Frequency of human herpesvirus 6 DNA detection in cerebrospinal fluid in immunocompetent children and its diagnostic value

Background: Human herpesvirus 6 is a widespread pathogen, well known as the causative agent of exanthema subitum in children. However, data on the frequency of human herpesvirus 6 detection in cerebrospinal fluid and its role in the development of meningoencephalitis in immunocompetent children remain limited.

Aim: To assess the frequency of referral for cerebrospinal fluid testing for human herpesvirus 6 DNA using qualitative polymerase chain reaction, and to determine the seasonal patterns and the diagnostic significance of human herpesvirus 6 DNA detection in cerebrospinal fluid of immunocompetent children with suspected meningoencephalitis. Additionally, to analyze the frequency, seasonality, and clinical course of human herpesvirus 6 meningoencephalitis in immunocompetent children.

Methods: We conducted a descriptive retrospective study that included immunocompetent children with suspected meningoencephalitis admitted to Filatov Children’s City Clinical Hospital No. 5 between 2007 and 2018. All patients were examined by a pediatric infectious disease specialist and a neurologist. Routine laboratory tests and lumbar puncture with subsequent cerebrospinal fluid analysis were performed. Qualitative polymerase chain reaction was used to detect human herpesvirus 6 DNA in cerebrospinal fluid. The analysis included the frequency of referral for cerebrospinal fluid testing for human herpesvirus 6, the frequency of human herpesvirus 6 DNA detection in cerebrospinal fluid, and the clinical diagnoses of patients with human herpesvirus 6 detected in cerebrospinal fluid.

Results: Over a 12-year period, 712 patients with suspected meningoencephalitis underwent cerebrospinal fluid testing for human herpesvirus 6. Human herpesvirus 6 DNA was detected in 2.9% of cases. Analysis of 15 medical records of children with detected human herpesvirus 6 showed that 7 patients had no pathological cerebrospinal fluid changes but presented with typical clinical manifestations of exanthema subitum or fever without rash. Among 8 patients with pathological cerebrospinal fluid changes, 2 cases of human herpesvirus 6 meningoencephalitis were confirmed. Thus, human herpesvirus 6 DNA detection in cerebrospinal fluid of immunocompetent children is rare and in most cases (86%) does not indicate human herpesvirus 6–induced meningoencephalitis.

Conclusion: Over 12 years, among 712 patients at Filatov Children’s City Clinical Hospital No. 5 with suspected meningitis and/or encephalitis, human herpesvirus 6 meningoencephalitis was confirmed in only 2 infants (0.3%). Human herpesvirus 6 DNA may be present in normal cerebrospinal fluid during primary herpesvirus infection. This should be considered when establishing a diagnosis and deciding on the initiation of antiviral therapy.