Varicella Zoster Virus Infections

1. VARICELLA ZOSTER VIRUS
Infections

2. Varicella Zoster Virus Infections
Human alphaherpesvirus 3, usually referred to
as the varicella-zoster virus (VZV), is one of
eight herpesviruses known to infect humans.
Electron micrograph of a Human alphaherpesvirus 3 virus

3. HERPESVIRUS TYPES
 Herpes simplex type I (HHV-1)
 Herpes simplex type II (HHV-2)
 Varicella-zoster virus (VZV/HHV-3)
 Epstein-Barr virus (EBV/HHV-4)
 Cytomegalovirus (CMV/HHV-5)
 Human herpesvirus type 6 (HBLV/HHV-6)
 Human herpesvirus type 7 (HHV-7)
 Kaposi's sarcoma herpesvirus (KSHV/HHV-8)

4.  HSV-1 causes Oral-facial infections, Gingivostomatitis and
pharyngitis
 HSV-2 is a sexually transmitted infection that causes genital
herpes
 Varicella-zoster virus causes Shingles (herpes zoster) and
Chickenpox
 Epstein-Barr virus causes Infectious mononucleosis
 Cytomegalovirus causes CMV mononucleosis and
immunocompromised host infections
 Human herpesvirus type 6 causes childhood illness known as
roseola infantum or sixth disease.
 Human herpesvirus type 7 cause a skin condition in infants
known as exanthema subitum,
 Human herpesvirus type 8 cause Sarcoma Kaposi's
HERPESVIRUS TYPES

6. Varicella Zoster and Chickenpox
Varicella-zoster virus (VZV) causes chickenpox and
herpes zoster (shingles).
Chickenpox follows initial exposure to the virus and
is typically a relatively mild, self-limited childhood
illness with a characteristic exanthem, but can
become disseminated in immunocompromised
children.
Reactivation of the dormant virus results in the
characteristic painful dermatomal rash of herpes
zoster, which is often followed by pain in the
distribution of the rash (postherpetic neuralgia).

7. Varicella Zoster
( Herpes Virus)
DNA Virus
Varicella - Chicken pox.
Contagious Disease Mainly
infects Children
Generalized Vesicular
eruptions on Skin and
Mucous membranes
Severe manifestations in
Adults and Immune
compromised.

8. Shingles (Herpes Zoster )
Rash Limited to
Distribution of Single
Sensory Ganglion
In Adults and immune
compromised
Sporadic

9. Herpes zoster
 Reactivation of latent VZV.
 Uncommon in childhood
 Zoster is not caused by exposure to a patient with
varicella
 The lifetime risk for herpes zoster for individuals
with a history of varicella is 10-20%
 75% of cases occurring after 45 yr of age.
 Herpes zoster is very rare in healthy children

10.  Herpes zoster in children tends to be milder than
disease in adults
 It occurs more frequently & disease is more severe if-
 Children is on immunosuppressive therapy
 HIV infected children.
Herpes zoster

11. Zoster
Associated with
Immune compromised.
Manifest with severe
pain
Vesicles on trunk ,
head, neck
Trigeminal Neuralgia

12. HERPES VARICELLA ZOSTER
Causes chicken pox -fever + characteristic
rash variable incubation period 14-21 days
usually mild in children and more severe in
adults
Complications
secondary infection - uncommon varicella
pneumonia
secondary bacterial pneumonia S aureus &
pneumococci
post-infetious encephalitis
generalized varicella (in immunocompromised
patients)
congenital and neonatal varicella

13. Zoster multiplex
Shingles may appear in multiple dermatomes, both
contiguous and noncontiguous, on either side of the
body Immunocompromised individuals are more
susceptible Terminology depends on the number of
involved dermatomes and on whether the condition
is unilateral or bilateral (eg, zoster duplex
unilateralis refers to the involvement of 2 unilateral
dermatomes) Cases of zoster simultaneously
occurring in 7 noncontiguous dermatomes have been
reported

14. Varicella-Zoster Virus
 Varicella (chickenpox)
 Acute, highly contagious viral disease with worldwide
distribution
 Majority of annual costs*
 80% to 85% of chickenpox : physician visits
 85% to 90% of chickenpox : hospitalization
 Most of which are related to productivity losses by
caregivers
 Mainly a childhood disease
 5 years of age : infection rate 50%
 12 years of age : infection rate 90%

15. Varicella-Zoster Virus
Mostly a mild disorder in childhood
Tends to be more severe in adults
It may be fatal
Neonates
Immunocompromised persons
4% to 13% of individuals who had previous varicella
infection : recurrences of varicella-like rash*
The risk factors
Young age (< 12 months) at first infection
A milder symptoms at first infection

16. Varicella-Zoster Virus
Fatality rates for varicella*
 Adults 30 deaths/100,000 cases
 Infants 7 deaths/100,000 cases
 1-19 yr of age 1-1.5 deaths/ 100,000 cases
In the United States
 Adults account for only 5% of cases but for 55% of the
approximately 100 chickenpox deaths each year
In Canada, from 1987 to 1996
 70% of the 53 reported chickenpox deaths occurred in those >
15 years of age.

17. The pathogen
A double-stranded DNA virus
human herpesvirus-3
subfamily Alphaherpersvirinae
Only one serotype is known
Humans are the only reservoir
VZV enters the host through the nasopharyngeal
mucosa, and almost invariably produces clinical
disease in susceptible individuals
Following varicella, the virus persists in sensory
nerve ganglia, from where it may later be reactivated
to cause herpes zoster (Shingles)

18. Properties of Virus
Like Herpes Virus
Icosahedrons shape ds
DNA
Virons are Spherical and 180–200
nm in diameter. Their lipid envelope
encloses the 100 nm nucleocapsid of
162 hexameric and pentameric
capsomeres arranged in an
icosahedral form. Its DNA is a single,
linear, double-stranded molecule,
125,000 nt long.

19. Progress of events in Varicella Zoster Infection

20. Culturing virus
Grows in Human
embryonic Tissue
Produce inclusion
bodies No difference
in virus In Chicken
pox and zoster
infection

21. Pathogenesis and Pathology
Varicella virus enter
through
URT/Conjunctiva.
Lymph nodes Viremia
Liver and spleen
Secondary viremia
Infects Mononuclear
Cells Rash Vesicle
formation

22. Entry of Varicella Zoster virus

23. Events in Varicella Zoster Infection

24. Pathogenesis
 VZV is transmitted in
 – by airborne spread - oropharyngeal secretion
 – through direct contact - fluid of skin lesions

25. Pathogenesis

26. Pathogenesis

27.  Vesicular rash that usually is dermatomal in
distribution.
 Necrotic changes may be produced in the associated
ganglia.
 The skin lesions of varicella and herpes zoster have
identical histopathology
 Infectious VZV is present in both.
Pathogenesis

28. Clinical Manifestation
 Varicella (Chicken pox)
 Varicella Zoster
 Breakthrough varicella
 Progressive varicella
 Neonatal varicella
 Congenital varicella syndrome

29. Varicella(Chickenpox)
Incubation period is 10 -21 days.
Subclinical varicella is rare
Prodromal symptoms
 Fever
 Malaise
 Anorexia
 Headache
 Mild abdominal pain
Lesions at all stages Macules,
Papules, Vesicles, Crusts.
May last 5 days, Hundreds of
eruptions.
Rash Trunk –Face –Limbs – Buccal
and Pharyngeal mucosa

30. Skin lesions of chickenpox

31. Varicella lesions
 Appear first on the scalp, face, or trunk.
 The initial exanthem consists of intensely pruritic
 Erythematous macules
 Papular stage
 Fluid-filled vesicles.
 Clouding and umbilication of the lesions begin in 24-48 hr.
Varicella(Chickenpox)

32. Skin lesions showing different stages

33. Chicken pox lesions in the buccal cavity

34. Pain and hyperesthesia

35. Shingles
Age (most common in
people over 60) Stress
Weakened immune system
(for example, people with
HIV/AIDS, or those
taking drugs to suppress
the immune system due
to autoimmune diseases
or organ transplants)
Having had chickenpox
before age 1

36. Skin Lesions
Inflammation of
Sensory Nerves and
Ganglia Single
Ganglion Dorsal root
Ganglion
Shingles

37. Herpes Zoster involving a Nerve segment

38. Ramsay-Hunt syndrome
This syndrome occurs
when the geniculate
ganglion is involved. The
clinical presentation
includes the following:
 A peripheral facial palsy
Pain in the ear and face
Vesicles in the external ear
canal (not always present)
 Additional auditory and
vestibular symptoms in
some case

39. Keratitis (herpes ophthalmicus)
Caused by reactivation of VZV
infection in the ophthalmic
division of the trigeminal nerve.
The presentation may include
conjunctivitis or corneal ulcers
Complications include blindness
Vesicles do not have to be present
Rarely, the virus migrates along
the intracranial branches of the
trigeminal nerve, causing
thrombotic cerebrovasculopathy
with severe headache and
hemiplegia

40. Varicella in Vaccinated Individuals
(“Breakthrough Varicella”)
One dose of varicella vaccine is >97% effective in
preventing severe varicella
85% effective in preventing all disease after exposure to
wild-type VZV.
Breakthrough disease is varicella that occurs in a person
vaccinated >42 days before rash onset and is caused by
wild-type VZV
Rash occurring < 14 days after vaccination was most
commonly wild-type VZV
Rash occurring 14-42 days after vaccination was due to
either
 – Wild-type VZV-------- breakthrough varicella
 – Vaccine strains---------vaccine-associated rash

41. Varicella in Vaccinated Individuals
(“Breakthrough Varicella”)

42. Progressive Varicella
Progressive varicella, is a severe complication of
primary VZV infection.
Continued new vesicular lesion development
Visceral organ involvement
Coagulopathy
Severe hemorrhage
Severe abdominal pain

43. Neonatal Varicella
Infants whose mothers demonstrate varicella in the
period from 5 days prior to delivery to 2 days
afterward are at high risk for severe varicella.

44.  The infant acquires the infection transplacentally
 The infant's rash usually occurs toward the end of
the 1st week to the early part of the 2nd week of life
 Maternal immunoglobulin G (IgG) is able to cross
the placenta if delivery occurs after 30 wk of
gestation
 Newborns whose mothers demonstrate varicella 5
days before to 2 days after delivery should receive 1
vial of VariZIG as soon as possible.
Neonatal Varicella

45. Neonatal Varicella

46. Congenital Varicella Syndrome
Risk of infection (No disease)
 Early part of pregnency- 25%
Risk of CVS
 Before 13 wks of gestation – 0.4%
 In between 13 – 20 wks - 2%

47. Congenital Varicella Syndrome

48. Congenital Varicella Syndrome

49. Diagnosis of varicella
Laboratory evaluation has not been considered
necessary
Leukopenia
Relative and absolute lymphocytosis.
liver function tests are mildly elevated
CSF in CNS complication
 Mild lymphocytic pleocytosis
 Moderate increase in protein content

50. Rapid laboratory diagnosis
 Direct fluorescence assay
 Rapid culture with specific immunofluorescence staining
 PCR amplification testing
 Multinucleated giant cells can be detected with nonspecific
stains Tzanck smear
VZV IgG antibodies:- Rise > 4 fold
Testing for VZV IgM antibodies is not useful
Diagnosis of varicella

51. Diagnosis of varicella
Laboratory Diagnosis.
•Smears --Scrapings from
Lesions
•Demonstration of Multi
nucleated giant cells
•Tzanck smears
•DNA Demonstration
•Cell cultures
•Fluorescent –antibody
•ELISA
•PCR

52. Treatment
Specific treatment is
indicated mainly in
Immunodeficient and
elderly subjects and also in
complicated with Varicella
pneumonia
,encephalitis,and
disseminated zoster
Acyclovir and Famiciclovir.

53. Acyclovir therapy is not recommended routinely for
treatment of uncomplicated varicella in the
otherwise healthy child
 The marginal benefit
 The cost of the drug
 Low risk for complications of varicella.
Oral acyclovir in children >12 mo of age with
 Chronic cutaneous or
 Pulmonary disorders
 Pt. Is on corticosteroid therapy
 Individuals receiving long-term salicylate therapy
Nonpregnant individuals > 13 years of age
Treatment

54. Intravenous Acyclovir therapy
Varicella with severe disease
 Pneumonia
 Severe hepatitis
 Thrombocytopenia
 Encephalitis
Varicella in immunocompromised patients
Dose:- IV acyclovir (500 mg/m2 every 8 hr IV) continued
for 7–10 days
Other molecules
 Famciclovir
 Valacyclovir
Acyclovir-resistant VZV:- intravenous foscarnet
Treatment

55. Varicella zoster Immune globulins
Varicella zoster immune globulin (VariZIG) is indicated for
administration to highrisk individuals within 10 days
(ideally within 4 days) of chickenpox (VZV) exposure.
High- risk groups include the following:
 Immunocompromised children and adults
 New-borns of mothers with varicella shortly before or
after delivery
 Premature infants
 Infants less than younger than 1 year of age
 Adults without evidence of immunity
 Pregnant women
Treatment

56. Epidemiology
Communicable
Disease World wide
prevalence Common
in < 10 year olds.
Zoster in Adults
Droplet spread is
common

57. Prevention of Chickenpox

58. Shankar Lal Jat (Ma1501o)