Skip to main content


Log in

Comparison of clinical and laboratory characteristics during two major paediatric meningitis outbreaks of echovirus 30 and other non-polio enteroviruses in Germany in 2008 and 2013

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript


Viral meningitis is mainly caused by non-polio enteroviruses (NPEV). Large-scale data on the clinical characteristics between different outbreaks within the same region are lacking. This study aimed to analyse a possible influence of the circulating NPEV genotype on the disease outcome of affected children. A retrospective cohort study analysing two major outbreaks of NPEV meningitis in Germany in 2008 and 2013 was conducted in cooperation with the National Reference Centre for Poliomyelitis and Enteroviruses (NRC PE) and five German children’s hospitals. A total of 196 patients with laboratory-confirmed NPEV meningitis were enrolled. In 2008, children with NPEV meningitis had significantly higher fever and showed more behavioural changes and less back pain. To better define typical findings in echovirus 30 (E-30) meningitis, patients were split into the following three groups: E-30 positive patients, patients with “Non E-30” infection and patients with “Untyped” NPEV infection. E-30 positive patients were significantly older and their disease course was more acute, with early admission to but also early discharge from hospital. E-30 positive patients showed a significantly higher rate of headache and meningism, and a lower rate of diarrhoea and clinically defined septicaemia when compared to the others. Regarding laboratory testing, E-30 positive patients presented with significantly elevated peripheral blood neutrophil counts when compared to patients with “Non E-30” or “Untyped” NPEV infection. In conclusion, E-30 meningitis in children shows a characteristic pattern of clinical features. To further characterise NPEV strains worldwide, continuous surveillance and typing of NPEV strains causing central nervous system disease is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others


  1. Rotbart HA (2000) Viral meningitis. Semin Neurol 20:277–292

    Article  CAS  PubMed  Google Scholar 

  2. Romero JR, Newland JG (2003) Viral meningitis and encephalitis: traditional and emerging viral agents. Semin Pediatr Infect Dis 14:72–82

    Article  PubMed  Google Scholar 

  3. Michos AG, Syriopoulou VP, Hadjichristodoulou C, Daikos GL, Lagona E, Douridas P et al (2007) Aseptic meningitis in children: analysis of 506 cases. PLoS One 2(7):e674

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rudolph H, Schroten H, Tenenbaum T (2016) Enterovirus infections of the central nervous system in children: an update. Pediatr Infect Dis J 35:567–569

    Article  PubMed  Google Scholar 

  5. Chadwick DR (2006) Viral meningitis. Br Med Bull 75–76:1–14

    Article  PubMed  Google Scholar 

  6. Roth B, Enders M, Arents A, Pfitzner A, Terletskaia-Ladwig E (2007) Epidemiologic aspects and laboratory features of enterovirus infections in Western Germany, 2000–2005. J Med Virol 79:956–962

    Article  PubMed  Google Scholar 

  7. Richter J, Koptides D, Tryfonos C, Christodoulou C (2006) Molecular typing of enteroviruses associated with viral meningitis in Cyprus, 2000–2002. J Med Microbiol 55:1035–1041

    Article  CAS  PubMed  Google Scholar 

  8. Tryfonos C, Richter J, Koptides D, Yiangou M, Christodoulou CG (2011) Molecular typing and epidemiology of enteroviruses in Cyprus, 2003–2007. J Med Microbiol 60:1433–1440

    Article  PubMed  Google Scholar 

  9. Mladenova Z, Buttinelli G, Dikova A, Stoyanova A, Troyancheva M, Komitova R et al (2014) Aseptic meningitis outbreak caused by echovirus 30 in two regions in Bulgaria, May–August 2012. Epidemiol Infect 142:2159–2165

    Article  CAS  PubMed  Google Scholar 

  10. Cabrerizo M, Echevarria JE, González I, de Miguel T, Trallero G (2008) Molecular epidemiological study of HEV-B enteroviruses involved in the increase in meningitis cases occurred in Spain during 2006. J Med Virol 80:1018–1024

    Article  PubMed  Google Scholar 

  11. Romero JR (2002) Diagnosis and management of enteroviral infections of the central nervous system. Curr Infect Dis Rep 4:309–316

    Article  PubMed  Google Scholar 

  12. Akhmadishina LV, Govorukhina MV, Kovalev EV, Nenadskaya SA, Ivanova OE, Lukashev AN (2015) Enterovirus A71 meningoencephalitis outbreak, Rostov-on-Don, Russia, 2013. Emerg Infect Dis 21:1440–1443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Milia MG, Cerutti F, Gregori G, Burdino E, Allice T, Ruggiero T et al (2013) Recent outbreak of aseptic meningitis in Italy due to Echovirus 30 and phylogenetic relationship with other European circulating strains. J Clin Virol 58:579–583

    Article  PubMed  Google Scholar 

  14. Savolainen-Kopra C, Paananen A, Blomqvist S, Klemola P, Simonen M-L, Lappalainen M et al (2011) A large Finnish echovirus 30 outbreak was preceded by silent circulation of the same genotype. Virus Genes 42:28–36

    Article  CAS  PubMed  Google Scholar 

  15. Dalwai A, Ahmad S, Al-Nakib W (2010) Echoviruses are a major cause of aseptic meningitis in infants and young children in Kuwait. Virol J 7:236

    Article  PubMed  PubMed Central  Google Scholar 

  16. Österback R, Kalliokoski T, Lähdesmäki T, Peltola V, Ruuskanen O, Waris M (2015) Echovirus 30 meningitis epidemic followed by an outbreak-specific RT-qPCR. J Clin Virol 69:7–11

    Article  PubMed  Google Scholar 

  17. Mantadakis E, Pogka V, Voulgari-Kokota A, Tsouvala E, Emmanouil M, Kremastinou J et al (2013) Echovirus 30 outbreak associated with a high meningitis attack rate in Thrace, Greece. Pediatr Infect Dis J 32:914–916

    PubMed  Google Scholar 

  18. Nougairede A, Bessaud M, Thiberville S-D, Piorkowski G, Ninove L, Zandotti C et al (2014) Widespread circulation of a new echovirus 30 variant causing aseptic meningitis and non-specific viral illness, South-East France, 2013. J Clin Virol 61:118–124

    Article  PubMed  Google Scholar 

  19. Takamatsu Y, Uchida L, Nga PT, Okamoto K, Nabeshima T, Thao DTT et al (2013) An approach for differentiating echovirus 30 and Japanese encephalitis virus infections in acute meningitis/encephalitis: a retrospective study of 103 cases in Vietnam. Virol J 10:280

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tseng F-C, Huang H-C, Chi C-Y, Lin T-L, Liu C-C, Jian J-W et al (2007) Epidemiological survey of enterovirus infections occurring in Taiwan between 2000 and 2005: Analysis of sentinel physician surveillance data. J Med Virol 79:1850–1860

    Article  CAS  PubMed  Google Scholar 

  21. Zhao YN, Perlin DS, Park S, Jiang RJ, Chen L, Chen Y et al (2006) FDJS03 isolates causing an outbreak of aseptic meningitis in China that evolved from a distinct Echovirus 30 lineage imported from countries of the Commonwealth of Independent States. J Clin Microbiol 44:4142–4148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Uysal G, Ozkaya E, Güven A (2000) Echovirus 30 outbreak of aseptic meningitis in Turkey. Pediatr Infect Dis J 19:490

    Article  CAS  PubMed  Google Scholar 

  23. Vieth UC, Kunzelmann M, Diedrich S, Timm H, Ammon A, Lyytikäinen O et al (1999) An echovirus 30 outbreak with a high meningitis attack rate among children and household members at four day-care centers. Eur J Epidemiol 15:655–658

    Article  CAS  PubMed  Google Scholar 

  24. Kim H-J, Kang B, Hwang S, Hong J, Kim K, Cheon D-S (2012) Epidemics of viral meningitis caused by echovirus 6 and 30 in Korea in 2008. Virol J 9:38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Harvala H, Griffiths M, Solomon T, Simmonds P (2014) Distinct systemic and central nervous system disease patterns in enterovirus and parechovirus infected children. J Infect 69(1):69–74

    Article  PubMed  Google Scholar 

  26. Sharp J, Harrison CJ, Puckett K, Selvaraju SB, Penaranda S, Nix WA et al (2013) Characteristics of young infants in whom human parechovirus, enterovirus or neither were detected in cerebrospinal fluid during sepsis evaluations. Pediatr Infect Dis J 32:213–216

    PubMed  PubMed Central  Google Scholar 

  27. de Graaf H, Pelosi E, Cooper A, Pappachan J, Sykes K, MacIntosh I et al (2016) Severe enterovirus infections in hospitalized children in the South of England: clinical phenotypes and causative genotypes. Pediatr Infect Dis J 35:723–727

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rao DC, Ananda Babu M, Raghavendra A, Dhananjaya D, Kumar S, Maiya PP (2013) Non-polio enteroviruses and their association with acute diarrhea in children in India. Infect Genet Evol 17:153–161

    Article  PubMed  Google Scholar 

  29. Zhou H-T, Yi H-S, Guo Y-H, Pan Y-X, Tao S-H, Wang B et al (2016) Enterovirus-related diarrhoea in Guangdong, China: clinical features and implications in hand, foot and mouth disease and herpangina. BMC Infect Dis 16:128

    Article  PubMed  PubMed Central  Google Scholar 

  30. Archimbaud C, Ouchchane L, Mirand A, Chambon M, Demeocq F, Labbé A et al (2013) Improvement of the management of infants, children and adults with a molecular diagnosis of Enterovirus meningitis during two observational study periods. PLoS One 8:e68571. doi:10.1371/journal.pone.0068571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Huizing KMN, Swanink CMA, Landstra AM, van Zwet AA, van Setten PA (2011) Rapid enterovirus molecular testing in cerebrospinal fluid reduces length of hospitalization and duration of antibiotic therapy in children with aseptic meningitis. Pediatr Infect Dis J 30:1107–1109

    Article  PubMed  Google Scholar 

  32. Bernit E, de Lamballerie X, Zandotti C, Berger P, Veit V, Schleinitz N et al (2004) Prospective investigation of a large outbreak of meningitis due to echovirus 30 during summer 2000 in Marseilles, France. Medicine (Baltimore) 83:245–253

  33. Hu Y, Jiang L, Peng H-L (2015) Clinical analysis of 134 children with nervous system damage caused by enterovirus 71 infection. Pediatr Infect Dis J 34:718–723

    Article  PubMed  Google Scholar 

Download references


We are grateful for the support offered by the staff of the involved children’s hospitals: University Children’s Hospital Mannheim, Children’s Hospital Ludwigsburg, Children’s Hospital, Evangelisches Krankenhaus Düsseldorf, University Children’s Hospital Erlangen and Children’s Hospital Auf der Bult, Hannover and the members of the involved German reference laboratories for enteroviral infections: Masyar Monazahian of the Governmental Institute of Public Health of Lower Saxony, Hannover; Ortwin Adams, Institute of Virology, University Hospital, Heinrich-Heine-University, Düsseldorf; Klaus Korn, Institute of Clinical and Molecular Virology, Erlangen; Axel Schubert, Institute of Virology, University Hospital Ulm; and Ralph Hahn, Laboratory Prof. Gisela Enders and colleagues, MVZ, Stuttgart.

Author information

Authors and Affiliations


Corresponding author

Correspondence to H. Rudolph.

Ethics declarations


This study was not funded. HR has been supported by a fellowship for women from the University of Heidelberg “Olympia Morata”.

Conflict of interest

There is no conflict of interest.

Ethical approval

Approval of this retrospective study was provided by the local ethics committees (Medical Faculty of Mannheim, Heidelberg University [2014-824R-MA]). Local ethics committees of the involved children’s hospitals were informed about the study and had no objections when performed in pseudonymous form.

Informed consent

Not applicable.

Electronic supplementary material

Below is the link to the electronic supplementary material.


(DOCX 736 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rudolph, H., Prieto Dernbach, R., Walka, M. et al. Comparison of clinical and laboratory characteristics during two major paediatric meningitis outbreaks of echovirus 30 and other non-polio enteroviruses in Germany in 2008 and 2013. Eur J Clin Microbiol Infect Dis 36, 1651–1660 (2017).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: