Transcript Denise – Varicella

VARICELLA-ZOSTER VIRUS
Varicella-zoster virus
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Varicella-zoster virus (VZV) causes primary, latent, and recurrentinfections.
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The primary infection is manifested as varicella (chickenpox) and results in establishment of a
lifelong latent infection of sensory ganglion neurons.
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Reactivation of the latent infection causes herpes zoster (shingles).
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Although often a mild illness of childhood, chickenpox can cause substantial morbidity and
mortality in otherwise healthy children; it increases morbidity and mortality in immunocompetent
infants, adolescents,adults, as well as in immunocompromised persons.
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it predisposes to severe group A streptococcus and Staphylococcus aureus infections
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Primary clinical disease can be prevented by immunization with live-attenuated VZV vaccine
(varicella vaccine).
Herpes zoster vaccine (zoster vaccine), higher potency, is recommended for persons ≥60 yr of age
to boost their immunity; painful postherpetic neuralgia.
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ETIOLOGY
 VZV is a neurotropic human herpesvirus with
similarities to herpes simplex virus, which is
also α-herpesvirus.
 These viruses are enveloped with doublestranded DNA genomes that encodemore
than 70 proteins, including proteins that are
targets of cellular and humoral immunity.
EPIDEMIOLOGY
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Most children were infected by 15 yr of age, withfewer than
5% of adults remaining susceptible. This pattern of
infection at younger ages is characteristic in all countries
intemperate climates.
In tropical areas, varicella occurs among older persons,
with many cases occurring among adults.
Varicella is a more serious disease in young infants, adults,
and immunocompromised persons, in whom there are
higher rates of complications and deaths than in healthy
children.
Patients with varicella are contagious 24-48 hr before the
rash is evident and until vesicles are crusted,
usually 3-7 days after onset of rash.
Susceptible persons may also acquire varicella after close,
direct contact with adults or children who have herpes
zoster.
predominantly in children in upper elementary school
rather than in the preschool years.
Herpes zoster is due to the reactivation of latent VZV.
Herpes zoster is uncommon to children and very rare in
healthy children <10 yr of age
Herpes zoster in children tends to be milder than disease in
adults
The risk for development of subsequent herpes zoster is
lower after vaccine than any natural vzv infection
PATHOGENESIS
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VZV is transmitted in oropharyngeal secretions and in the fluid
of skin lesions either by airborne spread or through direct
contact.
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Primary infection (varicella) results from inoculation of the virus
onto the mucosa of the upper respiratory tract and tonsillar
lymphoid tissue.
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During the early part of the 10- to 21-day incubation period,
virus replicates in the local lymphoid tissue, and then a brief
subclinical viremia spreads the virus to the reticuloendothelial
system.
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Widespread cutaneous lesionsoccur during a second viremic
phase that lasts 3-7 days.
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VZV is also transported back to the mucosa of the upper
respiratory tract and oropharynx during the late incubation
period, permitting spread to susceptible contacts 1-2 days
before the appearance of rash.
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Virus is transported in a retrograde manner through sensory
axons to the dorsal root ganglia throughout the spinal cord,
where the virus establishes latent infection in the neurons and
satellite cells associated with these axons.
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Subsequent reactivation of latent virus causes herpes zoster,
a vesicular rash that usually is dermatomalin distribution.
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During herpes zoster, necrotic changes may be produced in the
associated ganglia. The skin lesions of varicella and herpes
zoster have identical histopathology, and infectious VZV is
present in both.
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Suppression of cell-mediated immunity to VZV correlates with
an increased risk for VZV reactivation as herpes zoster.
CLINICAL MANIFESTATION
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Varicella is an acute febrile rash
illness that was common in children
in the USA before the universal
childhood vaccination program.
 It has variable severity but is usually
self limited. It may be associated
with severe complications, including
staphylococcal and streptococcal
superinfection, pneumonia,
encephalitis, bleeding disorders,
congenital infection, and lifethreatening perinatalinfection.
 Herpes zoster, uncommon in
children, causes localized cutaneous
symptoms but may disseminate in
immunocompromised patients.
Varicella
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The illness usually begins 14-16 days after
exposure, although the incubation period
can range from 10 to 21 days.
Prodromal symptoms may be present,
particularly in older children and
adults. Fever, malaise, anorexia, headache,
and occasionally mild abdominal pain may
occur 24-48 hours beforethe rash appears.
Temperature elevation is usually moderate,
usually 100-102°F, but may be as high as
106°F; fever and other systemic symptoms
usually resolve within 2-4 days after the
onset of the rash.
Varicella lesions often appear first on the
scalp, face, or trunk.
The distribution of the rash is
predominantly central or centripetal, in
contrast to that in smallpox, which is more
prominent on the face and distal
extremities.
 Ulcerative lesions involving the mucosa of oropharynx and
vagina are also common; many children have vesicular
lesions on the eyelids and conjunctivae, but corneal
involvement and serious ocular disease are rare.
 The average number of varicella lesions is about 300, but
healthy children may have fewer than 10 to more than
1,500 lesions
 The differential diagnosis of varicella includes vesicular
rashes caused by other infectious agents, such as herpes
simplex virus, enterovirus, monkey pox, rickettsial pox, and
S. aureus; drug reactions; disseminated herpes zoster;
contact dermatitis; and insect bites
 Severe varicella was the most common illness confused
with smallpox before the eradication of smallpox.
Varicella in Vaccinated Individuals
(“Breakthrough Varicella”)
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Breakthrough disease is varicella that
occurs in a person vaccinated >42 days
before rash onset and is caused by wildtype VZV
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In the early stages of the varicella
vaccination program, rash occurring
within the 1st 2 weeks after vaccination
was most commonly wild-type VZV,
reflecting exposure to varicella before
vaccination could provide protection.
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Rash occurring 14-42 days after
vaccination was due to either wild or
vaccine strains, reflecting breakthrough
varicella or vaccine-associated rash,
respectively.
 As varicella disease continues to decline, rashes in the interval 0
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42 days after vaccination will be less commonly caused by wildtype VZV.
The rash in breakthrough disease is frequently atypical and
predominantly maculopapular, vesicles are seen less commonly,
and the illness is most commonly mild with <50 lesions, shorter
duration of rash, fewer complications, and little or no fever.
However, approximately 25-30% of breakthrough cases are not
mild, with clinical features more similar to those of wild-type
infection.
Breakthrough cases are overall less contagious than wild-type
infections
children with breakthrough disease should be considered
potentially infectious and excluded from school until lesions have
crusted or, if there are no vesicles present, until no new lesions
are occurring.
Progressive Varicella
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Progressive varicella, with visceral organ
involvement, coagulopathy, severe hemorrhage, and
continued vesicular lesion development, is a severe
complication of primary VZV infection.
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Severe abdominal pain, which may reflect
involvement of mesenteric lymph nodes or the liver,
or the appearance of hemorrhagic vesicles in
otherwise healthy adolescents and adults,
immunocompromised children, pregnant women,
and newborns, may herald severe disease.
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Although rare in healthy children, the risk for
progressive varicella is highest in children with
congenital cellular immune deficiency disorders and
those with malignancy
varicella-related deaths usually occur within 3 days
after the diagnosis of varicella pneumonia
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Unusual clinical findings of varicella, including lesions
that develop a unique hyperkeratotic appearance
and continued new lesion formation for weeks or
months, have been described in children with
untreated,late stage HIV infection.
Neonatal Varicella
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Mortality is particularly high in neonates born to susceptible mothers who
contracted varicella around the time of delivery.
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.
The infant acquires the infection transplacentally as a result of maternal viremia,
which may occur up to 48 hr prior to onset of maternal rash.
The infant’s rash usually occurs toward the end of the 1st week to the early part
of the 2nd week of life (although it may be as soon as 2 days). Because the
mother has not yet developed a significant antibody response, the infant
receives a large dose of virus without the moderating effect of maternal anti-VZV
antibody.
If the mother demonstrates varicella >5 days prior to delivery, she still may pass
virus to the soon-to-be-born child, but infection is attenuated because of
transmission of maternal VZV-specific antibody across the placenta.
This moderating effect of maternal antibody is present if delivery occurs after 30
wk of gestation, when maternal immunoglobulin G (IgG) is able to cross the
placenta.
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The recommendations for human
varicella zoster immune globulin
(VariZIG) reflect the differing risks
to the exposed infant. Newborns
whose mothers demonstrate
varicella 5 days before to 2 days
after delivery should receive 1 vial of
VariZIG as soon as possible.
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If VariZIG is not available,
intravenous immune globulin (IGIV)
may provide some protection,
althoughvaricella-specific antibody
titers may vary from lot to lot.
Becauseperinatally acquired
varicella may be life threatening, the
infantshould be treated with
acyclovir (10 mg/kg every 8 hr IV)
whenlesions develop
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Infants with neonatal varicella who
receive prompt antiviral therapy
have an excellent prognosis.
Congenital Varicella Syndrome
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When pregnant women do contract varicella early
in pregnancy, experts estimate that as many as
25% of the fetuses may become infected.
Fortunately, clinically apparent disease in the
infant is uncommon: the congenital varicella
syndrome occurs in approximately 0.4% of infants
born to women who have varicella during
pregnancy before 13 wk of gestation and
approximately 2% of infants born to women with
varicella between 13 and 20 wk of gestation
The congenital varicella syndrome is
characterized by cicatricial skin scarring in a
zoster-like distribution, limb hypoplasia, and
neurologic (e.g., microcephaly, cortical atrophy,
seizures, and mental retardation),eye (e.g.,
chorioretinitis, microphthalmia, and cataracts),
renal(e.g., hydroureter and hydronephrosis) and
autonomic nervous system abnormalities
(neurogenic bladder, swallowing dysfunction,and
aspiration pneumonia).
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Most of the stigmata can be attributed to virus-induced injury to the
nervous system, although there is no obvious explanation why certain
regions of the body are preferentially infected during fetal VZV infection.
The characteristic cutaneous lesion has been called a cicatrix, a zigzag
scarring, in a dermatomal distribution, often associated withatrophy of the
affected limb
Many infants with severe manifestations of congenital varicella syndrome
(atrophy and scarring of a limb) have significant neurologic deficiencies.
The diagnosis of VZV fetopathy is based mainly on the history of gestational
varicella combined with the presence of characteristic abnormalities in the
newborn infant
Virus cannot be cultured from the affected newborn, but viral DNA may be
detected in tissue samples by polymerase chain reaction (PCR).
VZVspecificIgM antibody is detectable in the cord blood sample in some
infants, although the IgM titer drops quickly postpartum and can be
nonspecifically positive.
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Chorionic villus sampling and fetal blood collection for the detection of viral
DNA, virus, or antibody have been used in an attempt to diagnose fetal
infection and embryopathy but may primarily be that of reassurance when
the result is negative
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A persistently positive VZV IgG antibody titer at 12-18 mo of age is a reliable
indicator of prenatal infection in the asymptomatic child, as is the
development of zoster in the 1st year of life without evidence of postnatal
infection.
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Varicella immune globulin has often been administered to the susceptible
mother exposed to varicella, but whether this step modifies infection in the
fetus is uncertain.
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Acyclovir treatment may be given to the mother with severe varicella
antiviraltreatment of infants with congenital VZV syndrome is not indicated
Herpes Zoster
 Herpes zoster manifests as
vesicular lesions clustered within
1 or, less commonly, 2 adjacent
dermatomes
 the most frequent complication
is postherpetic neuralgia, a
painful conditionthat affects the
nerves despite resolution of the
shingles skin lesions
 zoster in children is infrequently
associated with localized pain,
hyperesthesia, pruritus, and lowgrade fever. In children, the rash
is mild, complete resolution
usually occurs within 1-2 wk.
DIAGNOSIS
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The atypical nature of breakthrough varicella, with a higher proportion
of rashes being papular rather than vesicular, will pose diagnostic
challenges. In addition, severe cases of varicella may need virologic
confirmation to distinguish them from pox virus infections.
Leukopenia is typical during the 1st 72 hours after onset of rash; it is
followed by a relative and absolute lymphocytosis.
Results of liver function tests are also usually (75%) mildly elevated.
Patients with neurologic complications of varicella or uncomplicated
herpes zoster have a mild lymphocytic pleocytosis and a slight to
moderate increase in protein content of the cerebrospinal fluid; the
cerebrospinal fluid glucose concentration is usually normal.
VZV can be identified quickly by direct fluorescence assay (DFA) of cells
from cutaneous lesions (vesicular fluid) in 15-20 min, by rapid culture
with specific immunofluorescence staining (shell vial technique) in 48-72
hr, and by PCR amplification testing (vesicular fluid, crusts) in 2 hr to
days, depending onavailability.
TREATMENT
 Antiviral treatment
modifies the course of both
varicella and herpes zoster.
 Antiviral drug resistance is
rare but has occurred in
children with HIV infection
who have been treated
with acyclovir
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foscarnet is the only drug
available for the treatment
of acyclovir-resistant VZV
infections.
Varicella
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The only antiviral drug available
in liquid formulation that is
licensed for pediatric use is
acyclovir.
Intravenous therapy is
indicated for severe disease and
for varicella in
immunocompromised patients
(even if begun 72 hr after onset
of rash). Acyclovir has been
used to treat varicellain
pregnant women; its safety for
the fetus has not been
established.
Some experts recommend the
use of famciclovir or
valacyclovir in older children
who can swallow tablets.
Herpes Zoster
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Antiviral drugs are effective for treatment of herpes zoster.
In healthy adults, acyclovir and valacyclovir reduce the
duration of the illness and the risk for development of
postherpetic neuralgia; concomitant corticosteroid use
improves the quality of life in the elderly.
treatment of uncomplicated herpes zoster in the child with
an antiviral agent may not always be necessary, although
some experts would treat with oral acyclovir (20
mg/kg/dose, maximum 800 mg/dose) to shorten the
duration of the illness
In contrast, herpes zoster in immunocompromised
children can be severe, and disseminated disease may be
life threatening.
Patients at high risk for disseminated disease should
receive acyclovir
Oral acyclovir, famciclovir, or valacyclovir are options for
immunocompromisedpatients with uncomplicated herpes
zoster and who are considered at low risk for visceral
dissemination.
Use of corticosteroids in the treatment of herpes zoster in
children is not recommended
COMPLICATIONS
 Bacterial Infections
A streptococci and S. aureus, may occur in up to 5% of children
with varicella. These range from impetigo to cellulitis,
lymphadenitis, and subcutaneous abscesses. An early
manifestationof secondary bacterial infection is erythema of the
base of a new vesicle.
 A streptococcus, can have a fatal outcome
 Varicella is a well-described risk factor for serious invasive
infections caused by group
 The more invasive infections, such as varicella gangrenosa,
bacterial sepsis, pneumonia, arthritis, osteomyelitis, cellulitis,
and necrotizing fasciitis, account for much of the morbidity and
mortality of varicella in otherwise healthy children.
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Encephalitis and Cerebellar Ataxia
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Encephalitis and acute cerebellar are
well-described neurologic
complicationsof varicella;
morbidity from CNS complications is
highest among patients younger than 5
yr or older than 20 yr
Nuchal rigidity, altered consciousness,
and seizures characterize
meningoencephalitis.
Patients with cerebellar ataxia have a
gradual onset of gait disturbance,
nystagmus, and slurred speech.
Neurologic symptoms usually begin 2-6
days after the onset of the rash but may
occur during the incubation period or
after resolutionof the rash.
Clinical recovery is typically rapid,
occurring within24-72 hr, and is usually
complete.
Pneumonia
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Varicella pneumonia is a severe
complication that accounts for
most of the increased morbidity
and mortality in adults and other
high-risk populations, but
pneumonia may also complicate
varicella in young children.
 Respiratory symptoms, which may
include cough, dyspnea, cyanosis,
pleuritic chest pain, and
hemoptysis, usually begin within 16 days after the onset of the rash
 Smoking has been described as a
risk factor for severe pneumonia
complicating varicella
PROGNOSIS
 Primary varicella has a mortality rate of 2-3/100,000 cases, with
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the lowest case fatality rates among children 1-9 yr of age
(~1death per 100,000 cases)
Compared with these age groups, Infants have a 4 times greater
risk of dying and adults have a 25times greater risk of dying.
the most common complications among people who died from
varicella were pneumonia, CNS complications, secondary
infections, and hemorrhagic conditions.
Neuritis with herpes zoster should be managed with appropriate
analgesics.
Postherpetic neuralgia can be a severe problem in adults and
may persist for months, requiring care by a specialist in pain
management.
PREVENTION
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VZV transmission is difficult to prevent because an infected person is
contagious for 24-48 hr before the rash appears.
Infection control practices, including caring for infected patients in isolation
rooms with filtered air systems, are essential.
All health care workers should have evidence of varicella immunity.
Unvaccinated health care workers without other evidence of immunity who
have had a close exposure to VZV should befurloughed for days 8-21 after
exposure because they are potentiallyinfectious during this period.
Vaccine
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Varicella is a vaccine-preventable disease
.Varicella vaccine contains live, attenuated VZV
(Oka strain) and is indicated for subcutaneous
administration.
Recommended for routine administration as a
2-dose regimen to healthy childrenat ages 1215 mo and 4-6 yr.
Catch-up vaccination with the second dose is
recommended for children and adolescents
who
received only 1 dose.
Vaccination with 2 doses is recommendedfor
all persons without evidence of immunity.
Varicella vaccine is contraindicated for
pregnant women andpersons with cellmediated immune deficiencies, including
those with leukemia, lymphoma, and other
malignant neoplasms affectingthe bone
marrow or lymphatic systems
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Vaccine-associated Adverse Events
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Transmission of vaccine virus to susceptible contacts is a very rare occurrence.
Postexposure Prophylaxis
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Vaccine given to healthy children within 3-5 days after exposure (as soon as
possible is preferred) is effective in preventing or modifying varicella, especially in
a household setting where exposure is very likely to result in infection. Varicella
vaccine is now recommended for postexposure use and for outbreak control.
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Oral acyclovir administered late in the incubation period may modify subsequent
varicella in the healthy child; however, its use in this manner is not recommended
until it can be further evaluated.
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High-titer anti-VZV immune globulin as postexposure prophylaxis is
recommended for immunocompromised children, pregnant women, and
newborns exposed to varicella.
If possible, adults should be tested for VZV IgG antibodies before VariZIG
administration, because many adults with no clinical history of varicella are
immune.
Close contact between a susceptible high-risk patient and a patient with herpes
zoster is an indication for VariZIG prophylaxis.
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