title: HHV-6 encephalitis may complicate the early phase after allogeneic hematopoietic stem cell transplantation: Detection by qualitative multiplex PCR and subsequent quantitative real-time PCR.
abstract: Viral reactivation following hematopoietic stem cell transplantation (HSCT) can cause various complications especially viral encephalitis. In this prospective study, we investigated the correlation of post-HSCT viral reactivation in blood with CNS dysfunction. We employed a multiplex PCR that detects 13 kinds of viruses as a first-line screening test and real-time PCR for subsequent quantitative evaluation. Five hundred ninety-one whole blood samples were collected from 105 patients from before until 42 days after HSCT. Seven patients developed CNS dysfunction such as altered consciousness. In six of the seven, the multiplex PCR test detected HHV-6 DNA in at least one sample. In contrast, DNA from other viruses, such as CMV, EBV, HHV-7, adenovirus, and HBV was never detected in any of the seven patients throughout the study period. Quantitative measurement of whole blood HHV-6 DNA levels demonstrated four of the six HHV-6 DNA loads were elevated at successive time points during the CNS dysfunction. In addition, the virus DNA peaks were temporally associated with the development of CNS dysfunction. CSF was tested in two of the four patients and high HHV-6 DNA levels comparable to those in whole blood were confirmed in both. These four patients were, thus, suspected to have developed HHV-6 encephalitis, a rate of 3.8% in the study population. Our results suggest that early diagnosis of probable HHV-6 encephalitis can be improved by confirming high HHV-6 DNA load in blood.
authors.affiliation: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Inazawa
authors.affiliation: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Hori
authors.affiliation: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hatakeyama
authors.affiliation: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoto
authors.affiliation: Department of Public health, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.affiliation: The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Virology Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsumi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D018792:Encephalitis, Viral / Q000453:epidemiology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D019349:Roseolovirus Infections / Q000453:epidemiology*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D019562:Viral Load; D014775:Virus Activation; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: HHV-6; encephalitis; hematopoietic stem cell transplantation; multiplex polymerase chain reaction; viral reactivation