This is the guideline for genital herpes simplex virus (HSV) management for the IUSTI/WHO Europe, 2010. They describe the epidemiology, diagnosis, clinical features, treatment and prevention of genital HSV infection. They include details on the management of HSV in pregnancy, those who are immunocompromised and the clinical investigation and management of suspected HSV-resistant disease.
KoutskyLA, StevensCE, HolmesKK, Underdiagnosis of genital herpes by current clinical and viral-isolation procedures. N Engl J Med1992;326:1533–9
5.
WaldA, HuangML, CarrellD, SelkeS, CoreyL. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis2003;188:1345–51
6.
RamaswamyM, McDonaldC, SmithM, Diagnosis of genital herpes by real-time PCR in routine clinical practice. Sex Transm Infect2004;80:406–10
7.
Van DoornumGJ, GuldemeesterJ, OsterhausAD, NiestersHG. Diagnosing herpesvirus infections by real-time amplification and rapid culture. J Clin Microbiol2003;41:576–80
8.
GerettiAM. Genital herpes. Sex Transm Infect2006;82(Suppl 4):iv31–4
9.
VeranoL, MichalskiFJ. Herpes simplex virus antigen direct detection in standard virus transport medium by Du Pont Herpchek enzyme-linked immunosorbent assay. J Clin Microbiol1990;28:2555–8
10.
SlomkaMJ, EmeryL, MundayPE, MoulsdaleM, BrownDW. A comparison of PCR with virus isolation and direct antigen detection for diagnosis and typing of genital herpes. J Med Virol1998;55:177–83
11.
ConeRW, SwensonPD, HobsonAC, RemingtonM, CoreyL. Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture. J Clin Microbiol1993;31:1774–6
12.
MundayPE, VuddamalayJ, SlomkaMJ, Role of type specific herpes simplex virus serology in the diagnosis and management of genital herpes. Sex Transm Infect1998;74:175–8
13.
AshleyRL, WaldA. Genital herpes: review of the epidemic and potential use of type-specific serology. Clin Microbiol Rev1999;12:1–8
14.
MalkinJE. Herpes simplex virus. Who should be tested. Herpes2002;9:31
15.
CopasAJ, CowanFM, CunninghamAL, MindelA. An evidence based approach to testing for antibody to herpes simplex virus type 2. Sex Transm Infect2002;78:430–4
16.
CoreyL, WaldA, PatelR, Once daily valaciclovir to reduce the risk of transmission of genital herpes. N Engl J Med2004;350:11–20
17.
RamaswamyM, McDonaldC, SabinC, Tenant-FlowersM, SmithM, GerettiAM. The epidemiology of genital infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in genitourinary medicine attendees in inner London. Sex Transm Infect2005;81:306–8
18.
BrownZA, SelkeS, ZehJ, The acquisition of herpes simplex virus during pregnancy. N Engl J Med1997;337:509–15
19.
RouseDJ, StringerJSA. An appraisal of screening for maternal type-specific herpes simplex antibodies to prevent neonatal herpes. Am J Obstet Gynecol2000;183:400–6
20.
TitaAT, GrobmanWA, RouseDJ. Antenatal herpes serologic screening: an appraisal of the evidence. Obstet Gynecol2006;108:1247–53
21.
WaldA, LinkK. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis2002;185:45–52
22.
StrickLB, WaldA, CelumC. Management of herpes simplex virus type 2 infection in HIV type 1-infected persons. Clin Infect Dis2006;43:347–56
23.
RamaswamyM, GerettiAM. Interactions and management issues in HSV and HIV coinfection. Expert Rev Infect Ther2007;5:231–43
24.
DrakeAL, John-StewartGC, WaldA, Herpes simplex virus type 2 and risk of intrapartum human immunodeficiency virus transmission. Obstet Gynecol2007;109:403–9
25.
BollenLJ, WhiteheadSJ, MockPA, Maternal herpes simplex virus type 2 coinfection increases the risk of perinatal HIV transmission: possibility to further decrease transmission?AIDS2008;22:1169–76
26.
ChenKT, TuomalaRE, ChuC, No association between antepartum serologic and genital tract evidence of herpes simplex virus-2 coinfection and perinatal HIV-1 transmission. Am J Obstet Gynecol2008;198:399.e1–5
27.
AshleyRL. Performance and use of HSV type-specific serology test kits. Herpes2002;9:38–45
28.
AshleyRL, BenedettiJ, CoreyL. Humoral immune response to HSV-1 and HSV-2 viral proteins in patients with primary genital herpes. J Med Virol1985;17:153–66
29.
AshleyRL. Type-specific antibodies to HSV-1 and 2: review of methodology. Herpes1998;5:33–8
30.
SmithJS, BaileyRC, WestreichDJ, Herpes simplex virus type 2 antibody detection performance in Kisumu, Kenya, using the Herpeselect ELISA, Kalon ELISA, Western blot and inhibition testing. Sex Transm Infect2009;85:92–6
31.
GopalR, GibbsT, SlomkaMJ, A monoclonal blocking EIA for herpes simplex virus type 2 antibody: validation for seroepidemiological studies in Africa. J Virol Methods2000;87:71–80
32.
MorrowRA, FriedrichD, KrantzE. Performance of the Focus and Kalon enzyme-linked immunosorbent assays for antibodies to herpes simplex virus type 2 glycoprotein G in culture-documented cases of genital herpes. J Clin Microbiol2003;41:5212–4
33.
VanE, BuveA, Performance of commercially available enzyme immunoassays for detection of antibodies against herpes simplex virus type 2 in African populations. J Clin Microbiol2004;42:2961–5
34.
GoldenMR, Ashley-MorrowR, SwensonP, HogrefeWR, HandsfieldHH, WaldA. Herpes simplex virus type 2 (HSV-2) Western blot confirmatory testing among men testing positive for HSV-2 using the focus enzyme-linked immunosorbent assay in a sexually transmitted disease clinic. Sex Transm Dis2005;32:771–7
35.
MorrowRA, FriedrichD, MeierA, CoreyL. Use of ‘biokit HSV-2 Rapid Assay’ to improve the positive predictive value of Focus HerpeSelect HSV-2 ELISA. BMC Infect Dis2005;5:84
36.
AshleyR, KrantzE, FriedrichD, WaldA. Clinical correlates of index values in the focus HerpeSelect ELISA for antibodies to herpes simplex virus type 2 (HSV-2). J Clin Virol2006;36:141–5
37.
NascimentoMC, FerreiraS, SabinoE, Performance of the HerpeSelect (Focus) and Kalon enzyme-linked immunosorbent assays for detection of antibodies against herpes simplex virus type 2 by use of monoclonal antibody-blocking enzyme immunoassay and clinicovirological reference standards in Brazil. J Clin Microbiol2007;45:2309–11
38.
LeGoffJ, MayaudP, GresenguetG, Performance of HerpeSelect and Kalon assays in detection of antibodies to herpes simplex virus type 2. J Clin Microbiol2008;46:1914–8
39.
GamielJL, TobianAA, LaeyendeckerOB, Improved performance of enzyme-linked immunosorbent assays and the effect of human immunodeficiency virus coinfection on the serologic detection of herpes simplex virus type 2 in Rakai, Uganda. Clin Vaccine Immunol2008;15:888–90
40.
SmithJS, BaileyRC, WestreichDJ, Herpes simplex virus type 2 antibody detection performance in Kisumu, Kenya, using the Herpeselect ELISA, Kalon ELISA, Western blot and inhibition testing. Sex Transm Infect2009;85:92–6
41.
LadermanEI, WhitworthE, DumaualE, Rapid, sensitive, and specific lateral-flow immunochromatographic point-of-care device for detection of herpes simplex virus type 2-specific immunoglobulin G antibodies in serum and whole blood. Clin Vaccine Immunol2008;15:159–63
42.
MorrowR, FriedrichD. 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 Infect2006;12:463–9
43.
CoreyL, BenedettiJ, CritchlowC, Treatment of primary first-episode genital herpes simplex virus infections with aciclovir: results of topical, intravenous and oral therapy. J Antimicrob Chemother1983;12(Suppl B):79–88
44.
FifeKH, BarbarashRA, RudolphT, DeGregorioB, RothR. Valaciclovir versus aciclovir in the treatment of first-episode genital herpes infection. Results of an international multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Virus Study Group. Sex Transm Dis1997;24:481–6
45.
ReyesM, ShaikNS, GraberJM, Acyclovir-resistant genital herpes among persons attending sexually transmitted disease and human immunodeficiency virus clinics. Arch Intern Med2003;163:76–80
46.
WeightmanW, TurnerT. Allergic contact dermatitis from lignocaine: report of 29 cases and review of the literature. Contact Dermatitis1998;39:265
47.
CarneyO, RossE, BunkerC, IkkosG, MindelA. A prospective study of the psychological impact on patients with a first episode of genital herpes. Genitourinary Med1994;70:40–5
48.
PatelR, TyringS, PriceMJ, Impact of suppressive antiviral therapy on the health related quality of life of patients with recurrent genital herpes infection. Sex Transm Infect1999;75:398–402
49.
GreenJ, KocsisA. Psychological factors in recurrent genital herpes. Genitourinary Med1997;73:253–9
50.
NilsenAE, AasenT, HalsosAM, Efficacy of oral aciclovir in the treatment of initial and recurrent genital herpes. Lancet1982;ii:571–3
51.
SpruanceSL, TyringTK, DeGregorioB, MillerC, BeutnerK and the Valaciclovir study group. A large-scale, placebo controlled, dose ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Arch Intern Med1996;156:1729–35
52.
SacksSL, AokiFY, Diaz-MitomaF, SellorsJ, ShafranSD, for the Canadian Famciclovir Study. Patient-initiated, twice daily, oral famciclovir for early recurrent genjnital herpes: a randomized, double-blind multicenter trial. JAMA1996;276:44–9
53.
SpruanceSL, OverallJC, KernER, The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. N Engl J Med1977:69–75
54.
WaldA, CarrellD, RemingtonM, Two-day regiment of acyclovir for treatment of recurrent genital herpes simplex virus type 2 infection. Clin Infect Dis2002;34:944–8
55.
BodsworthN, BlochM, McNultyA. 2-day versus 5-day famciclovir as treatment of recurrences of genital herpes: results of the FaST study. Sexual Health2008;5:219–25
56.
WaldA, CarrellD, RemingtonM, KexelE, ZehJ, CoreyL. Two-day regimen of aciclovir for treatment of recurrent genital herpes simplex virus type 2 infection. Clin Infect Dis2002;34:944–8
AbudaluM, TyringS, KoltunW, BodsworthN, HamedK. Single-day patient-initiated famciclovir therapy versus 3-day valaciclovir regimen for recurrent genital herpes: a randomized, double-blind, comparative trial. Clin Infect Dis2008;47:651–8
59.
LeonePA, TrottierS, MillerJM. Valaciclovir for episodic treatment of genital herpes: a shorter 3-day treatment course compared with 5-day treatment. Clin Infect Dis2002;34:958–62
60.
StrandA, PatelR, WulfHC, CoatesKM and The International Valaciclovir Study Group. Aborted genital herpes simplex virus lesions: findings from a randomised controlled trial with valaciclovir. Sex Transm Infect2002;78:435–9
61.
MertzGJ, JonesCC, MillsJ, Long-term aciclovir suppression of frequently recurring genital herpes simplex virus infection. A multicenter double-blind trial. JAMA1988;260:201–6
62.
MindelA, FahertyA, CarneyO, PatouG, FrerisM, WilliamsP. Dosage and safety of long-term suppressive aciclovir therapy for recurrent genital herpes. Lancet1988;331:926–8
63.
Lebrun-VignesB, A meta-analysis to assess the efficacy of oral antiviral treatment to prevent genital herpes outbreaks. J Am Acad Dermatol2007;57:238–46
64.
GerettiAM. Genital herpes. Sex Transm Infect2006;82Suppl 4:iv31–4
65.
CoreyL, WaldA, PatelR, Once-daily valaciclovir to reduce the risk of transmission of genital herpes. N Engl J Med2004;350:11–20
66.
RomanowskiB, AokiFY, MartelAY, LavenderEA, ParsonsJE, SaltzmanRL. Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex infection in HIV infected individuals. AIDS2000;14:1211–17
67.
ConantMA, SchackerTW, MurphyRL, GoldJ, CrutchfieldLT, CrooksRJ. International Valaciclovir HSV Study Group. Int J STD AIDS2002;13:12–21
68.
SchackerT, HuHL, KoelleDM, Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons. A double-blind, placebo-controlled trial. Ann Intern Med1998;128:21–8
69.
YouleMS, GazzardBG, JohnsonMA, Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease: a double-blind, placebocontrolled study. AIDS1994;8:641–9
70.
CooperDA, PehrsonPO, PedersenC, The efficacy and safety of zidovudine alone or as cotherapy with aciclovir for the treatment of patients with AIDS and AIDS-related complex: a double-blind, randomized trial. AIDS1993;7:197–207
71.
BellWB, ChulayJD, FeinbergJE. Manifestations resembling thrombomicroangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalovirus prophylaxis trial (ACTG 204). Medicine (Baltimore)1997;76:369–80
72.
DelanyS, MlabaN, ClaytonT, Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected women: a randomized placebo-controlled trial in South Africa. AIDS2009;23:461–9
73.
LingappaJR, BaetenJM, WaldA. Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial. Lancet2010;375:824–33
74.
SheffieldJS, HollierLM, HillJB, StuartGS, WendelGD. Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review. Obstet Gynecol2003;102:1396–403
75.
WattsDH, BrownZA, MoneyD, A doubleblind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of Herpes simplex virus shedding and cesarean delivery. Am J Obstet Gynecol2003;188:836–43
76.
ScottLL, HollierLM, McIntireD, SanchezPJ, JacksonGL, WendelGDJr. Acyclovir suppression to prevent recurrent genital herpes at delivery. Infect Dis Obstet Gynecol2002;10:71–7
77.
BrocklehurstP, KinghornG, CarneyO, A randomised placebo-controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection. Br J Obstet Gynaecol1998;105:275–80
78.
ScottLL, SanchezPJ, JacksonGL, ZerayF, WendelGDJr. Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes. Obstet Gynecol1996;87:69–73
79.
BraigS, LutonD, SibonyO, Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding. Eur J Obstet Gynecol Reprod Biol2001;96:55–8
80.
HollierLM, WendelGD. Third trimester antiviral prophylaxis for preventing maternal genital herpes simplx virus (HSV) recurrences and neonatal infection. Cochrane Database Syst Rev 2008;1:CD004946
81.
GardellaC, BrownZA, WaldA, Poor correlation between genital lesions and detection of herpes simplex virus in women in labor. Obstet Gynecol2005;106:268–74
82.
ChenKT, SeguM, LumeyLH, Genital herpes simplex virus infection and perinatal transmission of human immunodeficiency virus. Obstet Gynecol2005;106:1341–8
83.
DrakeAL, John-StewartGC, WaldA, Herpes simplex virus type 2 and the risk of intrapartum human immunodeficiency virus transmission. Obstet Gynecol2007;10:403–9
84.
ChenKT, TuomalaRE, ChuC, No association between antepartum serologic and genital tract evidence of herpes simplex virus-2 coinfection and perinatal HIV-1 transmission. Am J Obstet Gynecol2008;198:399
85.
ChenKT, TuomalaRE, ChuC, No association between antepartum serologic and genital tract evidence of herpes simplex virus-2 coinfection and perinatal HIV-1 transmission. Am J Obstet Gynecol2008;198: p399.e1–5
86.
PoeranJ, WildschutH, GaytantM, GalamaJ, SteegersE, van der MeijdenW. The incidence of neonatal herpes in The Netherlands. J Clin Virol2008;42:321–5
87.
Acyclovir and Valacyclovir in Pregnancy Registry final report. April 1999. See http://pregnancyregistry.gsk.com/acyclovir.html (last accessed 1 December 2010)
88.
AndrewsWW, KimberlinDF, WhitleyR, CliverS, RamsayPS, DeeterR. Valacyclovir therapy to reduce recurrent genital herpes in pregnant women. Am J Obstet Gynecol2006;194:774–8
89.
SheffieldJS, HillJB, HollierLM, Valacylovir prophylaxis to prevent recurrent herpes at delivery: a randomised clinical trial. Obstet Gynecol2006;108:141–7