title: Human herpesvirus 6 can be detected in cerebrospinal fluid without associated symptoms after allogeneic hematopoietic cell transplantation.
abstract: BACKGROUND
  Human herpesvirus 6 (HHV-6) is an opportunistic pathogen after hematopoietic cell transplantation (HCT) that is associated with central nervous system (CNS) dysfunction.
  
  
  OBJECTIVE
  The aim of this study was to determine the frequency and significance of HHV-6 DNA detection in cerebrospinal fluid (CSF) after HCT.
  
  
  METHODS
  We identified patients with HHV-6 DNA in CSF using quantitative PCR. Patients with neurologic symptoms and HHV-6 DNA in CSF without identification of an alternative etiology were categorized as having HHV-6 CNS dysfunction.
  
  
  RESULTS
  Among 3902 allogeneic HCT recipients from 1998 to 2012, 51 of 124 tested patients had HHV-6 DNA in CSF; 37 met criteria for HHV-6 CNS dysfunction and 14 (27%) did not. Patients with an alternative diagnosis had longer time to HHV-6 detection and lower viral load in CSF. Six patients without HHV-6 CNS dysfunction were not treated and had no morbidity attributable to HHV-6. Kaplan-Meier analysis demonstrated poor overall survival among all patients. Variables associated with higher all-cause mortality in a multivariable Cox model included alternative diagnosis (adjusted hazard ratio [aHR], 8.4; 95% CI, 1.7-40.9; P = 0.009) and higher peak plasma viral load (log(10) scale) (aHR, 1.4; 95% CI, 1.1-1.9; P = 0.01).
  
  
  CONCLUSIONS
  We identified a number of allogeneic HCT recipients with HHV-6 DNA in CSF who did not meet criteria for HHV-6 CNS dysfunction. All patients had poor survival. Whether CSF HHV-6 DNA detection in patients without associated CNS dysfunction independently contributes to mortality and warrants treatment is unclear; management of these patients warrants further investigation.
authors: Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United States; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States. Electronic address: joshuaah@uw.edu.
authors: Joshua A
authors: JA
authors: Hill
authors: Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United States; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
authors: Michael J
authors: MJ
authors: Boeckh
authors: Department of Laboratory Medicine, University of Washington, Seattle, WA, United States.
authors: Ruth Hall
authors: RH
authors: Sedlak
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Department of Laboratory Medicine, University of Washington, Seattle, WA, United States.
authors: Keith R
authors: KR
authors: Jerome
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Seattle Children's Research Institute, Seattle, WA, United States.
authors: Danielle M
authors: DM
authors: Zerr
mesh_terms: D000293:Adolescent; D000328:Adult; D002555:Cerebrospinal Fluid / Q000821:virology*; D002648:Child; D015331:Cohort Studies; D004279:DNA, Viral / Q000134:cerebrospinal fluid*; D018792:Encephalitis, Viral / Q000821:virology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015654:Herpesvirus 6, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D019349:Roseolovirus Infections / Q000821:virology*; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: CNS; Encephalitis; Herpesvirus; Neurologic; Transplant; hhv-6