Exploration of molecular diagnosis for HHV-6 encephalitis in immunocompetent individuals: A study combining mNGS and PCR.

PURPOSE: To evaluate clinical features, diagnosis, treatment, and prognosis of HHV-6 encephalitis in immunocompetent adults, a rare and challenging condition.

METHODS

In this retrospective, single-centre study, we enrolled six immunocompetent adults (mean age 60.67 ± 15.57 years) diagnosed with HHV-6 encephalitis at Hengshui People's Hospital between January 2022 and December 2024. Clinical data, laboratory variables, cerebrospinal fluid (CSF) parameters, brain magnetic resonance imaging (MRI) findings, and electroencephalography (EEG) recordings were systematically collected. CSF samples underwent metagenomic next-generation sequencing (mNGS) for unbiased pathogen detection. All HHV-6-positive findings were subsequently confirmed by quantitative real-time polymerase chain reaction (PCR).

RESULTS

HHV-6 encephalitis presented with fever, unconsciousness, convulsions, headache, and cognitive dysfunction. CSF analysis showed mild intracranial pressure elevation(median 186.67 mmH2O, IQR 157.50-217.50mmH2O), lymphocytic pleocytosis(58.6 ± 31.70 %), and normal or mildly elevated protein(0.234±0.99 g/L) and glucose(median 4.03 mmol/L, IQR 3.42-4.50 mmol/L) levels. MRI revealed high-FLAIR signals in the right temporal lobe in three patients and chronic foci in the frontal lobe and basal ganglia in three others. EEG abnormalities were noted in two patients. mNGS revealed an average of 578±512.09 unique HHV-6 reads, with HHV-6A identified in five patients and HHV-6B in one. All findings were confirmed by quantitative PCR. Prompt ganciclovir therapy led to complete recovery without sequelae in all six cases.

CONCLUSIONS

mNGS enables rapid detection of the rare but treatable HHV-6 meningitis in immunocompetent adults that conventional tests miss, prompting early antiviral therapy and better outcomes.