To determine the presence of vascular markers of premature atherosclerosis and metabolic correlates in a prospectively followed cohort of antiretroviral treated HIV-infected children. Vascular assessment included: carotid intima-media thickness and brachial artery reactivity using vascular ultrasound; peripheral pulse wave velocity (PWV) using photoplethysmography; central PWV, arterial stiffness and impedance indices using an Echo-Doppler method; and only at follow-up, augmentation index and PWV by applanation tonometry. Disease markers, oral glucose tolerance, fasting lipid profiles and abdominal fat (single slice CT scan) were also determined. Twenty children were assessed at baseline (median age 12.6 [range 8.5–18.5] years; 50

Launched in 2013, the SickKids-Caribbean Initiative (SCI) focuses on building sustainable, local capacity to diagnose, treat, and manage pediatric cancers and blood disorders in the region. As an early step in creating SCI, partnerships were formalized between the SickKids Centre for Global Child

We examined serum IL-6 and IgE assays as adjuncts to VL monitoring for PTLD. Paediatric solid organ transplant recipients were followed with VL monitoring. VL, IL-6, and IgE assays were compared between PTLD cases and non-cases at <3, 3-6 and >6 months after transplantation. Median IL-6 levels in PTLD cases were 15.5 (2.0-87.1) and 23.3 (2.1-276) pg/mL compared with 3.25 (0.92-114) and 3.5 (0.75-199.25) pg/mL in non-cases at 3-6 and >6 months, respectively (p = 0.006 and p = 0.005). At >6 months, IL-6 levels correlated with VL and PTLD occurrence (Spearman's coefficients = 0.40; p = 0.001 and 0.32; p = 0.003) in univariate analyses. No benefit was derived from performance of IgE levels. The sensitivity and specificity of high VL as a test of PTLD were 76.3% and 92.5%, while the negative predictive value and PPV of VL were 94.9% and 68.4%, respectively. Combining elevated IL-6 with high VL increased the PPV and specificity to 80% and 96.2%, respectively, and improved the receiver operating characteristic curve. Serum IL-6 levels can improve the clinician's ability to identify PTLD, among patients with elevated EBV viral loads.

The management of neonatal fungal infections poses several challenges, including the fact that the choices of available agents are limited, given the paucity of data relating to the use of newer antifungal agents in the group of infants. The information summarized herein represents in part the consensus of a group of clinicians involved in the care of neonates at risk of and with fungal infections. The document addresses the prophylaxis and treatment of fungal infections in neonates. It highlights the role of current and emerging antifungal agents, including the lipid amphotericin B products, echinocandins and triazoles.

The number of available antifungal agents has significantly increased in recent years. These agents are starting to take over niches that were previously occupied by conventional amphotericin B. For many of these agents, pediatric data from randomized trials are generally lacking and clinicians are faced with extrapolating from data generated in adult patients. This notwithstanding, this report summarizes recommendations that define the roles of newer antifungal agents in the treatment of selected scenarios among immunocompromised pediatric patients. The report includes the outcome of a Canadian conference on the use of antifungal agents in children, supplemented by literature reviews and incorporating information from existing national or international guidelines, where appropriate. The focus of the report is on febrile neutropenia, invasive aspergillosis, combination antifungal therapy and selected aspects of the management of invasive candidiasis.

Previous pediatric studies have failed to demonstrate a clear association between protease inhibitor (PI) therapy and abnormal glucose homeostasis in HIV-infected children. To define more precisely the impact of PI therapy on glucose homeostasis in this population, we performed the insulin-modified frequent-sampling iv glucose tolerance test on 33 PI-treated and 15 PI-naive HIV-infected children. Other investigations included fasting serum lipids; glucose, insulin, and C-peptide; single-slice abdominal computed tomography; and, in a subset of PI-treated children, an oral glucose tolerance test. There were no differences between the two groups with respect to fasting serum insulin or C-peptide, homeostatic model assessment insulin resistance, or quantitative insulin sensitivity check index. The mean insulin sensitivity index of PI-treated and PI-naive children was 6.93 +/- 6.37 and 10.58 +/- 12.93 x 10(-4)min(-1) [microU/ml](-1), respectively (P = 0.17). The mean disposition index for the two groups was 1840 +/- 1575 and 3708 +/- 3005 x 10(-4)min(-1) (P = 0.013), respectively. After adjusting for potential confounding variables using multiple regression analysis, the insulin sensitivity index and disposition index of PI-treated children were significantly lower than that of PI-naive children (P = 0.01 for both). In PI-treated but not PI-naive children, insulin sensitivity correlated inversely with visceral adipose tissue area (r = -0.43, P = 0.01) and visceral to sc adipose tissue ratio (r = -0.49, P = 0.004). Mildly impaired glucose tolerance was noted in four of 21 PI-treated subjects tested. Our results demonstrate not only that PI therapy reduces insulin sensitivity in HIV-infected children but also that it impairs the beta-cell response to this reduction in insulin sensitivity and, in a subset of children, leads to the development of impaired glucose tolerance. The presence of insulin resistance, dyslipidemia, and the significant correlation of reduced insulin sensitivity with increased visceral adipose tissue content suggest that PI-containing highly active antiretroviral therapy is associated with the emergence of early features of a metabolic syndrome-like phenotype.

Objective: Rectal thermometry, the criterion standard of temperature measurement in young children, has numerous disadvantages. This study examined the agreement between rectal versus a new temporal artery professional model (TAPM) thermometer and rectal versus a home device temporal artery consumer model (TACM) thermometer, investigated if the TAPM can safely screen for rectal fever, and determined if parents can detect rectal fever using the TACM.Design, Outcome Measures, and Subjects: In this cross-sectional agreement emergency department study, 327 children <24 months of age had their temperature measured rectally and by the TAPM and TACM by a single nurse and using the TACM by the parents. Agreements were analyzed by the Bland Altman plots. Temperature cutoff to detect rectal fever >38.0degreesC and >38.3degreesC with sensitivities of greater than or equal to90% and greater than or equal to95%, respectively, was determined for the TAPM.Results: The mean difference between the rectal minus TAPM was -0.19degreesC +/- 0.66degreesC, and minus the TACM home device, it was +0.11degreesC +/- 0.66degreesC. The sensitivities of TAPM temperature of greater than or equal to37.7degreesC to detect rectal fever greater than or equal to38.0degreesC and greater than or equal to38.3 C were 90% (95% confidence interval: 0.83; 0.94) and 97% (95% confidence interval: 0.92; 0.99), respectively. The parents detected 67% and 73% of rectal fevers 38.0degreesC and greater than or equal to38.3degreesC, respectively.Conclusions: The TAPM thermometer cannot replace the rectal. However, TAPM temperature of <37.7degreesC can be safely used as a screen to exclude rectal fever greater than or equal to38.3degreesC in infants 3 to 24 months of age. The TACM home device has insufficient ability to detect rectal fever. A multicenter trial is needed to validate these results across multiple emergency departments and numerous observers.

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 Pl-induced changes in glucose homeostasis and abdominal adipose tissue distribution. (C) 2003 Lippincott Williams Wilkins.

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.

While it seems unlikely that acts of bioterrorism would occur in Canada, bioterrorist attacks are of great concern in the United States (1–3). It is almost inconceivable that an event in the United States would not have some impact in Canada, given the frequency of international travel. Just as a resident of the greater Toronto area fell victim to West Nile Virus encephalitis following a visit to New York, New York during the 1999 summer epidemic, and hundreds of travellers returning to Canada develop malaria each year, infected travellers could return to Canada while in the incubation stage of an infection resulting from bioterrorism. Furthermore, diseases that are communicable by person-to-person contact, such as smallpox and pneumonic plague, can cause secondary cases that are in the incubation stage before the index case is recognized. While it is hoped that physicians in Canada will never face a crisis that would require the information presented in this paper, it behooves all involved in acute care to familiarize ourselves with the potential reality of bioterrorism and its management. A plan of action must be formulated and put in place before such a situation occurs – if it ever does occur. Unlike warfare, the target of the bioterrorist is the civilian population. Acute care staff needs to be able to diagnose diseases that are most likely the result of microbial bioterrorism. There must be a plan of medical management in place in the health care setting to ensure that preventive action, such as a quarantine, and the immediate and orderly distribution of vaccines and antimicrobial drugs, can be taken to minimize disease transmission. Colleagues who work in public health, laboratories, infection control and occupational health are vital partners in medical management, together with emergency services response groups (eg, police, ambulance, city authorities) and criminal investigation units.

Since its discovery in 1981, human immunodeficiency virus type 1 (HIV-1) has rapidly emerged as one of the most devastating infectious pathogens of this century (1-3). The World Health Organization (WHO) estimates that, as of 1995, there were at least 15 million HIV- infected men, women, and children worldwide, with the vast majority of infections occurring in developing countries and isolated rural regions where specimen collection, preparation and shipment are difficult (4). Simple and improved sampling methods that can be widely applied under difficult field conditions are needed to effectively monitor the changing dynamics of the HIV-1/AIDS pandemic, track the spread of HIV-1 variants among different population groups, and ensure that research and interventive activities are directed against biologically important variants of the virus. To date, at least eight major HIV-1 subtypes, designated A through H, have been identified (5,6). More recently, a ninth subtype, I, has been detected (7), as well as several highly divergent, or "outlying" variants of HIV-1 that have been tentatively classified as group O (8,9). This subtyping is based on a relatively small number of specimens collected from a few geographic areas and the full range and distribution of HIV-1 variants remains to be established. The collection of whole blood on filter paper provides an innovative and powerful approach for the systematic and unbiased collection of large numbers of field specimens for diagnostic and surveillance purposes (10-19).

The collection of dried blood spots (DBS) on filter paper provides a powerful approach for the development of large-scale, population-based screening programs. DBS methods are particularly valuable in developing countries and isolated rural regions where resources are limited. Large numbers of field specimens can be economically collected and shipped to centralized reference laboratories for genetic and (or) serological analysis. Alternatively, the dried blood can be stored and used as an archival resource to rapidly establish the frequency and distribution of newly recognized mutations, confirm patient identity or track the origins and emergence of newly identified pathogens. In this report, we describe how PCR-based technologies are beginning to interface with international screening programmes for the diagnosis and genetic characterization of human immunodeficiency virus type 1 (HIV-1). In particular, we review recent progress using DBS specimens to resolve the HIV-1 infection status of neonates, monitor the genetic evolution of HIV-1 during early infancy and establish a sentinel surveillance system for the systematic monitoring of HIV-1 genetic variation in Asia.