Note: there is a separate article covering genital herpes simplex in pregnancy.

Aetiology

Genital herpes simplex is caused by infection with the herpes simplex virus (HSV).

• Herpes simplex virus (HSV) is sub-divided into HSV type 1 (HSV-1) and HSV type 2 (HSV-2).
• Type 1 usually affects the oral region and causes cold sores (herpes labialis).
• Type 2 is associated with genital infection (penis, anus, vagina).
• However, both can infect the mouth and/or genitals due to oral sex or autoinoculation. In some developed countries, the prevalence of genital HSV-1 is increasing.

Epidemiology¹

Serological prevalence of HSV in adults is:

• HSV-1: 70% in developed countries and 100% in developing countries.
• HSV-2: varies, e.g. 7-40% in pregnant women and 60-95% in sex workers and HIV-positive persons in different parts of the world.

However, the majority of those with HSV-2 antibodies are unaware of their infection.

In the UK in 2004, there were 19,180 cases of a first episode of genital herpes.²

Transmission

Genital herpes is acquired from contact with:²

• Infectious secretions on oral, genital, or anal mucosal surfaces.
• Contact with lesions from other anatomical sites, e.g. eyes, skin or herpetic whitlow.

Therefore the infection is transmitted through vaginal, anal and oral sex, close genital contact and contact with other sites such as the eyes and fingers. Note:

• The individual transmitting the infection may be asymptomatic but still shedding the virus. This is how most transmission of genital HSV occurs.
• Transmission from asymptomatic individuals in monogamous relationships can occur after several years and can cause considerable distress.

Risk factors for acquiring infection

• Sexual promiscuity.
• Unprotected sexual encounters.
• Female sex.
• HIV - there is evidence that genital HSV increases the risk of acquiring HIV infection and that people with both HSV and HIV are more likely to transmit HIV infection.²

Presentation^3,4

Usually presents as multiple painful ulcers.

Primary infection

• This is the first time the virus is acquired.
• May be asymptomatic (common). If this is the case, the first symptomatic episode is called a non-primary first episode. Evidence of previous infection is shown by the presence of type-specific antibodies at the time of presentation.
• Symptoms include:
  • Febrile flu-like prodrome (5-7 days).
  • Tingling neuropathic pain in genital area/buttocks/legs.
  • Extensive bilateral crops of blisters/ulcers in the genital area (including the vagina and cervix in women).
  • Tender lymph nodes (inguinal).
  • Local oedema.
  • Dysuria.
  • Vaginal or urethral discharge.
• Can last up to 4 weeks if not treated.

Recurrent infection

• Following primary infection, the virus becomes latent in local sensory ganglia.
• There is periodic reactivation which can cause symptomatic lesions or asymptomatic, but still infectious, viral shedding.
• Episodes are usually shorter (up to 10 days).
• Symptoms may be mild and self-limiting.
• Lesions tend to be unilateral.
• Median recurrence rate after a symptomatic first episode is:
  • HSV-2: 0.34 recurrences per month (roughly 4 attacks in the subsequent 12 months).
  • HSV-1: 0.08 recurrences per month (roughly 1 attack in the subsequent 12 months).⁵
• Attacks usually become less frequent over time.
• Genital HSV caused by type 1 infection recurs less often.²

Investigations

Detection and identification of virus:⁴

• Suitable tests are:
  • Viral culture
  • DNA detection using polymerase chain reaction (PCR) of a swab from the base of an ulcer.
• The choice of test depends on local availability, practicalities (e.g. the need for careful handling and a 'cold chain' for culture specimens), cost and other factors.

Role of serology in HSV detection:⁴

• Type-specific serology tests can identify those with asymptomatic infection and can distinguish between the two types of HSV.
• Serological tests may take up to 12 weeks to become positive after primary infection.
• It may be useful:
  • If the patient's partner has genital herpes and the patient wants to know if they have been infected.
  • If there are recurrent/atypical genital ulcers with negative culture or PCR results.
  • For pregnant women and/or their partners, where relevant.
  • Possibly, to screen people at high risk of sexually transmitted infection.²

Differential diagnosis³

• Candida and scabies produce excoriation but not vesicles.
• The ulcers of syphilis are painless.
• Reiter's syndrome, Behçet's syndrome, drug reactions, chancroid, lichen planus, lichen simplex, lichen sclerosus, trauma (including dermatitis artefacta), and malignancy can cause genital ulceration.
• Herpes zoster is usually unilateral and confined to one dermatome.

Management³

There is no cure for genital HSV. Infection is lifelong although most people will eventually stop having recurrences.

Primary infection

Guidance from the Royal College of General Practitioners document states:³

• Refer a patient with suspected genital HSV infection to a genitourinary medicine (GUM) clinic the same day (ring to arrange).
• If a same/next day appointment is not possible, then:
  • Confirm diagnosis: swab base of ulcer or ulcer fluid for HSV (gently deroof blister if necessary using sterile needle²). A special swab with transport medium is required - discuss this with your local laboratory. For culture specimens, maintenance of the cold chain and rapid transport of specimens within 24 hours is needed. PCR has a highest detection rate and does not require such careful handling of samples.^2,4
  • Supportive treatment: advise saline bathing (1 teaspoon of salt in 1 pint warm water). Prescribe analgesia and consider topical lidocaine 5% ointment if very painful. Micturition whilst sitting in a bath can help prevent urinary retention.
  • Antiviral therapy:
    • There is no role for topical antivirals.
    • Give oral anti-herpes viral treatment if there are early symptoms - i.e. within 5 days of onset of symptoms, or if new lesions are still forming.
    • The standard treatment is aciclovir (at a dose of 200 mg orally 5 times daily OR 400 mg 3 times daily) for 5 days. Continue the treatment for longer if new lesions appear during treatment or if healing is incomplete.⁶
    • Higher-dose and longer courses are used for treating patients with HIV.^4,6
    • Other antivirals (valaciclovir, famciclovir) are also licensed for genital herpes but are much more expensive.
    • Antiviral therapy reduces the severity and duration of episodes but does not alter the natural history of the disease.⁴
  • Arrange follow-up: arrange an appointment at a GUM clinic in 2 to 3 weeks to allow patient education and a full sexually transmitted infection screen. Advise the patient to report to a GUM clinic sooner if the symptoms are not resolving. Provide written self-help information to the patient if possible.

Recurrent infection

• Supportive treatment only may be required (saline bathing, Vaseline® prn to ease pain due to friction, analgesia).
• Episodic treatment for each attack:
  • Antiviral treatment (as for management of primary infection, above).
  • It is helpful to give the patient a prescription so that they can start taking the treatment at first signs of a recurrence.
  • Diary keeping of attack frequency may be helpful.
• Suppressive treatment:
  • May be needed (usually if >6 attacks per year).
  • Usual treatment is aciclovir (various possible doses - see BNF⁶).
  • Consider the frequency of attacks and symptoms vs the cost and inconvenience of treatment.
  • Discontinue after 12 months to reassess attack frequency.
  • Minimum period of reassessment should include 2 further attacks.
  • If the recurrence rate is unacceptably high, suppressive treatment can be restarted.
  • Suppressive treatment also reduces the risk of asymptomatic shedding.

Counselling^4,2

• Diagnosis can cause distress.
• Contact tracing is needed (offer serological testing to asymptomatic contacts).
• Written information should be given to the patient.
• Need to cover:²
  • Natural history of genital herpes simplex virus (HSV).
  • The role of asymptomatic viral shedding in sexual transmission (more common in genital HSV-2 and in the first year after infection).
  • The fact that a first episode of genital HSV does not necessarily imply recent infection. (Relationship issues need to be addressed.)
  • Inform current or new sexual partners.
  • Use of antiviral drugs for symptom control including prescription in reserve for recurrent attacks and possible longer-term suppressive treatment.
  • If in a stable relationship, the other partner may not necessarily be infected. The daily use of valaciclovir by the infected partner can reduce the risk of transmission of HSV-2. Other antiviral drugs may be effective but have not been investigated in this scenario.⁴
  • Avoid sexual contact during symptomatic recurrences.
  • Condoms reduce (but do not completely prevent) the risk of transmission.
  • Pregnancy - all women with a diagnosis of genital herpes, or whose partner has genital herpes, should advise their GP and midwife of this at their first antenatal appointment, to consider how best to reduce the risk of neonatal infection. For more details see separate article Genital Herpes in Pregnancy.

Management in people with HIV

This requires specialist advice. More detailed information is given in the British Association for Sexual Health and HIV (BASHH) guidelines.⁴

Children

Recent National Institute for Health and Clinical Excellence (NICE) guidance on child protection states that sexual abuse should be suspected if a child has a sexually transmitted infection, including genital herpes. However, the guidance mentions that few published studies exist to inform whether sexual abuse is likely to be the mode of transmission in cases of genital herpes.⁷

Another review concluded that "child protection clinicians should be aware of the weakness of the evidence on the likelihood of sexual transmission of genital herpes in prepubertal children. The US guidance that child sexual abuse is 'suspicious' reflects the evidence better than the UK guidance that it is 'probable'."⁸

Complications

• Autonomic neuropathy, resulting in urinary retention. (Suprapubic catheterisation is preferred due to reduced risk of ascending infection, less painful procedure, allows normal micturition to be restored without multiple removals/recatheterisations.)⁴
• Aseptic meningitis.⁴
• Spread to extra-genital areas (in theory through self-inoculation).
• Secondary infection.
• Perinatal transmission if the woman is pregnant - may cause serious complications in the neonate (see separate article dealing with genital herpes and pregnancy).
• Psychological and psychosexual problems.
• HIV patients with primary infection and no HIV therapy - these patients may develop severe/prolonged mucocutaneous lesions. Other serious or life-threatening complications have been reported in this scenario, e.g,fulminant hepatitis, pneumonia, neurological disease and disseminated infection.⁴

Prevention

Transmission of herpes simplex virus (HSV) may be reduced by the following:

• Reduce the number of sexual partners.
• Use of condoms reduces, but does not completely prevent, transmission.
• Avoid sex with someone who has active genital herpes or active oral herpes (although viral shedding and transmission also occur from asymptomatic infections)
• Antiviral drugs may reduce transmission to partners (see Recurrent infection under Management section, above).
• Avoid sharing towels and flannels with a person who has active herpes infection (although it is unlikely that the virus would survive on an object long enough to be transmitted this way).⁹

Document references

1. Gupta R, Warren T, Wald A; Genital herpes. Lancet. 2007 Dec 22; 370(9605):2127-37. [abstract]
2. Sen P, Barton SE; Genital herpes and its management. BMJ. 2007 May 19;334(7602):1048-52.
3. Sexually Transmitted Infections in Primary Care, Royal College of General Practitioners (2006)
4. Management of genital herpes, British Association for Sexual Health and HIV (2007)
5. 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. [abstract]
6. British National Formulary; 58th Edition (September 2009) British Medical Association and Royal Pharmaceutical Society of Great Britain, London.
7. When to suspect child maltreatment, NICE Clinical Guideline (July 2009); Guidance on when to suspect child maltreatment
8. Reading R, Rannan-Eliya Y; Evidence for sexual transmission of genital herpes in children. Arch Dis Child. 2007 Jul;92(7):608-13. Epub 2006 Dec 5. [abstract]
9. Herpes simplex - genital, Clinical Knowledge Summaries (September 2008)

Internet and further reading

• Herpes Virus Association; website
• Gupta R, Warren T, Wald A; Genital herpes. Lancet. 2007 Dec 22; 370(9605):2127-37. [abstract]
• 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. [abstract]
• Vyse AJ, Gay NJ, Slomka MJ, 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. [abstract]
• Lingappa JR, Celum C; Clinical and therapeutic issues for herpes simplex virus-2 and HIV co-infection. Drugs. 2007;67(2):155-74. [abstract]
• Corey L, Bodsworth N, Mindel A, et al; An update on short-course episodic and prevention therapies for herpes genitalis. Herpes. 2007 Jun;14 Suppl 1:5A-11A. [abstract]

Acknowledgements