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Respiratory specimens collected from outpatients with influenza-like illness in three Canadian provinces (British Columbia (BC), Alberta and Quebec) participating in a community-based sentinel surveillance network were prospectively screened for enterovirus-D68 (EV-D68) from 1 August to 31 December 2014 and compared to specimens collected from 1 October 2013 to 31 July 2014. Eighteen (1%) of 1,894 specimens were EV-D68-positive: 1/348 (0.3%) collected from October to December 2013 and 11/460 (2.4%) from October to December 2014, an eight-fold increase in detection rates (p=0.01), consistent with epidemic circulation in autumn 2014. The remaining EV-D68 detections were in September 2014 (6/37). Enhanced passive surveillance was also conducted on all inpatient and outpatient EV-D68 cases (n=211) detected at the BC provincial reference laboratory from 28 August to 31 December 2014. Incidence of hospitalisations was 3/100,000 overall and 21, 17, 4 and 1/100,000 among those <5, 5–9, 10–19 and ≥20-years-old with male-to-female ratios >1 among paediatric but not adult cases. Three cases in BC with comorbidity or co-infection died and five exhibited neurological features persisting >9 months. Active surveillance in outpatient and inpatient settings is needed from more areas and additional seasons to better understand EV-D68 epidemiology and potential at-risk groups for severe or unusual manifestations.


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  1. Oberste MS, Maher K, Schnurr D, Flemister MR, Lovchik JC, Peters H, et al. Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses. J Gen Virol. 2004;85(Pt 9):2577-84. https://doi.org/10.1099/vir.0.79925-0  PMID: 15302951 
  2. Imamura T, Oshitani H. Global reemergence of enterovirus D68 as an important pathogen for acute respiratory infections. Rev Med Virol. 2015;25(2):102-14. https://doi.org/10.1002/rmv.1820  PMID: 25471236 
  3. Khetsuriani N, Lamonte-Fowlkes A, Oberst S, Pallansch MACenters for Disease Control and Prevention. Enterovirus surveillance--United States, 1970-2005. MMWR Surveill Summ. 2006;55(8):1-20. PMID: 16971890 
  4. Schieble JH, Fox VL, Lennette EH. A probable new human picornavirus associated with respiratory diseases. Am J Epidemiol. 1967;85(2):297-310. PMID: 4960233 
  5. Centers for Disease Control and Prevention (CDC). Clusters of acute respiratory illness associated with human enterovirus 68--Asia, Europe, and United States, 2008-2010. MMWR Morb Mortal Wkly Rep. 2011;60(38):1301-4. PMID: 21956405 
  6. Hasegawa S, Hirano R, Okamoto-Nakagawa R, Ichiyama T, Shirabe K. Enterovirus 68 infection in children with asthma attacks: virus-induced asthma in Japanese children. Allergy. 2011;66(12):1618-20. https://doi.org/10.1111/j.1398-9995.2011.02725.x  PMID: 21958204 
  7. Lauinger IL, Bible JM, Halligan EP, Aarons EJ, MacMahon E, Tong CY. Lineages, sub-lineages and variants of enterovirus 68 in recent outbreaks. PLoS One. 2012;7(4):e36005. https://doi.org/10.1371/journal.pone.0036005  PMID: 22536453 
  8. Meijer A, van der Sanden S, Snijders BE, Jaramillo-Gutierrez G, Bont L, van der Ent CK, et al. Emergence and epidemic occurrence of enterovirus 68 respiratory infections in The Netherlands in 2010. Virology. 2012;423(1):49-57. https://doi.org/10.1016/j.virol.2011.11.021  PMID: 22177700 
  9. Meijer A, Benschop KS, Donker GA, van der Avoort HG. Continued seasonal circulation of enterovirus D68 in the Netherlands, 2011-2014. Euro Surveill. 2014;19(42):20935. https://doi.org/10.2807/1560-7917.ES2014.19.42.20935  PMID: 25358039 
  10. Rahamat-Langendoen J, Riezebos-Brilman A, Borger R, van der Heide R, Brandenburg A, Schölvinck E, et al. Upsurge of human enterovirus 68 infections in patients with severe respiratory tract infections. J Clin Virol. 2011;52(2):103-6. https://doi.org/10.1016/j.jcv.2011.06.019  PMID: 21802981 
  11. Renois F, Bouin A, Andreoletti L. Enterovirus 68 in pediatric patients hospitalized for acute airway diseases. J Clin Microbiol. 2013;51(2):640-3. https://doi.org/10.1128/JCM.02640-12  PMID: 23224095 
  12. Tokarz R, Firth C, Madhi SA, Howie SR, Wu W, Sall AA, et al. Worldwide emergence of multiple clades of enterovirus 68. J Gen Virol. 2012;93(Pt 9):1952-8. https://doi.org/10.1099/vir.0.043935-0  PMID: 22694903 
  13. Midgley CM, Jackson MA, Selvarangan R, Turabelidze G, Obringer E, Johnson D, et al. Severe respiratory illness associated with enterovirus D68 - Missouri and Illinois, 2014. MMWR Morb Mortal Wkly Rep. 2014;63(36):798-9. PMID: 25211545 
  14. Centers for Disease Control and Prevention (CDC). Enterovirus D68 in the United States, 2014. Atlanta: CDC. [Accessed 3 August 2015]. Available from: http://www.cdc.gov/non-polio-enterovirus/about/ev-d68.html
  15. Bragstad K, Jakobsen K, Rojahn AE, Skram MK, Vainio K, Holberg-Petersen M, et al. High frequency of enterovirus D68 in children hospitalised with respiratory illness in Norway, autumn 2014. Influenza Other Respir Viruses. 2015;9(2):59-63. https://doi.org/10.1111/irv.12300  PMID: 25534826 
  16. Poelman R, Schuffenecker I, Van Leer-Buter C, Josset L, Niesters HG, Lina BESCV-ECDC EV-D68 study group. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014. J Clin Virol. 2015;71:1-9. https://doi.org/10.1016/j.jcv.2015.07.296  PMID: 26364237 
  17. Midgley SE, Christiansen CB, Poulsen MW, Hansen CH, Fischer TK. Emergence of enterovirus D68 in Denmark, June 2014 to February 2015. Euro Surveill. 2015;20(17):21105. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21105 https://doi.org/10.2807/1560-7917.ES2015.20.17.21105  PMID: 25955773 
  18. Reiche J, Böttcher S, Diedrich S, Buchholz U, Buda S, Haas W, et al. Low-level circulation of enterovirus D68-associated acute respiratory infections, Germany, 2014. Emerg Infect Dis. 2015;21(5):837-41. https://doi.org/10.3201/eid2105.141900  PMID: 25898320 
  19. Leshem EDivision of Viral Diseases, National Centers for Immunization and Respiratory Diseases, CDC; Division of Vector-Borne Diseases, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC; Children’s Hospital Colorado; Council of State and Territorial Epidemiologists. Notes from the field: acute flaccid myelitis among persons aged ≤21 years - United States, August 1-November 13, 2014. MMWR Morb Mortal Wkly Rep. 2015;63(53):1243-4. PMID: 25577990 
  20. Greninger AL, Naccache SN, Messacar K, Clayton A, Yu G, Somasekar S, et al. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. Lancet Infect Dis. 2015;15(6):671-82. https://doi.org/10.1016/S1473-3099(15)70093-9  PMID: 25837569 
  21. Ayscue P, Van Haren K, Sheriff H, Waubant E, Waldron P, Yagi S, et al. Centers for Disease Control and Prevention (CDC). Acute flaccid paralysis with anterior myelitis - California, June 2012-June 2014. MMWR Morb Mortal Wkly Rep. 2014;63(40):903-6. Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6340a6.htm?s_cid=mm6340a6_w PMID: 25299608 
  22. Pastula DM, Aliabadi N, Haynes AK, Messacar K, Schreiner T, Maloney J, et al. Centers for Disease Control and Prevention (CDC). Acute neurologic illness of unknown etiology in children - Colorado, August-September 2014. MMWR Morb Mortal Wkly Rep. 2014;63(40):901-2. PMID: 25299607 
  23. Lang M, Mirand A, Savy N, Henquell C, Maridet S, Perignon R, et al. Acute flaccid paralysis following enterovirus D68 associated pneumonia, France, 2014. Euro Surveill. 2014;19(44):20952. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20952 https://doi.org/10.2807/1560-7917.ES2014.19.44.20952  PMID: 25394254 
  24. Pfeiffer HC, Bragstad K, Skram MK, Dahl H, Knudsen PK, Chawla MS, et al. Two cases of acute severe flaccid myelitis associated with enterovirus D68 infection in children, Norway, autumn 2014. Euro Surveill. 2015;20(10):21062. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21062 https://doi.org/10.2807/1560-7917.ES2015.20.10.21062  PMID: 25788251 
  25. Statistics Canada. Population and dwelling counts, for Canada, provinces and territories, 2011 and 2006 censuses. Ottawa: Statistics Canada; 2015. Available from: http://www12.statcan.gc.ca/census-recensement/2011/dp-pd/hlt-fst/pd-pl/Table-Tableau.cfm?LANG=Eng&T=101&S=50&O=A
  26. Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Winter AL, Dickinson JA, et al. Integrated sentinel surveillance linking genetic, antigenic, and epidemiologic monitoring of influenza vaccine-virus relatedness and effectiveness during the 2013-2014 influenza season. J Infect Dis. 2015;212(5):726-39. https://doi.org/10.1093/infdis/jiv177  PMID: 25784728 
  27. Pabbaraju K, Wong S, Wong AA, Tellier R. Detection of enteroviruses and parechoviruses by a multiplex real-time RT-PCR assay. Mol Cell Probes. 2015;29(2):81-5. https://doi.org/10.1016/j.mcp.2015.02.001  PMID: 25681753 
  28. Drews SJ, Simmonds K, Usman HR, Yee K, Fathima S, Tipples G, et al. Characterization of enterovirus activity, including that of enterovirus D68, in pediatric patients in Alberta, Canada, in 2014. J Clin Microbiol. 2015;53(3):1042-5. https://doi.org/10.1128/JCM.02982-14  PMID: 25588657 
  29. Coiras MT, Aguilar JC, García ML, Casas I, Pérez-Breña P. Simultaneous detection of fourteen respiratory viruses in clinical specimens by two multiplex reverse transcription nested-PCR assays. J Med Virol. 2004;72(3):484-95. https://doi.org/10.1002/jmv.20008  PMID: 14748074 
  30. Pabbaraju K, Wong S, Chan ENY, Tellier R. Genetic characterization of a Coxsackie A9 virus associated with aseptic meningitis in Alberta, Canada in 2010. Virol J. 2013;10(1):93. Available from: http://www.virologyj.com/content/10/1/93 https://doi.org/10.1186/1743-422X-10-93  PMID: 23521862 
  31. Gregory JB, Litaker RW, Noble RT. Rapid one-step quantitative reverse transcriptase PCR assay with competitive internal positive control for detection of enteroviruses in environmental samples. Appl Environ Microbiol. 2006;72(6):3960-7. https://doi.org/10.1128/AEM.02291-05  PMID: 16751503 
  32. Nix WA, Oberste MS, Pallansch MA. Sensitive, seminested PCR amplification of VP1 sequences for direct identification of all enterovirus serotypes from original clinical specimens. J Clin Microbiol. 2006;44(8):2698-704. https://doi.org/10.1128/JCM.00542-06  PMID: 16891480 
  33. Hatchette TF, Drews SJ, Grudeski E, Booth T, Martineau C, Dust K, et al. Detection of enterovirus D68 in Canadian laboratories. J Clin Microbiol. 2015;53(5):1748-51. https://doi.org/10.1128/JCM.03686-14  PMID: 25740765 
  34. Imamura T, Okamoto M, Nakakita S, Suzuki A, Saito M, Tamaki R, et al. Antigenic and receptor binding properties of enterovirus 68. J Virol. 2014;88(5):2374-84. https://doi.org/10.1128/JVI.03070-13  PMID: 24371050 
  35. 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 
  36. BC Stats. Population estimates for 2014. Victoria: BC Stats. [Accessed 3 August 2015]. Available from: http://www.bcstats.gov.bc.ca/StatisticsBySubject/Demography/PopulationEstimates.aspx
  37. Sherwood MD, Gantt S, Connolly M, Dobson S. Acute flaccid paralysis in a child infected with enterovirus D68: a case report. B C Med J. 2014;56:495-8. Accessed 3 August 2015. Available from: http://www.bcmj.org/sites/default/files/BCMJ_56_Vol10_flaccid_paralysis.pdf
  38. Jiang L, Lee VJ, Lim WY, Chen MI, Chen Y, Tan L, et al. Performance of case definitions for influenza surveillance. Euro Surveill. 2015;20(22):21145. https://doi.org/10.2807/1560-7917.ES2015.20.22.21145  PMID: 26062645 
  39. Centers for Disease Control and Prevention (CDC). Manual for the surveillance of vaccine-preventable diseases. Enhancing Surveillance, Chapter 19. 5th ed., 2011. Atlanta: CDC. [Accessed 24 September 2015]. Available from: http://www.cdc.gov/vaccines/pubs/surv-manual/index.html
  40. Chen Y, Johansen H, Thillaiampalam S, Sambell C. Asthma. Statistics Canada Catalogue no. 82-003. Health Rep. 2005;16:43-6.
  41. Kynyk JA, Mastronarde JG, McCallister JW. Asthma, the sex difference. Curr Opin Pulm Med. 2011;17(1):6-11. https://doi.org/10.1097/MCP.0b013e3283410038  PMID: 21045697 
  42. Busse WW, Lemanske RF Jr, Gern JE. Role of viral respiratory infections in asthma and asthma exacerbations. Lancet. 2010;376(9743):826-34. https://doi.org/10.1016/S0140-6736(10)61380-3  PMID: 20816549 
  43. Jackson DJ, Johnston SL. The role of viruses in acute exacerbations of asthma. J Allergy Clin Immunol. 2010;125(6):1178-87, quiz 1188-9. https://doi.org/10.1016/j.jaci.2010.04.021  PMID: 20513517 
  44. Kloepfer KM, Lee WM, Pappas TE, Kang TJ, Vrtis RF, Evans MD, et al. Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations. J Allergy Clin Immunol. 2014;133(5):1301-7, 1307.e1-3. PMID: 24698319 
  45. Richman DD, Whitley RJ, Hayden FG. Clinical Virology. New York: Churchill Livingston, 1997.
  46. Smura TP, Junttila N, Blomqvist S, Norder H, Kaijalainen S, Paananen A, et al. Enterovirus 94, a proposed new serotype in human enterovirus species D. J Gen Virol. 2007;88(Pt 3):849-58. https://doi.org/10.1099/vir.0.82510-0  PMID: 17325357 
  47. Kreuter JD, Barnes A, McCarthy JE, Schwartzman JD, Oberste MS, Rhodes CH, et al. A fatal central nervous system enterovirus 68 infection. Arch Pathol Lab Med. 2011;135(6):793-6. PMID: 21631275 
  48. Centers for Disease Control and Prevention (CDC). Epidemiology and Prevention of Vaccine-Preventable Diseases. Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Washington D.C. Public Health Foundation, 2015. p. 299. Atlanta: CDC. [Accessed 3 August 2015]. Available from: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/polio.pdf
  49. Koskiniemi M. CNS manifestations associated with Mycoplasma pneumoniae infections: summary of cases at the University of Helsinki and review. Clin Infect Dis. 1993;17(Suppl 1):S52-7. https://doi.org/10.1093/clinids/17.Supplement_1.S52  PMID: 8399938 
  50. Hely MA, Williamson PM, Terenty TR. Neurological complications of Mycoplasma pneumoniae infection. Clin Exp Neurol. 1984;20:153-60. PMID: 6439446 
  51. Norder H, Magnius L. Can sequence data predict enterovirus D68 infection outcome? Lancet Infect Dis. 2015;15(6):620-1. https://doi.org/10.1016/S1473-3099(15)70107-6  PMID: 25837570 

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