scholarly journals Identification of Chromosomally Integrated Human Herpesvirus 6 by Droplet Digital PCR

2014 ◽  
Vol 60 (5) ◽  
pp. 765-772 ◽  
Author(s):  
Ruth Hall Sedlak ◽  
Linda Cook ◽  
Meei-Li Huang ◽  
Amalia Magaret ◽  
Danielle M Zerr ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Germ Line ◽  
Human Herpesvirus ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Cell Transplant ◽  
Plasma Samples ◽  
Human Herpesvirus 6 ◽  
Hematopoietic Stem ◽  
Herpesvirus 6

Abstract BACKGROUND Human herpesvirus 6 (HHV-6) latently infects a majority of adults. In about 1% of the population HHV-6 exists in a chromosomally integrated form (ciHHV-6) that resides in every somatic and germ cell and can be transmitted through the germ line. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated for active HHV-6 infection, sometimes with important side effects, based on results from quantitative molecular HHV-6 tests. METHODS A droplet digital PCR (ddPCR) assay was developed to identify ciHHV-6 in cellular patient samples by precisely determining the ratio of HHV-6 to cellular DNA. We validated the assay on confirmed ciHHV-6 patient samples and a cell line derived from a ciHHV-6 patient, and we analyzed hematopoietic stem cell transplant patients suspected of having ciHHV-6. We additionally evaluated whether the assay could be applied to stored plasma samples from a study of clinical correlates of HHV-6. RESULTS The ddPCR assay accurately identified ciHHV-6 in cellular samples (buffy coat, peripheral blood mononuclear cells), giving a ratio very close to 1 HHV-6/cell [mean (SD), 1.02 (0.03)] in fluorescence in situ hybridization–confirmed sample). In stored plasma samples, the assay performance was set by design to have 100% sensitivity, which resulted in 82% specificity for ciHHV-6. CONCLUSIONS The possibility of ciHHV-6 is often overlooked in patients with detectable HHV-6 viral loads by quantitative PCR. Our ddPCR test provides rapid and accurate laboratory identification of ciHHV-6 from easily obtained cellular samples. In addition, the assay provides excellent sensitivity and specificity using stored plasma samples, facilitating retrospective analysis of the clinical significance of ciHHV-6.

Human herpesvirus 6 encephalitis in a patient treated with everolimus for renal cell carcinoma

2020 ◽  
Vol 26 (8) ◽  
pp. 2052-2057
Author(s):  
Stefania Kokkali ◽  
Isabelle Oddou ◽  
Justine Gantzer ◽  
Aikaterini Fitsiori
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Antiviral Treatment ◽  
Brain Magnetic Resonance Imaging ◽  
Human Herpesvirus ◽  
Cell Transplant ◽  
Human Herpesvirus 6 ◽  
Hematopoietic Stem ◽  
Herpesvirus 6

Introduction Everolimus is a mammalian target of rapamycin inhibitor and is approved as second-line treatment or beyond for renal cell carcinoma. We report a case of a 75-year-old male treated with everolimus for metastatic renal cell carcinoma, after sunitinib treatment, who was diagnosed with human herpesvirus 6 encephalitis. Case report After 39 months of everolimus, 10 mg per day, our patient was admitted with fever, consciousness disorders and a partial epileptic crisis. Laboratory tests revealed lymphopenia (170 lymphocytes/mm3), and polymerase chain reaction in cerebrospinal fluid was positive for human herpesvirus 6. Brain magnetic resonance imaging study demonstrated hippocampal abnormality and a pontine lesion. Management and outcome The patient stopped everolimus treatment indefinitely. He received ganciclovir initially intravenously, with a rapid clinical improvement, as well as polyvalent immunoglobulins were given to correct hypogammaglobulinemia. Two months later, antiviral therapy was switched to oral ganciclovir, which was never stopped. A new lumbar puncture was performed one month after the initiation of antiviral treatment, which did not reveal human herpesvirus 6 DNA anymore. Discussion Human herpesvirus 6 encephalitis is more common in hematopoietic stem cell transplant recipients and HIV patients. This is the first case probably associated to everolimus treatment. In contrast to most patients diagnosed with this infection, who either die or develop neurologic sequelae, our patient almost fully recovered two months later.

scholarly journals Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts

2021 ◽  
Vol 8 (2) ◽  
pp. e942
Author(s):  
Giulia Berzero ◽  
Giulia Campanini ◽  
Elisa Vegezzi ◽  
Matteo Paoletti ◽  
Anna Pichiecchio ◽  
...  
Keyword(s):  
Brain Mri ◽  
Human Herpesvirus ◽  
Anterograde Amnesia ◽  
Altered Mental Status ◽  
Cell Transplant ◽  
Human Herpesvirus 6 ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Herpesvirus 6 ◽  
Immunocompromised Hosts

ObjectiveThe aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing.MethodsWe performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts.ResultsOf the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1.ConclusionsThe detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement.

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