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Detection of Herpes Simplex Virus in Cerebrospinal Fluid Using Real-Time PCR

  • Thomas F. Smith
  • Mark J. Espy
  • Matthew J. Binnicker
Chapter
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

Herpes simplex virus (HSV) is the most common, recognized cause of sporadic and severe encephalitis in the USA. The virus is estimated to account for at least 10–20 % of all viral encephalitis occurring in patients of all ages [30, 32, 57]. It is also important to underscore the worldwide impact of HSV infections in patients with superficial and systemic disease within every major organ system in both normal and immunocompromised hosts. Furthermore, this virus is usually the most frequent agent recovered in diagnostic laboratories from a variety of specimens using conventional (tube cell cultures) and rapid shell vial culture methods [18, 47]. Approximately 90 % of adults are seropositive for HSV, which is consistent with studies showing the detection of the viral genome in the trigeminal ganglia of 85–95 % of unselected autopsy cases [25]. Despite the high seroprevalence of HSV, the virus is rarely recovered from cerebrospinal fluid (CSF) specimens in viral culture, and this has been a major technical obstacle for the diagnosis of central nervous system (CNS) disease caused by this virus. Of 425 viral isolates recovered from CSF at the Mayo Clinic over a 12-year period (1984–1996), only 9 (2 %) were HSV [52].

Keywords

Herpes Simplex Virus Herpes Simplex Virus Type Central Nervous System Disease Herpes Simplex Virus Infection Molecular Beacon 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Afonso N, Gunasena S, Galla K, Podzorski R, Chandrasekar P, Alangaden G. Appropriate use of polymerase chain reaction for detection of herpes simplex virus 2 in cerebrospinal fluid of patients at an inner-city hospital. Diagn Microbiol Infect Dis. 2007;57:309–13.PubMedCrossRefGoogle Scholar
  2. 2.
    Akyldz BN, Gumus H, Kumandas S, Coskun A, Karakukucu M, Yklmaz A. Diffusion-weighted magnetic resonance is better than polymerase chain reaction for early diagnosis of herpes simplex encephalitis: a case report. Pediatr Emerg Care. 2008;24:377–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Al-Shekhlee A, Kocharian N, Suarez JJ. Re-evaluating the diagnostic methods in herpes simplex encephalitis. Herpes. 2006;13:17–9.PubMedGoogle Scholar
  4. 4.
    Aslanzadeh J, Osmon DR, Wilhelm MP, Espy MJ, Smith TF. A prospective study of the polymerase chain reaction for detection of herpes simplex virus in cerebrospinal fluid submitted to the clinical virology laboratory. Mol Cell Probes. 1992;6:367–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Avkan Oguz V, Yapar N, Sezak N, Alp Cavus S, Kuruuzum Z, Sayiner A, Ada E, Cakir N, Yuce A. Two cases of herpes encephalitis with normal cerebrospinal fluid findings. Mikrobiyol Bul. 2006;40:93–8.PubMedGoogle Scholar
  6. 6.
    Bell DJ, Suckling R, Rothburn MM, Blanchard T, Stoeter D, Michael B, Cooke RP, Kneen R, Solomon T. Management of suspected herpes simplex virus encephalitis in adults in a U.K. teaching hospital. Clin Med. 2009;9:231–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Bergallo M, Costa C, Margio S, Sidoti F, Terlizzi ME, Cavallo R. Development of a multiplex polymerase chain reaction for detection and typing of major human herpes viruses in cerebrospinal fluid. Can J Microbiol. 2007;53:1117–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Broude NE. Molecular beacons and other hairpin probes. In: Fuchs J, Podda M, editors. Encylclopedia of diagnostic genomics and proteomics. London, England: Informa Healthcare; 2005. p. 846–50.Google Scholar
  9. 9.
    CAP. Validation studies-specimen types, vol. MOL.31015; 2011.Google Scholar
  10. 10.
    CAP. Validation study comparison, vol. MOL.31130; 2011.Google Scholar
  11. 11.
    Department of Health and Human Services. Clinical laboratory improvement amendments of 1988: final rule. Fed Regist. 1992;57(40):7001–7186. 42 CFR part 493.1253.Google Scholar
  12. 12.
    Chesky M, Scalco R, Failace L, Read S, Jobim LF. Polymerase chain reaction for the laboratory diagnosis of aseptic meningitis and encephalitis. Arq Neuropsiquiatr. 2000;58:836–42.PubMedCrossRefGoogle Scholar
  13. 13.
    Davis L. Diagnosis and treatment of acute encephalitis. Neurologist. 2000;6:145–59.CrossRefGoogle Scholar
  14. 14.
    DeBiasi RL, Kleinschmidt-DeMasters BK, Weinberg A, Tyler KL. Use of PCR for the diagnosis of herpes virus infections of the central nervous system. J Clin Virol. 2002;25 Suppl 1:S5–11.PubMedCrossRefGoogle Scholar
  15. 15.
    Domingues RB, Lakeman FD, Pannuti CS, Fink MC, Tsanaclis AM. Advantage of polymerase chain reaction in the diagnosis of herpes simplex encephalitis: presentation of 5 atypical cases. Scand J Infect Dis. 1997;29:229–31.PubMedCrossRefGoogle Scholar
  16. 16.
    Espy MJ, Ross TK, Teo R, Svien KA, Wold AD, Uhl JR, Smith TF. Evaluation of LightCycler PCR for implementation of laboratory diagnosis of herpes simplex virus infections. J Clin Microbiol. 2000;38:3116–8.PubMedGoogle Scholar
  17. 17.
    Espy MJ, Rys PN, Wold AD, Uhl JR, Sloan LM, Jenkins GD, Ilstrup DM, Cockerill 3rd FR, Patel R, Rosenblatt JE, Smith TF. Detection of herpes simplex virus DNA in genital and dermal specimens by LightCycler PCR after extraction using the IsoQuick, MagNA Pure, and BioRobot 9604 methods. J Clin Microbiol. 2001;39:2233–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Espy MJ, Uhl JR, Mitchell PS, Thorvilson JN, Svien KA, Wold AD, Smith TF. Diagnosis of herpes simplex virus infections in the clinical laboratory by LightCycler PCR. J Clin Microbiol. 2000;38:795–9.PubMedGoogle Scholar
  19. 19.
    Espy MJ, Uhl JR, Sloan LM, Buckwalter SP, Jones MF, Vetter EA, Yao JD, Wengenack NL, Rosenblatt JE, Cockerill 3rd FR, Smith TF. Real-time PCR in clinical microbiology: applications for routine laboratory testing. Clin Microbiol Rev. 2006;19:165–256.PubMedCrossRefGoogle Scholar
  20. 20.
    Franzen-Rohl E, Tiveljung-Lindell A, Grillner L, Aurelius E. Increased detection rate in diagnosis of herpes simplex virus type 2 meningitis by real-time PCR using cerebrospinal fluid samples. J Clin Microbiol. 2007;45:2516–20.PubMedCrossRefGoogle Scholar
  21. 21.
    Frias C, Matas L, Ferre X, Millan M, Marti S, Hernandez A, Ausina V. Usefulness of adding multiplex nested-polymerase chain reaction assay of cerebrospinal fluid samples to routine diagnostic testing for herpes virus encephalitis. Eur J Clin Microbiol Infect Dis. 2001;20:670–2.PubMedGoogle Scholar
  22. 22.
    Harrison NA, MacDonald BK, Scott G, Kapoor R. Atypical herpes type 2 encephalitis associated with normal MRI imaging. J Neurol Neurosurg Psychiatry. 2003;74:974–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Issa NC, Espy MJ, Uhl JR, Smith TF. Sequencing and resolution of amplified herpes simplex virus DNA with intermediate melting curves as genotype 1 or 2 by LightCycler PCR assay. J Clin Microbiol. 2005;43:1843–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Jaaskelainen AJ, Piiparinen H, Lappalainen M, Vaheri A. Improved multiplex-PCR and microarray for herpesvirus detection from CSF. J Clin Virol. 2008;42:172–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Kennedy PG, Chaudhuri A. Herpes simplex encephalitis. J Neurol Neurosurg Psychiatry. 2002;73:237–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Kessler HH, Muhlbauer G, Rinner B, Stelzl E, Berger A, Dorr HW, Santner B, Marth E, Rabenau H. Detection of Herpes simplex virus DNA by real-time PCR. J Clin Microbiol. 2000;38:2638–42.PubMedGoogle Scholar
  27. 27.
    Kimberlin D. Herpes simplex virus, meningitis and encephalitis in neonates. Herpes. 2004;11 Suppl 2:65A–76.PubMedGoogle Scholar
  28. 28.
    Kohira I, Ninomiya Y. A case of recurrent aseptic meningitis (Mollaret meningitis) with back pain in which was detected the DNA of herpes simplex virus type 2 in cerebrospinal fluid. Rinsho Shinkeigaku. 2002;42:24–6.PubMedGoogle Scholar
  29. 29.
    Koskiniemi M, Rantalaiho T, Piiparinen H, von Bonsdorff CH, Farkkila M, Jarvinen A, Kinnunen E, Koskiniemi S, Mannonen L, Muttilainen M, Linnavuori K, Porras J, Puolakkainen M, Raiha K, Salonen EM, Ukkonen P, Vaheri A, Valtonen V. Infections of the central nervous system of suspected viral origin: a collaborative study from Finland. J Neurovirol. 2001;7:400–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Lakeman FD, Whitley RJ. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis. 1995;171:857–63.PubMedCrossRefGoogle Scholar
  31. 31.
    Mejias A, Bustos R, Ardura MI, Ramirez C, Sanchez PJ. Persistence of herpes simplex virus DNA in cerebrospinal fluid of neonates with herpes simplex virus encephalitis. J Perinatol. 2009;29:290–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Olson LC, Buescher EL, Artenstein MS, Parkman PD. Herpesvirus infections of the human central nervous system. N Engl J Med. 1967;277:1271–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Plentz A, Jilg W, Kochanowski B, Ibach B, Knoll A. Detection of herpesvirus DNA in cerebrospinal fluid and correlation with clinical symptoms. Infection. 2008;36:158–62.PubMedCrossRefGoogle Scholar
  34. 34.
    Powell KF, Anderson NE, Frith RW, Croxson MC. Non-invasive diagnosis of herpes simplex encephalitis. Lancet. 1990;335:357–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Puchhammer-Stockl E, Presterl E, Croy C, Aberle S, Popow-Kraupp T, Kundi M, Hofmann H, Wenninger U, Godl I. Screening for possible failure of herpes simplex virus PCR in cerebrospinal fluid for the diagnosis of herpes simplex encephalitis. J Med Virol. 2001;64:531–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Roos KL. Pearls and pitfalls in the diagnosis and management of central nervous system infectious diseases. Semin Neurol. 1998;18:185–96.PubMedCrossRefGoogle Scholar
  37. 37.
    Rowley AH, Whitley RJ, Lakeman FD, Wolinsky SM. Rapid detection of herpes-simplex-virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis. Lancet. 1990;335:440–1.PubMedCrossRefGoogle Scholar
  38. 38.
    Sankuntaw N, Sukprasert S, Engchanil C, Kaewkes W, Chantratita W, Pairoj V, Lulitanond V. Single tube multiplex real-time PCR for the rapid detection of herpes virus infections of the central nervous system. Mol Cell Probes. 2011;25:114–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Sauerbrei A, Wutzler P. Laboratory diagnosis of central nervous system infections caused by herpesviruses. J Clin Virol. 2002;25 Suppl 1:S45–51.PubMedCrossRefGoogle Scholar
  40. 40.
    Schiffer JT, Corey L. Herpes simplex virus. In: Mandell GL, Bennett JE, Dalin R, editors. Principles and practices of infectious diseases. 7th ed. Philadelphia, PA: Churchill Livingston; 2010. p. 1443–962.Google Scholar
  41. 41.
    Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E. Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol. 2009;81:1432–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Schmutzhard E. Viral infections of the CNS with special emphasis on herpes simplex infections. J Neurol. 2001;248:469–77.PubMedCrossRefGoogle Scholar
  43. 43.
    Scott LJ, Gunson RN, Carman WF, Winter AJ. A new multiplex real-time PCR test for HSV1/2 and syphilis: an evaluation of its impact in the laboratory and clinical setting. Sex Transm Infect. 2010;86:537–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Selvaraju SB, Wurst M, Horvat RT, Selvarangan R. Evaluation of three analyte-specific reagents for detection and typing of herpes simplex virus in cerebrospinal fluid. Diagn Microbiol Infect Dis. 2009;63:286–91.PubMedCrossRefGoogle Scholar
  45. 45.
    Shi J, Wu Y, Cai M, Shang S. Rapid diagnosis of herpetic encephalitis in children by PCR-microarray technology for simultaneous detection of seven human herpes viruses. Eur J Pediatr. 2010;169:421–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Simko JP, Caliendo AM, Hogle K, Versalovic J. Differences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) documented by detection of HSV DNA. Clin Infect Dis. 2002;35:414–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Smith TF, Espy MJ, Jones MF. Molecular virology: current and future trends. In: Persing DH, Tenover FC, Versalovic J, Tang YW, Unger ER, Relman DA, White TJ, editors. Molecular microbiology diagnostic principles and practices. Washington, DC: ASM Press; 2004. p. 543–8.Google Scholar
  48. 48.
    Smith TF, Espy MJ, Wold AD. Develpment, implementation, and optimization of lightcycler PCR assays for detection of herpes simplex virus and varicella-zoster virus from clinical specimens. In: Reischl U, Wittwer C, Cockerill F, editors. Rapid cycle real-time PCR methods and applications. Berlin, Germany: Springer; 2002. p. 189–200.CrossRefGoogle Scholar
  49. 49.
    State of New York. Department of Health. Approval of microbiology nucleic acid amplification assays. Microbiology Molecular Checklist; 2011. p. 1–11.Google Scholar
  50. 50.
    Stevenson J, Hymas W, Hillyard D. Effect of sequence polymorphisms on performance of two real-time PCR assays for detection of herpes simplex virus. J Clin Microbiol. 2005;43:2391–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Sun Y, Dhumpa R, Bang DD, Hogberg J, Handberg K, Wolff A. A lab-on-a-chip device for rapid identification of avian influenza viral RNA by solid-phase PCR. Lab Chip. 2011;11:1457–63.PubMedCrossRefGoogle Scholar
  52. 52.
    Tang YW, Mitchell PS, Espy MJ, Smith TF, Persing DH. Molecular diagnosis of herpes simplex virus infections in the central nervous system. J Clin Microbiol. 1999;37:2127–36.PubMedGoogle Scholar
  53. 53.
    Tang YW, Rys PN, Rutledge BJ, Mitchell PS, Smith TF, Persing DH. Comparative evaluation of colorimetric microtiter plate systems for detection of herpes simplex virus in cerebrospinal fluid. J Clin Microbiol. 1998;36:2714–7.PubMedGoogle Scholar
  54. 54.
    Tyler KL. Update on herpes simplex encephalitis. Rev Neurol Dis. 2004;1:169–78.PubMedGoogle Scholar
  55. 55.
    Weil AA, Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis. 2002;34:1154–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Whitley R, Arvin A, Prober C, Burchett S, Corey L, Powell D, Plotkin S, Starr S, Alford C, Connor J, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med. 1991;324:444–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res. 2006;71:141–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Whitley RJ. Herpes simplex viruses. In: Scheld WM, Whitley RJ, Durack DT, editors. Infections of the central nervous system. 2nd ed. Philadelphia, PA: Lippincott-Raven; 1997. p. 73–89.Google Scholar
  59. 59.
    Whitley RJ, Gnann Jr JW. Acyclovir: a decade later. N Engl J Med. 1992;327:782–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Wright PA, Espy MJ, Irish C, Smith TF, Pritt BS. Evaluation of a sample-conserving heat processing method for low volume csf specimens submitted for HSV PCR. Clinical virology symposium meeting, Daytona Beach, FL; 2010.Google Scholar
  61. 61.
    Ziyaeyan M, Alborzi A, Borhani Haghighi A, Jamalidoust M, Moeini M, Pourabbas B. Diagnosis and quantitative detection of HSV DNA in samples from patients with suspected herpes simplex encephalitis. Braz J Infect Dis. 2011;15:211–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Thomas F. Smith
    • 1
  • Mark J. Espy
    • 1
  • Matthew J. Binnicker
    • 1
  1. 1.Division of Clinical Microbiology, Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA

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