1887

Abstract

Viral infections are increasingly an important cause of central nervous system (CNS) complications.

There is no comprehensive insight about CNS infections due to viral agents among Iranian children.

This study aimed to investigate the viral aetiology, clinical and epidemiological profile of children with acute infections of the CNS.

A prospective study was conducted on children at the referral hospital in Isfahan, Iran, from June 2019 to June 2020. A multiplex PCR assay was used to detect the viral causative agent in cerebrospinal fluid and throat/rectal swab samples.

Among 103 patients with eligible criteria, a confirmed or probable viral aetiology was detected in 41 (39.8 %) patients, including enteroviruses – 56.1 %, herpes simplex virus 1/2 (HSV-1/2) – 31.7 %, Epstein-Barr virus – 17.1 %, varicella-zoster virus (VZV) – 9.7 %, influenza A virus (H1N1) –4.9 % and mumps – 2.4 %. There was a higher proportion of PCR-positive samples in infants than in other age groups. Encephalitis and meningoencephalitis were diagnosed in 68.3 % (28/41) and 22 % (9/41) PCR-positive cases, respectively.

The findings of this research provide insights into the clinical and viral aetiological patterns of acute CNS infections in Iran, and the importance of molecular methods to identify CNS viruses. HSV and VZV were identified as important causes of encephalitis in young children.

Funding
This study was supported by the:
  • Isfahan University of Medical Sciences (Award 398265)
    • Principle Award Recipient: ShararehMoghim
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001602
2022-10-27
2024-05-02
Loading full text...

Full text loading...

References

  1. Schlechter Salinas AK, Hains DS, Jones T, Harrell C, Meredith M. Testing for urinary tract infection in the influenza/respiratory syncytial virus-positive febrile infant aged 2 to 12 months. Pediatr Emerg Care 2019; 35:666–670 [View Article]
    [Google Scholar]
  2. Mallewa M, Vallely P, Faragher B, Banda D, Klapper P et al. Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study. Lancet Glob Health 2013; 1:e153–e160 [View Article]
    [Google Scholar]
  3. Ho Dang Trung N, Le Thi Phuong T, Wolbers M, Nguyen Van Minh H, Nguyen Thanh V et al. Aetiologies of central nervous system infection in Viet Nam: a prospective provincial hospital-based descriptive surveillance study. PLoS One 2012; 7:e37825 [View Article]
    [Google Scholar]
  4. Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 2013; 57:1114–1128 [View Article]
    [Google Scholar]
  5. Ben Abid F, Abukhattab M, Ghazouani H, Khalil O, Gohar A et al. Epidemiology and clinical outcomes of viral central nervous system infections. Int J Infect Dis 2018; 73:85–90 [View Article]
    [Google Scholar]
  6. Britton PN, Khoury L, Booy R, Wood N, Jones CA. Encephalitis in Australian children: contemporary trends in hospitalisation. Arch Dis Child 2016; 101:51–56 [View Article]
    [Google Scholar]
  7. Donoso Mantke O, Vaheri A, Ambrose H, Koopmans M, de Ory F et al. Analysis of the surveillance situation for viral encephalitis and meningitis in Europe. Euro Surveill 2008; 13:7–8 [View Article]
    [Google Scholar]
  8. Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 2010; 10:835–844 [View Article]
    [Google Scholar]
  9. Mailles A, Stahl J-P. Steering Committee and Investigators Group Infectious encephalitis in france in 2007: a national prospective study. Clin Infect Dis 2009; 49:1838–1847 [View Article]
    [Google Scholar]
  10. Long SS, Prober CG, Fischer M. Principles and Practice of Pediatric Infectious Diseases Philadelphia, PA: Elsevier; 2022
    [Google Scholar]
  11. Mailles A, Vaillant V, Stahl J-P. Infectious encephalitis in France from 2000 to 2002: the hospital database is a valuable but limited source of information for epidemiological studies. Med Mal Infect 2007; 37:95–102 [View Article]
    [Google Scholar]
  12. Cherry JD. Aseptic meningitis and viral meningitis. Textbook of Pediatric Infectious Disease Philadelphia, PA: Elsevier; 1992 pp 439–445
    [Google Scholar]
  13. Feigin RD, Demmler GJ, Cherry JD, Kaplan SL. Textbook of Pediatric Infectious Diseases Philadelphia, PA: Elsevier; 2004 p 3626
    [Google Scholar]
  14. Ibrahim AI, Obeid MT, Jouma MJ, Roemer K, Mueller-Lantzsch N et al. Prevalence of herpes simplex virus (types 1 and 2), varicella-zoster virus, cytomegalovirus, and human herpesvirus 6 and 7 DNA in cerebrospinal fluid of Middle Eastern patients with encephalitis. J Clin Microbiol 2005; 43:4172–4174 [View Article]
    [Google Scholar]
  15. Li S, Nguyen IP, Urbanczyk K. Common infectious diseases of the central nervous system-clinical features and imaging characteristics. Quant Imaging Med Surg 2020; 10:2227–2259 [View Article]
    [Google Scholar]
  16. Mawuntu AHP, Bernadus JBB, Dhenni R, Wiyatno A, Anggreani R et al. Detection of central nervous system viral infections in adults in Manado, North Sulawesi, Indonesia. PLoS One 2018; 13:e0207440 [View Article]
    [Google Scholar]
  17. Shabani M, Nasr Esfahani B, Sadegh Ehdaei B, Moghim S, Mirzaei A et al. Inhibition of herpes simplex virus type 1 replication by novel hsa-miR-7704 in vitro. Res Pharm Sci 2019; 14:167–174 [View Article]
    [Google Scholar]
  18. Horwood PF, Duong V, Laurent D, Mey C, Sothy H et al. Aetiology of acute meningoencephalitis in Cambodian children, 2010–2013. Emerg Microbes Infect 2017; 6:e35 [View Article]
    [Google Scholar]
  19. Britton PN, Blyth CC, Macartney K, Dale RC, Li-Kim-Moy J et al. The spectrum and burden of influenza-associated neurological disease in children: combined encephalitis and influenza sentinel site surveillance from Australia, 2013–2015. Clin Infect Dis 2017; 65:653–660 [View Article]
    [Google Scholar]
  20. Fowler A, Stödberg T, Eriksson M, Wickström R. Childhood encephalitis in Sweden: etiology, clinical presentation and outcome. Eur J Paediatr Neurol 2008; 12:484–490 [View Article]
    [Google Scholar]
  21. Koskiniemi M, Rantalaiho T, Piiparinen H, von Bonsdorff CH, Färkkilä M et al. Infections of the central nervous system of suspected viral origin: a collaborative study from Finland. J Neurovirol 2001; 7:400–408 [View Article]
    [Google Scholar]
  22. Davison KL, Crowcroft NS, Ramsay ME, Brown DWG, Andrews NJ. Viral encephalitis in England, 1989–1998: what did we miss?. Emerg Infect Dis 2003; 9:234–240 [View Article]
    [Google Scholar]
  23. Muenchhoff M, Goulder PJR. Sex differences in pediatric infectious diseases. J Infect Dis 2014; 209 (Suppl. 3):S120–S126 [View Article]
    [Google Scholar]
  24. do Valle DA, Santos M, Giamberardino HIG, Raboni SM, Scola RH. Acute childhood viral encephalitis in Southern Brazil. Pediatr Infect Dis J 2020; 39:894–898 [View Article]
    [Google Scholar]
  25. Ai J, Xie Z, Liu G, Chen Z, Yang Y et al. Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study. BMC Infect Dis 2017; 17:494 [View Article]
    [Google Scholar]
  26. Calleri G, Libanore V, Corcione S, De Rosa FG, Caramello P. A retrospective study of viral central nervous system infections: relationship amongst aetiology, clinical course and outcome. Infection 2017; 45:227–231 [View Article]
    [Google Scholar]
  27. Connolly KJ, Hammer SM. The acute aseptic meningitis syndrome. Infect Dis Clin North Am 1990; 4:599–622 [View Article]
    [Google Scholar]
  28. Kumar R. Understanding and managing acute encephalitis. F1000Res 2020; 9:60 [View Article]
    [Google Scholar]
  29. Trevejo RT. Acute encephalitis hospitalizations, California, 1990–1999: unrecognized arboviral encephalitis?. Emerg Infect Dis 2004; 10:1442–1449 [View Article]
    [Google Scholar]
  30. Le VT, Phan TQ, Do QH, Nguyen BH, Lam QB et al. Viral etiology of encephalitis in children in southern Vietnam: results of a one-year prospective descriptive study. PLoS Negl Trop Dis 2010; 4:e854 [View Article]
    [Google Scholar]
  31. Olsen SJ, Campbell AP, Supawat K, Liamsuwan S, Chotpitayasunondh T et al. Infectious causes of encephalitis and meningoencephalitis in Thailand, 2003–2005. Emerg Infect Dis 2015; 21:280–289 [View Article]
    [Google Scholar]
  32. Weinberg A, Bloch KC, Li S, Tang Y-W, Palmer M et al. Dual infections of the central nervous system with Epstein-Barr virus. J Infect Dis 2005; 191:234–237 [View Article]
    [Google Scholar]
  33. Kelly MJ, Benjamin LA, Cartwright K, Ajdukiewicz KMB, Cohen DB et al. Epstein-Barr virus coinfection in cerebrospinal fluid is associated with increased mortality in Malawian adults with bacterial meningitis. J Infect Dis 2012; 205:106–110 [View Article]
    [Google Scholar]
  34. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 2020; 395:1771–1778 [View Article]
    [Google Scholar]
  35. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020; 395:1607–1608 [View Article]
    [Google Scholar]
  36. Pouletty M, Borocco C, Ouldali N, Caseris M, Basmaci R et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort. Ann Rheum Dis 2020; 79:999–1006 [View Article]
    [Google Scholar]
  37. Khetsuriani N, Holman RC, Anderson LJ. Burden of encephalitis-associated hospitalizations in the United States, 1988–1997. Clin Infect Dis 2002; 35:175–182 [View Article]
    [Google Scholar]
  38. Glaser CA, Honarmand S, Anderson LJ, Schnurr DP, Forghani B et al. Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis 2006; 43:1565–1577 [View Article] [PubMed]
    [Google Scholar]
  39. Rathore SK, Dwibedi B, Kar SK, Dixit S, Sabat J et al. Viral aetiology and clinico-epidemiological features of acute encephalitis syndrome in eastern India. Epidemiol Infect 2014; 142:2514–2521 [View Article]
    [Google Scholar]
  40. Popiel M, Perlejewski K, Bednarska A, Dzieciątkowski T, Paciorek M et al. Viral etiologies in adult patients with encephalitis in Poland: a prospective single center study. PLoS One 2017; 12:e0178481 [View Article]
    [Google Scholar]
  41. Latifi-Navid S, Ghorashi SA, Siavoshi F, Linz B, Massarrat S et al. Ethnic and geographic differentiation of Helicobacter pylori within Iran. PLoS One 2010; 5:e9645 [View Article]
    [Google Scholar]
  42. Mackenzie JS, Gubler DJ, Petersen LR. Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 2004; 10:S98–S109 [View Article]
    [Google Scholar]
  43. Tanaka T, Kogawa K, Sasa H, Nonoyama S, Furuya K et al. Rapid and simultaneous detection of 6 types of human herpes virus (herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpes virus 6A/B, and human herpes virus 7) by multiplex PCR assay. Biomed Res 2009; 30:279–285 [View Article]
    [Google Scholar]
  44. Zhou Y, Attygalle AD, Chuang S-S, Diss T, Ye H et al. Angioimmunoblastic T-cell lymphoma: histological progression associates with EBV and HHV6B viral load. Br J Haematol 2007; 138:44–53 [View Article]
    [Google Scholar]
  45. Yu J, Zhao S, Rao H. Whole genomic analysis of a potential recombinant human adenovirus type 1 in Qinghai plateau, China. Virol J 2020; 17:111 [View Article]
    [Google Scholar]
  46. Zoll GJ, Melchers WJ, Kopecka H, Jambroes G, van der Poel HJ et al. General primer-mediated polymerase chain reaction for detection of enteroviruses: application for diagnostic routine and persistent infections. J Clin Microbiol 1992; 30:160–165 [View Article]
    [Google Scholar]
  47. Yoshida LM, Suzuki M, Yamamoto T, Nguyen HA, Nguyen CD et al. Viral pathogens associated with acute respiratory infections in central Vietnamese children. Pediatr Infect Dis J 2010; 29:75–77 [View Article]
    [Google Scholar]
  48. Joki-Korpela P, Hyypiä T. Diagnosis and epidemiology of echovirus 22 infections. Clin Infect Dis 1998; 27:129–136 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001602
Loading
/content/journal/jmm/10.1099/jmm.0.001602
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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