Herpes Simplex Virus

  • Nathalie H. Duroseau
  • Robyn R. MillerEmail author


Genital herpes is one of the most common sexually transmitted diseases globally, and is associated with significant physical and psychological morbidity. However, upwards of 90% of infected individuals are unaware they are infected. Genital herpes is caused by herpes simplex virus type 1 (HSV-1) or herpes simplex type 2 (HSV-2). While there are differences between HSV-1 and HSV-2, both strains can cause ocular, oral, cutaneous and genital infections. HSV must come in contact with mucosal surfaces or abraded skin to initiate infection. Once infected, HSV persists indefinitely in a dormant state within sensory nerve ganglia until it is reactivated and causes a recurrent infection (Herpes simplex virus infections. 2. 2nd ed. Detroit: Charles Scribners & Sons; 2010. p. 823–828; Groves Am Fam Physician 93(11):928, 2016; Solomon et al. N Engl J Med 375(7):666, 2016; Bernstein et al. Clin Infect Dis 56(3):344–51, 2013) The herpes virus typically causes painful ulcerations at the site of infection, but these lesions do not have to be present to transmit the infection (asymptomatic shedding). On the basis of clinical examination, it is often impossible to determine definitively whether a first symptomatic episode of genital herpes is initial or recurrent disease. There are several different modalities to test for HSV infection, but PCR has emerged as the most reliable and sensitive method to confirm infection. A primary episode of HSV should be treated with oral antiviral therapy to prevent prolonged clinical illness with severe genital ulcerations. Prevention of genital HSV should primarily focus on decreasing overall HSV transmission and decreasing the morbidity and psychological stress for those already infected.


Genital herpes Herpes simplex 1 Herpes simplex 2 Painful vaginal lesions Valacyclovir Acyclovir Famciclovir Asymptomatic shedding Primary episode Recurrent episode 


  1. 1.
    Herpes simplex virus infections, vol. 2, 2010. 2nd ed. Detroit: Charles Scribners & Sons. p. 823–8.Google Scholar
  2. 2.
    Groves MJ. Genital herpes: a review. Am Fam Physician. 2016;93(11):928. Scholar
  3. 3.
    Solomon CG, Gnann JW Jr, Whitley RJ. Genital herpes. N Engl J Med. 2016;375(7):666. Scholar
  4. 4.
    Bernstein DI, Bellamy AR, Hook EW 3rd, et al. Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women. Clin Infect Dis. 2013;56(3):344–51. Scholar
  5. 5.
    Fatahzadeh M. Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol. 2007;57(5):737–63. Scholar
  6. 6.
    Gutierrez KM. Rethinking herpes simplex virus infections in children and adolescents. J Pediatr. 2007;151(4):336–8. Scholar
  7. 7.
  8. 8.
    Bradley H, Markowitz LE, Gibson T, McQuillan GM. Seroprevalence of herpes simplex virus types 1 and 2—United States, 1999–2010. J Infect Dis. 2014;209(3):325–33. Scholar
  9. 9.
    Xu F. Seroprevalence of herpes simplex virus type 1 in children in the United States. J Pediatr. 2007;151(4):374–7. Scholar
  10. 10.
    Rana RK, Pimenta JM, Rosenberg DM, et al. Sexual behaviour and condom use among individuals with a history of symptomatic genital herpes. Sex Transm Infect. 2006;82(1):69–74. Scholar
  11. 11.
    U.S. Preventive Services Task Force. Behavioral counseling to prevent sexually transmitted infections: U.S. preventive services task force recommendation statement. Ann Intern Med. 2008;149(7):W95. Scholar
  12. 12.
    Auslander BA, Catallozzi M, Davis G, Succop PA, Stanberry LR, Rosenthal SL. Adolescents’ and young women’s use of a microbicide surrogate product when receiving oral sex. J Pediatr Adolesc Gynecol. 2014;27(1):37–40. Scholar
  13. 13.
    Fanfair R, Zaidi A, Taylor L, Xu F, Gottlieb S, Markowitz L. Trends in seroprevalence of herpes simplex virus type 2 among non-hispanic blacks and non-hispanic whites aged 14 to 49 years—United States, 1988 to 2010. Sex Transm Dis. 2013;40(11):860–4. Scholar
  14. 14.
    Xu F, Sternberg MR, Kottiri BJ, et al. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA. 2006;296(8):964–73. Scholar
  15. 15.
    Gnann JW, Whitley RJ. Genital herpes. N Engl J Med. 2016;375(7):666–74.CrossRefGoogle Scholar
  16. 16.
    Kimberlin DW, Rouse DJ. Genital herpes. N Engl J Med. 2004;350(19):1970–7.CrossRefGoogle Scholar
  17. 17.
    Ward PL, Roizman B. Herpes simplex genes: the blueprint of a successful human pathogen. Trends Genet. 1994;10:267–74.CrossRefGoogle Scholar
  18. 18.
    Garland SM, Steben M. Genital herpes. Best Pract Res Clin Obstet Gynaecol. 2014;28(7):1098–110. Scholar
  19. 19.
    Kukhanova M, Korovina A, Kochetkov S. Human herpes simplex virus: life cycle and development of inhibitors. Biochem Moscow. 2014;79(13):1635–52. Scholar
  20. 20.
    Wald A, Zeh J, Selke S, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000;342(12):844–50. Scholar
  21. 21.
    Fife KH, Williams JA, Thomas AL, Ofner S, Katz BP, Fortenberry JD. Herpes simplex virus type 2 infection in young adult women: risk factors for infection and frequency of viral shedding. Sex Transm Dis. 2010;37(4):248. Scholar
  22. 22.
    Merin A, Pachankis JE. The psychological impact of genital herpes stigma. J Health Psychol. 2011;16(1):80–90. Scholar
  23. 23.
    Sauerbrei A. Optimal management of genital herpes: current perspectives. Infect Drug Resist. 2016;9:129–41. Scholar
  24. 24.
    Dhankani V, Kutz JN, Schiffer JT. Herpes simplex virus-2 genital tract shedding is not predictable over months or years in infected persons. PLoS Comput Biol. 2014;10(11):e1003922. Scholar
  25. 25.
    Gupta R, Wald A, Krantz E, et al. Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract. J Infect Dis. 2004;190(8):1374–81. Scholar
  26. 26.
    Tronstein E, Johnston C, Huang M, et al. Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection. JAMA. 2011;305(14):1441–9. Scholar
  27. 27.
    Wald A, Corey L, Cone R, Hobson A, Davis G, Zeh J. Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment. J Clin Invest. 1997;99(5):1092–7. Scholar
  28. 28.
    Sexually transmitted diseases: summary of 2015 CDC treatment guidelines. J Miss State Med Assoc. 2015;56(12):372.
  29. 29.
    Singh A, Preiksaitis J, Romanowski B. The laboratory diagnosis of herpes simplex virus infections. Can J Infect Dis Med Microbiol. 2005;16(2):92–8. Scholar
  30. 30.
    Ramaswamy M, Mcdonald C, Smith M, et al. Diagnosis of genital herpes by real time PCR in routine clinical practice. Sex Transm Infect. 2004;80(5):406–10. Scholar
  31. 31.
    Moseley RC, Corey L, Benjamin D, Winter C, Remington ML. Comparison of viral isolation, direct immunofluorescence, and indirect immunoperoxidase techniques for detection of genital herpes simplex virus infection. J Clin Microbiol. 1981;13(5):913–8. Scholar
  32. 32.
    Ratnam S, Severini A, Zahariadis G, Petric M, Romanowski B. The diagnosis of genital herpes – beyond culture: an evidence-based guide for the utilization of polymerase chain reaction and herpes simplex virus type-specific serology. Can J Infect Dis Med Microbiol. 2007;18(4):233–40. Scholar
  33. 33.
    Strick LB, Wald A. Diagnostics for herpes simplex virus: is PCR the new gold standard? Mol Diag Ther. 2006;10(1):17–28. Scholar
  34. 34.
    Shevlin E, Morrow RA. Comparative performance of the uni-gold(TM) HSV-2 rapid: a point-of-care HSV-2 diagnostic test in unselected sera from a reference laboratory. J Clin Virol. 2014;61(3):378–81. Scholar
  35. 35.
    Warren T, Gilbert L, Mark H. Availability of serologic and virologic testing for herpes simplex virus in the largest sexually transmitted disease clinics in the United States. Sex Transm Dis. 2011;38(4):267. Scholar
  36. 36.
    Krantz I, Löwhagen G-B, Ahlberg BM, Nilstun T. Ethics of screening for asymptomatic herpes virus type 2 infection. BMJ Br Med J. 2004;329(7466):618–21. Scholar
  37. 37.
    Whittington WL, Celum CL, Cent A, Ashley RL. Use of a glycoprotein G-based type-specific assay to detect antibodies to herpes simplex virus type 2 among persons attending sexually transmitted disease clinics. Sex Transm Dis. 2001;28(2):99–104. Scholar
  38. 38.
    Wald A. Knowledge is power: a case for wider herpes simplex virus serologic testing. JAMA Pediatr. 2013;167(8):689–90. Scholar
  39. 39.
    Roth AM, Van Der Pol B, Fortenberry JD, et al. Herpes simplex virus type 2 serological testing at a community court: predictors of test acceptance and seropositivity among female defendants. Int J STD AIDS. 2013;24(3):169–74. Scholar
  40. 40.
    Patwardhan V, Bhalla P. Role of type-specific herpes simplex virus-1 and 2 serology as a diagnostic modality in patients with clinically suspected genital herpes: a comparative study in indian population from a tertiary care hospital. Indian J Pathol Microbiol. 2016;59(3):318–21. Scholar
  41. 41.
    Cernik C, Gallina K, Brodell RT. The treatment of herpes simplex infections: an evidence-based review. Arch Intern Med. 2008;168(11):1137–44. Scholar
  42. 42.
    Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350(1):11–20. Scholar
  43. 43.
    DeJesus E, Wald A, Warren T, et al. Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects. J Infect Dis. 2003;188(7):1009–16. Scholar
  44. 44.
    Warren T, Harris J, Brennan CA. Efficacy and safety of valacyclovir for the suppression and episodic treatment of herpes simplex virus in patients with HIV. Clin Infect Dis. 2004;39(S5):S266. Scholar
  45. 45.
    Fife KH, Crumpacker CS, Mertz GJ, Hill EL, Boone GS. Recurrence and resistance patterns of herpes simplex virus following cessation of > or = 6 years of chronic suppression with acyclovir. Acyclovir study group. J Infect Dis. 1994;169(6):1338. Scholar
  46. 46.
    Wald A, Langenberg AGM, Link K, et al. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA. 2001;285(24):3100–6. Scholar
  47. 47.
    Caulfield P, Willis D. P57 to disclose or not to disclose. An exploration of the multi-disciplinary team’s role in advising patients about disclosure when diagnosed with genital herpes simplex virus (HSV). Sex Transm Infect. 2015;91(Suppl 1):A34. Scholar
  48. 48.
    Davis A, Roth A, Brand JE, Zimet GD, Van Der Pol B. Coping strategies and behavioural changes following a genital herpes diagnosis among an urban sample of underserved midwestern women. Int J STD AIDS. 2016;27(3):207–12. Scholar
  49. 49.
    Royer HR, Falk EC, Heidrich SM. Genital herpes beliefs: implications for sexual health. J Pediatr Adolesc Gynecol. 2013;26(2):109–16. Scholar
  50. 50.
    Wald A, Krantz E, Selke S, Lairson E, Morrow RA, Zeh J. Knowledge of partners’ genital herpes protects against herpes simplex virus type 2 acquisition. J Infect Dis. 2006;194(1):42–52. Scholar
  51. 51.
    Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis. 2002;185(1):45–52. Scholar
  52. 52.
    Mujugira A, Magaret AS, Celum C, et al. Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial. J Infect Dis. 2013;208(9):1366–74. Scholar
  53. 53.
    Robinson NJ, Celum CL, Cohen MS. Potential effect of HIV type 1 antiretroviral and herpes simplex virus type 2 antiviral therapy on transmission and acquisition of HIV type 1 infection. J Infect Dis. 2005;191(3):S107.PubMedGoogle Scholar
  54. 54.
    Murdoch DM, Venter WD, Feldman C, Van Rie A. Incidence and risk factors for the immune reconstitution inflammatory syndrome in HIV patients in South Africa: a prospective study. AIDS. 2008;22(5):601.CrossRefGoogle Scholar
  55. 55.
    Mikuła T, Mian MM, Stańczak W, Cianciara J. The immune reconstitution inflammatory syndrome (IRIS) in HIV infected patient – case report. HIV AIDS Rev. 2007;6(3):25–31. Scholar
  56. 56.
    Acyclovir Pregnancy Registry and Valacyclovir Pregnancy Registry Interim Report, December 1997. Glaxo Wellcome, RTP, NC 27709.Google Scholar
  57. 57.
    Centers for Disease Control and Prevention: Metropolitan Atlanta Congenital Defects Program, revised January 1998.
  58. 58.
    Cone RW, Hobson AC, Brown Z, et al. Frequent detection of genital herpes simplex virus DNA by polymerase chain reaction among pregnant women. JAMA. 1994;272(10):792–6. Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Icahn School of Medicine at Mount Sinai HospitalNew YorkUSA
  2. 2.Division of Adolescent MedicineNemours/AI duPont Hospital for Children Sidney Kimmel College of Medicine at Thomas Jefferson UniversityWilmingtonUSA

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