Infectiology & Dermatology & Family Medicine
Genital herpes (HSV-2)
Genital herpes is a sexually transmitted infection (STI) caused mainly by herpes simplex virus type 2 (HSV-2), and increasingly by HSV-1 (oral-genital transmission). Herpes simplex viruses are enveloped double-stranded DNA viruses, members of the Herpesviridae family, which establish a lifelong latent infection in the sensory nerve ganglia - sacral (S2-S4) for genital HSV-2 - with periodic reactivations. Infection is extremely widespread: the global prevalence of HSV-2 is estimated at 11-13 % of the adult population (WHO 2016), but the vast majority of infected people are unaware of their status, with infection being asymptomatic or paucisymptomatic in 60-80 % of cases. In Canada, the prevalence of HSV-2 is estimated at 15-20 % in adults. Asymptomatic viral shedding - present 5-10 % of days in an untreated HSV-2 carrier - is responsible for the majority of transmissions, since partners unknowingly transmit the infection in 70 % of cases. Diagnosis is based on viral PCR of active lesions, which is much more sensitive than culture. Antiviral treatment with aciclovir or valaciclovir reduces the duration of outbreaks, the frequency of recurrences and the risk of transmission - without eradicating viral latency.
Virology, transmission, latency and clinical presentation
- Virology of HSV-2 - latency and reactivation : viral structure: 152 kb linear double-stranded DNA + icosahedral capsid + integument + lipid envelope → 4 major envelope glycoproteins: gB + gC + gD + gH/gL → gD : cell entry receptor (nectin + HVEM) → targets of neutralizing antibodies → VHS-1 vs VHS-2 differences: genomic homology 50 % → VHS-1: preferential oro-facial tropism + site of latency: trigeminal ganglion → VHS-2: preferential genital tropism + site of latency: sacral node (S2-S4) → but genital HSV-1 increasingly frequent (20-50 % of genital primary infections in high-income countries - Looker 2015 - PLOS ONE) → genital HSV-1: fewer symptomatic recurrences than HSV-2 genital (0.1-1 recurrences/year vs. 4-6/year); viral cycle and latency: primary infection → replication in epithelial cells → virions → infection of sensory nerve endings → retrograde axonal transport → sacral ganglion → latency: episomal circular viral DNA (no integration) + expression of LATs (Latency-Associated Transcripts) → maintains latency + protects neurons from apoptosis → reactivation: triggering stimuli → anterograde axonal transport → epithelium → replication → asymptomatic lesions or excretion → reactivation mechanisms: physical stress (UV + fever + local trauma + sexual intercourse) + emotional stress + immunosuppression + menstrual cycles (HSV-2 ++) + local immunological cycles; asymptomatic viral shedding (EVA): presents 5-10 % of days in untreated HSV-2 carrier (Corey 2004 - NEJM) → reduced to 1-3 % of days under suppressive therapy (valaciclovir 500 mg/d) → responsible for 70 % of transmissions (Langenberg 1999 - Annals of Internal Medicine) → not correlated with symptoms → nor with normal examination → condoms reduce AVE by 50 % but do not eliminate it (areas not covered)
- Transmission and epidemiology : transmission routes: direct skin-to-skin or mucous membrane-to-mucous membrane contact during sexual intercourse (vaginal + anal + oro-genital) → HSV-2: 10× more efficient transmission from man to woman than from woman to man (more vulnerable vaginal and cervical epithelium) → annual transmission rate in serodiscordant couples without treatment: 10-12 % (HIV-negative woman + HSV-2+ partner) vs. 4-5 % (HIV-negative man + HSV-2+ partner) → Valacyclovir Transmission Study trial (Corey 2004 - NEJM): valaciclovir 500 mg/d in HIV-positive partner → reduced transmission by 48 % + factors increasing transmission: absence of suppressive therapy + frequent recurrences + active lesions + intercourse without condom + HIV co-infection (HSV-2 ++ increases risk of HIV transmission ×3-4 → genital ulcers = gateway + local inflammation + increased HIV replication) + co-existing STIs (gonorrhea + chlamydia + syphilis); prevalence and risk groups: global HSV-2: 491 million people aged 15-49 (WHO 2016) + genital HSV-1: increasing prevalence in young adults → oral-genital transmission + high-risk groups: HARSAH + HIV co-infection (HSV-2 prevalence 70-90 % in PLHIV) + women (more anatomically vulnerable) + people with multiple partners + adolescents and young adults (primary infections); serological screening: type-specific serological tests (anti-gG2 IgG): Western blot or type-specific ELISA → enable HSV-1 vs. HSV-2 to be distinguished → limited clinical utility in asymptomatic universal screening (USPSTF 2023: against asymptomatic universal serological screening - potential negative psychological benefit + stigmatization) → useful in: serodiscordant couples + symptomatic partner with negative work-up + pregnancy + immunodepression → HSV-2 positive serology without active lesion → advice on VAS + suppressive treatment to be discussed
- Clinical presentation - primary infection, recurrences and atypical forms : genital herpetic primary infection (first true episode): incubation: 2-12 days post-exposure → clinical picture in symptomatic patients (20-40 % of primary infections): prodromes: pain + burning + pruritus + genital paresthesias 12-24h before lesions → multiple erythematous vesicular lesions → erosions + painful ulcers after rupture of vesicles → localization in women: vulva + vagina + cervix + perineum → in men: glans + prepuce + body of penis + scrotum → in both sexes: buttocks + inner thighs (extension by auto-inoculation) + urethra : dysuria + urethral discharge → aseptic meningitis: 10-30 % of women with primary HSV-2 infection → headache + nuchal stiffness + photophobia + fever → CSF: lymphocytic pleocytosis + normal glycorachy + HSV PCR positive → benign prognosis + urinary retention: 10-15 % of women → sacral autonomic neuropathy → temporary bladder catheterization + painful bilateral inguinal adenopathies + general symptoms: fever + myalgias + headache (especially HSV-2 primary infection) → total duration of untreated primary infection: 3-5 weeks; genital herpetic recurrences (HSV-2): frequency without treatment: 4-6 episodes/year on average for HSV-2 (1st year) → gradually decreases with years → genital HSV-1: 0.1-1 episode/year → prodromes preceding recurrence (50-70 % of patients): tingling + burning + radiating pain in buttock or thigh → 1-48h warning → allows early episodic treatment → recurrence lesions: less extensive + less painful + shorter duration (7-10 days untreated vs. 3 weeks primo) → often unilateral → healing without scarring → atypical forms (60-80 % of recurrences): discrete genital fissures + localized redness + edema + simple genital irritation → often unrecognized → diagnosis delayed or missed → extra-genital forms: gluteal herpes + sacral herpes (L3-S1): gluteal or sacral erosions → often diagnosed as folliculitis + furuncle + dermatitis → finger herpes (herpetic panaris) → ocular herpes (herpetic keratitis) by auto-inoculation; genital herpes and immunodepression: HIV + transplant patients + chemotherapy → more frequent + severe + prolonged recurrences + extensive chronic ulcers → disseminated form possible (encephalitis + pneumonia + hepatitis) → resistance to aciclovir (TK or DNA polymerase mutations) → foscarnet or cidofovir
Diagnosis, treatment and special situations
| Clinical situation | Diagnosis and treatment | Prevention and follow-up |
|---|---|---|
| Primary infection and recurrences - diagnosis and episodic treatment HSV PCR - valaciclovir - aciclovir - early treatment |
Virological diagnosis - methods and interpretation: HSV PCR on lesion swab: reference method → sensitivity 96-98 % + specificity 100 % → type-specific (HSV-1 vs HSV-2) → helps guide prognosis in terms of recurrence + optimal sampling: swab the bottom of a freshly opened blister (before scarring) → sensitivity falls rapidly with lesion scarring → transport in viral medium → results in 24-48h → viral culture: sensitivity 50-75 % only (vs. PCR) → still available in some centers → less widely used → type-specific serology (anti-gG2 IgG): does not confirm an active lesion → useful for screening and characterization of partner profile → positive result = latent infection (past or present) → IgM: not type-specific + also present in recurrence → not clinically useful → differential diagnosis of genital ulcers: syphilis (painless chancre + serologies T. pallidum serologies) + chancre mou (Haemophilus ducreyi → painful + suppurating ulcer + fluctuating adenopathy) + lymphogranuloma venereum (Chlamydia L1-L3 → papule then inguinal adenopathy) + Candida vaginitis (fissures + pruritus + leucorrhoea) + drug-induced erythema fixe + genital Crohn's disease + Behçet's genital aphthosis → full STI workup if genital ulcer: syphilis (VDRL + TPHA) + gonorrhea + chlamydia + HIV; treatment of primary genital herpetic infection: initiate on clinical suspicion - do not wait for PCR results: valaciclovir 1,000 mg PO × 2/d × 7-10 days → aciclovir profarmule → oral bioavailability 3-5× higher → 1st-line treatment in practice in Canada + aciclovir 400 mg PO × 3/d × 7-10 days : alternative - more daily doses → famciclovir 250 mg PO × 3/d × 7-10 days: equivalent alternative → initiation of treatment: within 72 h of onset of symptoms → maximum benefit if initiated early → late initiation reduces but does not eliminate benefit → severe pain : topical lidocaine 2 % gel → lukewarm sitz baths → systematic analgesia (paracetamol + ibuprofen) → urinary retention: bladder catheterization if drainage impossible → prevent bacterial superinfection of lesions: local care + avoid occlusive grease + in case of associated aseptic meningitis: aciclovir IV 5-10 mg/kg q8h if severe form → then oral relay | Treatment of genital herpes recurrence - two strategies: 1. Episodic treatment: initiate at prodrome or within 24 hours of lesion onset → valaciclovir 500 mg × 2/d × 3 days (Tyring 1998 - Archives of Internal Medicine) + or valaciclovir 1,000 mg × 1/d × 5 days + or aciclovir 400 mg × 3/d × 5 days + or famciclovir 1,000 mg × 2/d × 1 day (single dose) (Aoki 2006 - Journal of Infectious Diseases) → short regimens (1-3 days) are as effective as long regimens if initiated early → episodic treatment appropriate if : infrequent recurrences (9 recurrences/year → aciclovir 400 mg PO × 2/d : alternative + famciclovir 250 mg × 2/d: alternative → VALOR trial (Reitano 1998 - Journal of Infectious Diseases): valaciclovir 500 mg/d → reduction in recurrences by 78 % + Valacyclovir Transmission Study trial (Corey 2004 - NEJM): valaciclovir 500 mg/d in HSV-2+ partner → reduction in virological transmission by 48 % + reduction in clinical primary infection of HIV-negative partner by 75 % → suppressive therapy is safe in the long term: over 6 years of data without significant toxicity + annual reassessment: after 1 year of suppression → discuss discontinuation if less frequent recurrences |
| Genital herpes and pregnancy - prevention of neonatal herpes Neonatal herpes - aciclovir suppression - caesarean section - serological screening |
Neonatal herpes - epidemiology and pathophysiology: incidence: 1/3,000-1/20,000 live births according to studies + untreated mortality: 60 % + with disseminated lesions + neurological sequelae: 50 % of survivors → transmission mechanisms: perinatal (85-90 % of cases): passage through genital tract during active viral shedding (lesions or EVA) → or postnatal (5-8 %): contact with HSV-1 oro-labial lesion (herpes labialis parent + caregiver) → or trans-placental (≤5 %); risk according to maternal status: maximum transmission risk: genital HSV primary infection in 3rd trimester (particularly 4-6h with active lesions: discuss with team + weigh risk of prolonged exposure vs. surgical risk; primary infection in late pregnancy (<6 weeks preterm): IV aciclovir if severe → then oral aciclovir until delivery → caesarean section strongly recommended → exposed newborn: preventive treatment with IV aciclovir 20 mg/kg q8h × 10 days in newborn if exposed to maternal primary infection | Neonatal herpes - diagnosis and treatment in newborns: clinical forms: localized (skin + eyes + mouth - SEM): most benign → skin vesicles + kerato-conjunctivitis + stomatitis → low mortality if treated + CNS involvement: herpetic encephalitis → convulsions + lethargy + bulging fontanel + CSF : HSV PCR positive → mortality 10-15 % even if treated + frequent neurological sequelae + disseminated form: liver + lung + adrenal + DIC involvement → mortality 30 % even if treated → treatment: aciclovir IV 20 mg/kg q8h: SEM: 14 days + CNS and disseminated: 21 days → neurological and ophthalmological follow-up + post-treatment oral aciclovir suppression: aciclovir 300 mg/m² q8h × 6 months → improves neurocognitive development at 1 year (Kimberlin 2011 - NEJM); serological screening of couples in pregnancy: if HSV-2 seronegative woman and HIV-positive partner → advice: sexual abstinence at the end of pregnancy (3rd trimester) + condoms + avoid oro-genital intercourse if HSV-1 labial partner (risk of HSV-1 genital primary infection) + partner's suppressive treatment to be discussed → seronegative woman both: risk of primary infection not zero → vigilance if suggestive symptoms at the end of pregnancy → consult rapidly |
| Genital herpes and HIV - antiviral resistance - severe forms Immunodepression - chronic ulcers - foscarnet - aciclovir IV |
Genital herpes in people living with HIV (PLHIV): HSV-2 prevalence in PLHIV: 70-90 % → more frequent + severe recurrences + chronic non-healing ulcers → EVA 20-40 % days (vs 5-10 % in immunocompetent HSV-2+) → HSV-2 increases HIV replication in local CD4+ T cells → and HIV viral load in genital secretions → HSV-2 / HIV epidemiological synergism; systematic suppressive therapy recommended in HSV-2+ PLHIV: valaciclovir 500 mg × 2/d → double dose vs immunocompetent (Conant 2002 - Sexually Transmitted Diseases) → or aciclovir 400 mg × 3/d → reduction in recurrences + VAS + improvement in quality of life → suppressive treatment of HSV-2 suppressive therapy in PLHIV does not significantly reduce HIV transmission (HPTN 039 + Partners in Prevention HSV/HIV trials - Celum 2008 - NEJM + 2010 - NEJM) → but individual benefit (quality of life + ulcer reduction) well demonstrated ; antiviral resistance (aciclovir + valaciclovir + famciclovir): mechanism : mutations in viral thymidine kinase (TK) → aciclovir + valaciclovir + famciclovir cross-resistance (all require initial phosphorylation by viral TK) → prevalence: 0.1-0.7 % in immunocompetent + 4-7 % in immunocompromised + risk factors: profound immunodepression (CD4 <100) + repeated antiviral treatments → presentation: chronic genital ulcers persisting under treatment → non-healing → increasing size → resistance diagnosis: genotypic (TK sequencing + DNA polymerase) or phenotypic resistance test → treatment of resistant strains: foscarnet (phosphonoformic acid): directly inhibits viral polymerase without requiring phosphorylation by TK → 40-60 mg/kg IV q8h × 14-21 days → nephrotoxic (IV hydration mandatory) + hypocalcemia + hypomagnesemia → cidofovir: 5 mg/kg IV weekly × 2 then fortnightly → nephrotoxic (probenecid + hydration) → topical imiquimod 5 %: adjuvant option in localized resistant ulcers + brincidofovir (CMX001): in development for resistant HSV → special access programs Health Canada | Psychological impact of genital herpes and support: stigmatization and psychological distress: 50-80 % of newly diagnosed individuals report significant psychological distress (anxiety + depression + shame + fear of rejection + altered sexuality - Mindel 1996 - Sexually Transmitted Diseases) → distress is often disproportionate to the medical severity of the infection → diagnosis is often experienced as a rupture in personal and relational identity; key elements of therapeutic education and counseling: 1. Genital herpes is a managed infection, not a serious disease in the vast majority of cases + 2. The vast majority of transmissions come from people who don't know they're infected + 3. Treatment greatly reduces recurrence and the risk of transmission + 4. A fulfilling sex life is possible with genital herpes → partner disclosure management: coaching on how to announce the diagnosis + available resources: Canadian Infectious Diseases Society + ITSS Québec (Direction nationale de santé publique) + CLSC STI counseling program + support groups (HSO Canada - Herpes Support Online) + partner notification: recommended → anonymity of notified partner can be protected via public health services → in Quebec: mandatory reporting: genital herpes is NOT a reportable STI in Quebec (unlike syphilis + gonorrhea + chlamydia + HIV) → but partners should be informed to get tested and treated if symptomatic |
| Prevention, vaccines and new treatments Condoms - suppressive therapy - vaccines in development - pritelivir |
Prevention of transmission - recommended measures: male latex condoms: reduction in transmission of 30-50 % (Wald 2001 - Annals of Internal Medicine) → incomplete efficacy because areas not covered (perineum + buttocks + thigh roots) + suppressive treatment in partner HSV-2+ : valaciclovir 500 mg/d → 48 % reduction in transmission (Corey 2004 - NEJM) → combination condom + suppressive treatment → estimated 75 % reduction in transmission → abstinence during active outbreaks (visible lesions) → inform about VAS: absence of lesion does not mean absence of viral shedding → open communication with sexual partners → partner screening: type-specific serology (anti-gG2 IgG) → if partner seronegative → reinforced prevention measures + suppressive treatment of infected partner → in case of pregnancy → specific obstetrical protocol; HSV-2 vaccines - research status in 2024: no vaccine approved to date despite decades of research → main approaches in development or trials: gD2 subunit vaccine (GSK + Herpevac): HERPEVAC trial (Stanberry 2002 - NEJM) → protection in HSV-1/VHS-2-negative women - 73 % against clinical infection → but no protection in HSV-1+ men and women → gD2 protein not very immunogenic in certain populations → mRNA vaccine (Moderna mRNA-1608): in Phase I/II trial (2023-2024) → targeting gD + gC + gE → promising immunogenicity → results expected 2025-2026 → HSV529 vaccine (NIH/Sanofi): attenuated HSV-2 virus (UL5/UL29 deletion) → phase I completed → phase II underway → prophylactic + therapeutic vaccine (reduced relapses); pritelivir (helicase-primasae inhibitor): mechanism of action different from aciclovir → inhibits viral helicase-primase complex (UL5/UL8/UL52) → active without phosphorylation by TK → effective on aciclovir-resistant strains → phase II trial (Wald 2014 - NEJM): VAS reduction of 73 % vs 54 % for valaciclovir + recurrence reduction of 85 % → phase III trial underway (PRIMOHERP) → compassionate access possible (Health Canada) for severe resistant forms |
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70 % of HSV-2 transmissions occur without visible lesions : asymptomatic viral shedding (AVS) is present 5-10 % days in an untreated HSV-2 carrier. Suppressive therapy with valaciclovir 500 mg/d reduces AVE to 1-3 % days and decreases the risk of transmission by 48 % (Corey 2004 - NEJM). The combination of suppressive therapy + condoms reduces the risk of transmission by 75 %. Absence of symptoms does not mean absence of contagiousness.
Situations requiring urgent medical assessment
Newborn presenting skin vesicles + fever + lethargy + convulsions in the first 2-4 weeks of life, born to a mother with a history of genital herpes or primary infection at the end of pregnancy. → neonatal herpes → pediatric emergency → aciclovir IV 20 mg/kg q8h to be initiated immediately → HSV PCR on CSF + blood + skin surface → hospitalization in neonatal unit.
Genital herpetic primary infection + complete urinary retention + neck stiffness + intense headache + photophobia → herpetic aseptic meningitis + sacral autonomic neuropathy → medical emergencies → bladder catheterization if retention → aciclovir IV if meningitis confirmed by lumbar puncture (HSV PCR positive in CSF) → benign evolution but hospitalization recommended.
Chronic non-healing extensive genital ulcers on aciclovir or valaciclovir in an immunocompromised patient (HIV with low CD4 + transplant + chemotherapy) → probable aciclovir resistance → urgent referral to infectiology → VHS genotypic resistance testing → foscarnet IV 40-60 mg/kg q8h in hospital with sustained hydration → daily renal monitoring.
Pregnant woman with active genital herpes lesions in labor or rupture of membranes → genital herpes active at time of delivery → cesarean section recommended (SOGC 2021) → intraoperative IV aciclovir + neonatal coverage → obstetrics + pediatrics + infectiology consultation → do not wait for PCR results to decide on delivery route.
Consult at Clinique Omicron
Clinique Omicron physicians provide diagnosis, treatment and follow-up of genital herpes - primary infection, frequent recurrences, prescription of suppressive therapy, counseling and partner screening. Telemedicine consultations are available to facilitate fast, discreet access to care at several points of service in Quebec. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for informational purposes only and does not replace the advice of a physician or infectious disease specialist. Any genital lesion should be medically evaluated to exclude other STIs, including syphilis.
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