HERPES VIRUSES
Classification of Human Herpes Viruses
Transmmission and epidemiology
• HSV-1 by saliva i.e., direct contact.
• HSV-2 by sexual contact.
• The virus is easily inactivated at room temp. and drying, aerosol
and Fomite spread are unusual means of transmission.
• Special situation – oro- genital sex and auto inoculation is not
uncommon mode - HSV-2 in oral cavity – 10-20%.
HSV-1 in infection of genital tract.
• Transmission occurs actively if there is active lesion.
• It also occurs in asymptomatic cases where virus
shedding is present.
• Spread of HSV – 1 infection from oral secretions to
other skin areas is an occupational hazard – dentists,
respiratory care unit staff, wrestlers.
• Laboratory acquired, Nosocomial out breaks in hospital
and neonatal nurseries can occur.
• Most primary HSV-1 is thought to occur in child hood
because antibody is present in most of us.
• HSV-2 – occurs during phase of sexual activity –
antibody seen during that age.
Pathogenesis and Immunity• Initial site of infection – i.e. skin or mucous
membrane, replication occurs, Migrate in neuron
– latent in sensory ganglion cells
• HSV-1 – trigeminal ganglia
• HSV-2 - lumbar and sacral ganglia
• Precise mechanism unknown – may be by
lysogeny.
Reactivation
– Induced by sunlight hormonal changes, trauma, stress,
fever, U-V light.
• Migrate down the neuron and replication in skin causing
lesions.
• Skin lesion – vesicle – [serous fluid with virus particles, cell
debris].
• When rupture - vesicle release virions and can be
transmitted to others
Clinical features
1. Gingivostomatitis – children, fever, irritability and
vesicular lesion in the mouth. These heal by 2-3
weeks. But children may be asymptomatic also.
2. Herpes labialis – milder recurrent form of HSV
Infection.
• Also called fever blisters, cold sores – crops of
vesicles seen.
• Recurs frequently at the same site as previous one.
Gingivo-stomatitis
Herpes labialis
3. Keratoconjunctivitis – Corneal ulcer, lesion of
conjunctival epithelium scarring and
blindness following recurrence.
4. Encephalitis–
Temporal
lobe
involved
frequently, high mortality severe neurologic
sequelae with those who survive.
5. Herpetic whitlow - Pustular lesions of finger or
hand. Usually in medical personal as a result of
contact with patients lesion.
6. Disseminated – Oesophagitis, pneumonia
usually seen in immunocompromised because
of defect in the T cell.
HSV – 2 –
• there is primary and recurrent infection.
• 1. Genital – painful vesicular lesion – in both
sexes.
-Lesion in genital, anal area
-Primary disease is severe and protracted than in
recurrent disease
-There is inguinal lymphadenopathy & fever
• Asymptomatic disease also seen –
In men prostate, urethra
In female cervix.
• They are source for others.
• Also many people have antibody to HSV-2 but
no history of disease.
2. Neonatal herpes – Contact of vesicular lesions in
birth canal during delivery.
• Some cases have no visible lesions but still
asymptomatic shedding of virus by mother can
occur leading to child being infected.
• Lesion in child – asymptomatic or mild local
lesions or severe encephalitis or generalised
disease.
• Prevention – Caesarian section advised if lesions
are seen and positive viral culture of mother.
• Both HSV-1 & 2 can cause severe neonatal
infection after birth through carriers handling the
child.
• It does not cause congenital abnormalities alone.
3. Aseptic meningitis – by HSV-2 is usually mild, self
limiting and with few sequelae following recovery.
Lab diagnosis
1. Isolation of virus – Fibroblast cell culture
• CPE observed in 1-3 days
• Followed by fluorescent Ab staining of infected cells
or detection of virus specific glycoprotein by ELISA.
Rapid diagnosis – Tzanck smear
• [Giemsa or Toluidine blue] multinucleated
giant cell with Cowdry type A inclusion body.
PAP stain also for HSV-2.
Serology
Neutralization test used in diagnosis of primary
infection
• ELISA, CF - by observation of increase in Ab titer
by paired sera examination.
• Not useful in recurrent infection because adults
already have circulating Ig and recurrences rarely
cause rise in Ab titer.
Varicella Zoster [V-Z virus]
Disease:
Varicella–chickenpox –primary disease
Zoster – Shingles – recurrent form.
Properties • VZV structurally and morphologically similar
but antigenically different from HSV.
• There is a single serotype- same virus causes
both type of disease.
• Humans are the natural host.
• Replicative cycle – same as HSV.
Transmission and epidemiology
• By respiratory droplets, direct contact with
lesion.
• Highly contagious disease of children– 90%
population has Ab by 10 years of age.
• World wide in distribution.
Pathogenesis and immunity
• VZV infect mucosa of upper respiratory tract.
• Enter blood  skin
• Vesicular rash [typical] having multinucleated giant cell
and intranuclear inclusions in cells of base of lesion.
• Recovery
• Latency in dorsal root ganglion.
• Later in life especially if decrease in CMI, trauma
etc. – reactivation
• leads to vesicular skin lesion and also nerve pain.
• Immunity following Varicella is life long
• But Zoster can occur despite varicellar immunity.
• Zoster can also occur once but frequency
increases with age because of waning immunity.
Clinical feature• Varicella – incubation period 14-21 days.
• Brief prodromal period of fever and malaise.
• Followed by papulo vesicular rash
• Crops of them on trunk and later spreading to
head and extremities [centripetal rash]
• Leads to papules, vesicles, pustules, crusting
with severe itching.
• Usually varicella is mild in children but severe in adults.
• In adults- severe symptoms, profuse rash, which may
be sometimes hemorrhagic and bullous.
• Complications in aged are varicella pneumonia and
encephalitis, myocarditis, nephritis, cerebellar ataxia,
meningitis, erythema multiforme.
• Reyes syndrome – encephalopathy, liver degeneration
is associated with VZV, influenza B virus especially with
children given aspirin [unknown pathogenesis].
Zoster [shingles] – painful vesicles along the
course of a sensory nerve of the head or trunk.
• Pain lasts for weeks and post zoster neuralgia
can occur and is very debilitating requiring
ganglion surgery often as treatment.
• It can also cause Bell’s palsy - Zoster of facial
nerve.
• If there is tympanic involvement and Bell’s
palsy -it is called Ramsy Hunt Syndrome.
• In immunocompromised – systemic
dissemination – pneumonia which is life
threatening.
Laboratory diagnosis • Clinically chicken pox or shingles can be diagnosed
• Presumptively by Tzanck smear – similar to HSV.
• Definitive diagnosis by isolation in cell culture and use
of specific antiserum to identify growth inside the cell
line.
• Rise in titer of antibody [paired sera] useful for
diagnosis of chickenpox.
• Not useful for zoster because antibody already present.