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Encephalopathy After Whole-Cell Pertussis or Measles Vaccination: Lack of Evidence for a Causal Association in a Retrospective Case–Control Study

Ray, Paula MPH*; Hayward, Jean MD*; Michelson, David MD*; Lewis, Edwin MPH*; Schwalbe, Joan MS*; Black, Steve MD*; Shinefield, Henry MD*; Marcy, Michael MD; Huff, Ken MD; Ward, Joel MD; Mullooly, John MD; Chen, Robert MD§; Davis, Robert MD§The Vaccine Safety Datalink Group

The Pediatric Infectious Disease Journal: September 2006 - Volume 25 - Issue 9 - p 768-773
doi: 10.1097/01.inf.0000234067.84848.e1
Original Studies

Background: Whole-cell pertussis (wP) and measles vaccines are effective in preventing disease but have also been suspected of increasing the risk of encephalopathy or encephalitis. Although many countries now use acellular pertussis vaccines, wP vaccine is still widely used in the developing world. It is therefore important to evaluate whether wP vaccine increases the risk of neurologic disorders.

Methods: A retrospective case–control study was performed at 4 health maintenance organizations. Records from January 1, 1981, through December 31, 1995, were examined to identify children aged 0 to 6 years old hospitalized with encephalopathy or related conditions. The cause of the encephalopathy was categorized as known, unknown or suspected but unconfirmed. Up to 3 controls were matched to each case. Conditional logistic regression was used to analyze the relative risk of encephalopathy after vaccination with diphtheria–tetanus–pertussis (DTP) or measles–mumps–rubella (MMR) vaccines in the 90 days before disease onset as defined by chart review compared with an equivalent period among controls indexed by matching on case onset date.

Results: Four-hundred fifty-two cases were identified. Cases were no more likely than controls to have received either vaccine during the 90 days before disease onset. When encephalopathies of known etiology were excluded, the odds ratio for case children having received DTP within 7 days before onset of disease was 1.22 (95% confidence interval [CI] = 0.45–3.31, P = 0.693) compared with control children. For MMR in the 90 days before onset of encephalopathy, the odds ratio was 1.23 (95% confidence interval = 0.51–2.98, P = 0.647).

Conclusions: In this study of more than 2 million children, DTP and MMR vaccines were not associated with an increased risk of encephalopathy after vaccination.

From the *Kaiser Permanente Vaccine Study Center, Oakland, CA; the †Division of Neurology, Department of Pediatrics, Harbor–UCLA Medical Center, Torrance, CA; the ‡Center for Health Research, Kaiser Permanente, Portland, OR; the §National Immunization Program, Centers for Disease Control and Prevention, Atlanta, GA; and ∥Clinical Professor of Pediatrics, University of California San Francisco, CA.

Accepted for publication June 16, 2006.

Funded by the American Association of Health Plans as part of the CDC Vaccine Safety Datalink Project.

Address for correspondence: Steve Black, MD, Kaiser Vaccine Study Center, One Kaiser Plaza, 16th Floor Bayside, Oakland, CA 94612. E-mail

© 2006 Lippincott Williams & Wilkins, Inc.