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1. Severe enterovirus infections in patients with immune-mediated inflammatory diseases receiving anti-CD20 monoclonal antibodies

Author

Eric Hachulla, Alexis Mathian, Luc Mouthon, Bertrand Dunogue, Benjamin Terrier, Adrien Lemaignen, Fabienne Coury-Lucas, Virginie Rieu, Hélène Chaussade, Aurélie Ruet, Jerome Hadjadj, Gregoire Martin de Fremont, Maelle le Besnerais, Hélène Chabrolles, Audrey Mirand, Anne Sophie L'Honneur, Nicolas Mélé, David Boutboul, Meryem Farhat, Mouna Lazrek, Sonia Burrel, Isabelle Schuffenecker, Karl Stefic, Marion Carrette, and Veronique Avettand-Fenoel

Subjects
Medicine
Abstract

Objective Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs).Methods Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis.Results Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5–10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3–6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown.Conclusion EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.

Published
2024
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2. Sudden Infant Death Associated with Rhinovirus Infection

Author

Christelle Auvray, Stéphanie Perez-Martin, Isabelle Schuffenecker, Cécile Pitoiset, Georges Tarris, Katia Ambert-Balay, Laurent Martin, Nathalie Dullier-Taillefumier, Jean-Baptiste Bour, and Catherine Manoha

Subjects
infant, sudden death, rhinovirus, cerebrospinal fluid, fatal, virus, Microbiology, QR1-502
Abstract

A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant’s environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS.

Published
2024
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3. Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe

Author

Kimberley S.M. Benschop, Eeva K. Broberg, Emma Hodcroft, Dennis Schmitz, Jan Albert, Anda Baicus, Jean-Luc Bailly, Gudrun Baldvinsdottir, Natasa Berginc, Soile Blomqvist, Sindy Böttcher, Mia Brytting, Erika Bujaki, Maria Cabrerizo, Cristina Celma, Ondrej Cinek, Eric C.J. Claas, Jeroen Cremer, Jonathan Dean, Jennifer L. Dembinski, Iryna Demchyshyna, Sabine Diedrich, Susanne Dudman, Jake Dunning, Robert Dyrdak, Mary Emmanouil, Agnes Farkas, Cillian De Gascun, Guillaume Fournier, Irina Georgieva, Ruben Gonzalez-Sanz, Jolanda van Hooydonk-Elving, Anne J. Jääskeläinen, Ruta Jancauskaite, Kathrin Keeren, Thea K. Fischer, Sidsel Krokstad, Lubomira Nikolaeva–Glomb, Ludmila Novakova, Sofie E. Midgley, Audrey Mirand, Richard Molenkamp, Ursula Morley, Joël Mossong, Svajune Muralyte, Jean-Luc Murk, Trung Nguyen, Svein A. Nordbø, Riikka Österback, Suzan Pas, Laura Pellegrinelli, Vassiliki Pogka, Birgit Prochazka, Petra Rainetova, Marc Van Ranst, Lieuwe Roorda, Isabelle Schuffenecker, Rob Schuurman, Asya Stoyanova, Kate Templeton, Jaco J. Verweij, Androniki Voulgari-Kokota, Tytti Vuorinen, Elke Wollants, Katja C. Wolthers, Katherina Zakikhany, Richard Neher, Heli Harvala, and Peter Simmonds

Subjects
Molecular epidemiology, evolutionary trajectory, epidemiological monitoring, whole-genome sequencing, genetic recombination, neurological manifestations, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016–2018. Most E30 cases affected persons 0–4 years of age (29%) and 25–34 years of age (27%). Sequences were divided into 6 genetic clades (G1–G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.

Published
2021
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4. Severe Acute Flaccid Myelitis Associated With Enterovirus in Children: Two Phenotypes for Two Evolution Profiles?

Author

Melodie Aubart, Cyril Gitiaux, Charles Joris Roux, Raphael Levy, Isabelle Schuffenecker, Audrey Mirand, Nathalie Bach, Florence Moulin, Jean Bergounioux, Marianne Leruez-Ville, Flore Rozenberg, Delphine Sterlin, Lucile Musset, Denise Antona, Nathalie Boddaert, Shen Ying Zhang, Manoelle Kossorotoff, and Isabelle Desguerre

Subjects
enterovirus, myelitis, children, EV-D68, EV-A71, Neurology. Diseases of the nervous system, RC346-429
Abstract

Acute flaccid myelitis (AFM) is an acute paralysis syndrome defined by a specific inflammation of the anterior horn cells of the spinal cord. From 2014, worrying waves of life-threatening AFM consecutive to enterovirus infection (EV-D68 and EV-A71) have been reported. We describe 10 children displaying an AFM with an EV infection, the treatments performed and the 1 to 3-years follow-up. Two groups of patients were distinguished: 6 children (“polio-like group”) had severe motor disability whereas 4 other children (“brainstem group”) displayed severe brainstem weakness requiring ventilation support. Electrodiagnostic studies (n = 8) support the presence of a motor neuronopathy associated to myelitis. The best prognosis factor seems to be the motor recovery after the first 4 weeks of the disease.

Published
2020
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5. Analytical Performances of the Panther Fusion System for the Detection of Respiratory Viruses in the French National Reference Centre of Lyon, France

Author

Maxime Pichon, Martine Valette, Isabelle Schuffenecker, Geneviève Billaud, and Bruno Lina

Subjects
respiratory viruses, influenza, diagnostic PCR, performance evaluation, automation, respiratory tract samples, Biology (General), QH301-705.5
Abstract

Respiratory infection are mainly caused by viral pathogens. During the 2017–2018 epidemic season, Panther Fusion® Respiratory kits (Influenza virus A&B (FluA&B), respiratory syncytial virus (RSV), adenovirus (ADV), metapneumovirus (MPV), rhinovirus (RV), parainfluenzae virus (PIV), were compared to the Respiratory MultiWells System r-gene. Respiratory clinical specimens were tested retrospectively (n = 268) and prospectively (n = 463). Analytical performances were determined (sensitivity –Sep-, specificity –Spe- and κ) considering concordances of ≥2 molecular testing specific to each viral target (discrepant results were verified at the National Reference Centres for Enteroviruses or Respiratory viruses, Lyon, France). After retrospective (and prospective) testing, Sep, Spe, and κ were 100% (97.7%), 100% (99%) and 100% (94%) for FluA: 100% (95.5%), 100% (99.3%) and 100% (94%) for FluB, and 100% (88.5%), 100% (98.7%) and 100% (89%) for RSV; 82.1% (41.7%), 100% (99.5%) and 86% (54%) for ADV; 94.7% (73.7%), 96.1% (98.0%) and 91% (65%) for MPV; 96.1% (94.6%), 90.2% (98.5%) and 86% (91%) for HRV; and 90% (72.7%), 100% (99.3%) and 91% (72%), respectively, for PIV. Analytical performances were above 85% for all viruses except for ADV, MPV and PIV, confirming the analytical performance of the Panther Fusion system, a high throughput system with reduced turn-around-time, when compared to non-automated systems.

Published
2020
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6. Risk Assessment and Virological Monitoring Following an Accidental Exposure to Concentrated Sabin Poliovirus Type 3 in France, November 2018

Author

Marion Jeannoël, Denise Antona, Clément Lazarus, Bruno Lina, and Isabelle Schuffenecker

Subjects
poliovirus, incident, accident, risk assessment, containment breach, GAP III, Medicine
Abstract

The safe and secure containment of infectious poliovirus (PV) in facilities where live PV are handled is the condition to achieve and maintain poliomyelitis eradication. Despite precautions to minimize the risk of release of PV from such facilities to the environment, breaches of containment have already been documented. Here, we report the management of an incident that occurred on 30 November 2018 in a French vaccine manufacturing plant. Five adequately vaccinated operators were exposed to a Sabin poliovirus type 3 (PV3) spill. A microbiological risk assessment was conducted and the operators were monitored for PV shedding. On day 5 after exposure, Sabin PV3 was detected only in the stool sample of the most exposed worker. Shedding of Sabin PV3 (as detected by viral culture) was restricted to a very short period (less than 15 days). Monitoring of this incident was an opportunity to assess the relevance of our national response plan. We concluded that the measures undertaken and reported here were appropriate and proportional.

Published
2020
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9. Enterovirus and Parechovirus Coinfection in a Sudden Unexpected Infant Death

Author

Marion Jeannoel, Antoine Biron, Enagnon Kazali Alidjinou, Isabelle Schuffenecker, Marine Dorsi Di Meglio, and Ann-Claire Gourinat

Subjects
Male, Parechovirus, Virus diseases, medicine.disease_cause, Unexpected death, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Enterovirus Infections, Humans, Medicine, Sudden infant death, Enterovirus, Picornaviridae Infections, biology, business.industry, Infant, biology.organism_classification, medicine.disease, Virology, Infant mortality, Pediatrics, Perinatology and Child Health, Coinfection, business, Sudden Infant Death
Abstract

Viruses are suspected to play a role in the multifactorial pathogenesis of sudden infant death. We described a sudden and unexpected death in a 5-month-old boy, with detection of both enterovirus and parechovirus RNA in the blood. This is the first report of a dual viraemia of enterovirus and parechovirus and its potential association with a sudden unexpected infant death. Extensive sampling and testing especially using molecular methods currently available is needed to better understanding the “hypothetical” link between viral infections and sudden infant death.

Published
2020
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10. Severe Acute Flaccid Myelitis Associated With Enterovirus in Children: Two Phenotypes for Two Evolution Profiles?

Author

Delphine Sterlin, Charles Joris Roux, Flore Rozenberg, Mélodie Aubart, Florence Moulin, Isabelle Schuffenecker, Audrey Mirand, Nathalie Boddaert, Cyril Gitiaux, Marianne Leruez-Ville, Shen-Ying Zhang, Nathalie Bach, Manoelle Kossorotoff, Isabelle Desguerre, Denise Antona, Raphael Levy, Lucile Musset, Jean Bergounioux, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], Hôpital Cochin [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Bailly, Jean-Luc

Subjects
Pediatrics, medicine.medical_specialty, Weakness, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Myelitis, macromolecular substances, medicine.disease_cause, lcsh:RC346-429, 03 medical and health sciences, myelitis, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Anterior Horn Cell, children, EV-D68, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, 030212 general & internal medicine, lcsh:Neurology. Diseases of the nervous system, Original Research, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, enterovirus, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Spinal cord, Acute flaccid myelitis, 3. Good health, Poliomyelitis, EV-A71, medicine.anatomical_structure, Neurology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Enterovirus, Neurology (clinical), Brainstem, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

International audience; Acute flaccid myelitis (AFM) is an acute paralysis syndrome defined by a specific inflammation of the anterior horn cells of the spinal cord. From 2014, worrying waves of life-threatening AFM consecutive to enterovirus infection (EV-D68 and EV-A71) have been reported. We describe 10 children displaying an AFM with an EV infection, the treatments performed and the 1 to 3-years follow-up. Two groups of patients were distinguished: 6 children (“polio-like group”) had severe motor disability whereas 4 other children (“brainstem group”) displayed severe brainstem weakness requiring ventilation support. Electrodiagnostic studies (n = 8) support the presence of a motor neuronopathy associated to myelitis. The best prognosis factor seems to be the motor recovery after the first 4 weeks of the disease.

Published
2020
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11. Necrotizing Enterocolitis Cases Associated with Nosocomial Enterovirus Transmission in a Neonatal Unit

Author

Nadine Kacet, Enagnon Kazali Alidjinou, Anny Dewilde, Didier Hober, Ilka Engelmann, Mouna Lazrek, Isabelle Schuffenecker, Fabrice Lapeyre, and Béatrice Pindi

Subjects
Male, Microbiology (medical), viruses, medicine.disease_cause, Infant, Newborn, Diseases, Disease Outbreaks, 03 medical and health sciences, Spatio-Temporal Analysis, 0302 clinical medicine, Enterocolitis, Necrotizing, Intensive Care Units, Neonatal, 030225 pediatrics, Enterovirus Infections, medicine, Humans, 030212 general & internal medicine, Enterovirus, Cross Infection, business.industry, Transmission (medicine), Nosocomial transmission, Infant, Newborn, Outbreak, medicine.disease, Virology, Infectious Diseases, Pediatrics, Perinatology and Child Health, Necrotizing enterocolitis, France, business, Disease transmission
Abstract

Infectious agents including viruses are thought to play a role in the pathogenesis of necrotizing enterocolitis, a well-known gastrointestinal emergency in newborns. Enteroviruses are common pathogens in neonates and have been associated with outbreaks in neonatal units. Enterovirus-associated necrotizing enterocolitis has been described in 3 preterms. Spatiotemporal and molecular analyses have provided evidence of nosocomial transmission.

Published
2018
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12. Repeated viral meningitis in a newborn

Author

Abdulaziz Alhazmi, François Dubos, Enagnon Kazali Alidjinou, Isabelle Schuffenecker, Didier Hober, Ilka Engelmann, and Mouna Lazrek

Subjects
0301 basic medicine, viruses, Picornaviridae, Parechovirus, Disease, medicine.disease_cause, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Recurrence, Virology, Sepsis, medicine, Viral meningitis, Humans, Pleocytosis, Picornaviridae Infections, biology, business.industry, Reverse Transcriptase Polymerase Chain Reaction, Human parechovirus, Infant, Newborn, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, Meningitis, Viral, Enterovirus B, Human, 030104 developmental biology, Neurology, Enterovirus, RNA, Viral, Female, Neurology (clinical), business, Meningitis, 030217 neurology & neurosurgery
Abstract

Human enteroviruses (EV) are the most common cause of viral meningitis in children. Human parechoviruses (HPeV) are increasingly being recognized as a cause of central nervous system (CNS) infections and sepsis-like disease in children. Both viruses belong to Picornaviridae family. The clinical picture in EV and HPeV infections is usually nonspecific. Therefore, molecular detection of both viruses is needed for etiological diagnosis. In this case report, we describe and discuss clinical and laboratory findings of two consecutive episodes of viral meningitis caused by EV and HPeV, respectively, occurring in the first month of a newborn’s life.

Published
2019

13. Emergence of enterovirus D68 clade D1, France, August to November 2018

Author

Laurence Josset, Antonin Bal, Karen Brengel-Pesce, Thierry Wirth, Karl Stefic, F. Morfin, Marianne Coste-Burel, Bruno Lina, Mouna Lazrek, Marina Sabatier, Isabelle Schuffenecker, Centre National de Référence des Entérovirus, Hospices Civils de Lyon (HCL), Laboratoire de Virologie [HCL, Lyon] (Institut des Agents Infectieux), Hospices civils de Lyon (HCL)-HCL Groupement Hospitalier Nord [Lyon]-Centre National de Reference des virus des Infections Respiratoires France Sud [HCL, Lyon], Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BIOMERIEUX, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
0301 basic medicine, Male, Epidemiology, Genetic analysis, Communicable Diseases, Emerging, Disease Outbreaks, respiratory infection, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, Clade, Child, Respiratory Tract Infections, Phylogeny, Aged, 80 and over, Enterovirus D, Human, whole genome sequencing, Respiratory infection, Middle Aged, 3. Good health, Child, Preschool, Population Surveillance, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, Rapid Communication, Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Biology, 03 medical and health sciences, Young Adult, Virology, medicine, Enterovirus Infections, Humans, emergence, Aged, metagenomics, outbreak, Public Health, Environmental and Occupational Health, Outbreak, Infant, enterovirus D68, Sequence Analysis, DNA, Genetic divergence, Molecular Typing, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Enterovirus D68
Abstract

International audience; We report a seasonal increase of enterovirus D68 (EV-D68) cases in France, with 54 cases detected between 19 August and 14 November 2018. Molecular typing revealed that 20 of 32 of the isolates belonged to clade D1, only sporadically detected before in France. Median age of D1-cases was 42 years, 10 developed severe respiratory signs and one had neurological complications. The 2018-D1 viruses showed a genetic divergence of 3.34 % with D1 viruses identified previously.

Published
2019
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14. Aseptic meningitis outbreak associated with echovirus 4 in Northern Europe in 2013–2014

Author

Arthur Löve, Maija Lappalainen, Teemu Smura, Alexander Lukasev, Susanne Gjeruldsen Dudman, Mia Brytting, Sindy Böttcher, Sofie Midgley, Sabine Diedrich, Thea Kølsen Fischer, Elenor Hauzenberger, Isabelle Schuffenecker, Carita Savolainen-Kopra, Anne J. Jääskeläinen, Olga Ivanova, Bruno Lina, Soile Blomqvist, Pekka Kolehmainen, Petri Susi, HUSLAB, University of Helsinki, Helsinki University Hospital Area, Department of Virology, Clinicum, Medicum, Viral Zoonosis Research Unit, University of Helsinki, HUSLAB, University of Helsinki, Department of Virology, and University of Helsinki, Medicum

Subjects
0301 basic medicine, Echovirus, Picornavirus, SAMPLES, Northern Europe, medicine.disease_cause, Disease Outbreaks, 0302 clinical medicine, Germany, PICORNAVIRUS, Meningitis, Aseptic, 030212 general & internal medicine, Diagnostic screening, Finland, Phylogeny, 11832 Microbiology and virology, biology, Norway, Human parechovirus, ENTEROVIRUSES, Aseptic meningitis, Enterovirus B, Human, 3. Good health, Europe, Infectious Diseases, Adolescent, 030106 microbiology, Echovirus Infections, Viremia, TYPE-3, Young Adult, 03 medical and health sciences, CEREBROSPINAL-FLUID, Virology, medicine, Humans, Sweden, IDENTIFICATION, HUMAN PARECHOVIRUS INFECTIONS, SPAIN, Outbreak, biology.organism_classification, medicine.disease, Central nervous system, Parechovirus, Echovirus 4, 3111 Biomedicine
Abstract

Picornaviruses (family Picornaviridae) are small, nonenveloped, positive-sense, single-stranded RNA viruses. The members of this family are currently classified into 47 genera and 110 species. Of picornaviruses, entero-and parechoviruses are associated with aseptic meningitis. They are transmitted via fecal-oral and respiratory routes, and occasionally, these viruses may cause a brief viremia and gain access to central nervous system (CNS). During the diagnostic screening of entero-and parechovirus types in Finland in year 2013-14, we detected a cluster of echovirus 4 (E4) infections in young adults and adolescents. As E4 is infrequently detected in Finland, we contacted several Northern and Central European laboratories that conduct routine surveillance for enteroviruses and, for those who have had E4 cases, we send a query for E4 sequences and data. Here we report CNS infections caused by E4 in Finland, Sweden, Norway, Denmark, Iceland and Germany in 2013 and 2014, and show that the E4 detected in these countries form a single lineage. In contrast, E4 strains circulating in these countries preceding the year 2013, and those circulating elsewhere in Europe during 2013-2014, formed several independent clusters.

Published
2020
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15. Impact des Entérovirus tronqués sur la sévérité des myocardites aiguës

Author

Guyen, Yohan N., Anne-Laure Lebreil, Audrey Mirand, Glenet, M., French Enterovirus Myocarditis Study Group Femsg, Cecile Henquell, Bruno Lina, Isabelle Schuffenecker, Laurent Andreoletti, Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Université de Lyon, Hospices Civils de Lyon (HCL), Centre National de Référence (CNR) des Enterovirus et Parechovirus [HCL Lyon] (CNR - laboratoire associé), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), and Centre National de Référence (CNR) des Enterovirus et Parechovirus [HCL Lyon]

Subjects
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

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

Author

Thierry Wirth, Laurence Josset, Maxime Pichon, Isabelle Schuffenecker, Bruno Lina, Rolf Kramer, and Marina Sabatier

Subjects
0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Genotype, Epidemiology, 030106 microbiology, Molecular Sequence Data, Polymerase Chain Reaction, law.invention, Hospitals, University, 03 medical and health sciences, law, Virology, Enterovirus Infections, Medicine, Humans, Paralysis, Child, Lung, Respiratory Tract Infections, Screening study, Phylogeny, Paediatric patients, Asthma, Enterovirus D, Human, Viral Structural Proteins, Atomic force microscopy, business.industry, Public Health, Environmental and Occupational Health, Infant, medicine.disease, Intensive care unit, Acute flaccid myelitis, Hospitalization, 030104 developmental biology, Child, Preschool, Female, France, business, Enterovirus D68
Abstract

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 (Conclusions: Reinforcement of diagnostic capacities and clinical-based surveillance of EV-D68 infections is needed in Europe to assess the EV-D68 burden.

Published
2018

17. Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow

Author

Laurence Josset, Maxime Pichon, Florence Morfin, Martine Valette, Gaelle Vilchez, Bruno Lina, Sophie Trouillet-Assant, Jean-Sébastien Casalegno, Isabelle Schuffenecker, Guy Oriol, Caroline Picard, Lisa Billard, Antonin Bal, Karen Brengel-Pesce, Valérie Cheynet, Sophie Vallet, Yves Gillet, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des virus des Infections Respiratoires France Sud [HCL, Lyon], Biomérieux Lyon, BIOMERIEUX, Laboratoire de Virologie, Hospices Civils de Lyon (HCL), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), French foundation of innovation in infectious diseases, Bodescot, Myriam, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, medicine.medical_specialty, Viral metagenomics, Computational biology, Biology, Real-Time Polymerase Chain Reaction, Genome, DNA sequencing, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, chemistry.chemical_compound, Medical microbiology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, RNA Viruses, lcsh:RC109-216, Respiratory Tract Infections, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Respiratory samples, 030304 developmental biology, 0303 health sciences, Respiratory viruses, Clinical virology, 030306 microbiology, DNA Viruses, High-Throughput Nucleotide Sequencing, RNA, Quality control, 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Workflow, Parasitology, Technical Advance, chemistry, Metagenomics, DNA, Viral, Next-generation sequencing, RNA, Viral, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], DNA, SsDNA viruses
Abstract

BackgroundIn recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking.MethodsA total of 3 QCs were implemented and processed through the whole mNGS workflow: a notemplate-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7).ResultsThe optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6% to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R2 ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses).ConclusionsAlthough the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples.

Published
2018
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18. A Transmissible Rash of Palms and Soles in a 58-Year-Old Man

Author

Olivier Lortholary, Morgane Cheminant, Romain Guery, Claire Aguilar, Isabelle Schuffenecker, Marianne Leruez-Ville, Fanny Lanternier, Marc Lecuit, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Centre National de Référence (CNR) des Enterovirus et Parechovirus [HCL Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Adulte, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Centre National de Référence (CNR) des Enterovirus et Parechovirus [HCL Lyon] (CNR - laboratoire associé)

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, education, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, 030212 general & internal medicine, health care economics and organizations, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, virus diseases, Dermatology, Rash, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine.symptom, business, Palm, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Diagnosis: Atypical hand, foot, and mouth disease caused by coxsackievirus A6 (CVA6).

Published
2017
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19. A new real-time RT-PCR targeting VP4-VP2 to detect and quantify enterovirus D68 in respiratory samples

Author

Johan Geiser, Isabelle Schuffenecker, Caroline Tapparel, Léna Royston, and Laurence Josset

Subjects
0301 basic medicine, 030106 microbiology, Biology, Real-Time Polymerase Chain Reaction, medicine.disease_cause, Sensitivity and Specificity, Genome, Disease Outbreaks, 03 medical and health sciences, Virology, Enterovirus Infections, medicine, Humans, Respiratory Tract Infections, Respiratory samples, Phylogeny, Enterovirus D, Human, Viral Structural Proteins, ddc:616, Outbreak, 3. Good health, Infectious Diseases, Real-time polymerase chain reaction, Enterovirus, Seasons, Enterovirus D68
Abstract

Causing an international outbreak of respiratory disease, Enterovirus D68 quickly entered the closed circle of emerging viral pathogens of public health significance. As rapid and accurate detection of EV-D68 is essential for an efficient clinical management, we designed and validated a new highly efficient one-step quantitative rRT-PCR specific to EV-D68 VP4-VP2 region. With 100% specificity and 95.6% sensitivity to all EV-D68 strains, this new assay can be reliably used to detect and quantify EV-D68 in respiratory samples and represents an interesting additional tool for diagnosis as it targets an original region of the genome.

Published
2017

20. Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016

Author

Florence Moulin, Bruno Lina, Cécile Henquell, Audrey Mirand, Daniel Lévy-Bruhl, Isabelle Schuffenecker, Isabelle Desguerre, Marianne Leruez-Ville, Mélodie Aubart, Clément Bassi, Denise Antona, Manoelle Kossorotoff, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, Unité des maladies à prévention vaccinale, Institut de Veille Sanitaire (INVS), CHU Clermont-Ferrand, Service de Neuropédiatrie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, 0301 basic medicine, Pediatrics, Enterovirus Infections, Epidemiology, Enterovirus A71, medicine.disease_cause, Severity of Illness Index, Molecular typing, Medicine, Child, Respiratory Tract Infections, Phylogeny, ComputingMilieux_MISCELLANEOUS, Enterovirus D, Human, severe neurological symptoms, Respiratory tract infections, Coinfection, 3. Good health, Hospitalization, Child, Preschool, Female, France, Rapid Communication, medicine.medical_specialty, Adolescent, Genotype, 030106 microbiology, macromolecular substances, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, children, Virology, Humans, Enterovirus D68, business.industry, Public Health, Environmental and Occupational Health, Infant, Sequence Analysis, DNA, Enterovirus a71, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Enterovirus A, Human, Molecular Typing, 030104 developmental biology, Enterovirus, Nervous System Diseases, business, Sentinel Surveillance
Abstract

We report 59 cases of severe paediatric conditions linked with enterovirus (EV)-A71 and EV-D68 in France between May and October 2016. Fifty-two children had severe neurological symptoms. EV sequence-based typing for 42 cases revealed EV-A71 in 21 (18 subgenotype C1, detected for the first time in France) and EV-D68 in eight. Clinicians should be encouraged to obtain stool and respiratory specimens from patients presenting with severe neurological disorders for EV detection and characterisation.

Published
2016
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21. A major outbreak of conjunctivitis caused by coxsackievirus A24, Réunion, January to April 2015

Author

Frédéric Pagès, Nadège Marguerite, Isabelle Schuffenecker, Pascal Vilain, Marie Christine Jaffar-Bandjee, Elise Brottet, Laurent Filleul, and Laurence Josset

Subjects
Adult, Male, 0301 basic medicine, Veterinary medicine, Adolescent, Epidemiology, 030106 microbiology, Coxsackievirus Infections, Coxsackievirus, Disease Outbreaks, Young Adult, 03 medical and health sciences, Age Distribution, Risk Factors, Virology, Humans, Medicine, Sex Distribution, Child, Aged, Aged, 80 and over, biology, business.industry, Incidence, Incidence (epidemiology), Infant, Newborn, Public Health, Environmental and Occupational Health, Infant, Outbreak, Middle Aged, Population cohort, biology.organism_classification, Infant newborn, Enterovirus C, Human, 030104 developmental biology, Child, Preschool, Female, Age distribution, Conjunctivitis, Acute Hemorrhagic, business, Reunion, Sentinel Surveillance, Demography, Healthcare system
Abstract

From January to April 2015, Réunion experienced a major outbreak of acute haemorrhagic conjunctivitis (AHC) caused by coxsackievirus A24, which heavily impacted the healthcare system. According to the general practitioners’ (GP) sentinel network, the number of medical consultations due to conjunctivitis during this period was estimated at ca 100,000. This report describes the characteristics of the outbreak, which were obtained through several different yet complementary surveillance systems on the island. These included the network of hospital emergency departments (OSCOUR network), the GPs’ sentinel network, an Internet-based population cohort (‘Koman i lé’) participating in a survey on distinct symptoms including ‘red eyes’ and the monitoring of eye drop sales. Overall the results of the different surveillance approaches were in good agreement regarding the outbreak dynamic. A peak of patients with conjunctivitis was detected in the first 15 days of March (week 10 and 11), coinciding with increased eye drop sales on the island. Strains recovered from outbreak cases belonged to genotype IV and were most closely related to strains identified in AHC outbreaks in China, Egypt and Japan since 2010. Continued surveillance of AHC in Réunion remains important not only locally, but also because frequent exchanges between the island and mainland France may lead to introduction of this virus in Europe.

Published
2016
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22. Enterovirus infections in hospitals of Ile de France region over 2013

Author

Cécile Henquell, Lucie Molet, Kenda Saloum, Flore Rozenberg, Antoine Garbarg-Chenon, Stéphanie Marque-Juillet, Audrey Mirand, Isabelle Schuffenecker, Hélène Peigue-Lafeuille, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Clermont-Ferrand, French National Enterovirus/Parechovirus Reference centre, Hospices Civils de Lyon (HCL), Laboratoire de Virologie, and Hôpital Saint-Vincent de Paul

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Paris, Echovirus, Adolescent, Genotype, 030106 microbiology, Coxsackievirus, medicine.disease_cause, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Virology, Epidemiology, medicine, Enterovirus Infections, Humans, 030212 general & internal medicine, Child, Genotyping, Aged, Enterovirus, Retrospective Studies, Aged, 80 and over, biology, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Reverse Transcriptase Polymerase Chain Reaction, Infant, Newborn, Outbreak, Infant, Middle Aged, biology.organism_classification, Hospitals, 3. Good health, Infectious Diseases, Child, Preschool, Etiology, Female, business
Abstract

Background The monitoring and genotyping of Enterovirus (EV) infections can help to associate particular or severe clinical manifestations with specific EV types and to identify the aetiology of infectious outbreaks. Objectives To describe the epidemiological features of EV infections diagnosed during the year 2013 in the Greater Paris area (Ile de France). Study design During 2013, 2497 samples taken from 470 patients in 33 hospitals of Ile-de France were tested for EV genome by RT-PCR. EV genotyping was performed by the National Reference Centre (NRC) laboratories. EV infections were retrospectively reviewed by retrieving clinical and genotyping data from the NRC database. Results Of the 2497 samples, 490 (19.6%) was positive for EV genome detection. These EV infections represented 88.7% and 24.1%, respectively, of all reported regional and national infections. Twenty-seven different genotypes were identified. Echovirus 30 (E-30) accounted for 54.1% of all characterized strains and caused a large outbreak. Four severe neonatal infections were reported, of which two were caused by EV-A71. Respiratory infections involving EV-D68 were observed in two adults. One fatal case of Coxsackievirus A2-associated myocarditis was reported. Conclusion Monitoring EV infections in combination with EV genotyping via the French EV network characterized the epidemiology of EV infections in the Ile de France region in 2013 and documented severe EV infections associated with EV-A71 or CV-A2.

Published
2015
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23. Cross-boarder surveillance of enterovirus-D68 in Europe during the 2014 North-American outbreak

Author

Bruno Lina, Hubert G. M. Niesters, Laurence Josset, Coretta van Leer, Randy Poelman, and Isabelle Schuffenecker

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Environmental health, Clinical information, medicine, Epidemiological surveillance, Outbreak, business, Mild disease, Enterovirus D68, Clinical virology, Respiratory pathogens
Abstract

Introduction: During the summer op 2014 an outbreak of enterovirus-D68 (EV-D68) was observed in North-America. While clinical cases were rapidly accumulating, beginning in the USA no similar signal was detected in Europe. The question was raised if there was indeed no circulation of this virus in Europe, or whether the near absence of reports were due to insufficient testing or detection. Methods: The European society for Clinical Virology launched the European EV-D68 initiative, in collaboration with the ECDC, to investigate the circulation of EV-D68 both retrospectively and prospectively. Laboratories that contributed to the initiative, tested respiratory materials for EV-D68, and collected clinical information. In addition, the VP1 frangment of isolated EV-D68 was sequenced by these laboratories, to investigate if the stains found in Europe were related to the ones found in North America. Results: Overall, 42 laboratories from 17 countries participated. A total of 17,248 specimens were analysed, yielding 389 EV-D68 positives (2.26%) in 14 countries. The prevalence ranged between 0 to 25%. These infections were mainly detected in young children presenting with wheezing and immunocompromised adults. Te viruses were epidemiologically linked to the USA epidemic. Conclusions: EV-D68 has been circulating all over Europe during summer and fall 2014, at an unprecedented frequency but with a very mild disease burden. Through detection and virus typing adapted tools, the European laboratories rapidly provided a clear picture of the circulation of this emerging virus.. This study emphasizes the need of a better epidemiological surveillance of respiratory pathogens.

Published
2015
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24. Disseminated rhinovirus C8 infection with infectious virus in blood and fatal outcome in a child with repeated episodes of bronchiolitis

Author

Bruno Lina, Patrice Morand, Nathalie Lin-Marq, Samuel Constant, Laurent Kaiser, Julie Bardet, Christine Morel-Baccard, Isabelle Schuffenecker, Johannes Alexander Lobrinus, Caroline Tapparel, Julien Lupo, Valérie Payen, Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), French National Enterovirus/Parechovirus Reference centre, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Grenoble (CHU de Grenoble), CHU Grenoble, and University of Geneva [Switzerland]

Subjects
Microbiology (medical), Virus Cultivation, Fatal outcome, Rhinovirus, Respiratory System, Viremia, Case Reports, medicine.disease_cause, Feces, 03 medical and health sciences, Fatal Outcome, 0302 clinical medicine, Cerebrospinal fluid, stomatognathic system, medicine, Humans, 030212 general & internal medicine, Respiratory system, Cerebrospinal Fluid, 030304 developmental biology, ddc:616, 0303 health sciences, Picornaviridae Infections, business.industry, Infant, virus diseases, medicine.disease, Virology, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Blood, Bronchiolitis, Immunology, Female, Airway, business
Abstract

We report a fatal case of acute lower respiratory tract disease with human rhinovirus C (HRV-C) as the unique cause in a 19-month-old girl with a history of repeated episodes of bronchiolitis. HRV-C type 8 nucleic acids were observed in respiratory, stool, and cerebrospinal fluid samples, and infectious virions were isolated from patient serum after inoculation onto reconstituted airway epithelia.

Published
2015

25. Transmission patterns of human enterovirus 71 to, from and among European countries, 2003 to 2013

Author

Agnes Farkas, Jean-Luc Bailly, Christine Archimbaud, Chervin Hassel, Hartwig P. Huemer, Isabelle Schuffenecker, Audrey Mirand, Alexander N. Lukashev, Cécile Henquell, Sabine Diedrich, Elena Terletskaia-Ladwig, Hélène Peigue-Lafeuille, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Epidémiologie et pathogénie des infections à entérovirus (EPIE), and Université d'Auvergne - Clermont-Ferrand I (UdA)

Subjects
Genes, Viral, Genotype, Epidemiology, Molecular Sequence Data, Iceland, Zoology, Disease, Virus, Disease Outbreaks, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Enterovirus 71, Enterovirus Infections, media_common.cataloged_instance, Humans, European Union, European union, Phylogeny, 030304 developmental biology, media_common, 0303 health sciences, Molecular Epidemiology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Polymorphism, Genetic, Phylogenetic tree, biology, Molecular epidemiology, Geography, 030306 microbiology, Transmission (medicine), Norway, Public Health, Environmental and Occupational Health, Outbreak, Bayes Theorem, biology.organism_classification, 3. Good health, Enterovirus A, Human, Europe, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sentinel Surveillance, Switzerland
Abstract

International audience; Enterovirus 71 (EV-71) is involved in epidemics of hand, foot, and mouth disease (HFMD) and has been reported to occur with severe neurological complications in eastern and southeast Asia. In other geographical areas, the transmission of this virus is poorly understood. We used large sequence datasets (of the gene encoding the viral protein 1, VP1) and a Bayesian phylogenetic approach to compare the molecular epidemiology and geographical spread patterns of EV-71 subgenogroups B4, B5, C1, C2, and C4 in Europe relative to other parts of the world. For the study, European countries considered were European Union (EU) Member States and Iceland, Norway and Switzerland. Viruses of the B4, B5, and C4 subgenogroups circulate mainly in eastern and southeast Asia. In Europe sporadic introductions of these subgenogroups are observed, however C1 and C2 viruses predominate. The phylogenies showed evidence of multiple events of spread involving C1 and C2 viruses within Europe since the mid-1990s. Two waves of sporadic C2 infections also occurred in 2010 and 2013. The 2007 Dutch outbreak caused by C2 and the occurrence of B5 and C4 infections in the EU between 2004 and 2013 arose while the circulation of C1 viruses was low. A transmission chain involving a C4 virus was traced from Japan to the EU and then further to Canada between 2001 and 2006. Recent events whereby spread of viruses have occurred from, to, and within Europe appear to be involved in the long term survival of EV-71, highlighting the need for enhanced surveillance of this virus.

Published
2015
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27. Two-step strategy for the identification of SARS-CoV-2 variant of concern 202012/01 and other variants with spike deletion H69–V70, France, August to December 2020

Author

Bal, Antonin, Destras, Gregory, Gaymard, Alexandre, Stefic, Karl, Marlet, Julien, Eymieux, Sébastien, Regue, Hadrien, Semanas, Quentin, d’Aubarede, Constance, Billaud, Geneviève, Laurent, Frédéric, Gonzalez, Claudia, Mekki, Yahia, Valette, Martine, Bouscambert, Maude, Gaudy-Graffin, Catherine, Lina, Bruno, Morfin, Florence, Josset, Laurence, Casalegno, Jean-Sébastien, Frobert, Emilie, Escuret, Vanessa, Icard, Vinca, Jeannoel, Marion, Milon, Marie-Paule, Ramière, Christophe, Scholtès, Caroline, Tardy, Jean-Claude, Trabaud, Mary-Anne, Schuffenecker, Isabelle, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), The members of the COVID-Diagnosis HCL Study Group : Jean-Sébastien Casalegno, Emilie Frobert, Vanessa Escuret, Vinca Icard, Marion Jeannoel, Marie-Paule Milon, Christophe Ramière, Caroline Scholtès, Jean-Claude Tardy, Mary-Anne Trabaud, Isabelle Schuffenecker, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Marlet, Julien, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Two step, spike protein, variants, deletion, Genome, Viral, Biology, spike protein, Genome, 03 medical and health sciences, COVID-19, whole genome sequencing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Humans, Spike (database), Base sequence, Sequence Deletion, whole genome sequencing, variants, Base Sequence, deletion, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, 030104 developmental biology, Spike Glycoprotein, Coronavirus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Identification (biology), France, Rapid Communication
Abstract

International audience; We report the strategy leading to the first detection of variant of concern 202012/01 (VOC) in France (21 December 2020). First, the spike (S) deletion H69-V70 (ΔH69/ΔV70), identified in certain SARS-CoV-2 variants including VOC, is screened for. This deletion is associated with a S-gene target failure (SGTF) in the three-target RT-PCR assay (TaqPath kit). Subsequently, SGTF samples are whole genome sequenced. This approach revealed mutations co-occurring with ΔH69/ΔV70 including S:N501Y in the VOC.

Published
2021
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