Varicella Zoster Virus
:: Herpes virus (DNA) :: Primary Infection results in varicella (chickenpox)
:: Recurrent infection results in herpes zoster (shingles)
:: Short survival in environment

Varicella Pathogenesis
:: Respiratory transmission of virus :: Repeated episodes of viremia
:: Replication in nasopharynx and regional lymph nodes

Varicella (Chickenpox) in children
:: Self limiting and benign illness in children <10 yrs of age
:: Children more than 10 yrs of age, adolescence and adults are prone for complications.
:: Not recognized as a serious public health problem in India
:: Only 50% become sero positive by 10 yrs of age
:: It is estimated the 28 million cases occur annually in India
:: 15-20% with the history of prior exposure to chickenpox to develop zoster later in life with an estimated figure of 5-6 million cases annually.
:: Overall mortality 8 per 100,000 cases in <1 year old healthy children: 2 per 100,000 in children 1-8 yrs old: 25 per 100,000 in children more than 8 yrs old. In immunocompromised adolescence >10%: adults >20-40%

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

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
::Post herpetic neuralgia (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 2 days after delivery

Congenital Varicella Syndrome
::Results from maternal infection during pregnancy
::Low birth weight, atrophy of extremity with skin scarring, eye and neurological abnormalities

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)
::Communicability1-2 days before to 4-5 days after onset or rash May be longer in Immunocompromised
Varicella-Containing Vaccines
::Varicella vaccines available in India:
Okavax, Varilrix, Varivax,
::Measles-mumps-rubella-varicella vaccine (ProQuad)
- approved for children 15 months through 12 years in US
::Herpes zoster vaccine (Zostavax)
-approved for persons 60 years and older in US

Varicella Vaccine Immunogenicity and Efficacy
::Detectable antibody
- 97% of children 15 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 – I
::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
::Retrospective cohort study of 115,000 children vaccinated in US (January 1995 through December 1999)
::Risk of breakthrough varicella 2.5 times higher if varicella vaccine administered less than 28 days following MMR
::No increased risk if varicella vaccine given simultaneously or more than 28 days after MMR

Varicella Breakthrough Infection – II
::Breakthrough infection after varicella vaccination is common if:
:: - Vaccine is administered before 15 months of age
- Interval between varicella and MMR vaccine administration
is <28 days
time lapse is more than 3 yrs after 1st dose

Varicella Vaccine Recommendations in Children – I
::Routine vaccination at 15 months of age
::Routine second dose at 4-6 years of age in US
::Minimum interval between doses of varicella vaccine for children younger than 13 years of age is 3 months

Varicella Vaccine Recommendations in Children, Adolescence and Adults – II
::A single dose in countries where NO universal immunization exists.
::It is believed that immunity is reinforced persistently by sub-clinical reinfections due to epidemics in the community.
::In countries with universal varicella immunization with high coverage out breaks reported in over 90% of children in schools who have received a single dose already due to lack of natural immunity due to sub clinical infection in the community, shift of epidemiology to the right and threat of severe disease in adolescence and adults a second dose is recommended
::All persons 13 years of age and older without evidence of varicella immunity
::Two doses separated by at lease 4 weeks

Varicella Vaccine Recommendations Healthcare Personnel
::Recommended for all susceptible healthcare personnel
::Prevaccination serologic screening probably cost-effective
::Post vaccination testing not necessary or recommended

MMRV Vaccine
::Approved for children 12 months through 12 years of age (to age 13 years) abroad
::Do not use for persons 13 years and older
::May be used for both first and second doses of MMR and Varicella vaccines in children <12 yrs of age
::Minimum interval between doses is 3 months

Varicella Vaccine Post exposure 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 Immunity
:: written documentation of age – appropriate vaccination
:: Laboratory evidence of immunity or laboratory confirmation of diseases
:: Healthcare provider diagnosis or verification of varicella disease
:: History of herpes zoster based on healthcare provider diagnosis


Varicella Vaccine Adverse Reactions
:: Local reactions (pain, erythema)
- 19% (children)
- 24% (adolescents and adults)
:: Generalized rash – 4% -6%
- may be maculopapular rather than vesicular
- Average 5 lesions
:: Systemic reactions not common
:: Adverse reactions similar for MMV

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 post herpetic neuralgia

Varicella-Containing Vaccines Contraindications and Precautions
:: Severe allergic reactions 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 not 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

Transmission of Varicella Vaccine Virus

:: Transmission of vaccine virus is a rare event
:: Transmission appears to occurs 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 at +4oC-8oC all times
:: Store diluents at lower self of home refrigerator
:: Discard if not used within 30 minutes of reconstitution

Summary
Varicella infection and vaccination in children
:: A benign infection in children <10 yrs of age. In adolescence >10 yrs of age and adults serious complications may arise resulting in mortality
:: Highly contagious disease with greater morbidity in children resulting in infection within the family members and epidemics in the community.
:: Preventable through effective vaccination starting at 15 months of age or above
:: IAP recommends a single dose after 15 months of age on “one to one” counseling basis
:: Many Pediatricians in India have come across breakthrough infection in school going children who have received a single dose
:: My personal experience is also endorses this view and hence the practice of administering second dose of the vaccine at 4-6 yrs of age to minimize breakthrough infection is recommended in private practice.

Acknowledgments
1.Varicella: in EPIDEMIOLOGY AND PEVENTION OF VACCINE – PREVENTABLE DISEASES Eds. William Atkinson, Hamborsky J, McIntyre L, Wolfe S – Department of Health and Human Services – Centre For Disease Control and Prevention Atlanta, US – 10th Edition updated February 2007.
2.Varicella vaccination in children in A monograph on immunization - controversies answered Eds. Tapan Kr. Gosh, Jayadeep Choudhry, Ritabrata Kundu – May 2007 – National Conference on Immunization: ID Chapter Publication.