Recommendations for enterovirus diagnostics and characterisation within and beyond Europe

Heli Harvala (1) , Eeva Broberg (2) , Kimberley Benschop (3) , Natasa Berginc (4) , Shamez Ladhani (5, 6) , Petri Susi , Claus Christiansen (7) , James P. Mckenna (8) , David Allen (9) , Phoebe Makiello , Georgina Mcallister (10) , Mirabelli Carmen , Katherina Zakikhany (11) , Robert Dyrdak , Xiaohui Nielsen , Tina Madsen , Joel Paul , Catherine Moore (12) , Karin von Eije , Antonio Piralla , Mieke Carlier , Laura Vanoverschelde , Randy Poelman , Andrés Anton , F. Xavier López-Labrador , Laura Pellegrinelli , Kathrin Keeren , Melanie Maier , Hayley Cassidy , Stavros Derdas , Carita Savolainen-Kopra , Sabine Diedrich , Svein Nordbø , Javier Buesa , Jean-Luc Bailly (13) , Fausto Baldanti , Andrew Macadam , Audrey Mirand (14) , Susanne Dudman , Isabelle Schuffenecker (15) , Seilesh Kadambari , Johan Neyts (16) , Michael Griffiths , Jan Richter (17) , Cristina Margaretto , Sheila Govind (18) , Ursula Morley , Ortwin Adams , Sidsel Krokstad , Jonathan Dean , Margarita Pons-Salort , Birgit Prochazka , Maria Cabrerizo (19) , Manasi Majumdar (18) , Gaia Nebbia , Maryse Wiewel , Simon Cottrell , Peter V. Coyle , Javier Martin (18) , Catrin Moore , Sofie Midgley , Peter Horby , Katja Wolthers , Peter Simmonds (20) , Hubert Niesters (21, 22) , Thea Fischer

1 NHS Blood and Transplant [London, UK]
2 ECDC - European Centre for Disease Prevention and Control [Stockholm, Sweden]
3 RIVM - National Institute for Public Health and the Environment [Bilthoven]
4 Laboratory for Public Health Virology [Ljubljana, Slovenia]
5 Public Health England [London]
6 St George's, University of London
7 Nordic Bioscience A/S, CCBR
8 Uppsala Universitet [Uppsala]
9 IUCN - International Union for Conservation of Nature
10 Royal Infirmary of Edinburgh
11 Public Health Agency of Sweden
12 Scottish HPV Reference Laboratory [Edinburgh, UK]
13 EPIE - Epidémiologie et pathogénie des infections à entérovirus
14 LMGE - Laboratoire Microorganismes : Génome et Environnement
15 HCL - Hospices Civils de Lyon
16 Laboratory of Virology and Chemotherapy [KU Leuven]
17 Cyprus Institute of Neurology and Genetics
18 NIBSC - National Institute for Biological Standards and Control
19 Enterovirus and Viral Gastroenteritis [Madrid]
20 Edin. - University of Edinburgh
21 Department of Viroscience [Rotterdam, The Netherlands]
22 University of Groningen [Groningen]

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5′noncoding regions (5′NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5′NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.

Mots clés: Enterovirus; Detection; EV typing; Neurological infection; European non-polio enterovirus network (ENPEN); Diagnostics

Domaines: Maladies infectieuses; Virologie; Santé publique et épidémiologie

Heli Harvala, Eeva Broberg, Kimberley Benschop, Natasa Berginc, Shamez Ladhani, et al.. Recommendations for enterovirus diagnostics and characterisation within and beyond Europe. Journal of Clinical Virology, 2018, 101, pp.11-17. ⟨10.1016/j.jcv.2018.01.008⟩. ⟨hal-01984200⟩