#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.



#Severe atypical #HFMD in #adults due to #Coxsackievirus A6: #clinical presentation and Phylogenesis of CV-A6 Strains (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 17 November 2018 / In Press, Accepted Manuscript

Severe atypical hand-foot-and-mouth disease in adults DUE TO Coxsackievirus A6: clinical presentation and PHYLOGENESIS of CV-A6 STRAINS

F. Broccolo {a1}; F. Drago {b1}; G. Ciccarese {b}; A. Genoni {c}; A. Puggioni {c}; GM Rosa {d}; A. Parodi {b}; H.Manukyan {e}; M. Laassri {e}; K. Chumakov {e}; A. Toniolo {c}

{a} Department of Medicine and Surgery, School of Medicine, University of Milano-Bicocca, Monza, Italy; {b} DISSAL Department of Dermatology, IRCCS San Martino-IST, Genoa, Italy; {c} Clinical Microbiology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; {d} Department of Internal Medicine, Cardiology, Ospedale Policlinico San Martino, Genoa, Italy; {e} Office for Vaccines Research and Review, FDA Center for Biologics Evaluation and Research, Silver Spring, MD, USA

Received 26 July 2018, Revised 10 November 2018, Accepted 16 November 2018, Available online 17 November 2018.

DOI: https://doi.org/10.1016/j.jcv.2018.11.003



  • Typically, HFMD is a mild pediatric illness associated with group-A enteroviruses.
  • In Italy, unrelated adult cases of severe HFMD were caused by coxsackievirus A6.
  • Italian CV-A6 strains and that of a German child mapped into a single cluster.
  • The Italian and German strains were close to previous Chinese and Japanese strains.
  • CV-A6 is spreading worldwide with skin manifestations in both children and adults.




Typically, hand-foot-and-mouth disease (HFMD) is a mild childhood illness associated with coxsackievirus (CV)-A16, CV-A6, enterovirus (EV)-A71.


To identify the viral agents associated with severe cases of atypical HFMD in Italy.

Study design

Epidemiologically unrelated cases of severe atypical HFMD admitted to the Emergency Room (ER) of IRCCS San Martino IST (Genoa, Italy) in 2014-2016 were investigated. Serologic screening for viral positivity was performed against exanthem-inducing agents. Ten cases with serology indicative of recent EV infection were selected. Molecular assays were used to detect viral genomes in blood [EVs, Parvovirus B19 (PVB19), herpesviruses (CMV; EBV, HHV-6, -7, -8)].


CV-A6 was detected in 10 cases of severe atypical HFMD. Two cases were also infected with PVB19. Herpesviruses were not detected. Phylogenetic analysis mapped the CV-A6 strains into a single cluster related to two recent isolates from a German and an Asian child. Fever, systemic symptoms, severe vasculitis-like rash, and enanthem were predominant at presentation. Spontaneous recovery occurred in 1-3 weeks.


CV-A6 is emerging as a frequent cause of severe atypical HFMD in Italian adults. This viral agent is disseminating worldwide. Dermatologists must identify the manifold alterations caused by EVs and understand the diagnostic power of current virology methods.

Keywords: hand foot and mouth disease – enterovirus – coxsackievirus – CV-A6 – atypical – exanthem

{1} These authors contributed equally to the work.

© 2018 Elsevier B.V. All rights reserved.

Keywords: HFMD; Enterovirus; Coxsackievirus A6; Italy.


#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.


#Assessment of #blood #enterovirus #PCR testing in #paediatric populations with fever without source, #sepsis-like disease, or suspected #meningitis: a prospective, multicentre, observational cohort study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Assessment of blood enterovirus PCR testing in paediatric populations with fever without source, sepsis-like disease, or suspected meningitis: a prospective, multicentre, observational cohort study

Jérémy Lafolie, PharmD, Prof André Labbé, PhD *, Anne Sophie L’Honneur, PharmD *, Fouad Madhi, MD, Bruno Pereira, PhD, Marion Decobert, MD, Marie Noelle Adam, PhD, François Gouraud, MD, Frédéric Faibis, PhD, Francois Arditty, MD, Stéphanie Marque-Juillet, PhD, Marie Aline Guitteny, PhD, Gisele Lagathu, PhD, Matthieu Verdan, MD, Prof Flore Rozenberg, PhD, Audrey Mirand, PhD, Prof Hélène Peigue-Lafeuille, PhD, Prof Cécile Henquell, PhD †, Jean-Luc Bailly, PhD †, Christine Archimbaud, PhD on behalf of theBlood Enterovirus Diagnosis Infection (BLEDI) in paediatric population study team ‡

Published: October 30, 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30479-1




Enteroviruses are the most frequent cause of acute meningitis and are seen increasingly in sepsis-like disease and fever without source in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by PCR is the gold standard diagnostic test. Our aim was to assess a method of detecting enterovirus in blood specimens by PCR.


We did a prospective, multicentre, observational study at 35 French paediatric and emergency departments in 16 hospitals. We recruited newborn babies (aged ≤28 days) and infants (aged >28 days to ≤2 years) with fever without source, sepsis-like disease, or suspected meningitis, and children (aged >2 years to ≤16 years) with suspected meningitis, who were admitted to a participating hospital. We used a standardised form to obtain demographic, clinical, and laboratory data, which were anonymised. Enterovirus PCR testing was done in blood and CSF specimens.


Between June 1, 2015, and Oct 31, 2015, and between June 1, 2016, and Oct 31, 2016, we enrolled 822 patients, of whom 672 had enterovirus PCR testing done in blood and CSF specimens. Enterovirus was detected in 317 (47%) patients in either blood or CSF, or both (71 newborn babies, 83 infants, and 163 children). Detection of enterovirus was more frequent in blood samples than in CSF specimens of newborn babies (70 [99%] of 71 vs 62 [87%] of 71; p=0·011) and infants (76 [92%] of 83 vs 62 [75%] of 83; p=0·008), and was less frequent in blood samples than in CSF specimens of children (90 [55%] of 163 vs 148 [91%] of 163; p<0·0001). Detection of enterovirus was more frequent in blood samples than in CSF specimens of infants aged 2 years or younger with fever without source (55 [100%] of 55 vs 41 [75%] of 55; p=0·0002) or with sepsis-like disease (16 [100%] of 16 vs nine [56%] of 16; p=0·008). Detection of enterovirus was less frequent in blood than in CSF of patients with suspected meningitis (165 [67%] of 246 vs 222 [90%] of 246; p<0·0001).


Testing for enterovirus in blood by PCR should be an integral part of clinical practice guidelines for infants aged 2 years or younger. This testing could decrease the length of hospital stay and reduce exposure to antibiotics for low-risk patients admitted to the emergency department with febrile illness.


University Hospital Clermont-Ferrand.

Keywords: Enterovirus; Diagnostic tests.


#Enteroviral #Infection Leads To Transactive Response Dna-Binding Protein 43 #Pathology in vivo (Am J Pathol., abstract)

[Source: American Journal of Pathology, full page: (LINK). Abstract, edited.]

Enteroviral Infection Leads To Transactive Response Dna-Binding Protein 43 Pathology in vivo

Yuan Chao Xue, Chelsea M. Ruller, Gabriel Fung, Yasir Mohamud, Haoyu Deng, Huitao Liu, Jingchun Zhang, Ralph Feuer, Honglin Luo

DOI: https://doi.org/10.1016/j.ajpath.2018.08.013

Published online: September 28, 2018 – Accepted: August 30, 2018 – Received in revised form: August 17, 2018 – Received: March 7, 2018



(1) Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons in the cerebral cortex, brainstems, and spinal cord, leading to progressive paralysis and eventual death. About 95% of all ALS cases are sporadic without known causes. Enteroviruses have been suspected to play a role in ALS due to their ability to target motor neurons and cause muscle weakness and paralysis. I vitro enteroviral infection results in cytoplasmic aggregation and cleavage of transactive response DNA binding protein-43 (TDP-43), a pathological hallmark of ALS. However, whether enteroviral infection can induce ALS-like pathologies in vivo remains to be characterized. In this study, neonatal BALB/C mice were intracranially inoculated with either a recombinant coxsackievirus B3 expressing enhanced GFP or mock-infected for 2, 5, 10, 30, and 90 days. Histological and imunohistochemical analysis of brain tissues demonstrated sustained inflammation (microglia and astrogliosis) and lesions in multiple regions of the brain (hippocampus, cerebral cortex, striatum, olfactory bulb, and putamen) in parallel with virus detection as early as two days for up to 90 days post-infection. Most notably, ALS-like pathologies, including cytoplasmic mislocalization of TDP-43, p62-, and ubiquitin-positive inclusions, were observed in the areas of infection. These data provide the first pathological evidence supporting a possible link between enteroviral infection and ALS.

Funding: Supported by the Canadian Institutes of Health Research (PJT-159546, to H.L.), the ALS Canada (to H.L.), and the Natural Sciences and Engineering Research Council (RGPIN-2016-03811, to H.L.). Y.M. and D.H. are the recipients of a four-year PhD fellowship from the University of British Columbia.

Disclosures: None declared.

© 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Keywords: Enterovirus; Coxsackievirus; ALS; Animal Models; Neurology.


Emerging #Enteroviruses Causing #HFMD, #China, 2010–2016 (Emerg Infect Dis., abstract)

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

Volume 24, Number 10—October 2018 / Dispatch

Emerging Enteroviruses Causing Hand, Foot and Mouth Disease, China, 2010–2016

Yu Li1, Zhaorui Chang1, Peng Wu1, Qiaohong Liao, Fengfeng Liu, Yaming Zheng, Li Luo, Yonghong Zhou, Qi Chen, Shuanbao Yu, Chun Guo, Zhenhua Chen, Lu Long, Shanlu Zhao, Bingyi Yang, Hongjie Yu2  , and Benjamin J. Cowling

Author affiliations: Chinese Center for Disease Control and Prevention. Beijing, China (Y. Li, Z. Chang, Q. Liao, F. Liu, Y. Zheng, L. Luo, S. Yu, H. Yu); The University of Hong Kong, Hong Kong, China (Y. Li, P. Wu, B. Yang, B.J. Cowling); Fudan University, Shanghai, China (Y. Zhou, H. Yu); Hubei Center for Disease Prevention and Control, Wuhan, China (Q. Chen); Huazhong University of Science and Technology, Wuhan, China (C. Guo); Chengdu Center for Disease Prevention and Control, Chengdu, China (Z. Chen); Sichuan University, Chengdu, China (L. Long); Hunan Center for Disease Prevention and Control, Changsha, China (S. Zhao)



Coxsackievirus A6 emerged as one of the predominant causative agents of hand, foot and mouth disease epidemics in many provinces of China in 2013 and 2015. This virus strain accounted for 25.9% of mild and 15.2% of severe cases in 2013 and 25.8% of mild and 16.9% of severe cases in 2015.

Keywords: HFMD; Enterovirus; Coxsackievirus A6; China.


Hypoglycemic #Toxins and #Enteroviruses as Causes of #Outbreaks of Acute #Encephalitis-Like Syndrome in #Children, Bac Giang Province, Northern #Vietnam (Emerg Infect Dis., abstract)

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

Volume 24, Number 8—August 2018 / Research

Hypoglycemic Toxins and Enteroviruses as Causes of Outbreaks of Acute Encephalitis-Like Syndrome in Children, Bac Giang Province, Northern Vietnam

Nga Thi Phan1, Meriadeg Ar Gouilh1, Juliette Paireau, Loan Phuong, Justine Cheval, Nghia Duy Ngu, Charles Hébert, Tuan Hai Nguyen, Olivier Lortholary, Laura Tondeur, Jean-Claude Manuguerra, Robert Barouki, Johannes Sander, Nils Janzen, Hien Tran Nguyen, Paul T. Brey, Arnaud Fontanet2, and Marc Eloit2

Author affiliations: National Institute of Hygiene and Epidemiology, Hanoi, Vietnam (N.T. Phan, L.P. Do, N.D. Ngu, T.H. Nguyen, H.T. Nguyen); Institut Pasteur, Paris, France (M. Ar Gouilh, J. Paireau, L. Tondeur, J.-C. Manuguerra, A. Fontanet, M. Eloit); Centre National de la Recherche Scientifique, Paris (J. Paireau); Pathoquest, Paris (J. Cheval, C. Hébert, M. Eloit); Hôpital Necker-Enfants Malades, Paris (O. Lortholary, R. Barouki); Université Paris Descartes, Paris (O. Lortholary, R. Barouki); Institut National de la Santé et de la Recherche Médicale, Paris (R. Barouki); Screening Laboratory Hannover, Germany (J. Sander, N. Janzen); Hannover Medical School, Hannover (N. Janzen); Institut Pasteur du Laos, Vientiane, Laos (P.T. Bray); Conservatoire National des Arts et Métiers, Paris (A. Fontanet)



We investigated the cause of seasonal outbreaks of pediatric acute encephalitis-like syndrome associated with litchi harvests (May–July) in northern Vietnam since 2008. Nineteen cerebrospinal fluid samples were positive for human enterovirus B, and 8 blood samples were positive for hypoglycemic toxins present in litchi fruits. Patients who were positive for hypoglycemic toxins had shorter median times between disease onset and admission, more reports of seizures, more reports of hypoglycemia (glucose level ❤ mmol/L), lower median numbers of leukocytes in cerebrospinal fluid, and higher median serum levels of alanine aminotransferase and aspartate transaminase than did patients who were positive for enteroviruses. We suggest that children with rapidly progressing acute encephalitis-like syndrome at the time of the litchi harvest have intoxication caused by hypoglycemic toxins, rather than viral encephalitis, as previously suspected. These children should be urgently treated for life-threatening hypoglycemia.

Keywords: Encephalitis; Vietnam; Neurotoxins; Enterovirus.