Challenges in Interpreting Cerebrospinal Fluid Viral Polymerase Chain Reaction Results: Understanding the Results Related to HHV-6, HHV-7, and Enterovirus

Abstract

Objective: We have aimed to evaluate our experience in interpreting polymerase chain reaction (PCR) test results of cerebrospinal fluid (CSF) samples for human herpesvirus (HHV)-6, HHV-7, and enterovirus in children with suspected viral meningoencephalitis. Method: Children aged 1 month to 5 years underwent PCR analyses. Samples were collected via lumbar puncture and assessed using real-time PCR for the identification of enterovirus, HHV-6, and HHV-7. Results: Most (79.8%) of 109 CSF samples analyzed did not show the presence of any viral particles. Among the positive samples, 8.3% were positive only for HHV-6, 6.4% for HHV-7, and 1.9% for enterovirus. Two samples showed positivity for both HHV-6 and HHV-7; one sample for HHV-7 and enterovirus; and another sample for HHV-6, HHV-7, and enterovirus. Among the PCR-positive patients, fever (77%) and seizures (59%) were the most prevalent presenting symptoms. A statistically significantly higher incidence of seizures was observed in patients with HHV-7 positivity compared to those in whom no virus was detected (p=0.003). At discharge, three patients received alternative diagnoses. Conclusion: The most frequently detected virus was HHV-6, followed by HHV-7. Enterovirus was detected at a lower frequency than expected, most probably due to the rapid clearance of enterovirus from the CSF and coronavirus disease 2019 mitigation. Considering the possible latency or chromosomal integration (for HHV-6), clinical presentations, CSF findings, and patient-specific additional diagnostic work-up were influential on the decision-making process for diagnosis. In the absence of advanced molecular techniques, it is crucial to recognize that HHV-6 and HHV-7 may be bystanders, and other potential pathogens and diagnoses should be considered.

Keywords

• hhv-6
• hhv-7
• enterovirus
• meningoencephalitis