Detection of human herpesvirus type 6 DNA in cerebrospinal fluid is rarely clinically significant

Human herpesvirus 6 (HHV-6) is included in syndromic panels for diagnostics of CNS infections, but the clinical significance of the detection is often unclear. To investigate the clinical importance of detectable HHV-6 DNA in CSF We retrospectively investigated the clinical significance of detection of HHV-6 DNA in all clinical CSF samples that were analyzed between 2010-2021 using in-house PCR or the FilmArray meningitis/encephalitis (ME) panel. The clinical significance of HHV-6 was evaluated by review of electronic medical records (EMR) and categorized as unlikely, possible or likely for each case. Of 8778 samples from 8222 individuals, HHV-6 DNA was detected in CSF in 113 (1.4%). After EMR review, the clinical importance of HHV-6 was categorized as likely in three (3%; including one with meningoencephalitis), possible in 15 (14%) and unlikely in 95 (83%) cases. No significant difference in HHV-6 DNA levels was seen between these categories. Seven of ten initiated antiviral therapies were unnecessary (integrated HHV-6 n=4; primary infection without CNS complications n=3). In this large clinical sample, nearly all HHV-6 detections were either of unlikely diagnostic importance or did not require specific medical interventions. Moreover, in most cases where antiviral therapy was initiated, treatment was either erroneous (integration) or unmotivated (limited disease). These results indicate that the utility of including HHV-6 in routine syndromic diagnostic panels for CNS infections is questionable, and that appropriate guidance from the laboratory to aid attending clinicians is prudent to avoid unnecessary, expensive and potentially toxic therapy. • We analyzed the clinical importance of CSF HHV-6 DNA in a large retrospective sample • HHV-6 DNA was detected in 113/8222 (1.4%) studied individuals • HHV-6 was considered of probable clinical relevance in 3 patients (2.6%) • In 7/10 cases, initiated antiviral treatments were erroneous or unnecessary • The results question including HHV-6 in diagnostic panels for CNS infections