title: Global emergence of enterovirus D68: a systematic review.
abstract: Since its discovery in California in 1962, reports of enterovirus D68 have been infrequent. Before 2014, infections were confirmed in only 699 people worldwide. In August, 2014, two paediatric hospitals in the USA reported increases in the number of patients with severe respiratory illness, with an over-representation in children with asthma. Shortly after, the authorities recognised a nationwide outbreak, which then spread to Canada, Europe, and Asia. In 2014, more than 2000 cases of enterovirus D68 were reported in 20 countries. Concurrently, clusters of children with acute flaccid paralysis of unknown cause were reported in several US states and in Europe. Enterovirus D68 infection was confirmed in some of the paralysed children, but not all. Complications in patients who were severely neurologically affected resemble those caused by poliomyelitis. In this paper we systematically review reports on enterovirus D68 to estimate its global epidemiology and its ability to cause respiratory infections and neurological damage in children. We extracted data from 70 papers to report on prevalence, symptoms, hospitalisation and mortality, and complications of enterovirus D68, both before and during the large outbreak of 2014. The magnitude and severity of the enterovirus D68 outbreak underscores a need for improved diagnostic work-up of paediatric respiratory illness, not only to prevent unnecessary use of antibiotics, but also to ensure better surveillance of diseases. Existing surveillance systems should be assessed in terms of capacity and ability to detect and report any upsurge of respiratory viruses such as enterovirus D68 in a timely manner, and focus should be paid to development of preventive measures against these emerging enteroviruses that have potential for severe disease.
authors.affiliation: Virology Surveillance and Research Section, Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Charlotte Carina
authors.initials: CC
authors.lastname: Holm-Hansen
authors.affiliation: Virology Surveillance and Research Section, Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Sofie Elisabeth
authors.initials: SE
authors.lastname: Midgley
authors.affiliation: Virology Surveillance and Research Section, Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark; Center for Global Health and Department of Infectious Diseases, Clinical Institute, University of Southern Denmark, Odense, Denmark. Electronic address: thf@ssi.dk.
authors.forename: Thea Kølsen
authors.initials: TK
authors.lastname: Fischer
mesh_terms: D003371:Cough / Q000453:epidemiology / Q000821:virology; D004196:Disease Outbreaks; D030016:Enterovirus D, Human / Q000145:classification*; D004769:Enterovirus Infections / Q000453:epidemiology* / Q000821:virology; D014943:Global Health; D006760:Hospitalization; D006801:Humans; D010243:Paralysis / Q000209:etiology; D015995:Prevalence; D012141:Respiratory Tract Infections / Q000150:complications / Q000453:epidemiology* / Q000821:virology