Surveillance and outbreak report Open Access
Like 0


The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE.


Article metrics loading...

Loading full text...

Full text loading...



  1. Neuzil KM, Dupont WD, Wright PF, Edwards KM. Efficacy of inactivated and cold-adapted vaccines against influenza A infection, 1985 to 1990: the pediatric experience. Pediatr Infect Dis J. 2001;20(8):733-40.  https://doi.org/10.1097/00006454-200108000-00004  PMID: 11734733 
  2. Hoberman A, Greenberg DP, Paradise JL, Rockette HE, Lave JR, Kearney DH, et al. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. JAMA. 2003;290(12):1608-16.  https://doi.org/10.1001/jama.290.12.1608  PMID: 14506120 
  3. Sugaya N, Nerome K, Ishida M, Matsumoto M, Mitamura K, Nirasawa M. Efficacy of inactivated vaccine in preventing antigenically drifted influenza type A and well-matched type B. JAMA. 1994;272(14):1122-6.  https://doi.org/10.1001/jama.1994.03520140052037  PMID: 7933325 
  4. Eisenberg KW, Szilagyi PG, Fairbrother G, Griffin MR, Staat M, Shone LP, et al. New Vaccine Surveillance Network. Vaccine effectiveness against laboratory-confirmed influenza in children 6 to 59 months of age during the 2003-2004 and 2004-2005 influenza seasons. Pediatrics. 2008;122(5):911-9.  https://doi.org/10.1542/peds.2007-3304  PMID: 18977968 
  5. Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL, et al. Interim estimates of 2014/15 vaccine effectiveness against influenza A(H3N2) from Canada’s Sentinel Physician Surveillance Network, January 2015. Euro Surveill. 2015;20(4):21022.  https://doi.org/10.2807/1560-7917.ES2015.20.4.21022  PMID: 25655053 
  6. Pebody RG, Warburton F, Ellis J, Andrews N, Thompson C, von Wissmann B, et al. Low effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 mid-season results. Euro Surveill. 2015;20(5):21025.  https://doi.org/10.2807/1560-7917.ES2015.20.5.21025  PMID: 25677050 
  7. Flannery B, Clippard J, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, et al. Centers for Disease Control and Prevention. Early estimates of seasonal influenza vaccine effectiveness - United States, January 2015. MMWR Morb Mortal Wkly Rep. 2015;64(1):10-5. PMID: 25590680 
  8. Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR, Karron RA. Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep. 2015;64(30):818-25.  https://doi.org/10.15585/mmwr.mm6430a3  PMID: 26247435 
  9. Nohynek H, Baum U, Syrjänen R, Ikonen N, Sundman J, Jokinen J. Effectiveness of the live attenuated and the inactivated influenza vaccine in two-year-olds - a nationwide cohort study Finland, influenza season 2015/16. Euro Surveill. 2016;21(38):30346.  https://doi.org/10.2807/1560-7917.ES.2016.21.38.30346  PMID: 27684447 
  10. Pebody R, Warburton F, Ellis J, Andrews N, Potts A, Cottrell S, et al. Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results. Euro Surveill. 2016;21(38):30348.  https://doi.org/10.2807/1560-7917.ES.2016.21.38.30348  PMID: 27684603 
  11. Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, et al. CAIV-T Comparative Efficacy Study Group. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007;356(7):685-96.  https://doi.org/10.1056/NEJMoa065368  PMID: 17301299 
  12. Grohskopf LA, Sokolow LZ, Broder KR, Olsen SJ, Karron RA, Jernigan DB, et al. Prevention and Control of Seasonal Influenza with Vaccines. MMWR Recomm Rep. 2016;65(5):1-54.  https://doi.org/10.15585/mmwr.rr6505a1  PMID: 27560619 
  13. Reichert TA, Sugaya N, Fedson DS, Glezen WP, Simonsen L, Tashiro M. The Japanese experience with vaccinating schoolchildren against influenza. N Engl J Med. 2001;344(12):889-96.  https://doi.org/10.1056/NEJM200103223441204  PMID: 11259722 
  14. Shinjoh M, Sugaya N, Yamaguchi Y, Tomidokoro Y, Sekiguchi S, Mitamura K, et al. Keio Pediatric Influenza Research Group. Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results. PLoS One. 2015;10(8):e0136539.  https://doi.org/10.1371/journal.pone.0136539  PMID: 26317334 
  15. National Institute of Infectious Diseases. 2014/15 influenza season, Japan. Infectious Agents Surveillance Report. 2015;36:199-201. Japanese. Available from http://www.nih.go.jp/niid/ja/flu-m/flutoppage/592-idsc/iasr-topic/6076-tpc429-j.html
  16. World Health Organization (WHO). FluNet. Geneva: WHO. [Accessed 10 Jan 2016]. Available from: http://www.who.int/influenza/gisrs_laboratory/flunet/en/
  17. Hatakeyama S, Sakai-Tagawa Y, Kiso M, Goto H, Kawakami C, Mitamura K, et al. Enhanced expression of an alpha2,6-linked sialic acid on MDCK cells improves isolation of human influenza viruses and evaluation of their sensitivity to a neuraminidase inhibitor. J Clin Microbiol. 2005;43(8):4139-46.  https://doi.org/10.1128/JCM.43.8.4139-4146.2005  PMID: 16081961 
  18. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30(12):2725-9.  https://doi.org/10.1093/molbev/mst197  PMID: 24132122 
  19. Pharmaceuticals and Medical Devices Agency, Japan. Taigaishindanyou tenpubunsyo jouhou. [Package insert information of medical diagnostic devices]. Japanese. [Accessed 9 Jan 2016]. Available from: http://www.info.pmda.go.jp/tsearch/html/menu_tenpu_base.html
  20. Blyth CC, Jacoby P, Effler PV, Kelly H, Smith DW, Robins C, et al. WAIVE Study Team. Effectiveness of trivalent flu vaccine in healthy young children. Pediatrics. 2014;133(5):e1218-25.  https://doi.org/10.1542/peds.2013-3707  PMID: 24753525 
  21. Valenciano M, Kissling EI-MOVE Case-Control Study Team. Early estimates of seasonal influenza vaccine effectiveness in Europe: results from the I-MOVE multicentre case-control study, 2012/13. Euro Surveill. 2013;18(7):3. PMID: 23449183 
  22. Sullivan SG, Feng S, Cowling BJ. Potential of the test-negative design for measuring influenza vaccine effectiveness: a systematic review. Expert Rev Vaccines. 2014;13(12):1571-91.  https://doi.org/10.1586/14760584.2014.966695  PMID: 25348015 
  23. Sugaya N. Widespread use of neuraminidase inhibitors in Japan. J Infect Chemother. 2011;17(5):595-601.  https://doi.org/10.1007/s10156-011-0288-0  PMID: 21850418 
  24. Skowronski DM, Janjua NZ, De Serres G, Sabaiduc S, Eshaghi A, Dickinson JA, et al. Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses. PLoS One. 2014;9(3):e92153.  https://doi.org/10.1371/journal.pone.0092153  PMID: 24667168 
  25. Pebody R, Warburton F, Andrews N, Ellis J, von Wissmann B, Robertson C, et al. Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 end of season results. Euro Surveill. 2015;20(36):30013.  https://doi.org/10.2807/1560-7917.ES.2015.20.36.30013  PMID: 26535911 
  26. National Institute of Infectious Diseases. 2013/14 influenza season, Japan. Infectious Agents Surveillance Report. 2014;35:251-3. Available from: http://www.nih.go.jp/niid/en/iasr-e/865-iasr/5182-tpc417.html
  27. McLean HQ, Thompson MG, Sundaram ME, Kieke BA, Gaglani M, Murthy K, et al. Influenza vaccine effectiveness in the United States during 2012-2013: variable protection by age and virus type. J Infect Dis. 2015;211(10):1529-40.  https://doi.org/10.1093/infdis/jiu647  PMID: 25406334 
  28. Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2012;8(8):CD004879. PMID: 22895945 
  29. Cowling BJ, Chan KH, Feng S, Chan EL, Lo JY, Peiris JS, et al. The effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong, 2009-2013. Vaccine. 2014;32(41):5278-84.  https://doi.org/10.1016/j.vaccine.2014.07.084  PMID: 25092636 
  30. Ferdinands JM, Olsho LE, Agan AA, Bhat N, Sullivan RM, Hall M, et al. Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012. J Infect Dis. 2014;210(5):674-83.  https://doi.org/10.1093/infdis/jiu185  PMID: 24676207 
  31. Ritzwoller DP, Bridges CB, Shetterly S, Yamasaki K, Kolczak M, France EK. Effectiveness of the 2003-2004 influenza vaccine among children 6 months to 8 years of age, with 1 vs 2 doses. Pediatrics. 2005;116(1):153-9.  https://doi.org/10.1542/peds.2005-0049  PMID: 15995046 
  32. Kawai N, Ikematsu H, Iwaki N, Satoh I, Kawashima T, Tsuchimoto T, et al. A prospective, Internet-based study of the effectiveness and safety of influenza vaccination in the 2001-2002 influenza season. Vaccine. 2003;21(31):4507-13.  https://doi.org/10.1016/S0264-410X(03)00508-5  PMID: 14575760 
  33. Allison MA, Daley MF, Crane LA, Barrow J, Beaty BL, Allred N, et al. Influenza vaccine effectiveness in healthy 6- to 21-month-old children during the 2003-2004 season. J Pediatr. 2006;149(6):755-62.  https://doi.org/10.1016/j.jpeds.2006.06.036  PMID: 17137887 
  34. Orenstein EW, De Serres G, Haber MJ, Shay DK, Bridges CB, Gargiullo P, et al. Methodologic issues regarding the use of three observational study designs to assess influenza vaccine effectiveness. Int J Epidemiol. 2007;36(3):623-31.  https://doi.org/10.1093/ije/dym021  PMID: 17403908 
  35. Jackson ML, Rothman KJ. Effects of imperfect test sensitivity and specificity on observational studies of influenza vaccine effectiveness. Vaccine. 2015;33(11):1313-6.  https://doi.org/10.1016/j.vaccine.2015.01.069  PMID: 25659280 
  36. Suzuki M, Minh N, Yoshimine H, Inoue K, Yoshida LM, Morimoto K, et al. Vaccine effectiveness against medically attended laboratory-confirmed influenza in Japan, 2011-2012 Season. PLoS One. 2014;9(2):e88813.  https://doi.org/10.1371/journal.pone.0088813  PMID: 24551167 
  37. Mitamura K, Yamazaki M, Ichikawa M, Kimura K, Kawakami C, Shimizu H, et al. [Evaluation of an immunochromatography test using enzyme immunoassay for rapid detection of influenza A and B viruses]. Kansenshogaku Zasshi. 2004;78(7):597-603.Japanese.  https://doi.org/10.11150/kansenshogakuzasshi1970.78.597  PMID: 15359892 
  38. Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004;364(9436):759-65.  https://doi.org/10.1016/S0140-6736(04)16934-1  PMID: 15337401 
  39. Sugaya N, Sakai-Tagawa Y, Bamba M, Yasuhara R, Yamazaki M, Kawakami C, et al. Comparison between virus shedding and fever duration after treating children with pandemic A H1N1/09 and children with A H3N2 with a neuraminidase inhibitor. Antivir Ther. 2015;20(1):49-55.  https://doi.org/10.3851/IMP2798  PMID: 24832015 

Data & Media loading...

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error