This document discusses Varicella Zoster Virus (VZV) which causes chickenpox (varicella) and shingles (herpes zoster). VZV establishes latency in dorsal root ganglia after primary infection of chickenpox which can later reactivate and cause shingles. Both diseases present with characteristic vesicular rashes but shingles lesions are limited to a single dermatome. Complications of shingles include postherpetic neuralgia. VZV is diagnosed through virus isolation, serology, PCR or antigen detection and treated with antiviral drugs like acyclovir. Vaccination provides effective protection against chickenpox.

1. Varicella Zoster Virus
By- Sanju Sah
St. Xavier’s college, Maitighar, Kathmandu
Department of Microbiology

3. Varicella-Zoster Virus (VZV)
• Human alpha-herpesvirus3
• Varicella zoster virus (VZV) causes two distinct clinical entities in humans
• Causes varicella (chickenpox) and herpes zoster (shingles)
• Chickenpox is acquired by transmission from an infected host to a
susceptible host, whereas herpes zoster occurs as a result of reactivation of
the latent virus.
• Contact with a case of zoster or chickenpox may transmit chickenpox but
not herpes zoster.
• Primary VZV infection leads to varicella
• VZV establishes latency in dorsal root ganglia after primary infection
• 6VZV can reactivate at a later time, causing herpes zoster

4. Varicella-Zoster Virus (VZV)
• Varicella (chickenpox) is a mild, highly contagious disease, chiefly of
children, characterized clinically by a generalized vesicular eruption of the
skin and mucous membranes.
• The disease may be severe in adults and in immunocompromised children.
• Zoster (shingles) is a sporadic and is disease of adults or
immunocompromised individuals that is characterized by a rash limited in
distribution to the skin innervated by a single sensory ganglion.
• The lesions are similar to those of varicella.
• Both diseases are caused by the same virus.
• Varicella is the acute disease that follows primary contact with the virus,
whereas zoster is the response of the partially immune host to reactivation
of varicella virus present in latent form in neurons in sensory ganglia.

5. Reactivation
of
varicella
virus
present
in
latent
form

6. Properties of the Virus
• The virus has the smallest genome of all the human herpesviruses.
• It is an enveloped, dsDNA virus showing many similarities with the
HSV.
• The virus like that of the HSV encodes an enzyme thymidine kinase
and is susceptible to antiviral drugs.
• It produces characteristic blister-like lesions and also has the ability to
cause latent infections of nervous and recurrent disease.
• However, unlike HSV, VZV is transmitted mainly by the respiratory
secretions.

7. Properties of the Virus
• It has no animal reservoir.
• The virus propagates in cultures of human embryonic tissue and
produces typical intranuclear inclusion bodies
• The same virus causes chickenpox and zoster.
• Viral isolates from the vesicles of chickenpox or zoster patients exhibit
no significant genetic variation.
• Inoculation of zoster vesicle fluid into children produces chickenpox.
• Children who have recovered from zoster virus-induced infection are
resistant to varicella

8. Pathogenesis & Pathology
Varicella
• The route of infection is the mucosa of the upper respiratory tract or the
conjunctiva
• Following initial replication in regional lymph nodes, primary viremia
spreads virus and leads to replication in liver and spleen.
• Secondary viremia involving infected mononuclear cells transports virus to
the skin, where the typical rash develops.
• Swelling of epithelial cells, ballooning degeneration, and the accumulation
of tissue fluids result in vesicle formation
• Varicella-zoster virus replication and spread are limited by host humoral and
cellular immune responses.
• Interferon may also be involved.

11. Zoster
• The skin lesions of zoster are histopathologically identical to those of
varicella.
• There is also an acute inflammation of the sensory nerves and ganglia.
• Often only a single ganglion may be involved.
• As a rule, the distribution of lesions in the skin corresponds closely to
the areas of innervation from an individual dorsal root ganglion.
• It is not clear what triggers reactivation of latent varicella-zoster virus
infections in ganglia.

12. Zoster
• It is believed that waning immunity allows viral replication to occur in
a ganglion, causing intense inflammation and pain.
• Virus travels down the nerve to the skin and induces vesicle formation.
• Cell-mediated immunity is probably the most important host defense
in containment of varicella-zoster virus.
• Reactivations are sporadic and recur infrequently.

14. Latent and lytic infection.
• Lytic infection with varicella zoster virus (VZV) starts with attachment, fusion and uncoating of the
virion.
• The virus capsid is then transported to the cell nucleus, where the viral DNA becomes circular.
• The full set of viral proteins, including immediate early (IE), early (E) and late (L) proteins, are
expressed and enter the nucleus.
• New virions then bud in a two-step process. This full cycle of viral replication leads to substantial
cell damage and eventually lysis; the acidic environmental in the endosome damages the virus
particles and reduces their infectiousness.
• The micrograph shows VZV infection of guinea pig enteric neurons showing lytic infection47.
Isolated neurons were cultured invitro and infected with cell-free VZV to induce infection. The
cultures were fixed and immunostained with antibodies against VZV ORF29p (red) and
glycoprotein E (green).
• The neurons were analysed 48 h after infection with cell-associated virus; after lytic infection,
neurons die with 48–72 h. The neuron is filled with cytoplasmic glycoprotein E immunoreactivity
and the immunoreactivity of ORF29p has almost entirely translocated to the nucleus

16. Latent and lytic infection.
• The exact mechanisms of latent infection are unclear but viral replication is
thought to stop at the circular DNA stage and no or only limited protein
expression occurs.
• Furthermore, no viral proteins are found in the nucleus. Latent infection causes
no easily observable changes of cell morphology .The micrograph shows VZV
infection of guinea pig enteric neurons showing latent infection47.
• Isolated neurons were cultured invitro and infected with cell-free VZV to induce
infection.
• The cultures were fixed and immunostained with antibodies against VZV ORF29p
(red) and glycoprotein E (green).
• The neurons were analysed 2weeks after infection with cell-free VZV; after latent
infection, neurons survive invitro for as long as cultures can be maintained. Note
that ORF29p immunoreactivity is confined to the cytoplasm; there is no nuclear
immunoreactivity

18. Varicella: Clinical Features in Unvaccinated
Cases
• Persons with varicella may develop prodrome of fever, malaise,
headache, and abdominal pain 1-2 days before rash
• Rash involves 3 or more successive crops over several days; each crop
usually progresses within less than 24 h from macules to papules,
vesicles, pustules and crusts so that on any part of the body there are
lesions in different stages of development
• Rash usually starts on face and trunk, then spreads to extremities
• Rash usually involves 250-500 lesions that are pruritic
• Lesions are typically crusted 4-7 days after rash onset

19. Varicella: Clinical Features in Vaccinated
Persons (“breakthrough varicella”)
• Breakthrough varicella is defined as infection with wild-type varicella
disease occurring > 42 days after vaccination
• Approximately 15-20% of 1-dose vaccinated persons may develop
varicella if exposed to VZV
• Usually milder clinical presentation than varicella in unvaccinated
cases ;Usually low or no fever ;Develop < 50 lesions ;Experience
shorter duration of illness ;Rash predominantly maculopapular rather
than vesicular
• 25-30% of breakthrough varicella cases are not mild and have clinical
features more similar to varicella in unvaccinated persons

20. Varicella: Complications
• Secondary bacterial infection of skin lesions
• Central nervous system manifestations (meningoencephalitis,
cerebellar ataxia)
• Pneumonia (viral or bacterial)
• Hepatitis, hemorrhagic complications, thrombocytopenia, nephritis
occur less frequently
• Certain groups at increased risk for complications ;Adults
;Immunocompromised persons ; Pregnant Women ;Newborns

21. Clinical Features of Herpes Zoster
Prodrome: headache, photophobia, malaise, fever, abnormal skin
sensations and pain
Rash:
• Unilateral, involving 1-3 adjacent dermatomes
• Thoracic , cervical, ophthalmic involvement most common
• Initially erythematous, maculopapular
• Vesicles form over several days, then crust over
• Full resolution in 2-4 weeks
• Occasionally, rash never develops (zoster sine herpete)

22. Complications of Herpes Zoster
Postherpetic Neuralgia (PHN)
• Pain ≥ 30 days occurs in 18-30% of zoster cases
• Mild to excruciating pain after resolution of rash
• Constant, intermittent, or triggered by trivial stimuli
• May persist weeks, months or occasionally years
• Can disrupt sleep, mood, work, and activities of daily living and lead
to social withdrawal and depression
• Risk factors for PHN include age ≥ 50, severe pain before or after
onset of rash, extensive rash, and trigeminal or ophthalmic
distribution of rash

23. Complications of Herpes Zoster
Herpes Zoster Ophthalmicus
• ~15% of HZ cases
• Can occur when ophthalmic division of trigeminal nerve is involved
• Untreated, 50-70% develop acute ocular complications
• Can lead to chronic ocular complications, reduced vision, even blindness
Neurologic complication
• Myelitis, encephalitis, ventriculitis, meningoencephalitis, cranial nerve palsies, ischemic
stroke syndrome
VZV viremia
• Cutaneous dissemination, pneumonia, hepatitis, disseminated intravascular coagulation
Dermatologic complications
• Secondary infections of rash ; Permanent scarring and changes in pigmentation

24. Varicella: Transmission
• Transmitted person to person by direct contact, inhalation of aerosols from
vesicular fluid of skin lesions of acute varicella or zoster, or aerosolized
respiratory tract secretions
• Average incubation period: 14-16 days after exposure to rash (range: 10-21 days)
• Period of contagiousness: 1-2 days before rash onset until all lesions crusted or
disappear if maculopapular rash (typically 4-7 days)
• Varicella in unvaccinated persons is highly contagious (61- 100% secondary
household attack rate)
• Varicella in 1 dose-vaccinated persons half as contagious as unvaccinated cases –
One study indicated that varicella in 1-dose vacines with < 50 lesions was 1/3 as
contagious as unvaccinated persons although contagiousness in vacines with ≥ 50
lesions was similar to unvaccinated persons

25. VZV Transmission from Zoster
VZV can be transmitted from persons with zoster to persons with no history
of varicella disease or vaccine and cause varicella
• Risk of VZV transmission from zoster is much lower than from varicella
• Transmission is mainly through direct contact with zoster lesions, although
airborne transmission has been reported in healthcare settings
• Localized zoster is only contagious after the rash erupts and until the
lesions crust
• Transmission from localized zoster can be decreased by covering the lesions

26. Immunity
• Varicella and zoster viruses are identical, the two diseases being the
result of differing host responses.
• Previous infection with varicella is believed to confer lifelong
immunity to varicella.
• Antibodies induced by varicella vaccine persist for at least 20 years.
• The development of varicella-zoster virus-specific cell-mediated
immunity is important in recovery from both varicella and zoster.
• Appearance of local interferon may also contribute to recovery.

27. Laboratory Diagnosis
Specimens
• These include skin lesion specimens, respiratory secretions, or organ biopsy.
Direct antigen detection
• Direct fluorescent antibody test employing antibodies against viral membrane antigen
(fluorescent antibody to membrane antigen; FAMA) is used to detect membrane antigen
of the virus directly in the skin scrapings and biopsy specimens.
• The countercurrent immunoelectrophoresis using zoster immune serum is also used to
detect antigen directly in the vesicular fluid.
Isolation of the virus
• Specimens from buccal or skin lesions collected during early stage of the disease are
cultured on human amnion, human fibroblast, and HeLa or Vero cells.
• The VZV produces a CPE similar to that of HSV, but is less conspicuous and takes a long
time to develop

28. Laboratory Diagnosis
Serodiagnosis
• Both indirect fluorescent antibody and enzyme-linked immunosorbent assay
are employed to detect serum antibodies against VZV. These tests are useful
mainly for epidemiological studies rather than for diagnosis of individual
cases.
Molecular Diagnosis
• PCR is a highly sensitive method for detecting of viral genome in skin
scrapings or biopsy specimens.
Other tests Histology
• The Tzanck smear is useful to detect Cowdry type
• A intranuclear inclusions and syncytia in VZV-infected cells.

29. Treatment
• Varicella in normal children is a mild disease and requires no treatment.
• Neonates and immunocompromised patients with severe infections should
be treated.
• Gamma globulin of high varicella-zoster virus antibody titer (varicella-
zoster immune globulin) can be used to prevent the development of the
illness in patients exposed to varicella who are at high risk of developing
severe disease.
• It has no therapeutic value once varicella has started.
• Several antiviral compounds provide effective therapy for varicella,
including acyclovir, valacyclovir, famciclovir, and foscarnet.
• Acyclovir can prevent the development of systemic disease in varicella-
infected immunosuppressed patients and can halt the progression of zoster
in adults.
• Acyclovir does not appear to prevent postherpetic neuralgia.

31. Antiviral treatment in VZV disease
a )Antiviral treatment of varicella
• Is indicated in immunocompromised individuals, neonates, patients with
chronic skin or lung diseases and in individuals aged >13years.
• Patients receive oral acyclovir (ACV), valaciclovir (VACV) or famciclovir (FCV;
not approved by the FDA for use in children) unless they are clinically ill or
at high risk (most immunocompromised patients are considered to be at
high risk, except those who receive long-term, effective immunoglobulin
replacement therapy or those who received only mildly
immunosuppressive drugs a long time ago).
• Ill and high risk patients receive intravenous (IV) ACV or foscarnet if the
infection is caused by ACV-resistant VZV. Intravenous treatment always
needs careful consideration of kidney function.

33. Antiviral treatment in VZV disease
b )Antiviral treatment of zoster
• The treatment of zoster follows a similar algorithm; here
compromised immunity, illness, severe rash, involvement of eyes or
face, and other complications are indications for antiviral treatment.
• In addition to ACV, VACV and FCV, brivudin (BVDU; not approved by
the FDA) might be used.
• Patients who develop varicella or zoster in hospital will generally
receive antiviral therapy as part of an infection control strategy.

34. Prevention & Control
• A live attenuated varicella vaccine is available.
• The vaccine is highly effective at inducing protection from varicella in children
(80–85% effective), but less so in adults (70%).
• The vaccine is about 95% effective in preventing severe disease.
• About 5% of individuals develop a mild vaccine-associated rash 1 month after
immunization.
• Transmission of the vaccine virus is rare but can occur when the vaccinee has a
rash.
• The duration of protective immunity induced by the vaccine is unknown, but is
probably long term.
• Varicella infections can occur in vaccinated persons, but they are usually mild
illnesses.

35. Refrences
• CDC. Prevention of Varicella. MMWR 2007; 56(No. RR-4); Arvin Clin
Microb Rev 1996; Vaccine 5 th Edition
• Chaves J Infect Dis 2008; Arvin Clin Microb Rev 1996; CDC. Prevention
of Varicella. MMWR 2007; 56(No. RR-4)
• Gershon, Anne & Breuer, Judith & I. Cohen, Jeffrey & Cohrs, Randall &
Gershon, Michael & Gilden, Don & Grose, Charles & Hambleton,
Sophie & G. E. Kennedy, Peter & Oxman, Michael & Seward, Jane &
Yamanishi, Koichi. (2015). Varicella zoster virus infection. Nature
Reviews Disease Primers. 1. 15016. 10.1038/nrdp.2015.16.
• Subash Chandra Parija, Text book of Microbiology, 2nd Edition, page
no. 479-481