Chickenpox

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

•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)
HUMAN HERPESVIRUS TYPES

• 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

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

Human Herpesviruses
Chickenpox
also known as
Varicella,

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.
Human herpesvirusis
DEFINITION

Chickenpox 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

Electron micrograph of Varivella Zoster virus

A clinical association between varicella and herpes zoster has been
recognized for nearly 100 years.
Early in the twentieth century, similarities in the histopathologic
features of skin lesions resulting from varicella and herpes zoster
were demonstrated.
Viral isolates from patients with chickenpox and herpes zoster
produced similar alterations in tissue culture.
These results suggested that the viruses
were biologically similar.

Restriction endonuclease analyses of viral DNA
from a patient with chickenpox who subsequently
developed herpes zoster verified
the molecular identity
of the two viruses responsible for these different
clinical presentations.

• Chickenpox is an airborne disease which
spreads easily through the coughs and sneezes
of an infected person.
• It may be spread from one to two days before
the rash appears until all lesions have crusted
over.
• It may also spread through contact with the
blisters.

After initial inhalation of contaminated respiratory
droplets, the virus infects the conjunctivae or the mucosae
of the upper respiratory tract.
Viral proliferation occurs in regional lymph nodes of the
upper respiratory tract 2-4 days after initial infection; this
is followed by primary viremia on postinfection days 4-6.
A second round of viral replication occurs in the body's
internal organs, most notably the liver and the spleen,
followed by a secondary viremia 14-16 days post infection.
This secondary viremia is characterized by diffuse viral
invasion of capillary endothelial cells and the epidermis.
Pathophysiology

infection may involve localized blood vessels of the skin, resulting
in necrosis and epidermal hemorrhage. With the evolution of
disease, the vesicular fluid becomes cloudy because of the
recruitment of polymorphonuclear leukocytes and the presence of
degenerated cells and fibrin.
Ultimately, the vesicles either rupture and release their fluid (which
includes infectious virus) or are gradually reabsorbed.
During chickenpox, (Presumably), the virus infects dorsal root
ganglia where it remains latent and establishes lifelong residence
(latent infection) until reactivated.

Chickenpox occurs in all parts of the world. As of 2013 140
million cases of chickenpox occurred.
Before routine immunization the number of cases occurring each
year was similar to the number of people born.
Since immunization the number of infections in the United States
has decreased nearly 90%. In 2013 chickenpox resulted in 7,000
deaths globally.
Death occurs in about 1 per 60,000 cases. Chickenpox was not
separated from smallpox until the late 19th century.
The first documented use of the term chicken pox was in 1658.
Various explanations have been suggested for the use of "chicken"
in the name, one being the relative mildness of the disease.

Humans are the only known reservoir for VZV.
Chickenpox is highly contagious, with an attack rate of at least 90%
among susceptible (seronegative) individuals.
Persons of both sexes and all races are infected equally.
Chickenpox becomes epidemic among susceptible individuals
during seasonal peaks—namely, late winter and early spring in the
temperate zone.
Historically, children 5–9 years old are most commonly
affected and account for 50% of all cases.
VZV vaccination during the second year of life has dramatically
changed the epidemiology of infection, has coursed significant
decrease in the annualized incidence of chickenpox.

Clinical Manifestations
of Chickenpox

• Rash,
• low-grade fever,
• malaise.
The Main symptoms of chickenpox

• Incubation period (Phase)
• Prodromal period (Phase)
• Exanthem period (Phase)
• Reconvalencence period (Phase)
The Disease has 4 Phases

The incubation period of chickenpox ranges
from 10–21 days but is usually 14–17 days.
During these period patient is asymptomatic

A few patients develop a prodrome 1–2 days
before onset of the exanthem.
The prodromal symptoms in adolescents and
adults are nausea, loss of appetite, aching muscles,
and headache.
Prodromal period
Pre eruptive stage

In many children the illness is not usually
preceded by prodromal symptoms, and the first
sign is the rash or the spots in the oral cavity.
Prodromal period
Pre eruptive stage
Onset of symptoms usually is sudden, with mild or moderate fever
Malaise
This stage is lasts for about 24 hours in children and 2-3-days in adult

eruptive stage
Exanthem period (Phase)
The skin lesions—the hallmark of the infection
This stage is characterized by the
• Rapid evolution
• Pleomorfizm
• Fever

The rash begins as multiple small red bumps (papules) that look like
pimples or insect bites. These lesions are small and have an
erythematous (erythematous macules) base with a diameter of
5–10 mm.
After another 12 to 24 hours the spots typically become itchy, fluid-
filled bumps called vesicles, which continue to appear in crops
for the next 2 to 5 days.
The rash is very itchy, and cool baths or calamine lotion may help to
manage the itching.

The rash first appear (Within a few hours or days) on the scalp, neck ,
face or upper half of the trunk and very rapidly (over hours) spread to
involve other areas of the body
In any area of skin, lesions of a variety of stages can be
seen.
These blisters can spread to cover much of the skin, and in some cases
also may be found inside the mouth, nose, ears, vagina, or
rectum.
Successive crops appear over a 2- to 4-day period.

After the chickenpox red spot appears, it usually takes
about 1 or 2 days for the spot to go through all its stages.
This includes blistering, bursting, drying and crusting
over.
New red spots will appear every day for up to 5-7 days.
It usually takes about 10 days after the first symptoms
before all blisters have crusted over. This is when the person
with chickenpox can return to day care, school, or work.

A hallmark of chickenpox is that all stages (red bumps,
blisters (vesicles), and scabs) can appear on the body at the
same time.

Characteristic for varicella is presence of lesions
in different stages of development at the same time

Some individuals have very few lesions, while others have
as many as 2000.
Younger children tend to have fewer vesicles than older
individuals.
Disease severity varies from person to person, but older
patients tend to have more severe diseases.
Secondary and tertiary cases within families are associated
with a relatively large number of vesicles.
Disease severity

In the immunocompetent patient, chickenpox is usually a
benign illness associated with tiredness, weakness and with
body temperatures of 37.8°–39.4°C (100°–103°F) of 3–5
days’ duration.
Immunocompromised patients —both children and adults,
particularly those with leukemia—have lesions (often with a
hemorrhagic base) that are more numerous and take longer to
heal than those of immunocompetent patients.
Immunocompromised individuals are also at greater risk for
visceral complications, which occur in 30–50% of cases and
are fatal 15% of the time in the absence of antiviral therapy.
Disease severity

Patients are infectious ~ 48 h before
onset of the vesicular rash, during the
period of vesicle formation (which
generally lasts 4–5 days), and until all
vesicles are crusted.
When is patient infectious?
(VZV is communicable….)

The most common infectious complication of varicella is
secondary bacterial superinfection of the skin, which is
usually caused by Streptococcus pyogenes or
Staphylococcus including strains that are methicillin-
resistant..
Skin infection results from excoriation of lesions after
scratching.
Gram’s staining of skin lesions should help clarify the
etiology of unusually erythematous and pustulated lesions.
Bacterial superinfection

The most common extracutaneous site of
involvement in children is the CNS.
The syndrome of acute cerebellar ataxia and
meningeal
inflammation generally appears ~21 days after
onset of the rash and rarely develops in the pre
eruptive phase.
The cerebrospinal fluid (CSF) contains lymphocytes
and elevated levels of protein.
CNS complications

CNS involvement is a benign complication of VZV
infection in children and generally does not require
hospitalization.
Aseptic meningitis, encephalitis, transverse
myelitis, and Guillain-Barré syndrome can also
occur.
Encephalitis is reported in 0.1–0.2% of children
CNS complications

Varicella pneumonia, the most serious complication following
chickenpox, develops more commonly in adults (up to 20%
of cases) than in children and is particularly severe in pregnant
women.
Pneumonia due to VZV usually has its onset 3–5 days into
the illness and is associated with tachypnea, cough, dyspnea, and
fever. Cyanosis, pleuritic chest pain, and hemoptysis are common.
Roentgenographic evidence of disease consists of nodular infiltrates
and interstitial pneumonitis.
Resolution of pneumonitis parallels improvement of the skin rash;
however, patients may have persistent fever and compromised
pulmonary function for weeks.
Varicella pneumonia

Other complications of chickenpox include: myocarditis,
nephritis, arthritis, bleeding diatheses, acute
glomerulonephritis, and hepatitis.
Hepatic involvement, is usually asymptomatic, is common
in chickenpox and is generally characterized by elevated
levels of liver enzymes, particularly aspartate and alanine
aminotransferases.
Other complications

Perinatal varicella is associated with a high mortality rate when
maternal disease develops:
within 5 days before delivery or within 48 h thereafter.
Because the newborn does not receive protective
transplacental antibodies and has an immature immune system,
the illness may be unusually severe.
The reported mortality rate is as high as 30% in this group.
Congenital varicella , with clinical manifestations of limb
hypoplasia, cicatricial skin lesions, and microcephaly at birth, is
extremely uncommon.
Perinatal varicella

The diagnosis of chickenpox is not
difficult.
The characteristic rash and a
history of recent exposure should
lead to a prompt diagnosis.

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.

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 it is
very expensive

Medical management of chickenpox in the immunologically
normal host is directed toward the prevention of avoidable
complications.
Obviously, good hygiene includes daily bathing and soaks.
Secondary bacterial infection of the skin can be avoided by
scrupulous skin care, particularly with close cropping of fingernails.
Pruritus can be decreased with topical dressings or the
administration of antipruritic drugs. Water baths and wet compresses
are better than drying lotions for the relief of itching.

Administration of aspirin to children with
chickenpox should be avoided because of the
association of aspirin derivatives with the
development of Reye’s syndrome.

Acyclovir (800 mg by mouth five times daily),
or
valacyclovir (1 g three times daily),
or
Famciclovir (250 mg three times daily)
Treatment duration
for 5–7 days is recommended
Antiviral drugs
for adolescents and adults with chickenpox
Antiviral therapy can be helpful if started within
24-48 h of symptoms

Acyclovir (20 mg/kg every 6 h)
Antiviral drugs
For children <12 years of age acyclovir is recommended.

In severely immunocompromised hosts (e.g., transplant recipients,
patients with lymphoproliferative malignancies), chickenpox
(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.

• Passive Immunization by specific
immunoglobulin
• Active Immunization by Vaccine
• Antiviral drugs
Prophylaxis

First
A live attenuated varicella vaccine.
Is recommended for all children >1 year of age (up to 12 years of age)
who have not had chickenpox and for adults known to be seronegative
for VZV.
Two doses are recommended for all children: the first at 12–15
months of age and the second at ~4–6 years of age.
VZV seronegative persons >13 years of age should receive two doses
of vaccine at least 1 month apart. The vaccine is both safe and
efficacious.
Three methods are used for the prevention of VZV infections.

A second approach
is to administer varicella-zoster immune globulin (VZIG)
to individuals who are susceptible, are at high risk for
developing complications of varicella, and have had a
significant exposure.
This product should be given within 96 h (preferably
within 72 h) of the exposure.

third approach
Lastly, antiviral therapy can be given as prophylaxis to individuals
at high risk who are ineligible for vaccine or who are beyond the
96-h window after direct contact.
While the initial studies have used acyclovir, similar benefit can be
anticipated with either valacyclovir or famciclovir.
Therapy is instituted 7 days after intense exposure.
At this time, the host is midway into the incubation period. This
approach significantly decreases disease severity, if not totally
preventing disease.

Chickenpox

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