Attention and neurodevelopment in young children who are HIV-exposed uninfected.

ABSTRACTChildren 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.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Viral dynamics of the SARS-CoV-2 Omicron Variant in Paediatric Patients; A prospective cohort study.

BACKGROUND: There are limited data on the viral dynamics of SARS-CoV-2 in children. Understanding viral load changes over the course of illness and duration of viral shedding may provide insight into transmission dynamics to inform public health and infection control decisions. METHODS: We conducted a prospective cohort study of children 18 years and younger with PCR confirmed SARS-CoV-2 between February 1, 2022 and March 14, 2022. SARS-CoV-2 testing occurred on daily samples for 10 days; a subset of participants completed daily rapid antigen testing (RAT). Viral RNA trajectories were described in relation to symptom onset and resolution. The associations between both time since symptom onset/resolution and non-infectious viral load were evaluated using a Cox proportional hazards model. FINDINGS: Among 101 children aged 2 to 17 years, the median time to study-defined non-infectious viral load was 5 days post symptom onset, with 75% meeting this threshold by 7 days, and 90% by 10 days. On the day of and day after symptom resolution, 43 of 87 (49%) and 52 (60%) had met the non-infectious thresholds, respectively. Of the 50 participants completing RAT, positivity at symptom onset and on the day after symptom onset was 67% (16/24) and 75% (14/20). On the first day where the non-infectious threshold was met, 61% (n = 27/44) of participant RAT results were positive. INTERPRETATION: Children often met the study-defined non-infectiousness threshold on the day after symptom resolution. RAT tests were often negative early in the course of illness and should not be relied on to exclude infection. CLINICAL TRIALS REGISTRATION: NCT05240183.

Breastfeeding Among People With Human Immunodeficiency Virus in North America: A Multisite Study.

BACKGROUND: In North American countries, national guidelines have strongly recommended formula over breastmilk for people with human immunodeficiency virus (HIV) because of concern for HIV transmission. However, data from resource-limited settings suggest the risk is <1% among virally suppressed people. Information regarding breastfeeding experience in high-resource settings is lacking. METHODS: A retrospective multisite study was performed for individuals with HIV who breastfed during 2014-2022 in the United States (8 sites) and Canada (3 sites). Descriptive statistics were used for data analysis. RESULTS: Among the 72 cases reported, most had been diagnosed with HIV and were on antiretroviral therapy prior to the index pregnancy and had undetectable viral loads at delivery. Most commonly reported reasons for choosing to breastfeed were health benefits, community expectations, and parent-child bonding. Median duration of breastfeeding was 24 weeks (range, 1 day to 72 weeks). Regimens for infant prophylaxis and protocols for testing of infants and birthing parents varied widely among institutions. No neonatal transmissions occurred among the 94% of infants for whom results were available ≥6 weeks after weaning. CONCLUSIONS: This study describes the largest cohort to date of people with HIV who breastfed in North America. Findings demonstrate high variability among institutions in policies, infant prophylaxis, and infant and parental testing practices. The study describes challenges in weighing the potential risks of transmission with personal and community factors. Finally, this study highlights the relatively small numbers of patients with HIV who chose to breastfeed at any 1 location, and the need for further multisite studies to identify best care practices.

Prescribing patterns of antiretroviral treatments during pregnancy for women living with HIV in Canada 2004-2020: A surveillance study.

BACKGROUND: While treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies. METHODS: The Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as 'preferred/alternative' as per HHS HIV perinatal guidelines, or 'other than preferred/alternative'. RESULTS: We identified 3673 pregnancies from 2720 women. The proportion of women that conceived while on ARV treatment increased from 29% in 2003 to 90% in 2020. Other than preferred/alternative ARV treatments were received in 1112 (30%) of pregnancies and this was significantly associated with having initiated ARV treatment before conception. CONCLUSION: In Canada during the study period, a high number of women were prescribed an other than preferred/alternative ARV treatment during pregnancy. Further optimization of ARV treatment in women of childbearing age living with HIV is warranted.

The cost-effectiveness of maternal and neonatal screening for congenital cytomegalovirus infection in Japan.

Congenital cytomegalovirus infection is the most common congenital infection. Using a decision tree model, cost-effectiveness of maternal screening with subsequent prenatal valacyclovir treatment and newborn screening with neonatal valganciclovir treatment was evaluated. The incremental cost-effectiveness ratio (ICER) was calculated for (1) universal maternal antibody screening with prenatal valacyclovir treatment compared to targeted newborn screening, and (2) universal newborn screening with postnatal valganciclovir treatment compared to targeted newborn screening. We performed a one-way sensitivity analysis. Compared to targeted newborn screening, the ICERs for universal newborn screening and maternal screening were 2 966 296 Japanese Yen (JPY) (21 188 USD) and 1 026 984 JPY (7336 USD), respectively. In all scenarios in the one-way sensitivity analysis, the ICERs of the maternal screening and the universal newborn screening strategies were less than three gross domestic product per capita compared with the targeted newborn screening strategy. Both maternal and universal newborn screening strategies may be cost-effective than a targeted newborn screening program. The potential utility of the maternal screening with valacyclovir treatment strategy, while potentially cost effective in regions with lower baseline seroprevalence rates, requires further study as the modeling was based on limited evidence.

SARS-CoV-2 infection in technology-dependent children: a multicenter case series.

PURPOSE: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection. METHODS: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome. RESULTS: Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home. CONCLUSION: Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.

Video directly observed therapy to improve adherence of human immunodeficiency virus infected adolescents to combination antiretroviral therapy: a proof-of-concept study.

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.

La réduction du risque d'infection périnatale chez les nouveau-nés de mères dont les soins prénatals étaient inappropriés.

Le risque que des infections maternelles ne soient ni décelées ni traitées augmente lorsque les soins prénatals sont inappropriés, ce qui met la santé de la mère et de son nouveau-né à risque. Lorsqu'une femme enceinte se présente tardivement pour recevoir des soins, les tests systématiques qui influent sur la prise en charge du nouveau-né devraient inclure l'antigène de surface de l'hépatite B (AgHBs), la sérologie du virus de l'hépatite C (VHC), du virus de l'immunodéficience humaine (VIH) et de la syphilis, de même que le dépistage de la Chlamydia trachomatis et de la Neisseria gonorrhoeae. Si la mère ne s'est pas soumise aux dépistages avant ou après l'accouchement et qu'elle n'est pas disponible pour s'y soumettre, il faudrait procéder au dépistage du VIH, du virus de l'hépatite B (VHB), du VHC et de la syphilis chez le nouveau-né. Le dépistage de la C. trachomatis et de la N. gonorrhoeae est toutefois réservé aux cas où le nouveau-né démontre des manifestations cliniques compatibles avec ces infections. Il est optimal d'obtenir rapidement les résultats du dépistage du VIH, du VHB et de la syphilis, car l'utilisation des traitements préventifs est circonscrite dans le temps. Il existe des interventions préventives précoces et efficaces pour les nouveau-nés à risque de VIH, de VHB, de syphilis ou de gonorrhée. Un suivi clinique étroit et des tests de suivi s'imposent auprès des nouveau-nés de mères dont les soins prénatals étaient inappropriés, car il est impossible d'exclure pleinement toutes les infections pendant la période périnatale.

Reducing perinatal infection risk in newborns of mothers who received inadequate prenatal care.

Inadequate prenatal care increases risk for maternal infections going undetected and untreated, putting both the mother's health and that of her infant at risk. When pregnant women present late to care, routine testing that impacts infant management should include: hepatitis B surface antigen (HBsAg); serology for hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis; and testing for Chlamydia trachomatis and Neisseria gonorrhoeae. If the mother was not tested before or after delivery and is not available for testing, the infant should undergo testing for HIV, HBV, HCV, and syphilis. Testing for C. trachomatis and N. gonorrhoeae should be undertaken if the infant develops compatible clinical manifestations. Rapid turnaround of test results for HIV, HBV, and syphilis is optimal because preventive treatment decisions are time-sensitive. Early and effective preventive interventions are available for newborns at risk for HIV, HBV, syphilis, or gonorrhea. Close clinical follow-up and follow-up testing of infants born to mothers with inadequate prenatal care are warranted, as not all infections can be fully excluded perinatally.

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

INTRODUCTION: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited. METHODS: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes. RESULTS: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage. CONCLUSION: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.

Infants hospitalized for acute COVID-19: disease severity in a multicenter cohort study.

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)).    Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.

Elevated Blood Mitochondrial DNA in Early Life Among Uninfected Children Exposed to Human Immunodeficiency Virus and Combination Antiretroviral Therapy in utero.

BACKGROUND: Combination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life. METHODS: Whole-blood mtDNA content at birth and in early life (age 0-3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated. RESULTS: At birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life. CONCLUSION: The persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.

Urinary symptoms and quality of life in women living with HIV: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: To determine prevalence and quality of life impact of lower urinary tract symptoms (LUTS) in women living with HIV (WLWH). METHODS: Cross-sectional urinary questionnaires were included in a multicenter national prospective study of the HPV vaccine in WLWH. Demographic and clinical information was abstracted from the parent study. The Urinary Distress Inventory (UDI-6) and Urinary Impact Questionnaire (UIQ-7) were administered. Wilcoxon rank sum, two-sample chi-square or Fisher's exact tests were used as appropriate to compare women with UDI-6 score ≥ 25 to those with lower UDI-6 scores on demographic and HIV-related factors. Significant categorical variables were followed up with logistic regression to estimate odds ratios (OR). RESULTS: One hundred seventy-seven women completed urinary questionnaires (85.5% of cohort). Median age was 44.1 (37.2-50.6). Mean CD4 count was 621 (410-785), and 132 women (74.6%) were virologically suppressed. Median UDI-6 score was 4.2 (0-25). Fifty-one women (28.8%) had a UIQ-7 score > 0. Among those with a UDI-6 score of at least 25, median UIQ-7 was 9.5 (0-47.6). UDI-6 ≥ 25 was significantly associated with increasing age, higher BMI, Canada as country of origin, peri-/postmenopausal status (OR 3.37, 95% CI = 1.71 to 6.75) and being parous (OR 2.92, 95% CI = 1.27 to 7.59) (all p < 0.05). HIV-related factors were not associated with UDI-6 ≥ 25. CONCLUSIONS: LUTS were common, but we did not demonstrate a negative impact on quality of life in this sample of WLWH. Large comparative studies are needed to determine whether HIV is a risk factor for bothersome LUTS in women.

The management of infants, children, and youth at risk for hepatitis C virus infection.

Hepatitis C virus (HCV) infection affects 0.5% to 1.0% of the Canadian population. Most paediatric HCV infections are a consequence of vertical transmission or, among youth and young adults, the result of engaging in high-risk behaviours, such as injection drug use and unprotected sexual activity. It is now recommended that all infants, children, and youth with one or more risk factors be screened for HCV infection. Treating chronic HCV infection with direct-acting antivirals has been shown to achieve sustained virologic suppression in 97% to 100% of children as young as 3 years old. Paediatricians and family physicians have an important role in educating youth regarding HCV infection risks and prevention, and in advocating to government and public health authorities for comprehensive harm reduction interventions targeting at-risk youth, accessible treatments, and routine prenatal screening for HCV.

Clinical Correlates of Human Immunodeficiency Virus-1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years.

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.

Enteroviral and herpes simplex virus central nervous system infections in infants < 90 days old: a Paediatric Investigators' Collaborative Network on Infections in Canada (PICNIC) study.

BACKGROUND: The relative contribution of viruses to central nervous system (CNS) infections in young infants is not clear. For viral CNS infections, there are limited data on features that suggest HSV etiology or on predictors of unfavorable outcome. METHODS: In this cross-sectional retrospective study, seven centers from the Pediatric Investigators Collaborative Network on Infections in Canada identified infants < 90 days of age with CNS infection proven to be due to enterovirus (EV) or herpes simplex virus (HSV) January 1, 2013 through December 31, 2014. RESULTS: Of 174 CNS infections with a proven etiology, EV accounted for 103 (59%) and HSV for 7 (4%). All HSV cases and 41 (40%) EV cases presented before 21 days of age. Four HSV cases (57%) and 5 EV cases (5%) had seizures. Three (43%) HSV and 23 (23%) EV cases lacked cerebrospinal fluid (CSF) pleocytosis. HSV cases were more likely to require ICU admission (p = 0.010), present with seizures (p = 0.031) and have extra-CNS disease (p < 0.001). Unfavorable outcome occurred in 12 cases (11% of all EV and HSV infections) but was more likely following HSV than EV infection (4 (57%) versus 8 (8%); p = 0.002). CONCLUSIONS: Viruses accounted for approximately two-thirds of proven CNS infections in the first 90 days of life. Empiric therapy for HSV should be considered in suspected CNS infections in the first 21 days even in the absence of CSF pleocytosis unless CSF parameters are suggestive of bacterial meningitis. Neurodevelopmental follow-up should be considered in infants whose course of illness is complicated by seizures.

Adenovirus-Associated Central Nervous System Disease in Children.

OBJECTIVE: To characterize the spectrum and salient clinical features of adenovirus-associated neurologic disease in immunocompetent children. STUDY DESIGN: Previously healthy children (aged 1 month-18 years) with central nervous system (CNS) disease associated with adenovirus infection were identified via the Encephalitis Registry (1996-2016) and Microbiology Database (2000-2016) at The Hospital for Sick Children, Toronto, and by systematic review of the literature. The data were pooled and analyzed to identify the spectrum of illness, clinical outcome, and risk factors for death or neurologic impairment. RESULTS: Neurologic complications associated with adenovirus infection in our institution included febrile seizures, encephalitis, acute disseminated encephalomyelitis, and aseptic meningitis. A total of 48 immunocompetent children with adenovirus-associated CNS disease were included in the pooled analysis-38 from the literature and 10 from our institution. In 85% of cases, the virus was detected in the respiratory or gastrointestinal tract, but not the cerebrospinal fluid. Eighteen of the 48 (38%) patients either died or suffered permanent neurologic sequelae. Predictors of adverse outcome included younger age, coagulopathy, the absence of meningismus, serotype 2 virus, and the presence of seizures. After multivariable adjustment, only seizures remained a significant risk factor. CONCLUSION: Adenovirus is a rare cause of CNS disease in immunocompetent children. Disease spectrum is variable, ranging from mild aspetic meningitis and fully reversible encephalopathy to severe, potentially fatal, acute necrotizing encephalopathy.