# Presentation: 230206

## Varicella, Zoster, and Varicella Vaccines

**Epidemiology and Prevention of Vaccine-Preventable Diseases**
**National Immunization Program**
**Centers for Disease Control and Prevention**

**Revised January 2007**
**Update April 2007**

## Varicella Zoster Virus

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

## 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**

## 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**

## Herpes Zoster (Shingles)

**Reactivation of varicella zoster virus**
**Can occur years or even decades after illness with chickenpox**
**Generally associated with normal aging and with anything that causes reduced immunocompetence**
**Lifetime risk of 20 percent in the United States**
**Estimated 500,000- 1 million cases of zoster diagnosed annually in the U.S   **

## 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)**

## 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**

## Varicella Fatality Rate-United States, 1990-1994

***Deaths per 100,000 cases.  Meyer et al, *****J Infect Dis***** 2000;182:383-90**

## 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%)**

## 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)**

## 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**

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

***Rate per 100,000 population.  National Health Interview Survey data**

## Varicella Cases by Month -- Antelope Valley, CA, 1995–2004

**1995**

**1997**

**1998**

**1996**

**1999**

**2000**

**2001**

**2002**

**2003**

**2004**

## Reduction in Age-Specific Varicella Incidence RateVaricella Active Surveillance Project Sites, 1995 to 2004

| Age group | Antelope Valley, CA* (%) | West Philadelphia
(%) |
| --- | --- | --- |
| < 1  | 83 | 77 |
| 1-4 | 94 | 89 |
| 5-9 | 83 | 95 |
| 10-14 | 49 | 98 |
| 15-19 | 65 | 78 |
| 20+ | 81 | 67 |
|  Total | 83 | 93 |

***2003 population used for rate calculations**

**Notes:**
Reduction in varicella incidence has been observed in all age groups.  
However, the greatest reduction was in the 1-4 and 5-9 year old groups, the age groups primarily targeted by the vaccination program.  

## 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**

## Herpes Zoster

**500,000 to 1 million episodes occur annually in the United States**
**Lifetime risk of zoster estimated to be at least 20%**
**50% of persons living until age 85 years will develop zoster**

## 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**

## Varicella Vaccines

**All three vaccines contain the same live  Oka-Merck varicella vaccine virus but in different concentrations**
**-Varivax - 1,400 pfu**
**ProQuad - 9,800 pfu (7x Varivax)**
**Zostavax - 19,000 pfu (14x Varivax) **

## 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**

## Varicella Breakthrough Infection

**Immunity appears to be long-lasting for most recipients**
**Breakthrough disease much milder than in unvaccinated persons**
**Recent evidence that risk of breakthrough infection increases with time since vaccination***

***Chavez et al. *****New Eng J Med***** 2007;356:1121-9**

## 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***** 2001;50(47):1058-61**

## 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***** 2005;352(22):2271-84.**

## Varicella Vaccine RecommendationsChildren

**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**

***provisional recommendation as of January 2007**

## Varicella Vaccine RecommendationsAdolescents and Adults

**All persons 13 years of age and older without evidence of varicella immunity**
**Two doses separated by at least 4 weeks**
**Do not repeat first dose because of extended interval between doses**

## Varicella Vaccine-MinimumInterval Between Doses

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

**3 months**
**4 weeks**

## Varicella Vaccination of Healthcare Workers

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

## 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**

## Herpes Zoster Vaccine*

**Approved for 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 **

***provisional recommendations as of January 2007**

## 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 **

***provisional recommendations as of January 2007**

## Varicella VaccinePostexposure 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**

## Varicella Vaccine Adverse Reactions

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

## 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**

## Herpes Zoster Vaccine Adverse Reactions

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

## Varicella-Containing VaccinesContraindications 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)**

## Varicella-Containing VaccinesUse in Immunocompromised Persons

**Most immunocompromised persons should receive varicella-containing vaccines**
**Varicella vaccine may be administered to persons with isolated humoral immunodeficiency**
**Consider varicella vaccination for HIV-infected children with CD4%  of 15% or higher**

## Varicella VaccineUse in Immunocompromised Persons

**MMRV not approved for use in persons with HIV infection**
**Do not administer zoster vaccine to immunosuppressed persons**

## Varicella Vaccination in Pregnancy Registry

- 800.986.8999

## 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**

## Varicella-Containing VaccineStorage and Handling

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

## Varicella Vaccine Information

- 800-9VARIVAX

## National Immunization ProgramContact Information

**Telephone****	****	****800.CDC.INFO**** **
**Email****	****	****	****nipinfo@cdc.gov**** **
**Website****	****	****www.cdc.gov/nip**