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


RESULTS
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).


CONCLUSIONS
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.


BACKGROUND
None.
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA; Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: ydk5@cdc.gov.
Claire M
CM
Midgley
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
John T
JT
Watson
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
W Allan
WA
Nix
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Aaron T
AT
Curns
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Shannon L
SL
Rogers
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Betty A
BA
Brown
Illinois Department of Public Health, Chicago, IL, USA.
Craig
C
Conover
Children's Hospital Colorado, Aurora, CO, USA.
Samuel R
SR
Dominguez
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Daniel R
DR
Feikin
Cook County Department of Public Health, Oak Forest, IL, USA.
Samantha
S
Gray
Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
Ferdaus
F
Hassan
Illinois Department of Public Health, Chicago, IL, USA.
Stacey
S
Hoferka
Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
Mary Anne
MA
Jackson
The University of Chicago Comer Children's Hospital, Chicago, IL, USA.
Daniel
D
Johnson
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Eyal
E
Leshem
Colorado Department of Public Health and Environment, Denver, CO, USA.
Lisa
L
Miller
Colorado Department of Public Health and Environment, Denver, CO, USA.
Janell Bezdek
JB
Nichols
Children's Hospital Colorado, Aurora, CO, USA.
Ann-Christine
AC
Nyquist
The University of Chicago Comer Children's Hospital, Chicago, IL, USA.
Emily
E
Obringer
The University of Chicago Comer Children's Hospital, Chicago, IL, USA.
Ajanta
A
Patel
Cook County Department of Public Health, Oak Forest, IL, USA.
Megan
M
Patel
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Brian
B
Rha
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Eileen
E
Schneider
Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
Jennifer E
JE
Schuster
Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
Rangaraj
R
Selvarangan
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Jane F
JF
Seward
Missouri Department of Health and Senior Services, Jefferson City, MO, USA.
George
G
Turabelidze
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
M Steven
MS
Oberste
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Mark A
MA
Pallansch
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Susan I
SI
Gerber
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000150:complications / Q000821:virology; D002648:Child; D002675:Child, Preschool; D003120:Colorado / Q000453:epidemiology; D003371:Cough / Q000453:epidemiology / Q000821:virology; D003422:Critical Care / Q000706:statistics & numerical data; D004196:Disease Outbreaks / Q000706:statistics & numerical data*; D004417:Dyspnea / Q000453:epidemiology / Q000821:virology; D030016:Enterovirus D, Human; D004769:Enterovirus Infections / Q000150:complications / Q000453:epidemiology* / Q000821:virology; D005260:Female; D005334:Fever / Q000453:epidemiology / Q000821:virology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007087:Illinois / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008923:Missouri / Q000453:epidemiology; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012135:Respiratory Sounds; D012141:Respiratory Tract Infections / Q000150:complications / Q000453:epidemiology* / Q000821:virology; D014481:United States / Q000453:epidemiology; D055815:Young Adult