Varicella-zoster virus infection (VZV/HHV-3)

1. Human Herpesviruses
Varicella-zoster virus infection
(VZV/HHV-3)
Herpes Zoster
Associated Professor
Lali Sharvadze, MD, PhD
Infectious Diseases, AIDS & Clinical Immunology Research Center

2. •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)
HERPESVIRUS TYPES

3. • 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

4. Human Herpesviruses
Varicella-zoster virus causes
two diseases
Shingles (herpes zoster)
and
Chickenpox

5. Human Herpesviruses
Herpes Zoster
also known
as
Zona
or
Shingles

6. Zoster comes from Greek zōstēr, meaning
"belt" or "girdle", after the characteristic
belt-like dermatomal rash.
The common name for the disease, shingles,
derives from the Latin cingulus, a variant
of Latin cingulum meaning "girdle".
Etymology (origin)

7. Varicella-zoster virus (VZV) causes two distinct clinical
diseases:
varicella (chickenpox) and herpes zoster (shingles).
Chickenpox, a ubiquitous and extremely contagious infection, is
usually a benign illness of childhood characterized by an
exanthematous vesicular rash.
Herpes Zoster: With reactivation of latent VZV (which is
most common after the sixth decade of life),
Herpes zoster presents as a dermatomal
vesicular rash, usually associated with severe
pain.
Human herpesvirusisDEFINITION

8. ETIOLOGY

9. Herpes Zoster is caused by Varicella Zoster Virus
VZV is a member of the family Herpesviridae, sharing with other
members such structural characteristics as a lipid envelope
surrounding a nucleocapsid with icosahedral symmetry,
a total diameter of ~180–200 nm, and centrally
located double-stranded DNA that is ~125,000 bp in length.
The family of Herpesviridae.
The genus of varicellovirus
Etiology

10. Electron micrograph of Varivella Zoster virus

11. Epidemiology

12. Herpes zoster (shingles) is a sporadic disease that results
from reactivation of latent VZV infection.
Herpes zoster occurs at all ages, but its incidence is highest
(5–10 cases per 1000 persons) among individuals in the
sixth decade of life and beyond.
Data suggest that 1.2 million cases occur annually in the
United States.

13. The incidence rate of shingles ranges from 1.2 to 3.4 per
1,000 person/years among younger healthy individuals,
increasing to 3.9–11.8 per 1,000 person/years among those
older than 65 years,
The incidence rates worldwide are similar.
This relationship with age has been demonstrated in many
countries, and is attributed to the fact that cellular immunity
declines as people grow older.

14. Recurrent herpes zoster is very rare except in
immunocompromised hosts, especially those with
AIDS.
Shingles has no relationship to season and does not occur in
epidemics.
There is, however, a strong relationship with increasing age

15. Pathogenesis

16. Transmission of the virus occurs readily by the respiratory route
Transmission occurs mainly through respiratory droplets which
contains virus.
Direct person to person contact with lesions also spread the virus.
During chickenpox, (Presumably) , the virus infects dorsal root ganglia
where it remains latent and establishes lifelong residence
(latent infection) until reactivated.
Consequently, the dorsal root and cranial sensory ganglia of everyone
who has had Chickenpox are latently infected with VZV. They contain
genomic NDA of VZV, but not infectious virus.
Pathogenesis

17. The latent VZV eventually reactivates. The reactivated virus multiplies
and spreads within the ganglion, infecting many additional neurons
and supporting cells-a process that causes intense inflammation.
The virus than travel from the sensory ganglion back down the nerve to
the skin, where it produces the characteristic rash of herpes zoster.
The mechanism of reactivation of the virus is unknown
;
Pathogenesis

18. ViralViral
reactivationreactivation
Vesicular Rash
Pathogenesis
ViralViral
latencylatency
mononuclear cells
skin

19. Unless the immune system is compromised, it
suppresses reactivation of the virus and
prevents shingles outbreaks.
Why this suppression sometimes fails is poorly
understood, but shingles is more likely to
occur in people whose immune systems are
impaired due to aging, immunosuppressive
therapy, psychological stress, or other factors

20. 1) A cluster of small bumps 2) turns into blisters
3) The blisters fill with lymph, break open 4) crust over

21. Clinical Manifestations
of Herpes Zoster

22. Patients with herpes zoster can transmit
infection to seronegative individuals,
with consequent chickenpox.
Someone can not catch shingles, However
someone catch chickenpox through direct
contact with someone who has shingles

23. • Unilateral vesicular dermatomal eruption, (rash),
• Severe pain
The Main symptoms of Herpes Zoster

24. In the prodromal stage of herpes zoster, the
diagnosis can be exceedingly difficult and may
be made only after lesions have appeared or by
retrospective serologic assessment.
The earliest symptoms of shingles, which
include Headache, fever, and malaise are
nonspecific, and may result in an incorrect
diagnosis.

25. These symptoms are commonly followed by sensations of
burning pain, itching, hyperesthesia (oversensitivity),
or parenthesis ("pins and needles": tingling, pricking, or
numbness).
Pain can be mild to extreme in the affected dermatome,
with sensations that are often described as stinging,
tingling, aching, numbing or throbbing,
and can be intersperses with quick stabs of agonizing
pain.
Shingles in children is often painless, but people are more
likely to get shingles as they age, and the disease tends to
be more severe.

26. The pain and rash most commonly occurs on the torso, but
can appear on the face, eyes or other parts of the body.
At first the rash appears similar to the first appearance of
hives (urticaria); however, unlike hives, shingles
causes skin changes limited to a dermatome, normally
resulting in a stripe or belt-like pattern that is limited to
one side of the body and does not cross the midline.
Localization of the rash

27. The onset of disease is heralded by pain within
the dermatome, which may precede lesions by
48–72 h;
an erythematous maculopapular rash evolves
rapidly into vesicular lesions.
Sometimes pre eruptive period and pain lasts
as long as three weeks, and is followed by
the appearance of the characteristic skin
rash.

28. Later the rash becomes vesicular, forming
small blisters filled with a serous exudates, as
the fever and general malaise continue.
The painful vesicles eventually become cloudy
or darkened as they fill with blood, and crust
over within seven to ten days; usually the
crusts fall off and the skin heals, but
sometimes, after severe blistering, scarring and
discolored skin remain.
Development of the shingles rash

29. Day 2
Day 1
Day 5
Day 6
Development of the shingles rash

30. In the normal host, these lesions may remain
few in number and continue to form for only 3–5
days.
The total duration of disease is generally 7–10
days;
However, it may take as long as 2–4 weeks for
the skin to return to normal.

31. Zoster sine herpete ("zoster without herpes")
describes a person who has all of the symptoms
of shingles except this characteristic rash.
In a few patients, characteristic localization of pain
to a dermatome with serologic evidence of herpes
zoster has been reported in the absence of skin
lesions, an entity known as
Zoster sine herpetica

32. Herpes zoster is characterized by a unilateral
vesicular dermatomal eruption, often associated
with severe pain.
The dermatomes from T3 to L3 are
most frequently involved.

35. The factors responsible for the
reactivation of VZV are not
known.
In children, reactivation is usually
benign; in adults, it can be
debilitating because of severe pain.

36. When branches of the
trigeminal nerve are
involved, lesions may appear
on the face, in the mouth, in
the eye, or on the tongue.

37. The trigeminal nerve is the most commonly involved nerve.
The ophthalmic division of the trigeminal nerve is most commonly
involved branch.
When the virus is reactivated in this nerve branch it is termed Zoster
Ophtalmicus. The skin of the forehead, upper eyelid and orbit of the
eye may be involved.
Zoster ophthalmicus occurs in approximately 10% to 25% of cases.
In some people, symptoms may include conjunctivitis, keratitis,
uveitis and optic nervepalsies that can sometimes cause chronic
ocular inflammation, loss of vision, and debilitating pain.

38. Trigeminal shingles with uveitis and keratitis

39. If the ophthalmic branch of the trigeminal nerve is
involved, zoster ophthalmicus results.

40. In the Ramsay Hunt syndrome (herpes zoster
oticus), pain and vesicles appear in the external
auditory canal, and patients lose their sense of
taste in the anterior two-thirds of the tongue
while developing ipsilateral facial palsy.
The geniculate ganglion of the sensory branch of
the facial nerve is involved.

41. Complications

42. Shingles oticus, also known as Ramsay Hunt syndrome type II
involves the ear.
It is thought to result from the virus spreading from the
facial nerve to the vestibulocochlear nerve.
Symptoms include hearing loss and vertigo (rotational
dizziness).
Ramsay Hunt syndrome

43. In both normal and immunocompromised hosts, the
most debilitating complication of herpes zoster is pain
associated with acute neuritis and postherpetic
neuralgia.
Postherpetic neuralgia is uncommon in young
individuals;
However, at least 50% of zoster patients over age 50
report some degree of pain in the involved dermatome
months after the resolution of cutaneous disease.
Changes in sensation in the dermatome, resulting in
either hypo- or hyperesthesia, are common.
Postherpetic neuralgia

44. CNS involvement may follow localized herpes zoster.
Many patients without signs of meningeal irritation have
CSF pleocytosis and moderately elevated levels of CSF
protein.
Symptomatic meningoencephalitis is characterized by
headache, fever, photophobia, meningitis, and vomiting.
A rare manifestation of CNS involvement
is granulomatous angiitis with contralateral hemiplegia,
which can be diagnosed by cerebral arteriography. Other
neurologic manifestations
include transverse myelitis with or without motor
paralysis.
CNS complications

45. herpes zoster is more severe in immunocompromised
than immunocompetent individuals. Lesions continue to
form for >1 week, and scabbing is not complete in most
cases until 3 weeks into the illness. Patients with Hodgkin’s
disease and non- Hodgkin’s lymphoma are at greatest risk
for progressive herpes zoster.
Cutaneous dissemination develops in ~40% of these
patients. Among patients with cutaneous dissemination, the
risk of pneumonitis, meningoencephalitis, hepatitis, and
other serious complications is increased by 5–10%.
However, even in immunocompromised
patients, disseminated zoster is rarely fatal.

46. Herpes Zoster in HIV/AIDS patients

47. Recipients of hematopoietic stem cell transplants are at
particularly high risk of VZV infection. Of all cases of
posttransplantation.
VZV infection, 30% occur within 1 year (50% of these
within 9 months); 45% of the patients involved have
cutaneous or visceral dissemination. The mortality rate in
this situation is 10%.
Postherpetic neuralgia, scarring, and bacterial
superinfection are especially common in VZV infections
occurring within 9 months of transplantation.
Among infected patients, concomitant graft versus-
host disease increases the chance of dissemination and/
or death.

48. A case of shingles that demonstrates the typical dermatomal distribution, in
this case C8/T1

49. Diagnoses

50. The diagnosis of herpes Zoster is not
difficult.
The characteristic dermatomal
localization of the vesicular rash and
pain should lead to a prompt
diagnosis.
Clinical symptoms

51. When the rash is absent (early or
late in the disease, or in the case
of zoster sine herpete), shingles
can be difficult to diagnose.
Apart from the rash, most
symptoms can occur also in other
conditions.

52. Serology is the most common method of
laboratory diagnosis.
The detection of VZV –specific IgM is considered
diagnostic of acute infection.
Also, a fourfold or greater increase in VZV specific
IgG antibody levels between acute- and
convalescent-phase serum specimens.

53. Chickenpox also can be diagnosed by
detection of
VZV DNA
by reverse-transcriptase polymerase chain
reaction (RT-PCR) from clinical specimens
Isolation of VZV in culture also is possible but
very expensive

54. Differential Diagnoses

55. • Herpes Simplex
• Dermatitis Herpetiformis
• Impetigo
• Contact dermatitis
• Candidiasis
• certain drugs reaction
• insect bites.
Shingles can be confused with

56. Treatment

57. Patients with herpes zoster benefit from oral
antiviral therapy:
Antiviral therapy accelerates healing of lesions
and resolution of zoster-associated pain
The following antiviral drugs are used:
acyclovir,
valacyclovir,
famciclovir.

58. Treatment regimens:
Acyclovir
is administered at a dosage of
800 mg five times daily for 7–10 days.
Famciclovir
is administered at a dosage of
500 mg three times daily for 7 days
Valacyclovir
is administered at a dosage of
1 g by mouth three times daily for 5–7 days.
Antiviral therapy should be started as soon as possible (within
24-48 h of symptoms)

59. In severely immunocompromised hosts (e.g., transplant recipients,
patients with lymphoproliferative malignancies), Herpes Zoster
(including disseminated disease) should be treated, with IV
acyclovir, which reduces the occurrence of visceral complications.
The dose is 10 mg/kg every 8 h for 7 days.
For low-risk immunocompromised hosts, oral therapy with
valacyclovir or famciclovir appears beneficial.
If medically feasible, it is desirable to decrease
immunosuppressive treatment concomitant with the
administration of IV acyclovir.
For immunocompromised hosts:

60. Persons with zoster ophthalmicus should be referred
immediately to an ophthalmologist.
Therapy for this condition consists of the administration of
analgesics for severe pain and the use of atropine.
Acyclovir, valacyclovir, and famciclovir all accelerate
healing.
Decisions about the use of glucocorticoids
should be made by the ophthalmologist.
The management of acute neuritis and/or postherpetic
neuralgia
Treatment of zoster ophthalmicus

61. The management of postherpetic neuralgia is particularly difficult.
along with routine analgesic agents can be given the narcotic
derivatives, drugs such as:
• gabapentin,
• pregabalin,
• amitriptyline
• hydrochloride,
• lidocaine (patches),
• fluphenazine hydrochloride
These drugs are reportedly beneficial for pain relief.
Treatment of postherpetic neuralgia

62. Glucocorticoid therapy can accelerate quality-of-life improvements
including a return to usual activity.
The dose of prednisone:
Orally:
60 mg/d on days 1–7, 30 mg/d on days 8–14, and
15 mg/d on days 15–21.
This regimen is appropriate only for relatively healthy elderly persons
with moderate or severe pain at presentation. Patients with
osteoporosis, diabetes mellitus glycosuria, or hypertension may not be
appropriate candidates.
Glucocorticoids should not be used without concomitant antiviral
therapy.
Treatment of postherpetic neuralgia

63. CNS involvement may follow localized herpes zoster.
Many patients without signs of meningeal irritation have CSF
pleocytosis and moderately elevated levels of CSF protein.
Symptomatic meningoencephalitis is characterized by headache,
fever, photophobia, meningitis, and vomiting.
A rare manifestation of CNS involvement is granulomatous angiitis
with contralateral hemiplegia, which can be diagnosed by cerebral
arteriography.
Other neurologic manifestations include transverse myelitis with or
without motor paralysis.
CNS involvement

64. Prevention
of
Herpes Zoster

65. Active Immunization by Vaccine
Prophylaxis

66. Zoster vaccine (trade name Zostavax) is used fpr
prevention of Herpes Zoster.
Zostavax is a live vaccine developed by Merck &
Co.
The zoster vaccine is, essentially, a larger-than-
normal dose of the chickenpox vaccine (with 18
times the viral content).

67. In individuals >60 years of age, a VZV vaccine decreased
the incidence of shingles by 51%, the burden of
illness by 61%, and the incidence of postherpetic
neuralgia by 66%.
The Advisory Committee on Immunization Practices has
therefore recommended that persons in this age group be
offered this vaccine in order to reduce the frequency of
shingles and the severity of postherpetic neuralgia.
A second approach is to administer varicella

68. THENKS
FOR ATTENTION