Canadian Immunization Guide: Part 4 - Active Vaccines

Varicella (Chickenpox) Vaccine

Updated: September 2016

Key Information (refer to text for details)

What

  • Primary varicella zoster virus infection causes varicella (chickenpox) and reactivated infection results in herpes zoster (shingles).
  • Complications are more common in adolescents, adults and immunocompromised individuals. Individuals with impaired immunity are at risk of severe varicella and death.
  • Varicella-containing vaccine is available as univalent varicella vaccine or combined multivalent measles-mumps-rubella-varicella (MMRV) vaccine.
  • The efficacy of varicella vaccines in children is estimated to be 94.4% following a single dose and 98.3% following a second dose.
  • Reactions to univalent varicella vaccines include: pain, swelling and redness at the injection site in 10% to 20% of vaccine recipients; low grade fever in 10% to 15%; and a varicella-like rash in 3% to 5% of vaccine recipients after the first dose and 1% after the second dose.
  • Reactions to MMRV vaccine include: pain and redness at the injection site and fever less than 39°C in 10% or more of vaccine recipients; measles-like, rubella-like or varicella-like rash, swelling at the injection site and fever greater than 39°C in less than 10% of vaccine recipients.
  • When the first dose is administered to children 12 to 23 months of age as MMRV vaccine, there is a higher risk of fever and febrile seizures in the 7 to 10 days after vaccination when compared to separate administration of measles-mumps-rubella (MMR) and univalent varicella vaccine at the same visit.
  • Febrile seizures following vaccination with a varicella-containing vaccine should be reported as an Adverse Events Following Immunization.

Who

  • Univalent varicella or MMRV vaccine is recommended for routine immunization of healthy children aged 12 months to less than 13 years of age.
  • Univalent varicella vaccine is recommended for susceptible adolescents (13 to less than 18 years of age) and susceptible adults (18 to less than 50 years of age).
  • Univalent varicella vaccine may be considered for people with select immunodeficiency disorders.
  • Varicella immunization should be prioritized for the following susceptible individuals:
    • Non-pregnant women of childbearing age
    • Household contacts of immunocompromised individuals
    • Members of a household expecting a newborn
    • Health care workers
    • Adults who may be exposed occupationally to varicella (for example, people who work with young children)
    • Immigrants and refugees from tropical regions
    • People receiving chronic salicylate therapy (for example, acetylsalicylic acid [ASA])
    • People with cystic fibrosis
    • Susceptible adults exposed to a case of varicella

How

  • Routine childhood immunization: 2 doses of any varicella-containing (univalent varicella or MMRV) vaccine. The first dose of varicella-containing vaccine should be administered at 12 to 15 months of age and the second dose at 18 months of age or any time thereafter, but no later than around school entry.
  • Children aged 12 months to less than 13 years of age not immunized on the routine schedule: 2 doses of any varicella-containing vaccine.
  • Adolescents (13 to less than 18 years of age) and adults (18 to less than 50 years of age) susceptible to varicella: 2 doses of univalent varicella vaccine.
  • Salicylates (for example, ASA) should be avoided for 6 weeks after varicella vaccination.
  • Varicella-containing vaccine may be administered concomitantly with other routine childhood vaccines at different injection sites using separate needles and syringes.

Why

  • Varicella occurs worldwide.
  • In the pre-vaccine era, approximately 350,000 varicella cases and 1,500 to 2,000 varicella-related hospitalizations occurred each year in Canada, primarily among healthy children up to 12 years of age.
  • Adults, and in particular pregnant women, are at increased risk of severe disease.

Significant revisions included in this chapter are highlighted in the Table of Updates to the Canadian Immunization Guide.

Epidemiology

Disease description

Infectious agent

Varicella (chickenpox) is a generalized viral disease caused by varicella zoster virus (VZV), a deoxyribonucleic acid (DNA virus) of the Herpesvirus family. For additional information about VZV, refer to the Pathogen Safety Data Sheet.

Reservoir

Humans

Transmission

VZV is spread by the airborne route, as well as by direct contact with virus shed from skin lesions. The attack rate among susceptible contacts in household settings is estimated at 65% to 87%. The incubation period is from 10 to 21 days after exposure, usually 14 to 16 days. Infectiousness begins 1 to 2 days before onset of the rash and lasts until the last lesion has crusted.

Risk factors

Risk of varicella infection severity increases with age. Although in healthy children varicella is considered to be a relatively benign disease, serious complications can occur.

Persons at increased risk of severe varicella

The following groups of individuals are considered to be at increased risk of severe varicella:

  • Newborn infants of mothers who develop varicella from 5 days before until 48 hours after delivery.
  • Neonates in intensive care settings born at less than 28 weeks of gestation or weighing 1,000 g or less at birth, regardless of their mothers' evidence of immunity.
  • Susceptible pregnant women. Refer to Susceptibility and immunity for a definition of susceptible. Refer to Pregnancy and breastfeeding for additional information.
  • Susceptible immunocompromised persons, including HIV-infected persons with CD4 cell count <200 × 106/L or CD4 percentage <15%. Refer to Susceptibility and immunity for a definition of susceptible. Refer to HIV infection for additional information.
  • Recipients of hematopoietic stem cell transplantation (HSCT) regardless of pre-transplant varicella immune status or post-transplant immunization history including varicella disease, vaccination or positive serologic test results. Refer to Hematopoietic stem cell transplantation (HSCT) for additional information.
Seasonal and temporal patterns

The number of varicella disease cases increases during the school year and decreases sharply during summer vacation.

Spectrum of clinical illness

Symptoms of varicella include low-grade fever, mild constitutional symptoms, and a generalized, pruritic rash, with lesions at different stages that progress rapidly from macules to papules to vesicular lesions before crusting. The main complications of varicella include secondary bacterial skin and soft tissue infections, bacteremia, pneumonia, osteomyelitis, septic arthritis, necrotizing fasciitis, toxic shock-like syndrome, cerebellar ataxia, stroke and encephalitis. Varicella increases the risk of severe invasive group A streptococcal infection in previously healthy children by 40-fold to 60-fold. Complications are more common in adolescents, adults and people with conditions that compromise their immune system, in whom there are higher rates of pneumonia, encephalitis and death.

Congenital varicella syndrome is rare when infection occurs before the 13 or after the 20 weeks of gestation. The risk is approximately 2% when infection occurs between 13 and 19 weeks of gestation. Congenital infection results in a wide clinical spectrum, which may include low birth weight, ophthalmic abnormalities, skin scarring, limb atrophy, cerebral atrophy and a variety of other anomalies. Maternal varicella occurring in the 5 days before to 2 days after birth is associated with severe neonatal varicella in 17% to 30% of infants, with high case fatality for the newborn.

Disease distribution

In countries without vaccination programs, varicella is mainly a disease of childhood, developing in 50% of children by the age of 5 years and 90% by the age of 12 years. In the pre-vaccine era, approximately 350,000 varicella cases and 1,500 to 2,000 varicella-related hospitalizations occurred each year in Canada. Since the introduction of immunization programs in Canada, there has been a decrease in the burden of varicella.

For more information about varicella disease, including disease description, distribution and epidemiology, refer to the varicella (chickenpox) website.

Immunizing Agents Available for Use in Canada

Varicella-containing vaccines

  • VARIVAX®III (live, attenuated univalent varicella virus vaccine [Oka/Merck]), Merck Canada Inc. (Var)
  • VARILRIX® (live, attenuated univalent varicella virus vaccine [Oka/GSK]), GlaxoSmithKline Inc. (Var)
  • PRIORIX-TETRA® (live, attenuated combined measles, mumps, rubella and varicella vaccine), GlaxoSmithKline Inc. (MMRV)
  • PROQUAD™ (live, attenuated combined measles, mumps, rubella and varicella vaccine), Merck Canada Inc. (MMRV)

Varicella zoster immune globulin

  • VariZIG™ (varicella zoster immune globulin [human]), Cangene Corporation (VarIg)

For complete prescribing information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database.

Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for lists of vaccines and passive immunizing agents available for use in Canada and their contents.

Immunogenicity, Efficacy and Effectiveness

Immunogenicity

In healthy children 12 months to 12 years of age, a single univalent varicella vaccine dose results in a seroconversion rate of 98% at 4 to 6 weeks after vaccination, with antibodies persisting in 98% at 5 years and 96% at 7 years after vaccination. A second dose of a univalent varicella vaccine in children produces an improved immunologic response that is correlated with improved protection. In adults and adolescents 13 years of age and older, 2 vaccine doses administered 4 to 8 weeks apart result in seroconversion rates of 99% at 4 to 6 weeks after the second dose, with persistence of antibodies 5 years later in 97% of vaccine recipients.

In 12 month old children, a single dose of MMRV vaccine results in similar seroconversion rates and geometric mean titres as those achieved after concomitant administration of measles-mumps-rubella (MMR) vaccine and univalent varicella vaccine. For additional information about the immunogenicity of MMRV vaccine, refer to Measles Vaccine in Part 4.

Efficacy and effectiveness

The rate of breakthrough varicella disease in vaccine recipients following 1 dose of univalent varicella vaccine has been estimated at 7.2% over a 10 year follow-up period. A 2 dose primary schedule for children 12 months to 12 years of age has shown to reduce the cumulative risk of breakthrough disease 3.3-fold compared to children who received only 1 dose. The estimated vaccine effectiveness 10 years following the receipt of 2 doses of univalent varicella vaccine is estimated at over 98% against any varicella disease and 100% against severe varicella.

There are no data regarding the long-term effectiveness of MMRV vaccine.

Recommendations for Use

Healthy children (12 months to less than 18 years of age)

Schedule
Routine schedule
Healthy children (12 months to less than 13 years of age)

For routine immunization of children aged 12 months to less than 13 years, 2 doses of varicella-containing vaccine, using either univalent varicella or MMRV vaccine, should be administered. The first varicella-containing vaccine dose should be administered at 12 to 15 months of age and the second dose at 18 months of age or any time thereafter, but no later than around school entry. The minimum interval between 2 doses is 3 months.

The optimal interval between doses will depend on the goal of the immunization program. If the goal of immunization is to achieve higher antibody levels to prevent breakthrough disease among preschool age children, the second dose of the varicella-containing vaccine should be provided closer to the first dose (for example at 12 and 15 months of age, or at 12 and 18 months of age). Alternatively, reduction of primary vaccine failure among school age children is likely to be better achieved by providing the second dose of a varicella-containing vaccine closer to school entry (4 to 6 years of age).

Children with a history of varicella disease occurring before 12 months of age should receive routine immunization with 2 doses of varicella-containing vaccine after 12 months of age, because varicella disease at less than 12 months of age has been associated with an increased risk of a second episode of varicella. Children who receive 1 dose of varicella-containing vaccine and subsequently develop laboratory confirmed breakthrough infection do not require a second dose of a varicella-containing vaccine for varicella protection.

Catch-up and accelerated schedules
Children (12 months to less than 13 years of age)

Two doses of varicella-containing vaccine, using either univalent varicella or MMRV vaccine, should be administered to children less than 13 years of age who were not immunized on the routine schedule. For preschool aged children, 2 doses of varicella-containing vaccine should be administered before school entry (4 to 6 years of age). Although the recommended routine interval between doses for children less than 13 years of age is 3 months, when rapid protection is required, a minimum interval of 4 weeks may be used.

Adolescents (13 to less than 18 years of age)

Adolescents without contraindications who do not meet the definition for varicella immunity (refer to Susceptibility and immunity for a definition of susceptible) should receive 2 doses of a univalent varicella vaccine, as MMRV is not authorized for use in this age group. In adolescents with documentation of having received only 1 dose of a varicella-containing vaccine, a second dose should be offered. The minimum interval between doses is 4 weeks.

Refer to Timing of Vaccine Administration in Part 1 for additional information about delayed immunization schedules and accelerated immunization schedules.

Healthy adults (18 years of age and older)

Adults less than 50 years of age

Adults less than 50 years of age without contraindications who do not meet the definition for varicella immunity (refer to Susceptibility and immunity) should receive 2 doses of univalent varicella vaccine, as MMRV is not authorized for use in this age group. The minimum interval between doses is 4 weeks.

Susceptible women of childbearing age are considered to be a priority for varicella immunization because varicella-containing vaccine should not be given during pregnancy. Adults less than 50 years of age who have received only 1 dose of varicella vaccine should be offered a second dose.

Adults 50 years of age and older

In the rare circumstance that an adult 50 years of age and over is known to be serologically susceptible to varicella based on previous laboratory testing, the individual should be vaccinated with 2 doses of univalent varicella vaccine. The minimum interval between doses is 4 weeks. For other adults 50 years of age and over, refer to Herpes Zoster (Shingles) Vaccine in Part 4.

Refer to Immunization of Adults in Part 3 for additional information about routinely recommended immunization for adults as well as vaccines recommended for adults in specific risk situations. Refer to Timing of Vaccine Administration in Part 1 for additional information about delayed immunization schedules and accelerated immunization schedules.

Susceptibility and immunity

Individuals who have ANY of the following are considered immune to varicella:

  • Documented evidence of immunization with 2 doses of a varicella-containing vaccine
  • Laboratory evidence of immunity

If varicella occurred before the year of a one-dose vaccine program implementation (refer to Table 1), a self-reported history or health care provider diagnosis is considered a reliable correlate of immunity for healthy individuals, including pregnant women without significant exposure to VZV (refer to Significant exposures to VZV) and health care workers (HCW) who are currently or have previously been employed in a Canadian health care setting. In general, healthy adults 50 years of age and older, are presumed to be immune to varicella, even if the person does not remember having had chickenpox or herpes zoster (shingles, HZ).

If varicella occurred after the year of a one-dose immunization program implementation (refer to Table 1), a self-reported history or health care provider diagnosis cannot be considered a reliable correlate of immunity because one-dose immunization programs had a marked impact on the prevalence of wild-type varicella. A self-reported history or diagnosis of varicella or HZ by a health care provider is not considered an acceptable evidence of immunity for:

  • healthy pregnant women with significant exposure to VZV (refer to Significant exposures to VZV),
  • immunocompromised individuals, and
  • HCW who are newly hired into the Canadian health care system.

Recipients of a hematopoietic stem cell transplant (HSCT) should be considered susceptible in the post-transplantation period, regardless of a pre-transplant history of vaccination, positive serologic results or varicella or HZ disease. For the purposes of post-exposure prophylaxis, an immunosuppressed person with a negative antibody test should be considered as susceptible.

Table 1: Implementation of One Dose Varicella Immunization Programs in Canadian Provinces and Territories
Province or territory Year of program implementation
Prince Edward Island 2000
Alberta 2001
Northwest Territories 2001
Nova Scotia 2002
Nunavut 2002
Ontario 2004
New Brunswick 2004
Manitoba 2004
Newfoundland and Labrador 2005
Saskatchewan 2005
British Columbia 2005
Quebec 2006
Yukon 2007

Booster doses and re-immunization

Booster doses beyond the 2 recommended doses of varicella-containing vaccines are not necessary.

Post-exposure immunization and outbreak control (refer to Table 2)

Infection with VZV may occur as a result of contact with a person with varicella or HZ. Post-exposure immunization may be required depending on the level of exposure to VZV. Post-exposure management of healthy infants less than 12 months of age is not indicated as these infants are generally protected by maternal antibodies. For information about post-exposure serologic testing, refer to Serologic Testing. For information about post-exposure management in pregnancy, refer to Pregnancy and breastfeeding.

Significant exposures to varicella zoster vaccine

The following situations are considered significant exposures to VZV as result of contact with a person with varicella:

  • Continuous household contact (that is, living in the same dwelling) with a person with varicella
  • Being indoors for more than 1 hour with a person with varicella
  • Being in the same hospital room for more than 1 hour, or more than 15 minutes of face-to-face contact with a person with varicella
  • Touching the lesions or articles freshly soiled by discharges from vesicles of a person with active varicella

The following situations are considered significant exposures to VZV as result of contact with a person with HZ:

  • Continuous household contact (that is, living in the same dwelling) with an immunocompromised person with HZ or a person with disseminated HZ prior to or within first 24 hours of antiviral treatment
  • Being indoors for more than 1 hour with an immunocompromised person with HZ or a person with disseminated HZ prior to or within first 24 hours of antiviral treatment
  • Being in the same hospital room for more than 1 hour, or more than 15 minutes of face-to-face contact with an immunocompromised person with HZ or a person with disseminated HZ prior to or within first 24 hours of antiviral treatment
  • Touching the lesions or articles freshly soiled by discharges from vesicles of a person with active HZ
Post-exposure immunization
Univalent varicella vaccine

Univalent varicella vaccine is the post-exposure management of choice for susceptible, healthy, non-pregnant persons. For optimal effectiveness, univalent varicella vaccine should be given as soon as possible, preferably within 72 hours, after exposure. When given up to 5 days after exposure, it has been shown to be approximately 90% effective in preventing or reducing the severity of varicella. Individuals under 50 years of age who have received only 1 dose of varicella-containing vaccine should be offered a second dose. There are no data on the use of MMRV vaccine in varicella post-exposure situations.

Varicella zoster immune globulin

The decision to administer VarIg should be based on fulfilling all of the following four criteria:

  1. The exposed person is susceptible to varicella. Refer to Susceptibility and immunity.
  2. There has been a significant exposure to a person with varicella or HZ. Refer to Significant exposures to VZV.
  3. The exposed person is at increased risk of severe varicella. Refer to Persons at increased risk of severe varicella.
  4. Post-exposure immunization with univalent varicella vaccine is contraindicated. Refer to Contraindications and precautions.

VarIg is of maximal benefit if administered within 96 hours after first exposure. In case of prolonged exposure, when the exact timing of transmission may be unknown, it may be used within 96 hours of the most recent exposure. If more than 96 hours but less than 10 days have elapsed since the last exposure, VarIg may be used for the purpose of attenuating the disease. The benefit of administering VarIg after 96 hours is uncertain. If VarIg is being considered, consultation with an infectious diseases or infection control specialist is advised. Refer to Passive Immunizing Agents in Part 5 for additional information. For additional information about post-exposure immunization of pregnant women refer to Pregnancy and breastfeeding.

Table 2: Varicella Post-Exposure Management for SusceptibleTable 2 footnote 1 Individuals
Post-exposure intervention Individual
Healthy, non-pregnant
(12 months of ageTable 2 footnote 2 and older)
Pregnant ImmunocompromisedTable 2 footnote 3
Vaccinate with varicella vaccine Yes No No
Check VZV IgG No Yes Yes
If VZV IgG negative, administer VarIgTable 2 footnote 4 Not applicable Yes Yes

Outbreak control

Persons exposed to a case of varicella should be a priority for immunization. Post-exposure immunization is useful in preventing or limiting varicella outbreaks in hospitals, child care facilities and homeless shelters. Serologic testing for susceptibility is not necessary prior to immunization in an outbreak situation. There are no data on the use of MMRV vaccine in outbreak situations. For additional information refer to Post-exposure immunization.

Vaccination of Specific Populations

Persons with inadequate immunization records

Children and adults, who are susceptible to varicella, including those lacking adequate documentation of immunization, should be started on an immunization schedule appropriate for their age and risk factors. Varicella-containing vaccine may be given regardless of possible previous receipt of the vaccine, because adverse events associated with repeated immunization have not been demonstrated. Refer to Immunization of Persons with Inadequate Immunization Records in Part 3 for additional information.

Pregnancy and breastfeeding

Immunity to varicella should be reviewed in women of reproductive age and vaccination should be recommended to susceptible non-pregnant women. Women should delay pregnancy by at least 4 weeks following vaccination with a univalent varicella vaccine.

Varicella-containing vaccine is contraindicated in pregnancy because there is a theoretical risk to the fetus. However, there is no evidence to demonstrate a teratogenic risk from the vaccine and termination of pregnancy should not be recommended following inadvertent immunization with varicella vaccine on the basis of fetal risks following maternal immunization. Pregnant women who are not immune to varicella should have vaccination offered post-partum.

Following exposure to VZV in pregnancy, pregnant women should be evaluated for a history of varicella vaccination or disease. In the absence of such a history, immunity should be assessed by serologic testing as soon as possible. If serology results cannot be obtained within 96 hours, VarIg should be administered to pregnant women with significant exposure to VZV (refer to Significant exposures to VZV) who are presumed to be susceptible (refer to Susceptibility and immunity). Univalent varicella vaccine should be provided after delivery, ensuring that the recommended interval has passed since VarIg was administered. For recommendations on the interval between administration of VarIg and vaccination with varicella-containing vaccine, refer to Blood Products, Human Immune Globulin and Timing of Immunization in Part 1.

Susceptible individuals, including women who are breastfeeding, living in households expecting a newborn, should be vaccinated with a varicella-containing vaccine according to an age-appropriate schedule.

Refer to Blood Products, Human Immune Globulin and Timing of Immunization in Part 1 for information about varicella vaccination of post-partum women who have received Rh immune globulin (RhIg).Refer to Immunization in Pregnancy and Breastfeeding in Part 3 for additional information.

Patients in health care institutions

Most residents of long-term care facilities will be immune to varicella. Post-partum women susceptible to varicella should be vaccinated before discharge. Refer to Immunization of Patients in Health Care Institutions in Part 3 for additional information about varicella vaccination of patients in health care institutions.

Persons with chronic diseases

Asplenia or hyposplenia

Susceptible hyposplenic or asplenic (congenital absence, surgical removal or functional [for example, sickle cell disease]) individuals should receive 2 doses of univalent varicella vaccine, at least 3 months apart.

Chronic renal disease and patients on dialysis

Varicella vaccine is recommended for susceptible individuals with chronic renal disease or undergoing dialysis. Two doses of univalent varicella vaccine may be given, at least 3 months apart.

Neurologic disorders

People with conditions such as autism spectrum disorders or demyelinating disorders, including multiple sclerosis should receive all routinely recommended immunizations, including varicella-containing vaccine.

Chronic lung disease

Varicella immunization should be a priority for people with cystic fibrosis because they are at increased risk of complications from varicella infection, which may cause a transient worsening of lung function. Two doses of univalent varicella vaccine may be given, at least 3 months apart.

Chronic inflammatory diseases

Individuals with autoimmune disease not treated with immunosuppressive drugs are not considered significantly immunocompromised and should receive varicella immunization following consultation with their physician. Some rheumatic disease modifying agents such as hydroxychloroquine, sulfasalazine, or auranofin are not considered immunosuppressive, for the purposes of live vaccine administration.

Conditions requiring chronic salicylate therapy

For children and adolescents on chronic salicylate therapy (medications derived from salicylic acid, such as acetylsalicylic acid [ASA]), special consideration must be given when administering varicella vaccines because of an association between wild-type infection, salicylate therapy and Reye's syndrome. Ideally, these individuals should be considered a priority to receive varicella immunization prior to the initiation of chronic salicylate therapy. Refer to Drug-drug interactions for additional information regarding salicylate therapy following varicella vaccination.

Refer to Immunization of Persons with Chronic Diseases in Part 3 for additional general information about vaccination of people with chronic diseases.

Immunocompromised persons

In general, immunocompromised people should not receive live vaccines because of the risk of disease caused by the vaccine strains. When considering immunization of an immunocompromised person with a live vaccine, approval from the individual's attending physician should be obtained before vaccination. For complex cases, referral to a physician with expertise in immunization or immunodeficiency is advised. In cases in which, in the opinion of the physician, the benefits of immunization outweigh the risks, any of the univalent varicella vaccines can be used. MMRV vaccine has not been studied in persons with impaired immune function, including primary or secondary immunodeficiency disorders, and is not recommended for this group.

Children with a suspected history for immunodeficiency disorders (for example, known or suspected family history of congenital immunodeficiency disorder or HIV infection, or a history of failure to thrive and recurrent infections) should not be immunized until they have been fully investigated and T cell dysfunction has been ruled out.
Refer to Figure 1 and Immunization of Immunocompromised Persons in Part 3 for additional information about vaccination of individuals who are known or suspected to be immunocompromised.

Congenital (primary) immunodeficiency

All live vaccines, including varicella-containing vaccine, are contraindicated in people with defects in T cell function. Live vaccines are generally not recommended for people with other congenital immunodeficiency states, with the following exceptions:

  • B cell deficiencies: people with isolated humoral immunoglobulin deficiency disorders and known intact T cell systems who are not receiving regular immune globulin replacement therapy, may be vaccinated with 2 doses of univalent varicella vaccine, at least 3 months apart.
  • Phagocytic and neutrophil disorders: people with phagocytic or neutrophil disorders may be vaccinated with 2 doses of univalent varicella vaccine, at least 3 months apart.
  • Complement deficiency: people with complement deficiency disorders may be vaccinated with 2 doses of univalent varicella vaccine, at least 3 months apart.

Because immunity can decrease over time, assessment of antibody titres and re-immunization, if needed, should be considered.

Acquired (secondary) immunodeficiency
Malignant hematologic disorders

Varicella-containing vaccine is contraindicated in individuals with severe immunodeficiency due to conditions such as blood dyscrasias, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.

Varicella-containing vaccine is contraindicated in people undergoing immunosuppressive treatment for acute leukemia. Children with acute lymphocytic leukemia (ALL) may be vaccinated with univalent varicella vaccine if the disease has been in remission for at least 12 months, the child's total lymphocyte count is at least 1.2 × 109/L, the child is not receiving radiation therapy, and maintenance chemotherapy can be withheld for at least 1 week before to 1 week after immunization. Two doses of univalent varicella vaccine may be given, at least 3 months apart.

Malignant solid tumours

Varicella-containing vaccine is contraindicated in people undergoing immunosuppressive treatment for any malignant solid tumours.

Hematopoietic stem cell transplantation (HSCT)
Pre-transplantation

People awaiting HSCT should not receive varicella-containing vaccine. Vaccination of donors immediately before stem cell harvest is not recommended because there is no evidence that immunity can be transferred from the donor to the recipient.

Post-transplantation

Antibody titres to vaccine-preventable diseases decline after HSCT if the recipient is not re-vaccinated. Vaccination of seronegative HSCT recipients with 1 dose of univalent varicella vaccine may be considered at 24 months or more after transplantation, provided that there is no evidence of chronic graft-versus-host disease, immunosuppression has been discontinued for at least 3 months, and the person is considered immunocompetent by a transplant specialist. Serologic status should be checked prior to vaccination and vaccine administered only to persons shown to be susceptible to varicella by serology. Safety and immunogenicity data are not available regarding administration of more than 1 dose of varicella-containing vaccine after HSCT.

All individuals with HSCT should be considered susceptible in case of exposure to VZV and should be offered VarIg.

Solid organ transplantation

Varicella vaccination is recommended before transplantation for susceptible children and adults, as determined by serology. Ideally, and if time permits, 2 doses of univalent varicella vaccine should be given at least 3 months apart, with the second dose given at least 4 weeks prior to transplantation. If time does not permit administration of a 2 dose series, 1 dose of univalent varicella vaccine should be given and the transplant delayed by at least 4 weeks. Univalent varicella vaccine may be given to infants as early as 6 months of age if transplantation is anticipated before 12 to 15 months of age. Varicella-containing vaccine should not be given if an individual is receiving immunosuppressive treatment or after solid organ transplantation.

Immunosuppressive therapy

Vaccination status for varicella should be reviewed for immunocompetent persons who might be anticipating initiation of immunosuppressive treatments, individuals on immunosuppressive therapy and in those who have diseases that might lead to immunodeficiency.

Refer to Immunization of Immunocompromised Persons in Part 3 for additional information about varicella immunization and immunosuppressive therapy.

HIV infection

An infectious disease specialist or immunologist should be consulted for advice on varicella immunization in HIV-infected people. Based on expert opinion, post-exposure vaccination with univalent varicella vaccine is indicated for HIV-infected individuals who are not severely immunocompromised (CD4 cell count ≥200 × 106/L and CD4 percentage ≥15%). Varicella vaccine is contraindicated in severely immunocompromised persons (CD4 cell count <200 × 106/L or CD4 percentage <15%) with advanced HIV or AIDS. The safety and immunogenicity of MMRV vaccine in HIV-infected individuals has not been evaluated, and MMRV vaccine is not routinely recommended.

Children

HIV-infected children 12 months of age and older, and with Centers for Disease Control and Prevention (CDC) clinical category N, A, or B, and CD4 percentage ≥15% may receive 2 doses of univalent varicella vaccine 3 to 6 months apart. Univalent varicella vaccine may be administered concomitantly with measles-mumps-rubella (MMR) vaccine at different injection sites using separate needles and syringes. Previously immunized HIV-infected children may demonstrate significant waning of immunity at 1 to 2 years after receiving 2 doses of varicella vaccine; however, it is unknown if this implies an inability to mount an anamnestic response after exposure to varicella disease. Refer to Measles Vaccine, Mumps Vaccine and Rubella Vaccine in Part 4 for additional information.

Adolescents and adults

There are no published data on the use of varicella vaccine in susceptible HIV-infected adolescents and adults. HIV-infected adolescents and adults should be asked for a history of varicella disease or vaccination (refer to Susceptibility and immunity), and if both are negative, serology should be requested to confirm susceptibility. Based on expert opinion, immunization with 2 doses of univalent varicella vaccine administered 3 months apart may be considered for susceptible HIV-infected adolescents and adults with CD4 cell count ≥200 × 106/L and CD4 percentage ≥15%.

Household contacts

Susceptible household contacts of immunocompromised people should be considered a priority to receive varicella-containing vaccine as appropriate for age and risk factors. If the vaccine recipient develops a varicella-like rash, the rash should be covered and the vaccine recipient should avoid direct contact with the immunocompromised person for the duration of the rash. Secondary transmission from people with post-varicella vaccination varicella-like rashes is rare.

Refer to Post-exposure immunization and outbreak control and Contraindications and Precautions.

 

Figure 1: Varicella Vaccination for Immunocompromised Persons

Figure 1
Figure 1: Varicella Vaccination for Immunocompromised Persons - Text Equivalent

This figure is a decision-tree to provide advice to clinicians regarding varicella vaccination to immunocompromised persons. It begins by noting that the first step is to consult with the attending physician before vaccination and if necessary, refer the patient to a specialist with expertise in immunization and/or immunodeficiency. It directs the reader to refer to the chapter on Immunocompromised persons. It then identifies 6 groups of immunocompromised persons and what to do regarding varicella vaccine in each group. The first group includes: Persons with severe immunodeficiency, T cell defects, natural killer T cell defects, combined T and B cell deficiencies, mixed cell-mediated antibody defects, advanced HIV/AIDS, immunosuppressive treatment for malignant solid tumours, blood dyscrasias, lymphomas, malignant neoplasms affecting the bone marrow or lymphatic systems or active leukemia. For this group, vaccination is contraindicated. The second group includes: Persons with conditions requiring chronic immunosuppressive therapy or after solid organ transplantation. For this group, vaccination is not recommended, noting further safety and efficacy studies are needed. The third group includes: Persons with B cell deficiency, phagocytic defects, complement deficiency, neutrophil deficiency, chronic renal disease/dialysis, hyposplenism or asplenia, persons before solid organ transplantation, and children with acute lymphocytic leukemia in remission. For this group, a clinician may vaccinate with 2 doses of univalent varicella vaccine at least 3 months apart. The fourth group includes: Persons 2 years or more after hematopoietic stem cell transplant.  For this group, a clinician may consider vaccination with 1 dose of univalent varicella vaccine. The fifth group includes: HIV- infected children with CDC clinical category N, A or B, and immunologic category 1 or 2 (CD4 percentage ≥ 15%) For this group, the clinician may vaccinate with 2 doses of univalent varicella vaccine 3 to 6 months apart. The sixth group includes: HIV- infected adolescents and adults with CD4 cell count ≥ 200 × 106/L and percentage ≥ 15%. For this group, the clinician may vaccinate with 2 doses of univalent varicella vaccine 3 months apart. Below groups 3-6 (where vaccine may be given), it states: Consider checking varicella zoster virus antibody using local antibody tests 6 to 8 weeks after last dose. There are then two choices. If varicella zoster virus antibody is positive, no action is indicated. If varicella zoster virus antibody is negative, the clinician should consider offering VarIg on subsequent exposures to wild-type varicella.

Travellers

It is important that people travelling or living abroad be immune to varicella. In tropical climates varicella tends to occur at older ages (compared with temperate climates) and at any time of the year. Refer to Immunization of Travellers in Part 3 for additional information about varicella vaccination of travellers.

Persons new to Canada

Health care providers who see persons newly arrived in Canada should review the immunization status and update immunization for these individuals as necessary. People from tropical regions are more likely to be susceptible to varicella and should be a priority for varicella immunization. Refer to Immunization of Persons New to Canada in Part 3 for additional information about varicella vaccination of people who are new to Canada.

Workers

Varicella immunization should be a priority for susceptible workers (refer to Susceptibility and immunity for a definition of susceptible) including health care workers, child care workers, and teachers of young children. These groups are at occupational risk of exposure or may transmit disease to susceptible individuals. Two doses of varicella vaccine are recommended for susceptible workers, as is the case for all susceptible adults. A second dose of varicella vaccine should be offered to workers who have only received 1 dose of vaccine.

Following the exposure of HCW to varicella within health care settings, verification of susceptibility based on documented evidence of immunization with 2 doses of a varicella-containing vaccine or laboratory evidence of immunity should be a part of post-exposure protocols. All HCW should be immunized with two doses of univalent varicella vaccine when there is uncertainty about immunity to varicella.

Health care workers with a post-vaccine rash at the injection site may continue to work if the rash is covered. As a precaution, those with a varicella-like rash not confined to the injection site should be excluded from work in high-risk patient care areas (for example, where there are premature infants and immunocompromised patients) until lesions are crusted. Vaccine recipients with a post-vaccination varicella-like rash rarely transmit the vaccine-associated virus.

Refer to Immunization of Workers in Part 3 for additional information about varicella vaccination of workers.

Serologic Testing

Although useful for establishing immunity after wild-type infection, commercially available varicella antibody tests, such as the enzyme-linked immunosorbant assay (ELISA) and latex agglutination (LA), may not have sufficient sensitivity to detect antibody after vaccination. The glycoprotein ELISA (gpELISA) test is more sensitive, but is not routinely available. Previously vaccinated individuals who are inadvertently tested are likely to be immune to varicella, even if there is no detectable antibody.

Pre-immunization

Serologic testing is not recommended for healthy individuals. All healthy individuals who may be susceptible to varicella should be offered immunization with 2 doses of univalent varicella vaccine.

Post-immunization

Serologic testing is not recommended for healthy individuals. Certain immunocompromised individuals who are vaccinated with univalent varicella vaccine may have antibody testing performed 6 to 8 weeks after the last dose (refer to Figure 1).

Post-exposure and outbreak situations

Following significant exposure to VZV (refer to Significant exposure to VZV), serologic testing is indicated for susceptible immunocompromised individuals and pregnant women (refer to Susceptibility and immunity), and should be conducted as soon as possible. Healthy individuals that have been previously found to be seropositive do not need to be tested again. HSCT recipients are considered susceptible in the post-transplantation period, regardless of positive serologic results. Refer to Outbreak control for additional information regarding immunization in outbreak situations.

Administration Practices

Dose

Each dose of varicella vaccine is 0.5 mL.

Route of administration

Univalent varicella vaccine should be administered subcutaneously (SC). Although the intramuscular (IM) route is not recommended, there is evidence that it is not necessary to repeat a dose of univalent varicella vaccine if it is inadvertently given IM. MMRV vaccine should be administered SC or IM. Refer to Vaccine Administration Practices in Part 1 for additional information.

Interchangeability of vaccines

For a 2 dose schedule, it is recommended that the same manufacturer's univalent varicella vaccine or MMRV vaccine be used to complete the schedule, unless there are unavoidable barriers (for example, the vaccine used for the first dose is not available). All varicella-containing vaccines authorized for use in Canada contain the Oka strain of live attenuated varicella virus. Refer to Principles of Vaccine Interchangeability in Part 1 for additional information about interchangeability of varicella vaccines.

Concurrent administration of vaccines

Varicella-containing vaccines may be administered concomitantly with, or any time before or after, inactivated vaccines, live oral vaccines, and live intranasal influenza vaccine (LAIV).

Varicella-containing vaccines may be administered concomitantly with other routinely provided live parenteral vaccines. If not given concomitantly, a minimum interval of 4 weeks is recommended between administration of varicella-containing and other live parenteral vaccines. This recommendation is to address the risk of interference from the vaccine given first on the vaccine given later.

Different injection sites and separate needles and syringes must be used for concomitant parenteral injections. Refer to Timing of Vaccine Administration in Part 1 for additional information about concurrent administration of varicella vaccine with other vaccines.

Storage and Handling of Immunizing Agents

Refer to Storage and Handling of Immunizing Agents in Part 1 for storage and handling recommendations for varicella vaccines.

Refer to Passive Immunizing Agents in Part 5 for storage and handling recommendations for VarIg.

Safety and Adverse Events

Common and local adverse events

Univalent varicella vaccine

Reactions to univalent varicella vaccine are generally mild and include injection site pain, swelling and redness in 10% to 20% of recipients. A low-grade fever has been documented in 10% to 15% of vaccine recipients. A varicella-like rash occurs at the injection site or is generalized in 3% to 5% of vaccine recipients after the first dose. The rash usually appears within 5 to 26 days after immunization. As varicella-like rashes that occur within the first 2 weeks after immunization may be caused by wild-type virus (varicella virus circulating in the community), health care providers should obtain specimens from the vaccine recipient to determine whether or not the rash is due to a natural varicella infection or to the vaccine-derived strain.

The safety profile of a 2 dose regimen is comparable to that of a single dose with slightly higher incidence of injection site reactions observed within 3 days after vaccination (up to 26%) and slightly lower incidence of fever (up to 4%) and varicella-like rash (1%) after dose 2 compared to dose 1.
Measles-Mumps-Rubella-Vaccine vaccine

Pain and redness at the injection site or fever less than 39°C occur in 10% or more of vaccine recipients. Rash, including measles-like, rubella-like and varicella-like rash, as well as swelling at the injection site and fever greater than 39°C, occur in 1% to less than 10% of vaccine recipients. As varicella-like rashes that occur within the first 2 weeks after immunization may be caused by wild-type virus (varicella virus circulating in the community), health care providers should obtain specimens from the vaccine recipient to determine whether the rash is due to a natural varicella infection or to the vaccine-derived strain.

Varicella zoster immune globulin

Reactions to VarIg are rare. The most frequent treatment related adverse events are pain at the injection site (17%), headache (7%), and rash (5%).

Rubella-containing vaccines

Acute transient arthritis or arthralgia may occur 1 to 3 weeks after immunization with rubella-containing vaccine, such as MMRV. It lasts for about 1 to 3 weeks, and rarely recurs. It is more common in post-pubertal females, an age group for whom MMRV is not indicated. There is no evidence of increased risk of new onset chronic arthropathies.

Less common and serious or severe adverse events

Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association. Anaphylaxis following vaccination with varicella-containing vaccine may occur but is very rare.

Univalent varicella vaccine

Most reported serious adverse events have not been proven to be caused by the vaccine, with the exception of rare events linked to the varicella vaccine strain among immunocompromised individuals or those with other serious medical conditions.

Measles-Mumps-Rubella-Vaccine vaccine
Immune Thrombocytopenic Purpura (ITP)

Rarely, ITP occurs within 6 weeks after immunization with MMRV vaccine. In most children, post-immunization thrombocytopenia resolves within 3 months without serious complications. In individuals who experienced ITP with the first dose of MMRV vaccine, serologic status may be evaluated to determine whether an additional dose of vaccine is needed for protection. The potential risk to benefit ratio should be carefully evaluated before considering vaccination in such cases.

Encephalitis

Encephalitis has been reported in association with administration of measles vaccine in approximately 1 per million doses distributed in North America, which is much lower than the incidence observed with natural measles disease (1 per 1,000 cases).

Febrile seizures

Between the ages of 12 to 23 months, when the first dose of vaccine for measles and varicella is administered as the combined MMRV vaccine, there is a higher risk of fever and febrile seizures in the 7 to 10 days after vaccination when compared to separate administration of MMR and varicella vaccine at the same visit. For additional information about febrile seizures following the administration of MMRV vaccine, refer to Measles Vaccine in Part 4.

Varicella zoster immune globulin

There is a remote risk of an anaphylactic reaction to VarIg in individuals with hypersensitivity to blood products.

Other reported adverse events and conditions

Herpes zoster

HZ has been reported after varicella immunization. The risk of developing HZ is 4-fold to 12-fold lower in vaccinated as compared with unvaccinated children under 10 years of age who have had wild-type varicella. Severity of HZ has also shown to be reduced in vaccinated children compared to children with a history of wild-type VZV infection. The risk of HZ after vaccination with MMRV vaccine is unknown.

Transmission of vaccine virus

Transmission of vaccine strain virus from a healthy vaccine recipient is very rare. There have been few documented cases, all associated with a rash in the vaccine recipient.

Guidance on Reporting Adverse Events Following Immunization

Vaccine providers are asked to report the following AEFI in particular, through local public health officials:

  • Febrile seizures within 30 days after vaccination with varicella-containing vaccine.
  • Varicella that is moderate (50 to 500 lesions) or severe (more than 500 vesicular lesions or associated complications or hospital admission) and occurs within 7 to 21 days of vaccination with varicella-containing vaccine.
  • Any serious or unexpected adverse event temporally related to vaccination. An unexpected AEFI is an event that is not listed in available product information but may be due to the immunization, or a change in the frequency of a known AEFI.

Refer to Reporting Adverse Events Following Immunization (AEFI) in Canada and Vaccine Safety in Part 2 for additional information about AEFI reporting.

Contraindications and precautions

Varicella-containing vaccines and VarIg are contraindicated in persons with a history of anaphylaxis after previous administration of the product and in persons with proven immediate or anaphylactic hypersensitivity to any component of the product, with the exception of egg allergy for MMRV vaccine. Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for lists of vaccines and passive immunizing agents available in Canada and their contents.

In situations of suspected hypersensitivity or non-anaphylactic allergy to vaccine components, investigation is indicated which may involve immunization in a controlled setting. Consultation with an allergist is advised.

Although the measles and mumps components of MMRV vaccine are produced in chick embryo cell culture and may contain traces of residual egg and chicken protein, the trace amount of egg or chicken protein in the vaccine appears to be insufficient to cause an allergic reaction in egg-allergic individuals. Skin testing is not recommended prior to vaccination, as it does not predict reaction to the vaccine. MMRV vaccine can be administered in the routine manner to people who have a history of anaphylactic hypersensitivity to hens' eggs. Prior egg ingestion is not a prerequisite for immunization with egg protein-containing vaccine. For all vaccines, immunization should always be performed by personnel with the capability and facilities to manage adverse events post-vaccination. Refer to Anaphylactic Hypersensitivity to Egg and Egg-Related Antigens in Part 2 for additional information.

Children with a known or suspected family history of congenital or hereditary immunodeficiency that is a contraindication to vaccination with live vaccine should not receive live vaccines unless their immune competence has been established.

MMRV vaccine is contraindicated in persons with impaired immune function, including primary or secondary immunodeficiency disorders. Vaccination with univalent varicella vaccine may be considered in select disorders. Refer to Immunocompromised persons.

Varicella-containing vaccines are contraindicated during pregnancy because of theoretical risk to the fetus. Refer to Pregnancy and breastfeeding.

Varicella-containing vaccines are contraindicated in individuals with active, untreated tuberculosis as a precautionary measure. Although tuberculosis may be exacerbated by natural measles infection, there is no evidence that measles-containing or varicella-containing vaccines have such an effect. Nonetheless, anti-tuberculous therapy for active TB disease is advisable before administering varicella-containing vaccines and it may be prudent to avoid live viral vaccines in those with active TB disease until treatment is underway. Consultation with an expert in infectious diseases is recommended.

A history of febrile seizures or a family history of seizures is not a contraindication for the use of MMRV vaccine.

Administration of varicella-containing vaccine should be postponed in persons with severe acute illness. Following measles infection, immunization with varicella-containing vaccine should be delayed by at least 4 weeks, and ideally 6 weeks, if feasible. Persons with a minor acute illness, with or without fever, may be vaccinated.

Following MMRV vaccine, transmission of measles, mumps and rubella vaccine viruses from vaccine recipients to susceptible contacts has not been documented, and transmission of varicella vaccine virus may occur very rarely between healthy vaccine recipients who develop a varicella-like rash and their susceptible contacts.

It is recommended to avoid the use of salicylates for 6 weeks after immunization with varicella-containing vaccine. Refer to Drug-drug interactions.

Persons with specific immunoglobulin A (IgA) deficiency have increased potential for developing antibodies to IgA after receipt of blood products including VarIg and may be at risk for anaphylactic reactions to subsequent administration of blood products containing IgA, such as VarIg.

Refer to Contraindications, Precautions and Concerns in Part 2 and Passive Immunizing Agents in Part 5 for additional information.

Drug-drug interactions

Systemic antiviral therapy

Systemic antiviral therapy (such as acyclovir, valacyclovir, famciclovir) should be avoided in the peri-immunization period, as it may affect the reproduction of the vaccine virus and consequently may reduce the efficacy of varicella-containing vaccine. On the basis of expert opinion, it is recommended that people taking long-term antiviral therapy should discontinue these drugs, if possible, from at least 24 hours before administration of varicella-containing vaccine and should not restart antiviral therapy until 14 days after vaccine administration.

Tuberculin skin testing or Interferon Gamma Release Assay

The measles component in MMRV vaccine can temporarily suppress tuberculin reactivity, resulting in false-negative results. The effect of other live virus vaccines, such as univalent varicella vaccine on tuberculin reactivity is unknown. Until data are available, if tuberculin skin testing or an IGRA is required, it should be done on the same day as immunization or delayed for at least 4 weeks after varicella vaccination. Vaccination with a varicella-containing vaccine may take place at any time after tuberculin skin testing has been administered.

Salicylate therapy

Manufacturers of varicella-containing vaccines recommend avoidance of salicylate therapy (medications derived from salicylic acid, such as ASA) for 6 weeks after varicella immunization because of an association between wild-type varicella, salicylate therapy and Reye's syndrome. Health care providers should weigh the theoretical risks associated with varicella vaccine against the known risks associated with wild-type varicella infection. Because adverse events have not been reported with the use of salicylates after varicella immunization, people with conditions requiring chronic salicylate therapy should be considered for immunization, with close subsequent monitoring.

Human immune globulin or other blood products

Passive immunization with human Ig or receipt of most other blood products can interfere with the immune response to varicella-containing vaccine. These vaccines should be given at least 14 days prior to administration of an Ig preparation or other blood product or delayed until the antibodies in the Ig preparation or other blood product have degraded. If the interval between administration of vaccine and subsequent administration of an Ig preparation or other blood product is less than 14 days, or if the vaccine is administered before the antibody has degraded, the vaccine dose should be repeated after the recommended interval. The recommended interval between administration of an Ig preparation or other blood product and subsequent immunization with a varicella-containing vaccine varies, depending on the Ig preparation or blood product. Palivizumab (RSVAb) and washed red blood cell transfusion do not interfere with the antibody response to varicella-containing vaccines. Refer to Blood Products, Human Immune Globulin and Timing of Immunization in Part 1 for additional information.

Other Considerations

Surveillance

Virus identification from clinical specimens (for example, vesicle scraping) by laboratory methods to differentiate wild-type from vaccine-derived VZV should be considered when:

  • A severe post-vaccination rash occurs
  • A previously vaccinated child develops varicella (breakthrough varicella) that requires admission to hospital
  • HZ occurs in a previously immunized (especially immunocompromised) individual
  • A varicella-like illness occurs in an immunized health care worker with subsequent spread in the health care setting
  • A varicella-like illness develops in a pregnant or immunocompromised contact of a recent vaccine recipient with a varicella-like rash

Polymerase chain reaction testing to differentiate vaccine-derived from wild type varicella virus can be performed by the National Microbiology Laboratory in Winnipeg.

As wild type varicella disease decreases with vaccination, laboratory confirmation of suspected varicella cases will become more and more important. Moreover, enhanced surveillance for varicella cases is necessary to ensure that the current immunization programs do not transfer the burden of illness into older age groups (for example, young adults of reproductive age) who are at risk of more severe disease.

Selected References

  • American Academy of Pediatrics. In: Pickering LK, Baker CJ, Kimberlin DW, et al. (editors). Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.
  • Brisson M, Gay N, Edmunds W et al. Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox. Vaccine 2002;20(19-20):2500-7.
  • Cangene Corporation. Product Monograph - VariZIG. January 2008.
  • Centres Centers for Disease Control and Prevention. Prevention of Varicella Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep 2007;56:RR-04:1-40.
  • Centers for Disease Control and Prevention. The Pink Book: Epidemiology and Prevention of Vaccine Preventable Diseases. Updated 12th ed.; May 2012. Accessed April 2015.
  • Civen R, Chaves S, Jumaan A et al. The Incidence and Clinical Characteristics of Herpes Zoster Among Children and Adolescents After Implementation of Varicella Vaccination. Pediatr Infect Dis J 2009;28:954-959.
  • Galil K, Lee B, Strine T et al. Outbreak of varicella at a day-care center despite vaccination. N Engl J Med 2002;347(24):1909-15.
  • GlaxoSmithKline Inc. Product Monograph – PRIORIX-TETRA™. May 2010.
  • GlaxoSmithKline Inc. Product Monograph - VARILRIX®. September 2010.
  • Health Canada. Proceedings of the National Varicella Consensus Conference: Montreal, Quebec, May 5-7, 1999. Can Commun Dis Rep 1999;25(S5).
  • Kuter B, Matthews H, Shinefield H et al. Ten year follow-up of healthy children who received one or two injections of varicella vaccine. Pediatr Infect Dis J 2004;23(2):132-7.
  • LaRussa P, Steinberg S, Gershon AA. Varicella vaccine for immunocompromised children: results of collaborative studies in the United States and Canada. J Infect Dis 1996;174(Suppl 3):S320-3.
  • Law B, Scheifele D, MacDonald N et al. The Immunization Monitoring Program ACTtive (IMPACT) prospective surveillance of varicella zoster infections among hospitalized Canadian children: 1991-1996. Can Commun Dis Rep 2000;26(15):125-31.
  • Lee B, Feaver S, Miller C et al. An elementary school outbreak of varicella attributed to vaccine failure: policy implications. J Infect Dis 2004;190(3):477-83.
  • Levin M, Gershon A, Weinberg A et al. and the AIDS Clinical Trials Group 265 Team. Immunization of HIV-infected children with varicella vaccine. J Pediatr 2001;139(2):305-10.
  • Merck Frosst Canada Ltd. Product Monograph - VARIVAX® III. February 2009.
  • National Advisory Committee on Immunization. Updated recommendations for the use of varicella zoster immune globulin (VarIg) for the prevention of varicella in at-risk patients. Pending publication.
  • National Advisory Committee on Immunization. Update on Measles-Mumps-Rubella-Varicella Vaccine and Febrile Seizures. Pending publication.
  • National Advisory Committee on Immunization. Varicella Proof of Immunity - 2014 Update. Pending publication.
  • National Advisory Committee on Immunization. Literature Review on One and Two Dose Varicella Vaccination. Can Commun Dis Rep Report 2010:36(ACS-10):1-24.
  • National Advisory Committee on Immunization. Statement on measles-mumps-rubella-varicella vaccine (MMRV, PRIORIX-TETRA™, GlaxoSmithKline Inc.). Can Commun Dis Rep 2010;36(ACS-9):1-22.
  • National Advisory Committee on Immunization. Varicella vaccination two-dose recommendations. Can Commun Dis Rep 2010;36(ACS-8):1-26.
  • National Advisory Committee on Immunization. Updated recommendations for the use of varicella and MMR vaccines in HIV-infected individuals. Can Commun Dis Rep 2010;36(ACS-7):1-19.
  • National Advisory Committee on Immunization, VariZIG™ as the varicella zoster immune globulin for the prevention of varicella in at-risk patients. Can Commun Dis Rep 2006;32(ACS-8):1-8.
  • National Advisory Committee on Immunization. Update on varicella. Can Commun Dis Rep 2004;30(ACS-1):1-26.
  • Ndumbe P, Cradock-Watson J, Levinsky R. Natural and artificial immunity to varicella zoster virus. J Med Virol 1988;25(2):171-8.
  • Preblud S. Age-specific risks of varicella complications. Pediatrics 1981;68(1):14-7.
  • Scheifele D, Halperin S, Diaz-Mitoma F. Three-year follow-up of protection rates in children given varicella vaccine. Can J Infect Dis 2002;13(6):382-6.
  • Seward J, Watson B, Peterson C et al. Varicella disease after introduction of varicella vaccine in the United States, 1995-2000. JAMA 2002;287(5):606-11.
  • Sharrar R, LaRussa P, Galea S et al. The postmarketing safety profile of varicella vaccine. Vaccine 2000;19(7-8):916-23.
  • Shields K, Galil K, Seward J et al. Varicella vaccine exposure during pregnancy: data from the first 5 years of the pregnancy registry. Obstet Gynecol 2001;98(1):14-9.
  • Takashi M, Gershon A. Varicella vaccine. In: Plotkin SA, Mortimer EA, (editors). Vaccines, 2nd ed. WB Saunders Co, 1994:387-419.
  • Vazquez M, LaRussa P, Gershon A et al. The effectiveness of the varicella vaccine in clinical practice. N Engl J Med 2001;344(13):955-60.
  • Vessey S, Chan C, Kuter B et al. Childhood vaccination against varicella: persistence of antibody, duration of protection, and vaccine efficacy. J Pediatr 2001;139(2):297-304.
  • Watson B, Seward J, Yang A et al. Postexposure effectiveness of varicella vaccine. Pediatrics 2000;105(1 Pt1):85-8.
  • Weibel R, Neff B, Kuter B et al. Live attenuated varicella virus vaccine. Efficacy trial in healthy children. N Engl J Med 1984;310(22):1409-15.
  • Wise R, Salive M, Braun M et al. Postlicensure safety surveillance for varicella vaccine. JAMA 2000;284(10):1271-9.
  • Zhou F, Harpaz R, Jumaan A et al. Impact of varicella vaccination on health care utilization. JAMA 2005;294(7):797-802.
Date modified: