Enterovirus 68 natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2] Alejandro Lemor, M.D. [3]

Overview

The natural history of Enterovirus 68 is poorly understood due to scarcity of data. The virus may produce a spectrum of clinical disease, ranging from an asymptomatic course to severe respiratory symptoms necessitating hospitalization. Prognosis is generally good, but few reports of fatalities have been documented. Approximately 16-21% of patients suffer from enterovirus 68-associated complications. Common complications, such as superimposed infections and severe pneumonia requiring mechanical ventilation, are more likely to occur among patients with a history of pulmonary disease.

Natural History

  • Enterovirus 68 colonizes the respiratory mucosa. It is believed to be transmitted through respiratory droplets and is often detected by nasopharyngeal swabs of patients presenting with respiratory illness. Nonetheless, the incubation period of the virus is unknown.
  • The virus has been isolated among patients of all age groups, ranging from 1 month to 72 years. Although 4 to 5-year-old children are believed to be the most susceptible hosts, accounting for approximately 80% of all reported cases, newer reports are currently noting more adult infections.[1][2][3]
  • The clinical features of the virus are characterized by non-specific signs and symptoms including cough, dyspnea, wheezing, and other symptoms of bronchitis.[3][4][5][6]
  • Without treatment, symptoms generally self-resolve within 4-6 days of symptoms onset.
  • The disease may progress in the minority of untreated cases to pneumonia, asthma exacerbations, and severe respiratory distress. Patients may require hospitalization, oxygen supplementation, or less commonly mechanical ventilation. The majority of patients requiring intensive care hospitalization are those with a history of pulmonary disease, such as asthma, cystic fibrosis, or lung transplantation.[3][4][5][6]

Complications

Complications are observed among 16-21% of patients diagnosed with enterovirus 68. The majority of patients with complications have a history of pulmonary or systemic co-morbidities.[7] Complications that can develop as a result of enterovirus 68 are:

  • Lower respiratory infections[1]
    • Pneumonia is considered the most common complication of enterovirus 68
    • Bacterial super-infection is reported with organisms that are commonly associated with lower respiratory infections, such as Streptococcus pneumoniae, Hemophilus influenzae, Mycoplasma pnuemoniae, and Chlamydia pneumniae
    • Viral co-infection with RSV and CMV has been described
  • Respiratory failure[8]
  • Asthma exacerbation[8]
  • Febrile convulsions[8]
  • CNS sequelae[9]
    • Lymphocytic meningomyelitis and encephalitis were both reported in only 1 case of a previously healthy 5-year-old boy
  • Death[10]
    • Death due to enterovirus 68-associated complications is documented among both children and adults, but is considered a very rare event

Prognosis

  • Most patients recover uneventfully.
  • Asthmatic patient have an increased risk of developing severe disease.[11]
  • One case report describes a fatal case of enterovirus 68 infection associated with pneumonia, flaccid paralysis and neurologic impairment. [12]

References

  1. 1.0 1.1 Rahamat-Langendoen J, Riezebos-Brilman A, Borger R, van der Heide R, Brandenburg A, Schölvinck E; et al. (2011). "Upsurge of human enterovirus 68 infections in patients with severe respiratory tract infections". J Clin Virol. 52 (2): 103–6. doi:10.1016/j.jcv.2011.06.019. PMID 21802981.
  2. Tokarz R, Firth C, Madhi SA, Howie SR, Wu W, Sall AA; et al. (2012). "Worldwide emergence of multiple clades of enterovirus 68". J Gen Virol. 93 (Pt 9): 1952–8. doi:10.1099/vir.0.043935-0. PMC 3542132. PMID 22694903.
  3. 3.0 3.1 3.2 Jacobson, Lara M.; Redd, John T.; Schneider, Eileen; Lu, Xiaoyan; Chern, Shur-Wern W.; Oberste, M. Steven; Erdman, Dean D.; Fischer, Gayle E.; Armstrong, Gregory L.; Kodani, Maja; Montoya, Jennifer; Magri, Julie M.; Cheek, James E. (2012). "Outbreak of Lower Respiratory Tract Illness Associated With Human Enterovirus 68 Among American Indian Children". The Pediatric Infectious Disease Journal. 31 (3): 309–312. doi:10.1097/INF.0b013e3182443eaf. ISSN 0891-3668.
  4. 4.0 4.1 Lu, Q.-B.; Wo, Y.; Wang, H.-Y.; Wei, M.-T.; Zhang, L.; Yang, H.; Liu, E.-M.; Li, T.-Y.; Zhao, Z.-T.; Liu, W.; Cao, W.-C. (2013). "Detection of enterovirus 68 as one of the commonest types of enterovirus found in patients with acute respiratory tract infection in China". Journal of Medical Microbiology. 63 (Pt_3): 408–414. doi:10.1099/jmm.0.068247-0. ISSN 0022-2615.
  5. 5.0 5.1 Imamura, Tadatsugu; Suzuki, Akira; Lupisan, Socorro; Kamigaki, Taro; Okamoto, Michiko; Roy, Chandra Nath; Olveda, Remigio; Oshitani, Hitoshi (2014). "Detection of enterovirus 68 in serum from pediatric patients with pneumonia and their clinical outcomes". Influenza and Other Respiratory Viruses. 8 (1): 21–24. doi:10.1111/irv.12206. ISSN 1750-2640.
  6. 6.0 6.1 Piralla, Antonio; Girello, Alessia; Grignani, Michela; Gozalo-Margüello, Monica; Marchi, Antonietta; Marseglia, Gianluigi; Baldanti, Fausto (2014). "Phylogenetic characterization of enterovirus 68 strains in patients with respiratory syndromes in Italy". Journal of Medical Virology. 86 (9): 1590–1593. doi:10.1002/jmv.23821. ISSN 0146-6615.
  7. Meijer, Adam; van der Sanden, Sabine; Snijders, Bianca E.P.; Jaramillo-Gutierrez, Giovanna; Bont, Louis; van der Ent, Cornelis K.; Overduin, Pieter; Jenny, Shireen L.; Jusic, Edin; van der Avoort, Harrie G.A.M.; Smith, Gavin J.D.; Donker, Gé A.; Koopmans, Marion P.G. (2012). "Emergence and epidemic occurrence of enterovirus 68 respiratory infections in The Netherlands in 2010". Virology. 423 (1): 49–57. doi:10.1016/j.virol.2011.11.021. ISSN 0042-6822.
  8. 8.0 8.1 8.2 Kaida A, Kubo H, Sekiguchi J, Kohdera U, Togawa M, Shiomi M; et al. (2011). "Enterovirus 68 in children with acute respiratory tract infections, Osaka, Japan". Emerg Infect Dis. 17 (8): 1494–7. doi:10.3201/eid1708.110028. PMC 3381549. PMID 21801632.
  9. Kreuter JD, Barnes A, McCarthy JE, Schwartzman JD, Oberste MS, Rhodes CH; et al. (2011). "A fatal central nervous system enterovirus 68 infection". Arch Pathol Lab Med. 135 (6): 793–6. doi:10.1043/2010-0174-CR.1. PMID 21631275.
  10. Imamura T, Suzuki A, Lupisan S, Okamoto M, Aniceto R, Egos RJ; et al. (2013). "Molecular evolution of enterovirus 68 detected in the Philippines". PLoS One. 8 (9): e74221. doi:10.1371/journal.pone.0074221. PMC 3779236. PMID 24073203.
  11. Hasegawa, S.; Hirano, R.; Okamoto-Nakagawa, R.; Ichiyama, T.; Shirabe, K. (2011). "Enterovirus 68 infection in children with asthma attacks: virus-induced asthma in Japanese children". Allergy. 66 (12): 1618–1620. doi:10.1111/j.1398-9995.2011.02725.x. ISSN 0105-4538.
  12. Justin D. Kreuter, Arti Barnes, James E. McCarthy, Joseph D. Schwartzman, M. Steven Oberste, C. Harker Rhodes, John F. Modlin & Peter F. Wright (2011). "A fatal central nervous system enterovirus 68 infection". Archives of pathology & laboratory medicine. 135 (6): 793–796. doi:10.1043/2010-0174-CR.1. PMID 21631275. Unknown parameter |month= ignored (help)