Epidemiology of influenza‐associated encephalitis‐encephalopathy in Hokkaido, the northernmost island of Japan

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Abstract
Background : It is well known that acute onset brain dysfunction, which usually is diagnosed as encephalitis or encephalopathy, occurs in association with influenza. However, this may have been underestimated as a rather infrequent event. Sixty‐four infants and children developed encephalitis‐encephalopathy during the five recent influenza seasons in Hokkaido, the northernmost island of Japan. Methods : Inquiries were sent at the end of each season, from October 1994 to March 1999, to 94 hospitals and institutes in Hokkaido which accept pediatric age patients, asking if there were any admitted cases of encephalitis or encephalopathy. Results : The patients were 42 boys and 22 girls and 47 (73.4%) were 4 years of age or younger. None of them had received an influenza vaccine nor had an oral administration of aspirin. Most of the patients became comatose with or without convulsions within a few days of the onset of fever. Twenty‐eight (43.8%) patients died and 13 (20.3%) had neurological sequelae. Patients with clotting disorders, elevations of serum creatine kinase and/or aspartate aminotransferase and alanine aminotransferase, and brain CT abnormalities had a poor prognosis compared with patients without. Among these affected patients, the influenza genome (H3) was detected by polymerase chain reaction in nine cerebrospinal fluid samples, influenza virus A (H3N2) was isolated in 18 nasopharyngeal swab samples and a four‐fold or greater rise in serum hemagglutinin inhibition antibody titer against H3N2 was observed in seven patients. Conclusions : It appears urgent to promote vaccination against influenza in young children to prevent these devastating disease conditions.