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Background Few data relate interferon-γ-release-assay results in children to source case sputum status, the best predictor of infectiousness of tuberculosis (TB) patients. We evaluated the QuantiFERON-Gold-in-tube assay (QFT) and tuberculin skin test (TST) in children with different types of TB exposure. Methods The TST and QFT were performed in referred TB-exposed children and adolescents who had not undergone prior TST screening (tested in parallel), and the QFT was performed in referred TST-positive individuals. Source case characteristics were obtained from referring public health units. We excluded children with known immunocompromising conditions and those known to have TB disease at the time of evaluation. Results For 103 patients tested in parallel, overall test agreement was very good in the Bacillus Calmette-Guerein (BCG) unimmunized contacts (κ = 0.83) and contacts of household smear-positive (HS+) cases (κ = 0.67), but test agreement was poor in those with lower-risk contact (κ = 0.34). Only 3 of 59 HS+ patients were QFT-positive and TST-negative. On multivariate analysis, a positive QFT was strongly associated with HS+ exposure (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.2-20]) but not BCG; and a positive TST was associated with BCG alone. For 92 referred TST-positive individuals, the QFT was negative in 21% of HS+ contacts, 65% of lower-risk contacts (OR, 6.8; 95% CI, 1.9-25), and 82% of the patients with unknown contact history (OR, 15.5; 95% CI, 5-54). Application of the Canadian 2010 guidelines would exclude from treatment 43 (72%) of the 73 TST+, QFT- patients. Conclusions For close contacts of HS+ individuals, the QFT added little sensitivity to the TST for detection of TB infection. The QFT correlated much better with exposure than the TST, especially in BCG-immunized children, and it has the greatest potential benefit for evaluation of those at lower risk of latent TB infection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The utility of routine therapeutic drug monitoring (TDM) in children living with HIV has not been extensively studied. The purpose of this study was to assess this strategy. METHODS: This was a single-center, prospective observational study of routine TDM for protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and integrase strand transfer inhibitors (INSTIs) in children living with HIV who were receiving antiretroviral therapy (ART) between February and December 2014. Outcome measures included the proportion of serum antiretroviral (ARV) medication concentrations in the therapeutic range (target values extrapolated from adult data) and the effect of serum concentrations on virologic control, medication adherence, and toxicity. RESULTS: Forty-eight children with a median age of 13 years (interquartile range, 3-18) were included. Median viral load (VL) and CD4% were <40 copies/mL (range, <40-124) and 37.4% (range, 8.4-47.9), respectively. Adherence was considered excellent in 95.8% of patients. Of the 50 serum trough concentrations (PI n = 19 [38%]; NNRTI n = 27 [54%]; INSTI n = 4 [8%]), 66% (n = 33) were in the therapeutic range, 12% (n = 6) were subtherapeutic, and 22% (n = 11) were supratherapeutic. There was no statistically significant correlation between serum ARV concentrations and patient demographics, VL, CD4%, or adherence. No clinically significant adverse events were noted. One dose adjustment was made for a subtherapeutic serum raltegravir concentration, likely attributable to interaction with ritonavir. CONCLUSIONS: This study does not support routine TDM in healthy children living with HIV who are well controlled on antiretroviral medication regimens. A more targeted strategy, such as when adherence is questioned or when there are suspected drug interactions, may be more appropriate. [ABSTRACT FROM AUTHOR]

OBJECTIVES. During the severe acute respiratory syndrome outbreak of 2003, there was an impetus to provide clinical information to the medical community in a timely manner. Accordingly, a preliminary report of our experience of suspected severe acute respiratory syndrome-associated coronavirus infections in children was published without microbiological findings. This report provides an update on pediatric severe acute respiratory syndrome-associated coronavirus infections in Toronto, Ontario, Canada, that includes microbiological findings. METHODS. All of the children admitted to the Hospital for Sick Children between March 14 and June 15, 2003, with suspect severe acute respiratory syndrome-associated coronavirus infection were included. A proven case was defined as one that fulfilled the clinical criteria for suspect severe acute respiratory syndrome-associated coronavirus infection and demonstrated a serologic response to severe acute respiratory syndrome-associated coronavirus. Serology results, from a neutralizing antibody assay, were considered positive if the sera inhibited the development of a severe acute respiratory syndrome-associated coronavirus-specific cytopathic effect at a dilution of ⩾1:8. RESULTS. Neutralizing antibody to severe acute respiratory syndrome-associated coronavirus was demonstrated in 8 of 25 children admitted with suspect severe acute respiratory syndrome-associated coronavirus infection. In 3 of these 8 children, severe acute respiratory syndrome-associated coronavirus was also detected by reverse-transcription polymerase chain reaction in the stool. All 8 had documented exposure to ⩾ 1 severe acute respiratory syndrome-associated coronavirus-infected adults residing in the same household. Exposure that was limited to visiting a Toronto hospital at which severe acute respiratory syndrome-associated coronavirus-infected patients were admitted or travel from a country in which severe acute respiratory syndrome had been reported did not result in documented infection in any of our cases. On the basis of our clinical case definition, 6 of 8 microbiologically confirmed case had been classified as having probable severe acute respiratory syndrome-associated coronavirus infection. Clinical disease was mild, nonspecific, and self-limited and was indistinguishable from that reported with other common respiratory viruses. CONCLUSIONS. The factor most strongly associated with severe acute respiratory syndrome-associated coronavirus infection in Toronto children was a history of close contact with an adult severe acute respiratory syndromeassociated coronavirus case. This serves to reinforce the importance of routinely obtaining a thorough epidemiologic travel and exposure history for all subjects with suspected infectious diseases. [ABSTRACT FROM AUTHOR]

HIV-exposed uninfected (HEU) children during the preschool and early school ages may be at-risk for neurodevelopmental challenges due to in utero and perinatal exposure to HIV and/or antiretroviral (ARV) medications. HEU children and HIV-unexposed uninfected (HUU) children from the community were recruited and tested at 3 to 4 and 5 to 6 years of age. Demographic information, HIV/ARV exposure and measures of intelligence, visuomotor skills, and adaptive functioning were obtained. Nonparametric tests assessed group differences and multiple regression analyses adjusted for demographic variables. Additional multiple regression analyses were performed within the HEU group to investigate associations between neurodevelopmental measures and variables of HIV/ARV exposure. At 3 to 4 years, 211 HEU children and 31 HUU children were assessed, and 144 HEU children and 58 HUU children were assessed at 5 to 6 years of age. At 3 to 4 years of age, HEU children scored significantly lower on measures of Full-Scale IQ, Performance IQ, visual motor integration, and adaptive functioning. At 5 to 6 years of age, HEU children scored significantly lower on all neurodevelopmental measures. At both ages, children who were female and those with mothers who were employed achieved higher scores on measures intellectual ability and/or adaptive functioning. Within the HEU group, no consistent associations were found between neurodevelopmental measures and HIV/ARV specific variables. HEU children demonstrated significantly lower scores on neurodevelopmental measures than HUU children during early childhood. Gaps in verbal intellectual abilities were identified with age, highlighting the importance of monitoring neurodevelopment in this population over time. [ABSTRACT FROM AUTHOR]

Children HIV-exposed, uninfected (CHEU) are at risk for compromised developmental outcomes. Attention is important for behavioural, cognitive and academic skills, yet has not been thoroughly investigated compared to children HIV-unexposed uninfected (CHUU). Fifty-five CHEU and 51 CHUU children were recruited at 5.5 years of age. Measures of inattention (IA), hyperactivity/impulsivity (HI) and total scores were collected using the parent-reported ADHD-Rating-Scale-IV. Measures of intelligence, visuomotor skills, academics and adaptive functioning were obtained. Analyses of between-group differences were performed as were correlational and multiple regression models, accounting for maternal education, employment and delivery type. Few children met clinical cut-offs for probable ADHD (3.6% CHEU, 2.0% CHUU), and no group differences in measures of IA, HI and combined scores were found. CHEU scored significantly lower than CHUU on intelligence, visuomotor function, academic skills and aspects of adaptive behaviour, though within age expectations. Lower Full-Scale IQ and Processing Speed were associated with higher IA in CHEU and lower adaptive functioning with higher IA in CHUU. Across both groups, children of unemployed mothers had more HI symptoms. CHEU were not at increased risk for attention difficulties at 5.5 years of age. Maternal employment status highlights the contribution of sociodemographic factors in shaping behaviour and neurodevelopment. [ABSTRACT FROM AUTHOR]

To explore how the International Classification of Functioning, Disability and Health, a rehabilitation framework, can provide a holistic understanding of stigma experiences of three women living with human immunodeficiency virus in Lusaka, Zambia. A secondary analysis of three cases by drawing on interview transcripts collected as part of a larger longitudinal study with eighteen women living with the virus. The interview tool used the rehabilitation framework to ask questions about the impact of the virus on the body, daily activities, social participation and the future. Vignettes were produced for each of the eighteen women including information on stigma and the rehabilitation framework. Three case studies were developed from women who provided comprehensive accounts of stigma and the International Classification of Functioning, Disability and Health. Stigma experiences aligned well with three dimensions of the International Classification of Functioning, Disability and Health: participation restrictions, environmental and personal factors. These domains were used to understand stigma in three forms (i.e. enacted, self and structural stigma) as experienced by these women. More research is needed to ascertain how stigma and rehabilitation are related in other environments and populations and to explore how to mitigate stigma within the rehabilitation context. Rehabilitation professionals deal with aspects of stigma and discrimination in their clinical work and this analysis offers a way to consider HIV-related stigma within rehabilitation in an organized and theoretically-informed way. The insights from this study are important for the field of HIV and for advancing understanding of the complexities of stigma in the context of rehabilitation more broadly. This analysis offers guidance to rehabilitation providers about the nuanced and multi-faceted ways that stigma can occur in the context of rehabilitation, including within their own clinical practice. [ABSTRACT FROM AUTHOR]

HIV-exposed uninfected (HEU) children may be at-risk for poorer academic achievement compared to HIV-unexposed uninfected (HUU) children due to in utero and perinatal exposure to HIV and/or anti-retroviral (ARV) medication. Understanding the risk factors for academic underachievement is important for implementing timely intervention and academic supports. HEU (N = 110, mean (SD) age 5.59 (0.22) years) and HUU (N = 43, mean (SD) age 5.73 (0.64) years) children completed assessments of general intelligence (WPPSI-III) and academic achievement (WRAT-4). Parent interviews and medical record reviews were used to obtain sociodemographic and maternal health data. HUU children scored significantly higher than HEU children on single word reading (p = 0.006), math calculation skills (p = 0.003), Verbal IQ, Performance IQ, Full Scale IQ, and Processing Speed (all WPPSI-III measures p < 0.001). Verbal IQ at 3–4 years predicted academic achievement at 5–6 years of age, yet sociodemographic and medical factors did not. These findings demonstrate that HEU children obtained significantly lower scores of intellectual, reading, and math abilities during early childhood. Addressing these early gaps before HEU children enter primary school will be critical for optimizing their learning and academic potential. [ABSTRACT FROM AUTHOR]

Stigma theory is concerned with inclusion and opportunities that influence well-being. Rehabilitation is also concerned with social inclusion and well-being. This is a central concern in one of the leading rehabilitation theories, the World Health Organization's International Classification of Functioning, Disability and Health. Despite these shared concerns, the relationship between the fields of stigma and rehabilitation has not been well theorized to date. Using human immunodeficiency virus (HIV) as an example, this article presents an analysis of three ways that stigma may be conceptualized within the context of the International Classification of Functioning, Disability and Health. Three broad spheres of stigma are described: enacted, self, and structural stigma. These three forms of stigma are then aligned in unique ways with three particular constructs of the International Classification of Functioning, Disability and Health: participation restrictions, environmental, and personal contextual factors. This conceptualization illustrates how rehabilitation professionals and other practitioners, policy makers and researchers can better understand the dynamic and nuanced forms of stigma and how they relate to rehabilitation. Implications for rehabilitation: This article enables rehabilitation professionals to better understand stigma as it relates to rehabilitation and human immunodeficiency virus. Rehabilitation professionals have the important job of allies and advocates for persons experiencing restrictions in these domains as a result of stigma. [ABSTRACT FROM AUTHOR]

Background: Exposure to discarded needles or other objects put children at risk for infection with blood-borne pathogens (BBP), including human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C. Objective: The purpose of this study was to retrospectively analyze the epidemiology, management and outcome of children following such exposures in the greater Toronto community setting. Methods: A retrospective study of children <19 years of age who had community-based exposure to objects that could contain BBP between January 2001 and December 2014. Sexual and hospital inpatient exposures were excluded. Patients were identified by medical record review of all children who had HIV testing performed. Results: Sixty-six community-based exposures to objects potentially contaminated with BBP were identified (71.2% needlesticks). The median age was 6.3 years (interquartile range 3.8, 7.8). Exposures occurred outdoors in the community (45.5%), in schools (30.3%), homes (15.2%) and community/outpatient clinics (9.0%). Of 11 (16.7%) identified source subjects, 7 were known to be HIV infected. HIV post-exposure prophylaxis was prescribed to 22 (33.3%) children; 15 (71.4%) completed the course. Only 41.2% of previously unvaccinated children were documented to have completed a full HBV vaccine series post-exposure. No blood-borne infections were documented, but only 60.6% had documentation of adequate follow-up testing. Conclusions: Enhanced public health interventions in schools and other community settings are needed to reduce childhood risk of exposure to needlesticks or other objects potentially contaminated with BBP. [ABSTRACT FROM AUTHOR]

Adherence to antiretroviral therapy (ART) is a major challenge for many youth living with HIV (YLWH). In this prospective proof-of-concept study, we assessed the feasibility and acceptability of conducting a study of video directly observed therapy (VDOT) as a method of improving medication adherence in YLWH who had a history of poor adherence to ART. The study had four phases; phase I – VDOT daily (4 months) using Facetime®; phase II – daily texting (2 months); phase III – weekly texting (3 months); phase IV – no intervention (3 months). Participants were seen in clinic on a monthly basis for assessment and laboratory evaluation. Five of eight eligible participants were enrolled. All achieved virologic suppression one month after enrollment. Three of five completed the study protocol and maintained virologic suppression through the 12-month period of study. Participant responses to the end-of-study questionnaire indicated satisfaction with the intervention and thought VDOT was helpful to them. Healthcare providers thought that the intervention was effective for some youth but was at times burdensome. This proof-of-concept study demonstrated that VDOT may be effective at improving medication adherence in previously poorly adherent YLWH and that larger studies of VDOT for such patients are both feasible and warranted. [ABSTRACT FROM AUTHOR]

Perinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-sectional study of CLWH, enrolled in the Early Pediatric Initiation Canadian Child Cure Cohort Study (EPIC4). Plasma levels of CHI3L1, pro-inflammatory cytokines, and markers of microbial translocation were measured by enzyme-linked immunosorbent assays. Longitudinal clinical characteristics (viral load, neutrophil count, CD4+ and CD8+ T-lymphocyte counts, and antiretroviral (ARV) regimen) were abstracted from patient medical records. One-hundred-and-five (105) CLWH (median age 13 years, 62% female) were included in the study. Seventy-seven (81%) had viral suppression on combination antiviral therapy (cART). The median CHI3L1 level was 25 μg/L (IQR 19–39). CHI3L1 was directly correlated with neutrophil count (ρ = 0.22, p = 0.023) and inversely correlated with CD4/CD8 lymphocyte ratio (ρ = −0.35, p = 0.00040). Children with detectable viral load had higher levels of CHI3L1 (40 μg/L (interquartile range, IQR 33–44) versus 24 μg/L (IQR 19–35), p = 0.0047). CHI3L1 levels were also correlated with markers of microbial translocation soluble CD14 (ρ = 0.26, p = 0.010) and lipopolysaccharide-binding protein (ρ = 0.23, p = 0.023). We did not detect differences in CHI3L1 between different cART regimens. High levels of neutrophil activation marker CHI3L1 are associated with poor virologic control, immune dysregulation, and microbial translocation in CLWH on cART. [ABSTRACT FROM AUTHOR]

Background: Recombinant proteins of therapeutic use are ideally produced in human cells to ensure appropriate co- and post-translational modifications. However, purification of secreted proteins from the culture media is impeded by low expression from transfected cell lines and the presence of serum proteins. Here we describe a simple and cost-effective approach based on lentiviral vector-mediated gene delivery and expression of a secreted His-tagged protein from human embryonic kidney 293 T cells and direct affinity chromatography purification from the cell culture media. Results: Using a protein-based HIV entry inhibitor, soluble CD4 (sCD4), we demonstrated that 293 T cells transduced with a lentiviral vector mediated over 10-fold higher secretion of sCD4 in comparison to 293 T cells transfected with the corresponding plasmid. Secretion of sCD4 increased with the dose of the lentiviral vector up to a multiplicity of infection of 50. Exchanging the native signal peptide of sCD4 with the signal peptide of human alpha-1 antitrypsin increased expression by 50 %. There was no difference in expression from a monocistronic or bicistronic lentiviral vector. Reduction of the serum concentration in the culture media had no significant effect on the secretion of sCD4. Small-scale purification from 50 ml of culture media with reduced serum content yielded up to 1 mg of pure sCD4. Purified sCD4 bound to recombinant HIV envelope glycoprotein 120 (Env gp120) and inhibited HIV entry at concentrations comparable to published results. Conclusion: The procedure outlined in this study can be performed without the need for specialized reagents or equipment and could easily be adapted by any laboratory. Furthermore, the method could be used to produce sCD4 fusion proteins or other His-tagged proteins. [ABSTRACT FROM AUTHOR]

Background: Recombinant proteins of therapeutic use are ideally produced in human cells to ensure appropriate co- and post-translational modifications. However, purification of secreted proteins from the culture media is impeded by low expression from transfected cell lines and the presence of serum proteins. Here we describe a simple and cost-effective approach based on lentiviral vector-mediated gene delivery and expression of a secreted His-tagged protein from human embryonic kidney 293 T cells and direct affinity chromatography purification from the cell culture media. Results: Using a protein-based HIV entry inhibitor, soluble CD4 (sCD4), we demonstrated that 293 T cells transduced with a lentiviral vector mediated over 10-fold higher secretion of sCD4 in comparison to 293 T cells transfected with the corresponding plasmid. Secretion of sCD4 increased with the dose of the lentiviral vector up to a multiplicity of infection of 50. Exchanging the native signal peptide of sCD4 with the signal peptide of human alpha-1 antitrypsin increased expression by 50 %. There was no difference in expression from a monocistronic or bicistronic lentiviral vector. Reduction of the serum concentration in the culture media had no significant effect on the secretion of sCD4. Small-scale purification from 50 ml of culture media with reduced serum content yielded up to 1 mg of pure sCD4. Purified sCD4 bound to recombinant HIV envelope glycoprotein 120 (Env gp120) and inhibited HIV entry at concentrations comparable to published results. Conclusion: The procedure outlined in this study can be performed without the need for specialized reagents or equipment and could easily be adapted by any laboratory. Furthermore, the method could be used to produce sCD4 fusion proteins or other His-tagged proteins. [ABSTRACT FROM AUTHOR]

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 ROMor mode of delivery and MTCT in this cohort of 210 virally suppressed HIV-positive pregnant women. [ABSTRACT FROM AUTHOR]

Background The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus–1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years. Methods HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO). Results Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P <.001, P =.036, and P <.001, respectively) and age when SVS was achieved (P =.002, P =.038, and P <.001, respectively) and inversely with the proportion of life spent on effective cART (P <.001, P =.01, and P <.001, respectively) and proportion of life spent with SVS (P <.001, P =.079, and P <.001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P =.037) or later (rho = 0.87; P <.001). S/COs correlated with HIV-1 DNA (P =.003), but less so with inducible cell-free HIV-1 RNA (P =.09). Conclusions The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation, platelet dysfunction, and endothelial activation persist in people living with HIV despite sustained virologic suppression (SVS) with combined antiretroviral therapy (cART) and may lead to complications such as atherosclerosis and cardiovascular disease. Angiopoietin-1 (Ang-1) is a key regulator of angiogenesis and endothelial activation and has been studied as an objective biomarker in disease states such as atherosclerosis, sepsis, and severe malaria. Setting: Eight pediatric HIV care centers across Canada. Methods: Cross-sectional study of 61 children living with vertically acquired HIV on cART with undetectable RNA viral load. Plasma levels of Ang-1 were measured by ELISA and analyzed in relation to clinical characteristics abstracted from medical records. Results: Ang-1 levels were directly correlated with clinical indices of virologic control: cumulative proportion of life on effective cART (ρ = +0.35, P = 0.0078) and cumulative proportion of life with SVS (ρ = +0.36, P = 0.0049). Furthermore, higher Ang-1 levels were associated with younger age at SVS (ρ = −0.56, P < 0.0001). These associations remained statistically significant in multivariable linear regression models adjusting for potential confounders (P < 0.05 for all associations). Conclusions: Early effective cART and SVS were associated with higher Ang-1 levels in children living with vertically acquired HIV-1. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antimicrobial stewardship programs (ASPs) are targeted to optimize antimicrobial use. However, pediatric metrics used to measure outcomes of ASPs are not well established. Our aim for this project was to identify, refine, and develop consensus on standard metrics for pediatric ASPs. METHODS: By using a modified Delphi process, 2 surveys were sent to experts and stakeholders to establish consensus on the utility of metrics. These were subdivided into 4 ASP domains: (1) antimicrobial consumption, (2) microbiologic outcomes, (3) clinical outcomes, and (4) process measures. Respondents were asked to rank the scientific merit, impact, feasibility, and accountability of each metric. Metrics with ≥75% agreement for scientific merit were included and metrics with ≤25% agreement were discarded. Consensus was finalized with a face-to-face meeting and final survey. RESULTS: Thirty-eight participants from 15 pediatric hospitals across Canada completed all 3 rounds of the Delphi survey. In the domain of antimicrobial consumption, the 2 selected metrics were (1) days of therapy per 1000 patient-days and (2) total antimicrobial days. The clinical and process outcomes chosen were (1) 30-day readmission rate and (2) adherence to ASP recommendations, respectively. A microbiologic outcome was felt to be important and feasible, but consensus could not be obtained on a measure. Several barriers to implementation of the metrics were identified, including information technology limitations at various centers. CONCLUSIONS: We obtained consensus on 4 metrics to evaluate pediatric antimicrobial stewardship activities in Canada. Adoption of these metrics by pediatric ASPs will facilitate measurement of outcomes nationally and internationally. [ABSTRACT FROM AUTHOR]

Little is known about the neurodevelopmental outcomes of children older than 3 years of age born to HIV infected mother but who are HIV-uninfected (HEU), and who have been exposed in utero and early in life to HIV and to antiretroviral medications (ARVs). We conducted a longitudinal study of cognitive, visuomotor and adaptive function of HEU children, who were assessed at two ages, 3.5 and 5.5 years. Sixty-four children (33 female) were assessed. In comparison with population norms for their age, at 3.5 years of age they had scores significantly below age expectations on aspects of adaptive behavior, but at age 5.5 years, their scores did not significantly diverge from the population norms on any of the measures. Verbal intelligence was lower at age 5.5 than at age 3.5 years, although there were also improvements in some features of adaptive behavior. Exposure to PI-based ARVs (compared to NNRTIs) was associated with higher Performance IQ, visuomotor and communication scores at age 5.5 years. Birth, early growth, and sociodemographic variables were predictive of outcomes. This study is important in tracking the trajectory of neurocognitive development across the pre-school and early school age years. The findings suggest that the full impact of early ARV exposure may not be evident until a considerable period of development has occurred. The results raise the possibility of negative effects of early ARV exposure on neurodevelopment that emerge over time, and reiterate the importance of sociodemographic and early health variables for optimal development. [ABSTRACT FROM PUBLISHER]

Background: Nevirapine (NVP)-based combination antiretroviral therapy is routinely prescribed to infants deemed at high risk of vertical HIV infection in our centers. We evaluated NVP pharmacokinetics and safety of this regimen. Methods: Neonates were recruited prospectively between September 2012 and April 2015 or enrolled retrospectively if treated similarly before prospective study initiation. NVP was dosed at 150 mg/m2 daily for 14 days, then twice daily for 14 days. NVP levels were drawn at weeks 1, 2, and 4 [target trough (NVP-T): 3-8 mg/L]. Results: Thirty-three neonates were included (23 prospectively). Median gestational age (GA) and birth weight were 38 weeks (32-41 weeks) and 2.9 kg (1.5-4.2 kg), respectively. Median NVP-Ts were 8.2 mg/L (1.6-25.1 mg/L), 3.5 mg/L (1.6-6.8 mg/L), and 4.3 mg/L (0.1-19.9 mg/L) at weeks 1, 2, and 4, respectively. The proportions with therapeutic NVP-T were 42%, 61%, and 73% at these same timepoints. Median apparent oral clearance (CL/F) increased from 0.05 L⋅kg-1⋅h-1 (0.01-0.50 L⋅kg-1⋅h-1) at week 2 to 0.18 L⋅kg-1⋅h-1 (0.01-0.78 L⋅kg-1⋅h-1) at week 4. Increased drug exposure [area under the curve (AUCt)] correlated with younger GA (r = 0.459, P = 0.032) and lower birth weight (r = 0.542, P = 0.009). The most common adverse events potentially attributable to combination antiretroviral therapy were transient asymptomatic hyperlactatemia (26%), anemia (24.7%), and neutropenia (22.1%). Conclusions: Treatment dose NVP was generally well-tolerated and associated with normalization of trough levels over time in most cases without dose adjustment. Lower empiric dosing is recommended for infants <34 weeks of GA. Routine therapeutic drug monitoring may not be required for infants ≥34 weeks of GA. [ABSTRACT FROM AUTHOR]

This study examines EBV strains from transplant patients and patients with IM by sequencing major EBV genes. We also used NGS to detect EBV DNA within total genomic DNA, and to evaluate its genetic variation. Sanger sequencing of major EBV genes was used to compare SNVs from samples taken from transplant patients vs. patients with IM. We sequenced EBV DNA from a healthy EBV-seropositive individual on a HiSeq 2000 instrument. Data were mapped to the EBV reference genomes ( AG876 and B95-8). The number of EBNA2 SNVs was higher than for EBNA1 and the other genes sequenced within comparable reference coordinates. For EBNA2, there was a median of 15 SNV among transplant samples compared with 10 among IM samples (p = 0.036). EBNA1 showed little variation between samples. For NGS, we identified 640 and 892 variants at an unadjusted p value of 5 × 10−8 for AG876 and B95-8 genomes, respectively. We used complementary sequence strategies to examine EBV genetic diversity and its application to transplantation. The results provide the framework for further characterization of EBV strains and related outcomes after organ transplantation. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: Retrospective study on 148 cART and 145 Zidovudine (ZDV) monotherapy-exposed infants identified from four Canadian centres where cART for PEP has routinely been prescribed in high-risk situations. Physician-reported adverse events and clinical outcomes were extracted by chart review. Haematological and growth parameters at birth, one and six months of age were compared between cART and ZDV-exposed infants using multivariate mixed effects modelling. Results: Non-specific signs and symptoms were reported in 10.2% of cART recipients versus none of the ZDV recipients. Treatment was discontinued prematurely in 9.5% of cART recipients versus 2.1% of ZDV recipients (p=0.01). In the multivariate model, cART recipients had lower mean haemoglobin (decrease of 2.07 g/L) over the 6-month period compared with ZDV recipients (p=0.04), but no effect was seen on absolute neutrophil count. cART recipients had lower weight and smaller head circumference at birth and one month of age compared with ZDV-exposed infants; these differences were no longer significant at six months of age. Conclusions: cART administered at treatment doses for PEP in neonates was generally well tolerated, though a higher incidence of non-specific signs and symptoms and early treatment discontinuation occurred among cART recipients. [ABSTRACT FROM AUTHOR]

Nonadherence to antiretroviral treatment has serious health implications for HIV-infected children, at times warranting referral to child protective services (CPS). The current study of 134 children with perinatally acquired HIV infection aimed to investigate rates of treatment adherence and CPS involvement, multilevel variables associated with nonadherence, and the manner in which these risks operated together in the prediction of adherence outcomes. Risk factors for nonadherence were grouped on the basis of confirmatory factor models, and factor score regression was carried out to determine which factors were uniquely predictive of adherence. A series of indirect effects models were then tested in order to examine how these factors operated together in the prediction of adherence. Results showed that almost half of the sample demonstrated suboptimal adherence to treatment, and in one-fifth, CPS was involved for medical neglect. Caregiver Health, Caregiver Involvement, Caregiver Acceptance, and Child Adaptation were predictive of nonadherence, and together explained 54% of the variance in treatment adherence. There were significant indirect effects of Caregiver Health on adherence that operated through Caregiver Involvement and Child Adaptation and an indirect effect of Caregiver Involvement on adherence through Child Adaptation. Findings extend current literature that has independently linked various factors predictive of medical adherence in pediatric HIV by showing separate but simultaneous associations with nonadherence and unique pathways to adherence involving multilevel risks. Healthcare and child welfare implications are discussed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: HIV infected children are at increased risk of TB disease and require annual TB screening. Data on use of IGRA for TB screening in them are limited. We retrospectively evaluated the usefulness of Quantiferon Gold-in-tube test (QFT), an IGRA in screening for LTBI in relatively healthy, immunologically stable HIV infected children. Methods: HIV infected children with no prior history of TB were screened for latent TB as part of routine care. They underwent risk of TB assessment, TST and QFT. QFT was repeated twice or three times depending on the quantitative values. Independent test validation was also performed. Results: Eighty one children had 109 QFT tests. All had adequate mitogen responses. The initial QFT was positive in 15 (18.5%) children; quantitative IGRA responses were 0.35-1.0 IU/mL in 9 (60%), 1.0-10 IU/mL in 5 (33.3%) and >10 IU/mL in 1 (6.7%). None that tested positive had documented TB exposure or TB disease. Baseline characteristics in the QFT positive and negative groups were similar. Repeat testing within 17 weeks demonstrated reversion to negative in 79% of cases. Repeat blinded independent testing of all QFT positive results and a random selection of initial negative tests demonstrated concordance in 96% of cases. Seven children (QFT > 1.0 IU/mL or positive TST) were offered INH preventive therapy. In no case has TB disease developed in 2 years of close follow-up. Conclusions: QFT is a valid method for LTBI screening relatively healthy, immunologically stable HIV infected children. However, reversion to negative on repeat testing and lack of correlation with TST results and risk of TB exposure makes interpretation difficult. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on disease characteristics and outcomes of children with 2009 pandemic influenza A(H1N1) virus infection (pandemic H1N1 influenza) who have required hospital admission. Methods: We reviewed the charts of 58 children with pandemic H1N1 influenza admitted to a large pediatric hospital in Ontario, Canada, between May 8 and July 22, 2009. We compared risk factors, severity indicators and outcomes of these children with those of 200 children admitted with seasonal influenza A during the previous 5 years (2004/05 to 2008/09). Results: Children with pandemic H1N1 influenza were significantly older than those with seasonal influenza (median age 6.4 years v. 3.3 years). Forty-six (79%) of the children with pandemic H1N1 influenza had underlying medical conditions; of the other 12 who were previously healthy, 42% were under 2 years of age. Children admitted with pandemic H1N1 influenza were significantly more likely to have asthma than those with seasonal influenza (22% v. 6%). Two children had poorly controlled asthma, and 6 used inhaled medications only intermittently. The median length of stay in hospital was 4 days in both groups of children. Similar proportions of children required admission to the intensive care unit (21% of those with pandemic H1N1 influenza and 14% of those with seasonal influenza) and mechanical ventilation (12% and 10% respectively). None of the children admitted with pandemic H1N1 influenza died, as compared with 1 (0.4%) of those admitted with seasonal influenza. Interpretation: Pandemic H1N1 influenza did not appear to cause more severe disease than seasonal influenza A. Asthma appears to be a significant risk factor for severe disease, with no clear relation to severity of asthma. This finding should influence strategies for vaccination and pre-emptive anti viral therapy. [ABSTRACT FROM AUTHOR]

We hypothesized that aspects of the virus–host interaction could be measured to help predict progression to EBV–PTLD. We examined the spectrum of host genes differentially expressed and any relevant clustering in children at risk of EBV lymphoproliferation after organ transplantation. We compared the genes expressed among patients with different levels of viral loads. Gene expression was measured by microarray analysis of RNA from CD19+ B lymphocytes using the Human Genome U133 Plus 2.0 GeneChip. Among 27 samples from 26 transplant recipients, the viral load categories were: low or undetectable loads (LU), n = 14; high or intermediate loads (HI), n = 13. There were seven healthy EBV-seropositive (P) and -seronegative controls (N). Median time of post-transplantation was 0.5 yr (range 0.1–3.8). We identified 24–54 differentially expressed genes in each of four comparisons of HI vs. P, LU vs. P, HI vs. LU, and P vs. N. We identified patterns of 563 gene expressions, creating five clusters aligned with levels of viral load. PTLD occurred in four of five clusters. In summary, we demonstrated varying degrees of alignment between levels of VL and gene clusters. Analyses for differential expression of genes showed genes that could be implicated in the pathogenesis of EBV–PTLD. [ABSTRACT FROM AUTHOR]

Background. The effects of perinatal antiretroviral therapy (ART) on infant mitochondrial function are not well known. We compared blood mitochondrial DNA (mtDNA) levels and mtDNA gene expression (mtRNA) in human immunodeficiency virus (HIV)-uninfected, ART-exposed infants born to HIV-positive mothers with mtDNA levels and mtDNA gene expression in control infants born to uninfected women. Methods. In this prospective cohort study, longitudinal mtDNA:nuclearDNAand mtRNA: β-actin mRNA ratios were compared in blood samples obtained at various time points from birth to 8 months, using generalized estimating equation linear regression models. Results. Log10 mtDNA levels at birth were higher in ART-exposed infants, compared with levels in control infants, although the difference did not reach statistical significance (P = .07 for comparison of samples obtained 0-3 days after birth). ART-exposed infants' mtDNA levels increased further during the zidovudine prophylaxis period-from age 4 days to age 6 weeks-(P = .001) and remained significantly higher than the levels observed in control infants until the end of the study. In contrast, log10 mtRNA levels at birth were lower in ART-exposed infants than in control infants (P = .03), but were not statistically different later. Conclusions. When control infants and ART-exposed infants were compared, the mtDNA level was increased but mitochondrial gene expression was decreased in ART-exposed infants. These differences persisted after zidovudine was discontinued, suggesting that changes in mitochondrial proliferation and/or expression take place during and after ART exposure. These changes are likely the effects of the antiretroviral drugs on mitochondria. The clinical relevance and long-term impact of these alterations must be studied. [ABSTRACT FROM AUTHOR]

Background: The aim of the present paper was to determine whether monthly i.v. immunoglobulin (IVIG) could be safely discontinued in antiretroviral-treated human immunodeficiency virus (HIV)-infected children. Methods: In a double-blind cross-over trial, children ≤18 years with HIV infection, well controlled on antiretroviral therapy, were randomized to alternating courses of 3 consecutive months of IVIG (400 mg/kg once a month) and 3 consecutive months of placebo for 1 year. The primary outcome was days of fever per month. Secondary outcomes were frequency of serious infections, changes in HIV viral load (VL), CD4+ counts and IgG levels. Results: Fifteen children were enrolled. Using the revised pediatric HIV clinical classification system of the Centers for Disease Control and Prevention, eight were severely symptomatic (C), four were moderately symptomatic (B) and three were mildly symptomatic (A). There were no statistically significant outcome measures. The mean number of days of fever per month with IVIG versus placebo was 0.55 days versus 1.48 days ( P = 0.11). The difference was 0.9 days (95% confidence interval: +2.05 to −0.25). There were no serious infections in either period. For the IVIG versus placebo periods, mean CD4 counts were 970 cells/μL versus 906 cells/μL ( P = 0.12), VL 2.90 log10 copies/mL versus 2.82 log10 copies/mL ( P = 0.70) and IgG levels were 17.41 g/L versus 16.6 g/L ( P = 0.13). Conclusion: In antiretroviral-treated HIV-infected children short-term withdrawal of monthly IVIG was not associated with a significant increase in incidence of infections or a decline in immunologic function (CD4 count, viral load and IgG levels). These results suggest that monthly IVIG can be safely discontinued in HIV-infected children who are clinically stable and receiving combination antiretroviral therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is limited worldwide experience with severe acute respiratory syndrome (SARS) in pregnancy. We present a case of SARS complicating pregnancy in the third trimester, with outcome data on both the mother and baby. CASE: A 33-year-old gravida 2 para 1 fulfilling the World Health Organization case definition for probable SARS was admitted to our institution at 31 weeks of gestation with fever, a dry cough, and patchy infiltrates on chest X-ray. The patient was previously healthy and acquired SARS from close contact with an infected family member. Convalescent serology results were positive for antibodies to coronavirus. She stayed in hospital for 21 days and did not require intensive care admission or ventilatory support. Labor occurred spontaneously at term, and a healthy female baby was delivered with no evidence of infection. CONCLUSION: Severe acute respiratory syndrome in pregnancy is a potentially life-threatening illness with complicated management issues. Hospitalization and care by a multidisciplinary team may optimize chances for a good outcome. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children.Objective: The goal of this study was to characterize the radiographic presentation of children with SARS.Materials and Methods: We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy.Results: A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 degrees C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age>/=10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient.Conclusion: In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases. [ABSTRACT FROM AUTHOR]

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... [ABSTRACT FROM AUTHOR]

We examined a broad range of neuropsychological functioning in school-age children with vertically transmitted HIV infection and a control group made up of siblings of children with HIV infection. Fourteen children with HIV (2 asymptomatic, 8 mildly symptomatic, and 4 with AIDS) and 11 control children were administered a battery of neuropsychological tests assessing intelligence, receptive language, expressive language, visual and verbal memory, visual-motor speed and coordination, visual-motor and visual-spatial processing, fine motor skill, and academic achievement. Results revealed that school-age children with vertically transmitted HIV infection show many areas of cognitive function within the normal range. Despite normal cognitive development, subtle motor impairments were documented in children with vertically transmitted HIV infection. Our results are the first report of fine motor and motor strength deficits in school-age children with vertically transmitted HIV. Lastly, computed tomography (CT) results suggest that children with HIV who have documented structural anomalies in the brain may be at risk for deficits in visual-motor and visual-spatial processing. This finding should be explored with larger samples and other measures to determine its generalizability. [ABSTRACT FROM AUTHOR]

Abstract. A total of 11 cases of red man syndrome collected among 650 children who had received vancomycin in our hospital between 1986 and 1988 (estimated prevalence 1.6%) were retrospectively analyzed. These 11 children were compared with 11 age-matched children who received vancomycin in whom red man syndrome did not develop. Of the patients with red man syndrome, 73%, and of the patients with no reaction, 45.4% received vancomycin for penicillin-resistant Staphylococcus epidermidis-positive cultures, or because of history of penicillin allergy. No difference was observed in the dose per kilogram given to both groups (12.9 +/- 3.5 mg/kg per dose in those with red man syndrome vs 12.3 +/- 6.9 mg/kg per dose in control childrens. The duration (mean +/- standard deviation) of vancomycin infusion was 45.9 +/- 16.7 minutes (range 10 to 90 minutes) in patients with red man syndrome and 54.5 +/- 7.6 minutes (range 45 to 65 minutes) in the control group (P = .07). In the 5 children with red man syndrome rechallenged with vancomycin, slower infusion rates prevented or reduced the syndrome, which emphasized the fact that the rate of administration is the important determinant of red man syndrome in susceptible cases. Clinically, the syndrome developed at the end of the infusion in most patients, but appeared as early as 15 minutes after initiation of the infusion. It was mostly manifested as a flushed, erythematous rash on the face, neck, and around the ears. Less frequently, the rash was distributed all over the body. Pruritus was usually localized to the upper trunk but was also generalized (2 of 11 children). Associated signs and symptoms were hypotension, watery puffy eyes, tachycardia, respiratory distress, dizziness, agitation, and mild temperature increase. A premature infant with the red man syndrome had skin rash associated with poor... INSET: REVIEWS OF LAY LITERATURE... by F. GLASCOE, W. MOORE, E. MARTIN. [ABSTRACT FROM AUTHOR]

The article describes two cases of pediatric patients and discusses how health care providers address their problems. Topics covered include the food allergies experienced by a 12-year-old patient, cause of fever in a three-week-old baby and details of the cases. Also mentioned are comorbid health conditions diagnosed in the patients.

Focuses on a retrospective chart review of infants diagnosed with perinatally acquired HIV infection who were born to women who became pregnant subsequent to the introduction of universal prenatal HIV counselling in Ontario. Evaluation of the effectiveness of prenatal HIV counselling and testing programs in several countries; Diagnosis of children who were perinatally infected with HIV.