Vaccine 27 (2009) 7031–7035 Contents lists available at ScienceDirect Vaccine j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / v a c c i n e Inactivated inﬂuenza vaccine eﬀectiveness against inﬂuenza-like illness among young children in Japan—With special reference to minimizing outcome misclassiﬁcation Hirotaka Ochiai a,∗,1 , Megumi Fujieda a,1 , Satoko Ohfuji a , Wakaba Fukushima a , Kyoko Kondo a , Akiko Maeda a , Takashi Nakano b , Hitoshi Kamiya b , Yoshio Hirota a , for the Inﬂuenza Vaccine Epidemiology Study Group 2 a Department of Public Health, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan b National Mie Hospital, 357, Ozato-Kubota, Tsu, Mie 514-0125, Japan a r t i c l e i n f o Article history: Received 10 July 2009 Received in revised form 7 September 2009 Accepted 16 September 2009 Available online 26 September 2009 Keywords: Inﬂuenza Vaccine eﬀectiveness Misclassiﬁcation a b s t r a c t The aim of the present study was to investigate the inﬂuenza vaccine eﬀectiveness among young children in Japan. Study subjects were recruited from 43 pediatric clinics. Inﬂuenza-like illness (ILI) was deﬁned as an acute febrile illness with respiratory symptoms; ILI with a fever of ≥39 ◦ C was considered to be severe ILI (SILI). The adjusted OR of vaccination signiﬁcantly decreased to 0.75 for SILI. Inﬂuenza vaccination for young children had a protective eﬀect on the occurrences of SILI. This study also indicated that three key tools (case surveillance with equal scrutiny, conﬁning observation to the peak epidemic period, and adoption of strict criteria for ILI) could minimize outcome misclassiﬁcation and thus provide adequate methodology for monitoring vaccine eﬀectiveness without laboratory conﬁrmation. © 2009 Elsevier Ltd. All rights reserved. 1. Introduction Although inﬂuenza viruses can cause disease among persons in any age group [1–3], rates of inﬂuenza virus infection are highest among children [4].It has been reported that children aged 6–23 months are at substantially increased risk for inﬂuenza-related hos- pitalizations, and those aged 24–59 months are at increased risk for inﬂuenza-related clinic and emergency department visits [5]. A number of studies have investigated the eﬀectiveness or eﬃcacy of the inﬂuenza vaccine among young children [6–14]. However, these results are not consistent.Some studies failed to detect vaccine eﬀectiveness even though applying case surveillance with laboratory conﬁrmation, while other studies reported vaccine eﬀectiveness of 24–69%. Furthermore, studies conducted in Japan to date have been too limited. In Japan, the vaccine dose for young children (<1 year old, 0.1 ml; 1–5 years, 0.2 ml; 6–12 years, 0.3 ml; 13 years or over, 0.5 ml of trivalent vaccine including 30 ␮g haemagglutinin/ml of each ∗ Corresponding author at: Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Tel.: +81 3 3784 8134; fax: +81 3 3784 7733. E-mail address: h-ochiai@med.showa-u.ac.jp (H. Ochiai). 1 Both authors contributed equally to this work. 2 Other members of the Study Group are listed in Appendix A. strain) is smaller than that in the USA or Europe and it is disputable whether this dose leads to suﬃcient seroresponse. Therefore, it is important to evaluate the vaccine eﬀectiveness of the current dose among young children in Japan. Accordingly, we precisely analyzed data collected among Japanese children under 6 years of age during the 2000–2001 sea- son to assess inﬂuenza vaccine eﬀectiveness.Then, the eﬀect of outcome misclassiﬁcation was thoroughly considered by using sev- eral outcomes and conﬁning observation to the peak epidemic period. 2. Materials and methods 2.1. Study subjects Subjects comprised children under 6 years of age recruited from 43 pediatric clinics, where this study group members belonged, in seven diﬀerent areas of Japan: (from north to south) Hokkaido (2 clinics), Iwate (12 clinics), Tokyo (6 clinics), Mie (7 clinics), Osaka (2 clinics), Shikoku (10 clinics), and Fukuoka (4 clinics). Children who received an inﬂuenza vaccine at each clinic upon parental request (vaccinee) were entered into the vaccinated group. Then, one or two children who visited the pediatri- cian subsequent to each vaccinee and whose parents did not request to have their children vaccinated (nonvaccinee) were enrolled into the unvaccinated group. A total of 2353 children 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.09.067