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INTRODUCTION — Primary infection with varicella zoster virus (VZV) causes varicella (chickenpox) in susceptible hosts. While varicella is a self-limited infection in most healthy children, the incidence of hospitalization and even mortality in selected groups is significant. Varicella can cause significant complications, such as soft tissue infection, pneumonia, hepatitis, and encephalitis. Patients at increased risk of complications include adults, pregnant women, and immunocompromised hosts.
The use of varicella vaccine to prevent primary varicella infection will be discussed here. Post-exposure prophylaxis to prevent primary varicella infection, the clinical manifestations and treatment of primary varicella infection, and the use of the zoster vaccine to prevent herpes zoster are discussed separately:
BENEFITS OF IMMUNIZATION — Systematic reviews, randomized trials, and observational studies from a variety of countries indicate that routine immunization against varicella zoster virus (VZV) prevents varicella (chickenpox) (figure 1), reduces disease severity in breakthrough cases, reduces the risk of transmission [1-11], and reduces varicella-associated health care utilization [12-15]. Herd immunity extends protection to infants too young to be vaccinated and unvaccinated adults [16-18].
●80 percent in preventing varicella disease of any severity
●95 to 98 percent in preventing moderate (generally defined by 50 to 500 lesions) or severe disease (generally defined by >500 lesions, complications requiring medical care, hospitalization, or death)
●≥99 percent in preventing severe disease
Two doses appeared to be more effective than one dose in preventing varicella disease of any severity, providing a mean effectiveness of approximately 92 to 93 percent (range 84 to 98 percent) [19,20].
In surveillance in the United States, routine childhood immunization for varicella was associated with a 79 percent decrease in overall varicella incidence between 2000 and 2010 (from 43 to 9 per 100,000 population) ; a 90 percent decrease in the incidence of varicella in infants between 1995 and 2008 (from 15.6 to 1.6 cases per 1000 population) ; an 88 percent decrease in varicella hospitalization between 1994 and 2002 (from 2.3 to 0.3 per 100,000 population) ; and an 88 percent decrease in varicella mortality between 1990-1994 and 2005-2007 (from 0.41 to 0.05 per million population) . (See "Epidemiology of varicella-zoster virus infection: Chickenpox", section on 'Epidemiology of disease after introduction of varicella vaccine'.)
Vaccination after an exposure to varicella also decreases the risk of infection and the severity of disease . The use of vaccination for post-exposure prophylaxis is discussed elsewhere. (See "Post-exposure prophylaxis against varicella-zoster virus infection", section on 'Varicella vaccine administration' and "Prevention and control of varicella-zoster virus in hospitals", section on 'Post-exposure prophylaxis'.)
EVIDENCE OF IMMUNITY — Evidence of immunity to varicella includes any of the following [22,23]:
●Documentation of age-appropriate varicella immunization:
•For children <4 years – One dose after age 12 months
•For children ≥4 years, adolescents, and adults – Two doses separated by at least 28 days and administered after age 12 months
●Laboratory evidence of immunity or laboratory confirmation of disease; commercially available antibody assays detect disease-induced antibody, but may not reliably detect vaccine-induced antibody (see 'Post-vaccination serology' below and "Diagnosis of varicella-zoster virus infection").
●Diagnosis or verification of prior typical varicella infection or herpes zoster infection by a health care provider.
For people reporting a history of mild or atypical varicella (often having occurred in infants younger than one year), verification requires: 1) documentation of an epidemiologic link to a typical case or to a laboratory confirmed case; or 2) laboratory confirmation of the previous episode, because other diseases can mimic mild or atypical varicella.
●For people born in the United States – Birth before 1980 (when the prevalence of varicella disease was high) unless they are immunosuppressed, pregnant, or a health care worker (such individuals must have serologic evidence of immunity, documentation of completed immunization, or verification of typical disease because they are at high risk of being exposed to varicella, are more likely to develop severe infection, and/or are likely to transmit varicella to those at risk for severe disease).
●People born outside the United States before 1980 must satisfy one of the other criteria for evidence of immunity because the prevalence of varicella in the country of origin may not be known.
INDICATIONS AND SCHEDULES
Priority groups — Even though some countries recommend universal varicella vaccination, to prevent severe or complicated varicella infection in high-risk groups, and to prevent outbreaks, it is particularly important to immunize people who [22,24]:
●Have close contact with people at high risk for severe disease (eg, health care workers and family contacts of immunocompromised people)
●Are at high risk for exposure or transmission, including:
•Teachers of young children
•Child care employees
•Residents and staff members of institutional settings, including correctional institutions
•Adolescents and adults living in households with children
•Nonpregnant women of childbearing age
●Are immigrants and refugees [25-28]
Schedules in the United States — Two doses of varicella vaccine are recommended for routine immunization of immunocompetent children, adolescents, and adults without evidence of immunity [22,24,29]. The recommended routine and "catch-up" schedules vary according to age. (See 'Evidence of immunity' above and 'Children <13 years' below and 'Adolescents and adults' below.)
The United States switched from a one-dose to a two-dose schedule in 2007 . Despite a single-dose effectiveness of >80 percent, outbreaks of varicella continued to occur in highly vaccinated populations [30-32]. The second dose was added to stimulate an immune response in the up to 25 percent of varicella vaccine recipients who fail to respond to a single dose [22,33,34]. Compared with a single dose, two doses of varicella vaccine are associated with increased rates of seroconversion, increased antibody titers, increased effectiveness, and longer lasting immunity [1,4,10,35-42]. (See 'Breakthrough varicella' below.)
The superiority of the two-dose schedule was demonstrated in a multicenter randomized trial in 5285 healthy children age 12 to 22 months . The efficacy of two doses of varicella vaccine (administered as MMRV) in preventing laboratory or epidemiologically confirmed varicella was 95 percent (97.5% CI 92-97 percent) and the efficacy of a single dose was 65 percent (97.5% CI 57-72 percent). Breakthrough infection was seven times (95% CI 5-10 times) less likely with two doses than with a single dose. In addition, the overall incidence of varicella decreased by 85 percent after the two-dose schedule was instituted (from 25.4 per 100,000 population during 2005-2006 to 3.9 per 100,000 population during 2013-2014 ).
Children <13 years — In children, the first dose of varicella vaccine is usually administered at age 12 through 15 months and the second dose at age 4 through 6 years [22,29]. A discussion on how to administer the vaccine (eg, choice of vaccine, dose, route) is found below. (See 'Administration' below.)
The minimum age for the first dose is 12 months. Doses administered before age 12 months should not be counted and the child should be revaccinated at 12 through 15 months of age (and ≥3 months after the initial dose) .
The second dose may be administered earlier than age 4 years (eg, during a varicella outbreak). For children <13 years, the recommended minimum interval between doses is 3 months . However, if the second dose is administered at least 28 days after the first, it need not be repeated .
Children age <13 years who have received <2 doses of varicella vaccine should receive one or two doses as necessary to be "caught up" [22,29,44]. The schedule does not need to be restarted if the interval between the first and second dose exceeds the recommended interval.
Adolescents and adults — Adolescents ≥13 years and adults who have not received varicella vaccine and have no evidence of chickenpox should receive two doses of single-antigen varicella vaccine, separated by four to eight weeks [22,24,45]. (See 'Evidence of immunity' above.)
Our approach to prevaccination serology varies with age:
●We generally do not perform prevaccination serology in adolescents without a history of varicella because they are unlikely to have been exposed to wild-type virus.
●We typically perform prevaccination serology in adults born after 1980 or outside the United States because they are more likely to have had varicella. However, previous history of varicella is not a contraindication to varicella vaccine and providing vaccine without serologic testing is a reasonable alternative.
The World Health Organization suggests that the first dose of varicella vaccine be administered at age 12 to 18 months and that the second dose (for countries with a two-dose schedule) be administered at the recommended minimum interval provided by the vaccine manufacturer (ranging from 4 weeks to 3 months) .
Special circumstances — The routine immunization schedule may need to be altered in certain circumstances, including:
Recent receipt of immune globulin or blood — The receipt of parenterally administered immune globulin or antibody-containing blood products can blunt or block the host response to certain live-virus vaccines (eg, measles). Whether these products affect the antibody response to varicella vaccine is not known . However, because of potential inhibition of the immune response, the administration of varicella vaccine should be delayed in people who have received immune globulin or blood products. The suggested interval is the same as that recommended for measles-containing vaccines (table 1) .
Postpartum administration of varicella vaccine to women who received anti-D (Rho) immune globulin or blood products during the last trimester of pregnancy or at delivery is discussed separately. (See "Immunizations during pregnancy", section on 'Postpartum immunization'.)
If immune globulin or blood products must be given within 14 days after administration of a varicella-containing vaccine, another dose of the vaccine should be administered after the interval suggested in the table (table 1).
Antiviral therapy — Varicella vaccine virus is susceptible to acyclovir, valacyclovir, and famciclovir. These agents should be avoided from 1 day before until 21 days after receipt of varicella vaccine .
Salicylate therapy — It is not known whether Reye syndrome results from administration of salicylates after varicella immunization. However, because of the association between salicylates, natural varicella, and Reye syndrome, the vaccine manufacturer recommends that salicylates be avoided for at least six weeks after VZV vaccine [22,29]. (See "Acute toxic-metabolic encephalopathy in children", section on 'Reye syndrome'.)
Vaccine formulations — Two live, attenuated VZV vaccines are licensed in the United States for the prevention of varicella [22,23]:
●A single-antigen varicella vaccine that contains a minimum of 1350 plaque-forming units (PFU) of the Oka strain of VZV and is licensed for use in people age ≥12 months
●A combination measles, mumps, rubella, and varicella vaccine (MMRV) that contains a minimum of 9772 PFU of VZV and is licensed for use in people age 12 months through 12 years
In other countries, varicella vaccines may contain different amounts of VZV (typically ranging from 1000 to 17,000 PFU) and be licensed for people age ≥9 months .
Herpes zoster vaccine contains a minimum of 19,400 PFU of VZV and is discussed separately . (See "Vaccination for the prevention of shingles (herpes zoster)".)
Choice of vaccine
●Immunocompetent children <13 years may receive either single-antigen varicella vaccine or combination measles, mumps, rubella, and varicella vaccine (MMRV).
The routine schedule for varicella vaccine generally is the same as that for measles, mumps, and rubella vaccine (MMR) (figure 2). For children who require both varicella and MMR vaccine, the decision to use MMRV or separate varicella and MMR vaccines should be made on a case-by-case basis after a discussion of the risks and benefits of each strategy with the child's parents . The Centers for Disease Control and Prevention (CDC) provides information and a fact sheet to help parents understand their options. (See 'Local and systemic reactions' below.)
If the parents do not have a preference:
•For the first doses of varicella and MMR vaccines:
-We suggest separate varicella and MMR vaccines for children 12 through 47 months of age (ie, administered at the same visit, but at different sites)
-We suggest MMRV for children 48 months through 12 years of age
•For the second doses of varicella and MMR vaccines in children 15 months through 12 years of age, we suggest MMRV
The immunogenicity of MMRV is similar to that when varicella and MMR vaccines are administered at separate injection sites . However, the risk of febrile seizures is increased when MMRV is administered for the first dose in young children. In several large post-licensure studies, administration of MMRV at age 12 to 23 months was associated with an approximately twofold increased risk of febrile seizures one to two weeks after immunization compared with separate injections of varicella and MMR (approximately 1 in 1250 versus 1 in 2500) (table 2) [50-54]. In another large post-licensure study, neither MMRV nor separate injections of MMR and varicella vaccine was associated with an increased risk of febrile seizures at age 4 to 6 years . (See 'Local and systemic reactions' below.)
Our preferences are consistent with the recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) [48,54,56].
●Children <13 years with HIV infection without severe immunosuppression may receive single-antigen varicella vaccine, but should not receive MMRV. (See "Immunizations in HIV-infected patients", section on 'Varicella vaccine'.)
●Adolescents and adults should receive single-antigen varicella vaccine.
If an adult or adolescent inadvertently receives a dose of the herpes zoster vaccine rather than the varicella zoster vaccine, the dose of zoster vaccine can be counted as one dose of varicella vaccine .
Dose and route — The dose of varicella vaccine (single-antigen or MMRV) is 0.5 mL. Varicella-containing vaccines are administered subcutaneously, usually in the upper outer triceps. Doses that are administered intramuscularly need not be repeated; intramuscular administration results in similar rates of seroconversion .
●Severe allergic reaction (eg, anaphylaxis) to a previous dose of varicella vaccine or component of varicella vaccine (eg, neomycin, gelatin); varicella vaccines do not contain egg protein (see "Allergic reactions to vaccines")
●Pregnancy or trying to become pregnant; immunization before and after pregnancy is discussed separately (see "Immunizations during pregnancy")
●Severe immunosuppression due to:
•Hematologic and solid tumors or current receipt of chemotherapy (see "Immunizations in patients with cancer", section on 'Varicella vaccine')
•Congenital or acquired T-lymphocyte immunodeficiency (see "Immunizations in patients with primary immunodeficiency", section on 'Live vaccines')
B-lymphocyte (humoral) deficiencies (eg, hypogammaglobulinemia) are not a contraindication to single-antigen varicella vaccine, but the blood products used to treat humoral deficiencies may interfere with the immune response (see 'Recent receipt of immune globulin or blood' above)
•HIV infection; HIV-infected patients without severe immunosuppression may receive single-antigen varicella vaccine (see "Immunizations in HIV-infected patients", section on 'Varicella vaccine')
•Current receipt of immunosuppressive agents, such as those administered to patients who have undergone solid organ or hematopoietic stem cell transplant, as well as those receiving biologic agents for autoimmune conditions (eg, IL-1 receptor antagonists [eg, anakinra], tumor necrosis factor-alpha inhibitors [eg, etanercept, infliximab, adalimumab], and anti-CD20 agents [eg, rituximab]) (see "Immunizations in solid organ transplant candidates and recipients", section on 'Varicella' and "Immunizations in hematopoietic cell transplant candidates and recipients", section on 'Varicella and zoster (live)' and "Tumor necrosis factor-alpha inhibitors: Bacterial, viral, and fungal infections", section on 'Live virus vaccines' and "Overview of biologic agents and kinase inhibitors in the rheumatic diseases")
•Long-term high-dose systemic glucocorticoid therapy (≥2 weeks of prednisone ≥20 mg per day or prednisone ≥2 mg/kg per day [for children who weigh <10 kg] or equivalent)
●Untreated active tuberculosis
Precautions are conditions that may increase the risk of adverse reactions, diminish the immune response, or make it difficult to differentiate between a clinical manifestation of the condition and a vaccine adverse effect (eg, fever, seizure) . When precautions are present, the risks and benefits of immunization (versus postponing the immunization) should be considered on a case-by-case basis. Precautions to administration of varicella vaccine include (table 3) [22,23,29,34,59]:
●Varicella vaccination should be deferred in patients at risk for congenital or hereditary immunodeficiency (ie, parent or sibling with hereditary immunodeficiency) until the immunocompetence of the potential vaccinee is clinically substantiated or verified with laboratory testing
●Salicylate therapy (see 'Salicylate therapy' above)
●A personal history of seizure or history of seizures in a sibling or parent is a precaution for the combination measles, mumps, rubella, and varicella vaccine, but not for single-antigen varicella vaccine [53,61]
●Moderate or severe acute illness with or without fever (ie, illness more severe than upper respiratory infection, otitis media, gastroenteritis); immunization may superimpose vaccine adverse effects on the underlying illness; manifestations of the underlying illness may be mistakenly attributed to the vaccine
Administration with other vaccines — Varicella vaccine may be administered at the same visit as other vaccines. If varicella vaccine is not administered on the same day as MMR, the two vaccines should be separated by at least 28 days [23,62].
ADVERSE EVENTS — Varicella vaccine is generally well tolerated [63-65]. Data from the Vaccine Adverse Events Reporting System in the United States suggest that serious events (ie, those resulting in hospitalization, life-threatening illness, permanent disability, or death) are rare (2.6/100,000 doses administered) . Serious adverse events suspected to have been caused by varicella vaccines should be reported to the Vaccine Adverse Event Reporting System (VAERS).
Local and systemic reactions
●Injection site reactions – Approximately 20 percent of children, and 25 percent of adolescents and adults, complain of pain, tenderness, or redness at the injection site [29,37,63,66,67].
●Rash – Approximately 1 to 3 percent of patients who receive varicella vaccine develop a localized rash consisting of two to five lesions at the injection site, and another 3 to 5 percent develop a generalized varicella-like rash within one month of immunization . Most of the vesicular rashes that occur within the first two weeks after varicella immunization are caused by wild-type VZV .
People who develop a rash after varicella vaccine should refrain from physical contact with people who are susceptible to varicella, particularly those who are immunocompromised, until the rash has resolved [29,68,69]. (See 'Transmission of vaccine virus' below.)
●Fever and febrile seizures – Temperature >38.9ºC (102ºF) occurs in approximately 15 percent of children younger than 13 years and temperature >37.8ºC (100ºF) occurs in approximately 10 percent of adolescents and adults .
The risk of febrile seizure one to two weeks after separate administration of varicella vaccine and MMR is approximately 1 in 2500 [53,54]. The risk is increased approximately twofold (ie, 1 in 1250) when combination MMRV is administered to children age 12 to 23 months [50,51]. Neither MMRV nor separate injections of MMR and varicella vaccine appear to be associated with an increased risk of febrile seizures at age 4 to 6 years . (See 'Choice of vaccine' above.)
Disseminated vaccine virus — Rarely, patients can develop disseminated varicella or meningitis from vaccine virus. Case reports have identified disseminated disease in immunocompetent, as well as immunocompromised, patients [63,70-72]. To minimize the risk of disseminated disease, vaccination is contraindicated in individuals who are receiving immunosuppressive therapy or have primary or acquired immunodeficiencies. (See 'Contraindications and precautions' above and 'Immunocompromised hosts' below.)
Transmission of vaccine virus — Transmission of vaccine virus from a healthy patient to a susceptible contact is rare and is mostly described in case reports [63,66,73-76]. However, transmission of vaccine virus from an immunocompromised host to a susceptible contact appears to be more likely. As an example, in one study, transmission of vaccine virus occurred in 17 percent of 88 susceptible siblings of children with leukemia who developed a rash after varicella immunization .
People who develop a rash after varicella vaccine should refrain from physical contact with people who are susceptible to varicella, particularly those who are immunocompromised and pregnant women, until the rash has resolved [29,68,69]. However, since secondary cases of vaccine associated varicella are expected to be mild, varicella-zoster immune globulin (VariZIG) is not routinely recommended [22,29]. (See "Post-exposure prophylaxis against varicella-zoster virus infection", section on 'Passive immunization'.)
Risk of vaccine-associated zoster — Immunocompromised patients who receive the varicella vaccine are at risk for developing severe and/or disseminated herpes zoster infection with the vaccine strain of the virus [70,78]. In such patients, zoster can develop months after vaccination. Wild-type VZV also has been identified in persons with herpes zoster after immunization, indicating that herpes zoster in immunized persons also may result from antecedent natural varicella infection . The impact of varicella vaccination on the incidence of herpes zoster is discussed separately. (See "Epidemiology and pathogenesis of varicella-zoster virus infection: Herpes zoster", section on 'Impact of varicella vaccine on incidence of herpes zoster'.)
POST-VACCINATION SEROLOGY — Post-vaccination serology is not recommended for any recipients of varicella vaccine, including health care personnel. Commercially available antibody assays are not sensitive enough to reliably detect vaccine-induced antibody, which may result in false negative results and unnecessary revaccination .
Pregnant women — Varicella vaccine is contraindicated in women who are pregnant or are trying to become pregnant. Prevention of varicella during pregnancy and varicella immunization before or after pregnancy are discussed separately. (See "Varicella-zoster virus infection in pregnancy", section on 'Post-exposure prophylaxis' and "Varicella-zoster virus infection in pregnancy", section on 'Pre-exposure prophylaxis' and "Immunizations during pregnancy".)
Immunocompromised hosts — Varicella vaccine is a live attenuated vaccine. It is contraindicated in people with severe immunosuppression (table 3) [22,59,80,81]. (See 'Contraindications and precautions' above.)
However, varicella vaccine may be beneficial for certain immunocompromised hosts who are not highly immunocompromised, as described below . Immunization of these patients should only be undertaken with expert guidance and consultation . (See "Immunizations in patients with primary immunodeficiency", section on 'Live vaccines'.)
●Children with leukemia – Varicella immunization may be suitable for certain children with leukemia who are in remission. Varicella vaccination for children with acute lymphocytic leukemia is discussed separately. (See "Overview of the treatment of acute lymphoblastic leukemia in children and adolescents", section on 'Varicella vaccine'.)
●HIV-infected patients – Varicella immunization may be administered to HIV-infected adults and children without evidence of severe immunodeficiency. A more detailed discussion of immunization in patients with HIV infection is found elsewhere. (See "Immunizations in HIV-infected patients", section on 'Varicella vaccine'.)
●Patients with T cell abnormalities – Varicella vaccination may be suitable for certain patients with partial congenital or acquired T-lymphocyte defects who are not severely immunosuppressed. (See "Immunizations in patients with primary immunodeficiency", section on 'Live vaccines'.)
●Glucocorticoid recipients – Patients who have received high doses of systemic glucocorticoids (ie, prednisone ≥20 mg per day or prednisone ≥2 mg/kg per day [for children who weigh <10 kg] or equivalent) may receive varicella vaccine after glucocorticoids have been discontinued. The recommended interval between discontinuation of high-dose systemic glucocorticoids and varicella vaccination depends upon the duration of glucocorticoid therapy :
•If glucocorticoids have been administered for <14 days, varicella vaccination can be administered immediately after discontinuation of treatment, although some experts would delay immunization until two weeks after discontinuation
•If glucocorticoids have been administered for ≥14 days, the recommended interval between discontinuation of treatment and varicella vaccination is one month
Low dose daily or alternate day systemic glucocorticoids (ie, prednisone <20 mg per day or prednisone <2 mg/kg per day [for children who weigh <10 kg] or equivalent), topical, replacement, and aerosolized glucocorticoids are not a contraindication to varicella vaccine .
Contacts of immunocompromised hosts — Healthy household contacts of immunocompromised patients should be given varicella vaccine to prevent acquisition of wild-type VZV and subsequent transmission to the immunocompromised contact [22,29,59,84-86]. Pre-licensure trials and postmarketing surveillance indicate that transmission of vaccine virus from healthy people to susceptible contacts is rare [63,66,73-77].
If the vaccine recipient develops vesicular skin lesions after vaccination, physical contact with immunocompromised individuals should be avoided until the rash resolves [22,29,68,69]. (See 'Transmission of vaccine virus' above.)
Health care providers — Health care providers should be screened for varicella immunity at the time of employment. Those who lack evidence of immunity and do not have a contraindication to immunization should be immunized. Varicella immunization for health care providers is discussed separately. (See "Immunizations for health care providers", section on 'Varicella vaccine' and "Prevention and control of varicella-zoster virus in hospitals", section on 'Prevention of varicella among health care personnel'.)
POST-EXPOSURE PROPHYLAXIS — The use of varicella vaccine for post-exposure prophylaxis is discussed separately. (See "Post-exposure prophylaxis against varicella-zoster virus infection", section on 'Who is eligible for varicella vaccine?'.)
BREAKTHROUGH VARICELLA — "Breakthrough varicella" or "mild varicella-like syndrome" (MVLS) refers to infection after exposure to wild-type virus in those who have been previously vaccinated. Most studies have noted MVLS occurring in <1 to 3 percent of vaccinated children each year after vaccination [87-89]. Most documented cases of varicella in vaccinated children are mild . Fever is often absent; the rash may be maculopapular rather than vesicular, with <50 lesions (compared with a median of 300 in unvaccinated children) [87-89]. However, children with breakthrough infection can still transmit varicella virus to other children [3,91]. (See "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Impact of vaccine on clinical manifestations'.)
Breakthrough varicella may arise from primary or secondary vaccine failure. "Primary vaccine failure" refers to the failure to mount a protective immune response to a dose of vaccine; "secondary vaccine failure" refers to the gradual loss of immunity after initial vaccine response (ie, waning immunity). Primary vaccine failure after a single dose may occur in as many as one-quarter of patients. As an example, in an observational study in which varicella antibody was assessed with a research assay (fluorescent antibody to membrane antigen), which is more sensitive than commercially available varicella antibody assays, primary vaccine failure occurred in 24 percent of 148 children . Primary vaccine failure occurs in <1 percent of people who receive two doses [22,45,92,93]. Studies evaluating secondary vaccine failure after a single dose of varicella vaccine have inconsistent results [40,94-96].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Varicella-zoster virus" and "Society guideline links: Immunizations in children and adolescents".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Why does my child need vaccines? (Beyond the Basics)" and "Patient education: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)" and "Patient education: Chickenpox prevention and treatment (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Routine immunization with two doses of varicella vaccine is at least 90 percent effective in preventing primary varicella infection and 99 percent effective in preventing severe varicella disease. It also reduces the risk of transmission and varicella-related health care utilization. (See 'Benefits of immunization' above.)
●Evidence of immunity includes documentation of age-appropriate immunization; laboratory evidence of immunity or laboratory confirmation of disease; diagnosis or verification of typical primary varicella infection by a health care provider; or, for people born in the United States, birth before 1980 unless they are immunosuppressed, pregnant, or a health care worker. (See 'Evidence of immunity' above.)
●In the United States, we recommend varicella immunization for children ≥12 months of age, adolescents, and adults without evidence of immunity, as recommended by the Advisory Committee on Immunization Practices (Grade 1A). Two doses of varicella vaccine are administered to reduce the risk of breakthrough varicella:
•In children, the two doses are typically administered at age 12 through 15 months and at age 4 through 6 years. (See 'Children <13 years' above.)
•In adolescents ≥13 years and adults, the two doses are usually separated by 4 to 8 weeks. (See 'Adolescents and adults' above.)
●Routine schedules for varicella vaccine vary from country to country. Schedules for individual countries are available through the World Health Organization. (See 'Schedules in other countries' above.)
●Varicella immunization is particularly important for health care providers, contacts of immunocompromised hosts, and other individuals at high risk of exposure or transmission (eg, teachers of young children, military personnel, etc). (See 'Priority groups' above.)
●Contraindications to varicella vaccine include severe allergic reaction to a previous dose or vaccine component (eg, gelatin, neomycin), pregnancy, and being severely immunocompromised (table 3). (See 'Contraindications and precautions' above.)
●The dose of varicella vaccine (single-antigen varicella vaccine or combination measles, mumps, rubella, and varicella vaccine) is 0.5 mL. Varicella-containing vaccines are administered subcutaneously, usually in the upper outer triceps. Varicella vaccine may be administered at the same visit as other vaccines. If varicella vaccine is not administered on the same day as measles, mumps, and rubella vaccine, the two vaccines should be separated by at least 28 days. (See 'Administration' above.)
●Varicella vaccine is generally well tolerated; local injection reactions, rash, and febrile seizures have been reported. Transmission of vaccine virus is rare. However, people who develop a rash after varicella vaccine should refrain from physical contact with people who are susceptible to varicella, particularly those who are immunocompromised, until the rash has resolved. (See 'Local and systemic reactions' above and 'Transmission of vaccine virus' above.)
●Varicella immunization in special populations is discussed separately:
•Women trying to become pregnant and postpartum women (see "Immunizations during pregnancy", section on 'Preconception immunization' and "Immunizations during pregnancy", section on 'Postpartum immunization')
•Patients with cancer (see "Immunizations in patients with cancer", section on 'Varicella vaccine')
•Patients who have undergone solid organ transplant (see "Immunizations in solid organ transplant candidates and recipients", section on 'Live virus vaccines')
•Patients with HIV infection (see "Immunizations in HIV-infected patients", section on 'Varicella vaccine')
•Patients with primary and secondary immunodeficiency (see "Immunizations in patients with primary immunodeficiency", section on 'Live vaccines')
•Children with acute lymphoblastic leukemia (see "Overview of the treatment of acute lymphoblastic leukemia in children and adolescents", section on 'Varicella vaccine')
•Health care providers (see "Immunizations for health care providers", section on 'Varicella vaccine')
- Seward JF, Marin M, Vázquez M. Varicella vaccine effectiveness in the US vaccination program: a review. J Infect Dis 2008; 197 Suppl 2:S82.
- Vázquez M, LaRussa PS, Gershon AA, et al. The effectiveness of the varicella vaccine in clinical practice. N Engl J Med 2001; 344:955.
- Seward JF, Zhang JX, Maupin TJ, et al. Contagiousness of varicella in vaccinated cases: a household contact study. JAMA 2004; 292:704.
- Kuter BJ, Weibel RE, Guess HA, et al. Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies. Vaccine 1991; 9:643.
- Sadzot-Delvaux C, Rentier B, Wutzler P, et al. Varicella vaccination in Japan, South Korea, and Europe. J Infect Dis 2008; 197 Suppl 2:S185.
- Macartney KK, Burgess MA. Varicella vaccination in Australia and New Zealand. J Infect Dis 2008; 197 Suppl 2:S191.
- Centers for Disease Control and Prevention (CDC). Evolution of varicella surveillance--selected states, 2000-2010. MMWR Morb Mortal Wkly Rep 2012; 61:609.
- Marin M, Zhang JX, Seward JF. Near elimination of varicella deaths in the US after implementation of the vaccination program. Pediatrics 2011; 128:214.
- Lee BR, Feaver SL, Miller CA, et al. An elementary school outbreak of varicella attributed to vaccine failure: policy implications. J Infect Dis 2004; 190:477.
- Perella D, Wang C, Civen R, et al. Varicella Vaccine Effectiveness in Preventing Community Transmission in the 2-Dose Era. Pediatrics 2016; 137.
- Streng A, Grote V, Rack-Hoch A, Liese JG. Decline of Neurologic Varicella Complications in Children During the First Seven Years After Introduction of Universal Varicella Vaccination in Germany, 2005-2011. Pediatr Infect Dis J 2017; 36:79.
- Zhou F, Harpaz R, Jumaan AO, et al. Impact of varicella vaccination on health care utilization. JAMA 2005; 294:797.
- Reynolds MA, Watson BM, Plott-Adams KK, et al. Epidemiology of varicella hospitalizations in the United States, 1995-2005. J Infect Dis 2008; 197 Suppl 2:S120.
- Davis MM, Patel MS, Gebremariam A. Decline in varicella-related hospitalizations and expenditures for children and adults after introduction of varicella vaccine in the United States. Pediatrics 2004; 114:786.
- Lopez AS, Zhang J, Brown C, Bialek S. Varicella-related hospitalizations in the United States, 2000-2006: the 1-dose varicella vaccination era. Pediatrics 2011; 127:238.
- Marin M, Watson TL, Chaves SS, et al. Varicella among adults: data from an active surveillance project, 1995-2005. J Infect Dis 2008; 197 Suppl 2:S94.
- Chaves SS, Lopez AS, Watson TL, et al. Varicella in infants after implementation of the US varicella vaccination program. Pediatrics 2011; 128:1071.
- Waye A, Jacobs P, Tan B. The impact of the universal infant varicella immunization strategy on Canadian varicella-related hospitalization rates. Vaccine 2013; 31:4744.
- World Health Organization. Systematic review of available evidence on effectiveness and duration of protection of varicella vaccines. April 2014. http://www.who.int/immunization/sage/meetings/2014/april/presentations_background_docs/en/ (Accessed on October 20, 2015).
- Marin M, Marti M, Kambhampati A, et al. Global Varicella Vaccine Effectiveness: A Meta-analysis. Pediatrics 2016; 137:e20153741.
- Verstraeten T, Jumaan AO, Mullooly JP, et al. A retrospective cohort study of the association of varicella vaccine failure with asthma, steroid use, age at vaccination, and measles-mumps-rubella vaccination. Pediatrics 2003; 112:e98.
- Marin M, Güris D, Chaves SS, et al. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007; 56:1.
- Centers for Disease Control and Prevention. Varicella. In: Epidemiology and Prevention of Vaccine-Preventable Diseases. The Pink Book: Course Textbook, 13th ed, Hamborsky J, Kroger A, Wolfe S, (Eds). Public Health Foundation, Washington, DC 2015. http://www.cdc.gov/vaccines/pubs/pinkbook/index.html (Accessed on July 09, 2015).
- Kim DK, Riley LE, Harriman KH, et al. Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2017. Ann Intern Med 2017; 166:209.
- Lee GM. Varicella vaccination in adults: is it cost-effective? Clin Infect Dis 2007; 44:1049.
- Kjersem H, Jepsen S. Varicella among immigrants from the tropics, a health problem. Scand J Soc Med 1990; 18:171.
- Centers for Disease Control and Prevention (CDC). Varicella outbreaks among Mexican adults--Alabama, 2000. MMWR Morb Mortal Wkly Rep 2000; 49:735.
- Merrett P, Schwartzman K, Rivest P, Greenaway C. Strategies to prevent varicella among newly arrived adult immigrants and refugees: a cost-effectiveness analysis. Clin Infect Dis 2007; 44:1040.
- American Academy of Pediatrics. Varicella-zoster virus infections. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.846.
- Lopez AS, Guris D, Zimmerman L, et al. One dose of varicella vaccine does not prevent school outbreaks: is it time for a second dose? Pediatrics 2006; 117:e1070.
- Bayer O, Heininger U, Heiligensetzer C, von Kries R. Metaanalysis of vaccine effectiveness in varicella outbreaks. Vaccine 2007; 25:6655.
- Tugwell BD, Lee LE, Gillette H, et al. Chickenpox outbreak in a highly vaccinated school population. Pediatrics 2004; 113:455.
- Michalik DE, Steinberg SP, Larussa PS, et al. Primary vaccine failure after 1 dose of varicella vaccine in healthy children. J Infect Dis 2008; 197:944.
- Kroger AT, Duchin J, Vázquez M. General best practice guidelines for immunization. Best practices guidance of the Advisory Committee on Immunization Practices (ACIP). Available at: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html (Accessed on April 27, 2017).
- Ngai AL, Staehle BO, Kuter BJ, et al. Safety and immunogenicity of one vs. two injections of Oka/Merck varicella vaccine in healthy children. Pediatr Infect Dis J 1996; 15:49.
- 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; 23:132.
- Prymula R, Bergsaker MR, Esposito S, et al. Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial. Lancet 2014; 383:1313.
- Shapiro ED, Vazquez M, Esposito D, et al. Effectiveness of 2 doses of varicella vaccine in children. J Infect Dis 2011; 203:312.
- Leung J, Lopez AS, Blostein J, et al. Impact of the US Two-dose Varicella Vaccination Program on the Epidemiology of Varicella Outbreaks: Data from Nine States, 2005-2012. Pediatr Infect Dis J 2015; 34:1105.
- Baxter R, Ray P, Tran TN, et al. Long-term effectiveness of varicella vaccine: a 14-Year, prospective cohort study. Pediatrics 2013; 131:e1389.
- Siedler A, Rieck T, Tolksdorf K. Strong Additional Effect of a Second Varicella Vaccine Dose in Children in Germany, 2009-2014. J Pediatr 2016; 173:202.
- Leung J, Harpaz R. Impact of the Maturing Varicella Vaccination Program on Varicella and Related Outcomes in the United States: 1994-2012. J Pediatric Infect Dis Soc 2016; 5:395.
- Lopez AS, Zhang J, Marin M. Epidemiology of Varicella During the 2-Dose Varicella Vaccination Program - United States, 2005-2014. MMWR Morb Mortal Wkly Rep 2016; 65:902.
- Marin M, Nguyen HQ, Keen J, et al. Importance of catch-up vaccination: experience from a varicella outbreak, Maine, 2002-2003. Pediatrics 2005; 115:900.
- Kuter BJ, Ngai A, Patterson CM, et al. Safety, tolerability, and immunogenicity of two regimens of Oka/Merck varicella vaccine (Varivax) in healthy adolescents and adults. Oka/Merck Varicella Vaccine Study Group. Vaccine 1995; 13:967.
- Varicella and herpes zoster vaccines: WHO position paper, June 2014. Wkly Epidemiol Rec 2014; 89:265.
- American Academy of Pediatrics. Active immunization of people who recently received immune globulin and other blood products. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.38.
- McLean HQ, Fiebelkorn AP, Temte JL, et al. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013; 62:1.
- ProQuad measles, mumps, rubella, and varicella virus vaccine for subcutaneous injection. US Food & Drug (FDA) approved product information. Revised March 2014. US National Library of Medicine. Available at: www.dailymed.nlm.nih.gov (Accessed on May 06, 2015).
- Jacobsen SJ, Ackerson BK, Sy LS, et al. Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting. Vaccine 2009; 27:4656.
- Klein NP, Fireman B, Yih WK, et al. Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures. Pediatrics 2010; 126:e1.
- MacDonald SE, Dover DC, Simmonds KA, Svenson LW. Risk of febrile seizures after first dose of measles-mumps-rubella-varicella vaccine: a population-based cohort study. CMAJ 2014; 186:824.
- Marin M, Broder KR, Temte JL, et al. Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2010; 59:1.
- Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP). Update: recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine. MMWR Morb Mortal Wkly Rep 2008; 57:258.
- Klein NP, Lewis E, Baxter R, et al. Measles-containing vaccines and febrile seizures in children age 4 to 6 years. Pediatrics 2012; 129:809.
- Committee on Infectious Diseases. Policy statement—Prevention of varicella: update of recommendations for use of quadrivalent and monovalent varicella vaccines in children. Pediatrics 2011; 128:630.
- Immunzation Action Coalition. Ask the experts: Varicella. http://www.immunize.org/askexperts/experts_var.asp (Accessed on October 21, 2015).
- Dennehy PH, Reisinger KS, Blatter MM, Veloudis BA. Immunogenicity of subcutaneous versus intramuscular Oka/Merck varicella vaccination in healthy children. Pediatrics 1991; 88:604.
- Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58:e44.
- American Academy of Pediatrics. Appendix V. Guide to contraindications and precautions to immunizations. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW, Brady MT, Jackson MA, Long SS. (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.994.
- American Academy of Pediatrics. Measles. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.535.
- Centers for Disease Control and Prevention (CDC). Simultaneous administration of varicella vaccine and other recommended childhood vaccines--United States, 1995-1999. MMWR Morb Mortal Wkly Rep 2001; 50:1058.
- Galea SA, Sweet A, Beninger P, et al. The safety profile of varicella vaccine: a 10-year review. J Infect Dis 2008; 197 Suppl 2:S165.
- Chaves SS, Haber P, Walton K, et al. Safety of varicella vaccine after licensure in the United States: experience from reports to the vaccine adverse event reporting system, 1995-2005. J Infect Dis 2008; 197 Suppl 2:S170.
- Su JR, Leroy Z, Lewis PW, et al. Safety of Second-Dose Single-Antigen Varicella Vaccine. Pediatrics 2017; 139.
- Weibel RE, Neff BJ, Kuter BJ, et al. Live attenuated varicella virus vaccine. Efficacy trial in healthy children. N Engl J Med 1984; 310:1409.
- Varivax. US Food & Drug Administration (FDA) approved product information. Revised October, 2014. US National Librafy of Medicine. www.dailymed.nlm.nih.gov (Accessed on October 22, 2015).
- Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention (CDC). Immunization of health-care personnel: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011; 60:1.
- Kamboj M, Sepkowitz KA. Risk of transmission associated with live attenuated vaccines given to healthy persons caring for or residing with an immunocompromised patient. Infect Control Hosp Epidemiol 2007; 28:702.
- Bhalla P, Forrest GN, Gershon M, et al. Disseminated, persistent, and fatal infection due to the vaccine strain of varicella-zoster virus in an adult following stem cell transplantation. Clin Infect Dis 2015; 60:1068.
- Gershon AA, Gershon MD. Pathogenesis and current approaches to control of varicella-zoster virus infections. Clin Microbiol Rev 2013; 26:728.
- Levin MJ, DeBiasi RL, Bostik V, Schmid DS. Herpes zoster with skin lesions and meningitis caused by 2 different genotypes of the Oka varicella-zoster virus vaccine. J Infect Dis 2008; 198:1444.
- Salzman MB, Sharrar RG, Steinberg S, LaRussa P. Transmission of varicella-vaccine virus from a healthy 12-month-old child to his pregnant mother. J Pediatr 1997; 131:151.
- LaRussa P, Steinberg S, Meurice F, Gershon A. Transmission of vaccine strain varicella-zoster virus from a healthy adult with vaccine-associated rash to susceptible household contacts. J Infect Dis 1997; 176:1072.
- Diaz PS, Au D, Smith S, et al. Lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings. Pediatrics 1991; 87:166.
- Grossberg R, Harpaz R, Rubtcova E, et al. Secondary transmission of varicella vaccine virus in a chronic care facility for children. J Pediatr 2006; 148:842.
- Tsolia M, Gershon AA, Steinberg SP, Gelb L. Live attenuated varicella vaccine: evidence that the virus is attenuated and the importance of skin lesions in transmission of varicella-zoster virus. National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study Group. J Pediatr 1990; 116:184.
- Gonzales JA, Levison AL, Stewart JM, et al. Retinal necrosis following varicella-zoster vaccination. Arch Ophthalmol 2012; 130:1355.
- American Academy of Pediatrics. Committee on Infectious Diseases. Varicella vaccine update. Pediatrics 2000; 105:136.
- Centers for Disease Control and Prevention (CDC). Varicella-related deaths among adults--United States, 1997. MMWR Morb Mortal Wkly Rep 1997; 46:409.
- Cohen JI, Brunell PA, Straus SE, Krause PR. Recent advances in varicella-zoster virus infection. Ann Intern Med 1999; 130:922.
- Levin MJ. Varicella vaccination of immunocompromised children. J Infect Dis 2008; 197 Suppl 2:S200.
- American Academy of Pediatrics. Immunization in immunocompromised children. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS. (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.74.
- Kappagoda C, Shaw P, Burgess M, et al. Varicella vaccine in non-immune household contacts of children with cancer or leukaemia. J Paediatr Child Health 1999; 35:341.
- Centers for Disease Control and Prevention (CDC). Notes from the field: severe varicella in an immunocompromised child exposed to an unvaccinated sibling with varicella--Minnesota, 2011. MMWR Morb Mortal Wkly Rep 2012; 61:541.
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on September 21, 2016).
- Watson BM, Piercy SA, Plotkin SA, Starr SE. Modified chickenpox in children immunized with the Oka/Merck varicella vaccine. Pediatrics 1993; 91:17.
- White CJ, Kuter BJ, Ngai A, et al. Modified cases of chickenpox after varicella vaccination: correlation of protection with antibody response. Pediatr Infect Dis J 1992; 11:19.
- Clements DA. Modified varicella-like syndrome. Infect Dis Clin North Am 1996; 10:617.
- Gould PL, Leung J, Scott C, et al. An outbreak of varicella in elementary school children with two-dose varicella vaccine recipients--Arkansas, 2006. Pediatr Infect Dis J 2009; 28:678.
- Shapiro ED. Second dose of varicella vaccine for children: are we giving it too late? J Infect Dis 2008; 197:935.
- Gershon AA, Steinberg SP, LaRussa P, et al. Immunization of healthy adults with live attenuated varicella vaccine. J Infect Dis 1988; 158:132.
- Wallace MR, Bowler WA, Murray NB, et al. Treatment of adult varicella with oral acyclovir. A randomized, placebo-controlled trial. Ann Intern Med 1992; 117:358.
- Black S, Ray P, Shinefield H, et al. Lack of association between age at varicella vaccination and risk of breakthrough varicella, within the Northern California Kaiser Permanente Medical Care Program. J Infect Dis 2008; 197 Suppl 2:S139.
- Vázquez M, LaRussa PS, Gershon AA, et al. Effectiveness over time of varicella vaccine. JAMA 2004; 291:851.
- Chaves SS, Gargiullo P, Zhang JX, et al. Loss of vaccine-induced immunity to varicella over time. N Engl J Med 2007; 356:1121.