title: Clinical disease due to enterovirus D68 in adult hematologic malignancy patients and hematopoietic cell transplant recipients.
abstract: The United States Centers for Disease Control and Prevention reported over 1000 cases of severe respiratory disease in pediatric patients associated with enterovirus D68 (EV-D68) in the fall of 2014. We sought to identify and define the clinical burden of disease due to EV-D68 in adult patients with hematologic malignancy or undergoing hematopoietic cell transplant (HCT). Real-time reverse-transcriptase polymerase chain reaction (PCR) for EV-D68 was performed on all respiratory samples positive for human rhinovirus (HRV) or negative for all respiratory viruses by a laboratory-developed respiratory viral PCR panel from August 11, 2014, to November 7, 2014. Presumptive cases were defined as those with an EV-D68 PCR cycle threshold (CT) at least 4 cycles lower than the HRV CT for HRV-positive samples or any EV-D68 CT value for HRV-negative samples. Sequencing of a 150-bp fragment of the 5' noncoding region confirmed EV-D68 in 16 of 506 respiratory samples. Eight patients had a history of hematologic malignancy, and 6 of these had undergone HCT. Presentation ranged from mild upper respiratory symptoms to respiratory failure. EV-D68 can infect adult patients with hematologic malignancy and HCT recipients and may be associated with severe respiratory disease. Current commercial diagnostic assays cannot differentiate EV-D68 from other enteroviruses or HRV, and improved rapid diagnostic tools are needed.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, WA; Seattle Children's Hospital, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: Alpana
authors.identifier: http://orcid.org/0000-0003-2268-9470
authors.initials: A
authors.lastname: Waghmare
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, Division of Allergy and Infectious Diseases, and.
authors.forename: Steven A
authors.identifier: http://orcid.org/0000-0002-6333-5196
authors.initials: SA
authors.lastname: Pergam
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Laboratory Medicine, Division of Virology, University of Washington, Seattle, WA.
authors.forename: Keith R
authors.identifier: http://orcid.org/0000-0002-8212-3789
authors.initials: KR
authors.lastname: Jerome
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, WA; Seattle Children's Hospital, Seattle, WA;
authors.forename: Janet A
authors.identifier: http://orcid.org/0000-0003-1134-4178
authors.initials: JA
authors.lastname: Englund
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, Division of Allergy and Infectious Diseases, and.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0003-1538-7984
authors.initials: M
authors.lastname: Boeckh
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Laboratory Medicine, Division of Virology, University of Washington, Seattle, WA.
authors.forename: Jane
authors.identifier: http://orcid.org/0000-0002-0189-0274
authors.initials: J
authors.lastname: Kuypers
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D030016:Enterovirus D, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D004769:Enterovirus Infections / Q000150:complications* / Q000175:diagnosis*; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000150:complications* / Q000175:diagnosis*; D012229:Rhinovirus / Q000235:genetics / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D004279:DNA, Viral