#EVD68 #outbreak #detection through a syndromic disease #epidemiology #network (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology / Available online 16 January 2020, 104262 / In Press, Journal Pre-proof

Enterovirus D68 outbreak detection through a syndromic disease epidemiology network

Authors: Lindsay Meyers a, Jennifer Dien Bard bc, Ben Galvin a, Jeff Nawrocki a, Hubert G.M. Niesters d, Kathleen A. Stellrecht e, Kirsten St. George f, Judy A. Daly gh, Anne J. Blaschke i, Christine Robinson j, Huanyu Wang k, Camille V. Cook a, Ferdaus Hassan l, Sam R. Dominguez j, Kristin Pretty j, Samia Naccache b, Katherine E. Olin a, Benjamin M. Althousem n, Jay D. Jones a, Christine C. Ginocchioao p, Mark A. Poritz q2, Amy Leber k1, Rangaraj Selvarangan l1

{a} BioFire Diagnostics, Salt Lake City, UT, 84103, United States; {b} Department of Pathology and Laboratory Medicine, Children’s Hospital of Los Angeles, Los Angeles, CA 90027, United States; {c} Keck School of Medicine, University of Southern California, Los Angeles, CA 90039, United States; {d} The University of Groningen, University Medical Center Groningen, Department of Medical Microbiology, Division of Clinical Virology, Groningen, The Netherlands; {e} Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States; {f} New York State Department of Health, Albany, NY, 12202, United States; {g} Department of Pathology, University of Utah, Salt Lake City, UT 84132, United States; {h} Division of Inpatient Medicine, Primary Children’s Hospital, Salt Lake City, UT 84132, United States; {i} Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84132, United States; {j} Department of Pathology and Laboratory Medicine, Children’s Colorado, Aurora, CO 80045, United States; {k} Department of Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, United States; {l} Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital, Kansas City, MO 64108, United States; {m} Information School, University of Washington, Seattle, WA, 98105, United States; {n} Department of Biology, New Mexico State University, Las Cruces, NM, 88003, United States; {o} Global Medical Affairs, bioMérieux, Durham, NC 27712, United States; {p}
Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, United States; {q} BioFire Defense, Salt Lake City, UT 84107, United States

Received 3 June 2019, Revised 8 January 2020, Accepted 14 January 2020, Available online 16 January 2020. DOI: https://doi.org/10.1016/j.jcv.2020.104262



  • An algorithm to predict the presence enterovirus D68 among hinovirus/Enterovirus results obtained from a commercial respiratory disease diagnostic test was developed
  • The algorithm was used in conjunction with test results exported to a cloud-based epidemiology network for use in real-time monitoring and historical outbreak prediction
  • Historical outbreak predictions coincide with known periods of high EV-D68 circulation in 2014 and 2016
  • The algorithm alerted participating clinical laboratories of the potential circulation of EV-D68 in 2018, prompting clinical testing for EV-D68 at one site

Keywords: EV-D68; USA.


Characteristics of #Patients with Acute Flaccid #Myelitis [#AFM], #USA, 2015–2018 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / CME ACTIVITY – Research

Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015–2018

Nilay McLaren, Adriana Lopez, Sarah Kidd, John X. Zhang, W. Allan Nix, Ruth Link-Gelles, Adria Lee, and Janell A. Routh

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA



Observed peaks of acute flaccid myelitis (AFM) cases have occurred biennially since 2014 in the United States. We aimed to determine if AFM etiology differed between peak and nonpeak years, considering that clinical features of AFM differ by virus etiology. We compared clinical and laboratory characteristics of AFM cases that occurred during peak (2016 and 2018, n = 366) and nonpeak (2015 and 2017, n = 50) years. AFM patients in peak years were younger (5.2 years) than those in nonpeak years (8.3 years). A higher percentage of patients in peak years than nonpeak years had pleocytosis (86% vs. 60%), upper extremity involvement (33% vs. 16%), and an illness preceding limb weakness (90% vs. 62%) and were positive for enterovirus or rhinovirus RNA (38% vs. 16%). Enterovirus D68 infection was associated with AFM only in peak years. Our findings suggest AFM etiology differs between peak and nonpeak years.

Keywords: EV-D68; Enterovirus; Rhinovirus; AFM; USA.


#Respiratory #illness and acute flaccid #myelitis in the #Tokai district in 2018 (Pediatr Int., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pediatr Int. 2019 Dec 30. doi: 10.1111/ped.14128. [Epub ahead of print]

Respiratory illness and acute flaccid myelitis in the Tokai district in 2018.

Okumura A1, Numoto S1, Iwayama H1, Kurahashi H1, Natsume J2, Saitoh S3, Yoshikawa T4, Fukao T5, Hirayama M6, Takahashi Y2; Aichi Pediatric Clinical Study Group.

Author information: 1 Department of Pediatrics, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan. 2 Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. 3 Department of Pediatrics, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan. 4 Department of Pediatrics, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. 5 Department of Pediatrics, Gifu University Graduate School of Medical Sciences, 1-1 Yanagido, Gifu City, 501-1194, Japan. 6 Department of Pediatrics, Mie University Graduate School of Medical Sciences, 2-174 Edobashi, Tsu, Mie, 5148507, Japan.




An outbreak of acute flaccid myelitis was chronologically correlated with that of severe respiratory illness in Japan in 2015. We hypothesized that increases in children hospitalized with severe respiratory illnesses might be associated with increase in acute flaccid myelitis also in autumn 2018.


We explored the temporal correlations between respiratory illness outbreaks and acute flaccid myelitis during autumn season between 2016 and 2018 using questionnaire surveys. One questionnaire explored the monthly numbers of children with acute flaccid myelitis, Guillain-Barre syndrome, and other acute flaccid paralyses. The other questionnaire explored the monthly numbers of children hospitalized with respiratory illnesses associated with wheezing. A correlation between the monthly numbers of children with acute flaccid myelitis and those with respiratory illness was analyzed by the Pearson correlation test.


Although the number of patients hospitalized with respiratory illness did not correlate with the number of those admitted with myelitis, increases in children aged 7-12 and 13-19 years requiring ICU admission correlated temporally with an outbreak of acute flaccid myelitis.


An increase in intensive care unit admissions to treat respiratory disease occurred in association with a cluster of acute flaccid myelitis. An increase in the number of ICU admission due to respiratory illness may be a clue to expect the occurrence of acute flaccid myelitis.

© 2019 Japan Pediatric Society.

KEYWORDS: acute flaccid myelitis; enterovirus D68; outbreak; respiratory illness; temporal correlation

PMID: 31886594 DOI: 10.1111/ped.14128

Keywords: EV-D68; Pediatrics; Japan; AFM.


A #decade of #Enterovirus #genetic diversity in #Belgium (J Clin Invest., abstract)

[Source: Journal of Clinical Investigation, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology / Available online 25 October 2019, 104205 / In Press, Journal Pre-proof

A decade of Enterovirus genetic diversity in Belgium

Elke Wollants a, Leen Beller b, Kurt Beuselinck c, Mandy Bloemen a, Katrien Lagrou d,e, Marijke Reynders f, Marc Van Ranst a,e

{a} KU Leuven, Rega Institute, Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical & Epidemiological Virology, BE-3000 Leuven, Belgium; {b} KU Leuven, Rega Institute, Department of Microbiology, Immunology and Transplantation, Laboratory of Viral Metagenomics, BE-3000 Leuven, Belgium; {c} Department of Laboratory Medicine, University Hospitals Leuven, BE-3000, Leuven, Belgium; {d} KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Bacteriology and Mycology, BE-3000 Leuven, Belgium; {e}
Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, BE-3000, Leuven, Belgium; {f} Unit of Molecular Microbiology, Medical Microbiology, Department of Laboratory Medicine, AZ Sint-Jan Brugge AV, BE-8000 Bruges, Belgium

Received 6 June 2019, Revised 15 October 2019, Accepted 22 October 2019, Available online 25 October 2019. DOI: https://doi.org/10.1016/j.jcv.2019.104205



  • A decade of molecular genotyping of Enteroviruses in Belgium.
  • 89 % molecularly genotyped over 12 years with our genotyping strategy.
  • 35 different enterovirus genotypes in 1521 samples.
  • An upsurge of enterovirus D68 in 2018.
  • Coexistence of multiple EV-D68 clades proved by phylogenetic analysis.




Enteroviruses are responsible for a wide range of clinical symptoms.Enterovirus D68 was already known to cause mild to severe respiratory infections, but in the last few years, it has also been associated with neurological symptoms and acute flaccid paralysis.


In this epidemiological surveillance in Belgium, 1521 enteroviruspositive samples were genotyped.

Study design

Enterovirus-positive patient samples were collected from the University Hospitals Leuven and other hospitals and medical practices in Belgium from 2007 to 2018. Molecular typing was done by RT-PCR using different primers sets. EV-A and EV-B were typed by sequencing part of VP1. For EVC and EV-D, the VP4/VP2 region was used together with the non-coding region.


In this epidemiological survey with samples collected over 12 years, 35 different EV types were detected in 1521 patient samples. Enterovirus species B was by far the most dominant species in our samples (93%).Echovirus 30 was most frequently found (24%), followed by echovirus 6 (8%) and echovirus 9 (7%). In 2018, there was an outbreak for the first time of enterovirus D68 with severe respiratory infections but no acute flaccid paralysis. Phylogenetic analyses showed that the collected outbreak strains coexist in different clades.


For more than a decade, the circulating enterovirus strains were investigated in Belgium. During this time span, echovirus 30 was the most frequently detected and peaked every 3 years. Enterovirus D68 began an upsurge in 2018, but thus far without being clinically associated with acute flaccid paralysis.

Keywords: Enterovirus typing – Genetic Diversity – EV-D68 phylogenetic analyses

© 2019 Published by Elsevier B.V.

Keywords: Enterovirus; EV-D68; Echovirus 30; Belgium.


#Neurotropism of #Enterovirus D68 Isolates Is Independent of #Sialic Acid and Is Not a Recently Acquired Phenotype (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Neurotropism of Enterovirus D68 Isolates Is Independent of Sialic Acid and Is Not a Recently Acquired Phenotype

Amy B. Rosenfeld, Audrey L. Warren, Vincent R. Racaniello

DOI: 10.1128/mBio.02370-19



Acute flaccid myelitis (AFM) is a rare but serious illness of the nervous system, specifically affecting the gray matter of the spinal cord, motor-controlling regions of the brain, and cranial nerves. Most cases of AFM are pathogen associated, typically with poliovirus and enterovirus infections, and occur in children under the age of 6 years. Enterovirus D68 (EV-D68) was first isolated from children with pneumonia in 1962, but an association with AFM was not observed until the 2014 outbreak. Organotypic mouse brain slice cultures generated from postnatal day 1 to 10 mice and adult ifnar knockout mice were used to determine if neurotropism of EV-D68 is shared among virus isolates. All isolates replicated in organotypic mouse brain slice cultures, and three isolates replicated in primary murine astrocyte cultures. All four EV-D68 isolates examined caused paralysis and death in adult ifnar knockout mice. In contrast, no viral disease was observed after intracranial inoculation of wild-type mice. Six of the seven EV-D68 isolates, including two from 1962 and four from the 2014 outbreak, replicated in induced human neurons, and all of the isolates replicated in induced human astrocytes. Furthermore, a putative viral receptor, sialic acid, is not required for neurotropism of EV-D68, as viruses replicated within neurons and astrocytes independent of binding to sialic acid. These observations demonstrate that EV-D68 is neurotropic independent of its genetic lineage and can infect both neurons and astrocytes and that neurotropism is not a recently acquired characteristic as has been suggested. Furthermore, the results show that in mice the innate immune response is critical for restricting EV-D68 disease.



Since 2014, numerous outbreaks of childhood infections with enterovirus D68 (EV-D68) have occurred worldwide. Most infections are associated with flu-like symptoms, but paralysis may develop in young children. It has been suggested that infection only with recent viral isolates can cause paralysis. To address the hypothesis that EV-D68 has recently acquired neurotropism, murine organotypic brain slice cultures, induced human motor neurons and astrocytes, and mice lacking the alpha/beta interferon receptor were infected with multiple virus isolates. All EV-D68 isolates, from 1962 to the present, can infect neural cells, astrocytes, and neurons. Furthermore, our results show that sialic acid binding does not play a role in EV-D68 neuropathogenesis. The study of EV-D68 infection in organotypic brain slice cultures, induced motor neurons, and astrocytes will allow for the elucidation of the mechanism by which the virus infection causes disease.

Keywords: Enterovirus; EV-D68; Acute flaccid myelitis; Neuroinvasion.


#Enterovirus D68 #serosurvey: evidence for #endemic circulation in the #Netherlands, 2006 to 2016 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Enterovirus D68 serosurvey: evidence for endemic circulation in the Netherlands, 2006 to 2016

Eveliina Karelehto1, Gerrit Koen1, Kimberley Benschop2, Fiona van der Klis2, Dasja Pajkrt3, Katja Wolthers1

Affiliations: 1 Department of Medical Microbiology, Laboratory of Clinical Virology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2 National Institute for Public Health and the Environment, Bilthoven, the Netherlands; 3 Department of Pediatric Infectious Diseases, Emma Children’s Hospital, University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

Correspondence:  Katja C Wolthers

Citation style for this article: Karelehto Eveliina, Koen Gerrit, Benschop Kimberley, van der Klis Fiona, Pajkrt Dasja, Wolthers Katja. Enterovirus D68 serosurvey: evidence for endemic circulation in the Netherlands, 2006 to 2016. Euro Surveill. 2019;24(35):pii=1800671. https://doi.org/10.2807/1560-7917.ES.2019.24.35.1800671

Received: 12 Dec 2018;   Accepted: 05 Jun 2019




Enterovirus D68 (EV-D68) has caused major outbreaks of severe respiratory illness worldwide since 2010.


Our aim was to evaluate EV-D68 circulation in the Netherlands by conducting a serosurvey of EV-D68 neutralising antibodies (nAb) among the Dutch general population.


We screened 280 sera from children and adults in the Netherlands and used two independent sets of samples collected in the years 2006 and 2007 and in the years 2015 and 2016, time points before and after the first EV-D68 upsurge in 2010. Neutralisation capacity of the sera was tested against the prototype Fermon EV-D68 strain isolated in 1962 and against a recent EV-D68 strain (genotype B3) isolated in France in 2016.


Regardless of the time of serum collection, we found remarkably high overall seropositivity (94.3–98.3%) for nAb against both EV-D68 strains. Geometric mean titres increased in an age-dependent manner.


Our data suggest that EV-D68 has been circulating in the Netherlands for decades and that the enterovirus surveillance does not accurately capture the prevalence of this clinically relevant pathogen.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Enterovirus; EV-D68; Pediatrics; Netherlands; Seroprevalence.


#Molecular and #Clinical #Comparison of #Enterovirus D68 #Outbreaks among Hospitalized #Children, #Ohio, #USA, 2014 and 2018 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 11—November 2019 / Research

Molecular and Clinical Comparison of Enterovirus D68 Outbreaks among Hospitalized Children, Ohio, USA, 2014 and 2018

Huanyu Wang, Alejandro Diaz, Katherine Moyer1, Maria Mele-Casas2, Maria Fatima Ara-Montojo3, Isabel Torrus2, Karen McCoy, Asuncion Mejias, and Amy L. Leber

Author affiliations: Nationwide Children’s Hospital, Columbus, Ohio, USA (H. Wang, A. Diaz, K. Moyer, M. Mele-Casas, M.F. Ara-Montojo, I. Torrus, K. McCoy, A. Mejias, A.L. Leber); The Ohio State University, Columbus, Ohio, USA (H. Wang, A. Mejias, A.L. Leber).



Enterovirus D68 (EV-D68) causes respiratory tract infections and neurologic manifestations. We compared the clinical manifestations from 2 EV-D68 outbreaks in 2014 and 2018 and a low-activity period in 2016 among hospitalized children in central Ohio, USA, and used PCR and sequencing to enable phylogenetic comparisons. During both outbreak periods, infected children had respiratory manifestations that led to an increase in hospital admissions for asthma. The 2018 EV-D68 outbreak appeared to be milder in terms of respiratory illness, as shown by lower rates of pediatric intensive care unit admission. However, the frequency of severe neurologic manifestations was higher in 2018 than in 2014. During the same period in 2016, we noted neither an increase in EV-D68 nor a significant increase in asthma-related admissions. Phylogenetic analyses showed that EV-D68 isolates from 2018 clustered differently within clade B than did isolates from 2014 and are perhaps associated with a different EV-D68 subclade.

Keywords: Enterovirus; EV-D68; Neurology; Pediatrics; Ohio; USA.