Background: Influenza virus infection has been associated with a variety of neurologic complications. The objective of this study was to evaluate prospectively the role of influenza viruses in acute childhood encephalitis/encephalopathy (ACE). Methods: All children admitted to the Hospital for Sick Children, Toronto, during an 11-year period with ACE and evidence of acute influenza virus infection were included. Acute influenza virus infection was defined by detection of the organism in the nasopharynx by direct immunofluorescence microscopy or viral culture and/or by a 4-fold or greater rise in complement fixation titer. Results: A total of 311 children with ACE were evaluated; evidence of influenza infection was detected in 7% (22 of 311). Eight were excluded from the main analysis because of evidence implicating other potential pathogens. Eleven of the 14 included subjects were <5 years of age. A respiratory prodrome was documented in 93% of subjects. In 64% neurologic manifestations developed within 5 days of onset of respiratory symptoms. Neuroimaging abnormalities were more common in children <2 years of age. Neurologic sequelae occurred in more than one-half of subjects. Conclusions: In this prospective registry, influenza virus infection was associated with 5% of ACE cases. The majority of children were <5 years of age and the prevalence of neuroimaging abnormalities was higher in children <2 years of age suggesting that younger children are predisposed to the neurologic complications of influenza. An acute rather than a postinfectious process was suggested by the briefness of the respiratory prodrome in most cases.

We studied a cohort of children initiated on treatment doses of combination antiretroviral therapy within 72 hours of birth. In children who achieved sustained virologic suppression, measures of HIV-1 reservoir size in peripheral blood were very low. Background. A human immunodeficiency virus type 1 (HIV-1)–infected infant started on combination antiretroviral therapy (cART) at 30 hours of life was recently reported to have no detectable plasma viremia after discontinuing cART. The current study investigated the impact of early cART initiation on measures of HIV-1 reservoir size in HIV-1–infected children with sustained virologic suppression. Methods. Children born to HIV-1–infected mothers and started on cART within 72 hours of birth at 3 Canadian centers were assessed. HIV serology, HIV-1–specific cell-mediated immune responses, plasma viremia, cell-associated HIV-1 DNA and RNA, presence of replication-competent HIV-1, and HLA genotype were determined for HIV-1–infected children with sustained virologic suppression. Results. Of 136 cART-treated children, 12 were vertically infected (8.8%). In the 4 who achieved sustained virologic suppression, HIV serology, HIV-1–specific cell-mediated immune responses (Gag, Nef), and ultrasensitive viral load were negative. HIV-1 DNA was not detected in enriched CD4⁺ T cells of the 4 children (<2.6 copies/10⁶ CD4⁺ T cells), whereas HIV-1 RNA was detected (19.5–130 copies/1.5 µg RNA). No virion-associated HIV-1 RNA was detected following mitogenic stimulation of peripheral blood CD4⁺ T cells (5.4–8.0 million CD4⁺ T cells) in these 4 children, but replication competent virus was detected by quantitative co-culture involving a higher number of cells in 1 of 2 children tested (0.1 infectious units/10⁶ CD4⁺ T cells). Conclusions. In perinatally HIV-1–infected newborns, initiation of cART within 72 hours of birth may significantly reduce the size of the HIV-1 reservoirs. Cessation of cART may be necessary to determine whether functional HIV cure can be achieved in such children.

Background. The spectrum of neurologic disease attributable to Mycoplasma pneumoniae in children is incompletely understood in part because of limitations of microbiologic diagnostic methods. Our objective was to characterize the neurologic complications of M. pneumoniae in children using stringent diagnostic criteria. Methods. All children admitted to the Hospital for Sick Children over a 16-year period with acute neurologic manifestations and polymerase chain reaction (PCR)–confirmed M. pneumoniae infection were eligible for inclusion. Cases were categorized as definite, probable, or possible according to strength of evidence implicating M. pneumoniae. Children with underlying noninfectious neurologic conditions or an alternative infectious cause were excluded. Results. A total of 365 children had M. pneumoniae detected in the cerebrospinal fluid (CSF) or respiratory tract by PCR, 42 (11.5%) of whom had neurologic disease attributable to M. pneumoniae. The most common clinical syndromes were encephalitis (52%), acute disseminated encephalomyelitis (12%), transverse myelitis (12%), and cerebellar ataxia (10%). Two distinct disease patterns were observed, one with a prolonged prodrome (≥7 days), respiratory manifestations, an immunoglobulin M (IgM) response in peripheral blood, and detection of M. pneumoniae in the respiratory tract, but not the CSF, and one with a brief (<7 days) or no prodrome, less frequent respiratory manifestations and IgM response, and detection of M. pneumoniae in the CSF, but not the respiratory tract. Conclusions. Our findings support the hypothesis of two separate pathogenetic mechanisms for M. pneumoniae–associated neurologic disease, one related to direct infection of the central nervous system and one indirect, likely immunologically mediated.