#Enterovirus A71 #Infection and #Neurologic Disease, Madrid, #Spain, 2016 (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 1—January 2019 / CME ACTIVITY – Synopsis

Enterovirus A71 Infection and Neurologic Disease, Madrid, Spain, 2016

Carmen Niño Taravilla1  , Isabel Pérez-Sebastián1, Alberto García Salido, Claudia Varela Serrano, Verónica Cantarín Extremera, Anna Duat Rodríguez, Laura López Marín, Mercedes Alonso Sanz, Olga María Suárez Traba, and Ana Serrano González

Author affiliations: Hospital Infantil Universitario Niño Jesús, Madrid, Spain



We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

Keywords: EV-A71; Encephalitis; Spain.



#Surveillance of #enteroviruses from #paediatric patients attended at a tertiary #hospital in #Catalonia from 2014 to 2017 (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 30 November 2018 / In Press, Accepted Manuscript

Surveillance of enteroviruses from paediatric patients attended at a tertiary hospital in Catalonia from 2014 to 2017

Cristina Andrés a, Jorgina Vila b, Laura Gimferrer a , Maria Piñana a, Juliana Esperalba a, Maria Gema Codina a, Meritxell Barnés b, Mariadel Carmen Martín a, Francisco Fuentes a, Susana Rubio a, Pilar Alcubilla a, Carlos Rodrigo b, Tomàs Pumarola a, Andrés Antón a

{a} Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; {b} Paediatric Hospitalisation Unit, Department of Paediatrics, Hospital Universitari Maternoinfantil Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

Received 4 September 2018, Revised 26 October 2018, Accepted 16 November 2018, Available online 30 November 2018.

DOI: https://doi.org/10.1016/j.jcv.2018.11.004



  • The study reports virological and clinical enterovirus surveillance in Catalonia.
  • The four enterovirus species cocirculated, distinguishing up to 27 different types.
  • Most of neurological studied cases were from the 2016 spring outbreak.
  • EV-A71 was one of the most detected EV, mostly during the outbreak.
  • Rhombencephalitis cases were related to EV-A71 infection.
  • EV-D68 was associated with lower respiratory tract infections.
  • Necessity to perform EV surveillance in primary care settings.




Enterovirus (EV) infections are usually asymptomatic or mild, but symptomatic infections can evolve to severe complications. Outbreaks of EV-A71 and EV-D68 have been recently reported worldwide, sometimes related to severe clinical outcomes.


To describe EV genetic diversity and the clinical outcomes from paediatric patients attended at a tertiary university hospital in Barcelona (Catalonia, Spain) from 2014 to 2017.

Study design

Specimens were collected from paediatric (<17 years old) cases with suspicion of respiratory tract infection or EV infection. EV laboratory-confirmation was performed by specific real-time multiplex RT-PCR assay. Partial viral VP1 protein was sequenced for genetic characterisation by phylogenetic analyses.


A total of 376 (7%) from 5,703 cases were EV laboratory-confirmed. Phylogenetic analyses of VP1 (210; 81%) sequences distinguished up to 27 different EV types distributed within EV-A (82; 40%), EV-B (90; 42%), EV-C (5; 2%), and EV-D (33; 15%), in addition to 50 (19%) rhinoviruses. The most predominant were EV-A71 (37; 45%) and EV-D68 (32; 99%). EV-A71 was highly related to neurological complications (25/39, 63%), of which 20/39 were rhombencephalitis, and most EV-D68 (28/32, 88%) were associated with lower respiratory tract infections (LRTI), and exceptionally one (3%) with flaccid paralysis.


EV-A71 and EV-D68 were the most detected EV in respiratory specimens. EV-A71 was highly related to neurological disease and EV-D68 was often associated with LRTI. However, both potential relatedness to neurological diseases makes the monitoring of EV circulation obligatory.

Keywords: enteroviruses – respiratory infections – surveillance – genetic diversity – molecular epidemiology – paediatric population

© 2018 Elsevier B.V. All rights reserved.

Keywords: Enterovirus; EV-A71; EV-D68; Rhomboencephalitis; AFP; Spain.


#Varicella-zoster Virus #Clades Circulating in #Spain over two decades (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 28 November 2018 / In Press, Accepted Manuscript

Varicella-zoster Virus Clades Circulating in Spain over two decades

Irene González 1, Alejandro Molina 1, Pilar Pérez-Romero, Juan Emilio Echevarría, Lante He, David Tarragó

Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III, Majadahonda, Spain

Received 5 June 2018, Revised 30 August 2018, Accepted 26 November 2018, Available online 28 November 2018.

DOI: https://doi.org/10.1016/j.jcv.2018.11.008



  • In this first Spanish molecular epidemiological study, encephalitis was more frequent in patients infected with VZV clades within genogroup E, suggesting earlier introduction of these clades.
  • First evidence of recombination in Spain: VZV clade 1 and clade 3 recombinants were found in six cases.
  • VZV clade 2 vaccine strains were found in three patients with herpes zoster and one with neurological disease (encephalitis and retinitis).




Despite childhood universal VZV immunization was introduced in 2015, there are no data on VZV clade distribution in Spain.


To characterize the varicella-zoster virus strains circulating in Spain between 1997 and 2016.

Study Design

In this retrospective study, we determined the VZV clades in 294 patients with different pathologies (mainly encephalitis, zoster and varicella) by sequencing three fragments within ORF 22, ORF 21 and ORF 50 and, subsequently analyzing 7 relevant SNPs.


Among these 294 patients, 132(44.9%) patients were infected by clade 1, 42(14.3%) patients by clade 3, 19(6.5%) by clade 5, 29(9.9%) by clade VI and 3(1%) by clade 4. Four patients (1.4%) were infected by clade 2 vOKA strains, who received one dose of live-attenuated varicella vaccine. Putative recombinant clade 1/3 was identified in 6 cases (2.0%). Results obtained from partial sequences were assigned to clade 1 or 3 in 56(19%) patients and clade 5 or VI in 3(1.0%) patients. In the multivariate analysis, encephalitis was independently associated with clades 1 and 3 and age >14y.o. (P = 0.035 and P = 0.021, respectively). Additionally, Madrid had significant fewer cases of encephalitis compared with the rest of regions analyzed (P = 0.001).


Higher prevalence of clades 1 and 3 and their relation with encephalitis and age >14y.o. suggest earlier introduction of this clades in Spain. Putative interclade 1 and 3 recombinants are circulating in patients with encephalitis, herpes zoster and varicella. Several cases were related to vOKA vaccination but vaccine strains do not seem to circulate in the general population.

Abbreviations: VZV: Varicella-zoster virus – CSF: Cerebral Spinal Fluid – ORF: Open reading frame – vOKA: vaccine-OKA – bp: base pair – y.o.: years old – SNPs: Single Nucleotide Polymorphisms

Keywords: Varicella zoster virus – Recombination – Clade – Genotype – Vaccine – Molecular epidemiology

{1} These authors contributed equally to this study.

© 2018 Elsevier B.V. All rights reserved.

Keywords: Varicella; Encephalitis; Spain; VZV.


Potential role of #dengue virus, #chikungunya virus and #Zika virus in #neurological diseases (Mem Inst Oswaldo Cruz, abstract)

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

Mem Inst Oswaldo Cruz. 2018 Oct 29;113(11):e170538. doi: 10.1590/0074-02760170538.

Potential role of dengue virus, chikungunya virus and Zika virus in neurological diseases.

Vieira MADCES1,2,3, Costa CHN4, Linhares ADC5, Borba AS2, Henriques DF6, Silva EVPD6, Tavares FN5, Batista FMA7, Guimarães HCL7, Martins LC6, Monteiro TAF3,5, Cruz ACR6, Azevedo RDSDS6, Vasconcelos PFDC6.

Author information: 1 Secretaria de Estado da Saúde do Piauí, Instituto de Doenças Tropicais Natan Portella, Departamento de Neurologia, Teresina, PI, Brasil. 2 Fundação Municipal de Saúde de Teresina, Diretoria de Vigilância em Saúde, Teresina, PI, Brasil. 3 Instituto Evandro Chagas, Programa de Pós-Graduação em Virologia, Ananindeua, PA, Brasil. 4 Secretaria de Estado da Saúde do Piauí, Instituto de Doenças Tropicais Natan Portella, Departamento de Infectologia, Teresina, PI, Brasil. 5 Instituto Evandro Chagas, Seção de Virologia Geral, Ananindeua, PA, Brasil. 6 Instituto Evandro Chagas, Seção de Arbovirologia e Febres Hemorrágicas, Ananindeua, PA, Brasil. 7 Secretaria de Estado da Saúde do Piauí, Diretoria da Unidade de Vigilância e Assistência à Saúde, Teresina, PI, Brasil.



This study showed that laboratory markers of recent infection by dengue, Zika or chikungunya arboviruses were detected in the biological samples of approximately one-third of patients with encephalitis, myelitis, encephalomyelitis or Guillain-Barré syndrome, in a surveillance programme in Piauí state, Brazil, between 2015-2016. Fever and myalgia had been associated with these cases. Since in non-tropical countries most infections or parainfectious diseases associated with the nervous system are attributed to herpesviruses, enteroviruses, and Campylobacter jejuni, the present findings indicate that in tropical countries, arboviruses may now play a more important role and reinforce the need for their surveillance and systematic investigation in the tropics.

PMID: 30379197 DOI: 10.1590/0074-02760170538

Keywords: Arbovirus; Chikungunya Fever; Dengue Fever; Zika Virus; Encephalitis; GBS; Encephalomyelitis.


#Upsurge in #echovirus 30 detections in five #EU/EEA countries, April to September, 2018 (Euro Surveill., abstract)

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

Upsurge in echovirus 30 detections in five EU/EEA countries, April to September, 2018

Eeva K Broberg1, Benedetto Simone1, Josep Jansa1, the EU/EEA Member State contributors1

Affiliations: 1 European Centre for Disease Prevention and Control, Stockholm, Sweden

Citation style for this article: Broberg Eeva K, Simone Benedetto, Jansa Josep, the EU/EEA Member State contributors. Upsurge in echovirus 30 detections in five EU/EEA countries, April to September, 2018. Euro Surveill. 2018;23(44):pii=1800537. https://doi.org/10.2807/1560-7917.ES.2018.23.44.1800537

Received: 02 Oct 2018;   Accepted: 30 Oct 2018



An upsurge in Echovirus 30 (E30) infections, associated with meningitis/meningoencephalitis, has been observed in Denmark, Germany, the Netherlands, Norway and Sweden in the period April to September 2018, compared with 2015–2017. In total, 658 E30 infections among 4,537 enterovirus infections were detected in 15 countries between January and September 2018 and affected mainly newborns and 26–45 year-olds. National public health institutes are reminded to remain vigilant and inform clinicians of the ongoing epidemic.

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

Keywords: Echovirus 30; Enterovirus; Viral meningitis; Encephalitis; European Region.


#Human #pegivirus‐1 associated #leukoencephalitis: Clinical and molecular features (Ann Neurol., abstract)

[Source: Annals of Neurology, full page: (LINK). Abstract, edited.]

Human pegivirus‐1 associated leukoencephalitis: Clinical and molecular features

E. Balcom BSc,  M. Doan BSc,  W. G. Branton MSc,  J. Jovel PhD,  G. Blevins MSc MD, B. Edguer MD, T.C. Hobman PhD,  E. Yacyshyn MD,  D. Emery MD,  A. Box MD,  F.K.H. van Landeghem MD, C. Power MD

First published: 24 September 2018 / DOI:  https://doi.org/10.1002/ana.25343

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ana.25343.



Etiologic diagnosis is uncertain in 35‐50% of patients with encephalitis despite its substantial global prevalence and disease burden. We report two adult female patients with fatal leukoencephalitis associated with human pegivirus‐1 (HPgV‐1) brain infection. Neuroimaging showed inflammatory changes in cerebral white matter. Brain‐derived HPgV‐1 RNA sequences clustered phylogenetically with other pegiviruses despite an 87‐nucleotide deletion in the viral NS2 gene. Neuropathology disclosed lymphocyte infiltration and gliosis predominantly in brain white matter. HPgV‐1 NS5A antigen was detected in lymphocytes as well as in astrocytes and oligodendrocytes. HPgV‐1 neuroadaptation should be considered in the differential diagnosis of progressive leukoencephalitis in humans.

This article is protected by copyright. All rights reserved.

Keywords: Encephalitis; Pegivirus 1; Human.


Molecular #epidemiology of #coxsackievirus A6 circulating in #HK reveals common #neurological manifestations and emergence of novel recombinant groups (J Clin Virol., abstract)

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

Molecular epidemiology of coxsackievirus A6 circulating in Hong Kong reveals common neurological manifestations and emergence of novel recombinant groups

Susanna K.P. Lau, Pyrear S.H. Zhao1, Siddharth Sridhar, Cyril C.Y. Yip, Kam Leng Aw-Yong, Elaine Y.Y. Chow, Kelvin C.M. Cheung, Rex W.H. Hui, Ryan Y.H. Leung, Yuki S.K. Lai, Alan K.L. Wu, Kelvin K.W. To, Patrick C.Y. Woo, Kwok-Yung Yuen

DOI: https://doi.org/10.1016/j.jcv.2018.09.002

Published online: September 08, 2018 – Accepted: September 7, 2018 – Received in revised form: August 21, 2018 – Received: May 28, 2018



  • HFMD was the most common diagnosis among patients with CV-A6 infection.
  • Neurological manifestations were commonly observed (25%).
  • CV-A6 circulating in Hong Kong mainly belonged to genotype D5.
  • Three novel recombinant strains (two novel groups RL and RM) were identified.
  • 3D gene was a common recombination site in CV-A6.




Coxsackievirus A6 (CV-A6) represents the predominant enterovirus serotype in Hong Kong, but its epidemiology in our population was unknown.


To examine the clinical and molecular epidemiology of CV-A6 and detect emerging recombinant strains in Hong Kong.

Study design

Nasopharyngeal aspirates (NPAs) from patients with febrile or respiratory illness were subject to RT-PCR for CV-A6 and sequencing of 5′-NCR and VP1. CV-A6-positive samples were further subject to 2C and 3D gene sequencing. Complete genome sequencing was performed on potential recombinant strains.


Thirty-six (0.35%) NPAs were positive for CV-A6 by 5’-NCR RT-PCR and sequencing, 28 of which confirmed by partial VP1 gene sequencing. Among the 28 patients (mainly young children) with CV-A6 infection, hand-foot-and-mouth disease (HFMD) (43%), herpangina (18%) and tonsillitis (11%) were the most common diagnoses. Seven (25%) patients had neurological manifestations, including febrile seizures, encephalitis and meningitis. VP1 gene analysis showed that 24 CV-A6 strains circulating in Hong Kong belonged to genotype D5, while 4 strains belonged to D4. Further 2C and 3D gene analysis revealed eight potential recombinant strains. Genome sequencing of five selected strains confirmed four recombinant strains: HK459455/2013 belonging to recombination group RJ arisen from CV-A6/CV-A4, HK458288/2015 and HK446377/2015 representing novel group RL arisen from CV-A6/CV-A4, and HK462069/2015 representing novel group RM arisen from CV-A6/EV-A71. Recombination breakpoints located at 3D were identified in the latter three recombinant strains, with HK462069/2015 (from a child with encephalitis) having acquired 3D region from EV-A71.


We identified novel recombinant CV-A6 strains in Hong Kong, with 3D being a common recombination site.

Keywords: coxsackievirus A6, hand-foot-and-mouth disease, novel, recombination, epidemiology, Hong Kong

1 Authors contributed the same to the manuscript.

© 2018 Published by Elsevier B.V.

Keywords: HFMD; Coxsackievirus A6; Encephalitis; Meningitis; HK PRC SAR.