Published online August 1, 2007
PEDIATRICS Vol. 120 No. 2 August 2007, pp. 314-321 (doi:10.1542/peds.2006-3743)
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ARTICLE

Risk of Serious Neurologic Disease After Immunization of Young Children in Britain and Ireland

Katherine N. Ward, MA, MB, BChir, PhD, FRCPatha, Naomi J. Bryant, MSca, Nick J. Andrews, MScb, Jennifer S. Bowley, BSca, Anu Ohrling, MDa, Christopher M. Verity, MA, BM, BCh, FRCP, FRCPCH, DCHc, Euan M. Ross, MD, FRCP, FRCPCH, FFPH, DCHd and Elizabeth Miller, BSc, MB, BS, FRCPath, FFPHb

a Centre for Virology (UCL Campus), Division of Infection and Immunity, Royal Free and University College Medical School, Windeyer Institute of Medical Sciences, London, United Kingdom
b Centre for Infections, Health Protection Agency, London, United Kingdom
c Child Development Centre, Addenbrooke's Hospital, Cambridge, United Kingdom
d Child Studies Department, King's College, Strand, London, United Kingdom

OBJECTIVE. We sought to investigate the risk of serious neurologic disease after immunization in early childhood.

METHODS. The results of a 3-year prospective study of children (2–35 months old) in Britain and Ireland with encephalitis and/or severe illness with convulsions and fever were linked to each child's vaccine history. Cases were reported via the British Paediatric Surveillance Unit's network. The self-controlled case-series method was used to investigate associations between immunization and acute potential adverse events. The risk periods investigated were 0 to 3 and 0 to 7 days post–diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type b or meningococcal C conjugate vaccine and 6 to 11 and 15 to 35 days post–measles, mumps, rubella vaccine.

RESULTS. A total of 157 disease episodes from 155 children met the analytical case definition. There were 11 cases of herpes simplex encephalitis and 23 cases of primary human herpesvirus 6 and/or 7 infection. There was no evidence of a raised relative incidence of serious neurologic disease in any of the specified risk periods with the exception of a raised relative incidence of 5.68 in the 6–11 days after measles, mumps, rubella vaccine. Based on this relative incidence, between 3 and 6 of the 6 cases in this period were estimated to be attributable to the vaccine with a best estimate of 5. The 6 cases all had fever with convulsions lasting >30 minutes; in all but 1, there was complete recovery by discharge from hospital. Of the 5 patients who recovered, 1 had a concurrent primary human herpesvirus 6 infection and one a primary human herpesvirus 7.

CONCLUSIONS. Six to 11 days after measles, mumps, rubella vaccine there is an increased risk of fever and convulsions lasting >30 minutes. All 6 of the episodes temporally related to immunization met the criteria for complex febrile convulsions. The estimated attributable risk of serious neurological disease was similar to that previously found for measles vaccine.

Key Words: encephalitis • febrile convulsions • status epilepticus • vaccine • HHV-6/HHV-7

Abbreviations: DTP—diphtheria, tetanus, whole cell pertussis • Hib—Haemophilus influenzae type b • MMR—measles, mumps, rubella • NCES—National Childhood Encephalopathy Study • HHV-6—human herpesvirus 6 • HHV-7—human herpesvirus 7 • HPA—Health Protection Agency • MenC—meningococcal C conjugate • CSF—cerebrospinal fluid • RI—relative incidence • CI—confidence interval

Accepted Mar 27, 2007.