Epidemiology and long‐term neurological sequelae of childhood herpes simplex CNS infection

Abstract

Aim Herpes simplex CNS infection is a rare but important cause of neurological disability. Long term outcomes after HSV CNS infection in Australia have not yet been fully described. We sought to provide a comprehensive review of HSV CNS infection in children using a retrospective 13‐year evaluation of statewide laboratory and clinical records and a parent survey conducted at least one year after the initial infection. Methods All positive PCR HSV 1 and 2 results from cerebrospinal fluid (CSF) or brain tissue were obtained from Queensland pathology providers for children aged 0–16 years between 1 January 2005 and 31 December 2017. Clinical data were obtained from patient records and longer‐term outcomes via parent survey at least 1 year after initial infection. Results Forty‐three children were identified over the 13‐year period, 17 (39.5%) neonates and 26 (60.4%) non‐neonates. The annual incidence for HSV CNS infection in Queensland children aged ≤16 years was 0.3/100 000 (95% confidence intervals (CIs): 0.2–0.4) with neonates at highest risk (incidence 2.5/100 000 live births, 95% CI: 1.5–3.9). HSV 1 was the predominant serotype in both neonates and non‐neonates (9/17, 52.9% neonates and 19/26, 73.1% non‐neonates). Seven (16.3%) children died, five (5/17, 29.4% neonates), directly attributable to HSV CNS infection (all neonates). Twenty‐five (58.1%) had neurological morbidity at discharge (9/17 neonates (52.9%) vs. 16/26 (61.5%) non‐neonates) and 20/27 (74.1%) reported long‐term neurological morbidity at follow‐up (5/9 neonates (55.6%) vs. 15/18 non‐neonates (83.3%)). Seven children (two neonates and four non‐neonates) with long‐term neurological sequelae had no neurological morbidity identified at discharge. Conclusion Significant long‐term neurologic sequelae were seen in children with HSV CNS infection even in children with no neurological disability identified at discharge from hospital. Careful neurodevelopmental follow‐up of all children is recommended.

TLR3/TRIF pathway confers protection against herpes simplex encephalitis through NK cell activation mediated by a loop of type I IFN and IL‐15 from epithelial and dendritic cells

“…Childhood HSE, which is a devastating disease apart from treatment, is a rare complication of primary infection with HSV-1 [3,4]. The advent of acyclovir has decreased the mortality associated with HSE, but most survivors live with profound neurological sequelae, including recurrent seizures and mental retardation [5,6]. The survival improvement with acyclovir treatment has enabled long-term monitoring of children with HSE, and those studies indicate that HSE strikes otherwise healthy children with normal resistance to other viral infections [6].…”

“…The advent of acyclovir has decreased the mortality associated with HSE, but most survivors live with profound neurological sequelae, including recurrent seizures and mental retardation [5,6]. The survival improvement with acyclovir treatment has enabled long-term monitoring of children with HSE, and those studies indicate that HSE strikes otherwise healthy children with normal resistance to other viral infections [6]. Even severely immunocompromised children are not particularly prone to HSE [3], suggesting that effector molecules produced by cellular components of innate and adaptive immunity do not provide essential protection against HSE.…”