Ari Bitnun

A 12-Year Prospective Study of Childhood Herpes Simplex Encephalitis: Is There a Broader Spectrum of Disease?

OBJECTIVE. The purpose of this study was to review the experience with herpes simplex encephalitis at the Hospital for Sick Children over the past 12 years. METHODS. All patients who were admitted to our institution with acute encephalitis between January 1994 and December 2005 were enrolled prospectively in an encephalitis registry. Children from the registry with herpes simplex encephalitis were included in this study; we detailed the clinical presentations, laboratory findings, electroencephalographic findings, diagnostic imaging findings, treatments, and outcomes for all cases. RESULTS. Of 322 cases of acute encephalitis, 5% were caused by herpes simplex virus. Initially negative herpes simplex virus cerebrospinal fluid polymerase chain reaction results were found in 2 cases (13%), but results became positive in repeat cerebrospinal fluid analyses. Classic clinical presentations were seen in 75% of cases, cerebrospinal fluid pleocytosis was found in 94%, elevated cerebrospinal fluid protein levels were found in 50%, electroencephalographic changes were observed in 94%, and diagnostic imaging abnormalities were noted in 88%. All patients were treated with intravenous acyclovir. Neurologic sequelae occurred in 63% of cases, including seizures in 44% and developmental delays in 25%. There were no deaths in this study group. CONCLUSIONS. 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.

Acute childhood encephalitis and encephalopathy associated with influenza: a prospective 11-year review.

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.

A national review of vertical HIV transmission

Objectives:Prevention of vertical HIV transmission has evolved significantly in Canada over the last two decades. The aim of this analysis is to describe the surveillance programme used, rate of vertical HIV transmission and changing epidemiology of HIV-affected pregnancies in Canada. Design:National perinatal HIV surveillance programme. Methods:From 1990, annual retrospective data was collected on demographic and clinical characteristics of HIV-infected mothers and their infants referred to 22 participating sites across Canada either before/during pregnancy or within 3 months after delivery. Factors impacting HIV transmission and demographic features were explored. Results:Two thousand, six hundred and ninety-two mother–infant pairs were identified. The overall rate of vertical HIV transmission was 5.2%, declining to 2.9% since 1997. The rate of transmission for mothers who received HAART was 1%, and 0.4% if more than 4 weeks of HAART was given. Forty percent of women delivered by caesarean section, with no difference in transmission rate compared with vaginal delivery for women treated with HAART (1.4 vs. 0.6%, P = 0.129) but significant risk reduction for those who did not receive HAART (3.8 vs. 10.3%, P = 0.016). Black women were the largest group; proportions of black and aboriginal women increased significantly over time (P < 0.001 for both). Heterosexual contact was the most common risk category for maternal infection (65%), followed by injection drug use (IDU) (25%). Conclusion:Vertical HIV transmission in Canada has decreased dramatically for women treated with HAART therapy. All pregnant women should be evaluated for HIV infection and programmes expanded to reach vulnerable populations including aboriginal, immigrant and IDU women.

Serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor-treated and naive HIV-infected children.

Objective: To determine the extent and degree of abnormalities of serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor (PI)‐treated and PI‐naive HIV‐infected children. Design: A cross‐sectional study involving HIV‐infected children, 3–18 years of age, in a paediatric tertiary care centre. Main outcome measures: Total, HDL and LDL‐cholesterol, triglycerides, glucose, insulin, proinsulin and C‐peptide were determined in the fasting state. Insulin resistance was assessed using the homeostatic model assessment–insulin resistance (HOMA–IR). Abdominal adipose tissue distribution was determined by single‐slice computed tomography at the umbilical level. Results: Thirty PI‐treated and 20 PI‐naive children were evaluated (76% prepubertal). PI‐treated children had significantly higher total cholesterol (P = 0.0021), LDL‐cholesterol (P = 0.019) and triglycerides (P = 0.0018). Serum glucose, insulin, proinsulin and C‐peptide, the insulin: glucose ratio, HOMA–IR and abdominal adipose tissue distribution were similar in the two groups. Clinical and immunological HIV categories, viral load, CD4 cell count and stavudine therapy were not significantly associated with serum lipids, insulin resistance or abdominal adipose tissue distribution. The predictor variable most strongly associated with fasting serum insulin and HOMA–IR was the Tanner stage. Age was the most significant predictor variable of the visceral: subcutaneous adipose tissue ratio. Conclusion: In this cohort of predominantly prepubertal HIV‐infected children, PI therapy was associated with an atherogenic dyslipidemia but not with insulin resistance or abnormal abdominal adipose tissue distribution. The results suggest that children, particularly prepubertal children, are less susceptible than adults to PI‐induced changes in glucose homeostasis and abdominal adipose tissue distribution.

Bacterial endocarditis in a child presenting with acute arterial ischemic stroke: should thrombolytic therapy be absolutely contraindicated?

Thrombolysis is considered to be contraindicated in acute ischemic stroke secondary to infective endocarditis (IE). We report a 12‐year‐old female who presented with acute dense right hemiparesis and aphasia. Cranial magnetic resonance imaging and angiography showed multiple diffusion‐restricted lesions in the left hemisphere and absence of flow in the left internal carotid artery. She was treated with intra‐arterial tissue plasminogen activator within 6 hours of her presentation. Subsequently she was diagnosed with pneumococcal endocarditis and underwent debridement of vegetations and patch repair of the mitral valve. The patient did not have hemorrhagic complications following thrombolytic therapy or surgery. Pathological analysis of the mitral valve vegetations revealed mostly fibrin thrombus. Follow‐up imaging showed complete recanalization of the left internal carotid artery, and the patient had a remarkable neurological recovery. This is the first case report of successful intra‐arterial thrombolytic therapy in childhood IE‐related stroke. We believe that thrombolytic therapy contributed to a favorable outcome in our patient and may be safe in selected patients with childhood IE‐related acute ischemic stroke.

HIV Mother-to-Child Transmission, Mode of Delivery, and Duration of Rupture of Membranes: Experience in the Current Era

Objective. To evaluate whether the length of time of rupture of membranes (ROM) in optimally managed HIV-positive women on highly active antiretroviral therapy (HAART) with low viral loads (VL) is predictive of the risk of mother to child transmission (MTCT) of the human immunodeficiency virus (HIV). Study Methods. A retrospective case series of all HIV-positive women who delivered at two academic tertiary centers in Toronto, Canada from January 2000 to November 2010 was completed. Results. Two hundred and ten HIV-positive women with viral loads <1,000 copies/ml delivered during the study period. VL was undetectable (<50 copies/mL) for the majority of the women (167, 80%), and <1,000 copies/mL for all women. Mode of delivery was vaginal in 107 (51%) and cesarean in 103 (49%). The median length of time of ROM was 0.63 hours (range 0 to 77.87 hours) for the entire group and 2.56 hours (range 0 to 53.90 hours) for those who had a vaginal birth. Among women with undetectable VL, 90 (54%) had a vaginal birth and 77 (46%) had a cesarean birth. Among the women in this cohort there were no cases of MTCT of HIV. Conclusions. There was no association between duration of ROM or mode of delivery and MTCT in this cohort of 210 virally suppressed HIV-positive pregnant women.

Invasive aspergillosis in cystic fibrosis: a fatal case in an adolescent and review of the literature.

Invasive aspergillosis is a rare complication of cystic fibrosis. In this article, we describe a case of an adolescent with cystic fibrosis, which was well-controlled previously, colonized with Aspergillus fumigatus. The patient developed fatal disseminated aspergillosis in the absence of any preexisting risk factors after a short course of intravenous corticosteroid treatment.

Natural History of Pandemic H1N1 2009 Influenza Infection in Healthy Pediatric Outpatients

OBJECTIVE The pandemic influenza H1N1 2009 (pH1N1) virus is expected to remain a prominent circulating strain in the current and subsequent influenza seasons. The objective of this study was to compare the clinical course of infection with laboratory-confirmed pH1N1 and seasonal influenza A and B in a cohort of previously healthy children managed in the outpatient setting without antiviral therapy. METHODS Previously healthy children 17 years of age or younger were prospectively enrolled during the first wave of the 2009 pandemic (May-July 2009) and the 2 preceding influenza seasons from a single primary care physician office and a tertiary childrens hospital emergency department. Inclusion criteria were: age ≤17 years; laboratory-confirmed influenza; and not receiving antiviral agents. Follow-up telephone interviews were conducted approximately 2 days and 14 days after presentation to assess symptom duration. RESULTS A total of 251 patients (101 with pH1N1, 90 with seasonal influenza A, 60 with seasonal influenza B) were included. Presenting symptoms and duration of symptoms associated with pH1N1 were similar to those with seasonal influenza. Median fever duration in pH1N1 was 3 days and had resolved within 8 days in 95% of patients. Among patients with pH1N1, abnormalities on chest auscultation (10 of 101), the hospitalization rate (2 of 101), the proportion of children receiving intravenous fluid therapy (1 of 101) or supplemental oxygen (1 of 101) were not significantly different from patients with seasonal influenza. CONCLUSIONS In most children without underlying risk factors for severe influenza, pH1N1 virus causes an uncomplicated respiratory tract illness, no more severe than seasonal influenza.

Prevention of Vertical HIV Transmission and Management of the HIV-Exposed Infant in Canada in 2014

The standard of care for the prevention of vertical transmission (VT) of HIV in Canada and other developed countries includes routine prenatal HIV testing for all pregnant women, and for those testing positive: antepartum combination antiretroviral therapy (cART); intrapartum intravenous zidovudine; six weeks of postnatal oral zidovudine to the infant; and exclusive formula feeding of the infant. With these interventions, the rate of VT has been reduced from 25% to 40%, to 4 weeks before delivery. The purpose of the present article is to highlight recent changes in management guidelines and important caveats to these changes with regard to prevention of VT in the Canadian context. There is a global trend to replace the use of the previous conventional terminology of ‘mother-to-child transmission’ with ‘vertical transmission’ or ‘perinatal transmission’ to remove implications of blame from the mother. In the present article, ‘vertical transmission’ is used throughout. HIV testing during pregnancy HIV testing is recommended for all pregnant women in Canada, with appropriate pre- and post-test counselling. Women whose HIV status is unknown at the time of delivery should undergo rapid HIV antibody testing. For women at increased risk for HIV infection (eg, intravenous drug use, commercial sex work, frequent unprotected intercourse with multiple partners, HIV-negative woman of a serodiscordant couple) who test negative early in pregnancy, repeat testing late in pregnancy (beginning of the third trimester) and at delivery is strongly encouraged. When such women present in labour, advice regarding maternal HIV diagnosis and management should be sought from obstetric and adult HIV experts on an urgent basis; similarly, pediatric HIV experts should be consulted regarding infant management in such situations. Women living with HIV, either previously diagnosed or identified during pregnancy, should be followed by a specialist with expertise in the management of HIV during pregnancy, treated with cART and monitored for viral suppression. Prelabour elective Cesarean section delivery should be planned for those not on cART and/or anticipated or documented to have inadequate viral suppression near delivery (viral load >1000 copies/mL). For women who were previously diagnosed with HIV in whom viral load is not documented to be fully suppressed in the four weeks preceding onset of labour and for women diagnosed with HIV infection at the time of labour, urgent consultation with adult and pediatric HIV experts and an obstetrician with expertise in the management of HIV is essential. Recommendation 1: Pediatricians and other health care providers involved in the care of HIV-infected pregnant women and their children should advocate for universal HIV testing of all pregnant women with appropriate pre- and post-test counselling so that appropriate preventive measures can be implemented in a timely manner. When this fails, testing of the mother at delivery, or of the infant if maternal testing is not possible, should be ensured. Ideally, no infant should be discharged from hospital without the HIV status of the mother being known. Pediatricians and family physicians who perform routine neonatal examinations should verify that the HIV status of the mother or child is known and documented. Recommendation 2: Urgent consultation with an obstetrician with HIV expertise and an adult HIV expert is recommended for diagnosis and management of women deemed to be at high risk for HIV infection with unknown status at the time of labour. Similarly, a pediatric HIV expert should be consulted regarding infant management in such situations.

Safety of combination antiretroviral prophylaxis in high-risk HIV-exposed newborns: a retrospective review of the Canadian experience

The optimal management of infants born to HIV‐positive mothers who are untreated or have detectable viral load prior to delivery remains controversial. Despite the increasing use of combination antiretroviral therapy (cART) for post‐exposure prophylaxis (PEP) of neonates at high risk of HIV infection, there is little safety and pharmacokinetic data to support this approach. The objective of this study was to evaluate the safety and tolerability of cART for PEP in HIV‐exposed neonates.