Grand Rounds

An infant with seizures with positive human herpes virus 6 on multiplex PCR and positive herpes simplex virus 1 on uniplex PCR - How to interpret?

Ramsha Ansari, Aditi Gupta, Zahabiya Nalwalla, Ira Shah
Department of Pediatric Infectious Diseases, B J Wadia Hospital for Children, Mumbai, India

Address for Correspondence: Dr. Ramsha Ansari, Flat No. 1, Noor Jahan CHS Ltd, 322 S. G. Barve Marg, Kurla West, Mumbai – 400070, India. Email: ramsha97ansari@gmail.com

Keywords: Multiplex PCR, Film array, Meningitis/Encephalitis Panel, CNS infections, Human herpes virus 6, Herpes simplex virus 1

Clinical Problem:
A 6 month old boy presented in May 2024 with fever, cough and cold for 10 days along with generalized tonic clonic convulsions on day 8 of fever followed by excessive irritability and refusal to feed. He was born at full term by vaginal delivery and birth weight was 3 kg. There were no antenatal or post-natal complication. He had gained his milestones appropriately for his age. On examination, weight was 8 kg (between 50^th-75^th centile according to WHO [World Health Organisation] growth charts), height was 69 cm (between 75^th-85^th centile according to WHO growth charts). There were no meningeal signs. Anterior fontanelle was normal. Other systemic examination was normal. MRI brain showed symmetrical diffusion restriction with T2 hyperintensity in bilateral corpus striatum, no abnormal brain parenchymal or meningeal enhancement was noted. Cerebrospinal fluid (CSF) analysis showed 1 cell/mm³ with 100% lymphocytes, 55 mg/dl of sugar and 27 mg/dl of proteins. However, CSF multiplex Filmarray polymerase chain reaction (PCR) for meningitis/encephalitis panel detected human herpes virus 6 (HHV-6) and negative for herpes simplex virus 1 (HSV-1), for which patient was treated with intravenous (IV) acyclovir (20 mg/kg/dose 8 hourly). The child was also given anti-pyretics and anti-epileptics. CSF uniplex HSV-1 PCR was done after 2 days which was positive. Child was treated with IV acyclovir for 14 days. Repeat CSF HSV PCR done after 14 days was negative. The child subsequently recovered well, without any loss of attained milestones or complications.

Why did multiplex PCR not pick up HSV-1 and what is the significance of HHV-6 PCR on CSF with normal CSF findings?