Characteristics of neonatal herpes simplex central nervous system disease in Australia (1997–2020)

•Male newborns carry the burden of neurological herpes simplex virus disease.•Newborn HSV neurological disease presents later than other forms of HSV disease.•Disability and deaths from newborn HSV neurological disease persist. Neonatal herpes simplex virus (HSV) central nervous system (CNS) disease can occur in isolation or as part of disseminated infection. We sought to describe neonatal HSV CNS disease in Australia over 24 years. Neonates (≤28 days) with confirmed HSV infection, reported prospectively to the Australian Paediatric Surveillance Unit (1997–2020), were evaluated for HSV CNS disease (laboratory confirmation with clinical evidence of encephalitis, e.g., lethargy, seizures, focal signs; and/or abnormalities on neuroimaging or electroencephalogram), and compared with neonates without CNS disease. CNS-restricted disease was compared with CNS-disseminated disease. Of 195 neonates with HSV disease; 87 (45%) had CNS disease (1.29 cases/100,000 live births per year, 95% CI: 1·04–1·59). Neonates with CNS disease were significantly more likely to be male than neonates without CNS disease (60% versus 39%, OR=2·32, 95% CI 1·29–4·18). Of the neonates with CNS disease, those with CNS-restricted disease (52/87, 60%) presented later than neonates with CNS-disseminated disease (35/87, 40%), (mean 12 versus 6 days). Twenty (23%) neonates with CNS disease died, the majority with CNS-disseminated disease (n = 19). Most neonates received aciclovir therapy (94·3%), however five neonates with unrecognised CNS disseminated disease (diagnosed at autopsy) had not been treated. Survivors of CNS disease were significantly more likely to have adverse neurological sequelae, compared with those without CNS disease (30% versus 4%, OR: 9·60, 95% CI: 2·6–35·0). Male neonates have a higher burden of HSV CNS disease. Despite the use of antiviral agents, morbidity following neonatal HSV CNS disease remains high. Evaluation of adjunctive therapies to improve outcomes is needed.