Human herpesvirus 6 can be detected in cerebrospinal fluid without associated symptoms after allogeneic hematopoietic cell transplantation

J Clin Virol. 2014 Oct;61(2):289-92. doi: 10.1016/j.jcv.2014.07.001. Epub 2014 Jul 12.


Background: Human herpesvirus 6 (HHV-6) is an opportunistic pathogen after hematopoietic cell transplantation (HCT) that is associated with central nervous system (CNS) dysfunction.

Objectives: The aim of this study was to determine the frequency and significance of HHV-6 DNA detection in cerebrospinal fluid (CSF) after HCT.

Study design: 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).

Conclusion: 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.

Keywords: CNS; Encephalitis; Herpesvirus; Neurologic; Transplant; hhv-6.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cerebrospinal Fluid / virology*
  • Child
  • Cohort Studies
  • DNA, Viral / cerebrospinal fluid*
  • Encephalitis, Viral / virology*
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 6, Human / isolation & purification*
  • Humans
  • Male
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Roseolovirus Infections / virology*
  • Survival Analysis
  • Transplantation, Homologous / adverse effects*
  • Young Adult


  • DNA, Viral