title: Delayed primary HHV-7 infection and neurologic disease.
abstract: BACKGROUND
  Primary human herpesvirus 7 (HHV-7) infection occurs almost universally during the first 5 years of life and is rarely accompanied by central nervous system (CNS) symptoms such as febrile seizures. The present retrospective study investigated the role of primary HHV-7 infection in CNS disease in children, including adolescents.
  
  
  METHODS
  The study included all children who had neurologic disease aged younger than 18 years seen at the Hospital for Sick Children, Toronto, Canada, between April 1, 1998 and December 31, 2011, whose cerebrospinal fluid (CSF) was found by polymerase chain reaction to contain HHV-7 DNA. Where sera were available, HHV-7 IgG antibody titers and avidity were measured to differentiate primary from past infection.
  
  
  RESULTS
  HHV-7 DNA was detected in the CSF of 57 (1.9%) of the 2972 children tested. In 3 adolescents primary HHV-7 infection (low avidity IgG) was confirmed as the cause of neurologic disease, 2 who had encephalitis and 1 who had Guillain-Barré syndrome. Eighteen children had possible HHV-7 disease (no alternative cause identified and indeterminate antibody result or serum not available), 7 encephalitis, 8 meningitis, and 3 demyelinating disorders. HHV-7 disease was excluded in 36 children on the basis of past infection (high IgG avidity) and/or an alternative cause.
  
  
  CONCLUSIONS
  Primary HHV-7 infection delayed into adolescence can cause serious neurologic disease. HHV-7 DNA in CSF alone is insufficient to prove an etiologic association. Combining CSF polymerase chain reaction with serology is essential to prove primary infection when investigating HHV-7 CNS disease.
authors.affiliation: Division of Infectious Diseases, Department of Paediatrics, kevin.schwartz@sickkids.ca.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Schwartz
authors.affiliation: Division of Microbiology, Department of Paediatric Laboratory Medicine, and.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Richardson
authors.affiliation: Virus Reference Department, Health Protection Agency Microbiology Service Division, London, United Kingdom;Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom; and.
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Ward
authors.affiliation: Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom; and.
authors.forename: Callum
authors.initials: C
authors.lastname: Donaldson
authors.affiliation: Divisions of Neurology, Department of Paediatrics.
authors.forename: Daune
authors.initials: D
authors.lastname: MacGregor
authors.affiliation: Department of Pediatrics Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Institute, The Hospital for Sick Children, University of Toronto, Toronto, Canada;
authors.forename: Brenda
authors.initials: B
authors.lastname: Banwell
authors.affiliation: Division of Paediatric Medicine, Department of Paediatrics.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mahant
authors.affiliation: Division of Infectious Diseases, Department of Paediatrics.
authors.forename: Ari
authors.initials: A
authors.lastname: Bitnun
mesh_terms: D000367:Age Factors; D002494:Central Nervous System Infections / Q000175:diagnosis* / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000134:cerebrospinal fluid; D018792:Encephalitis, Viral / Q000175:diagnosis / Q000453:epidemiology; D020275:Guillain-Barre Syndrome / Q000175:diagnosis / Q000453:epidemiology; D016199:Herpesvirus 7, Human / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008587:Meningitis, Viral / Q000175:diagnosis / Q000453:epidemiology; D009864:Ontario; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012307:Risk Factors; D019349:Roseolovirus Infections / Q000175:diagnosis* / Q000453:epidemiology*
chemical_list: D004279:DNA, Viral
keywords: CNS; Guillain-Barré syndrome; HHV-7; child; encephalitis; meningitis