Comprehensive Report on Use of the Chicken Pox (Varicella) Vaccine
courtesy of the Centers for Disease Control

               


RECOMMENDATIONS FOR THE USE OF VARICELLA VIRUS VACCINE

Persons <13 Years of Age

Varicella virus vaccine has been approved for use among healthy children 12 months–12 years of age. Children in this age group should receive one 0.5-mL dose of vaccine subcutaneously. Children who have a reliable history of varicella are considered immune, and those who do not have such a history or who have an uncertain history of varicella are considered susceptible. Serologic testing of children before vaccination is not warranted because a) most children 12 months–12 years of age who do not have a clinical history of varicella are susceptible and b) the vaccine is well tolerated in seropositive persons.

12–18 Months of Age

All children should be routinely vaccinated at 12–18 months of age. Varicella virus vaccine may be administered to all children at this age— regardless of a history of varicella; however, vaccination is not necessary for children who have reliable histories of varicella. Varicella virus vaccine preferably should be administered routinely to children at the same time as measles-mumps-rubella (MMR) vaccine. Varicella virus vaccine is safe and effective in healthy children 12 months of age when administered at the same time as MMR vaccine at separate sites and with separate syringes or when administered separately 30 days apart. The number and types of adverse events in children who have received VARIVAX â and MMR concurrently have not differed from those in children who have been administered the vaccines at different visits (Merck and Company, Inc., unpublished data). Data concerning the effect of simultaneous administration of VARIVAX â with variouscombinations of MMR-, diphtheria and tetanus toxoids and pertussis (DTP)-, and Haemophilus influenzae type b (Hib)-containing vaccines have not yet been published. However, data regarding simultaneous administration of an investigational quadrivalent vaccine containing varicella (MMRII VÔ) with diphtheria and tetanus toxoids and acellular pertussis (DTaP) and Hib vaccines suggest that no notable interactions exist between varicella and any other vaccines that are routinely administered to young children (e.g., measles, mumps, rubella, diphtheria, tetanus, pertussis, and Haemophilus influenzae type b vaccines). Furthermore, the simultaneous administration of most widely used live, attenuated and inactivated vaccines has not resulted in impaired antibody response or an increased rate of adverse events. Therefore, varicella virus vaccine may be administered simultaneously with all of the vaccines recommended for children 12–18 months of age. Simultaneous administration is particularly important when health-care providers anticipate that, because of certain factors (e.g., previously missed vaccination opportunities), a child may not return for subsequent vaccination.

19 Months–12 Years of Age

Varicella vaccine is recommended for all susceptible children by their 13th birthday. After 12 years of age, natural varicella is more severe and complications are more frequent. Recently, ACIP recommended establishing a routine immunization visit at 11–12 years of age to review immunization status and to administer necessary vaccinations. Although vaccine may be administered at any time after 18 months of age, varicella virus vaccine should be administered to susceptible children during this routine visit.

Persons 13 Years of Age

Varicella vaccine is approved for use among healthy adolescents and adults. Because natural VZV infection can be severe in older adolescents and adults, varicella immunity is desirable in these age groups. Persons 13 years of age should be administered two 0.5-mL doses of vaccine, subcutaneously, 4–8 weeks apart. If >8 weeks elapse following the first dose, the second dose can be administered without restarting the schedule. Persons 13 years of age who have reliable histories of varicella are considered immune. Those who do not have such histories are considered susceptible and can be tested to determine immune status or can be vaccinated without testing. Because 71%–93% of adults who do not have a reliable history of varicella are actually immune, serologic testing before vaccination is likely to be cost effective for both adults and adolescents. Adolescents and adults should be assessed for varicella immune status, and those who are susceptible should be vaccinated. Priority should be given to vaccination of susceptible adolescents and adults who are at high risk for exposure and for transmitting disease; specific assessment efforts are targeted to these persons.

Health-Care Workers

All susceptible health-care workers should ensure that they are immune to varicella. In health-care institutions, serologic screening of personnel who have a negative or uncertain history of varicella is likely to be cost effective. Routine testing for varicella immunity after two doses of vaccine is not necessary for the management of vaccinated health-care workers who may be exposed to varicella, because 99% of persons are seropositive after the second dose. Seroconversion, however, does not always result in full protection against disease. Testing vaccinees for seropositivity immediately after exposure to VZV is a potentially effective strategy for identifying persons who remain at risk for varicella. Prompt serologic results may be obtained using the LA test. Varicella is unlikely to develop in persons who have detectable antibody; persons who do not have such antibody can be retested in 5–6 days to determine if an anamnestic response is present, in which case development of disease is unlikely. Persons who remain susceptible may be furloughed. Alternatively, persons can be monitored daily to determine clinical status and then furloughed at the onset of manifestations of varicella. Institutional guidelines are needed for the management of exposed vaccinees who do not have detectable antibody and for persons who develop clinical varicella. More information is needed concerning the risk for transmission of vaccine virus from vaccinees in whom varicella-like rash develops following vaccination. On the basis of available data, the risk appears to be minimal, and the benefits of vaccinating susceptible health-care workers outweigh this potential risk. As a safeguard, institutions may wish to consider precautions for personnel in whom rash develops

· Vaccination is recommended for susceptible persons who have close contact with persons at high risk for serious complications (e.g., health-care workers and family contacts of immunocompromised persons).

· Vaccination should be considered for susceptible persons in the following groups who are at high risk for exposure:

a) Persons who live or work in environments in which transmission of VZV is likely (e.g., teachers of young children, day-care employees, and residents and staff in institutional settings).

b) Persons who live or work in environments in which varicella transmission can occur (e.g., college students, inmates and staff of correctional institutions, and military personnel).

c) Nonpregnant women of childbearing age. Vaccination of women who are not pregnant—but who may become pregnant in the future—will reduce the risk for VZV transmission to the fetus. Varicella immunity may be ascertained at any routine health-care visit or in any setting in which vaccination history may be reviewed (e.g., upon college entry). Women should be asked if they are pregnant and advised to avoid pregnancy for 1 month following each dose of vaccine.

d) International travelers. Vaccination should be considered for international travelers who do not have evidence of immunity to VZV (e.g., serologic tests), especially if the traveler expects to have close personal contact with local populations, because varicella is endemic in most countries.

· Vaccination of other susceptible adolescents and adults is desirable and may be offered during routine health-care visits. Vaccination of persons 13 years of age following vaccination and for other vaccinated personnel who will have contact with susceptible persons at high risk for serious complications. Vaccination should be considered for unvaccinated health-care workers who are exposed to varicella and whose immunity is not documented. However, because the protective effects of postexposure vaccination are unknown, persons vaccinated after an exposure should be managed in the manner recommended for unvaccinated persons.

Household Contacts of Immunocompromised Persons

Immunocompromised persons are at high risk for serious varicella infections. Disseminated disease occurs in approximately 30% of such persons who have primary infection. Vaccination of household contacts provides protection for immunocompromised persons by decreasing the likelihood that wild-type varicella virus will be introduced into the household. Vaccination of household contacts of immunocompromised persons theoretically may pose a minimal risk of transmission of vaccine virus to immunocompromised persons, although in one study, no evidence of transmission of vaccine virus was found after vaccinating 37 healthy siblings of 30 children with malignancy.

Available data indicate that disease caused by vaccine virus in immunocompromised persons is milder than wild-type disease and can be treated with acyclovir. More information is needed concerning the risk for transmission of the vaccine virus from both vaccinees who have and who do not have varicella-like rash following vaccination. On the basis of available data, the benefits of vaccinating susceptible household contacts of immunocompromised persons outweigh the potential risk for transmission of vaccine virus to immunocompromised contacts.

VACCINE-ASSOCIATED ADVERSE EVENTS

Varicella virus vaccine has been well tolerated when administered to >11,000 healthy children, adolescents, and adults during clinical trials. Inadvertent vaccination of persons immune to varicella has not resulted in an increase in adverse events. In a double-blind, placebo-controlled study of 914 healthy, susceptible children and adolescents, pain and redness at the injection site were the only adverse events that occurred significantly more often (p<0.05) in vaccine recipients than in placebo recipients.

Persons 12 Months–12 Years of Age

In uncontrolled clinical trials of approximately 8,900 healthy children (Merck and Company, Inc., package insert) who were administered one dose of vaccine and then monitored for up to 42 days, 14.7% developed fever (i.e., oral temperature ³102 F [³39 C]); these febrile episodes occurred throughout the 42-day period and were usually associated with intercurrent illness. A total of 19.3% of vaccine recipients had complaints regarding the injection site (e.g., pain/soreness, swelling, erythema, rash, pruritus, hematoma, induration, and stiffness), 3.4% had a mild, varicella-like rash at the injection site consisting of a median number of two lesions and occurring at a peak of 8–19 days postvaccination, and 3.8% had a nonlocalized, varicella-like rash consisting of a median number of five lesions and occurring at a peak of 5–26 days postvaccination. Febrile seizures following vaccination occurred in <0.1% of children; a causal relationship has not been established.

Persons 13 Years of Age

In uncontrolled trials of persons 13 years of age, approximately 1,600 vaccinees who received one dose and 955 who received two doses of varicella vaccine were monitored for 42 days for adverse events (Merck and Company, Inc., package insert). After the first and second doses, 10.2% and 9.5% of vaccinees, respectively, developed fever (i.e., oral temperature ³100 F [37.7 C]); these febrile episodes occurred throughout the 42-day period and were usually associated with intercurrent illness. After one and two doses, 24.4% and 32.5% of vaccinees, respectively, had complaints regarding the injection site (e.g., soreness, swelling, erythema, rash, pruritus, hematoma, pyrexia, induration, and numbness); a varicella-like rash at the injection site consisting of a median number of two lesions and occurring at a peak of 6–20 days and 0–6 days postvaccination, respectively, developed in 3% and 1% of vaccinees, respectively; and a nonlocalized rash consisting of a median number of five lesions developed in 5.5% and 0.9% of vaccinees, respectively, and occurred at a peak of 7– 21 days and 0–23 days postvaccination, respectively.

Postlicensure Adverse Vaccine Events During the first 12 months following vaccine licensure, more than 2.3 million doses of vaccine were distributed in the United States. The Vaccine Adverse Events Reporting System (VAERS) and the vaccine manufacturer have received a limited number of reports of serious medical events occurring within 6 weeks after varicella virus vaccination, including encephalitis (n=4), ataxia (n=7), and erythema multiforme (n=10). Three cases of anaphylaxis have occurred within 10 minutes of vaccination. A causal relationship between the vaccine and these events has not been determined. Potential delayed or underreporting of events to VAERS may have occurred. Physicians and health-care providers are encouraged to report any suspected adverse events that occur after varicella virus vaccination.

CONTRAINDICATIONS AND PRECAUTIONS

Allergy to Vaccine Components

The administration of live varicella virus vaccine rarely results in hypersensitivity. The information in the package insert should be carefully reviewed before vaccine is administered; vaccination is contraindicated for persons who have a history of anaphylactic reaction to any component of the vaccine, including gelatin. Varicella virusvaccine does not contain preservatives or egg protein—substances that have caused hypersensitive reactions to other vaccines. Varicella virus vaccine should not be administered to persons who have a history of anaphylactic reaction to neomycin. Neomycin allergy is usually manifested as a contact dermatitis, which is a delayedtype immune response rather than anaphylaxis. For persons who experience such a response, the adverse reaction, if any, would be an erythematous, pruritic nodule or papule present 48–96 hours after vaccination. A history of contact dermatitis to neomycin is not a contraindication to receiving varicella virus vaccine.

Illness

Vaccination of persons who have severe illness should be postponed until recovery. The decision to delay vaccination depends on the severity of symptoms and on the etiology of the disease. Vaccine can be administered to susceptible children who have mild illnesses with or without low-grade fever (e.g., diarrhea or upper-respiratory infection). Studies suggest that failure to vaccinate children with minor illnesses can impede vaccination efforts. Although no data exist regarding whether either varicella or live varicella virus vaccine exacerbates tuberculosis, vaccination is not recommended for persons who have untreated, active tuberculosis. Tuberculin skin testing, however, is not a prerequisite for varicella vaccination.

Altered Immunity

Varicella virus vaccine is not licensed for use in persons who have any malignant condition, including blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems. However, vaccine is available to any physician free of charge from the manufacturer through a research protocol for use in patients who have acute lymphoblastic leukemia (ALL) who a) are 12 months–17 years of age, b) have disease that has been in remission for at least 12 continuous months, c) have a negative history of varicella disease, d) have a peripheral blood-lymphocyte count of >700 cells/mm 3 , and e) have a platelet count of >100,000 cells/mm 3 within 24 hours of vaccination. The vaccine is well tolerated, immunogenic, and protective in children who meet these criteria ( 105–110 ). The most common reaction to the vaccine in patients who have ALL is a mild to moderate varicella-like rash (i.e., two to 200 lesions), which occurs in approximately 5% of children who have completed their chemotherapy before vaccination and 40% of vaccinees on maintenance chemotherapy ( 106 ).

Varicella virus vaccine should not be administered to persons who have primary or acquired immunodeficiency, including immunosuppression associated with acquired immunodeficiency syndrome (AIDS) or other clinical manifestations of human immunodeficiency virus (HIV) infections, cellular immunodeficiencies, hypogammaglobulinemia, and dysgammaglobulinemia. The use of varicella virus vaccine in persons who are infected with HIV has not been studied; therefore, vaccination of these persons is not recommended, although routine screening for HIV beforevaccination also is not recommended. The use of varicella virus vaccine in HIV-infected children is being investigated. If inadvertent vaccination of HIV-infected persons results in clinical disease, the use of acyclovir may modify the severity of disease.

Varicella virus vaccine should not be administered to persons who have a family history of congenital or hereditary immunodeficiency in first-degree relatives (e.g., parents and siblings) unless the immune competence of the potential vaccine recipient has been clinically substantiated or verified by a laboratory.

Varicella virus vaccine should not be administered to persons receiving immuno-suppressive therapy—except children who have ALL in remission, as previously described. Such persons are more susceptible to infections than healthy persons. Administration of live, attenuated varicella virus vaccine can result in a more extensive vaccine-associated rash or disseminated disease in persons receiving immuno-suppressive doses of corticosteroids. This contraindication does not apply to persons who are receiving corticosteroid-replacement therapy.

Children Who Have Conditions That Require Steroid Therapy

No data have been published concerning whether susceptible children receiving only inhaled doses of steroids can be vaccinated safely. However, most experts concur, on the basis of clinical experience, that vaccination of these children is safe. Susceptible children who are receiving systemic steroids for certain conditions (e.g., asthma) and who are not otherwise immunocompromised can be vaccinated if they are receiving <2 mg/kg of body weight or a total of 20 mg/day of prednisone or its equivalent. Antibody status should be assessed 6 weeks postvaccination, and children who have not seroconverted should be revaccinated. Some experts suggest withholding steroids for 2–3 weeks following vaccination when possible. Data from one study conducted in Japan indicated that children taking steroids for nephrosis were vaccinated safely when the steroids were suspended for 1–2 weeks before vaccination, although no serious reactions occurred among children vaccinated when steroid therapy was not suspended.
Children who are receiving high doses of systemic steroids (i.e., 2 mg/kg prednisone) for 2 weeks may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with the general recommendations for the use of live-virus vaccines; however, withholding steroids for at least 1 month before varicella vaccination is probably sufficient.

Exposure of Immunocompromised Persons to Vaccinees

Healthy persons in whom varicellalike rash develops following vaccination appear to have a minimal risk for transmission of vaccine virus to their close contacts (e.g., family members). Seroconversion has been documented in healthy siblings of healthy vaccinees in whom rash did not develop, although such an occurrence is rare. Vaccinees in whom vaccine-related rash develops, particularly health-care workers and household contacts of immunocompromised persons, should avoid contact with susceptible persons who are at high risk for severe complications. If a susceptible, immunocompromised person is inadvertently exposed to a person who has a vaccine- related rash, VZIG need not be administered because disease associated with this type of transmission is expected to be mild. Recent Administration of Blood, Plasma, or Immune Globulin Although passively acquired antibody is known to interfere with response to measles and rubella vaccines, the effect of the administration of immune globulin (IG) on the response to varicella virus vaccine is unknown. The duration of interference with the response to measles vaccination depends on the dosage and ranges from 3–11 months. Because of the potential inhibition of the response to varicella vaccination by passively transferred antibodies, varicella virus vaccine should not be administered for at least 5 months after administration of blood (except washed red blood cells), plasma, IG, or VZIG. In addition, IG and VZIG should not be administered for 3 weeks after vaccination unless the benefits exceed those of vaccination. In such cases, the vaccinee should either be revaccinated 5 months later or tested for immunity 6 months later and then revaccinated if seronegative.

Use of Salicylates

No adverse events associated with the use of salicylates after varicella vaccination have been reported. However, the vaccine manufacturer recommends that vaccine recipients avoid using salicylates for 6 weeks after receiving varicella virus vaccine because of the association between aspirin use and Reye syndrome following varicella.

Vaccination with subsequent close monitoring should be considered for children who have rheumatoid arthritis or other conditions requiring theraputic aspirin because the risk for serious complications associated with aspirin is likely to be greater in children in whom natural varicella disease develops than in children who receive the vaccine containing attenuated VZV. No association has been documented between Reye syndrome and analgesics or antipyretics that do not contain salicylic acid.

Pregnancy

The effects of the varicella virus vaccine on the fetus are unknown; therefore, pregnant women should not be vaccinated. Nonpregnant women who are vaccinated should avoid becoming pregnant for 1 month following each injection. For susceptible persons, having a pregnant household member is not a contraindication to vaccination. If a pregnant woman is vaccinated or becomes pregnant within 1 month of vaccination, she should be counseled about potential effects on the fetus. Wild-type varicella poses only a very small risk to the fetus (see Prenatal and Perinatal Exposure). Because the virulence of the attenuated virus used in the vaccine is less than that of the wild-type virus, the risk to the fetus, if any, should be even lower. In most circumstances, the decision to terminate a pregnancy should not be based on whether vaccine was administered during pregnancy. The manufacturer, in collaboration with CDC, has established the VARIVAX â Pregnancy Registry to monitor the maternal-fetal outcomes of pregnant women who are inadvertently administered varicella virus vaccine 3 months before or at any time during pregnancy (telephone: [800] 986-8999).

Nursing Mothers

Whether attenuated vaccine VZV is excreted in human milk and, if so, whether the infant could be infected are not known. Most live vaccines have not beendemonstrated to be secreted in breast milk. Attenuated rubella vaccine virus has been detected in breast milk but has produced only asymptomatic infection in the nursing infant. Therefore, varicella virus vaccine may be considered for a nursing mother.

Summary of Recommendations for Varicella Vaccination

PERSONS <13 YEARS OF AGE

Persons of this age group should receive one 0.5-mL dose of vaccine subcutaneously. Children who have not been vaccinated previously and who lack a reliable history of varicella infection are considered susceptible.

12–18 Months of Age

All children should be routinely vaccinated at 12–18 months of age. Varicella virus vaccine may be administered to all children at this age regardless of prior history of varicella; however, vaccination is not necessary for children who have reliable histories of varicella.

19 Months–12 Years of Age

Varicella vaccine is recommended for immunization of all susceptible children by the 13th birthday. Varicella virus vaccine should be administered to susceptible children during the routine immunization visit at 11–12 years of age but may be administered at any time during childhood.

PERSONS 13 YEARS OF AGE

Persons in this age group should be administered two 0.5-mL doses of vaccine, subcutaneously, 4–8 weeks apart. Vaccination is recommended for susceptible persons who have close contact with persons at high risk for serious complications (e.g., health-care workers and family contacts of immunocompromised persons).

Vaccination should be considered for susceptible persons in the following groups who are at high risk for exposure:

a) Persons who live or work in environments in which transmission of VZV is likely (e.g., teachers of young children, day-care employees, and residents and staff in institutional settings).

b) Persons who live or work in environments in which varicella transmission can occur (e.g., college students, inmates and staff of correctional institutions, and military personnel).

c) Nonpregnant women of childbearing age. Vaccination of women who are not pregnant—but who may become pregnant in the future—will reduce the risk for VZV transmission to the fetus. Varicella immunity may be ascertained at any routine health-care visit or in any setting in which vaccination history may be reviewed (e.g., upon college entry). Women should be asked if they are pregnant and advised to avoid pregnancy for 1 month following each dose of vaccine. Summary of

d) International travelers. Vaccination should be considered for international travelers who do not have evidence of immunity to VZV (e.g., serologic tests), especially if the traveler expects to have close personal contact with local populations, because varicella is endemic in most countries.

· Vaccination of other susceptible adolescents and adults is desirable and may be offered during routine health-care visits.