Approach Considerations

In outpatient settings, ensure that the patient has an asthma action plan to control asthma long-term and understands how to manage worsening asthma or attacks. Provide instructions concerning when to call his or her primary physician or to seek emergency treatment.^[38]

Patients with severe respiratory infection should be hospitalized for supportive treatment, as follows:

Oxygen if the patient is hypoxic
Bronchodilator therapy if the patient presents with clinical evidence of bronchospasm
Endotracheal intubation and mechanical ventilation may be needed in patients with impending respiratory failure

No specific intervention has been shown definitive efficacy in EV-D68 infections with acute flaccid myelitis. Human intravenous immunoglobulin (IVIG) may offer some benefit, as reported by Zhang et al, who found high levels of neutralizing antibodies to EV-D68.^[40]Studies performed in mice with EV-D68 infection with paralytic myelitis showed that human IVIG reduced paralysis and decreased spinal cord paralysis, while fluoxetine had no effect and dexamethasone resulted in worse motor impairment and increased mortality and increased viral loads.^[41]However, in a small review of 5 cases of poliolike syndrome, steroids, intravenous immunoglobulin, and plasma exchange showed no apparent clinical benefit.^[42]

No data on the efficacy of antivirals in humans exist. Promising data have shown that rupintrivir, an irreversible inhibitor of the human rhinovirus 3C protease, and novel diketopiperazines have in vitro activity against EV-D68.^[43]Other antiviral drugs have been proposed as drug candidates for EV-D68 targetting different viral particles.^{[44, 45, 46]}

Consultations

Consider consultation with an infectious disease specialist and/or neurologist.

Prevention

No vaccinations are available for EV-D68 infection. As no suitable animal model still exists for EV-D68, a full understanding of the pathogenesis and immune response against EV-D68 is incomplete. Studies are underway to establish animal models and the effect of EV-D68 on their immune system to investigate antiviral therapies and vaccines.^{[21, 47]}

Medication

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.
Modlin JF. Epidemiology, pathogenesis, treatment, and prevention of enterovirus and parechovirus infections. UpToDate. Available at http://www.uptodate.com/contents/epidemiology-pathogenesis-treatment-and-prevention-of-enterovirus-and-parechovirus-infections.
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].
Acute Flaccid Myelitis (AFM) Cases and Outbreaks. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.html. April 5, 2021; Accessed: May 1, 2021.
McLaren N, Lopez A, Kidd S, Zhang JX, Nix WA, Link-Gelles R, et al. Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015-2018. Emerg Infect Dis. 2020 Feb. 26 (2):[QxMD MEDLINE Link]. [Full Text].
Kidd S, Lopez AS, Konopka-Anstadt JL, Nix WA, Routh JA, Oberste MS. Enterovirus D68-Associated Acute Flaccid Myelitis, United States, 2020. Emerg Infect Dis. 2020 Oct. 26 (10):[QxMD MEDLINE Link]. [Full Text].
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].
Sejvar JJ, Lopez AS, Cortese MM, Leshem E, Pastula DM, Miller L, et al. Acute Flaccid Myelitis in the United States, August-December 2014: Results of Nationwide Surveillance. Clin Infect Dis. 2016 Sep 15. 63 (6):737-745. [QxMD MEDLINE Link]. [Full Text].
Garcia J, Espejo V, Nelson M, Sovero M, Villaran MV, Gomez J, et al. Human rhinoviruses and enteroviruses in influenza-like illness in Latin America. Virol J. 2013 Oct 11. 10:305. [QxMD MEDLINE Link]. [Full Text].
Ayscue P, Van Haren K, Sheriff H, Waubant E, Waldron P, Yagi S, et al. Acute flaccid paralysis with anterior myelitis - California, June 2012-June 2014. MMWR Morb Mortal Wkly Rep. 2014 Oct 10. 63(40):903-6. [QxMD MEDLINE Link].
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].
Centers for Disease Control and Prevention. Enterovirus D68 for Health Care Professionals. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/non-polio-enterovirus/hcp/EV-D68-hcp.html. Accessed: December 20, 2014.
Wylie TN, Wylie KM, Buller RS, Cannella M, Storch GA. Development and Evaluation of an Enterovirus D68 Real-Time Reverse Transcriptase PCR Assay. J Clin Microbiol. 2015 Aug. 53 (8):2641-7. [QxMD MEDLINE Link].
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].
Smee DF, Evans WJ, Nicolaou KC, et al. Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds. Antiviral Research. 2016 Jul. 131:61-65. [QxMD MEDLINE Link]. [Full Text].
Ma C, Hu Y, Zhang J, Wang J. Pharmacological Characterization of the Mechanism of Action of R523062 , a Promising Antiviral for Enterovirus D68. ACS Infect Dis. 2020 Aug 14. 6 (8):2260-2270. [QxMD MEDLINE Link]. [Full Text].
Ma C, Hu Y, Zhang J, Musharrafieh R, Wang J. A Novel Capsid Binding Inhibitor Displays Potent Antiviral Activity against Enterovirus D68. ACS Infect Dis. 2019 Nov 8. 5 (11):1952-1962. [QxMD MEDLINE Link]. [Full Text].
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].
Patel MC, Wang W, Pletneva LM, et al. Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus). Public Library of Science. 2016 Nov 04. [QxMD MEDLINE Link]. [Full Text].
Rhoden E, Zhang M, Nix WA, et al. In Vitro Efficacy of Antiviral Compounds against Enterovirus D68. Antimicrobial Agents and Chemotherapy. 2015 Dec. [QxMD MEDLINE Link]. [Full Text].
Kim Y, Kankanamalage AC, Damalanka VC, et al. Potent inhibition of enterovirus D68 and human rhinoviruses by dipeptidyl aldehydes and α-ketoamides. Antiviral Research. 2016 Jan. [QxMD MEDLINE Link]. [Full Text].

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.

of 2

Enterovirus D68 Treatment & Management

Approach Considerations

Consultations

Prevention

References

Tables

Contributor Information and Disclosures

What would you like to print?