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PEDIATRICS Vol. 112 No. 2 August 2003, pp. e98-e103

ELECTRONIC ARTICLE

A Retrospective Cohort Study of the Association of Varicella Vaccine Failure With Asthma, Steroid Use, Age at Vaccination, and Measles-Mumps-Rubella Vaccination

Thomas Verstraeten, MD, MSc*,{ddagger}, Aisha O. Jumaan, PhD, MPH{ddagger}, John P. Mullooly, PhD§, Jane F. Seward, MBBS, MPH{ddagger}, Hector S. Izurieta, MD, MPH, Frank DeStefano, MD, MPH{ddagger}, Steven B. Black, MD||, Robert T. Chen, MD, MA{ddagger} the Vaccine Safety Datalink Research Group

* Epidemic Intelligence Service Program, Epidemiology Program Office
{ddagger} National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia
§ Center for Health Research, Northwest Kaiser Permanente, Portland, Oregon
Pan American Health Organization, Washington, DC
|| Pediatric Vaccine Study Center, Northern California Kaiser Permanente, Oakland, California

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.

Key Words: varicella vaccine • asthma • steroids • measles-mumps-rubella vaccine • chickenpox

Abbreviations: Th2, T helper type 2 • RR, relative risk • CI, confidence interval • VSD, Vaccine Safety Datalink • MMR, measles-mumps-rubella vaccine • HMO, health maintenance organization • ICD9, International Classification of Diseases, Ninth Revision • aRR, adjusted relative risk

Received for publication Dec 2, 2002; Accepted Mar 24, 2003.


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