Herpes Simplex Questions & Answers

1. Schiffer J, Corey L. Herpes Simplex Virus. Mandell Gl, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 8th ed. Pennsylvania: Elsevier; 2015. Vol 2: 1713-30.

2. Kimberlin DW, Rouse DJ. Clinical practice. Genital herpes. N Engl J Med. 2004 May 6. 350(19):1970-7. [QxMD MEDLINE Link].

3. Mark KE, Wald A, Magaret AS, Selke S, Olin L, Huang ML. Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults. J Infect Dis. 2008 Oct 15. 198(8):1141-9. [QxMD MEDLINE Link].

4. Ayoub HH, Chemaitelly H, Abu-Raddad LJ. Characterizing the transitioning epidemiology of herpes simplex virus type 1 in the USA: model-based predictions. BMC Med. 2019 Mar 11. 17 (1):57. [QxMD MEDLINE Link].

5. Bernstein DI, Bellamy AR, Hook EW 3rd, Levin MJ, Wald A, Ewell MG, 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 Feb. 56 (3):344-51. [QxMD MEDLINE Link].

6. Roberts CM, Pfister JR, Spear SJ. Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis. 2003 Oct. 30 (10):797-800. [QxMD MEDLINE Link].

7. Xu F, Sternberg MR, Kottiri BJ, McQuillan GM, Lee FK, Nahmias AJ, et al. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA. 2006 Aug 23. 296 (8):964-73. [QxMD MEDLINE Link].

8. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. 1997 Oct 16. 337(16):1105-11. [QxMD MEDLINE Link].

9. Arduino PG, Porter SR. Oral and perioral herpes simplex virus type 1 (HSV-1) infection: review of its management. Oral Dis. 2006 May. 12(3):254-70. [QxMD MEDLINE Link].

10. Spruance SL, Overall JC Jr, Kern ER, Krueger GG, Pliam V, Miller W. The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. N Engl J Med. 1977 Jul 14. 297(2):69-75. [QxMD MEDLINE Link].

11. Scoular A, Gillespie G, Carman WF. Polymerase chain reaction for diagnosis of genital herpes in a genitourinary medicine clinic. Sex Transm Infect. 2002 Feb. 78 (1):21-5. [QxMD MEDLINE Link].

12. Bernstein DI, Bellamy AR, Hook EW 3rd, Levin MJ, Wald A, Ewell MG, 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 Feb. 56 (3):344-51. [QxMD MEDLINE Link].

13. Jin F, Prestage GP, Mao L, Kippax SC, Pell CM, Donovan B, et al. Transmission of herpes simplex virus types 1 and 2 in a prospective cohort of HIV-negative gay men: the health in men study. J Infect Dis. 2006 Sep 1. 194 (5):561-70. [QxMD MEDLINE Link].

14. Tunbäck P, Bergström T, Andersson AS, Nordin P, Krantz I, Löwhagen GB. Prevalence of herpes simplex virus antibodies in childhood and adolescence: a cross-sectional study. Scand J Infect Dis. 2003. 35 (8):498-502. [QxMD MEDLINE Link].

15. Reeves WC, Corey L, Adams HG, Vontver LA, Holmes KK. Risk of recurrence after first episodes of genital herpes. Relation to HSV type and antibody response. N Engl J Med. 1981 Aug 6. 305 (6):315-9. [QxMD MEDLINE Link].

16. Vyse AJ, Gay NJ, Slomka MJ, Gopal R, Gibbs T, Morgan-Capner P, et al. The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes. Sex Transm Infect. 2000 Jun. 76 (3):183-7. [QxMD MEDLINE Link].

17. Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000 Mar 23. 342 (12):844-50. [QxMD MEDLINE Link].

18. Wald A, Zeh J, Selke S, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infections. N Engl J Med. 1995 Sep 21. 333(12):770-5. [QxMD MEDLINE Link].

19. Benedetti JK, Zeh J, Corey L. Clinical reactivation of genital herpes simplex virus infection decreases in frequency over time. Ann Intern Med. 1999 Jul 6. 131(1):14-20. [QxMD MEDLINE Link].

20. Sköldenberg B, Jeansson S, Wolontis S. Herpes simplex virus type 2 and acute aseptic meningitis. Clinical features of cases with isolation of herpes simplex virus from cerebrospinal fluids. Scand J Infect Dis. 1975. 7(4):227-32. [QxMD MEDLINE Link].

21. Singh A, Preiksaitis J, Ferenczy A, Romanowski B. The laboratory diagnosis of herpes simplex virus infections. Can J Infect Dis Med Microbiol. 2005 Mar. 16 (2):92-8. [QxMD MEDLINE Link].

22. Lafferty WE, Krofft S, Remington M, Giddings R, Winter C, Cent A, et al. Diagnosis of herpes simplex virus by direct immunofluorescence and viral isolation from samples of external genital lesions in a high-prevalence population. J Clin Microbiol. 1987 Feb. 25 (2):323-6. [QxMD MEDLINE Link].

23. Whitley RJ. Herpes simplex virus infections of the central nervous system. A review. Am J Med. 1988 Aug 29. 85(2A):61-7. [QxMD MEDLINE Link].

24. Aurelius E, Johansson B, Skoldenberg B, Staland A, Forsgren M. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet. 1991 Jan 26. 337(8735):189-92. [QxMD MEDLINE Link].

25. Liang QN, Zhou JW, Liu TC, Lin GF, Dong ZN, Chen ZH, et al. Development of a time-resolved fluorescence immunoassay for herpes simplex virus type 1 and type 2 IgG antibodies. Luminescence. 2014 Nov 5. [QxMD MEDLINE Link].

26. Tyler KL. Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's. Herpes. 2004 Jun. 11 Suppl 2:57A-64A. [QxMD MEDLINE Link].

27. Álvarez DM, Castillo E, Duarte LF, Arriagada J, Corrales N, Farías MA, et al. Current Antivirals and Novel Botanical Molecules Interfering With Herpes Simplex Virus Infection. Front Microbiol. 2020. 11:139. [QxMD MEDLINE Link].

28. Cernik C, Gallina K, Brodell RT. The treatment of herpes simplex infections: an evidence-based review. Arch Intern Med. 2008 Jun 9. 168 (11):1137-44. [QxMD MEDLINE Link].

29. Gnann JW Jr, Whitley RJ. Herpes Simplex Encephalitis: an Update. Curr Infect Dis Rep. 2017 Mar. 19 (3):13. [QxMD MEDLINE Link].

30. Bacon TH, Levin MJ, Leary JJ, Sarisky RT, Sutton D. Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy. Clin Microbiol Rev. 2003 Jan. 16 (1):114-28. [QxMD MEDLINE Link].

31. Baker D, Eisen D. Valacyclovir for prevention of recurrent herpes labialis: 2 double-blind, placebo-controlled studies. Cutis. 2003 Mar. 71 (3):239-42. [QxMD MEDLINE Link].

32. Rooney JF, Straus SE, Mannix ML, Wohlenberg CR, Alling DW, Dumois JA, et al. Oral acyclovir to suppress frequently recurrent herpes labialis. A double-blind, placebo-controlled trial. Ann Intern Med. 1993 Feb 15. 118 (4):268-72. [QxMD MEDLINE Link].

33. Farr Zuend C, Nomellini JF, Smit J, Horwitz MS. Generation of a Dual-Target, Safe, Inexpensive Microbicide that Protects Against HIV-1 and HSV-2 Disease. Sci Rep. 2018 Feb 12. 8 (1):2786. [QxMD MEDLINE Link].

34. Johnston C, et al. Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomized, open-label, cross-over trials [published online ahead of print January 5, 2012]. Lancet. doi:10.1016/S0140-6736(11)61750-9.

35. Whitley R, Baines J. Clinical management of herpes simplex virus infections: past, present, and future. F1000Res. 2018. 7:[QxMD MEDLINE Link].

36. Chen YC, Sheng J, Trang P, Liu F. Potential Application of the CRISPR/Cas9 System against Herpesvirus Infections. Viruses. 2018 May 29. 10 (6):[QxMD MEDLINE Link].

37. Green LK, Pavan-Langston D. Herpes simplex ocular inflammatory disease. Int Ophthalmol Clin. 2006 Spring. 46(2):27-37. [QxMD MEDLINE Link].

38. Bedoui S, Greyer M. The role of dendritic cells in immunity against primary herpes simplex virus infections. Front Microbiol. 2014. 5:533. [QxMD MEDLINE Link]. [Full Text].

39. Byers RJ, Hasleton PS, Quigley A, Dennett C, Klapper PE, Cleator GM, et al. Pulmonary herpes simplex in burns patients. Eur Respir J. 1996 Nov. 9 (11):2313-7. [QxMD MEDLINE Link].

40. Baras L, Farber CM, Van Vooren JP, Parent D. Herpes simplex virus tracheitis in a patient with the acquired immunodeficiency syndrome. Eur Respir J. 1994 Nov. 7 (11):2091-3. [QxMD MEDLINE Link].

41. Taplitz RA, Jordan MC. Pneumonia caused by herpesviruses in recipients of hematopoietic cell transplants. Semin Respir Infect. 2002 Jun. 17 (2):121-9. [QxMD MEDLINE Link].

42. Bouza E, Giannella M, Torres MV, Catalán P, Sánchez-Carrillo C, Hernandez RI, et al. Herpes simplex virus: a marker of severity in bacterial ventilator-associated pneumonia. J Crit Care. 2011 Aug. 26 (4):432.e1-6. [QxMD MEDLINE Link].

43. Hutto C, Arvin A, Jacobs R, Steele R, Stagno S, Lyrene R, et al. Intrauterine herpes simplex virus infections. J Pediatr. 1987 Jan. 110 (1):97-101. [QxMD MEDLINE Link].

44. Ratanajamit C, Vinther Skriver M, Jepsen P, Chongsuvivatwong V, Olsen J, Sørensen HT. Adverse pregnancy outcome in women exposed to acyclovir during pregnancy: a population-based observational study. Scand J Infect Dis. 2003. 35 (4):255-9. [QxMD MEDLINE Link].

45. Management of Genital Herpes in Pregnancy: ACOG Practice Bulletinacog Practice Bulletin, Number 220. Obstet Gynecol. 2020 May. 135 (5):e193-e202. [QxMD MEDLINE Link].

46. Scott LL, Hollier LM, McIntire D, Sanchez PJ, Jackson GL, Wendel GD Jr. Acyclovir suppression to prevent clinical recurrences at delivery after first episode genital herpes in pregnancy: an open-label trial. Infect Dis Obstet Gynecol. 2001. 9 (2):75-80. [QxMD MEDLINE Link].

47. Stránská R, Schuurman R, Nienhuis E, Goedegebuure IW, Polman M, Weel JF, et al. Survey of acyclovir-resistant herpes simplex virus in the Netherlands: prevalence and characterization. J Clin Virol. 2005 Jan. 32 (1):7-18. [QxMD MEDLINE Link].

48. Stone KM, Reiff-Eldridge R, White AD, Cordero JF, Brown Z, Alexander ER, et al. Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999. Birth Defects Res A Clin Mol Teratol. 2004 Apr. 70 (4):201-7. [QxMD MEDLINE Link].

49. James SH, Kimberlin DW. Neonatal herpes simplex virus infection: epidemiology and treatment. Clin Perinatol. 2015 Mar. 42 (1):47-59, viii. [QxMD MEDLINE Link].

50. Harris JB, Holmes AP. Neonatal Herpes Simplex Viral Infections and Acyclovir: An Update. J Pediatr Pharmacol Ther. 2017 Mar-Apr. 22 (2):88-93. [QxMD MEDLINE Link].

51. Looker KJ, Elmes JAR, Gottlieb SL, Schiffer JT, Vickerman P, Turner KME, et al. Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis. Lancet Infect Dis. 2017 Dec. 17 (12):1303-1316. [QxMD MEDLINE Link].

52. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2006 Jan 2. 20 (1):73-83. [QxMD MEDLINE Link].

53. Corey L, Wald A, Celum CL, Quinn TC. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J Acquir Immune Defic Syndr. 2004 Apr 15. 35(5):435-45. [QxMD MEDLINE Link].

54. Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007 Feb 22. 356(8):790-9. [QxMD MEDLINE Link].

55. Baeten JM, Strick LB, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, et al. Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial. J Infect Dis. 2008 Dec 15. 198(12):1804-8. [QxMD MEDLINE Link]. [Full Text].

56. Posavad CM, Wald A, Kuntz S, Huang ML, Selke S, Krantz E, et al. Frequent reactivation of herpes simplex virus among HIV-1-infected patients treated with highly active antiretroviral therapy. J Infect Dis. 2004 Aug 15. 190 (4):693-6. [QxMD MEDLINE Link].

Folusakin O Ayoade, MD Assistant Professor of Clinical Medicine, Division of Infectious Diseases, Department of Medicine, University of Miami, Leonard M Miller School of Medicine; Attending Physician in Infectious Diseases, Jackson Health System; Attending Physician in Infectious Diseases, University of Miami Hospital

Folusakin O Ayoade, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Medical Association, Infectious Diseases - International Research Initiative, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Shuba Balan, MD, DFM Chief Fellow, Division of Infectious Diseases, Jackson Health System, University of Miami, Leonard M Miller School of Medicine

Shuba Balan, MD, DFM is a member of the following medical societies: American College of Physicians, American Association of Clinical Endocrinologists, Infectious Diseases Society of America, Royal College of General Practitioners

Disclosure: Nothing to disclose.

John R Todd, IV, MD Professor of Clinical Medicine, Department of Medicine, Section of Infectious Diseases, Louisiana State University School of Medicine in Shreveport

John R Todd, IV, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine in New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for Physician Leadership, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physicians, American Federation for Medical Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, The Scientific Research Honor Society, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, Southwestern Association of Clinical Microbiology, The Foundation for AIDS Research

Disclosure: Receives royalties from Baxter International for: Takeda-receives royalties; UpToDate-receives royalties.

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Larry I Lutwick, MD, FACP Editor-in-Chief, ID Cases; Moderator, Program for Monitoring Emerging Diseases; Adjunct Professor of Medicine, State University of New York Downstate College of Medicine

Larry I Lutwick, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American Association for the Study of Liver Diseases, American College of Physicians, American Federation for Clinical Research, American Society for Microbiology, Infectious Diseases Society of America, Infectious Diseases Society of New York, International Society for Infectious Diseases, New York Academy of Sciences, Veterans Affairs Society of Practitioners in Infectious Diseases

Disclosure: Nothing to disclose.

Meena Seenivasan, MD Fellow, Department of Infectious Disease, State University of New York Health Science Center at Brooklyn

Disclosure: Nothing to disclose.

Thomas J Marrie, MD Dean of Faculty of Medicine, Dalhousie University Faculty of Medicine, Canada

Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Association of Medical Microbiology and Infectious Disease Canada, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Swati Kumar, MD Assistant Professor of Pediatrics, Division of Infectious Diseases, Medical College of Wisconsin, Consulting Staff, Children's Specialty Group, Children's Hospital of Wisconsin

Swati Kumar, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Michelle R Salvaggio, MD, FACP Assistant Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine; Medical Director of Infectious Diseases Institute, Director, Clinical Trials Unit, Director, Ryan White Programs, Department of Medicine, University of Oklahoma Health Sciences Center; Attending Physician, Infectious Diseases Consultation Service, Infectious Diseases Institute, OU Medical Center

Michelle R Salvaggio, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Received honoraria from Merck for speaking and teaching.

• Print this section
• Print the entire contents of
• Print the entire contents of article