Varicella and Varicella Vaccines

1

• Varicella and Varicella Vaccines

Epidemiology and Prevention of Vaccine-Preventable
Diseases National Center for Immunization and
Respiratory Diseases Centers for Disease Control
and Prevention
Revised May 2009
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Varicella Zoster Virus

• Herpesvirus (DNA)
• Primary infection results in varicella
  (chickenpox)
• Recurrent infection results in herpes zoster
  (shingles)
• Short survival in environment

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Varicella Pathogenesis

• Respiratory transmission of virus
• Replication in nasopharynx and regional lymph
  nodes
• Repeated episodes of viremia
• Multiple tissues, including sensory ganglia,
  infected during viremia

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Varicella Clinical Features

• Incubation period 14-16 days (range 10-21 days)
• Mild prodrome for 1-2 days
• Rash generally appears first on head most
  concentrated on trunk
• Successive crops over several days with lesions
  present in several stages of development

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Herpes Zoster (Shingles)

• Reactivation of varicella zoster virus
• Associated with
• aging
• immunosuppression
• intrauterine exposure
• varicella at younger than 18 months of age

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Varicella Complications

• Bacterial infection of skin lesions
• Pneumonia (viral or bacterial)
• Central nervous system manifestations
• Reye syndrome
• Hospitalization 2-3 per 1,000 cases
• Death 1 per 60,000 cases
• Postherpetic neuraligia (complication of zoster)

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Groups at Increased Risk of Complications of
Varicella

• Persons older than 15 years
• Infants younger than 1 year
• Immunocompromised persons
• Newborns of women with rash onset within 5 days
  before to 48 hours after delivery

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Complications of Herpes Zoster

• Postherpetic neuralgia (PHN)
• Ophthalmic zoster
• Dissemination with generalized skin eruptions and
  involvement of the central nervous system, lungs,
  liver and pancreas

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• Varicella Fatality Rate-United States, 1990-1994

Deaths per 100,000 cases. Meyer et al, J Infect
Dis 2000182383-90
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Congenital Varicella Syndrome

• Results from maternal infection during pregnancy
• Period of risk may extend through first 20 weeks
  of pregnancy
• Low birth weight, atrophy of extremity with skin
  scarring, eye and neurologic abnormalities
• Risk appears to be small (less than 2)

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Varicella Laboratory Diagnosis

• Isolation of varicella virus from clinical
  specimen
• Rapid varicella virus identification using PCR
  (preferred, if available) or DFA
• Significant rise in varicella IgG by any standard
  serologic assay (e.g., enzyme immunoassay)

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Varicella Epidemiology

• Reservoir Human
• Transmission Airborne droplet Direct
  contact with lesions
• Temporal pattern Peak in winter and early
  spring (U.S.)
• Communicability 1-2 days before to 4-5 days
  after onset of rash May be longer in
  immunocompromised

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• Varicella Age-Specific Incidence United States,
  1990-1994

Rate per 100,000 population. National Health
Interview Survey data
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Varicella Cases by Month -- Antelope Valley, CA,
19952004
1995
1997
1998
1996
1999
2000
2001
2002
2003
2004
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Reduction in Age-Specific Varicella Incidence
RateVaricella Active Surveillance Project Sites,
1995 to 2004
2003 population used for rate calculations
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Varicella in the United States

• Increasing proportion of cases are a result of
  breakthrough infection
• Outbreaks reported in schools with high varicella
  vaccination coverage
• Persons with breakthrough infection may transmit
  virus

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Herpes Zoster

• 500,000 to 1 million episodes occur annually in
  the United States
• Lifetime risk of zoster estimated to be 32
• 50 of persons living until age 85 years will
  develop zoster

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Varicella-Containing Vaccines

• Varicella vaccine (Varivax)
• approved for persons 12 months and older
• Measles-mumps-rubella-varicella vaccine (ProQuad)
• approved for children 12 months through 12 years
• Herpes zoster vaccine (Zostavax)
• approved for persons 60 years and older

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Varicella Vaccine Immunogenicity and Efficacy

• Detectable antibody
• 97 of children 12 months-12 years following 1
  dose
• 99 of persons 13 years and older after 2 doses
• 70-90 effective against any varicella disease
• 95-100 effective against severe varicella
  disease

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Varicella Breakthrough Infection

• Immunity appears to be long-lasting for most
  recipients
• Breakthrough disease much milder than in
  unvaccinated persons
• No consistent evidence that risk of breakthrough
  infection increases with time since vaccination

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Varicella Breakthrough Infection

• Retrospective cohort study of 115,000 children
  vaccinated in 2 HMOs during January 1995 through
  December 1999
• Risk of breakthrough varicella 2.5 times higher
  if varicella vaccine administered less than 30
  days following MMR
• No increased risk if varicella vaccine given
  simultaneously or more than 30 days after MMR

MMWR 200150(47)1058-61
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Herpes Zoster Vaccine Efficacy

• Compared to the placebo group the vaccine group
  had
• 51 fewer episodes of zoster
• Lower efficacy for older recipients
• Less severe disease
• 66 less postherpetic neuralgia
• Duration of immunity unknown

NEJM 2005352(22)2271-84.
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Varicella Vaccine RecommendationsChildren

• Routine vaccination at 12-15 months of age
• Routine second dose at 4-6 years of age
• Minimum interval between doses of varicella
  vaccine for children younger than 13 years of age
  is 3 months

MMWR 2007 56 (No. RR-4)1-40
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Varicella Vaccine RecommendationsOlder Children
and Adults

• 2 doses recommended for all persons older than 4
  to 6 years who do not have evidence of varicella
  immunity
• Second dose recommended for persons of any age
  who have only received one dose

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Minimum Intervals Between Doses of Varicella
Vaccine

• 12 months through 12 years of age
• 13 years of age or older

• 3 months
• 4 weeks

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Varicella Vaccination of Healthcare Personnel

• Recommended for all susceptible healthcare
  workers
• Prevaccination serologic screening probably
  cost-effective
• Postvaccination testing not necessary or
  recommended

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MMRV Vaccine

• Approved for children 12 months through 12 years
  of age (to age 13 years)
• Do not use for persons 13 years and older
• May be used for both first and second doses of
  MMR and varicella vaccines
• Minimum interval between doses is 3 months

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Herpes Zoster Vaccine

• ACIP recommends a single dose among persons 60
  years and older
• May vaccinate regardless of prior history of
  herpes zoster (shingles)
• Persons with a chronic medical condition may be
  vaccinated unless a contraindication or
  precaution exists for the condition

MMWR 200857(No. RR-5)
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Varicella Immunity

• Written documentation of age-appropriate
  vaccination
• Laboratory evidence of immunity or laboratory
  confirmation of disease
• Born in the United States before 1980
• Healthcare provider diagnosis or verification of
  varicella disease
• History of herpes zoster based on healthcare
  provider diagnosis

except healthcare personnel and pregnant women.
MMWR 200756(No. RR-4)
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Varicella VaccinePostexposure Prophylaxis

• Varicella vaccine is recommended for use in
  persons without evidence of varicella immunity
  after exposure to varicella
• 70-100 effective if given within 72 hours of
  exposure
• not effective if administered more than 5 days
  after exposure but will produce immunity if not
  infected

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Varicella Vaccine Adverse Reactions

• Local reactions (pain, erythema)
• 19 (children)
• 24 (adolescents and adults)
  
  
• Rash 3-4
• may be maculopapular ratherthan vesicular
• average 5 lesions
• Systemic reactions not common
• Adverse reactions similar for MMRV

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Zoster Following Vaccination

• Most cases in children
• Not all cases caused by vaccine virus
• Risk from vaccine virus less than from wild-type
  virus
• Usually a mild illness without complications such
  as postherpetic neuralgia

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Herpes Zoster Vaccine Adverse Reactions

• Local reactions - 34
• (pain, erythema)
• No increased risk of fever
• No serious adverse reactions identified

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Adverse Reactions Following MMRV or MMRV
Shinefield et al, PIDJ 2005 CDC unpublished data
2008
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Adverse Reactions Following MMRV and MMRV

• Fever is more common in the 5-12 days after
  vaccination following MMRV (22) than following
  MMRV (15)
• Data from CDC Vaccine Safety Datalink sites
  indicate the rate of febrile seizures following
  MMRV (9 per 10,000 vaccinated ) was approximately
  2 times higher than among those receiving MMRV
  at the same visit (4 per 10,000 vaccinated)

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Adverse Reactions Following MMRV and MMRV

• During the 7-10 days after vaccination about one
  additional febrile seizure would be expected to
  occur for every 2,000 children who receive MMRV
  vaccine rather than separate MMR and varicella
  vaccines
• In February 2007 ACIP voted to have no preference
  for the use of MMRV over the use of MMR and
  varicella vaccines administered separately

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Varicella-Containing VaccinesContraindications
and Precautions

• Severe allergic reaction to vaccine component or
  following a prior dose
• Immunosuppression
• Pregnancy
• Moderate or severe acute illness
• Recent blood product (except herpes zoster
  vaccine)

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Varicella-Containing VaccinesUse in
Immunocompromised Persons

• Most immunocompromised persons should not receive
  varicella-containing vaccines
• Varicella vaccine may be administered to persons
  with isolated humoral immunodeficiency
• Do not administer zoster vaccine to
  immunosuppressed persons

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Varicella Vaccine and HIV Infection

• MMRV not approved for use in persons with HIV
  infection
• Consider varicella vaccination for HIV-infected
  children with CD4 of 15 or higher
• Consider varicella vaccination for HIV-infected
  older children and adults with CD4 count of 200
  or higher

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• Varicella Vaccination in Pregnancy Registry

800.986.8999
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Zoster VaccineContraindications and Precautions

• Severe allergic reaction to a vaccine component
  or following a prior dose
• Pregnancy or planned pregnancy within 4 weeks
• Immunosuppression from any cause

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Zoster VaccineContraindications Immunosuppression

• Leukemia, lymphoma or other malignant neoplasm
  affecting the bone marrow or lymphatic system
• AIDS or other clinical manifestation of HIV
  infection
• High-dose corticosteroid therapy
• Recombinant human immune mediators and immune
  modulators

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Zoster VaccinePrecautions

• Moderate or severe acute illness
• Current treatment with an antiviral drug active
  against herpesviruses
• Recent receipt of a blood product is NOT a
  precaution

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Transmission of Varicella Vaccine Virus

• Transmission of vaccine virus is a rare event
• Transmission appears to occur only if the
  vaccinee develops a rash
• Transmission of vaccine virus from recipients of
  zoster vaccine has not been reported

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Varicella-Containing VaccineStorage and Handling

• Store frozen at 5F (-15C ) or lower at all
  times
• Store diluent at room temperature or refrigerate
• Discard if not used within 30 minutes of
  reconstitution

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Vaccine Storage and HandlingMMRV Vaccine

• Must be stored at an average temperature of 5oF
  (-15oC ) or colder at all times
• May be stored at refrigerator temperature for up
  to 72 hours but must then be discarded if not
  used (do not refreeze)
• Must be administered within 30 minutes of
  reconstitution or must be discarded

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• Varicella Vaccine Information

800-9VARIVAX
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CDC Vaccines and ImmunizationContact Information

• Telephone 800.CDC.INFO
• Email nipinfo_at_cdc.gov
• Website www.cdc.gov/vaccines