Epidemiology of parecho- and enterovirus infections
Human parechoviruses (HPeV) belong to the family Picornaviridae (also including enteroviruses) and are positive-strand RNA viruses with a genome of approximately 7,200 bp. Human parechoviruses have a worldwide distribution and are associated with gastrointestinal and respiratory tract infection. In general, illness remains clinically mild but severe cases of neonatal sepsis and encephalitis/meningitis are an issue of concern.
To date, 19 different HPeV types are known and the majority have been described only recently. Historically, HPeV infections have been infrequently recognized mainly because of insensitive diagnostic methods. The advent of PCR technology has contributed much to our understanding of HPeV infections although still little is known about the epidemiology and relevance of the recently described HPeV types.
We aim to investigate the epidemiology and clinical impact of HPeV infections in children. We investigated an upsurge of HPeV A3 infections in Freiburg in 2018 (Figure). Typing of HPeV is accomplished by Sanger sequencing fragments of the genome of positive HPeV samples. We aim to characterize HPeV using classical tools like virus isolation in cell culture and virus neutralization assays. In addition, we are involved in ongoing and international studies on the epidemiology of enterovirus infections (Figure 2, Simoes et al., J Infect Dis 2024).
Selected publications from our group:
Simoes MP, Hodcroft EB, Simmonds P, Albert J, Alidjinou EK, Ambert-Balay K, Andres C, Anton A, Auvray C, Bailly JL, Baldanti F, Bastings C, Beard S, Berengua C, Berginc N, Bloemen M, Blomqvist S, Bosma F, Bottcher S, Bubba L, Buderus S, Cabrerizo M, Calvo C, Celma C, Ceriotti F, Clark G, Costa I, Coste-Burel M, Coudere K, Cremer J, Del Cuerpo Casas M, Daehne T, de Beer J, de Ceano-Vivas M, De Gascun C, de Rougemont A, Dean J, Dembinski JL, Diedrich S, Diez-Domingo J, Dillner L, Dorenberg DH, Ducancelle A, Dudman S, Dyrdak R, Eis-Huebinger AM, Falces-Romero I, Farkas A, Feeney S, Fernandez-Garcia MD, Flipse J, Franck KT, Galli C, Garrigue I, Geeraedts F, Georgieva I, Giardina F, Guiomar R, Hauzenberger E, Heikens E, Henquell C, Hober D, Honemann M, Howson-Wells H, Hruskar Z, Ikonen N, Imbert B, Jansz AR, Jeannoel M, Jirincova H, Josset L, Keeren K, Kramer-Lindhout N, Krokstad S, Lazrek M, Le Guillou-Guillemette H, Lefeuvre C, Lind A, Lunar MM, Maier M, Marque-Juillet S, McClure CP, McKenna J, Meijer A, Menasalvas Ruiz A, Mengual-Chulia B, Midgley S, Mirand A, Molenkamp R, Montes M, Moreno-Docon A, Morley U, Murk JL, Navascues-Ortega A, Nijhuis R, Nikolaeva-Glomb L, Nordbo SA, Numanovic S, Oggioni M, Onate Vergara E, Pacaud J, Pacreau ML, Panning M, Pariani E, Pekova L, Pellegrinelli L, Petrovec M, Pietsch C, Pilorge L, Pineiro L, Piralla A, Poljak M, Prochazka B, Rabella N, Rahamat-Langendoen JC, Rainetova P, Reynders M, Riezebos-Brilman A, Roorda L, Savolainen-Kopra C, Schuffenecker I, Smeets LC, Stoyanova A, Stefic K, Swanink C, Tabain I, Tjhie J, Thouault L, Tumiotto C, Uceda Renteria S, Ursic T, Vallet S, Van Ranst M, Van Wunnik P, Verweij JJ, Vila J, Wintermans B, Wollants E, Wolthers KC, Xavier Lopez-Labrador F, Fischer TK, Harvala H, Benschop KSM. Epidemiological and Clinical Insights into the Enterovirus D68 Upsurge in Europe 2021-2022 and Emergence of Novel B3-Derived Lineages, ENPEN Multicentre Study. J Infect Dis 2024;230:e917-e28.
Midgley SE, Benschop K, Dyrdak R, Mirand A, Bailly JL, Bierbaum S, Buderus S, Bottcher S, Eis-Hubinger AM, Honemann M, Jensen VV, Hartling UB, Henquell C, Panning M, Thomsen MK, Hodcroft EB, Meijer A. Co-circulation of multiple enterovirus D68 subclades, including a novel B3 cluster, across Europe in a season of expected low prevalence, 2019/20. Euro Surveill 2020;25.
Elling R, Bottcher S, du Bois F, Muller A, Prifert C, Weissbrich B, Hofmann J, Korn K, Eis-Hubinger AM, Hufnagel M, Panning M. Epidemiology of Human Parechovirus Type 3 Upsurge in 2 Hospitals, Freiburg, Germany, 2018. Emerg Infect Dis 2019;25:1384-8.
Collaboration:
Center for Pediatrics and Adolescent Medicine/Center for Chronic Immunodeficiency, Freiburg
National Reference Center for Polio- and Enteroviruses, Robert-Koch-Institute, Berlin
European non-polio enterovirus network (ENPEN), ESCV
Figure 2: Figure 3. A–C, Phylodynamic analysis of EV-D68 with Nextstrain using 692 partial study VP1 sequences > 300 bp and 3307 publicly available VP1 sequences. B and C, Zoomed views of areas of the tree containing the 2 novel lineages. D, Neighbor-joining phylogenetic tree of complete genome from the study samples (n = 82) and 1025 sequences with data annotations from GenBank. E, Neighbor-joining phylogenetic tree of VP1 region sequences (positions 2501–2842, numbered using the Fermon prototype sequence, KU844179) from the study samples (n = 559) and 3306 sequences with data annotations from GenBank. (Simoes et al., J Infect Dis 2024)

Head:
Prof. Dr. med. Hartmut Hengel
hartmut.hengel@uniklinik-freiburg.de
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