1887
Research Open Access
Like 0

Abstract

Background

In 2023, a European alert was issued regarding an increase in severe enterovirus (EV) neonatal infections associated with echovirus 11 (E11) new lineage 1.

Aim

To analyse E11-positive cases between 2019 and 2023 to investigate whether the new lineage 1 circulated in Spain causing severe neonatal infections.

Methods

EV-positive samples from hospitalised cases are sent for typing to the National Reference Enterovirus Laboratory. Available samples from 2022–23 were subjected to metagenomic next-generation sequencing.

Results

Of 1,288 samples genotyped, 103 were E11-positive (98 patients: 6 adults, 33 neonates, 89 children under 6 years; male to female ratio 1.9). E11 detection rate was similar before and after detection of the new lineage 1 in Spain in June 2022 (9.7% in 2019 vs 10.6% in 2023). The proportion of E11-infected ICU-admitted neonates in 2019–2022 (2/7) vs 2022–2023 (5/12) did not significantly differ (p = 0.65). In severe neonatal infections, 4/7 E11 strains were not linked to the new lineage 1. The three novel E11 recombinant genomes were associated with severe (n = 2) and non-severe (n = 1) cases from 2022–2023 and clustered outside the new lineage 1. Coinfecting pathogenic viruses were present in four of 10 E11-positive samples.

Conclusion

The emergence of the new lineage 1 is not linked with an increase in incidence or severity of neonatal E11 infections in Spain. The detection of two novel E11 recombinants associated with severe disease warrants enhancing genomic and clinical surveillance.

Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2024.29.44.2400221
2024-10-31
2024-11-01
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2024.29.44.2400221
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/29/44/eurosurv-29-44-5.html?itemId=/content/10.2807/1560-7917.ES.2024.29.44.2400221&mimeType=html&fmt=ahah

References

  1. Abzug MJ. Presentation, diagnosis, and management of enterovirus infections in neonates. Paediatr Drugs. 2004;6(1):1-10.  https://doi.org/10.2165/00148581-200406010-00001  PMID: 14969566 
  2. Verboon-Maciolek MA, Nijhuis M, van Loon AM, van Maarssenveen N, van Wieringen H, Pekelharing-Berghuis MA, et al. Diagnosis of enterovirus infection in the first 2 months of life by real-time polymerase chain reaction. Clin Infect Dis. 2003;37(1):1-6.  https://doi.org/10.1086/375222  PMID: 12830402 
  3. Lin TY, Kao HT, Hsieh SH, Huang YC, Chiu CH, Chou YH, et al. Neonatal enterovirus infections: emphasis on risk factors of severe and fatal infections. Pediatr Infect Dis J. 2003;22(10):889-94.  https://doi.org/10.1097/01.inf.0000091294.63706.f3  PMID: 14551490 
  4. Yang X, Duan L, Zhan W, Tang Y, Liang L, Xie J, et al. Enterovirus B types cause severe infection in infants aged 0-3 months. Virol J. 2023;20(1):5.  https://doi.org/10.1186/s12985-023-01965-9  PMID: 36624466 
  5. Hu YL, Lin SY, Lee CN, Shih JC, Cheng AL, Chen SH, et al. Serostatus of echovirus 11, coxsackievirus B3 and enterovirus D68 in cord blood: The implication of severe newborn enterovirus infection. J Microbiol Immunol Infect. 2023;56(4):766-71.  https://doi.org/10.1016/j.jmii.2023.05.004  PMID: 37330377 
  6. Grapin M, Mirand A, Pinquier D, Basset A, Bendavid M, Bisseux M, et al. Severe and fatal neonatal infections linked to a new variant of echovirus 11, France, July 2022 to April 2023. Euro Surveill. 2023;28(22):2300253.  https://doi.org/10.2807/1560-7917.ES.2023.28.22.2300253  PMID: 37261730 
  7. European Centre for Disease Prevention and Control (ECDC). Epidemiological update: Echovirus 11 infections in neonates. Stockholm: ECDC; 2023. Available from: https://www.ecdc.europa.eu/en/news-events/epidemiological-update-echovirus-11-infections-neonates.
  8. World Health Organization (WHO). Enterovirus-Echovirus 11 Infection in the European Region. Disease Outbreak News. Geneva: WHO; 2023. Available from: https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON474.
  9. Piralla A, Borghesi A, Di Comite A, Giardina F, Ferrari G, Zanette S, et al. Fulminant echovirus 11 hepatitis in male non-identical twins in northern Italy, April 2023. Euro Surveill. 2023;28(24):2300289.  https://doi.org/10.2807/1560-7917.ES.2023.28.24.2300289  PMID: 37318763 
  10. Trallero G, Avellon A, Otero A, De Miguel T, Pérez C, Rabella N, et al. Enteroviruses in Spain over the decade 1998-2007: virological and epidemiological studies. J Clin Virol. 2010;47(2):170-6.  https://doi.org/10.1016/j.jcv.2009.11.013  PMID: 20007023 
  11. Bubba L, Broberg EK, Jasir A, Simmonds P, Harvala H, Redlberger-Fritz M, et al. Circulation of non-polio enteroviruses in 24 EU and EEA countries between 2015 and 2017: a retrospective surveillance study. Lancet Infect Dis. 2020;20(3):350-61.  https://doi.org/10.1016/S1473-3099(19)30566-3  PMID: 31870905 
  12. Cabrerizo M, Díaz-Cerio M, Muñoz-Almagro C, Rabella N, Tarragó D, Romero MP, et al. Molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in Spain. J Med Virol. 2017;89(3):435-42.  https://doi.org/10.1002/jmv.24658  PMID: 27505281 
  13. Echevarria Mayo JE, Oteo Iglesias J, Jado Garcia I, editors. Programas de Vigilancia Microbiológica Centro Nacional de Microbiología. Volumen 2. 2021-2022. [Microbiological Surveillance Programmes, National Center for Microbiology. Volume 2. 2021-2022]. Instituto de Salud Carlos III; 2023. Spanish. Available from: https://repisalud.isciii.es/rest/api/core/bitstreams/b559792d-6b4b-4f43-9a17-7e53247ec0c7/content
  14. Cabrerizo M, Echevarria JE, González I, de Miguel T, Trallero G. Molecular epidemiological study of HEV-B enteroviruses involved in the increase in meningitis cases occurred in Spain during 2006. J Med Virol. 2008;80(6):1018-24.  https://doi.org/10.1002/jmv.21197  PMID: 18428125 
  15. González-Sanz R, Taravillo I, Reina J, Navascués A, Moreno-Docón A, Aranzamendi M, et al. Enterovirus D68-associated respiratory and neurological illness in Spain, 2014-2018. Emerg Microbes Infect. 2019;8(1):1438-44.  https://doi.org/10.1080/22221751.2019.1668243  PMID: 31571527 
  16. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22(22):4673-80.  https://doi.org/10.1093/nar/22.22.4673  PMID: 7984417 
  17. Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J, et al. GenBank. Nucleic Acids Res. 2013;41D1;D36-42.
  18. Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, et al. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol. 1999;73(1):152-60.  https://doi.org/10.1128/JVI.73.1.152-160.1999  PMID: 9847317 
  19. Babraham Bioinformatics. FastQC: A Quality Control Tool for High Throughput Sequence Data. [Accessed: 15 Oct]. Available from: http://www.bioinformatics.babraham.ac.uk/projects/fastqc/
  20. Chen S, Zhou Y, Chen Y, Gu J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34(17):i884-90.  https://doi.org/10.1093/bioinformatics/bty560  PMID: 30423086 
  21. Nurk S, Meleshko D, Korobeynikov A, Pevzner PA. metaSPAdes: a new versatile metagenomic assembler. Genome Res. 2017;27(5):824-34.  https://doi.org/10.1101/gr.213959.116  PMID: 28298430 
  22. National Center for Biotechnology Information. BLAST Command Line Applications User Manual. Bethesda: National Center for Biotechnology Information; 2008. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279690/
  23. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9(4):357-9.  https://doi.org/10.1038/nmeth.1923  PMID: 22388286 
  24. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. , 1000 Genome Project Data Processing Subgroup. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25(16):2078-9.  https://doi.org/10.1093/bioinformatics/btp352  PMID: 19505943 
  25. Kalantar KL, Carvalho T, De Bourcy CFA, Dimitrov B, Dingle G, Egger R, et al. IDseq-An open source cloud-based pipeline and analysis service for metagenomic pathogen detection and monitoring. Gigascience. 2020;15;9(10):giaa111. PMID: 33057676 
  26. Schep AN, Kummerfeld SK. iheatmapr: Interactive complex heatmaps in R. J Open Source Softw. 2017;2(16):359.  https://doi.org/10.21105/joss.00359 
  27. Harvala H, Robertson I, McWilliam Leitch EC, Benschop K, Wolthers KC, Templeton K, et al. Epidemiology and clinical associations of human parechovirus respiratory infections. J Clin Microbiol. 2008;46(10):3446-53.  https://doi.org/10.1128/JCM.01207-08  PMID: 18753351 
  28. Li J, Yan D, Chen L, Zhang Y, Song Y, Zhu S, et al. Multiple genotypes of Echovirus 11 circulated in mainland China between 1994 and 2017. Sci Rep. 2019;9(1):10583.  https://doi.org/10.1038/s41598-019-46870-w  PMID: 31332200 
  29. Oberste MS, Nix WA, Kilpatrick DR, Flemister MR, Pallansch MA. Molecular epidemiology and type-specific detection of echovirus 11 isolates from the Americas, Europe, Africa, Australia, southern Asia and the Middle East. Virus Res. 2003;91(2):241-8.  https://doi.org/10.1016/S0168-1702(02)00291-5  PMID: 12573503 
  30. Cabrerizo M, Díaz-Cerio M, Muñoz-Almagro C, Rabella N, Tarragó D, Romero MP, et al. Molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in Spain. J Med Virol. 2017;89(3):435-42.  https://doi.org/10.1002/jmv.24658  PMID: 27505281 
  31. McWilliam Leitch EC, Cabrerizo M, Cardosa J, Harvala H, Ivanova OE, Kroes ACM, et al. Evolutionary dynamics and temporal/geographical correlates of recombination in the human enterovirus echovirus types 9, 11, and 30. J Virol. 2010;84(18):9292-300.  https://doi.org/10.1128/JVI.00783-10  PMID: 20610722 
  32. Gámbaro F, Pérez AB, Agüera E, Prot M, Martínez-Martínez L, Cabrerizo M, et al. Genomic surveillance of enterovirus associated with aseptic meningitis cases in southern Spain, 2015-2018. Sci Rep. 2021;11(1):21523.  https://doi.org/10.1038/s41598-021-01053-4  PMID: 34728763 
  33. Benschop KSM, Broberg EK, Hodcroft E, Schmitz D, Albert J, Baicus A, et al. Molecular epidemiology and evolutionary trajectory of emerging echovirus 30. Emerg Infect Dis. 2021;27(6):1616-26.  https://doi.org/10.3201/eid2706.203096  PMID: 34013874 
  34. Cabrerizo M, Trallero G, Simmonds P. Recombination and evolutionary dynamics of human echovirus 6. J Med Virol. 2014;86(5):857-64.  https://doi.org/10.1002/jmv.23741  PMID: 24114692 
  35. Muslin C, Mac Kain A, Bessaud M, Blondel B, Delpeyroux F. Recombination in enteroviruses, a multi-step modular evolutionary process. Viruses. 2019;11(9):859.  https://doi.org/10.3390/v11090859  PMID: 31540135 
  36. Harvala H, Wolthers KC, Simmonds P. Parechoviruses in children: understanding a new infection. Curr Opin Infect Dis. 2010;23(3):224-30.  https://doi.org/10.1097/QCO.0b013e32833890ca  PMID: 20414971 
  37. Kidd S, Yee E, English R, Rogers S, Emery B, Getachew H, et al. National Surveillance for Acute Flaccid Myelitis - United States, 2018-2020. MMWR Morb Mortal Wkly Rep. 2021;70(44):1534-8.  https://doi.org/10.15585/mmwr.mm7044a2  PMID: 34735423 
  38. Sooksawasdi Na Ayudhya S, Sips GJ, Bogers S, Leijten LME, Laksono BM, Smeets LC, et al. Detection of intrathecal antibodies to diagnose enterovirus infections of the central nervous system. J Clin Virol. 2022;152:105190.  https://doi.org/10.1016/j.jcv.2022.105190  PMID: 35640402 
  39. Mori D, Ranawaka U, Yamada K, Rajindrajith S, Miya K, Perera HKK, et al. Human bocavirus in patients with encephalitis, Sri Lanka, 2009-2010. Emerg Infect Dis. 2013;19(11):1859-62.  https://doi.org/10.3201/eid1911.121548  PMID: 24188380 
  40. Calvo C, Gallardo P, Torija P, Bellón S, Méndez-Echeverría A, Del Rosal T, et al. Enterovirus neurological disease and bacterial coinfection in very young infants with fever. J Clin Virol. 2016;85:37-9.  https://doi.org/10.1016/j.jcv.2016.10.020  PMID: 27833059 
/content/10.2807/1560-7917.ES.2024.29.44.2400221
Loading

Data & Media loading...

Supplementary data

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error