{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:20:42Z","timestamp":1791836442853,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,11,24]],"date-time":"2015-11-24T00:00:00Z","timestamp":1448323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68) is an emergent viral pathogen. Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks. In recent years, many reports from different countries have described an increasing number of patients with respiratory diseases due to EV-D68 associated with relevant clinical severity. In particular, an unexpectedly high number of children have been hospitalized for severe respiratory disease due to EV-D68, requiring intensive care such as intubation and mechanical ventilation. Moreover, EV-D68 has been associated with acute flaccid paralysis and cranial nerve dysfunction in children, which has caused concerns in the community. As no specific antiviral therapy is available, treatment is mainly supportive. Moreover, because no vaccines are available, conventional infection control measures (i.e., standard, for contacts and droplets) in both community and healthcare settings are recommended. However, further studies are required to fully understand the real importance of this virus. Prompt diagnosis and continued surveillance of EV-D68 infections are essential to managing and preventing new outbreaks. Moreover, if the association between EV-D68 and severe diseases will be confirmed, the development of adequate preventive and therapeutic approaches are a priority.<\/jats:p>","DOI":"10.3390\/v7112925","type":"journal-article","created":{"date-parts":[[2015,11,24]],"date-time":"2015-11-24T12:08:12Z","timestamp":1448366892000},"page":"6043-6050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Enterovirus D68 Infection"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-2837","authenticated-orcid":false,"given":"Susanna","family":"Esposito","sequence":"first","affiliation":[{"name":"Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Bosis","sequence":"additional","affiliation":[{"name":"Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Niesters","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Division of Clinical Virology, University Medical Center, The University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Principi","sequence":"additional","affiliation":[{"name":"Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1513\/AnnalsATS.201412-592FR","article-title":"Enterovirus D68: A focused review and clinical highlights from the 2014 United States outbreak","volume":"12","author":"Oermann","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/oxfordjournals.aje.a120693","article-title":"A probable new human picornavirus associated with respiratory disease","volume":"85","author":"Schieble","year":"1967","journal-title":"Am. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Principi, N., and Esposito, S. (2015). Enterovirus D-68: An emerging cause of infection. Expert Rev. Respir. Med.","DOI":"10.1586\/17476348.2015.1109451"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1128\/JVI.73.3.1941-1948.1999","article-title":"Molecular evolution of the human enteroviruses: Correlation of serotype with VP1 sequence and application to picornavirus classification","volume":"73","author":"Oberste","year":"1999","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/rmv.1820","article-title":"Global reemergence of enterovirus D68 as an important pathogen for acute respiratory infections","volume":"25","author":"Imamura","year":"2015","journal-title":"Rev. Med. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1099\/vir.0.79925-0","article-title":"Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses","volume":"85","author":"Oberste","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1128\/JVI.03070-13","article-title":"Antigenic and receptor binding properties of enterovirus 68","volume":"88","author":"Imamura","year":"2014","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1002\/jmv.23821","article-title":"Phylogenetic characterization of enterovirus 68 strains in patients with respiratory syndromes in Italy","volume":"86","author":"Piralla","year":"2014","journal-title":"J. Med. Virol."},{"key":"ref_9","first-page":"798","article-title":"Severe respiratory illness associated with enterovirus D68-Missouri and Illinois, 2014","volume":"63","author":"Midgley","year":"2014","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2807\/1560-7917.ES2014.19.42.20935","article-title":"Continued seasonal circulation of enterovirus D68 in The Netherlands, 2011\u20132014","volume":"19","author":"Meijer","year":"2014","journal-title":"Eur. Surveill."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1128\/JCM.03362-14","article-title":"Molecular epidemiology of entrovirus D68 from 2013 to 2014 in Philippines","volume":"53","author":"Furuse","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3201\/eid2101.141605","article-title":"Genome sequence of enterovirus D68 from St Louis, Missuri, USA","volume":"21","author":"Wylie","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vongpunsaward, S., Prachayagprecha, S., Chnsaenroj, J., Haagmans, B.L., Smits, S.L., and Poovorawan, Y. (2015). Genome sequence of enterovirus D68 and clinical disease, Thailand. Emerg. Infect. Dis., 21.","DOI":"10.3201\/eid2102.141742"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"916","DOI":"10.3201\/eid2105.150036","article-title":"Enterovirus D68-associated severe pneumonia, China 2014","volume":"21","author":"Zhang","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3201\/eid2105.141900","article-title":"Low-level circulation of enterovirus D68-associated acute respiratory infections, Germany, 2014","volume":"21","author":"Reiche","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"728","DOI":"10.3201\/eid2104.141766","article-title":"Enterovirus D68 infection, Chile, spring 2014","volume":"21","author":"Torres","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_17","first-page":"1","article-title":"The emergence of enterovirus D68 in a Dutch University Medical Centre and the necessity for routinely scrrening for respiratory viruses","volume":"62","author":"Poelmann","year":"2015","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2807\/1560-7917.ES2015.20.17.21105","article-title":"Emergence of enterovirus D68 in Denmark, June 2014 to February 2015","volume":"20","author":"Midgley","year":"2015","journal-title":"Eur. Surveill."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.eimc.2015.01.008","article-title":"First enterovirus D68 (EV-D68) cases detected in hospitalized patients in a tertiary care university hospital in Spain, October 2014","volume":"33","author":"Gimferrer","year":"2015","journal-title":"Enferm. Infect. Microbiol. Clin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jcv.2015.05.017","article-title":"Enterovirus D68-associated community-acquired pneumonia in children living in Milan, Italy","volume":"68","author":"Esposito","year":"2015","journal-title":"J. Clin. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1128\/JCM.02982-14","article-title":"Characterization of enterovirus activity, including that of enterovirus D68, in pediatric patients in Alberta, Canada in 2014","volume":"53","author":"Drews","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Carney, S., Brown, D., Siqueira, M.M., Dias, J.P., and da Silva, E.E. (2015). Enterovirus D68 detected in children with severe acute respiratory illness in Brazil. Emerg. Microbes Infect., 4.","DOI":"10.1038\/emi.2015.66"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Messacar, K., Abzug, M.J., and Dominguez, S.R. (2015). 2014 outbreak of enterovirus D68 in North America. J. Med. Virol.","DOI":"10.1002\/jmv.24410"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S2213-2600(15)00335-5","article-title":"Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation","volume":"3","author":"Midgley","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1473-3099(15)70093-9","article-title":"A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012\u201314): A retrospective cohort study","volume":"15","author":"Greninger","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2807\/1560-7917.ES2015.20.10.21062","article-title":"Two cases of acute severe flaccid myelitis associated with enterovirus D68 infection in children, Norway, autumn 2014","volume":"20","author":"Pfeiffer","year":"2015","journal-title":"Eur. Surveill."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2807\/1560-7917.ES2014.19.44.20952","article-title":"Acute flaccid paralysis following enterovirus D68 associated pneumonia, France, 2014","volume":"19","author":"Lang","year":"2014","journal-title":"Eur. Surveill."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/irv.12300","article-title":"High frequentcy of enterovirus D68 in children hospitalized with respiratory illness in Norway, autumn 2014","volume":"9","author":"Bragstad","year":"2015","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/S0140-6736(14)62457-0","article-title":"A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA","volume":"385","author":"Massacar","year":"2015","journal-title":"Lancet"},{"key":"ref_30","unstructured":"Centers for Disease Control and Prevention (CDC) (2011). Cluster of acute respiratory illness associated with human enterovirus 68-Asia, Europe and United States, 2008\u20132010. MMWR Morb. Mortal. Wkly. Rep., 60, 1301\u20131304."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/jspn.12104","article-title":"Enterovirus D68: What pediatric healthcare professionals need to know","volume":"20","author":"Murray","year":"2015","journal-title":"J. Spec. Pediatr. Nurs."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1016\/j.virol.2011.11.021","article-title":"Emergence and epidemic occurrence of enterovirus 68 respiratory infections in the Netherlands in 2010","volume":"423","author":"Meijer","year":"2012","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcv.2015.07.296","article-title":"ESCV-ECDC EV-D68 Study Group. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014","volume":"71","author":"Poelman","year":"2015","journal-title":"J. Clin. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S2213-2600(15)00335-5","article-title":"Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): A descriptive epidemiological investigation","volume":"3","author":"Midgley","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1099\/vir.0.043935-0","article-title":"Worldwide emergence of multiple clades of enterovirus 68","volume":"93 Pt 9","author":"Tokarz","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1128\/JCM.40.11.4218-4223.2002","article-title":"Human rhinovirus 87 and enterovirus 68 represent a unique serotype with rhinovirus and enterovirus features","volume":"40","author":"Blomqvist","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_37","first-page":"1494","article-title":"Enterovirus D68 in children with acute respiratory tract infection, Osaka, Japan","volume":"17","author":"Kaida","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jcv.2011.06.019","article-title":"Upsurge of human enterovirus 68 infections in patients with severe respiratory tract infections","volume":"52","author":"Borger","year":"2011","journal-title":"J. Clin. Virol."},{"key":"ref_39","first-page":"903","article-title":"Acute flaccid paralysis with anterior myelitis\u2014California, June 2012\u2013June 2014","volume":"63","author":"Ayscue","year":"2014","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"793","DOI":"10.5858\/2010-0174-CR.1","article-title":"A fatal central nervous system enterovirus 68 infection","volume":"135","author":"Kreuter","year":"2011","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3174\/ajnr.A4188","article-title":"MRI findings in children with acute flaccid paralysis and cranial nerve dysfunction occurring during the 2014 enterovirus D68 outbreak","volume":"36","author":"Maloney","year":"2015","journal-title":"Am. J. Neuroradiol."},{"key":"ref_42","unstructured":"World Health Organization Enterovirus Surveillance Guidelines. Guidelines for Enterovirus Surveillance in Support of the Polio Eradication Initiative. Available online: http:\/\/www.euro.who.int\/__data\/assets\/pdf_file\/0020\/272810\/EnterovirusSurveillanceGuidelines.pdf."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jviromet.2013.02.010","article-title":"September through October 2010 multi-centre study in the Netherlands examining laboratory ability to detect enterovirus 68, an emerging respiratory pathogen","volume":"190","author":"Benschop","year":"2013","journal-title":"J. Virol. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"799.e5","DOI":"10.1016\/j.cmi.2015.04.021","article-title":"Molecular epidemiology of severe respiratory disease by human rhinoviruses and enteroviruses at a tertiary paediatric hospital in Barcelona, Spain","volume":"21","author":"Launes","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e0118529","DOI":"10.1371\/journal.pone.0118529","article-title":"Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform","volume":"10","author":"McAllister","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Rhoden, E., Zhang, M., Nix, W.A., and Oberste, M.S. (2015). In vitro efficacy of antiviral compounds against enterovirus D68. Antimicrob. Agents Chemother.","DOI":"10.1128\/AAC.00766-15"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sun, L., Meijer, A., Froeyen, M., Zhang, L., Thibaut, H.J., Baggen, J., George, S., Vernachio, J., van Kuppeveld, F.J., and Leyssen, P. (2015). Antiviral activity of broad-spectrum and enterovirus-specific inhibitors against clinical isolates of enterovirus D68. Antimicrob. Agents Chemother.","DOI":"10.1128\/AAC.01375-15"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/11\/2925\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:52:38Z","timestamp":1760215958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/11\/2925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,24]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2015,11]]}},"alternative-id":["v7112925"],"URL":"https:\/\/doi.org\/10.3390\/v7112925","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,24]]}}}