG class antibodies to HSV‑1 in human serum and plasma 100
Elecsys® HSV-1 IgG b) 100
Elecsys® HSV-2 IgG a) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of IgG class antibodies to HSV‑2 in human serum and plasma 100
Elecsys® HSV-1 IgG b) 100
cobas® HSV 1 and 2 Test c) Nucleic acid amplification test for the detection and typing of HSV-1 and HSV-2 DNA in clinician-collected anogenital lesion specimens 80
240

a) for use on the cobas® e 411 analyzer and the cobas® e 601 / 602 modules
b) for use on the cobas® e 402 and cobas® e 801 analytical units
c) for use on the cobas® 4800 System

HSV-1 IgG HSV-2 IgG HSV 1/2 DNA Results indicate
- - - Susceptible; consider at risk of infection to both types.
- - + Profile suggestive of an initial primary first episode of genital herpes
+ + Type 1 or 2 + Profile suggestive of recurrence.
+ - Type 1 +
- + Type 2 +
- + Type 1 + Profile suggestive of a non-primary first episode of genital herpes.
+ - Type 2 +
+ - - Profile suggestive of latent HSV-1
+ + - Profile suggestive of latent HSV-1 and HSV-2
- + - Profile suggestive of latent HSV-2
+ - + Profile suggestive of simultanous mixed infections
- + +
- - +

Adapted from:

  1. Workowski, KA, et al. Sexually Transmitted Diseases Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70:29-36. [Internet; updated 2022 Sep 21; cited 2024 Mar 5]. Available from: https://www.cdc.gov/std/treatment-guidelines/herpes.htm.
  2. Piret J, et al. Immunomodulatory strategies in herpes simplex virus encephalitis. Clin Microbiol Rev. 2020;33:e00105-19.
  3. Sénat MV, et al. Prevention and management of genital herpes simplex infection during pregnancy and delivery: Guidelines from the French College of Gynaecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Repr Biol. 2018;224:93-101.
  4. Sauerbrei A. Optimal management of genital herpes: current perspectives. Infection and Drug Resistance. 2016;9:129–141.
  5. Kaneko H, et al. Evaluation of Mixed Infection Cases With Both Herpes Simplex Virus Types 1 and 2. Journal of Medical Virology. 2008;80:883–887.
  6. Brown ZA, et al. Genital herpes complicating pregnancy. Obstet Gynecol. 2005;106:845-856.
  7. Brown ZA. Use of Herpes Type-specific Serology to Prevent Neonatal Herpes Simplex Virus Infection. NeoReviews. 2004;5:e16-e21.
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Step 1
Pregnant woman with genital lesions without known history of herpes
Pregnant woman with genital lesions and known history of herpes
Suspected HSV infection without genital lesions/pregnant at risk for HSV infection
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Step 1

Perform HSV type-specific DNA testing* from lesion swabs and HSV-1 and HSV-2 IgG tests

(*if unavailable perform virus culture)

HSV-1 IgG
HSV-2 IgG
HSV-1 DNA
HSV-2 DNA
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Summary

Swabbing is not recommended. If the lesion is atypical, perform PCR or culture to confirm a recurrence. Begin antiviral prophylaxis at 36 weeks of gestation until delivery, to reduce the risk of cesarean delivery because of herpes lesions.
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Step 1

Perform HSV-1 IgG and HSV-2 IgG tests in parallel

HSV-1 IgG
HSV-2 IgG
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Summary

Check the immune status of the partner
Counselling about strategies to prevent a new infection with either virus type during pregnancy.

Partner is HSV-1 and HSV-2 non-reactive: Counselling if seronegative woman and her partner are in high risk group, educate them about the potential risks of HSV-2 infections and protection.

Partner is HSV-1 and/or HSV-2 IgG reactive: Proposed management strategy.

  • Perform PCR from the genital swab sample of the woman if lesions occur
  • Educate the woman and her partner:
    • Avoid genital contact
    • Use condoms
    • Antiviral treatment (suppression of the virus) for the partner
  • Step 1
  • Step 2

Summary

Susceptible for HSV-1 or HSV-2 infection
Consider differential diagnosis.

Acquisition of genital HSV-2 or HSV-1 toward the end of pregnancy carries a 30-50% risk of neonatal herpes.

Check the partner.

  • If the partner is HSV-1 positive:
    • Avoid giving oral sex to woman
    • Avoid giving contact; sexual abstinence
    • Use condoms
    • Antiviral treatment (suppression of the virus) for the partner
  • If the partner is HSV-2 positive:
    • Avoid giving contact; sexual abstinence
    • Use condoms
    • Antiviral treatment (suppression of the virus) for the partner
  • Step 1
  • Step 2

Summary

Previous HSV-1 infection (latent HSV-1)
Risk of transmission to the neonate is small as maternal antibodies are protective.

Check the partner. If the partner is HSV-2 positive:

  • Avoid giving contact; sexual abstinence
  • Use condoms
  • Antiviral treatment (suppression of the virus) for the partner
  • Step 1
  • Step 2

Summary

Previous HSV-1 and HSV-2 infection (latent HSV-1 and HSV-2)
Risk of transmission to the neonate is small as maternal antibodies are protective.

Check the partner. If the partner is HSV-2 positive

  • Avoid giving contact; sexual abstinence
  • Use condoms
  • Antiviral treatment (suppression of the virus) for the partner
  • Step 1
  • Step 2

Summary

Previous HSV-2 infection (latent HSV-2)

Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.

  • Step 1
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Summary

Propose management strategy
Educate the woman and the partner.

Suppression of the virus.

Perform HSV DNA testing from genital swab samples if lesions occur.

Avoid vaginal delivery if lesions occur.

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Step 2

Test newborn for HSV DNA within 24h

HSV DNA
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Summary

HSV DNA negative
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

No further sampling required until asymptomatic.

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Summary

HSV DNA positive
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

Start treatment of newborn.

  • Step 1
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Step 2

Test newborn for HSV DNA within 24h

HSV DNA
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  • Step 3

Summary

HSV DNA negative
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

No further sampling required until asymptomatic.

  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA positive
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

Start treatment of newborn.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA negative
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

No further sampling required until asymptomatic.

  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA positive
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

Start treatment of newborn.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA negative
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

No further sampling required until asymptomatic.

  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA positive
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

Start treatment of newborn.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA negative
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

No further sampling required until asymptomatic.

  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA positive
Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.
HIV serological test and screening for other STIs recommended.
Abstain from sexual relations in the presence of ulcerations.
If lesions are present at labor, cesarean delivery is recommended.

Start treatment of newborn.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA negative
Major risk. Consider the appropriate antiviral treatment options based on the HSV type involved.

No further sampling required until asymptomatic.

  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA positive
Major risk. Consider the appropriate antiviral treatment options based on the HSV type involved.

Start treatment of newborn.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA negative
Major risk. Consider the appropriate antiviral treatment options based on the HSV type involved.

No further sampling required until asymptomatic.

  • Step 1
  • Step 2
  • Step 3

Summary

HSV DNA positive
Major risk. Consider the appropriate antiviral treatment options based on the HSV type involved.

Start treatment of newborn.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

No further sampling required until asymptomatic
  • Step 1
  • Step 2
  • Step 3

Summary

Discuss further sampling.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

No further sampling required until asymptomatic
  • Step 1
  • Step 2
  • Step 3

Summary

Discuss further sampling.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

No further sampling required until asymptomatic
  • Step 1
  • Step 2
  • Step 3

Summary

Discuss further sampling.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

No further sampling required until asymptomatic
  • Step 1
  • Step 2
  • Step 3

Summary

Discuss further sampling.

  • Step 1
  • Step 2
  • Step 3
Step 2

Test newborn for HSV DNA within 24h

HSV DNA
  • Step 1
  • Step 2
  • Step 3

Summary

No further sampling required until asymptomatic
  • Step 1
  • Step 2
  • Step 3

Summary

Discuss further sampling.

Back
Next Restart simulation
Step
Result
Interpretation
1
Testing of pregnant women = ...
1
Pregnant woman with genital lesions without known history of herpes
1
Pregnant woman with genital lesions and known history of herpes
1
Suspected HSV infection without genital lesions/pregnant at risk for HSV infection
1
HSV-1 IgG = ...
HSV-2 IgG = ...
HSV-1 DNA = ...
HSV-2 DNA = ...
waiting for input
1
HSV-1 IgG = negative
HSV-2 IgG = negative
HSV-1 DNA = negative
HSV-2 DNA = negative
Suspectible for HSV-1 or HSV-2 infection
1
HSV-1 IgG = positive
HSV-2 IgG = negative
HSV-1 DNA = negative
HSV-2 DNA = negative

Previous HSV-1 infection (latent HSV-1)

1
HSV-1 IgG = positive
HSV-2 IgG = positive
HSV-1 DNA = negative
HSV-2 DNA = negative

Previous HSV-1 and HSV-2 infections (latent HSV-1 and HSV-2)

1
HSV-1 IgG = negative
HSV-2 IgG = positive
HSV-1 DNA = negative
HSV-2 DNA = negative

 Previous HSV-2 infection (latent HSV-2)

1
HSV-1 IgG = negative
HSV-2 IgG = negative
HSV-1 DNA = positive
HSV-2 DNA = negative
Initial primary first episode of HSV-1 / acute HSV-1 infection

Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.

HIV serological test and screening for other STIs recommended.

Abstain from sexual relations in the presence of ulcerations.

If lesions are present at labor, cesarean delivery is recommended

Test newborn for HSV DNA within 24 h.
1
HSV-1 IgG = negative
HSV-2 IgG = negative
HSV-1 DNA = negative
HSV-2 DNA = positive

Initial primary first episode of HSV-2 / acute HSV-2 infection

Suppression at 36 weeks, education about HSV, avoid invasive procedures at delivery.

HIV serological test and screening for other STIs recommended.

Abstain from sexual relations in the presence of ulcerations.

If lesions are present at labor, cesarean delivery is recommended

Test newborn for HSV DNA within 24 h.

1
HSV-1 IgG = negative
HSV-2 IgG = negative
HSV-1 DNA = positive
HSV-2 DNA = positive

Simultaneous primary HSV-1 and HSV-2 infection /mixed infection (rare)

Test newborn for HSV DNA within 24 h.

1
HSV-1 IgG = positive
HSV-2 IgG = negative
HSV-1 DNA = positive
HSV-2 DNA = positive

Simultaneous recurrent  HSV-1 and primary HSV-2 infection / mixed infection (rare)
​​​​​​​
Test newborn for HSV DNA within 24 h.

1
HSV-1 IgG = negative
HSV-2 IgG = positive
HSV-1 DNA = positive
HSV-2 DNA = positive

Simultaneous recurrent HSV-2 and primary HSV-1 infection /mixed infection

Test newborn for HSV DNA within 24 h.

1
HSV-1 IgG = positive
HSV-2 IgG = negative
HSV-1 DNA = negative
HSV-2 DNA = positive
Non primary HSV-1, first episode of HSV-2.

Major risk. Consider the appropriate antiviral treatment options based on the HSV type involved.

Test newborn for HSV DNA within 24 h.
1
HSV-1 IgG = negative
HSV-2 IgG = positive
HSV-1 DNA = positive
HSV-2 DNA = negative

Non primary HSV-2, first episode of HSV-1.

Major risk. Consider the appropriate antiviral treatment options based on the HSV type involved.

Test newborn for HSV DNA within 24 h.

1
HSV-1 IgG = positive
HSV-2 IgG = negative
HSV-1 DNA = positive
HSV-2 DNA = negative
Recurrent HSV-1 infection

Minor risk. Consider antiviral treatment options.

Test newborn for HSV DNA within 24 h.
1
HSV-1 IgG = positive
HSV-2 IgG = positive
HSV-1 DNA = positive
HSV-2 DNA = positive

Simultaneous recurrent HSV-1 and HSV-2 infection / mixed infection

Minor risk. Consider antiviral treatment options.

Test newborn for HSV DNA within 24 h.

1
HSV-1 IgG = negative
HSV-2 IgG = positive
HSV-1 DNA = negative
HSV-2 DNA = positive

Recurrent HSV-2 infection

Minor risk. Consider antiviral treatment options.

Test newborn for HSV DNA within 24 h.

1
HSV-1 IgG = positive
HSV-2 IgG = positive
HSV-1 DNA = negative
HSV-2 DNA = positive

Recurrent HSV-2 infection, latent HSV-1 infection

Minor risk. Consider antiviral treatment options.

Test newborn for HSV DNA within 24 h.

1
HSV-1 IgG = positive
HSV-2 IgG = positive
HSV-1 DNA = positive
HSV-2 DNA = negative
Recurrent HSV-1 infection

Minor risk. Consider antiviral treatment options.

Test newborn for HSV DNA within 24 h.
1
HSV-1 IgG = ...
HSV-2 IgG = ...
waiting for input
1
HSV-1 IgG = positive
HSV-2 IgG = negative
Check the immune status of the partner
1
HSV-1 IgG = negative
HSV-2 IgG = positive
Propose management strategy
1
HSV-1 IgG = positive
HSV-2 IgG = positive

Propose management strategy

1
HSV-1 IgG = negative
HSV-2 IgG = negative
Check the immune status of the partner
2
HSV DNA = ...
waiting for input
2
HSV DNA = negative
2
HSV DNA = positive
2
HSV DNA = ...
waiting for input
2
HSV DNA = negative
2
HSV DNA = positive
2
newborn HSV DNA = ...
waiting for input
2
newborn HSV DNA = negative
No further sampling required until asymptomatic.
2
newborn HSV DNA = positive

Discuss further sampling

End of test sequence