Varicella is an acute, contagious disease caused by varicella zoster
virus (VZV). The recurrent infection (herpes zoster, also known as
shingles) has been recognized since ancient times. Primary varicella
infection (chickenpox) was not reliably distinguished from smallpox
until the end of the 19th century. In 1875, Steiner demonstrated
that chickenpox was caused by an infectious agent by inoculating
volunteers with the vesicular fluid from a patient with acute varicella.
Clinical observations of the relationship between varicella and
herpes zoster were made in 1888 by von Bokay, when susceptible
children acquired varicella after contact with herpes zoster.VZV was
isolated from vesicular fluid of both chickenpox and zoster lesions in
cell culture by Thomas Weller in 1954. Subsequent laboratory studies
of the virus led to the development of a live attenuated varicella
vaccine in Japan in the 1970s. The vaccine was licensed for use in
healthy children and adults in the United States in March 1995.

VARICELLA ZOSTER VIRUS (VZV)
VZV is a DNA virus, and is a member of the herpes virus group.
Like other herpes viruses, VZV has the capacity to persist in the
body after the primary (first) infection as a latent infection.VZV
persists in sensory nerve ganglia. Primary infection with VZV results
in chickenpox. Herpes zoster (shingles) is the result of recurrent
infection. The virus is believed to have a short survival time outside
the infected host.

PATHOGENESIS
VZV enters through the respiratory tract and conjunctiva. The virus
is believed to replicate at the site of entry in the nasopharynx and in
regional lymph nodes. A primary viremia occurs 4-6 days after
infection, which disseminates the virus to other organs, such as the
liver, spleen, and sensory ganglia. Further replication occurs in the
viscera, followed by a secondary viremia, with viral infection of the
skin. Virus can be cultured from mononuclear cells of an infected
person from 5 days before to 1 or 2 days following the appearance
of the rash.

CLINICAL FEATURES
The incubation period is from 14 to 16 days from exposure, with
a range of 10 to 21 days. The incubation period may be prolonged
in immunocompromised patients and those who have received varicella
zoster immune globulin (VZIG). The incubation period may
be up to 28 days after VZIG.

PRIMARY INFECTION (CHICKENPOX)
A mild prodrome may precede the onset of a rash. Adults may
have 1 to 2 days of fever and malaise prior to rash onset, but in children
the rash is often the first sign of disease.
The rash is generalized, pruritic, and rapidly progresses from macules
to papules to vesicular lesions before crusting. The rash usually
appears first on the scalp, followed by the trunk, and then the
extremities, with the highest concentration of lesions on the trunk
(centripetal distribution). Lesions also can occur on mucous membranes
of the oropharynx, respiratory tract, vagina, conjunctiva, and
the cornea. Lesions are usually 1 to 4 mm in diameter. The vesicles
are superficial and delicate, and contain clear fluid on an erythematous
base.Vesicles may rupture or become purulent before they dry
and crust. Successive crops appear over several days, with lesions
present in several stages of development. For example, macular
lesions may be observed in the same area of skin as mature vesicles.
Healthy children usually have 200-500 lesions in 2 to 4 successive
crops.
The clinical course in healthy children is generally mild, with
malaise, pruritus (itching), and fever up to 102 degrees F for 2 to 3 days.
Adults may have more severe disease and have a higher incidence of
complications. Respiratory and gastrointestinal symptoms are
absent. Children with lymphoma and leukemia may develop a
severe progressive form of varicella characterized by high fever,
extensive vesicular eruption, and high complication rates. Children
infected with human immunodeficiency virus may also have severe,
prolonged illness.
Recovery from primary varicella infection usually results in lifetime
immunity. In otherwise healthy persons, a second occurrence of
chickenpox is uncommon, but may occur, particularly in immunocompromised
persons. As with other viral diseases, reexposure to
natural (wild) varicella may lead to reinfection that boosts antibody
titers without causing clinical illness or detectable viremia.

RECURRENT DISEASE (HERPES ZOSTER)
Herpes zoster, or shingles, occurs when latent VZV reactivates and
causes recurrent disease.The immunologic mechanism that controls
latency of VZV is not well understood. However, factors associated
with recurrent disease include aging, immunosuppression, intrauterine
exposure to VZV, and varicella at a young age (<18 months). In
immunocompromised persons, zoster may disseminate, causing generalized
skin lesions, and central nervous system, pulmonary, and
hepatic involvement.
The vesicular eruption of zoster generally occurs unilaterally in the
distribution of a dermatome supplied by a dorsal root or
extramedullary cranial nerve sensory ganglion. Most often, this
involves the trunk or the area of the fifth cranial nerve.Two to four
days prior to the eruption there may be pain and paresthesia in the
segment involved. There are few systemic symptoms. Postherpetic
neuralgia, or pain in the area of the recurrence which persists after
the lesions have resolved, is a distressing complication of zoster, with
no adequate therapy currently available. Postherpetic neuralgia may
last as long as a year after the episode of zoster. Ocular nerve and
other organ involvement with zoster can occur, often with severe
sequelae.

COMPLICATIONS
Acute varicella is generally mild and self-limited, but may be associated
with complications. The most common complications of varicella
include secondary bacterial infections of skin lesions, dehydration,
pneumonia, and central nervous system involvement.
Secondary bacterial infections of skin lesions with staphylococcus or
streptococcus are the most common cause of hospitalization and
outpatient medical visits. Secondary infection with invasive group A
streptococci may cause serious illness and lead to hospitalization or
death. Pneumonia following varicella is usually viral, but may be
bacterial. Secondary bacterial pneumonia is more common in children
<1 year of age.
Central nervous system manifestations of varicella range from
aseptic meningitis to encephalitis. Involvement of the cerebellum,
with resulting cerebellar ataxia, is the most common and generally
has a good outcome. Encephalitis is an infrequent complication of
varicella (estimated 1.8 per 10,000 cases), and may lead to seizures
and coma. Diffuse cerebral involvement is more common in adults
than in children.
Reye syndrome is an unusual complication of varicella and
influenza and occurs almost exclusively in children who take aspirin
during the acute illness. The etiology of Reye syndrome is unknown.
There has been a dramatic decrease in the incidence of Reye syndrome
during the past decade, presumably related to decreased use
of aspirin by children.
Rare complications of varicella include aseptic meningitis, transverse
myelitis, Guillain-Barré syndrome, thrombocytopenia, hemorrhagic
varicella, purpura fulminans, glomerulonephritis, myocarditis,
arthritis, orchitis, uveitis, iritis, and clinical hepatitis.
In the prevaccine era, approximately 11,000 persons with varicella
required hospitalization each year. Hospitalization rates were
approximately 2-3 per 1,000 cases among healthy children and 8
per 1,000 cases among adults. Death occurred in approximately 1 in
60,000 cases. From 1990 through 1996, an average of 103 deaths
from varicella was reported each year. Most deaths occur in
immunologically normal children and adults.
The risk of complications from varicella varies with age.
Complications are infrequent among healthy children. They are
much higher in persons >15 years of age and infants <1 year of age.
For instance, among children 1-14 years of age, the fatality rate of
varicella is approximately 1 per 100,000 cases. Among persons 15-
19 years, the fatality rate is 2.7 per 100,000 cases, and among adults
30-49 years of age, 25.2 per 100,000 cases. Adults account for only
5% of reported cases of varicella, but account for approximately
35% of mortality.
Immunocompromised persons have a high risk of serious varicella
infection and a high risk of disseminated disease (up to 36% in one
report). These persons may have multiple organ system involvement,
and the disease may become fulminant and hemorrhagic.The
most frequent complications in immunocompromised persons are
pneumonia and encephalitis. Children with HIV infection are at
increased risk for morbidity from varicella and herpes zoster.

PERINATAL INFECTION
The onset of maternal varicella from 5 days before to 2 days after
delivery may result in overwhelming infection of the neonate and a
fatality rate as high as 30%. This severe disease is believed to result
from fetal exposure to varicella virus without the benefit of passive
maternal antibody. Infants born to mothers with onset of maternal
varicella 5 days or more prior to delivery usually have a benign
course, presumably due to passive transfer of maternal antibody
across the placenta.

CONGENITAL VZV INFECTION
Primary varicella infection in the first 20 weeks of gestation is occasionally
associated with a variety of abnormalities in the newborn,
including low birth weight, hypoplasia of an extremity, skin scarring,
localized muscular atrophy, encephalitis, cortical atrophy, chorioretinitis,
and microcephaly. This constellation of abnormalities, collectively
known as congenital varicella syndrome, was first recognized
in 1947. The risk of congenital abnormalities from primary maternal
varicella infection during the first trimester appears to be very low
(<2%). Rare reports of congenital birth defects following maternal
zoster exist, but virologic confirmation of maternal lesions is lacking.
Intrauterine infection with VZV, particularly after 20 weeks gestation,
is associated with zoster in those infants at an earlier age; the
exact risk is unknown.

LABORATORY DIAGNOSIS
Laboratory diagnosis is not routinely required, but is useful if confirmation
of the diagnosis or determination of susceptibility is necessary.
While rarely necessary for diagnosis, varicella zoster virus may be
isolated in tissue culture. The most frequent source of isolation is
vesicular fluid. Laboratory techniques allow differentiation of wild
type and vaccine strains of VZV.
Rapid varicella zoster virus identification. Rapid virus identification
techniques are indicated for a case with severe or unusual
disease to initiate specific antiviral therapy. The direct fluorescent
antibody (DFA) test is the method of choice for rapid clinical
diagnosis. This test is sensitive, specific, and widely available. Results
are available within several hours. Specimens are best collected by
unroofing a vesicle, preferably a fresh fluid-filled vesicle, and then
rubbing the base of a skin lesion with a polyester swab. Crusts from
lesions are also excellent specimens. Other specimen sources such as
nasopharyngeal secretions, saliva, blood, urine, bronchial washings,
and cerebrospinal fluid are considered less desirable sources than
skin lesions since positive test results from such specimens are much
less likely. Because viral proteins persist after cessation of viral replication,
DFA may be positive when viral cultures are negative.
Additional information concerning virus isolation and strain differentiation
can be found at http://www.cdc.gov/nip/publications/surv-manual/
A reliable history of chickenpox has been found to be a valid measure
of immunity to varicella because the rash is distinctive, and subclinical
cases are unusual. As a result, serologic testing of children is
generally not necessary. However, serologic testing may be useful
in adult vaccination programs.
A variety of serologic tests for varicella antibody are available.
Available tests include compliment fixation (CF), indirect fluorescent
antibody (IFA), fluorescent antibody to membrane antigen
(FAMA), neutralization, indirect hemagglutination (IHA), immune
adherence hemagglutination (IAHA), radioimmunoassay (RIA),
latex agglutination (LA), and enzyme-linked immunosorbent assay
(ELISA). Enzyme linked immunosorbent assay (ELISA) is sensitive
and specific, simple to perform, and is widely available commercially.
A commercially available latex agglutination (LA) is sensitive, and
simple and rapid to perform. LA is generally more sensitive than
commercial ELISA tests. Either of these tests would be useful for
screening for varicella immunity.
Antibody resulting from vaccination is generally of lower titer than
antibody resulting from varicella disease. Commercial antibody
assays, particularly the latex agglutination test, may not be sensitive
enough to detect vaccine-induced antibody in some recipients.
Because of the potential for false negative serologic tests, routine
postvaccination serologic testing is not recommended. For the
diagnosis of acute varicella infection, serologic confirmation would
include a significant rise in varicella IgG by any standard serologic
assay. Testing using commercial kits for IgM antibody is not recommended
since available methods lack sensitivity and specificity; false
positive IgM results are common in the presence of high IgG levels.
The National VZV Laboratory at CDC has developed a reliable
IgM capture assay. Call 404-639-0066, 404-639-3667, or email
vzvlab@cdc.gov for details about collecting and submitting specimens
for testing.

EPIDEMIOLOGY
OCCURRENCE
Varicella and herpes zoster occur worldwide. There are data that
suggest that varicella infection is less common in childhood in tropical
areas, where chickenpox occurs more commonly among adults.
The reason(s) for this difference in age distribution are not known
with certainty, but may be due to lack of childhood varicella infection
in rural populations.
Varicella
RESERVOIR
Varicella is a human disease. No animal or insect source or vector is
known to exist.

TRANSMISSION
Infection with VZV occurs through the respiratory tract. The most
common mode of transmission of VZV is believed to be person-toperson
from infected respiratory tract secretions.Transmission may
also occur by respiratory contact with airborne droplets, or by direct
contact or inhalation of aerosols from vesicular fluid of skin lesions
of acute varicella or zoster.

TEMPORAL PATTERN
In temperate areas, varicella has a distinct seasonal fluctuation, with
the highest incidence occurring in winter and early spring. In the
United States, incidence is highest between March and May, and
lowest between September and November. Less seasonality is
reported in tropical areas. Herpes zoster has no seasonal variation
and occurs throughout the year.

COMMUNICABILITY
The period of communicability extends from 1 to 2 days before the
onset of rash through the first 4 to 5 days, or until lesions have
formed crusts. Immunocompromised patients with varicella are
probably contagious during the entire period new lesions are
appearing. The virus has not been isolated from crusted lesions.
Varicella is highly contagious. It is less contagious than measles, but
more so than mumps and rubella. Secondary attack rates among
susceptible household contacts of persons with varicella are as high
as 90% (that is, 9 out of 10 susceptible household contacts of persons
with varicella will become infected).

SECULAR TRENDS IN THE UNITED STATES
In the prevaccine era, varicella was endemic in the United States
and virtually all persons acquired varicella by adulthood. As a result,
the number of cases occurring annually was estimated to approximate
the birth cohort, or approximately 4 million per year. Varicella
was removed from the list of nationally notifiable conditions in
1991, but some states continued to report cases to CDC. Between
100,000 to 200,000 cases of varicella are reported annually.
In the prevaccine era, the majority of cases (approximately 85%)
occurred among children less than 15 years of age. The highest agespecific
incidence of varicella was among children 1-4 years of age,
who accounted for 39% of all cases. This age distribution was probably
a result of earlier exposure to VZV in preschool and child care
settings. Children 5-9 years of age account for 38% of cases.
Adults 20 years of age and older accounted for only 7% of cases
 (National Health Interview Survey data, 1990-1994).
Data from three active varicella surveillance areas indicate that the
incidence of varicella, as well as varicella-related hospitalizations,
have fallen significantly since licensure of vaccine in 1995. In 2001,
varicella vaccination coverage among children 19-35 months in
these areas was estimated to be 74%-84%. Compared with 1995,
varicella cases declined 76%-86% in 2001. Cases declined most
among children aged 1-4 years, but cases declined in all age groups
including infants and adults, indicating reduced transmission of the
virus in these communities.

HERPES ZOSTER
Herpes zoster is not a notifiable condition. An estimated 300,000
episodes of zoster occur annually. Ninety-five percent of these
episodes are first occurrences, and 5% are recurrences. The risk of
zoster increases with increasing age. By age 80, almost 15% of persons
will have experienced at least one episode of zoster.

VARICELLA VACCINE
CHARACTERISTICS
Varicella zoster vaccine is a live attenuated viral vaccine, derived
from the Oka strain of VZV. The vaccine virus was isolated by
Takahashi in the early 1970s from vesicular fluid from a healthy
child with varicella disease.Varicella vaccine was licensed for general
use in Japan and Korea in 1988. It was licensed in the United States
in 1995. The virus was attenuated by sequential passage in human
embryonic lung cell culture, embryonic guinea pig fibroblasts, and
in WI-38 human diploid cells. The Oka/Merck vaccine has undergone
further passage through MRC-5 human diploid cell cultures
for a total of 31 passages.
The reconstituted vaccine contains small amounts of sucrose,
processed porcine gelatine, sodium chloride, monosodium L-glutamate,
sodium diphosphate, potassium phosphate, and potassium
chloride, and trace quantities of residual components of MRC-5
cells (DNA and protein), EDTA, neomycin, and fetal bovine serum.
The vaccine does not contain egg, ovalbumin, or preservative.

IMMUNOGENICITY AND VACCINE EFFICACY
After one dose of vaccine, 97% of children 12 months to 12 years of
age develop detectable antibody titers. Over 90% of vaccine responders
maintain antibody for at least 6 years. In Japanese studies, 97%
of children had antibody 7 to 10 years after vaccination.Vaccine efficacy
is estimated to be 80%-90% against infection, and 85%-95%
against moderate or severe disease.
Among healthy adolescents and adults, an average of 78% develop
antibody after one dose and 99% develop antibody after a second
dose given 4 to 8 weeks later. Antibody has persisted for at least 1
year in 97% of vaccinees after the second dose given 4 to 8 weeks
after the first dose. Studies on the persistence of antibody and clinical
efficacy in both children and adults are ongoing.
Immunity appears to be longlasting, and is probably permanent in
the majority of vaccinees. However, approximately 1% of vaccinees
per year have developed breakthrough infections (i.e., developed
varicella disease even though they had responded to the vaccine).
Breakthrough infection is significantly milder, with fewer lesions
(generally fewer than 50), many of which are maculopapular rather
than vesicular. Most persons with breakthrough infection do not
have fever.
Although the findings of some studies have suggested otherwise,
most investigations have not identified time since vaccination as a
risk factor for breakthrough varicella. Some, but not all, recent
investigations have also identified the presence of asthma and/or use
of steroids, and earlier age (i.e., <15 months) as a risk factor for
breakthrough varicella. However, because of the inconsistency of
these data, ACIP has not changed it's recommendations for use of
varicella vaccine (see below).
Breakthrough varicella infection could be a result of several factors,
including interference of vaccine virus replication by circulating
antibody, impotent vaccine due to storage or handling errors, or
inaccurate recordkeeping. Interference from live viral vaccine
administered before varicella vaccine could also reduce vaccine
effectiveness. A study in two health maintenance organizations
found that children who received varicella vaccine less than 30 days
after MMR vaccination had a 2.5-fold increased risk of breakthrough
varicella compared with those who received varicella vaccine
before, simultaneous with, or more than 30 days after MMR.
Inactivated vaccines (DTaP, Hib, IPV, and hepatitis B) and OPV did
not increase the risk of breakthrough varicella if administered <30
days prior to varicella vaccine.

VACCINATION SCHEDULE AND USE
Varicella virus vaccine is recommended for all children without
contraindications at 12-18 months of age. The vaccine may
be given to all children at this age regardless of prior history of varicella.
However, vaccination is not necessary for children with reliable
histories of chickenpox.
Varicella vaccine is also recommended for all susceptible
children by the 13th birthday. Children who have not been vaccinated
previously and who do not have a reliable history of chickenpox
are considered susceptible. Efforts should be made to assure
varicella immunity by this age, because after 13 years of age varicella
disease is more severe, complications are more frequent, and two
doses of vaccine are required.
Varicella vaccine should be administered subcutaneously. It has
been shown to be safe and effective in healthy children when admin-
istered at the same time as measles-mumps-rubella (MMR) vaccine
at separate sites and with separate syringes. If varicella and MMR
vaccines are not administered at the same visit, they should be separated
by at least 28 days.Varicella vaccine may also be administered
simultaneously (but at separate sites with separate syringes) as all
other childhood vaccines. The Advisory Committee on
Immunization Practices (ACIP) strongly recommends that varicella
vaccine be administered simultaneously with all other vaccines recommended
at 12 to 18 months of age.
Children with a reliable history of chickenpox can be assumed to be
immune to varicella. A parental history is acceptable, and physician
documentation is not necessary. Children without a reliable history,
or with an uncertain history of chickenpox should be considered
susceptible. Serologic testing of such children prior to vaccination is
not warranted, because the majority of children between 12 months
and 12 years of age without a clinical history of chickenpox are susceptible.
Prior history of chickenpox is not a contraindication to
varicella vaccination.
Varicella vaccine should be administered to all susceptible adolescents
and adults. Approximately 80% of adolescents and adults
respond to a single dose of varicella vaccine. In contrast, at least
97% of healthy children will develop detectable antibody after a single
dose. As a result, persons 13 years of age and older should
receive two doses of varicella vaccine separated by 4 to 8 weeks. If
there is a lapse of more than 8 weeks after the first dose, the second
dose may be administered at any time without repeating the first
dose.
Adolescents and adults with reliable parental or personal histories of
chickenpox can be assumed to be immune. Those without a reliable
history can be considered to be susceptible, or may be tested to
determine varicella immunity. Epidemiologic and serologic studies
indicate that up to 90% of adults are immune to varicella, including
those who do not recall having had chickenpox. As a result, serologic
testing prior to vaccination is likely to be cost effective for adults.
As with children, a prior history of chickenpox is not a contraindication
to varicella vaccination.
Assessment of varicella immunity of all adolescents and adults, and
vaccination of those who are susceptible, is desirable to protect these
individuals from the higher risk of complications from acquired varicella.
Vaccination may be offered at the time of routine healthcare
visits. However, specific assessment efforts should be focused on
adolescents and adults who are at highest risk of exposure, and
those most likely to transmit varicella to others.
Varicella vaccination should be considered for susceptible adolescents
and adults who are at high risk of exposure to varicella.
This group includes persons who live or work in environments in
which there is a high likelihood of transmission of varicella, such as
teachers of young children, daycare workers, and residents and staff
in institutional settings; persons who live or work in environments in
which varicella transmission may occur (e.g. college students,
inmates and staff of correctional institutions, and military personnel);
nonpregnant women of childbearing age, in order to reduce
the risk of VZV transmission to the fetus if the susceptible woman
should develop varicella during pregnancy; and international travelers.
Varicella vaccination is also recommended for susceptible adolescents
and adults who will have close contact with persons at
high risk for serious complications of acquired varicella. This
group would include healthcare workers and susceptible family contacts
of immunocompromised individuals.
The ACIP recommends that all healthcare workers be immune to
varicella, either from a reliable history of varicella disease or vaccination.
In healthcare settings, serologic screening of personnel who are
uncertain of their varicella history, or who claim not to have had the
disease, is likely to be cost effective. Testing for varicella immunity
following two doses of vaccine is not necessary because
99% of persons are seropositive after the second dose.
Seroconversion may not always result in full protection against disease
(see section on immunogenicity and vaccine efficacy for information
on breakthrough infection). If a vaccinated healthcare worker
is exposed to varicella, the exposed person should be tested for
varicella antibody as soon as possible following the exposure.
Persons with detectable antibody are unlikely to develop varicella.
Persons without antibody can be retested 5-6 days later to determine
if an anamnestic response is present (i.e., antibody appears
quickly after exposure). If antibody is present less than 7 days after
exposure it is unlikely that the exposed person will develop disease.
Persons who remain susceptible (i.e., antibody negative) 7 days following
exposure should be furloughed, or monitored very closely
and then furloughed at the onset of symptoms suggestive of varicella.
The risk of transmission of vaccine virus from a vaccinated person
to a susceptible contact appears to be very low (see Transmission of
Varicella Vaccine Virus, below), and the benefits of vaccinating susceptible
healthcare workers clearly outweigh this potential risk.
Transmission of vaccine virus appears to occur primarily if and
when the vaccinee develops a vaccine-associated rash. As a safeguard,
institutions may wish to consider precautions for personnel
who develop a rash following vaccination (e.g., avoidance of contact
with persons at high risk of serious complications, such as susceptible
immunosuppressed persons).

POSTEXPOSURE PROPHYLAXIS
Data from the United States and Japan in a variety of settings indicate
that varicella vaccine is effective in preventing illness or modifying
the severity of illness if used within 3 days, and possibly up to
5 days, of exposure. ACIP recommends the vaccine for use in
susceptible persons following exposure to varicella. If exposure to
varicella does not cause infection, postexposure vaccination should
induce protection against subsequent exposure. If the exposure
results in infection, there is no evidence that administration of varicella
vaccine during the incubation period or prodromal stage of
illness increases the risk for vaccine-associated adverse reactions.
Although postexposure use of varicella vaccine has potential applications
in hospital settings, preexposure vaccination of all susceptible
health care workers is the recommended and preferred method
for preventing varicella in healthcare settings.
Varicella outbreaks in some settings (e.g., child care facilities and
schools) can persist up to 6 months. Varicella vaccine has been
used successfully to control these outbreaks. Varicella vaccine
should be used for outbreak control by advising exposed susceptible
persons to contact their healthcare providers for vaccination or
by offering vaccination through the health department. Guidelines
for varicella outbreak investigation and control are available from
state health departments and from the National Immunization
Program.

ADVERSE REACTIONS FOLLOWING VACCINATION
The most common adverse reactions following varicella vaccine are
injection site complaints such as pain, soreness, redness, and
swelling. Based on information from the manufacturer’s clinical trials
of varicella vaccine, local reactions are reported by 19% of children,
and by 24% of adolescents and adults (33% following the second
dose). These local adverse reactions are generally mild and selflimited.
A varicella-like rash at injection site is reported by 3% of
children, and by 1% of adolescents and adults following the second
dose. In both circumstances, there has been a median of two lesions.
These lesions generally occur within 2 weeks, and are most commonly
maculopapular rather than vesicular.
A generalized varicella-like rash is reported by 4% to 6% of recipients
of varicella vaccine (1% after the second dose in adolescents
and adults), with a median of five lesions. Most of these generalized
rashes occur within 3 weeks and most are maculopapular.
Fever within 42 days of vaccination is reported by 15% of children
and 10% of adolescents and adults. The majority of these episodes
of fever have been attributed to intercurrent illness rather than to
the vaccine.
Varicella vaccine is a live virus vaccine, and may result in a latent
infection, similar to that caused by wild varicella virus.
Consequently, zoster caused by the vaccine virus has been
reported, mostly among vaccinated children. Not all these cases
have been confirmed as having been caused by vaccine virus.The
risk of zoster following vaccination appears to be less than that following
infection with wild type virus. The majority of cases of
zoster following vaccine have been mild and have not been associated
with complications, including postherpetic neuralgia.
Varicella
CONTRAINDICATIONS AND PRECAUTIONS TO
VACCINATION
Contraindications and precautions to varicella vaccine are similar to
those for other live attenuated vaccines. Persons with a severe
allergic reaction to a vaccine component or following a prior
dose of vaccine should not receive varicella vaccine.Varicella vaccine
contains minute amounts of neomycin and gelatin, but does
not contain egg protein or preservatives.
Persons with immunosuppression due to leukemia, lymphoma,
generalized malignancy, immune deficiency disease, or immunosuppressive
therapy should not be vaccinated. However, treatment with
low dose (<2 mg/kg/day), alternate day, topical, replacement, or
aerosolized steroid preparations is not a contraindication to varicella
vaccination. Persons whose immunosuppressive therapy with
steroids has been stopped for 1 month (3 months for chemotherapy)
may be vaccinated.Varicella vaccine is available from the manufacturer
through a research protocol for special use in certain
patients with acute lymphoblastic leukemia in remission. Please consult
the ACIP statement or contact the manufacturer for further
information.
Varicella vaccine should not be administered to persons with cellular
immunodeficiency. However, in 1999, ACIP recommended
that persons with isolated humoral immunodeficiency (e.g.,
hypogamma-globulinemia and agammaglobulinemia) should be
vaccinated.
Persons with moderate or severe cellular immunodeficiency resulting
from infection with human immunodeficiency virus (HIV),
including persons diagnosed with acquired immune deficiency syndrome
(AIDS) should not receive varicella vaccine. However, vaccination
should be considered for children with asymptomatic or
mildly symptomatic HIV infection (CDC class N1 or A1, age-specific
CD4+ T-lymphocyte percentage of >25%). These children
should receive two doses of varicella vaccine with a 3 month interval
between doses. Because persons with impaired cellular immunity
are potentially at greater risk for complications after vaccination
with a live vaccine, these vaccinees should be encouraged to
return for evaluation if they experience a postvaccination varicellalike
rash.
Women known to be pregnant or attempting to become pregnant
should not receive varicella vaccine. The effects of varicella vaccine
on a developing fetus are unknown. Since infection with wild varicella
virus poses only a small risk to the fetus, and the vaccine virus
is attenuated, the risk to the fetus, if any, should be even lower.
Although the manufacturer’s package insert states otherwise, ACIP
and the American Academy of Pediatrics recommend that pregnancy
be avoided for 1 month following receipt of varicella vaccine.
The manufacturer, in collaboration with the Centers for Disease
Control and Prevention has established a Varicella Vaccination in
Pregnancy registry to monitor the maternal-fetal outcomes of
pregnant women inadvertently given varicella vaccine. The telephone
number for the Registry is 800-986-8999.
Vaccination of persons with moderate or severe acute illnesses
should be postponed until the condition has improved. This precaution
is intended to prevent complicating the management of an ill
patient with a potential vaccine adverse event, such as fever. Minor
illness, such as otitis media and upper respiratory infections, concurrent
antibiotic therapy, and exposure or recovery from other illnesses
are not contraindications to varicella vaccine. Although there is
no evidence that either varicella or varicella vaccine exacerbates
tuberculosis, vaccination is not recommended for persons known to
have untreated active tuberculosis.Tuberculosis skin testing is not a
prerequisite for varicella vaccination.
The effect of the administration of antibody-containing blood
products (e.g., immune globulin, whole blood or packed red blood
cells, intravenous immune globulin, varicella zoster immune globulin
[VZIG]) on the response to varicella vaccine virus is unknown.
Because of the potential inhibition of the response to varicella vaccination
by passively transferred antibodies, varicella vaccine should
not be administered for 3-11 months after antibody-containing
blood products. ACIP recommends applying the same intervals
used to separate antibody-containing products and MMR to varicella
vaccine (see the chapter on General Recommendations on
Immunization for additional details). Immune globulin or VZIG
should not be given for 3 weeks following vaccination unless the
benefits exceed those of the vaccine. In such cases, the vaccinees
should either be revaccinated or tested for immunity >3 months
later (depending on the antibody-containing product administered)
and revaccinated if seronegative.
No adverse events following varicella vaccination related to the use
of salicylates (e.g., aspirin) have been reported to date. However,
the manufacturer recommends that vaccine recipients should avoid
the use of salicylates for 6 weeks after receiving varicella vaccine
because of the association between aspirin use and Reye syndrome
following chickenpox.

TRANSMISSION OF VARICELLA VACCINE VIRUS
Available data suggest that transmission of vaccine virus is a rare
event. Instances of suspected secondary transmission of vaccine
virus have been reported. However, in few instances has the secondary
clinical illness been shown to be caused by vaccine virus.
Several cases of suspected secondary transmission have been determined
to have been caused by wild varicella virus. However, in
studies of household contacts, several instances of asymptomatic
seroconversion have been observed. It appears that transmission
occurs mainly, and perhaps only, when the vaccinee develops a rash.
If a vaccinated child develops a rash, it is recommended that close
contact with susceptible persons at high-risk of complications of
varicella, such as immunocompromised persons, be avoided until
the rash has resolved.

VACCINE STORAGE AND HANDLING
Varicella vaccine is very fragile and must be handled with extreme
care.To maintain potency, the lyophilized vaccine must be stored
frozen at an average temperature of +5 degrees  F (-15 degrees C). Household freezers,
including frost-free models, manufactured within the last 5-10
years, are designed to maintain temperatures as low as -4 degrees F (-20 degrees C),
and are acceptable for storage of the vaccine. Refrigerators with ice
compartments that are not tightly enclosed or are enclosed with
unsealed, uninsulated doors (i.e., small dormitory-style
refrigerator/freezer combinations) are not be capable of maintaining
the required storage temperature. Regardless of the type of freezer,
providers should check the adequacy of their freezer storage before
obtaining vaccine by monitoring and verifying the temperature of
their freezer.
The vaccine diluent should be stored separately at room temperature
or in the refrigerator. The vaccine should be reconstituted
according to the directions in the package insert and only with the
diluent supplied, which does not contain preservative or other antiviral
substances that might inactivate the vaccine virus. Once reconstituted,
the vaccine must be used immediately to minimize loss of
potency. The vaccine must be discarded if not used within 30 minutes
of reconstitution.
If varicella vaccine is inadvertently placed in the refrigerator, or if
unreconstituted vaccine is left at room temperature for a short time,
it may still be potent enough to use. Mishandled vaccine should be
clearly marked and replaced in the freezer separate from properly
handled vaccine. After storing the vaccine, the manufacturer must
be contacted for recommendations before any of the mishandled
vaccine is used. The Merck Vaccine Division varicella information
telephone number is 800-9VARIVAX (800-982-7482). If the vaccine
has been kept cold, or has been exposed to room temperature
for a very short time, the manufacturer may recommend that the
expiration date be shortened, and that the vaccine be used as quickly
as possible. Mishandled vaccine should never be destroyed until
the manufacturer has been consulted.
Because of the lability of varicella vaccine, transport of the vaccine
from a central clinic or storage area to an off-site clinic can be difficult.
If off-site transport is attempted, a high-quality container
should be used, the vaccine should be transported on dry ice, and
the temperature should be monitored continuously, to assure that
the appropriate storage temperature is maintained. The vaccine may
be kept at refrigerator temperature for up to 72 hours, but must
then be discarded if not used. The vaccine should not be refrozen.

VARICELLA ZOSTER IMMUNE GLOBULIN (VZIG)
VZIG is a human blood product that contains high titers of varicella
zoster virus antibody. It was licensed in 1981, and is available
from the distributor (FFF Enterprises, Inc.,Temecula, CA)
by calling 800-843-7477. If administered within 96 hours of exposure,
VZIG can modify or prevent clinical varicella and prevent
complications or death, especially in susceptible immunocompromised
individuals.
The decision to administer VZIG should be based on whether the
patient is susceptible either by having a negative history of chickenpox
or by lacking documentation of vaccination, whether the exposure
is likely to result in infection and, most importantly, whether
the patient is at greater risk of complications than the general population.
VZIG is expensive ($400-$500 for the maximum dose in an
adult) and provides only temporary protection.
VZIG is indicated for use in susceptible individuals at high risk for
complications who have had a significant exposure (continuous
household contact; playmate contact of more than an hour; hospital
contact in the same 2- to 4-bed room; or prolonged direct contact)
to a person with varicella. It is most commonly used for postexposure
prophylaxis of immunocompromised children (immune deficiencies,
neoplastic disease, or on immunosuppressive therapy), and
newborns of mothers with varicella onset 5 days before to 48 hours
after delivery. It is also recommended for premature infants with
postnatal exposure, including those born at less than 28 weeks gestation
or less than 1,000 gram birth weight (who may not have
received adequate maternal antibody regardless of whether the
mother is immune), or premature infants whose mother is not
immune to varicella.
Healthy and immunocompromised adults and pregnant women are
at increased risk of complications of varicella. VZIG should be considered
if such individuals are susceptible. There is no evidence that
VZIG will prevent congenital varicella if given as postexposure prophylaxis
to a pregnant woman.
VZIG is supplied in vials containing 125 or 625 units. The recommended
dose considered likely to prevent or modify varicella is 125
units per 10 kilograms of body weight, up to a maximum of 625
units, or five vials. Higher doses can be considered for immunosuppressed
persons. VZIG is given intramuscularly, and must never be
given intravenously. It should be given within 96 hours of exposure,
preferably as soon as possible. The administration of VZIG may prolong
the incubation period of varicella to 28 days or longer postexposure.
More detailed information on the evaluation of a person exposed to
varicella and the use of VZIG may be found in the varicella ACIP
statement.

SPECIAL VARICELLA EXPOSURE SITUATIONS
HOSPITAL PERSONNEL
Susceptible workers with significant exposure to varicella should be
relieved from direct patient contact from day 10 to day 21 after
exposure. If workers develop chickenpox, varicella lesions must be
crusted before they return to direct patient contact. Receipt of VZIG
does not change this recommendation for reassignment. Since VZIG
can prolong the incubation period, the period of removal from
direct patient contact should be lengthened by 1 week or more.

NEWBORNS
Newborn with maternal rash onset 5 days before to 48 hours after
delivery should receive VZIG. Since about 50% of infants who
receive VZIG will develop varicella, if these infants remain hospitalized
beyond age 10 days, they should be kept in strict isolation for
the entire incubation period (until day 28 or longer).

ANTIVIRAL THERAPY
Several antiviral drugs are active against varicella zoster virus,
including acyclovir, valacyclovir, famciclovir, and foscarnet.
Famciclovir and valacyclovir are approved for use only in adults.
Clinical studies indicate that these drugs may be beneficial if given
within 24 hours of onset of rash, resulting in a reduction in the
number of days new lesions appeared, in the duration of fever, and
in the severity of cutaneous and systemic signs and symptoms.
Antiviral drugs have not been shown to decrease transmission of
varicella, reduce the duration of absence from school, or reduce
complications.
The decision to use antiviral therapy, and the duration and route of
therapy should be determined by specific host factors, the extent of
infection, and the initial response to therapy. ACIP has not made
recommendations regarding the use of antiviral therapy for varicella.
The American Academy of Pediatrics (AAP) does not recommend
routine antiviral therapy for otherwise healthy infants or children
with varicella. Oral acyclovir can be considered in otherwise healthy
adolescents and adults or secondary cases in the household, because
of the increased risk of severe illness in these groups. Antiviral therapy
may also be considered for persons with a chronic cutaneous or
pulmonary disorders, persons receiving long-term salicylate therapy,
and for children receiving short, intermittent or aerosolized courses
of corticosteroids. If the child is immunocompromised, intravenous
administration is indicated. Corticosteroids should be discontinued,
if possible, after exposure. Antiviral drugs are not recommended for
routine postexposure prophylaxis.
Oral acyclovir is not routinely recommended for pregnant adolescents
or adults with uncomplicated varicella because the risks and
benefits to the fetus and mother are not known. However, some
experts recommend oral acyclovir for pregnant women with
varicella, particularly during the second and third trimesters.
Varicella
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Asano Y, Suga S,Yoshikawa T, et al. Experience and reason: twenty
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CDC. Prevention of varicella. Recommendations of the Advisory
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CDC. Simultaneous administration of varicella vaccine and other
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