Skip to main content
Top

Open Access 27-09-2024 | Research

First whole genome sequencing and analysis of human parechovirus type 3 causing a healthcare-associated outbreak among neonates in Hungary

Authors: Nóra Deézsi-Magyar, Nikolett Novák, Adrienne Lukács, Katalin Réka Tarcsai, Ágnes Hajdu, László Takács, Ferenc Balázs Farkas, Zita Rigó, Erzsébet Barcsay, Zoltán Kis, Katalin Szomor

Published in: European Journal of Clinical Microbiology & Infectious Diseases

Login to get access

Abstract

Purpose

In November 2023, the National Reference Laboratory for Enteroviruses (Budapest, Hungary) received stool, pharyngeal swab and cerebrospinal fluid samples from five newborns suspected of having human parechovirus (PEV-A) infection. The neonates were born in the same hospital and presented with fever and sepsis-like symptoms at 8–9 days of age, and three of them showed symptoms consistent with central nervous system involvement. PEV-A positivity was confirmed by quantitative reverse transcription polymerase chain reaction.

Methods

To determine the PEV-A genotype responsible for the infections, fecal samples of four neonates were subjected to metagenomic sequencing. For further analyses, amplicon-based whole genome sequencing was performed directly from the clinical samples.

Results

On the basis of whole genome analysis, sequences were allocated to PEV-A genotype 3 (PEV-A3) and consensus sequences were identical. Two ambiguities were identified in the viral protein 1 (VP1) region of all sequences at a frequency of 17.7–53.7%, indicating the simultaneous presence of at least two quasispecies in the clinical samples. The phylogenetic analysis and similarity plotting showed that all sequences clustered without any topological inconsistencies between the P1 capsid and P2, P3 non-capsid regions, suggesting that recombination events during evolution were unlikely.

Conclusion

Our findings suggest that the apparent cluster of cases were microbiologically related, and the results may also inform future investigations on the evolution and pathogenicity of PEV-A3 infections.
Appendix
Available only for authorised users
Literature
6.
go back to reference Centers for Disease Control and Prevention (CDC) (2022) Recent reports of human parechovirus (PeV) in the United States—2022. CDC Health Alert Netw. July 12 Centers for Disease Control and Prevention (CDC) (2022) Recent reports of human parechovirus (PeV) in the United States—2022. CDC Health Alert Netw. July 12
10.
go back to reference Benschop K, Minnaar R, Koen G, van Eijk H, Dijkman K, Westerhuis B, Molenkamp R, Wolthers K (2010 Oct) Detection of human enterovirus and human parechovirus (PEV-A) genotypes from clinical stool samples: polymerase chain reaction and direct molecular typing, culture characteristics, and serotyping. Diagn Microbiol Infect Dis 68(2):166–173. https://doi.org/10.1128/JCM.00086-10 Benschop K, Minnaar R, Koen G, van Eijk H, Dijkman K, Westerhuis B, Molenkamp R, Wolthers K (2010 Oct) Detection of human enterovirus and human parechovirus (PEV-A) genotypes from clinical stool samples: polymerase chain reaction and direct molecular typing, culture characteristics, and serotyping. Diagn Microbiol Infect Dis 68(2):166–173. https://​doi.​org/​10.​1128/​JCM.​00086-10
12.
14.
go back to reference Harvala H, Robertson I, McWilliam Leitch EC, Benschop K, Wolthers KC, Templeton K, Simmonds P Epidemiology and clinical associations of human parechovirus respiratory infections. J Clin Microbiol 2008 Oct;46(10):3446–3453. https://doi.org/10.1128/JCM.01207-08 Harvala H, Robertson I, McWilliam Leitch EC, Benschop K, Wolthers KC, Templeton K, Simmonds P Epidemiology and clinical associations of human parechovirus respiratory infections. J Clin Microbiol 2008 Oct;46(10):3446–3453. https://​doi.​org/​10.​1128/​JCM.​01207-08
15.
go back to reference Chamings A, Liew KC, Reid E, Athan E, Raditsis A, Vuillermin P, Yoga Y, Caly L, Druce J, Alexandersen S (2019 Oct) An Emerging Human Parechovirus Type 5 Causing Sepsis-Like Illness in infants in Australia. Viruses 3(10):913. https://doi.org/10.3390/v11100913 Chamings A, Liew KC, Reid E, Athan E, Raditsis A, Vuillermin P, Yoga Y, Caly L, Druce J, Alexandersen S (2019 Oct) An Emerging Human Parechovirus Type 5 Causing Sepsis-Like Illness in infants in Australia. Viruses 3(10):913. https://​doi.​org/​10.​3390/​v11100913
16.
go back to reference Bubba L, Broberg EK, Fischer TK, Simmonds P, Harvala H (2024 Feb) European non-polio Enterovirus Network working group. Parechovirus a circulation and testing capacities in Europe, 2015–2021. Emerg Infect Dis 30(2):234–244. https://doi.org/10.3201/eid3002.230647PMID: 38270192; PMCID: PMC10826775 Bubba L, Broberg EK, Fischer TK, Simmonds P, Harvala H (2024 Feb) European non-polio Enterovirus Network working group. Parechovirus a circulation and testing capacities in Europe, 2015–2021. Emerg Infect Dis 30(2):234–244. https://​doi.​org/​10.​3201/​eid3002.​230647PMID: 38270192; PMCID: PMC10826775
17.
go back to reference Patil PR, Ganorkar NN, Gopalkrishna V (2018 Jan) Epidemiology and genetic diversity of human parechoviruses circulating among children hospitalised with acute gastroenteritis in Pune, Western India: a 5-years study. Epidemiol Infect 146(1):11–18. https://doi.org/10.1017/S095026881700262X Patil PR, Ganorkar NN, Gopalkrishna V (2018 Jan) Epidemiology and genetic diversity of human parechoviruses circulating among children hospitalised with acute gastroenteritis in Pune, Western India: a 5-years study. Epidemiol Infect 146(1):11–18. https://​doi.​org/​10.​1017/​S095026881700262​X
18.
go back to reference Tauriainen S, Martiskainen M, Oikarinen S, Lönnrot M, Viskari H, Ilonen J, Simell O, Knip M, Hyöty H (2007 Apr) Human parechovirus 1 infections in young children–no association with type 1 diabetes. J Med Virol 79(4):457–462. https://doi.org/10.1002/jmv.20831 Tauriainen S, Martiskainen M, Oikarinen S, Lönnrot M, Viskari H, Ilonen J, Simell O, Knip M, Hyöty H (2007 Apr) Human parechovirus 1 infections in young children–no association with type 1 diabetes. J Med Virol 79(4):457–462. https://​doi.​org/​10.​1002/​jmv.​20831
20.
go back to reference Boros Á, Hamarics Z, Fenyvesi H, Liptai Z, Nyul Z, Pankovics P, Reuter G (2019 Mar) A humán parechovírusok klinikai jelentősége súlyos újszülött- és csecsemőkori fertőzésekben hazánkban [The clinical significance of severe human parechovirus infections in newborns and infants in Hungary]. Orv Hetil 160(10):386–395 In Hungarian. https://doi.org/10.1556/650.2019.31304 Boros Á, Hamarics Z, Fenyvesi H, Liptai Z, Nyul Z, Pankovics P, Reuter G (2019 Mar) A humán parechovírusok klinikai jelentősége súlyos újszülött- és csecsemőkori fertőzésekben hazánkban [The clinical significance of severe human parechovirus infections in newborns and infants in Hungary]. Orv Hetil 160(10):386–395 In Hungarian. https://​doi.​org/​10.​1556/​650.​2019.​31304
22.
23.
go back to reference Majumdar M, Klapsa D, Wilton T, Bujaki E, Fernandez-Garcia MD, Faleye TOC, Oyero AO, Adewumi MO, Ndiaye K, Adeniji JA, Martin J (2021 Feb) High Diversity of Human Non-polio Enterovirus Serotypes Identified in Contaminated Water in Nigeria. Viruses 5(2):249. https://doi.org/10.3390/v13020249 Majumdar M, Klapsa D, Wilton T, Bujaki E, Fernandez-Garcia MD, Faleye TOC, Oyero AO, Adewumi MO, Ndiaye K, Adeniji JA, Martin J (2021 Feb) High Diversity of Human Non-polio Enterovirus Serotypes Identified in Contaminated Water in Nigeria. Viruses 5(2):249. https://​doi.​org/​10.​3390/​v13020249
25.
go back to reference Vilsker M, Moosa Y, Nooij S, Fonseca V, Ghysens Y, Dumon K, Pauwels R, Alcantara LC Ewout Vanden Eynden, Anne-Mieke Vandamme, Koen Deforche, Tulio De Oliveira: genome detective: an Automated System for Virus Identification from high-throughput sequencing data. Bioinformatics, bty695, https://doi.org/10.1093/bioinformatics/bty695 Vilsker M, Moosa Y, Nooij S, Fonseca V, Ghysens Y, Dumon K, Pauwels R, Alcantara LC Ewout Vanden Eynden, Anne-Mieke Vandamme, Koen Deforche, Tulio De Oliveira: genome detective: an Automated System for Virus Identification from high-throughput sequencing data. Bioinformatics, bty695, https://​doi.​org/​10.​1093/​bioinformatics/​bty695
26.
go back to reference Sievers F, Barton GJ, Higgins DG (2020) Multiple Sequence Alignment. Bioinformatics 227, pp 227–250, AD Baxevanis, GD Bader, DS Wishart (Eds) Sievers F, Barton GJ, Higgins DG (2020) Multiple Sequence Alignment. Bioinformatics 227, pp 227–250, AD Baxevanis, GD Bader, DS Wishart (Eds)
28.
go back to reference Nei M, Kumar S (2000) Molecular Evolution and Phylogenetics. Oxford University Press, New YorkCrossRef Nei M, Kumar S (2000) Molecular Evolution and Phylogenetics. Oxford University Press, New YorkCrossRef
31.
go back to reference Mizuta K, Itagaki T, Chikaoka S, Wada M, Ikegami T, Sendo D, Iseki C, Shimizu Y, Abe S, Komabayashi K, Aoki Y, Ikeda T (2022 Sep) Recombinant parechovirus A3 possibly causes various clinical manifestations, including myalgia; findings in Yamagata, Japan in 2019. Infect Dis (Lond) 54(9):632–650. https://doi.org/10.1080/23744235.2022.2069857 Mizuta K, Itagaki T, Chikaoka S, Wada M, Ikegami T, Sendo D, Iseki C, Shimizu Y, Abe S, Komabayashi K, Aoki Y, Ikeda T (2022 Sep) Recombinant parechovirus A3 possibly causes various clinical manifestations, including myalgia; findings in Yamagata, Japan in 2019. Infect Dis (Lond) 54(9):632–650. https://​doi.​org/​10.​1080/​23744235.​2022.​2069857
32.
go back to reference Bialasiewicz S, May M, Tozer S, Day R, Bernard A, Zaugg J, Gartrell K, Alexandersen S, Chamings A, Wang CYT, Clark J, Grimwood K, Heney C, Schlapbach LJ, Ware RS, Speers D, Andrews RM, Lambert S (2023 Jan) Novel Human parechovirus 3 diversity, recombination, and clinical impact across 7 years: an Australian story. J Infect Dis 11(2):278–287. https://doi.org/10.1093/infdis/jiac311 Bialasiewicz S, May M, Tozer S, Day R, Bernard A, Zaugg J, Gartrell K, Alexandersen S, Chamings A, Wang CYT, Clark J, Grimwood K, Heney C, Schlapbach LJ, Ware RS, Speers D, Andrews RM, Lambert S (2023 Jan) Novel Human parechovirus 3 diversity, recombination, and clinical impact across 7 years: an Australian story. J Infect Dis 11(2):278–287. https://​doi.​org/​10.​1093/​infdis/​jiac311
Metadata
Title
First whole genome sequencing and analysis of human parechovirus type 3 causing a healthcare-associated outbreak among neonates in Hungary
Authors
Nóra Deézsi-Magyar
Nikolett Novák
Adrienne Lukács
Katalin Réka Tarcsai
Ágnes Hajdu
László Takács
Ferenc Balázs Farkas
Zita Rigó
Erzsébet Barcsay
Zoltán Kis
Katalin Szomor
Publication date
27-09-2024
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-024-04950-4

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Read more