Dr. med. Dirk Manski



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Herpes Genitalis: Genital Infection with Herpes Simplex Virus

References: (CDC Guidelines, 2006) (Kimberlin and Rouse, 2004) (Whitley and Roizman, 2001).

Definition of genital herpes

Genital herpes is an infection of the external genitals with herpes simplex virus (HSV-1 or -2), resulting in clusters of genital sores (inflamed papules and vesicles).

Epidemiology

There is an age-related increase in HSV-2 prevalence for women from 7% (15–19 years) to 28% (40–44 years). Also with HSV-1, there exists an age-related increase in prevalence, with far greater manifestation: 20% (<5 years), 40–60% (20–40 years). Risk group for the HSV-2 infection: sexually active young people with multiple partners, sex workers, lack of condom use, homosexual people, living in an urban area.

Etiology of genital herpes

Pathogen:

Herpes simplex virus 1 (oral type) or 2 (genital type). HSV-2 causes more genital recurrences (99% recurrence).

Morphology of herpes simplex virus:

The family of herpes viruses is of icosahedral shape, they contain double-stranded DNA (84 proteins). The capsid (a protein cage) encases the DNA, which is wrapped by an envelop (lipid bilayer).

Mechanisms of genital herpes infection:

After binding of the virus to cell membrane receptors, endocytosis and dissolution of the viral shell (envelope) follows. The capsid gets via axoplasmic transport to the nucleus of the sensory neuron. Viral proteins are generated in three cycles (immediate early, early and late proteins). After the outbreak and healing of herpes genitalis, HSV-DNA remains in the nucleus of the neuron without viral replication (latency). After a certain time, various factors (see below) may trigger a further clinical manifestation of herpes genitalis (recurrence). Viral shedding may remain asymptomatic.

Immune response after HSV infection:

HSV inhibits the presentation of immunologically important protein fragments on the MHC class 1 proteins. Furthermore, HSV inhibits the apoptosis of the host cell in response to the viral infection. Furthermore, HSV inhibits DNA transcription, destroys mRNA and splicing of RNA from the host cell.

Transmission of genital herpes:

HSV is transmitted through oral-genital or genital contact.

HIV:

Genital herpes is a strong risk factor for an HIV-infection.

Signs and Symptoms

Genital sores:

Grouped papels or vesicles on an erythematous base are pathognomonic for genital herpes. After rupturing, they form an ulcer and heal within 1–4 weeks.

First Manifestation of Herpes Genitalis:

Balanitis, urethritis or herpetic vulvovaginitis, sometimes without typical genital sores. The primary symptoms are more pronounced with secondary recurrent genital herpes and are induced by both virus types. If there already has been an oral HSV-1 infection, the symptoms of primary genital herpes are attenuated.

Complications of Genital Herpes:

1% of the patients with primary genital herpes develop an autonomic dysfunction with urinary retention, erectile dysfunction, constipation and sensory losses. Sometimes, a (intermittent) catheterization for weeks is necessary.

Mild meningitis is relatively common with primary herpes (13–20%). Herpes encephalitis is less common and has a mortality rate around 70%.

Neonatal herpes simplex develops after vaginal birth due to an infected mother. Neonatal herpes simplex presents either with a local infection (skin, eye or mouth), disseminated manifestation (internal organs) or central manifestation (CNS).

Recurrent Genital Herpes:

Recurrent genital herpes is often caused by HSV-2 with typical genital sores (see above). The lesions are painful, there may be a inguinal lymphadenopathy. Frequently, patients feel genital paresthesias before a manifestation of recurrent herpes genitalis becomes visible. A third of the patients develop frequent recurrences (>6 per year), while a third very rarely develop recurrences (<1 relapse per year).

Trigger of recurrent genital herpes:

The following factors may trigger recurrent genital herpes: physical or emotional stress, fever (cold sores), UV light, injury, local infections...

Diagnosis of Genital Herpes

The diagnosis is based on signs and symptoms (see above). A detailed history and examination of any partner sexual partner is necessary.

The detection of the virus is possible by a cell culture or PCR from cerebrospinal fluid or vesicles. Furthermore, serological tests can reveal a HSV infection in the past, but disease activity cannot be measured.

Treatment of genital herpes

Aciclovir:

200 mg Aciclovir 1-1-1-1-1 p.o. for 5 days, 800 mg 1-1-1 p.o. or 5 mg/kg 1-1-1 i.v. Intravenous administration is only necessary in severe disease (e.g. encephalitis). Systemic administration of aciclovir relieves the symptoms and accelerates the healing of the lesions, but cannot influence the probability of disease recurrence. For a successful antiviral systemic therapy, an immediate start of therapy is crucial.

In recurrent genital herpes, the patients should have the medication prepared at home and should begin the therapy by themselves. The start of therapy with begin of prodromal symptoms can prevent the outbreak of the disease relapse. With more than 8 relapses per year, a permanent acyclovir therapy 200–400 mg 1-0-1 p.o. should be considered. Even then, an asymptomatic viral shedding can infect the partner, but the therapy improves the quality of life.

Other antiviral substances:

On the basis of aciclovir, pro-drugs such as famciclovir or valacyclovir have been developed. Advantages are a higher bioavailability with oral administration. Dosage: famciclovir 125 mg p.o. 1-0-1 or valacyclovir 1000 mg 1-0-0 or 500 mg 1-0-1 p.o.

Local Therapy:

Local therapy is an alternative to systemic therapy; the genital lesions are treated with antiviral cream. The local anti-viral therapy has only a limited clinical effect.

Prophylaxis of genital herpes:

Condom use; sexual abstinence, especially concerning partners with genital lesions.

Experimental Therapy:

Vaccinations in animal experiments show promising results, clinical trials should be awaited.






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References

Center for Disease Control and Prevention.:
Sexually transmitted diseases treatment guidelines 2006.
in: MMWR
2006; 55 (No. RR-11): 1–93.

Kimberlin und Rouse 2004 KIMBERLIN, D. W. ; ROUSE, D. J.:
Clinical practice. Genital herpes.
In: N Engl J Med
350 (2004), Nr. 19, S. 1970–7

Whitley und Roizman 2001 WHITLEY, R. J. ; ROIZMAN, B.:
Herpes simplex virus infections.
In: Lancet
357 (2001), S. 1513–18

 

 

 

 

 

 

 

 

 





  Deutsche Version: Herpes genitalis