We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.

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In a prospective 5-year study of children with acute encephalitis, evidence of Mycoplasma pneumoniae infection was demonstrated in 50 (31%) of 159 children. In 11 (6.9%) of these patients, M. pneumoniae was determined to be the probable cause of encephalitis on the basis of its detection in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) or by positive results of serologic tests for M. pneumoniae and detection of the organism in the throat by PCR. CSF PCR positivity correlated with a shorter prodromal illness (P=.015) and lack of respiratory symptoms (P=.06). Long-term neurologic sequelae occurred in 64% of probable cases. Thirty children (18.9%) who were seropositive for M. pneumoniae but did not have the organism detected by culture or PCR had convincing evidence implicating other organisms as the cause of encephalitis, suggesting that current serologic assays for M. pneumoniae are not sufficiently specific to establish a diagnosis of M. pneumoniae encephalitis.

Background The overall global impact of COVID-19 in children and regional variability in pediatric outcomes are presently unknown. Methods To evaluate the magnitude of global COVID-19 death and intensive care unit (ICU) admission in children aged 0–19 years, a systematic review was conducted for articles and national reports as of December 7, 2020. This systematic review is registered with PROSPERO (registration number: CRD42020179696). Results We reviewed 16,027 articles as well as 225 national reports from 216 countries. Among the 3,788 global pediatric COVID-19 deaths, 3,394 (91.5%) deaths were reported from low- and middle-income countries (LMIC), while 83.5% of pediatric population from all included countries were from LMIC. The pediatric deaths/1,000,000 children and case fatality rate (CFR) were significantly higher in LMIC than in high-income countries (HIC) (2.77 in LMIC vs 1.32 in HIC; p < 0.001 and 0.24% in LMIC vs 0.01% in HIC; p < 0.001, respectively). The ICU admission/1,000,000 children was 18.80 and 1.48 in HIC and LMIC, respectively (p < 0.001). The highest deaths/1,000,000 children and CFR were in infants < 1 year old (10.03 and 0.58% in the world, 5.39 and 0.07% in HIC and 10.98 and 1.30% in LMIC, respectively). Conclusions The study highlights that there may be a larger impact of pediatric COVID-19 fatality in LMICs compared to HICs.

and GBS remain the most common causes of bacterial meningitis in the first 90 days of life. For empirical therapy of suspected bacterial meningitis, one should consider a third-generation cephalosporin (plus ampicillin for at least the first month), potentially substituting a carbapenem for the cephalosporin if there is evidence for Gram-negative meningitis.

ABSTRACT.Objective. An outbreak of severe acute respiratory syndrome (SARS) occurred in the greater Toronto area between February and June 2003. We describe the clinical, laboratory, and epidemiologic features of children who were admitted to the Hospital for Sick Children, Toronto, with a presumptive diagnosis of suspect or probable SARS.Methods. A prospective investigational study protocol was established for the management of children with a presumptive diagnosis of suspect or probable SARS. All were ultimately classified as having probable SARS, suspect SARS, or another cause on the basis of their epidemiologic exposure, clinical and radiologic features, and results of microbiologic investigations.Results. Twenty-five children were included; 10 were classified as probable SARS and 5 were classified as suspect SARS, and in 10 another cause was identified. The exposure consisted of direct contact with at least 1 adult probable SARS case in 11 children, travel from a World Health Organization-designated affected area in Asia in 9 children, and presence in a Toronto area hospital in which secondary SARS spread had occurred in 5 children. The predominant clinical manifestations of probable cases were fever, cough, and rhinorrhea. With the exception of 1 teenager, none of the children developed respiratory distress or an oxygen requirement, and all made full recoveries. Mild focal alveolar infiltrates were the predominant chest radiograph abnormality. Lymphopenia; neutropenia; thrombocytopenia; and elevated alanine aminotransferase, aspartate aminotransferase, and creatine kinase were present in some cases. Nasopharyngeal swab specimens were negative for the SARS-associated coronavirus by an in-house reverse transcriptase-polymerase chain reaction in all 25 children.Conclusions. Our results indicate that SARS is a relatively mild and nonspecific respiratory illness in previously healthy young children. The presence of fever in conjunction with a SARS exposure history should prompt one to consider SARS as a possible diagnosis in children irrespective of the presence or absence of respiratory symptoms. Reverse-transcriptase polymerase chain reaction analysis of nasopharyngeal specimens seems to be of little utility for the diagnosis of SARS during the early symptomatic phase of this illness in young children. Pediatrics 2003;112:e261-e268. URL: http: //www.pediatrics.org/cgi/content/full/112/4/e261; severe acute respiratory syndrome, reverse-transcriptase polymerase chain reaction, probable SARS, suspect SARS.

Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been documented, including encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barré syndrome. These manifestations can occur alone or coincidentally with the clinical picture of infectious mononucleosis. Since 1994, The Hospital for Sick Children has maintained a prospective registry of all children admitted with acute encephalitis. This report summarizes all cases of Epstein-Barr virus-associated encephalitis compiled from 1994 to 2003. Twenty-one (6%) of 216 children, median age 13 years (range 3-17 years), in the Encephalitis Registry were identified as having evidence of Epstein-Barr virus infection. This evidence consisted of convincing Epstein-Barr virus serology and/or positive cerebrospinal fluid polymerase chain reaction (PCR). One patient had symptoms of classic infectious mononucleosis; all others had a nonspecific prodrome, including fever (n = 17; 81%) and headache (n = 14; 66%). Slightly less than half (n = 10; 48%) had seizures and often had electroencephalograms showing a slow background (n = 12; 57%). Many demonstrated cerebrospinal fluid pleocytosis (n = 17; 81%), and 71% (n = 15) had abnormal magnetic resonance imaging findings. Two patients died, 2 suffered mild deficits, and 16 were neurologically normal at follow-up. Most patients with Epstein-Barr virus encephalitis do not show typical symptoms of infectious mononucleosis. Establishing a diagnosis of Epstein-Barr virus encephalitis can be difficult, and, consequently, a combination of serologic and molecular techniques should be used when investigating a child with acute encephalitis. Most children make full recoveries, but residual neurologic sequelae and even death can and do occur.

Herpes simplex encephalitis continues to be associated with poor long-term neurologic outcomes despite appropriate therapy. Cerebrospinal fluid polymerase chain reaction results may be negative early in the course of herpes simplex encephalitis; therefore, repeat cerebrospinal fluid analysis should be considered if herpes simplex encephalitis is suspected. Atypical forms of herpes simplex virus central nervous system disease may occur in children.