Transcript Measles

VIRAL EXANTHEMS
21 Nov 2013
Danize Buemio
Mary April Chan
MEASLES
Measles
• Etiology
– Measles virus
– Single-stranded lipid enveloped
RNA virus
– Family Paramyxoviridae, genus
Morbilivirus
– 6 major structural proteins
• Hemagglutinin (H) protein
• Fusion (F) protein – antibodies limit
proliferation
Measles
• Transmission
– Contact with large droplets or small droplet
aerosols in which virus is suspended
– Entry into respiratory tract or conjunctivae
– Approx. 90% of exposed individuals develop
measles
– Face-fece contact is not necessary
– Viable virus may be suspended in the air up to 1
hour
• Pathology
Measles
– Necrosis of the respiratory tract
epithelium with lymphocytic
infiltrate
– Small vessel vasculitis on the
skin and oral mucosa
– Histological findings
• Rash reveals intracellular edema
and dyskeratosis
• Epidermal syncytial giant cells with
up to 26 nuclei
• Lymphoid hyperplasia
• Fusion of infected cells 
multinucleated giant cells
– Warthin-Finkeldey giant cells:
pathognomonic for measles, up to
100 nuclei
Measles
Incubation
Period
Prodromal
Illness
Exanthematous
Phase
Recovery
Measles
Incubation
Period
Prodromal
Illness
Exanthematous
Phase
Recovery
• Incubation period: 8-12 days
• Virus migrates to regional lymph nodes
• Primary viremia disseminates the virus to the
reticuloendothelial system
• Secondary viremia spreads virus to body surfaces
Measles
Incubation
Period
Prodromal
Illness
Exanthematous
Phase
Recovery
• Prodromal Phase: mild fever, Conjunctivitis with photophobia,
Coryza, Cough
• Enanthem: Koplik spots  pathognomonic
– Appears 1-4 days before rash
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Symptoms increase in intensity for 2-4 days until 1st day of the rash
Epithelial necrosis
Giant cell formation
Viral shedding
Viral replication
Measles
Incubation
Period
Prodromal
Illness
Exanthematous
Phase
Recovery
• Exanthem: maculopapular rash begins around forehead
(hairline), behind the ears, upper neck  torso 
extremities
• Antibody production  viral replication and symptoms
subside, rash fades over 7 days  desquamation
• Infection of CD4 T cells  suppresion of immune response
Inapparent Measles Infection
• Subclinical form of measles
• Individuals with passively acquired antibody
– Infants, recepients of blood products
• Rash may be indistinct, brief or absent
• Do not shed measles virus or transmit
infection
Atypical measles
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Original formalin-inactivated measles vaccine
More severe form
High onset of fever and headache
Maculopapular rash on the extremities 
petechial and purpuric
– Progress in centripetal direction
• Frequently complicated by pneumonia and
pleural effusion
• Circulating immune complexes due to abnormal
response to vaccine
Diagnostics
• CBC
– Reduction in WBC count
– Decrease in lymphocytes > neutrophils
– ESR and C-protein normal
• Serologic confirmation: IgM and IgG
– IgM: appears 1-2 days after onset of rash, remains
detectable for ~1month
– IgG: 4-fold rise In specimens take 2-4 weeks later
• Viral isolation and PCR
Differential Diagnoses
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Rubella
Adenoviruses
Epstein-Barr virus
Kawasaki Disease – presents with
thrombocytosis, lacks Koplik spots and severe
cough
• Drug eruptions
Treatment
• Supportive
• Goals of therapy:
– Hydration, oxygenation, comfort
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ORS, IV fluids
Airway humidification and supplemental O2
Ventilatory support for croup or pneumonia
Antipyretics
Prophylactic antimicrobial tx is NOT indicated
Antiviral therapy is NOT effective in otherwise
normal patients
Treatment
• Measles in immunocompromised is highly
lethal
– Ribavarin with or without intravenous gamma
globulin
Treatment
• Vitamin A
– Measles lowers serum retinol
– Higher morbidity and mortality
Complications
• Morbidity and mortality are greatest in <5
years and >20 years
• Crowding – larger inoculum dose
• Severe malnutrition – suboptimal immune
response
• Measles in immunocompromised
Complications
• Dehydration
– Fever, diarrhea, vomiting
• Known to suppress PPD skin test
responsiveness
– May have an increased rate of PTB activation
Complications
• Pneumonia – most common cause of death
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Giant cell pneumonia caused by virus
Superimposed bacterial infection
Final pathway: bronchiolitis obliterans
Croup, tracheitis
• Otitis Media – most common complication
• Sinusitis, mastoiditis, retropharygeal abscess
• Encephalitis
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Postinfectious immunologically mediated process
Seizures (56%), lethargy (45%), coma (28%), irritability (26%)
CSF: lymphocytic pleocytosis, elevated protein
Approx 15% death, 20-40% mental retardation, deafness, motor
disabilities
• Hemorrhagic or “black measles”: hemorrhagic skin eruption, fatal
• Myocarditis: rare
• Subacute Sclerosing Paraencephalitis (SSPE)
Subacute Sclerosing Paraencephalitis
(SSPE)
• Rare disease
• Results from a persistent infection with an
altered measles virus harbored in CNS for
years
• After 7-10 years, virus regains virulence and
attacks cells in CNS that offered the virus
protection
• Inflammation and cell death 
neurodegenerative process
Subacute Sclerosing Paraencephalitis
(SSPE)
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Age of onset: <1 to <30 years
Usually in children in adolescents
Measles at an early age favors SSPE development
Males affected twice as often as females
Defective measles virus
Defective or immature immune system
Immature virus able to reside within neural cells
for long periods
Subacute Sclerosing Paraencephalitis
(SSPE)
• Symptoms begin 7-13 years after primary measles infection
• 1st stage: Subtle changes in behavior
– Irritability, reduced attention span, temper outbursts
– Fever, headache, signs of encephalitis are absent
• 2nd stage: massive myoclonus
– Extension of inflammatory process to deeper brain structures
including basal ganglia
• 3rd stage: choreoathetosis, immobility, dystonia, lead pipe
rigidity
– Sensorium deteriorates: dementia  stupor  coma
– involuntary movements disappear
• 4th stage
– Loss of centers supporting breathing, heart rate, BP
– Death
MUMPS
Mumps
• Etiology
– Mumps virus
– Single-stranded pleomorphic
RNA virus
– Family Paramyxoviridae, Genus
Rubulavirus
– Encapsulated in a lipoprotein
envelope
– 7 structural proteins
• Hemagglutin-neuraminidase (HN)
• Fusion (F)
– Humans are the only natural
host
Mumps
• Transmission
– Spread from person-person via respiratory
droplets
– Virus appears in saliva 7 days before and 7 days
after the onset of parotid swelling
– Period of maximum infectiousness: 1-2 days
before to 5 days after parotid swelling
Mumps
• Pathology
– Targets the salivary glands, CNS,
pancreas, testes
– Thyroid, ovaries, heart, kidneys,
liver, joint synovia
– Initial viral replication in the
upper respiratory tract
– Spread to adjacent lymph nodes
 target tissues
– Necrosis of infected cells
– Salivary gland ducts are lined
with necrotic epithelium,
interstitium lined with
lymphocytes
Mumps
Incubation
Period
Prodromal
Illness
Exanthematous
Phase
Recovery
• Incubation Period: 12-25 days, usu. 16-18
Mumps
Incubation
Period
Prodromal
Illness
Parotitis
Recovery
• Prodrome: 1-2 days
• Fever, headache, vomiting, achiness
Mumps
Incubation
Period
Prodromal
Illness
Parotitis
Recovery
• Parotid swelling appears
• May be unilateral initially, but becomes
bilateral 70%
• Peaks in 3 days, subsides over 7 days
• Submandibular glands may also be involved
Mumps
• Parotid gland is tender
• May be preceeded by ear
pain
• Angle of jaw is obscured
• Earlobe lifted upward
and outward
• Sour or acidic food may
enhance pain
• Morbiliform rash is rarely
seen
Mumps
Incubation
Period
Prodromal
Illness
Parotitis
Recovery
• Fever resolves in 3-5 days along with other
systemic symptoms
Diagnostics
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History of exposure to mumps infection
Clinical findings
Elevated amylase level
Relative lymphocytosis
Serologic testing
– Increase in mumps IgG, IgM
– IgG may cross react with antibodies to parainfluenza
virus
• Isolation of the virus in cell culture, PCR,
immunofluorescence
Treatment
• No specific antiviral therapy is available for
mumps
• Pain control
• Adequate hydration
• Antipyretics for fever
Complications
• Encephalitis, meningitis, meningoencephalitis
– Usually manifests 5 days after parotid swelling
– Infants, young children: fever, malaise, lethargy
– Older children: headache, meningeal signs
• Pancreatitis
– Epigastric pain, vomiting
• Orchitis
– 2nd to parotitis as a common finding
– After puberty, occurs 30-40%
– High fever, chills, pain and swelling of testes
• Oophoritis
– Uncommon in postpubertal females
– Severe pain
Prognosis
• Excellent
• Some fatal cases of encephalitis were reported
Prevention
• 2 dose MMR vaccine
– MMR1: 12-15 mos
– MMR2: 4-6 years
ROSEOLA
Roseola Infantum
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Exanthem subitum or Sixth disease
Mild febrile exanthematous illness
Occurs almost exclusively during infancy
>95% occur in children younger than 3, peak at 6-15 mos
Etiology
– Human herpesvirus (HHV) types 6 and 7
– Genus: Roseolovirus
– Subfamily: Betaherpesvirinae
• Transmission
– Droplet
– From saliva of healthy persons, enters host through oral, nasal or
conjunctival mucosa
Roseola Infantum
• Prodrome
– Usually asymptomatic
– Mild URTI signs: minimal rhinorrhea, slight
pharyngeal inflammation, mild conjunctival
redness
– Mild cervical or occipital lymphadenoathy
– Mild palpebral edema
Roseola Infantum
• High fever (average: 39C), lasts for 3-5 days
• Rhinorrhea, sore throat, abdominal pain,
vomiting, diarrhea
• Nagayama spots: ulcers at uvulopalatoglossal
junction
• Rash appears within 12-24 hours of fever lysis
– Rose-colored, discrete, 2-5mm, slightly raised lesions
on trunk  neck  face  proximal ext
– Usu. Non-pruritic, no vesicles or pustules
– Fades after 1-3 days
Clinical Manifestation
Abrupt onset of high
fever with fussiness
Rash: faint pink or rosecolored, nonpruritic, 2- to
3-mm morbilliform rash
Diagnostics
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Clinical presentation
Serology
Virus culture
PCR
Treatment
• Supportive therapy
• HHV-6 inhibit by ganciclovir, cidofovir,
foscarnet (but not acyclovir)
• HHV-7 inhibited by cidovir and foscarnet
• No approved treatment
• Treatment is warranted for
immunocompromised children with severe
disease
– Gangciclovir, cidofovir for 2-3 weeks
RUBELLA
Rubella
• German measles
• Three-day measles
• Rash similar to that of mild rubeola or scarlet
fever
• Enlargement and tenderness of the
postoccipital, retroauricular, and posterior
cervical lymph nodes
• Rubella in early pregnancy may cause the
congenital rubella syndrome
Etiology
• RNA virus
• Genus Rubivirus
• Family Togaviridae
Epidemiology
• Humans are the only natural host of rubella
virus
• Distributed worldwide, affects both sexes
equally
• Spread by:
– Oral droplet
– Transplacentally to the fetus
Epidemiology
• Peak incidence: 5-14 years of age
• In closed populations, such as institutions and
military barracks, almost 100% of susceptible
individuals may become infected.
• In family settings, 50-60% of susceptible
family members acquire the disease.
Epidemiology
• Virus is shed in nasopharyngeal secretions,
blood, feces, and urine
• Virus is present in the nasopharynx 7 days
before exanthem, and 7-8 days after its
disappearance
• Subclinical disease is also infectious
Pathogenesis
• Not well understood
• Virus can be found from both infected and
uninfected areas of the skin
– Immune processes may be important
Pathogenesis
• Primary maternal infection during the 1st
trimester: greatest risk of congenital defects
• <11th wk AOG: 90%
• End of trimester: 10-20%
• >16th wk AOG: low risk for congenital defects
• Overall risk for first trimester infection: 70%
Clinical Manifestations
• Incubation period: 14-21 days
• Prodromal phase of mild catarrhal symptoms
is shorter than that of measles
Clinical Manifestations
• Retroauricular, posterior cervical, and
postoccipital lymphadenopathy
– Most characteristic
• Evident at least 24 hours before the onset of
rashes
• May last up to 1 week
Clinical Manifestations
• Exanthem begins on the face and spreads
quickly
Discrete maculopapules
present in large
numbers + Large areas
of flushing
24 HOURS
Pinpoint appearance
over the trunk,
resembling scarlet fever
+ mild itching
2ND DAY
Eruption + Minimal
desquamation
3RD DAY
Clinical Manifestations
• Forchheimer spots
– Discrete rose-colored
spots on the soft palate
that may coalesce into a
red blush and extend
over the fauses
Clinical Manifestations
• Pharyngeal mucosa and conjunctivae are
slightly inflamed
• No photophobia (in contrast to rubeola)
• Fever is low grade or absent and usually lasts
only for 3 days
• Polyarthritis may occur with arthralgia,
swelling, tenderness, and effusion but usually
without any residuum
• NOT common: headache, malaise, anorexia
Differential Diagnosis
Roseola infantum (exanthem subitum)
Higher fever
Appearance of rash at the end of febrile
episode
Infectious mononucleosis
Associated with generalized
lymphadenopathy
Characteristic atyopical lymphocytosis
Enteroviral infections
Accompanied by gastrointestinal or
respiratory manifestations in the absence
of lymphadenopathy
Drug rashes
History of drug intake
No lymphadenopathy
Diagnosis
• Clinical
• Objective findings:
– Enlarged spleen
– Normal or slightly reduced WBC count
– Thrombocytopenia (rare)
• Confirmed by serology or virus culture
Diagnosis
• Rubella virus can be cultured from the
nasopharynx and blood.
• It is detected by the ability of rubella-infected
African green monkey kidney (AGMK) cells to
resist challenge with enterovirus.
Diagnosis
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Hemagglutination-inhibition (HI) antibody
Latex agglutination
enzyme immunoassay
passive hemagglutination, and
fluorescent immunoassay
Diagnosis
• Immunoglobulin (Ig) M antibodies
– detectable in the first few days of illness
– Also useful for the diagnosis of congenital rubella
syndrome.
• Seroconversion, or a fourfold increase in IgG
titer, is diagnostic.
Treatment
• Supportive treatment
• No specific antiviral therapy
• Antipyretics for fever
Prognosis
• Excellent.
• Infection usually confers permanent immunity,
although reinfection may occur.
Complications
• Encephalitis
– Occurs in about 1 in 6,000 cases
– Overall mortality rate of 20%
– Symptoms usually resolve within 1-3 wk without
neurologic sequelae
• Thrombocytopenic purpura occurs at an
overall rate of 1 in 3,000 cases.
Complications
• The most important consequence of rubella in
a pregnant woman is congenital rubella
syndrome.
• Progressive rubella panencephalitis is a
persistent, slowly progressive rubella infection
of the central nervous system
Congenital Rubella Syndrome
• Intrauterine growth
retardation: most
common manifestations
• Common findings:
– Cataracts
– Myocarditis and structural
cardiac defects
– Blueberry muffin skin
lesions
– Sensorineural hearing loss
– Meningoencephalitis
Congenital Rubella Syndrome
• Diagnosis:
– Rubella-specific IgM antibody in the neonatal
serum, or by culturing rubella virus from the
infant (nasopharynx, urine, or tissues)
– Isolating the virus from amniotic fluid or by
identification of rubella-specific IgM in cord blood.
Congenital Rubella Syndrome
• Prognosis
– Better for infants with fewer stigmata of the
syndrome, presumably those who were initially
infected later in gestation.
– Only 30% of infants with encephalitis appear to
escape residual neuromotor deficitis, including an
autistic syndrome
Reinfection
• The incidence of reinfection
– 3-10% on exposure to wild virus among those with
a history of previous rubella
– 14-18% among those immunized with the RA 27/3
vaccine.
• May lead only to an IgG booster response, to
both an IgM and IgG response, or to clinical
rubella.
Prevention
• Rubella vaccine is derived from the RA 27/3
strain of rubella virus
• Induces antibody in more than 99% of
seronegative recipients and has protective
efficacy in more than 90%
• Vaccine virus may be shed from the
nasopharynx in low titers for as long as 18-25
days after vaccination
Prevention
• MMR
– 1st: recommended at 12-15 mo of age.
– 2nd: recommended routinely at 4-6 yr of age but
may be administered at any time during childhood
provided at least 4 wk have elapsed since the first
dose.
• Pregnant women should not be given live
rubella virus vaccine and should avoid
becoming pregnant for 3 mo after they have
been vaccinated
Prevention
• Symptoms that may follow rubella
immunization include
– Fever (5-15%),
– Rash (5%),
– Lymphadenopathy, and
– Arthralgias and arthritis
Postexposure prophylaxis
• Nonpregnant susceptible contacts of persons
with rubella should be vaccinated
– does not prevent infection but ensures protection
for future rubella exposures
• All pregnant women, regardless of
immunization history, should make every
effort to avoid exposure to rubella.
ERYTHEMA INFECTIOSUM
Parvovirus B19
• Erythema infectiosum
• Fifth disease
Etiology
• Parvovirus B19
– Genus Erythrovirus
– Family Parvoviridae
• Only Parvovirus pathogenic in humans
• Composed of an icosahedral protein capsid
without an envelope that contains singlestranded DNA
• It is relatively heat- and solvent-resistant.
• Replicate in mitotically-active cells
– require host cell factors present in late S phase to
replicate
Epidemiology
• Most prevalent in school-aged children
– 70% of cases occurring between 5 and 15 yr of age
• Transmission:
– respiratory route (large droplet)
• Other mode:
– Blood and blood products
– Fomite
Pathogenesis
• Erythroid cell line
– Primary target
– Specifically erythroid precursors near the
pronormoblast stage
• Viral infection produces lysis of these cells
– progressive depletion and a transient arrest of
erythropoiesis
• Erythrocyte P blood group antigen serves as a
cellular receptor for the virus.
– Found in Endothelial cells, placenta, and fetal
myocardial cells also possess this antigen
Pathogenesis
7-11 days
Biphasic
illness
Viremia,
nasopharyngeal viral
shedding, drop in
reticulocyte count
Fever, malaise,
rhinorrhea
17-18 days
Rash associated with
arthralgia
Pathogenesis
• B19 is associated with nonimmune fetal
hydrops and stillbirth in women experiencing
a primary infection
• Not teratogenic
Clinical Manifestation
• Most common manifestation: erythema
infectiosum
• Benign self-limited exanthematous
• Incubation period: 4-28 days (ave: 16-17 days)
Clinical Manifestation
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Low-grade fever
Headache
Symptoms of mild URTI
Hallmark: characteristic
rash
Clinical Manifestation
• Spares palms and soles
• Prominent on extensor surfaces
• Afebrile and NOT ill-appearing
Erythematous facial
flushing – “slapped
cheek”
Spreads to trunk and
proximal extremities
as diffuse macular
erythema
Central clearing of
macular lesions –
“lacy, reticulated”
Clinical Manifestation
• Papular-purpuric "gloves and socks" syndrome
(PPGSS)
– Fever
– Pruritus
– Painful edema and erythema localized to the distal
extremities in a distinct glove and sock
distribution
– Acral petechiae and oral lesions
Diagnosis
• Clinical
• Serologic tests
– B19-specific IgM: persists for 6-8 wk
– Anti-B19 IgG: marker of past infection/immunity
– Anti-B19 IgM: best marker of recent/acute
infection
– seroconversion of anti-B19 IgG antibodies can also
be used to confirm recent infection
Diagnosis
• Cannot be isolated by culture
– PCR or nucleic acid hybridization are necessary
Differential Diagnosis
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Rubella
Measles
Enteroviral infections
Drug reactions
Juvenile rheumatoid arthritis
SLE
Treatment
• No specific antiviral therapy
• Administration of IVIG may give only a
temporary remission, and periodic reinfusions may be required.
Complications
• Arthralgia or arthritis
– May persist after the rash
• Thrombocytic purpura
• Aseptic meningitis
• Virus-associated hemophagocytic syndrome
Prevention
• Children with erythema infectiosum are not
likely to be infectious at presentation because
the rash and arthropathy represent immunemediated, postinfectious phenomena.
• No vaccine
• No data to support post-exposure prophylaxis
VARICELLA
Varicella-Zoster
• Primary
– Varicella (chickenpox)
– Establishment of lifelong latent infection of
sensory ganglion neurons
• Reactivation
– herpes zoster (shingles)
Etiology
• Neurotropic human herpesvirus
• Double-stranded DNA genomes
Epidemiology
• Within households, transmission to
susceptible individuals occurs at a rate of 6586%;
• More casual contact is associated with lower
attack rates among susceptible children
Epidemiology
• Contagious period:
– From 24-48 hr BEFORE the rash appears
– Until 3-7 days after onset of rash (crusted vesicles)
• Susceptible children may also acquire varicella
after close, direct contact with adults or
children who have herpes zoster.
Epidemiology
• Lifetime risk for herpes zoster is 10-15%
• 75% of cases occurring after 45 yr of age
Pathogenesis
• Transmission:
– Respiratory secretions (airborne)
– Fluid of skin lesions (direct contact)
Pathogenesis
• Incubation period: 10-21 days
– Virus replicates in the respiratory tract followed by
a brief subclinical viremia
– During the late incubation period, virus is
transported back to respiratory mucosal sites
facilitating transmission even before appearance
of rash
• Second viremic phase: Widespread cutaneous
lesions
Pathogenesis
• VZV establishes latent infection in sensory
ganglia cells in all individuals who experience
primary infection.
• Subsequent reactivation: herpes zoster
– a vesicular rash that usually is dermatomal
– necrotic changes may be produced in the
associated ganglia
Clinical Manifestations
• Acute febrile rash illness
• Variable severity but usually self-limited
• Herpes zoster, uncommon in children, causes
localized cutaneous symptoms
Clinical Manifestations
• Illness usually begins 14-16 days after
exposure
Clinical Manifestations
• Fever, malaise, anorexia, headache, and
occasionally mild abdominal pain may occur
24-48 hr before the rash appears.
• Fever and other systemic symptoms persist
during the first 2-4 days after the onset of the
rash.
Clinical Manifestations
• Lesions appear first on
the scalp, face, trunk
• Characteristic: lesions in
various stages
Initial: pruritic
erythematous
macules
Papular stage:
clear, fluidfilled vesicles
Clouding and
umbilication
Clinical Manifestations
• Distribution: central or centripetal
– As opposed to smallpox where rashes are
prominent on the face and distal extremities
Clinical Manifestations
• Hypopigmentation or hyperpigmentation of
lesion sites persists for days to weeks in some
children, but severe scarring is unusual unless
the lesions were secondarily infected
Differential Diagnosis
• Includes vesicular rashes caused by other
infectious agents
– herpes simplex virus
– enterovirus, or
– Staphylococcus aureus;
• Drug reactions
• Contact dermatitis
• Insect bites.
Diagnosis
• Leukopenia is typical during the first 72 hours;
it is followed by a relative and absolute
lymphocytosis. Results of liver function tests
are also usually (75%) mildly elevated
Diagnosis
• VZV can be identified quickly by direct
fluorescence assay (DFA) of cells from
cutaneous lesions, which is widely available,
and by polymerase chain reaction (PCR)
amplification testing. Although multinucleated
giant cells can be detected with nonspecific
stains (Tzanck smear), they have poor
sensitivity and do not differentiate VZV and
herpes simplex virus infections.
Diagnosis
• Infectious virus may be recovered using tissue
culture methods; newer methods have decreased
time needed for culture from 7-10 days to 3-4
days. VZV immunoglobulin G (IgG) antibodies can
be detected by several methods and a 4-fold rise
in IgG antibodies is also confirmatory of acute
infection. VZV IgG antibody tests can also be
valuable to determine the immune status of
individuals whose clinical history of varicella is
unknown or equivocal.
Treatment
• Antiviral treatment modifies the course of
both varicella and herpes zoster.
• Acyclovir
• Foscarnet for acyclovir-resistant VZV
Treatment
• Oral therapy with acyclovir (20 mg/kg/dose;
maximum: 800 mg/dose) given as 4 doses per
day for 5 days should be used to treat
uncomplicated varicella
• To be most effective, treatment should be
initiated as early as possible, preferably within
24 hr of the onset of the exanthem.
Complications
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Bacterial super-infection
Pneumonia
Encephalitis
Bleeding disorders
Congenital infection
Life-threatening perinatal infection