Herpes Viruses

• Herpesviridae virus family:

  • Herpes Simplex Virus 1 and 2
  • Varicella Zoster Virus
  • Cytomegalovirus
  • Epstein Barr Virus
  • Human Herpes Virus 6
  • Human Herpes Virus 7
  • Human Herpes Virus 8 (Kaposi's sarcoma associated herpes virus)
• Herpesviridae virology:

  • Enveloped
  • Double-stranded DNA
  • 150 kilobase pairs
  • Lytic infection (actively replicating) and latent infection (no active virus replication)
• Herpes Simplex Virus - Types 1 and 2:

  • Primary infection - first infection with either HSV 1 or HSV 2
  • Active viral replication in mucosal tissues
  • Latency - nerve cell bodies in spinal cord
  • No viral replication
  • Reactivation - latent virus reactivates
  • Active viral replication in mucosal tissues

  
• HSV - primary oral herpes:

  • Primary infection with HSV 1 (more commonly) or HSV 2
  • Usually asymptomatic
  • Can be severe gingivostomatitis

  
• HSV - oral reactivation:

  • Reactivation usually HSV 1
  • Usually asymptomatic
  • Can cause cold sores
  • Borders of lips
  • Rarely intra-oral
  • Reactivation can be random
  • Non-specific triggers
  • e.g. stress, fever, menstruation, cold, UV radiation
  • Can be tingling or itching before vesicles (full of infective fluid)
  • Lasts 5-12 days

  
• HSV - genital disease:

  • Primary infection with HSV 1 or HSV 2
  • Reactivation usually HSV 2
  • Primary more severe than reactivation
  • Reactivation often asymptomatic
• HSV - main complications:

  • Secondary bacterial infection
  • If it reactivates in eye - corneal ulcers, risk of scarring, loss of vision
  • If it reactivates in CNS - meningitis, self-limited, usually HSV 2, can be recurrent (Mollaret's meningitis)
  • Herpes Simplex Encephalitis, life-threatening, usually HSV 1 - requires prompt, aggressive treatment
  • Neonatal Herpes Simplex - life-threatening
  • Life-threatening infection in the immunocompromised
• HSV - herpetic whitlow: can occur if children suck their thumb and have lesions on the skin or if health professionals, who come into contact with oral/genital fluid, don't use correct PPE.

  
• HSV - encephalitis:

  • Commonest cause of viral encephalitis
  • 70% mortality untreated
  • High rate of poor neurological outcome

  
• Diagnosis of HSV:

  • Direct Viral Detection (PCR = polymerase chain reaction)
  • Lesion swab
  • Cerebrospinal fluid
• Treatment of HSV:

  • Acyclovir
  • Needs activating by a viral enzyme - thymidine kinase - so specific for infected cells
  • Poor oral bioavailability, 5x per day dosing
  • Valacyclovir
  • Prodrug of acyclovir
  • Good oral bioavailability, but more expensive
• Life cycle of the varicella zoster virus (chicken pox):

  
• VZV - primary infection - chickenpox:

  • Prodrome of fever before rash is common
  • Centripedal distribution (affects head, neck and trunk)
  • Macules -> Papules -> Vesicles -> Pustules
  • Crops of lesions at different stages
  • More severe in adults
  • Oral vesicles can occur before those elsewhere and can be extremely painful
• Chickenpox - epidemiology:

  • UK > 90% seroprevalence (naturally immune)
  • Outbreaks mainly in winter/spring
  • Attack rates for household contacts is 90%
  • Peak age is now < 5 years
  • Respiratory transmission or direct contact
  • Incubation period 8-21 days (average 14 days)
  • Infectious from 2 days before rash to full crusting of vesicles
• VZV reactivation - zoster (shingles):

  • Ophthalmic zoster
  • Affecting trigeminal nerve
  • Ocular complications particularly likely if nasociliary branch is involved (lesion on side of nose)

  
• Diagnosis of VZV reactivation (shingles):

  • Clinical
  • Direct Viral Detection
  • Now detection of viral DNA by PCR
  • Lesion swab
  • Cerebrospinal fluid
• Post-exposure prophylaxis for VZV:

  • For those at increased risk
  • Pregnant women
  • Immunocompromised
  • Zoster Immunoglobulin (VZIG - IM injection)
  • Give if significant contact:
  • Varicella: face to face contact or >15 minutes in the same room
  • Zoster: exposure to uncovered rash
  • And not immune to varicella
• Varicella vaccine:

  • Live attenuated vaccine
  • Used as part of childhood vaccine schedule for 15 years in USA (2 doses with MMR)
  • Indications in UK
  • Healthcare workers
  • VZV IgG negative contacts of immunosuppressed children (vaccine contraindicated in the immunosuppressed)
• Shingles vaccine:

  • Aim to boost immunity and prevent reactivation
  • All 70 year olds from September 2013
• Cytomegalovirus (CMV):

  • Transmission via direct contact with infected secretions (saliva, sexual...)
  • Primary infection
  • Usually asymptomatic
  • Occasionally Glandular Fever-like picture (Lymphadenopathy, Hepatitis)
  • Reactivation intermittently
  • Asymptomatic in the immunocompetent
• Cytomegalovirus (CMV) concerns:

  • Congenital infection
  • Pregnant healthcare workers not at greater risk of acquiring infection than other pregnant women
  • Standard precautions sufficient to prevent transmission
  • Severe disease in the immunocompromised
• Epstein-Barr Virus:

  • Young children - asymptomatic or sore throat
  • Adolescents - glandular fever/infectious mononucleosis
  • Also associated with variety of lymphomas and cancer
  • Most people infected by adulthood
  • EBV is latent in B lymphocytes
  • Intermittent asymptomatic reactivation results in shedding in saliva
  • Transmission via saliva or sexual contact
• Epstein-Barr Virus (EBV) causes oral hairy leukoplakia, which is associated with HIV

  
• Human Herpes Virus 6 and 7 both cause Roseola Infantum (a rash illness in infants)

  
• Human Herpes Virus 8 is the virus associated with Kaposi's sarcoma.