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Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes.
PLoS One. 2016; 11(11):e0167111.Plos

Abstract

BACKGROUND

An outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014.

METHODS

May through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time.

RESULTS

In 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011-13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B.

CONCLUSIONS

This is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68 circulated before 2014, the outbreak isolates clustered differently than those from prior years.

Authors+Show Affiliations

Department of Pediatrics, Division of Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio, United States of America.Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States of America.Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States of America.Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States of America.Department of Pediatrics, Division of Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio, United States of America. Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27875593

Citation

Moyer, Katherine, et al. "Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes." PloS One, vol. 11, no. 11, 2016, pp. e0167111.
Moyer K, Wang H, Salamon D, et al. Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes. PLoS One. 2016;11(11):e0167111.
Moyer, K., Wang, H., Salamon, D., Leber, A., & Mejias, A. (2016). Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes. PloS One, 11(11), e0167111. https://doi.org/10.1371/journal.pone.0167111
Moyer K, et al. Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes. PLoS One. 2016;11(11):e0167111. PubMed PMID: 27875593.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes. AU - Moyer,Katherine, AU - Wang,Huanyu, AU - Salamon,Douglas, AU - Leber,Amy, AU - Mejias,Asuncion, Y1 - 2016/11/22/ PY - 2016/08/26/received PY - 2016/11/08/accepted PY - 2016/11/23/entrez PY - 2016/11/23/pubmed PY - 2017/6/24/medline SP - e0167111 EP - e0167111 JF - PloS one JO - PLoS One VL - 11 IS - 11 N2 - BACKGROUND: An outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014. METHODS: May through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time. RESULTS: In 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011-13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B. CONCLUSIONS: This is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68 circulated before 2014, the outbreak isolates clustered differently than those from prior years. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27875593/Enterovirus_D68_in_Hospitalized_Children:_Sequence_Variation_Viral_Loads_and_Clinical_Outcomes_ L2 - https://dx.plos.org/10.1371/journal.pone.0167111 DB - PRIME DP - Unbound Medicine ER -