National surveillance of influenza-associated encephalopathy in Japan over six years, before and during the 2009-2010 influenza pandemic.

Influenza-associated encephalopathy (IAE) is a serious complication of influenza and is reported most frequently in Japan. This paper presents an assessment of the epidemiological characteristics of influenza A (H1N1) 2009-associated encephalopathy in comparison to seasonal IAE, based on Japanese national surveillance data of influenza-like illness (ILI) and IAE during flu seasons from 2004-2005 through 2009-2010. In each season before the pandemic, 34-55 IAE cases (mean 47.8; 95% confidence interval: 36.1-59.4) were reported, and these cases increased drastically to 331 during the 2009 pandemic (6.9-fold the previous seasons). Of the 331 IAE cases, 322 cases were reported as influenza A (H1N1) 2009-associated encephalopathy. The peaks of IAE were consistent with the peaks of the influenza epidemics and pandemics. A total of 570 cases of IAE (seasonal A, 170; seasonal B, 50; influenza A (H1N1) 2009, 322; unknown, 28) were reported over six seasons. The case fatality rate (CFR) ranged from 4.8 to 18.2% before the pandemic seasons and 3.6% in the 2009 pandemic season. The CFR of pandemic-IAE was 3.7%, which is lower than that of influenza A-/B-associated encephalopathy (12.9%, p<0.001; 14.0%, p = 0.002; respectively). The median age of IAE was 7 years during the pandemic, which is higher than that of influenza A-/B-associated encephalopathy (4, p<0.001; 4.5, p = 0.006; respectively). However, the number of pandemic-IAE cases per estimated ILI outpatients peaked in the 0-4-year age group and data both before and during the pandemic season showed a U-shape pattern. This suggests that the high incidence of influenza infection in the 0-4 year age group may lead to a high incidence of IAE in the same age group in a future influenza season. Further studies should include epidemiologic case definitions and clinical details of IAE to gain a more accurate understanding of the epidemiologic status of IAE.