History

The spectrum of clinical presentation of enterovirus D68 (EV-D68) infection can range from mild respiratory infection to severe disease, warranting intensive care unit admission, bi-level positive airway ventilation, or even intubation. Some cases have resulted in death.^{[3, 25]}

Potential manifestations of EV-D68 infection are as follows:

Acute onset
Cough
Fever (although a considerable percentage of cases without fever reported in the latest outbreaks)
Rhinorrhea
Sore throat
Fatigue
Headache
Myalgia
Dyspnea
Diarrhea
Bronchiolitis^[2]

Physical

Physical examination may reveal the following:

Wheezing
Rhinorrhea
Fever
Hypoxemia^[2]

Cases involving acute neurological illness may have the following characteristics^{[29, 36]}:

Preceding febrile illness with upper respiratory tract symptoms or GI prodrome occurring 3-16 days before onset of neurological illness
Limb paresis or flaccid paralysis
Ptosis, facial droop, dysarthria, dysphagia, diplopia
Absence of sensory deficits
Meningismus in cases of meningoencephalitis (one case described in 2008 in New Hampshire^[26])

Differential Diagnoses

Brown DM, Hixon AM, Oldfield LM, Zhang Y, Novotny M, Wang W, et al. Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells. mBio. 2018 Oct 16. 9 (5):[QxMD MEDLINE Link]. [Full Text].
Meijer A, Benschop KS, Donker GA, van der Avoort HG. Continued seasonal circulation of enterovirus D68 in the Netherlands, 2011-2014. Euro Surveill. 2014 Oct 23. 19(42):[QxMD MEDLINE Link].
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 Sep 12. 63(36):798-9. [QxMD MEDLINE Link].
Brown BA, Nix WA, Sheth M, Frace M, Oberste MS. Seven Strains of Enterovirus D68 Detected in the United States during the 2014 Severe Respiratory Disease Outbreak. Genome Announc. 2014 Nov 20. 2(6):[QxMD MEDLINE Link]. [Full Text].
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 Feb 5. 423(1):49-57. [QxMD MEDLINE Link].
Shaw J, Welch TR, Milstone AM. The role of syndromic surveillance in directing the public health response to the enterovirus D68 epidemic. JAMA Pediatr. 2014 Nov. 168(11):981-2. [QxMD MEDLINE Link].
Cabrerizo M, García-Iñiguez JP, Munell F, et al. First Cases of Severe Flaccid Paralysis Associated With Enterovirus D68 Infection in Spain, 2015-2016. Pediatric Infectious Disease. 2017 Dec 01. [QxMD MEDLINE Link]. [Full Text].
Antona D, Kossorotoff M, Schuffenecker I, et al. Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016. EuroSurveillance. 2016 Nov 17. [QxMD MEDLINE Link]. [Full Text].
Dyrdak R, Grabbe M, Hammas B, et al. Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016. EuroSurveillance. 2016 Nov 17. [QxMD MEDLINE Link]. [Full Text].
Ruggieri V, Paz MI, Peretti MG, et al. Enterovirus D68 infection in a cluster of children with acute flaccid myelitis, Buenos Aires, Argentina, 2016. European Journal of Paediatric Neurology. 2017 Nov 01. [QxMD MEDLINE Link].
Xiang Z, Li L, Ren L, et al. Seroepidemiology of enterovirus D68 infection in China. Emerging Microbes & Infections. 2017 May 10. [QxMD MEDLINE Link]. [Full Text].
Chong PF, Kira R, Mori H, et al. Clinical Features of Acute Flaccid Myelitis Temporally Associated with an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 2015. Clinical Infectious Diseases. 2017 Oct 06. [QxMD MEDLINE Link]. [Full Text].
Kaida A, Iritani N, Yamamoto SP, et al. Distinct genetic clades of enterovirus D68 detected in 2010, 2013, and 2015 in Osaka City, Japan. Public Library of Science. 2017 Sep 13. [QxMD MEDLINE Link]. [Full Text].
Baggen J, Thibaut HJ, Staring J, Jae LT, Liu Y, Guo H, et al. Enterovirus D68 receptor requirements unveiled by haploid genetics. Proc Natl Acad Sci U S A. 2016 Feb 2. 113 (5):1399-404. [QxMD MEDLINE Link]. [Full Text].
Liu Y, Sheng J, Baggen J, Meng G, Xiao C, Thibaut HJ, et al. Sialic acid-dependent cell entry of human enterovirus D68. Nat Commun. 2015 Nov 13. 6:8865. [QxMD MEDLINE Link]. [Full Text].
Wang ZY, Zhong T, Wang Y, et al. Human Enterovirus 68 Interferes with the Host Cell Cycle to Facilitate Viral Production. Frontiers in Cellular and Infection Microbiology. 2017 Feb 8. [QxMD MEDLINE Link]. [Full Text].
Schwartz RA. Enteroviruses. Medscape. Available at http://emedicine.medscape.com/article/217146-overview. Accessed: December 20, 2014.
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Wei W, Guo H, Chang J, et al. ICAM-5/Telencephalin Is a Functional Entry Receptor for Enterovirus D68. Cell Host & Microbe. 2016 Oct 27. [QxMD MEDLINE Link]. [Full Text].
Schieble JH, Fox VL, Lennette EH. A probable new human picornavirus associated with respiratory diseases. Am J Epidemiol. 1967 Mar. 85(2):297-310. [QxMD MEDLINE Link].
Zheng HW, Sun M, Guo L, et al. Nasal Infection of Enterovirus D68 Leading to Lower Respiratory Tract Pathogenesis in Ferrets (Mustela putorius furo). Viruses. 2017 May 10. [QxMD MEDLINE Link]. [Full Text].
Rui Y, Su J, Wang H, et al. Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68. Journal of Virology. 2017 Jun 09. [QxMD MEDLINE Link]. [Full Text].
Lei X, Xiao X, Wang J. Innate Immunity Evasion by Enteroviruses: Insights into Virus-Host Interaction. Viruses. 2016 Jan 15. [QxMD MEDLINE Link]. [Full Text].
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 Nov 6. 19(44):[QxMD MEDLINE Link].
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 Sep. 93:1952-8. [QxMD MEDLINE Link]. [Full Text].
Imamura T, Oshitani H. Global reemergence of enterovirus D68 as an important pathogen for acute respiratory infections. Rev Med Virol. 2014 Dec 3. [QxMD MEDLINE Link].
Enterovirus D68. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/non-polio-enterovirus/about/ev-d68.html. 2020 Aug 08; Accessed: May 01, 2021.
Shaw J, Welch TR, Milstone AM. The role of syndromic surveillance in directing the public health response to the enterovirus D68 epidemic. JAMA Pediatr. 2014 Nov. 168(11):981-2. [QxMD MEDLINE Link].
Pastula DM, Aliabadi N, Haynes AK, Messacar K, Schreiner T, Maloney J, et al. Acute neurologic illness of unknown etiology in children - Colorado, August-September 2014. MMWR Morb Mortal Wkly Rep. 2014 Oct 10. 63(40):901-2. [QxMD MEDLINE Link].
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Messacar K, Asturias EJ, Hixon AM, Van Leer-Buter C, Niesters HGM, Tyler KL, et al. Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causality. Lancet Infect Dis. 2018 Aug. 18 (8):e239-e247. [QxMD MEDLINE Link]. [Full Text].
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Maloney JA, Mirsky DM, Messacar K, Dominguez SR, Schreiner T, Stence NV. MRI Findings in Children with Acute Flaccid Paralysis and Cranial Nerve Dysfunction Occurring during the 2014 Enterovirus D68 Outbreak. AJNR Am J Neuroradiol. 2014 Nov 20. [QxMD MEDLINE Link].
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Zhang Y, Moore DD, Nix WA, et al. Neutralization of Enterovirus D68 isolated from the 2014 US outbreak by commercial intravenous immune globulin products. Journal of Clinical Virology. 2015 Aug. 69:172-175. [QxMD MEDLINE Link]. [Full Text].
Hixon AM, Clarke P, Tyler KL. Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis. The Journal of Infectious Diseases. 2017 Sep 13. 216:1245-1253. [QxMD MEDLINE Link].
Roux, Alexandra, and Sabeen Lulu. A Polio-Like Syndrome in California: Clinical, Radiologic, and Serologic Evaluation of Five Children Identified by a Statewide Laboratory over a Twelve-Months Period. Neurology. April 2014. [Full Text].
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Musharrafieh R, Ma C, Zhang J, Hu Y, Diesing JM, Marty MT, et al. Validating Enterovirus D68-2A^pro as an Antiviral Drug Target and the Discovery of Telaprevir as a Potent D68-2A^pro Inhibitor. J Virol. 2019 Apr 1. 93 (7):[QxMD MEDLINE Link]. [Full Text].
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Media Gallery

Electron micrograph of a thin section of enterovirus D68 (EV-D68), showing the numerous, spherical viral particles. Courtesy of the CDC.
Electron micrograph of a thin section of numerous spherical enterovirus D68 (EV-D68) viral particles. Some of the particles appear to be "empty," missing their contents of single-stranded RNA. Courtesy of the CDC.

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Enterovirus D68 Clinical Presentation

History

Physical

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