title: Real-time PCR detection of human herpesvirus 1-5 in patients lacking clinical signs of a viral CNS infection.
abstract: BACKGROUND
  Infections of the central nervous system (CNS) with herpes- or enterovirus can be self-limiting and benign, but occasionally result in severe and fatal disease. The polymerase chain reaction (PCR) has revolutionized the diagnostics of viral pathogens, and by multiple displacement amplification (MDA) prior to real-time PCR the sensitivity might be further enhanced. The aim of this study was to investigate if herpes- or enterovirus can be detected in cerebrospinal fluid (CSF) from patients without symptoms.
  
  
  METHODS
  Cerebrospinal fluid (CSF) samples from 373 patients lacking typical symptoms of viral CNS infection were analysed by real-time PCR targeting herpesviruses or enteroviruses with or without prior MDA.
  
  
  RESULTS
  In total, virus was detected in 17 patients (4%). Epstein-Barr virus (EBV) was most commonly detected, in general from patients with other conditions (e.g. infections, cerebral hemorrhage). MDA satisfactorily amplified viral DNA in the absence of human nucleic acids, but showed poor amplification capacity for viral DNA in CSF samples, and did not increase the sensitivity for herpes virus-detection with our methodology.
  
  
  CONCLUSIONS
  Viral pathogens are rarely detected in CSF from patients without signs of CNS infection, supporting the view that real-time PCR is a highly specific method to detect symptomatic CNS-infection caused by these viruses. However, EBV may be subclinically reactivated due to other pathological conditions in the CNS.
authors.affiliation: Div Clinical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sundén
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.forename: Tina
authors.initials: T
authors.lastname: Falkeborn
authors.forename: Jakob
authors.initials: J
authors.lastname: Paues
authors.forename: Urban
authors.initials: U
authors.lastname: Forsum
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindh
authors.forename: Liselotte
authors.initials: L
authors.lastname: Ydrenius
authors.forename: Britt
authors.initials: B
authors.lastname: Akerlind
authors.forename: Lena
authors.initials: L
authors.lastname: Serrander
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058070:Asymptomatic Diseases; D020805:Central Nervous System Viral Diseases / Q000175:diagnosis*; D002555:Cerebrospinal Fluid / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006564:Herpesviridae / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D014773:Virology / Q000379:methods*; D055815:Young Adult