Download PDF
J Pediatr Infect Dis 2018; 13(03): 178-184
DOI: 10.1055/s-0038-1639616
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Laboratory Diagnosis of Pediatric Herpesvirus Infections of the Central Nervous System by a Multiplex Polymerase Chain Reaction Assay and Intrathecal Antibodies

Bahadır Feyzioğlu
1   Department of Medical Microbiology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey
,
Sibel Yavru
2   Department of Virology, Faculty of Veterinary Medicine, University of Selcuk, Konya, Turkey
,
Mehmet Özdemir
1   Department of Medical Microbiology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey
› Author Affiliations
Further Information

Publication History

03 December 2017

01 March 2018

Publication Date:
28 March 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction Central nervous system (CNS) viral infections are a serious problem requiring accurate diagnosis and treatment. Human herpesviruses (HHVs) are an important cause of these infections. Recent research has focused on new diagnostic methods allowing accurate and rapid identification of viral infections because there are still diagnostic difficulties for these infections. This study was done to determine the etiologic role of human herpes viruses and to obtain information that will contribute to the diagnostic algorithm in suspected cases of viral encephalitis or aseptic meningitis.

Materials and Methods In our study, herpes simplex virus (HSV)-1, HSV-2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and HHV-6 DNA was detected in the cerebrospinal fluid (CSF) by multiplex polymerase chain reaction (PCR) and virus-specific immunoglobulin G (IgG) antibodies in CSF and serum by EIA in pediatric encephalitis/meningitis cases.

Results HSV-1 and VZV were detected in 5 and 3.3% of aseptic meningitis cases, respectively, but no encephalitis cases. Other viruses were not identified as etiologic agents. The seroprevalences were determined as 72.4, 34.3, 81.9, 93.3, 88.6, and 80.9%, respectively for HSV-1, HSV-2, VZV, CMV, EBV, and HHV-6. The performance of specific IgG CSF/serum antibody index (AI) was not satisfactory.

Conclusion Our study indicates that the multiplex PCR method is the most suitable for the diagnosis of CNS infections caused by HHVs. However, due to the high cost of the PCR method, the positive results of the specific AI may be significant, but the negative results are unreliable, especially in limited health care facilities.

Keywords

antibody index - human herpes viruses - multiplex PCR
 

  • References

  • 1 Mutlu E, Özhak B, Çolak D. Human herpes viruses. In: Başustaoğlu A. , ed. Medical Microbiology. Ankara: 2010: 585-606
    Google Scholar
  • 2 Whitley RJ, Kimberlin DW. Herpes simplex encephalitis: children and adolescents. Semin Pediatr Infect Dis 2005; 16 (01) 17-23
    CrossrefPubMedGoogle Scholar
  • 3 Momméja-Marin H, Lafaurie M, Scieux C, Galicier L, Oksenhendler E, Molina JM. Herpes simplex virus type 2 as a cause of severe meningitis in immunocompromised adults. Clin Infect Dis 2003; 37 (11) 1527-1533
    CrossrefPubMedGoogle Scholar
  • 4 Monteyne P, Albert F, Weissbrich B. , et al; European Union Concerted Action on Virus Meningitis and Encephalitis. The detection of intrathecal synthesis of anti-herpes simplex IgG antibodies: comparison between an antigen-mediated immunoblotting technique and antibody index calculations. J Med Virol 1997; 53 (04) 324-331
    CrossrefPubMedGoogle Scholar
  • 5 Jibaly R, LaChance J, Abuhammour W. Herpes simplex esophagitis: report of 4 pediatric cases in immunocompetent patients. J Pediatr Infect Dis 2011; 6 (03) 205-209
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Kimberlin DW. Herpes simplex virus infections of the central nervous system. Semin Pediatr Infect Dis 2003; 14 (02) 83-89
    CrossrefPubMedGoogle Scholar
  • 7 Sauerbrei A, Wutzler P. Laboratory diagnosis of central nervous system infections caused by herpesviruses. J Clin Virol 2002; 25 (Suppl. 01) S45-S51
    CrossrefPubMedGoogle Scholar
  • 8 Gilden DH, Mahalingam R, Cohrs RJ, Tyler KL. Herpesvirus infections of the nervous system. Nat Clin Pract Neurol 2007; 3 (02) 82-94
    PubMedGoogle Scholar
  • 9 Arseven G, Tuncel E, Tuncel S, Sönmez E, Gülen AK. Distribution of HSV-1 and HSV-2 antibodies in pregnant women [in Turkish]. Mikrobiyol Bul 1992; 26 (04) 359-366
    PubMedGoogle Scholar
  • 10 Dereli D, Ertem E, Tavmergen EN. , et al. Screening for herpes simplex virus in infertile women. Genitourin Med 1995; 71 (02) 131-132
    PubMedGoogle Scholar
  • 11 Duran N, Yarkin F, Evruke C, Koksal F. Asymptomatic herpes simplex virus type 2 (HSV-2) infection among pregnant women in Turkey. Indian J Med Res 2004; 120 (02) 106-110
    PubMedGoogle Scholar
  • 12 Dolar N, Serdaroglu S, Yilmaz G, Ergin S. Seroprevalence of herpes simplex virus type 1 and type 2 in Turkey. J Eur Acad Dermatol Venereol 2006; 20 (10) 1232-1236
    CrossrefPubMedGoogle Scholar
  • 13 Topbaş M, Çan E, Kaklıkkaya N, Yavuzyılmaz A, Özkan G, Çan G. Herpes simplex virus type-2 seroprevalence among adults aged 20–49 in Trabzon. Nobel Med 2012; 8 (02) 85-90
    PubMedGoogle Scholar
  • 14 Najioullah F, Bosshard S, Thouvenot D. , et al. Diagnosis and surveillance of herpes simplex virus infection of the central nervous system. J Med Virol 2000; 61 (04) 468-473
    CrossrefPubMedGoogle Scholar
  • 15 Markoulatos P, Georgopoulou A, Siafakas N, Plakokefalos E, Tzanakaki G, Kourea-Kremastinou J. Laboratory diagnosis of common herpesvirus infections of the central nervous system by a multiplex PCR assay. J Clin Microbiol 2001; 39 (12) 4426-4432
    CrossrefPubMedGoogle Scholar
  • 16 Whitley RJ, Gnann JW. Viral encephalitis: familiar infections and emerging pathogens. Lancet 2002; 359 (9305): 507-513
    CrossrefPubMedGoogle Scholar
  • 17 Buxbaum S, Geers M, Gross G, Schöfer H, Rabenau HF, Doerr HW. Epidemiology of herpes simplex virus types 1 and 2 in Germany: what has changed?. Med Microbiol Immunol (Berl) 2003; 192 (03) 177-181
    CrossrefPubMedGoogle Scholar
  • 18 Ibrahim AI, Obeid MT, Jouma MJ, Roemer K, Mueller-Lantzsch N, Gärtner BC. 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 (08) 4172-4174
    CrossrefPubMedGoogle Scholar
  • 19 Koskiniemi M, Rantalaiho T, Piiparinen H. , et al; Study Group. Infections of the central nervous system of suspected viral origin: a collaborative study from Finland. J Neurovirol 2001; 7 (05) 400-408
    CrossrefPubMedGoogle Scholar
  • 20 Kennedy PG. Viral encephalitis: causes, differential diagnosis, and management. J Neurol Neurosurg Psychiatry 2004; 75 (Suppl. 01) i10-i15
    CrossrefPubMedGoogle Scholar
  • 21 van Rijckevorsel GG, Damen M, Sonder GJ, van der Loeff MF, van den Hoek A. Seroprevalence of varicella-zoster virus and predictors for seronegativity in the Amsterdam adult population. BMC Infect Dis 2012; 12 (12) 140
    CrossrefPubMedGoogle Scholar
  • 22 Kanra G, Tezcan S, Badur S. ; Turkish National Study Team. Varicella seroprevalence in a random sample of the Turkish population. Vaccine 2002; 20 (9–10): 1425-1428
    CrossrefPubMedGoogle Scholar
  • 23 Alp H, Altinkaynak S, Ertekin V, Kiliçaslan B, Giiraksin A. Seroepidemiology of varicella-zoster virus infection in a cosmopolitan city (Erzurum) in the eastern Turkey. Health Policy 2005; 72 (01) 119-124
    CrossrefPubMedGoogle Scholar
  • 24 Kurugöl Z, Koturoğlu G, Akşit S, Özacar T. Varicella seroprevalence in Turkish population in Cyprus. Acta Paediatr 2007; 96 (06) 861-863
    CrossrefPubMedGoogle Scholar
  • 25 Lee BE, Davies HD. Aseptic meningitis. Curr Opin Infect Dis 2007; 20 (03) 272-277
    CrossrefPubMedGoogle Scholar
  • 26 Logan SA, MacMahon E. Viral meningitis. BMJ 2008; 336 (7634): 36-40
    CrossrefPubMedGoogle Scholar
  • 27 Persson A, Bergström T, Lindh M, Namvar L, Studahl M. Varicella-zoster virus CNS disease--viral load, clinical manifestations and sequels. J Clin Virol 2009; 46 (03) 249-253
    CrossrefPubMedGoogle Scholar
  • 28 Sloutskin A, Yee MB, Kinchington PR, Goldstein RS. Varicella-zoster virus and herpes simplex virus 1 can infect and replicate in the same neurons whether co- or superinfected. J Virol 2014; 88 (09) 5079-5086
    CrossrefPubMedGoogle Scholar
  • 29 Thiry E, Dubuisson J, And Pastoret P. Pathogenesis, latency and reactivation of infections by herpesviruses. Rev Sci Tech Off Int. Epiz 1986; 5 (04) 809-819
    PubMedGoogle Scholar
  • 30 Preston CM, Efstathiou S. Molecular basis of HSV latency and reactivation. In: Arvin A, Campadelli-Fiume G, Mocarski E. , et al., eds. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007. :Chapter 33
    Google Scholar
  • 31 Aarnisalo J, Ilonen J, Vainionpää R, Volanen I, Kaitosaari T, Simell O. Development of antibodies against cytomegalovirus, varicella-zoster virus and herpes simplex virus in Finland during the first eight years of life: a prospective study. Scand J Infect Dis 2003; 35 (10) 750-753
    CrossrefPubMedGoogle Scholar
  • 32 Gaytant MA, Steegers EAP, Semmekrot BA, Merkus HMMW, Galama JMD. Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv 2002; 57 (04) 245-256
    CrossrefPubMedGoogle Scholar
  • 33 Durupınar B, Özkuyumcu C, Dikmen N. Investigation of cytomegalovirus IgG and IgM in blood donors. Infection J 1992; 6: 261-262
    PubMedGoogle Scholar
  • 34 Maschke M, Kastrup O, Diener HC. CNS manifestations of cytomegalovirus infections: diagnosis and treatment. CNS Drugs 2002; 16 (05) 303-315
    CrossrefPubMedGoogle Scholar
  • 35 Arribas JR, Storch GA, Clifford DB, Tselis AC. Cytomegalovirus encephalitis. Ann Intern Med 1996; 125 (07) 577-587
    CrossrefPubMedGoogle Scholar
  • 36 Feyzioglu B, Ozdemir M, Baykan M, Baysal B. Comparative evaluation of indirect immunofluorescence assay and ELISA methods for the diagnosis of Epstein-Barr virus infection. Selcuk Tıp Derg 2011; 27 (02) 77-82
    PubMedGoogle Scholar
  • 37 Dowd JB, Palermo T, Brite J, McDade TW, Aiello A. Seroprevalence of Epstein-Barr virus infection in U.S. children ages 6-19, 2003-2010. PLoS One 2013; 8 (05) e64921
    CrossrefPubMedGoogle Scholar
  • 38 Karadag A, Yanık K, Usta E, Gunduz M, Eroglu C, Gunaydın M. Seroposıtıvıty of Epsteın-Barr virus (EBV) infection in children and adults and evaluation in terms of the years. Acta Med Mediter 2014; 30: 1215
    PubMedGoogle Scholar
  • 39 Domachowske JB, Cunningham CK, Cummings DL, Crosley CJ, Hannan WP, Weiner LB. Acute manifestations and neurologic sequelae of Epstein-Barr virus encephalitis in children. Pediatr Infect Dis J 1996; 15 (10) 871-875
    CrossrefPubMedGoogle Scholar
  • 40 Doja A, Bitnun A, Jones EL. , et al. Pediatric Epstein-Barr virus-associated encephalitis: 10-year review. J Child Neurol 2006; 21 (05) 385-391
    PubMedGoogle Scholar
  • 41 Okuno T, Takahashi K, Balachandra K. , et al. Seroepidemiology of human herpesvirus 6 infection in normal children and adults. J Clin Microbiol 1989; 27 (04) 651-653
    PubMedGoogle Scholar
  • 42 Hakim F. Investigation of Seroprevalence of Human Herpes Virus 6 (HHV-6) in Izmir [PhD dissertation]. İzmir: Ege University; 2008
    Google Scholar
  • 43 Alvarez-Lafuente R, García-Montojo M, De Las Heras V. , et al. Herpesviruses and human endogenous retroviral sequences in the cerebrospinal fluid of multiple sclerosis patients. Mult Scler 2008; 14 (05) 595-601
    CrossrefPubMedGoogle Scholar
  • 44 Garcia-Montojo M, De Las Heras V, Dominguez-Mozo M. , et al; HHV-6 and Multiple Sclerosis Study Group. Human herpesvirus 6 and effectiveness of interferon β1b in multiple sclerosis patients. Eur J Neurol 2011; 18 (08) 1027-1035
    CrossrefPubMedGoogle Scholar
  • 45 Ferrò MT, Franciotta D, Prelle A, Bestetti A, Cinque P. Active intrathecal herpes simplex virus type 1 (HSV-1) and human herpesvirus-6 (HHV-6) infection at onset of multiple sclerosis. J Neurovirol 2012; 18 (05) 437-440
    CrossrefPubMedGoogle Scholar
  • 46 Virtanen JO, Pietiläinen-Nicklén J, Uotila L, Färkkilä M, Vaheri A, Koskiniemi M. Intrathecal human herpesvirus 6 antibodies in multiple sclerosis and other demyelinating diseases presenting as oligoclonal bands in cerebrospinal fluid. J Neuroimmunol 2011; 237 (1–2): 93-97
    CrossrefPubMedGoogle Scholar
  • 47 Chan PK, Ng HK, Hui M, Cheng AF. Prevalence and distribution of human herpesvirus 6 variants A and B in adult human brain. J Med Virol 2001; 64 (01) 42-46
    CrossrefPubMedGoogle Scholar
  • 48 Hill JA, Venna N. Human herpesvirus 6 and the nervous system. Handb Clin Neurol 2014; 123: 327-355
    PubMedGoogle Scholar
  • 49 Shin SY, Kwon KC, Park JW, Kim JM, Shin SY, Koo SH. Evaluation of the Seeplex® Meningitis ACE Detection kit for the detection of 12 common bacterial and viral pathogens of acute meningitis. Ann Lab Med 2012; 32 (01) 44-49
    CrossrefPubMedGoogle Scholar