Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation

Abstract

Background: Enterovirus D68 (EV-D68) has been infrequently reported historically, and is typically associated with isolated cases or small clusters of respiratory illness. Beginning in August, 2014, increases in severe respiratory illness associated with EV-D68 were reported across the USA. We aimed to describe the clinical, epidemiological, and laboratory features of this outbreak, and to better understand the role of EV-D68 in severe respiratory illness.

Methods: We collected regional syndromic surveillance data for epidemiological weeks 23 to 44, 2014, (June 1 to Nov 1, 2014) and hospital admissions data for epidemiological weeks 27 to 44, 2014, (June 29 to Nov 1, 2014) from three states: Missouri, Illinois and Colorado. Data were also collected for the same time period of 2013 and 2012. Respiratory specimens from severely ill patients nationwide, who were rhinovirus-positive or enterovirus-positive in hospital testing, were submitted between Aug 1, and Oct 31, 2014, and typed by molecular sequencing. We collected basic clinical and epidemiological characteristics of EV-D68 cases with a standard data collection form submitted with each specimen. We compared patients requiring intensive care with those who did not, and patients requiring ventilator support with those who did not. Mantel-Haenszel χ(2) tests were used to test for statistical significance.

Findings: Regional and hospital-level data from Missouri, Illinois, and Colorado showed increases in respiratory illness between August and September, 2014, compared with in 2013 and 2012. Nationwide, 699 (46%) of 1529 patients tested were confirmed as EV-D68. Among the 614 EV-D68-positive patients admitted to hospital, age ranged from 3 days to 92 years (median 5 years). Common symptoms included dyspnoea (n=513 [84%]), cough (n=500 [81%]), and wheezing (n=427 [70%]); 294 (48%) patients had fever. 338 [59%] of 574 were admitted to intensive care units, and 145 (28%) of 511 received ventilator support; 322 (52%) of 614 had a history of asthma or reactive airway disease; 200 (66%) of 304 patients with a history of asthma or reactive airway disease required intensive care compared with 138 (51%) of 270 with no history of asthma or reactive airway disease (p=0·0004). Similarly, 89 (32%) of 276 patients with a history of asthma or reactive airway disease required ventilator support compared with 56 (24%) of 235 patients with no history of asthma or reactive airway disease (p=0·039).

Interpretation: In 2014, EV-D68 caused widespread severe respiratory illness across the USA, disproportionately affecting those with asthma. This unexpected event underscores the need for robust surveillance of enterovirus types, enabling improved understanding of virus circulation and disease burden.

Funding: None.

Figure 1

Syndromic surveillance of respiratory illness among patients younger than 18 years of age in northern Illinois, by year (A) Visits to the emergency department for respiratory illness and (B) hospital admissions for respiratory illness are depicted as a percentage of total visits or admissions, respectively. Data for respiratory illness from hospitals in northern Illinois were extracted from ESSENCE Surveillance System. Data for the same time period in 2012, 2013, and 2014 were extracted for comparison.

Figure 2

Respiratory illness detected in three hospitals in the USA, by year Data for hospital admissions (A) and paediatric intensive care unit admissions (B) for respiratory illness were collected from three hospitals: University of Chicago Comer Children's Hospital, IL, USA (CCH-Chicago-IL), Children's Mercy Hospital in Kansas City, MO, USA (CMH-Kansas City-MO), and Children's Hospital Colorado (CHC-Aurora-CO). Data were collected for the same time periods in 2014, 2013, and 2012, for comparison. Available data are shown; comparative hospital admission data were not available from Children's Mercy Hospital, and comparative paediatric intensive care unit admission data were not available from Children's Hospital Colorado.

Figure 3

Maximum-likelihood phylogeny of EV-D68 strains associated with respiratory disease clusters or outbreaks from 2008 to 2014 Complete viral protein 1 gene sequences from the US 2014 outbreak (solid circles are EV-D68 KM85851225-KM851231 sequenced at CDC; hollow circles are other US 2014 EV-D68 VP1 genes from GenBank) were compared with EV-D68 strains from Europe and Asia. The major (>91% of cases) and minor (>7% of cases) cocirculating outbreak strains are indicated. Bootstrap values >80% are shown. The scale bar represents genetic change in base substitutions per site. A single EV-D68, distantly related to an older lineage, was identified in Kentucky. ITA=Italy. THA=Thailand. JPN=Japan. PHL=Philippines. NEZ=New Zealand.