title: A retrospective cohort study of the association of varicella vaccine failure with asthma, steroid use, age at vaccination, and measles-mumps-rubella vaccination.
abstract: OBJECTIVE
  Varicella breakthrough, the occurrence of varicella disease >42 days after vaccination, is indicative of vaccination failure. A sevenfold increased risk of breakthrough among vaccinated children with asthma was observed in a 1996 varicella outbreak in a child care center. More recent outbreak investigations have also identified age at vaccination as a potential risk factor for breakthrough. We assessed the association of varicella breakthrough with asthma, steroids, age at varicella vaccination, and timing of measles-mumps-rubella (MMR) vaccination.
  
  
  METHODS
  We performed a retrospective cohort study among children born after 1993 and followed up through 1999 at 2 health maintenance organizations ([HMOs] A and B) in the United States. Information was obtained from automated vaccination, clinic, hospital discharge, and pharmacy records.
  
  
  RESULTS
  We identified 268 and 97 breakthrough cases among 80 584 and 8181 children vaccinated against varicella at HMOs A and B, respectively. Varicella breakthrough was not associated with asthma, inhaled steroids prescribed at any time, and oral steroids prescribed before vaccination. An increased risk of varicella breakthrough was found in the 3 months immediately after prescription for oral steroids at HMO A (adjusted relative risk [aRR]: 2.4; 95% confidence interval [CI]: 1.3-4.4) and HMO B (aRR: 2.8; 95% CI: 1.0-7.8), when varicella vaccine was given before 15 months of age at HMO A (aRR: 1.4; 95% CI: 1.1-1.9), and when varicella vaccination followed MMR vaccine within 28 days at HMO A (aRR: 3.1; 95% CI: 1.5-6.4).
  
  
  CONCLUSIONS
  Varicella vaccine failure in children was not associated with asthma or the use of inhaled steroids, but with the use of oral steroids. Administration of varicella vaccine before the age of 15 months may be associated with a slightly increased risk of breakthrough disease. As currently recommended, varicella vaccination should not be administered for 28 days after MMR vaccination.
authors.affiliation: Epidemic Intelligence Service Program, Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. thomas.verstraeten@gskbio.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Verstraeten
authors.forename: Aisha O
authors.initials: AO
authors.lastname: Jumaan
authors.forename: John P
authors.initials: JP
authors.lastname: Mullooly
authors.forename: Jane F
authors.initials: JF
authors.lastname: Seward
authors.forename: Hector S
authors.initials: HS
authors.lastname: Izurieta
authors.forename: Frank
authors.initials: F
authors.lastname: DeStefano
authors.forename: Steven B
authors.initials: SB
authors.lastname: Black
authors.forename: Robert T
authors.initials: RT
authors.lastname: Chen
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000367:Age Factors; D001249:Asthma / Q000150:complications* / Q000188:drug therapy; D002644:Chickenpox / Q000150:complications*; D019433:Chickenpox Vaccine; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D000305:Adrenal Cortex Hormones; D019433:Chickenpox Vaccine; D022542:Measles-Mumps-Rubella Vaccine