Infection Triggered Encephalopathies in Australian Children: A National Multicentre Case Series 2013-2024.

Authors

Joshua I Chang, Russell C Dale, Shekeeb Mohammed, Rebecca Burrell, Katherine Phan, Christopher C Blyth, Jeremy P Carr, Julia E Clark, Nigel W Crawford, Joshua R Francis, Helen Marshall, Brendan McMullan, Emma Carey GDipCritCareNurs, Nicholas Wood, Cheryl A Jones, Philip N Britton, PAEDS Network

Published in

The Journal of pediatrics. Pages 115291. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Infection Triggered Encephalopathy Syndrome (ITES) is a rare but potentially severe complication of infections in children. ITES is a syndrome of acute encephalopathy that occurs in the context of a febrile illness and hypothesised to result from a cytokine mediated infection-triggered cytotoxicity in the central nervous system (CNS) without parenchymal inflammatory cell infiltration. ITES is considered distinct from infectious and immune-mediated encephalitis. We aimed to describe the demographics, associated pathogens, clinical spectrum and outcomes of ITES in Australian children from May 2013 until June 2024.
We extracted and analysed data from the prospective, multicentre Australian Childhood Encephalitis (ACE) study. Cases of ITES aged ≤14 years were reviewed and categorised by a multidisciplinary expert panel. We estimated the incidence for specific sub-types of ITES.
Of 1160 cases of Australian children with suspected encephalitis, 220 met criteria for ITES. In 83% (n=183) an associated pathogen was detected of which influenza (50%; n=109), enterovirus (8%; n=18), SARS-CoV-2 (COVID-19) (7%; n=15), and adenovirus (6%; n=13) were most common. The median age of affected children was 4.3 years (IQR 2-8.1). Of sub-types of ITES, the most frequent was Acute Necrotising Encephalopathy (ANE) (n=28, 13%), followed by Acute Encephalopathy with biphasic Seizures and late reduced Diffusion (AESD) (n=20, 9%), then Mild Encephalopathy with Reversible Splenial lesion (MERS) (n=21, 10%), although most children did not have a specific sub-type (n=135, 61%). For ITES sub-types, incidence was highest for ANE (0.82 per 1,000,000), and lowest for Febrile Infection Related Epilepsy Syndrome (FIRES, 0.23 per 1,000,000). Most children with ITES (60%; n=132) recovered fully. Poorer outcomes were seen in children diagnosed with ITES sub-types including ANE, AESD, and Acute Fulminant Cerebral Edema (AFCE).
ITES is an uncommon complication of common infections in Australian children. Influenza was the most frequently associated pathogen, with ANE the most frequent specific ITES sub-type. Outcomes are variable, but concerningly poor for some ITES sub-types including ANE.

PMID:
42628786
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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