Enterovirus D68 Infection in Children With Acute Flaccid Myelitis, Colorado, USA, 2014

Negar Aliabadi; Kevin Messacar; Daniel M. Pastula; Christine C. Robinson; Eyal Leshem; James J. Sejvar; W. Allan Nix; M. Steven Oberste; Daniel R. Feikin; Samuel R. Dominguez


Emerging Infectious Diseases. 2016;22(8):1387-1394. 

In This Article

Abstract and Introduction


During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis.


Enterovirus D68 (EV-D68) shares features with rhinoviruses[1] and primarily causes respiratory disease. Clusters of respiratory disease caused by EV-D68 have been reported in Asia, Europe, and the United States.[2,3] Although EV-D68 has been identified in the central nervous system of 2 patients with limb weakness,[4,5] its role in causing neuroinvasive disease has not been clearly defined.

From August 8, 2014, through October 14, 2014, a cluster of cases of acute limb weakness, cranial nerve dysfunction, or both, in children with characteristic radiologic findings of myelitis were identified at Children's Hospital Colorado (CHCO), in Aurora, Colorado, USA. These cases represented a substantial increase over the number of children admitted with this same constellation of signs and symptoms in the previous 4 years at CHCO.[6–8] This cluster prompted the Centers for Disease Control and Prevention (CDC) to create a case definition for acute flaccid myelitis (AFM; a subset of acute flaccid paralysis, characterized by appearance of myelitis on radiologic scans) and publish a national call for cases through a health alert announcement,[9] which led to identification of cases nationally[10] and an additional case in Colorado.

The Colorado AFM cluster occurred during an outbreak of EV-D68 respiratory disease.[3] During this period, CHCO emergency department visits and admissions for respiratory complaints to the hospital increased over prior years;[11] EV-D68 detection among hospitalized patients subsequently increased.[7] Although no etiology for the neurologic disease was identified among the Colorado cluster of patients (despite extensive testing, including metagenomic sequencing of cerebrospinal fluid), EV-D68 was found in the nasopharynx of 45% of these patients.[7,12] We further investigated a possible epidemiologic association between EV-D68 and AFM by conducting a case–control study comparing the presence of EV-D68 in upper respiratory specimens of case-patients and 2 groups of control children. This analysis was determined by human subjects review at CDC and CHCO to be nonresearch and was conducted as a public health investigation.