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Enteroviral Central Nervous System Infections in Children of the Region of Monastir, Tunisia: Diagnosis, Laboratory Findings of Cerebrospinal Fluid and Clinical Manifestations

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Abstract

Human enteroviruses (HEV) are one of the major causes of central nervous system (CNS) infections in pediatrics. A prospective study was conducted to assess the epidemiological, clinical, and laboratory characteristics of enterovirus (EV) infections of the CNS in children under 15-years-old, suspected of having viral CNS infections and admitted to the Pediatric Department of Monastir University Hospital, Tunisia. Enteroviral RNA was detected by 5′ NCR nested RT-PCR assay in 33 % (20 out of 60) of cerebrospinal fluid specimens, whereas only six samples (10 %) were EV positive in cell culture. EV-positive patients were clustered according to their clinical manifestations, predominantly diagnosed as aseptic meningitis (65 %) and meningoencephalitis (20 %). Fever, headache, vomiting, and neck stiffness were the most pronounced symptoms. Pleocytosis with the predominance of lymphocytes was observed in 60 % of EV positive specimens. Although patients suffering from EV infections were encountered throughout the year, most occurred during spring and summer months. Using VP1-2A nested RT-PCR and sequence analysis, three of the 20 positive HEV were identified as Echovirus (E)-9. This is the first report of a cluster of aseptic meningitis cases caused by E-9 in Monastir.

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References

  1. Abdallah H, Rezig D, Bahri O, Ben Yahia A, Kechrid A, Khaldi F, Barsaoui S, Bousnina S, Kanoun F, Bouzouia N, Triki H. Place des entérovirus dans les méningites aseptiques en Tunisie. La Tunisie médicale. 2003;81:919–25.

    PubMed  CAS  Google Scholar 

  2. Absug MJ, Rotbart HA. Enterovirus infections of neonates and infants. Sem Ped Infect Dis. 1999;10:169–76.

    Article  Google Scholar 

  3. Bahri O, Rezig D, Ben Nejma-Oueslatin B, Ben Yahia A, Ben Sassi J, Hogga N, Sadraoui A, Triki H. Enteroviruses in Tunisia: virological surveillance over 12 years (1992–2003). J Med Microbiol. 2005;54:63–9.

    Article  PubMed  CAS  Google Scholar 

  4. Bailly JL, Beguet A, Chambon M, Henquell C, Peigue-Lafeuille H. Nosocomial transmission of echovirus 30: molecular evidence by phylogenetic analysis of the VP1 encoding sequence. J Clin Microbiol. 2000;38:2889–92.

    PubMed  CAS  Google Scholar 

  5. Berlin LE, Rorabaugh ML, Heldrich F, Roberts K, Doran T, Modlin JF. Aseptic meningitis in infants <2 years of age: diagnosis and etiology. J Infect Dis. 1993;168:888–92.

    Article  PubMed  CAS  Google Scholar 

  6. Bernit E, de Lamballerie X, Zandotti C, Berger P, Veit V, Schleinitz N, de Micco P, Harlé JR, Charrel RN. Prospective investigation of a large outbreak of meningitis due to echovirus 30 during summer 2000 in Marseilles, France. Medicine. 2004;83:245–53.

    Article  PubMed  Google Scholar 

  7. Bottner A, Daneschnejad S, Handrick W, Schuster V, Liebert UG, Kiess W. A season of aseptic meningitis in Germany: epidemiologic, clinical and diagnostic aspects. Pediatr Infect Dis J. 2002;21:1126–32.

    Article  PubMed  Google Scholar 

  8. Caro V, Guillot S, Delpeyroux F, Crainic R. Molecular strategy for “serotyping” of human enteroviruses. J Gen Virol. 2001;82:79–91.

    PubMed  CAS  Google Scholar 

  9. Casas I, Tenorio A, Echevarria JM, Klapper PE, Cleator GM. Detection of enteroviral RNA and specific DNA of herpesviruses by multiplex genome amplification. J Virol Methods. 1997;66:39–50.

    Article  PubMed  CAS  Google Scholar 

  10. Casas I, Palacios GF, Trallero G, Cisterna D, Freire MC, Tenorio A. Molecular characterization of human enteroviruses in clinical samples: comparison between VP2, VP1, and RNA polymerase regions using RT nested PCR assays and direct sequencing of products. J Med Virol. 2001;65:138–48.

    Article  PubMed  CAS  Google Scholar 

  11. Cherry JD. Enteroviruses. In: Remington JS, Klein JO, editors. Infections in the fetus and newborn infant. Philadelphia: WB Saunders; 1995. p. 374–7.

    Google Scholar 

  12. Ciardi M, Giacchetti G, Fedele CG, Tenorio A, Brandi A, Libertone R. Acute cerebellitis caused by Herpes Simplex Virus Type 1. Clin Infect Dis. 2003;36:e50–4.

    Article  PubMed  Google Scholar 

  13. Connolly KJ, Hammer SM. The acute aseptic meningitis syndrome. Infect Dis Clin North Am. 1990;4:599–622.

    PubMed  CAS  Google Scholar 

  14. Dommergues MA, Harzic M, Gobert ME, Landre C, De Truchis A, Charara O, Foucaud P. Seasonal outbreak of enteroviral meningitis during summer 2005: experience of a French pediatric unit. Arch Pediatr. 2007;14:964–70.

    Article  PubMed  Google Scholar 

  15. Dumaidi K, Frantzidou F, Papa A, Diza E, Antoniadis A. Enterovirus meningitis in Greece from 2003–2005: diagnosis, CSF laboratory findings, and clinical manifestations. J Clin Lab Anal. 2006;20:177–83.

    Article  PubMed  CAS  Google Scholar 

  16. Elmore JG, Horwitz RI, Quagliarello VJ. Acute meningitis with a negative Grams stain: clinical and management outcomes in 171 episodes. Am J Med. 2000;100:78–84.

    Article  Google Scholar 

  17. Gharbi J, Jaïdane H, Ben M’hadheb M, El Hiar R, Chouchene C, Gueddiche MN, Aouni M. Epidemiological study of non-polio enterovirus neurological infections in children in the region of Monastir, Tunisia. Diagn Microbiol Infect Dis. 2006;54:31–6.

    Article  PubMed  Google Scholar 

  18. Graham AK, Murdoch DR. Association between cerebrospinal fluid pleocytosis and enteroviral meningitis. J Clin Microbiol. 2005;43:1491.

    Article  PubMed  Google Scholar 

  19. Guney C, Ozkaya E, Yapar M, Gumus I, Kubar A, Doganci L. Laboratory diagnosis of enteroviral infections of the central nervous system by using a nested RT-polymerase chain reaction (PCR) assay. Diagn Microbiol Infect Dis. 2003;47:557–62.

    Article  PubMed  CAS  Google Scholar 

  20. Henquell C, Chambon M, Bailly JL, Alcaraz S, De Champs C, Archimbaud C, Labbé A, Charbonné F, Peigue-Lafeuille H. Prospective analysis of 61 cases of enteroviral meningitis: interest of systematic genome detection in cerebrospinal fluid irrespective of cytologic examination results. J Clin Virol. 2001;21:29–35.

    Article  PubMed  CAS  Google Scholar 

  21. Hosoya M, Sato M, Honzumi K, Katayose M, Kawasaki Y, Sakuma H, Kato K, Shimada Y, Ishiko H, Suzuki H. Association of nonpolio enteroviral infection in the central nervous system of children. Pediatrics. 2001;107:1–5.

    Article  Google Scholar 

  22. Hosoya M, Sato M, Honzumi K, Katayose M, Sakuma H, Ishiko H, Shimada Y, Kato K, Suzuki H. Application of polymerase chain reaction and subsequent phylogenetic analysis to the diagnosis of enteroviral infection in the central nervous system. J Clin Virol. 2002;25:S27–38.

    Article  PubMed  CAS  Google Scholar 

  23. Ishiko H, Shimada Y, Yonaha M, Hashimoto O, Hayashi A, Sakae K, Takeda N. Molecular diagnosis of human enteroviruses by phylogeny-based classification by use of the VP4 sequence. J Infect Dis. 2002;185:744–54.

    Article  PubMed  CAS  Google Scholar 

  24. Jaidane H, Chouchane C, Gharbi J, Chouchane S, Merchaoui Z, Ben Meriem C, Aouni M, Guediche MN. Entéroviroses neuroméningées en Tunisie: profil épidémiologique, clinique et évolutif. À propos de 26 cas pédiatriques. Med Mal Infect. 2005;35:33–8.

    Article  PubMed  CAS  Google Scholar 

  25. Kämmerer U, Kunkel B, Korn K. Nested PCR for specific detection and rapid identification of human picornaviruses. J Clin Microbiol. 1994;32:285–91.

    PubMed  Google Scholar 

  26. Knowles NJ, Hovi T, Hyypiä T, King AMQ, Lindberg M, Pallansch MA, Palmenberg AC, Simmonds P, Skern T, Stanway G, Yamashita T, Zell R. Picornaviridae. In: King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ, editors. Virus taxonomy: classification and nomenclature of viruses: ninth report of the International Committee on Taxonomy of Viruses. San Diego: Elsevier; 2011. p. 855–80.

    Google Scholar 

  27. Kuan MM. Detection and rapid differentiation of human enteroviruses following genomic amplification. J Clin Microbiol. 1997;35:2598–601.

    PubMed  CAS  Google Scholar 

  28. Kupila L, Vuorinen T, Vainionpää R, Hukkanen V, Marttila RJ, Kotilainen P. Etiology of aseptic meningitis and encephalitis in an adult population. Neurology. 2006;66:75–80.

    Article  PubMed  CAS  Google Scholar 

  29. Landry ML. Frequency of normal cerebrospinal fluid protein level and leukocyte count in enterovirus meningitis. J Clin Virol. 2005;32:73–4.

    Article  PubMed  Google Scholar 

  30. Lina B, Pozzetto B, Andreoletti L, Beguier E, Bourlet T, Dussaix E, Grangeot-Keros L, Gratacap-Cavallier B, Henquell C, Legrand-Quillien MC, Novillo A, Palmer P, Petitjean J, Sandres K, Dubreuil P, Fleury H, Freymuth F, Leparc-Goffart I, Hober D, Izopet J, Kopecka H, Lazizi Y, Lafeuille H, Lebon P, Aymard M. Multicenter evaluating of a commercially available PCR assay for diagnosing enterovirus infection in a panel of cerebrospinal fluid specimens. J Clin Microbiol. 1996;34:3002–6.

    PubMed  CAS  Google Scholar 

  31. Logotheti M, Pogka V, Horefti E, Papadakos K, Giannaki M, Pangalis A, Sgouras D, Mentis A. Laboratory investigation and phylogenetic analysis of enteroviruses involved in an aseptic meningitis outbreak in Greece during the summer of 2007. J Clin Virol. 2009;46:270–4.

    Article  PubMed  CAS  Google Scholar 

  32. McIntyre JP, Keen GA. Laboratory surveillance of viral meningitis by examination of cerebrospinal fluid in Cape Town, 1981–9. Epidemiol Infect. 1993;111:357–71.

    Article  PubMed  CAS  Google Scholar 

  33. Mistchenko AS, Viegas M, Latta MP, Barrero PR. Molecular and epidemiologic analysis of enterovirus B neurological infection in Argentine children. J Clin Virol. 2006;37:293–9.

    Article  PubMed  Google Scholar 

  34. Morens DM. Enteroviral disease in early infancy. J Pediatr. 1978;92:374–7.

    Article  PubMed  CAS  Google Scholar 

  35. Muir P, Kämmerer U, Korn K, Mulders MN, Poyry T, Weissbrich B, Kandolf R, Cleator GM, van Loon AM. Molecular typing of enteroviruses: current status and future requirements. The European Union Concerted Action on Virus Meningitis and Encephalitis. Clin Microbiol Rev. 1998;11:202–27.

    PubMed  CAS  Google Scholar 

  36. Mulford WS, Buller RS, Arens MQ, Storch GA. Correlation of cerebrospinal fluid (CSF) cell counts and elevated CSF protein levels with enterovirus reverse transcription-PCR results in pediatric and adult patients. J Clin Microbiol. 2004;42:4199–203.

    Article  PubMed  CAS  Google Scholar 

  37. Nasri D, Bouslama L, Omar S, Saoudin H, Bourlet T, Aouni M, Pozzetto B, Pillet S. Typing of human enterovirus by partial sequencing of VP2. J Clin Microbiol. 2007;45:2370–9.

    Article  PubMed  CAS  Google Scholar 

  38. Nicholson F, Meetoo G, Aiyar S, Banatvala JE, Muir P. Detection of enterovirus RNA in clinical samples by nested polymerase chain reaction for rapid diagnosis of enterovirus infection. J Virol Methods. 1994;48:155–66.

    Article  PubMed  CAS  Google Scholar 

  39. Norder H, Bjerregaard L, Magnius L. Homotypic echoviruses share aminoterminal VP1 sequence homology applicable for typing. J Med Virol. 2001;63:35–44.

    Article  PubMed  CAS  Google Scholar 

  40. Nowak DA, Boehmer R, Fuchs HH. A retrospective clinical, laboratory, and outcome analysis of 43 cases of acute aseptic meningitis. Euro J Neurol. 2003;10:271–80.

    Article  CAS  Google Scholar 

  41. Oberste MS, Maher K, Kilpatrick DR, Flemister MR, Brown BA, Pallansch MA. Typing of human enterovirus by partial sequencing of VP1. J Clin Microbiol. 1999;37:1288–93.

    PubMed  CAS  Google Scholar 

  42. Oberste MS, Maher K, Kilpatrick DR, Pallansch MA. Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J Virol. 1999;73:1941–8.

    PubMed  CAS  Google Scholar 

  43. Oberste MS, Maher K, Flemister MR, Marchetti G, Kilpatrick DR, Pallansch MA. Comparison of classic and molecular approaches for the identification of untypeable enteroviruses. J Clin Microbiol. 2000;38:1170–4.

    PubMed  CAS  Google Scholar 

  44. Ponka A, Pettersson T. The incidence and aetiology of central nervous system infections in Helsinki in 1980. Acta Neurol Scand. 1982;66:529–35.

    Article  PubMed  CAS  Google Scholar 

  45. Rotbart HA. Enteroviral infections of the central nervous system. Clin Infect Dis. 1995;20:971–81.

    Article  PubMed  CAS  Google Scholar 

  46. Rotbart HA, Sawyer MH, Fast S, Lewinski C, Murphy N, Keyser EF, Spadoro J, Kao SY, Loeffelhoz M. Diagnosis of enteroviral meningitis by using PCR with a colorimetric microwell detection assay. J Clin Microbiol. 1994;32:2590–2.

    PubMed  CAS  Google Scholar 

  47. Rotbart HA, Ahmed A, Hickey S, Dagan R, McCracken GH Jr, Whitley RJ, Modlin JF, Cascino M, O’Connell JF, Menegus MA, Blum D. Diagnosis of enterovirus infection by polymerase chain reaction of multiple specimen types. Pediatr Infect Dis J. 1997;16:409–11.

    Article  PubMed  CAS  Google Scholar 

  48. Rubio G, Mintegui S, Gaztelurrutia L, Sánchez J. Meningitis by enterovirus in pediatrics. Clinical characteristics and virologic diagnosis. Enferm Infecc Microbiol Clin. 1998;16:14–8.

    PubMed  CAS  Google Scholar 

  49. Santti J, Hyypiä T, Kinnunen L, Salminen M. Evidence of recombination among enteroviruses. J Virol. 1999;73:8741–9.

    PubMed  CAS  Google Scholar 

  50. Sato M, Hosoya M, Honzumi K, Watanabe M, Ninomiya N, Shigeta S, Suzuki H. Cytokine and cellular inflammatory sequence in enteroviral meningitis. Pediatrics. 2003;112:1103–7.

    Article  PubMed  Google Scholar 

  51. Sawyer MH. Enterovirus Infections: diagnosis and treatment. Sem Ped Infect Dis. 2002;13:40–7.

    Article  Google Scholar 

  52. Shoja ZO, Tabatabai H, Sarijloo M, Shahmahmoodi S, Azad TM, Nategh R. Detection of enteroviruses by reverse-transcriptase polymerase chain reaction in cell culture negative stool specimens of patients with acute flaccid paralysis. J Virol Methods. 2007;142:95–7.

    Article  PubMed  CAS  Google Scholar 

  53. Steinlin M, Wehrli E, Berne. L’accident vasculaire ischémique en pédiatrie. Quand y penser-quoi faire !*. Paediatrica. 2009;20:22–6.

    Google Scholar 

  54. Tardieu M, Dussaix E, Lebon P, Landrieu P. Prospective study of 59 cases of viral meningitis in children. Clinical and virologic diagnosis. Epidemiology and physiopathology. Arch Fr Pediatr. 1986;43:9–14.

    PubMed  CAS  Google Scholar 

  55. Thoelen I, Lemey P, Van Der Donck I, Beuselinck K, Lindberg AM, Van Ranst M. Molecular typing and epidemiology of enteroviruses identified from an outbreak of aseptic meningitis in Belgium during the summer of 2000. J Med Virol. 2003;70:420–9.

    Article  PubMed  CAS  Google Scholar 

  56. Thoren A, Widell A. PCR for the diagnosis of enteroviral meningitis. Scand J Infect Dis. 1994;26:249–54.

    Article  PubMed  CAS  Google Scholar 

  57. Trallero G, Avellon A, Otero A, De Miguel T, Pérez C, Rabella N, Rubio G, Echevarria JE, Cabrerizo M. Enteroviruses in Spain over the decade 1998–2007: virological and epidemiological studies. J Clin Virol. 2010;47:170–6.

    Article  PubMed  CAS  Google Scholar 

  58. Verstrepen WA, Bruynseels P, Mertens AH. Evaluation of a rapid real-time RT-PCR assay for detection of enterovirus RNA in cerebrospinal fluid specimens. J Clin Virol. 2002;25:S39–43.

    Article  PubMed  CAS  Google Scholar 

  59. Yerly S, Gervaix A, Simonet V, Caflisch M, Perrin L, Wunderli W. Rapid and sensitive detection of enteroviruses in specimens from patients with aseptic meningitis. J Clin Microbiol. 1996;34:199–201.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Ministère de l’Enseignement Supérieur et de la Recherche Scientifique (LR 99 ES 27), University of Monastir, Tunisia. We want to express our gratitude to the staff of the Pediatrics Department of Fattouma Bourguiba Hospital of Monastir. The authors are grateful to Rachel Décor (B.C.T. Consulting, Rue du 13 Août 1956, 5000 Monastir, Tunisia) for the English revision of this manuscript.

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EL Hiar, R., Haddad, S., Jaïdane, H. et al. Enteroviral Central Nervous System Infections in Children of the Region of Monastir, Tunisia: Diagnosis, Laboratory Findings of Cerebrospinal Fluid and Clinical Manifestations. Indian J. Virol. 23, 294–302 (2012). https://doi.org/10.1007/s13337-012-0104-1

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