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					                  HERPES VIRUSES

Learning objectives
  • At the end of the lecture the student should be able to:
  • Know the details of herpes simplex virus
  • Identify the clinical features of herpes and vericella
  • Know the details of vericella

Properties of herpesviruses
• Enveloped double stranded DNA viruses.
• Genome consists of long and short fragments in either direction,
  giving a total of 4 isomers.
• Three subfamilies:
   – Alpha herpes viruses - HSV-1, HSV-2, VZV
   – Beta herpes viruses - CMV, HHV-6, HHV-7
   – Gamma herpes viruses - EBV, HHV-8

• Latent or persistent infection following
  primary infection
• Reactivation during periods of
• Both primary infection and reactivation are
  likely to be more serious in
  immunocompromised patients.
Herpes Simplex Viruses
•   Man is the only natural host
•   Latent infection is established frequently. Reactivation in
    immunosuppressed conditions and some cause cancers.
•   The virus is shed in saliva, tears, genital and other
    secretions and spreads by contact.
•   There are 2 peaks of incidence, the first at 0 - 5 years and
    the second in the late teens.
•   Unbroken skin is resistant to infection.

HSV Types 1&2
• Infect epithelial cells and establish latent infections
  in the neurons.
• Type 1 : Associated with oropharyngeal lesions.
    – Recurrent attacks of fever blisters. Trigeminal ganglia
      are infected
• Type 2 : Associated with infection of genital lesions.
  – Sacral ganglia are involved.

• Replication At the site of entry.VP16 a tegument protein
  initiates viral gene expresion.
• Invasion Local nerve endings
• Disseminates spreading to the craniospinal ganglia and
  transported to the dorsal root ganglia through retrograde
  axonal flow.
• Latency is established in the dorsal root ganglia.
Pathology of lesions
    • Cytolytic lesions (necrosis)
    • Ballooning of infected cells
    • Intranuclear inclusion bodies Cowdry type A first
      fill the nucleus, condense then separated by a
      halo from the chromatin at the nuclear margin.
    • Cell to cell spread occurs by cell
      fusion.Margination of chromatin and formation of
      multinucleated giant cells occurs.

Latent infections
•   The virus resides in a non replicating state
•   Only a few viral genes are expressed.
•   A small RNA (micro RNA) encoded by a latency
    associated viral gene that prevents cell death
•   Virus not recovered between periods of recurrence.

•   Physical or psychological stress,
•   Infection (especially pneumococcal and meningococcal)
•   Fever
•   Irradiation including sunlight, menstruation trigger and can
    provoke a recurrence.
Clinical Manifestations
1. Acute gingivostomatitis
2. Herpes Labialis (cold sore)
3. Ocular Herpes
4. Herpes Genitalis
5. Other forms of cutaneous herpes
7. Meningitis
8. Encephalitis
9. Neonatal herpes

Acute Gingivostomatitis
Commonest manifestation of primary
herpetic infection
1 - 8 mm ulcers with necrotic bases
are present. Neck glands are
commonly enlarged accompanied by

Herpes labialis
A recurrence of oral HSV
A prodrome of tingling, warmth or itching at
the site usually heralds the recurrence. About
12 hours later, redness appears followed by
papules and then vesicles
Ocular Herpes
Includes mild superficial lesions involving the external eye, to
  severe sight-threatening diseases of the inner eye
   – Primary HSV keratitis – dendritic ulcers
   – Recurrent HSV keratitis
   – HSV conjunctivitis
   – Iridocyclitis, chorioretinitis and cataract

Genital Herpes
•  Primary, or recurrent
 Sites involved : The penis, vagina,
  cervix, anus, vulva, bladder, the sacral
  nerve routes, the spinal and the
 Prone to secondary bacterial infections
   eg. S.aureus, Streptococcus,
   Trichomonas and Candida Albicans
• Dysuria in severe cases may result in
  urinary retention.
• Radiculitis. Mild meningitis may be present.
• 60% of patients with genital herpes will experience recurrences.
Herpes Simplex Encephalitis
• One of the most serious complications
• Neonatal Herpes Simplex.
• Usually acquired perinatally (during passage through the birth
  canal premature rupturing of the membranes)
• Oral lesions from the mother or a herpetic whitlow in a nurse
• The brain is almost liquefied. The mortality rate approaches
  100%. Other sources such as oral lesions from the mother or a
  herpetic whitlow in a nurse
• The only means of prevention is to offer caesarean section to
  mothers with florid genital HSV lesions

Disseminated Herpes
Immunocompromised individuals
• Widespread vesicular rash.
• May involve liver, spleen, lungs, and CNS
    – Eczema herpeticum.
    – Herpetic whitlow typically affects the fingers.
    – “zosteriform herpes simplex".a rare
        presentation lesions appear in a dermatomal distribution
        similar to herpes zoster.

Laboratory Diagnosis
•   1-Direct Detection .
    –   Electron microscopy of vesicle fluid .
    – Immunofluorescence of skin scrappings - can
      distinguish between HSV and VZV
•   3-Virus Isolation.
    –   (from lesions,skin,cornea,brain,CSF,stool or throat).
    –   (ELISA,Radioimmunoassay,complement fixation test).
•   5-PCR
The high cost of antiviral drugs being a main consideration.
 Acyclovir –
   • I.V. (HSV infection in normal and immunocompromised patients)
   • Oral (treatment and long term suppression of mucocutaneous
     herpes and prophylaxis of HSV in immunocompromised patients)
   • Cream (HSV infection of the skin and mucous membranes)
   • Ophthalmic ointment
 Famciclovir and valacyclovir – oral only, more expensive than
 Other older agents – e.g. idoxuridine, trifluorothymidine, Vidarabine
   • These agents are highly toxic and is suitable for topical use for
     opthalmic infection only

Varicella- Zoster Virus
    •   Alpha herpes virus subfamily
    •   Double stranded DNA enveloped virus
    •   Genome size 125 kbp, long and short fragments.
    •   One antigenic serotype only, although there is some
        cross reaction with HSV.
    •   Same virus is responsible for chickenpox (varicella)
        and zoster.
    •   Morphologically identical to herpes simplex virus.
•   One of the classic diseases of childhood, with the highest
    prevalence occurring in the 4 - 10 years old age group
•   Incubation period of 14 -21 days
•   Fever, lymphadadenopathy and a generalised vesicular eruption
    of skin and mucous membranes
•   Severe in adults and immunocompromised
        Stage 1                                   Stage 2

         Stage 3                                      Stage 4
    • Complications rare but more frequent and with greater
      severity in adults and immunocompromised patients.
        – Secondary bacterial infection
        – Pneumonia
        – Encephalititis
        – Haemorrhage

Z o s te r
•   A sporadic, incapacitating disease that occurs in adults or
    immunocompromised individuals
•   The virus remains latent in the cerebral or posterior root
    ganglia. Recurrent infection occurs after several decades
•   A rash on skin innervated by a single sensory ganglion (in
    the distribution of a dermatome)
•   Zoster immunoglobulin should be given to susceptible
    pregnant women.
•   Infants whose mothers develop varicella during the last 7
    days of pregnancy or the first 14 days after delivery

•   Epithelial cells swell (ballooning degeneration).
•   Tissue fluid accumulates resulting in the formation of
•   In Zoster the skin lesions are histopathologically similar to
    those of varicella but there is also an acute inflamation of
    sensory nerves and ganglia.
Congenital VZV Infection
Virus can cross the placenta in the late stages of pregnancy .
• Up to 3% chance of transmission to the fetus, recognised congenital
        varicella syndrome;
         – Scarring of skin
         – Hypoplasia of limbs
         – CNS and eye defects
         – Death in infancy normal

Laboratory Diagnosis
. Tzanck       smear shows multinucleate giant cells.
    –    Virus Isolation
    –    Direct detection - electron microscopy may be used for vesicle
         fluids but cannot distinguish between HSV and VZV.
         Immunofluorescense on skin scrappings can distinguish
         between the two.
    –    Serology –Specific antibody titre.
    –    DNA based diagnosis.

• Uncomplicated varicella is a self limited disease and requires no specific
• Acyclovir in immunocompromised individuals and normal individuals
  with serious complications such as pneumonia and encephalitis.
• Management of Post herpetic neuralgia is the main problem .
• Antiviral therapy should be offered routinely to all patients over 50 years
  of age.Three drugs are available: Acyclovir, Valicyclovir, and
• Preventive measures should be considered for individuals at risk of
  contracting severe varicella infection e.g. leukaemic children, neonates,
  and pregnant women
• Passive immunization by Zoster immunoglobulin (ZIG)
•       A live attenuated vaccine is available.

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