HSV

Question 1

How does HSV get transmitted

Answer 1

• Penetrates susceptible mucosal surfaces or broken skin
• The virus is transported from epithelial cells to sacral ganglia along peripheral nerve axons where HSV establishes a “latent phase”
• HSV is never cleared by immune system so this becomes lifelong reservoir
• Unsure what mechanisms change it from latent to active infection
• Transmission occurs via contact with the mucosa or epithelial surface of a person who is shedding virus or in genital or oral secretions
• Sexual transmission occur via genital-to-genital, oral to genital or genital to oral contact
• Auto transmission, eg: fingertips

Question 2

Clinical features of HSV

Answer 2

First episode: Approximately 25% of patients who present with a first clinical episode of HSV-2 have a positive HSV-2 antibody test, meaning they had previous unrecognized or asymptomatic acquisition of HSV-2. (Non Primary)

Primary Genital Infection is defined as the first infection with absence of antibody.

Classic: Severe multiple bilateral genital ulcers, pain, itching, dysuria, vaginal or urethral discharge, and tender inguinal adenopathy

Systemic symptoms (fever, myalgias, headaches, aseptic meningitis or symptoms of autonomic nervous system dysfunction such as urinary retention) peak within 3 to 5 days of onset of lesions and gradually recede over 3 to 4 days.

Without antivirals this part can last 14-21 days.

More than 85% of persons infected with genital herpes are unaware of their infection, and asymptomatic shedding of HSV in these persons accounts for the majority of transmitted genital HSV infections.

Prodromal symptoms - localised tingling and burning

Question 3

Complications of HSV

Answer 3

Aseptic meningitis 
Benign recurrent lymphocytic meningitis (Mollaret's meningitis) 
Radicular pain 
Sacral paraesthesia
Transverse myelitis 
Autonomic dysfunction 
Disseminated viremic infection 
Fulminant hepatitis
Neonatal herpes

Question 4

HSV and HIV

Answer 4

HSV is considered a risk factor for ACQUIRING AND TRANSMITTING HIV (think breaking integrity of skin)

May require tenofovir + aciclovir

Question 5

Diagnosis of HSV

Answer 5

Gold Standard: HSV culture or nucleic acid amplification methods including polymerase chain reaction assays for HSV DNA are preferred HSV test for genital ulcer + mucocutaneous lesions

1. Serology - IgG only
2. Antigen detection: DFA (direct immunofluorescence assay)
3. HSV-2 ELISA + western blot

Vesicles if present should be unroofed and the base of the ulcer swabbed to obtain adequate cells for viral culture/PCR

Question 6

Treatment for HSV and goal of treatment

Answer 6

Goal: to shorten the duration of viral shedding, improve symptoms and accelerate healing

Tx: (FAV) - Famciclovir, Acyclovir, Valacyclovir

1st Episode 
- Acyclovir 400mg TDS for 10 days or
- Valacyclovir 500mg BD for 10 days 
Window: 4-5 days
- Famciclovir 

Recurrent Episode

• Window: first 72 hours best, tx the sooner the better
• Valaciclovir 1g BD for 3-5 days or acyclovir 400mg TDS for 5 days

Question 7

Indications for HSV suppression therapy

Answer 7

• Indications: >6 episodes/year
• Reduces frequency of recurrences by 75%

Suppression doses:
Acyclovir 400mg BD
Valacyclovir 1g daily
Famciclovir 250mg BD

Question 8

HSV acyclovir resistant strains

• Mechanism
• What medications can be used

Answer 8

Mechanism of resistance is due to TK (tyrosine kinase) mutation which knocks out acyclovir, ganciclovir and valganciclovir

Antiviral Options

• Forscarent
• Cidofovir
• Imiquimod cream

Note: ganciclovir + valganciclovir will not work

Question 9

HSV prevention

Answer 9

Combination

• Antiviral suppressive therapy reduces HSV2 shedding by 70-80% but does not eradicate it
• Condom use decreases transmission in serodiscordant couples by 30%