scholarly journals Molecular diversity and biennial circulation of enterovirus D68: a systematic screening study in Lyon, France, 2010 to 2016

2018 ◽  
Vol 23 (37) ◽  
Author(s):  
Rolf Kramer ◽  
Marina Sabatier ◽  
Thierry Wirth ◽  
Maxime Pichon ◽  
Bruno Lina ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Effective Population ◽  
Systematic Screening ◽  
Acute Flaccid Myelitis ◽  
Hospitalised Patients ◽  
Screening Study ◽  
Severe Infections ◽  
Enterovirus D68 ◽  
Viral Protein 1 ◽  
Underlying Diseases

Background Understanding enterovirus D68 (EV-D68) circulation patterns as well as risk factors for severe respiratory and neurological illness is important for developing preventive strategies. Methods: Between 2010 and 2016, 11,132 respiratory specimens from hospitalised patients in Lyon, France, were screened for EV-D68 by PCR. Phylogenetic relationships of the viral-protein-1 sequences were reconstructed using maximum-likelihood and Bayesian-Markov-Chain-Monte-Carlo approaches. Results: Overall, 171 infections with a biennial pattern were detected, including seven, one, 55, none, 42, one and 65 cases annually during 2010–16. Children (< 16 years-old; n = 150) were mostly affected and 71% (n = 121) of the total patients were under 5 years-old. In 146 patients with medical reviews, 73% (n = 107) presented with acute respiratory distress. Among paediatric patients with medical reviews (n = 133), 55% (n=73) had an asthma/wheezing history, while among adults (n = 13), 11 had underlying diseases. In total, 45 patients had severe infections and 28 patients needed intensive care unit stays. No acute flaccid myelitis (AFM) was detected. We found genotypes A, B1, B2 B3 and D circulating, and no associations between these and clinical presentations. During the study, new genotypes continuously emerged, being replaced over time. We estimated that ancestors of currently circulating genotypes emerged in the late-1990s to 2010. Rises of the EV-D68 effective population size in Lyon coincided with infection upsurges. Phylogenetic analyses showed ongoing diversification of EV-D68 worldwide, coinciding with more infections in recent years and increases of reported AFM paediatric cases. Conclusions: Reinforcement of diagnostic capacities and clinical-based surveillance of EV-D68 infections is needed in Europe to assess the EV-D68 burden.

scholarly journals Detection of enterovirus D68 in patients hospitalised in three tertiary university hospitals in Germany, 2013 to 2014

2016 ◽  
Vol 21 (19) ◽  
Author(s):  
Sindy Böttcher ◽  
Christiane Prifert ◽  
Benedikt Weißbrich ◽  
Ortwin Adams ◽  
Souhaib Aldabbagh ◽  
...  
Keyword(s):  
Binding Sites ◽  
Sequence Data ◽  
Phylogenetic Analyses ◽  
University Hospitals ◽  
Capsid Region ◽  
Hospitalised Patients ◽  
Significant Difference ◽  
Tertiary Hospitals ◽  
Enterovirus D68 ◽  
Viral Protein 1

Enterovirus D68 (EV-D68) has been recognised as a worldwide emerging pathogen associated with severe respiratory symptoms since 2009. We here report EV-D68 detection in hospitalised patients with acute respiratory infection admitted to three tertiary hospitals in Germany between January 2013 and December 2014. From a total of 14,838 respiratory samples obtained during the study period, 246 (1.7%) tested enterovirus-positive and, among these, 39 (15.9%) were identified as EV-D68. Infection was observed in children and teenagers (0–19 years; n=31), the majority (n=22) being under five years-old, as well as in adults > 50 years of age (n=8). No significant difference in prevalence was observed between the 2013 and 2014 seasons. Phylogenetic analyses based on viral protein 1 (VP1) sequences showed co-circulation of different EV-D68 lineages in Germany. Sequence data encompassing the entire capsid region of the genome were analysed to gain information on amino acid changes possibly relevant for immunogenicity and revealed mutations in two recently described pleconaril binding sites.

scholarly journals Molecular epidemiological study of enterovirus D68 in hospitalised children in Hong Kong in 2014–2015 and their complete coding sequences

2019 ◽  
Vol 6 (1) ◽  
pp. e000437
Author(s):  
Haichao Wang ◽  
Kinpong Tao ◽  
Cheuk Yin Leung ◽  
Kam Lun Hon ◽  
C M Apple Yeung ◽  
...  
Keyword(s):  
Hong Kong ◽  
Vaccine Development ◽  
Public Awareness ◽  
Respiratory Illness ◽  
Molecular Classification ◽  
Human Enterovirus ◽  
Coding Sequences ◽  
Acute Flaccid Myelitis ◽  
Hospitalised Patients ◽  
Enterovirus D68

BackgroundHuman enterovirus D68 (EV-D68) was first isolated in 1962 and has aroused public concern recently because of a nationwide outbreak among children in 2014–2015 in the USA. The symptoms include fever, runny nose, sneezing, cough and muscle pains. It might be associated with severe respiratory illness in individuals with pre-existing respiratory conditions and its potential association with acute flaccid myelitis is under investigation. In Asia, EV-D68 cases have been reported in several countries.The studyWe aimed to understand the EV-D68 prevalence and their genetic diversity in Hong Kong children.MethodsA total of 10 695 nasopharyngeal aspirate (NPA) samples from hospitalised patients aged <18 years were collected from September 2014 to December 2015 in two regional hospitals. NPAs tested positive for enterovirus/rhinovirus (EV/RV) were selected for genotyping. For those identified as EV-D68, their complete coding sequences (CDSs) were obtained by Sanger sequencing. A maximum-likelihood phylogeny was constructed using all EV-D68 complete coding sequences available in GenBank (n=482).Results2662/10 695 (24.9%) were tested positive with EV/RV and 882/2662 (33.1%) were selected randomly and subjected to molecular classification. EV-D68 was detected in 15 (1.70%) samples from patients with clinical presentations ranging from wheezing to pneumonia and belonged to subclade B3. Eight CDSs were successfully obtained. A total of 10 amino acid residue polymorphisms were detected in the viral capsid proteins, proteases, ATPase and RNA polymerase.ConclusionB3 subclade was the only subclade found locally. Surveillance of EV-D68 raises public awareness and provides the information to determine the most relevant genotypes for vaccine development.

Enterovirus D-68 Molecular Virology, Epidemiology, and Treatment: an update and way forward

2020 ◽  
Vol 20 ◽  
Author(s):  
Mahmoud Ahmed Ebada ◽  
Notila Fayed ◽  
Souad Alkanj ◽  
Ahmed Wadaa Allah
Keyword(s):  
Current Knowledge ◽  
Rna Virus ◽  
Neurological Diseases ◽  
Cross Reactivity ◽  
Serological Tests ◽  
Molecular Virology ◽  
Acute Flaccid Myelitis ◽  
The Family ◽  
Pcr Products ◽  
Enterovirus D68

: Enterovirus D68 (EV-D68) is a single-stranded positive-sense RNA virus, and it is one of the family Picornaviridae. Except for EV-D68, the family Picornaviridae has been illustrated in literature. EV-D68 was first discovered and isolated in California, USA, in 1962. EV-D68 has resulted in respiratory disorders’ outbreaks among children worldwide, and it has been detected in cases of various neurological diseases such as acute flaccid myelitis (AFM). A recent study documented a higher number of EV-D68 cases associated with AFM in Europe in 2016 compared to the 2014 outbreak. EV-D68 is mainly diagnosed by quantitative PCR, and there is an affirmative strategy for EV-D68 detection by using pan-EV PCR on the untranslated region and/or the VP1 or VP2, followed by sequencing of the PCR products. Serological tests are limited due to cross-reactivity of the antigens between the different serotypes. Many antiviral drugs for EV-D68 have been evaluated, and showed promising results. In our review, we discuss the current knowledge about EV-D68 and its role in the development of AFM.

scholarly journals Enteroviruses in Respiratory Samples from Paediatric Patients of a Tertiary Care Hospital in Germany

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 882
Author(s):  
Susanne Baertl ◽  
Corinna Pietsch ◽  
Melanie Maier ◽  
Mario Hönemann ◽  
Sandra Bergs ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Analyses ◽  
Tertiary Care ◽  
Oxygen Demand ◽  
Care Hospital ◽  
Paediatric Patients ◽  
Enterovirus A71 ◽  
Coxsackievirus A6 ◽  
Enterovirus D68 ◽  
Tract Infections

Enteroviruses are associated with various diseases accompanied by rare but severe complications. In recent years, outbreaks of enterovirus D68 and enterovirus A71 associated with severe respiratory infections and neurological complications have been reported worldwide. Since information on molecular epidemiology in respiratory samples is still limited, the genetic diversity of enteroviruses was retrospectively analysed over a 4-year period (2013–2016) in respiratory samples from paediatric patients. Partial viral major capsid protein gene (VP1) sequences were determined for genotyping. Enteroviruses were detected in 255 (6.1%) of 4187 specimens. Phylogenetic analyses of 233 (91.4%) strains revealed 25 different genotypes distributed to Enterovirus A (39.1%), Enterovirus B (34.3%), and Enterovirus D (26.6%). The most frequently detected genotypes were enterovirus D68 (26.6%), coxsackievirus A6 (15.9%), and enterovirus A71 (7.3%). Enterovirus D68 detections were associated with lower respiratory tract infections and increased oxygen demand. Meningitis/encephalitis and other neurological symptoms were related to enterovirus A71, while coxsackievirus A6 was associated with upper respiratory diseases. Prematurity turned out as a potential risk factor for increased oxygen demand during enterovirus infections. The detailed analysis of epidemiological and clinical data contributes to the non-polio enterovirus surveillance in Europe and showed high and rapidly changing genetic diversity of circulating enteroviruses, including different enterovirus D68 variants.

scholarly journals Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016

2019 ◽  
Vol 24 (7) ◽  
Author(s):  
Rubén González-Sanz ◽  
Didac Casas-Alba ◽  
Cristian Launes ◽  
Carmen Muñoz-Almagro ◽  
María Montserrat Ruiz-García ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Phylogenetic Analyses ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Asia Pacific ◽  
Enterovirus A71 ◽  
Hospitalised Patients ◽  
Wide Range ◽  
Large Outbreak

Introduction Enterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, however, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions. Aim Our objective was to investigate the epidemiology and clinical characteristics of the outbreak. Methods We carried out a retrospective study which included 233 EV-A71-positive samples collected during 2016 from hospitalised patients. We analysed the clinical manifestations associated with EV-A71 infections and performed phylogenetic analyses of the 3’-VP1 and 3Dpol regions from all Spanish strains and a set of EV-A71 from other countries. Results Most EV-A71 infections were reported in children (mean age: 2.6 years) and the highest incidence was between May and July 2016 (83%). Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Moreover, we found a clear association of EV-A71-C1 infection with severe neurological disorders, brainstem encephalitis being the most commonly reported. Conclusion An emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases.

Genetic analysis of Enterovirus D68 associated with pneumonia in children from South India

2021 ◽  
Vol 70 (5) ◽  
Author(s):  
Ramachandran Erathodi Sanjay ◽  
Sasidharanpillai Sabeena ◽  
Sudandiradas Robin ◽  
John T. Shaji ◽  
M. P. Jayakrishnan ◽  
...  
Keyword(s):  
South India ◽  
Single Case ◽  
Respiratory Illness ◽  
Neurological Complications ◽  
The Novel ◽  
Acute Flaccid Myelitis ◽  
Sporadic Cases ◽  
Enterovirus D68 ◽  
Kerala State ◽  
Unique Amino Acid

EV-D68 is an emerging enterovirus infection associated with severe acute respiratory illness (SARI), acute flaccid myelitis (AFM) and acute flaccid paralysis (AFP). While EV-D68 outbreaks and sporadic cases are reported globally, a single case has been reported from India. The present study aims to investigate the molecular epidemiology and clinical characteristics of EV-D68-associated SARI cases from South India. We screened influenza-negative archived throat swab specimens from Influenza-Like Illness (ILI) and SARI cases (n=959; 2016 to 2018 period) for enteroviruses by pan-enterovirus real-time RT-PCR. Thirteen samples positive for enteroviruses were typed by PCR and sequencing based on VPI, VP2 and/or 5′NCR regions. One EV-D68 RNA sample was subjected to next-generation sequencing for whole genome characterisation. Among 13 enterovirus cases, four were ECHO-11, three EV-D68, two CV-A16 and one each EV-71, CV-B1, CV-B2 and CV-A9. All three cases of EV-D68 infection were reported in children below 2 years of age from Kerala state of South India during June and July 2017. The patients developed pneumonia without any neurological complications. Sequencing based on VPI and 5′NCR regions showed that EV-D68 strains belong to the novel subclade B3. The EV-D68 complete genome identified with two unique amino acid substitutions in VP1 (T-246-I) and 3D (K-344-R) regions. This study reiterates the EV-D68 novel subclade B3 circulation in India and indicates the urgent need for structured EV-D68 surveillance in the country to describe the epidemiology.

scholarly journals Acute Flaccid Myelitis Cases Presenting During a Spike in Respiratory Enterovirus D68 Circulation: Case Series From a Single Pediatric Referral Center.

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S305-S306 ◽  
Author(s):  
Samia Naccache ◽  
Jeffery Bender ◽  
Jay Desai ◽  
Tam Van ◽  
Lindsay Meyers ◽  
...  
Keyword(s):  
Case Series ◽  
Acute Onset ◽  
Case Definition ◽  
Rt Pcr ◽  
Significant Past Medical History ◽  
Upper Respiratory Infection ◽  
Acute Flaccid Myelitis ◽  
Enterovirus D68 ◽  
Ebv Dna ◽  
Work Up

Abstract Background In 2014, a global outbreak of Enterovirus D68 (EV-D68) caused severe respiratory disease and was associated with an increase in acute flaccid myelitis (AFM) cases. Despite heightened surveillance, both EV-D68 detection and AFM reporting dropped in 2015. As AFM reporting increased in 2016, we sought to better understand AFM and EV-D68 epidemiology at our institution. Methods Chart review of clinical presentation and workup was conducted on patients meeting the case definition for AFM for 2015-16. To determine EV-D68 prevalence at CHLA, samples positive for Rhinovirus/Enterovirus (RV/EV) by FilmArray® Respiratory Panel (FA-RP) in September 2016 were screened for EV-D68 by RT-PCR. Results were compared with a research algorithm developed within the FilmArray®Trend epidemiology software. After establishing accurate EV-D68 prediction, the algorithm was used on historic FA-RP assays to measure EV-D68 prevalence at CHLA in 2015 and 2016. Results 7 patients with a median age of 3.3 years and no significant past medical history presented with AFM between July 15 - October 15, 2016, while none were identified in 2015. All had acute onset patchy weakness involving mostly the upper limbs and grey matter involvement on MRI. 6/7 reported fever/upper respiratory infection prior to AFM onset. CSF from 7/7 was negative by FilmArray®meningitis/encephalitis Panel and 2/7 were positive for EBV DNA. Further work up on CSF and blood were negative. 4/7 (57.1%) patients were RV/EV positive from respiratory samples and 3 were confirmed as EV-D68 by RT-PCR. IVIG was given in 7/7 cases. Patients were discharged after an average of 8.8 (4.8-13.6) days. The FilmArray Trend monitoring revealed that during the time of AFM presentation in 2016, 226/778 patients tested for respiratory viruses by the FA-RP were positive for RV/EV. Of those, 29.2% (66/226) were positive for EV-D68 compared with 0.02% (2/224) over the same period in 2015. Conclusion As shown by CDC surveillance data, we saw a resurgence of AFM cases in 2016 compared with 2015. All 7 patients identified were previously healthy and had persistent weakness at discharge. Cases were accompanied by increases in circulating respiratory EV-D68. Further investigation of the correlation between EV-D68 resurgence and AFM is warranted. Disclosures L. Meyers, BioFire Diagnostics: Employee, Salary. J. Jones, Biofire Diagnostics LLC: Employee, Salary. J. Dien Bard, BioFire: Consultant and Investigator, Research grant and Speaker honorarium.

scholarly journals Cardiopulmonary failure as a result of brainstem encephalitis caused by enterovirus D68

2019 ◽  
Vol 12 (11) ◽  
pp. e231990 ◽  
Author(s):  
Naoki Yogo ◽  
Tomohiko Imamura ◽  
Yuichiro Muto ◽  
Katsuki Hirai
Keyword(s):  
Severe Illness ◽  
Brainstem Encephalitis ◽  
Limb Weakness ◽  
Respiratory Illnesses ◽  
Acute Flaccid Myelitis ◽  
Cardiopulmonary Failure ◽  
Enterovirus A71 ◽  
Bulbar Paralysis ◽  
The Usa ◽  
Enterovirus D68

Enterovirus D68 (EV-D68) causes respiratory illnesses such as pneumonia, and has been reported to cause acute flaccid myelitis. Enterovirus A71 (EV-A71) is known to cause cardiopulmonary failure due to brainstem encephalitis, but there have been few reports of these conditions being associated with EV-D68. Outbreaks of EV-D68 infection have occurred in the USA, Canada, Europe and Asia. Clinical management is largely supportive and there are no specific antivirals available. The case patient, a 4-year-old girl, had cardiopulmonary failure due to brainstem encephalitis. EV-D68 was isolated from a throat swab. On admission, she had cardiopulmonary failure, which required intensive care using a ventilator and inotropic agents. Her cardiac function improved, but she had residual bulbar paralysis and limb weakness, which resolved over a 6-month period. This case confirms that EV-D68, may cause severe illness due to brainstem encephalitis, similar to that caused by EV-A71.

scholarly journals Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Alison M. Hixon ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Sialic Acid ◽  
Motor Neuron ◽  
Axonal Transport ◽  
Motor Neurons ◽  
The United States ◽  
Retrograde Axonal Transport ◽  
Spinal Motor Neurons ◽  
Acute Flaccid Myelitis ◽  
Spinal Motor ◽  
Enterovirus D68

ABSTRACTEnterovirus D68 (EV-D68) is an emerging virus that has been identified as a cause of recent outbreaks of acute flaccid myelitis (AFM), a poliomyelitis-like spinal cord syndrome that can result in permanent paralysis and disability. In experimental mouse models, EV-D68 spreads to, infects, and kills spinal motor neurons following infection by various routes of inoculation. The topography of virus-induced motor neuron loss correlates with the pattern of paralysis. The mechanism(s) by which EV-D68 spreads to target motor neurons remains unclear. We sought to determine the capacity of EV-D68 to spread by the neuronal route and to determine the role of known EV-D68 receptors, sialic acid and intracellular adhesion molecule 5 (ICAM-5), in neuronal infection. To do this, we utilized a microfluidic chamber culture system in which human induced pluripotent stem cell (iPSC) motor neuron cell bodies and axons can be compartmentalized for independent experimental manipulation. We found that EV-D68 can infect motor neurons via their distal axons and spread by retrograde axonal transport to the neuronal cell bodies. Virus was not released from the axons via anterograde axonal transport after infection of the cell bodies. Prototypic strains of EV-D68 depended on sialic acid for axonal infection and transport, while contemporary circulating strains isolated during the 2014 EV-D68 outbreak did not. The pattern of infection did not correspond with the ICAM-5 distribution and expression in either human tissue, the mouse model, or the iPSC motor neurons.IMPORTANCEEnterovirus D68 (EV-D68) infections are on the rise worldwide. Since 2014, the United States has experienced biennial spikes in EV-D68-associated acute flaccid myelitis (AFM) that have left hundreds of children paralyzed. Much remains to be learned about the pathogenesis of EV-D68 in the central nervous system (CNS). Herein we investigated the mechanisms of EV-D68 CNS invasion through neuronal pathways. A better understanding of EV-D68 infection in experimental models may allow for better prevention and treatment strategies of EV-D68 CNS disease.

scholarly journals Enteroviruses: A Gut-Wrenching Game of Entry, Detection, and Evasion

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 460 ◽  
Author(s):  
Alexandra I. Wells ◽  
Carolyn B. Coyne
Keyword(s):  
Enterovirus 71 ◽  
Febrile Illness ◽  
Oral Route ◽  
Life Cycles ◽  
Innate Immune ◽  
Acute Flaccid Myelitis ◽  
Innate Immune Signaling ◽  
Intracellular Proteins ◽  
Enterovirus D68 ◽  
Gastrointestinal Epithelium

Enteroviruses are a major source of human disease, particularly in neonates and young children where infections can range from acute, self-limited febrile illness to meningitis, endocarditis, hepatitis, and acute flaccid myelitis. The enterovirus genus includes poliovirus, coxsackieviruses, echoviruses, enterovirus 71, and enterovirus D68. Enteroviruses primarily infect by the fecal–oral route and target the gastrointestinal epithelium early during their life cycles. In addition, spread via the respiratory tract is possible and some enteroviruses such as enterovirus D68 are preferentially spread via this route. Once internalized, enteroviruses are detected by intracellular proteins that recognize common viral features and trigger antiviral innate immune signaling. However, co-evolution of enteroviruses with humans has allowed them to develop strategies to evade detection or disrupt signaling. In this review, we will discuss how enteroviruses infect the gastrointestinal tract, the mechanisms by which cells detect enterovirus infections, and the strategies enteroviruses use to escape this detection.

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