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Causes and Clinical Features of Childhood Encephalitis: A Multicenter, Prospective Cohort Study
Philip N Britton1,2,3, Russell C Dale1,4, Christopher C Blyth5,6,7
1Discipline of Child and Adolescent Health, Sydney Medical School, Children's Hospital at Westmead, New South Wales.
Insights
Infectious and immune-mediated encephalitis are key causes of childhood encephalitis in Australia, with viral infections predominating. One-third of children experienced mortality or neurological issues, highlighting the need for continued surveillance and prevention strategies.
Area of Science:
- Pediatric Neurology
- Infectious Diseases
- Immunology
Background:
- Encephalitis in children presents a significant public health challenge.
- Understanding contemporary causes and outcomes is crucial for effective management.
- Australia faces unique epidemiological patterns in childhood encephalitis.
Purpose of the Study:
- To identify current causes of encephalitis in Australian children.
- To describe the clinical features and short-term outcomes of pediatric encephalitis.
- To analyze etiologic subgroups and their associated characteristics.
Main Methods:
- Prospective national surveillance of suspected encephalitis cases in children (≤14 years) from May 2013 to December 2016.
- Utilized the Paediatric Active Enhanced Disease Surveillance (PAEDS) Network across 5 major pediatric hospitals.
- Cases were reviewed by a multidisciplinary panel and categorized using established definitions.
Main Results:
- Of 287 confirmed encephalitis cases, 57% were infectious (enterovirus, parechovirus, bacterial meningoencephalitis, influenza, HSV, Mycoplasma pneumoniae) and 25% were immune-mediated (ADEM, anti-NMDAR encephalitis).
- Infectious encephalitis was more common in younger children (median age 1.7 years) versus immune-mediated (median age 7.6 years).
- Mortality occurred in 5% of cases, primarily with infectious causes; 27% experienced moderate to severe neurological sequelae at discharge.
Conclusions:
- Epidemic viral infections are the predominant causes of childhood encephalitis in Australia, including vaccine-preventable diseases.
- Significant variations exist in age, clinical presentation, and outcomes among different encephalitis etiologies.
- Approximately one-third of children experienced mortality or short-term neurological morbidity.
Background:
We aimed to determine the contemporary causes, clinical features, and short-term outcome of encephalitis in Australian children.
Methods:
We prospectively identified children (≤14 years of age) admitted with suspected encephalitis at 5 major pediatric hospitals nationally between May 2013 and December 2016 using the Paediatric Active Enhanced Disease Surveillance (PAEDS) Network. A multidisciplinary expert panel reviewed cases and categorized them using published definitions. Confirmed encephalitis cases were categorized into etiologic subgroups.
Results:
From 526 cases of suspected encephalitis, 287 children met criteria for confirmed encephalitis: 57% (95% confidence interval [CI], 52%-63%) had infectious causes, 10% enterovirus, 10% parechovirus, 8% bacterial meningoencephalitis, 6% influenza, 6% herpes simplex virus (HSV), and 6% Mycoplasma pneumoniae; 25% (95% CI, 20%-30%) had immune-mediated encephalitis, 18% acute disseminated encephalomyelitis, and 6% anti-N-methyl-d-aspartate receptor encephalitis; and 17% (95% CI, 13%-21%) had an unknown cause. Infectious encephalitis occurred in younger children (median age, 1.7 years [interquartile range {IQR}, 0.1-6.9]) compared with immune-mediated encephalitis (median age, 7.6 years [IQR, 4.6-12.4]). Varicella zoster virus encephalitis was infrequent following high vaccination coverage since 2007. Thirteen children (5%) died: 11 with infectious causes (2 influenza; 2 human herpesvirus 6; 2 group B Streptococcus; 2 Streptococcus pneumoniae; 1 HSV; 1 parechovirus; 1 enterovirus) and 2 with no cause identified. Twenty-seven percent (95% CI, 21%-31%) of children showed moderate to severe neurological sequelae at discharge.
Conclusions:
Epidemic viral infections predominated as causes of childhood encephalitis in Australia. The leading causes include vaccine-preventable diseases. There were significant differences in age, clinical features, and outcome among leading causes. Mortality or short-term neurological morbidity occurred in one-third of cases.
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