D

Genital Herpes

Overview of Herpesviruses

  • There are over 100 herpesviruses known to infect various organisms including mammals, birds, reptiles, and oysters.

Definition and Clinical Importance

  • Herpesvirus: Derived from Greek "herpein" meaning "to creep", referring to the spread of lesions.

  • Distinctive Characteristic: Herpesviruses establish latent infections in the host, which can reactivate causing recurrent disease. This latency is critical in clinical settings.

Structure of Herpesviruses

  • The structure includes:

    • Envelope proteins (gB-gN)

    • Tegument

    • DNA

    • Nucleocapsid

    • Lipid envelope

Herpesviridae Family

Sub-Families and Human Herpesviruses

  • Human Herpesvirus Sub-Family includes:

    • Herpes simplex virus type 1: Causes recurrent oral disease (fever blister or cold sore).

    • Herpes simplex virus type 2: Causes recurrent genital disease (genital herpes).

    • Varicella-zoster virus: Causes chickenpox and shingles.

    • Cytomegalovirus: Associated with congenital defects and opportunistic disease in AIDS patients.

    • Human herpesvirus 6: Causes roseola.

    • Human herpesvirus 7: Also associated with roseola.

    • Epstein-Barr virus: Causes infectious mononucleosis.

    • Human herpesvirus 8: Linked to Kaposi’s sarcoma in AIDS patients.

Transmission

  • Herpes simplex virus infections are primarily transmitted through close contact with an infected person shedding the virus. Transmission occurs via:

    • Inoculation onto susceptible mucosal surfaces

    • Small cracks in the skin

Epidemiology

Herpes Simplex Virus Type 1 (HSV-1)

  • Global prevalence: Approximately 3.8 billion people worldwide under 50 years are infected.

  • U.S. prevalence: About 200 million individuals under 50 are infected.

Herpes Simplex Virus Type 2 (HSV-2)

  • An estimated 1 in 6 individuals aged 15-49 years in the U.S. are infected.

Primary Infection Results

  • Primary infection with HSV-1 can result in:

    • Gingivostomatitis (90% of cases)

    • Symptomless (9% of cases)

    • Minor illnesses and diseases: keratitis (1%), genital herpes, eczema herpeticum, encephalitis, disseminated herpes, whitlow (herpetic infection of the finger), herpes gladiatorum.

Latency and Reactivation

Latency

  • Latent virus DNA is found in human trigeminal ganglia (for HSV-1) and sacral ganglia (for HSV-2).

  • Exclusive site of latency in neurons with extrachromosomal viral genome configuration. Each neuron may harbor multiple copies of the genome (approximately 25% of neurons)

    • Trigeminal ganglion can harbor up to 6000 neurons with latent virus.

    • Latency-Associated Transcript (LAT): A virus-encoded mRNA that accumulates in neuron nuclei, playing a role in downregulating apoptosis to prevent neuron death. LAT serves as a marker for HSV-1 and HSV-2 latency.

Reactivation Triggers

  • Reactivation from latency can be initiated by:

    • Local stimuli (e.g., tissue injury)

    • Systemic conditions (e.g., fever, stress, sunlight)

  • Reactivation is not associated with neuron destruction.

Recurrent Disease

Herpes Simplex Virus Type 1

  • Commonly leads to conditions like:

    • Oral disease (fever blisters/cold sores)

    • Ocular disease (stromal keratitis)

    • Whitlow (in fingers)

Vesicles

  • Lesions from HSV-1 appear similar to blisters containing high amounts of infectious virus. They eventually dry and crust over.

Encephalitis

  • Herpes Simplex Encephalitis:

    • Extremely severe with over 70% mortality.

    • Death generally occurs 10 days post-symptom onset.

    • Survivors may face severe neurological deficits.

    • Typically affects temporal lobes in immunocompetent adults.

Herpes Simplex Virus Type 2 (HSV-2) - Genital Herpes

Primary Infection

  • Predominant cause of genital herpes; can also be initiated by HSV-1.

  • Incubation period: Typically 6-8 days, up to 14 days.

  • Prominent symptom: Development of numerous, painful vesicles which form crusts within 20 days.

Complications of Primary Genital Herpes

  • Complications include meningitis (28%) and autoinoculation (21%).

Recurrence

  • Patients may experience prodromal symptoms prior to vesicle appearance:

    • Symptoms often include unilateral and localized vesicles, which are typically fewer and less painful compared to the primary infection. Healing occurs in approximately 12 days.

  • Patients often experience asymptomatic shedding of the virus.

Changing Perspectives

  • Initial belief that vesicles must be present for transmission has been proven false:

    • Asymptomatic shedding can occur frequently (ongoing clinical studies indicate asymptomatic shedding every 6-12 hours).

    • Innate immunity appears to control asymptomatic shedding, preventing clinical disease.

    • Chronic persistent inflammation occurs in the genital mucosa.

Neonatal Infection

  • Incidence ranges from 1 in 3,000 to 1 in 5,000 deliveries per year.

  • Higher risk associated with primary maternal infections (30-50%) compared to recurrent maternal infections (3%).

  • May lead to skin vesicles, corneal disease, and panencephalitis. Without antiviral treatment, mortality rates exceed 80%.

Antiviral Management

Acyclovir (Zovirax)

  • Therapeutic Index: High, indicating low toxicity.

  • Effective for treating HSV-1 and HSV-2,

  • Mechanism of action requires the virus-encoded enzyme thymidine kinase.

Valacyclovir (Valtrex)

  • Developed as a second-generation acyclovir, it has five times higher oral bioavailability.

  • Converted to acyclovir within cells with identical mechanism of action.

Vaccination

  • As of now, there is no existing vaccine for the prevention of HSV-1 or HSV-2 infections, as well as for genital herpes.