Objective:

To determine the value of HHV-6 detection in CSF ME PCR panel in clinical practice.

Background:

The causal role of human herpesvirus 6 (HHV-6) in neurologic infections in adults is unclear beyond the encephalitic syndrome in patients post-hemopoietic stem cell transplantation (HSCT). Importantly, 1-2% of the human population has HHV-6 DNA benignly integrated into their germline.  The FilmArray Meningitis-Encephalitis (ME) multiplex panel is an FDA-approved, nucleic acid-based test that detects 14 microorganisms in cerebrospinal fluid (CSF), including HHV-6. Although HHV-6 is occasionally detected in patients with neurological symptoms, establishing a definitive clinical relationship remains challenging. 

Design/Methods:

All results from ME panel orders 7/2017-12/2024 were retrieved using laboratory information system and retrospective chart review performed.

Results:

Of 3,281 patients tested, 45 (1.37%) tested positive for HHV-6 on ME panel: 27 males and 18 females aged 18-95 years. Eight of the 45 (17.8%) were initially thought to have possible clinically significant disease, though ultimately only 3 had probable CNS disease (2 recent HSCT recipients with encephalitic syndromes; 1 on immunosuppressant drugs with temporal lobe encephalitis in setting of drug hypersensitivity syndrome). Of the remaining 5 [immunocompetent], 1 had suspected reactivation and 4 had aseptic meningitis managed without antivirals. Ultimately, 93% of positive results were without significant clinical value. 

Conclusions:

Our experience suggests that a positive HHV-6 PCR on ME panel is not clinically significant in most patients, consistent with findings from another academic institution. Positive HHV-6 may be due to false positivity, asymptomatic reactivation, and chromosomal integration, the last of which matches the HHV-6 positivity rate from our panel and expected population frequency of 1-2%. Clinical context must be considered when interpreting ME PCR results and caution should be exercised in interpreting/reporting HHV-6 results in immunocompetent individuals to minimize patient and provider misinterpretations and unnecessary testing/treatment.