Chronic and Latent Viral Infections and Leukocyte Telomere Length across the Lifespan of Female and Male Individuals Living with or without HIV.

BACKGROUND: Chronic/latent viral infections may accelerate immunological aging, particularly among people living with HIV (PLWH). We characterized chronic/latent virus infections across their lifespan and investigated their associations with leukocyte telomere length (LTL). METHODS: Participants enrolled in the CARMA cohort study were randomly selected to include n = 15 for each decade of age between 0 and >60 y, for each sex, and each HIV status. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), herpes simplex virus 1 (HSV-1), and HSV-2 infection were determined serologically; HIV, hepatitis C (HCV), and hepatitis B (HBV) were self-reported. LTLs were measured using monochrome multiplex qPCR. Associations between the number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modeling. RESULTS: The study included 187 PLWH (105 female/82 male) and 190 HIV-negative participants (105 female/84 male), ranging in age from 0.7 to 76.1 years. Living with HIV, being older, and being female were associated with harbouring a greater number of chronic/latent non-HIV viruses. Having more infections was in turn bivariately associated with a shorter LTL. In multivariable analyses, older age, living with HIV, and the female sex remained independently associated with having more infections, while having 3-4 viruses (vs. 0-2) was associated with a shorter LTL. CONCLUSIONS: Our results suggest that persistent viral infections are more prevalent in PLWH and females, and that these may contribute to immunological aging. Whether this is associated with comorbidities later in life remains an important question.

Imported congenital malaria caused by Plasmodium ovale: A case report.

We describe a 5-week-old term infant with Plasmodium ovale severe congenital malaria in a non-endemic setting. She presented with diarrhea, poor feeding, lethargy, hepatosplenomegaly, and severe anemia. She was fortuitously diagnosed with malaria on routine blood smear, and successfully treated with intravenous artesunate. Subsequent history revealed maternal malaria diagnosis and treatment during pregnancy in Nigeria. This case underscores the importance of obtaining maternal exposure history and considering malaria testing in pregnant women and infants with unexplained illness. It also contributes to the limited literature on congenital malaria and severe malaria caused by P. ovale.

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.

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.

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.

A 20-year Study of Intracranial Pyogenic Complications of Sinusitis in Children.

BACKGROUND: Intracranial pyogenic complications of sinusitis in children can lead to serious sequelae. We characterize the clinical, epidemiologic and microbiologic characteristics of children with such complications over a 20-year period. METHODS: Single-center retrospective chart review. Cases were identified based on International Classification of Diseases diagnostic codes (ICD)-9 and ICD-10 depending on the year and by reviewing all intracranial microbiological samples. RESULTS: A total of 104 cases of complicated sinusitis were included after review of 1591 charts. Median age was 12 (IQR 9-14); 72 were male (69%). The most frequent complications were epidural empyema (n = 50, 48%), subdural empyema (n = 46, 44%) and Pott's puffy tumor (n = 27, 26%). 52% (n = 54) underwent neurosurgery and 46% (n = 48) underwent otolaryngological surgery. The predominant pathogen isolated from sterile site specimens was Streptococcus anginosus (n = 40, 63%), but polymicrobial growth was common (n = 24; 38%). The median duration of intravenous antibiotic therapy was 51 days (IQR 42-80). Persistent neurological sequelae (or death, n = 1) were found in 24% (n = 25) and were associated with the presence of cerebritis and extensive disease on neuroimaging ( P = 0.02 and P = 0.04, respectively). CONCLUSIONS: Intracranial complications of sinusitis continue to cause significant morbidity in children. Polymicrobial infections are common, which reinforces the need for broad-spectrum empiric antibiotic therapy and cautious adjustment of the antibiotic regimen based primarily on sterile site cultures. The association of neurologic sequelae with the presence of cerebritis and extensive intracranial involvement on neuroimaging suggest that delayed diagnosis may be a contributor to adverse outcome.

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.

Canadian Pediatric & Perinatal HIV/AIDS Research Group consensus recommendations for infant feeding in the HIV context.

Background: Providing comprehensive infant feeding guidance to families affected by HIV is complex and requires a multidisciplinary approach. While exclusive formula feeding remains the preferred recommendation for infants born to women living with HIV (WLWH) in high-income countries, a more nuanced approach that may include the option of breastfeeding under certain circumstances is emerging in many resource-rich countries. Methods: The Canadian Pediatric & Perinatal HIV/AIDS Research Group (CPARG) hosted a Canadian Institute of Health Research-funded meeting in 2016 to develop consensus among multidisciplinary providers around counselling and recommendations for infant feeding. After presentations by adult and paediatric health care providers, basic scientists, and community-based researchers, a subgroup drafted summary evidence-informed recommendations. Along with revisions among CPARG members, a community review was performed by a convenience sample of WLWH who had given birth in the past 5 years from Ontario and Quebec. A legal review was also conducted to ensure understanding of the criminalization potential and concern of HIV transmission and exposure. Results: The Canadian consensus guidelines continue to support formula feeding as the preferred method of infant feeding as it eliminates any residual risk of postnatal vertical transmission. Formula should be made available for all infants born to mothers living with HIV for their first year of life. A comprehensive approach to counselling WLWH is outlined to assist providers to effectively counsel on current evidence to ensure WLWH are fully informed in their decision making. For women meeting criteria to and elect to breastfeed, frequent maternal virologic monitoring and follow-up is required of both mother and infant. Antiretroviral prophylaxis and monitoring are recommended for breastfed infants. The community review highlighted the importance of other supports and counselling needed for implementing effective formula feeding, aside from access to formula. The legal review provided clarifying language around child protection services involvement and the need to provide referral to legal resources or information upon request. Surveillance systems to monitor for cases of breastmilk transmission should be in place to improve gaps in care and develop further knowledge in this area. Conclusion: The Canadian infant feeding consensus guideline is designed to inform and enable better care for WLWH and their babies. Ongoing evaluation of these guidelines as new evidence emerges will be important.

Historique: La transmission de conseils détaillés sur l'alimentation du nourrisson aux familles touchée par le VIH est complexe et exige une approche multidisciplinaire. Il est recommandé de recourir exclusivement aux préparations commerciales chez les nourrissons de mères vivant avec le VIH (MVIH) dans les pays à revenu élevé, mais une approche plus nuancée, qui peut inclure l'allaitement dans certaines situations, émerge dans de nombreux pays riches en ressources. Méthodologie: Le Groupe canadien de recherche pédiatrique et périnatale sur le VIH/sida (CPARG) a tenu un congrès financé par Les Instituts de recherche en santé du Canada en 2016 pour parvenir à un consensus de la part des professionnels multidisciplinaires sur le counseling et les recommandations à l'égard de l'alimentation du nourrisson. Après les présentations de professionnels de la santé pédiatrique, de chercheurs fondamentaux et de chercheurs communautaires, un sous-groupe a rédigé une synthèse des recommandations reposant sur des données probantes. En plus des révisions proposées par les membres de la CPARG, un échantillon de commodité de MVIH qui avaient accouché dans les cinq années précédentes en Ontario et au Québec a procédé à un examen communautaire. Une révision juridique a également permis de bien comprendre le potentiel de criminalisation et les inquiétudes quant à la transmission du VIH et à l'exposition à ce virus. Résultats: Les lignes directrices consensuelles canadiennes continuent de préconiser l'utilisation des préparations commerciales pour l'alimentation des nourrissons, car elles éliminent tout risque résiduel de transmission verticale après la naissance. Ces préparations doivent être mises à la disposition de tous les nourrissons nés de MVIH jusqu'à l'âge d'un an. Une approche détaillée du counseling auprès des MVIH est présentée pour aider les professionnels à leur donner des conseils efficaces sur les données probantes à jour, afin qu'elles puissent prendre une décision pleinement éclairée. Chez les femmes qui respectent les critères et qui choisissent d'allaiter, la surveillance virologique fréquente de la mère et un suivi de la mère et du nourrisson s'imposent. La prophylaxie antirétrovirale et la surveillance des nourrissons allaités sont recommandées. La révision communautaire a fait ressortir l'importance d'autres mesures de soutien et de counseling pour mettre en place une alimentation efficace à l'aide des préparations commerciales, en plus de l'accès à ces préparations. L'analyse juridique a permis de préciser les énoncés entourant la participation des services de protection de l'enfance et la nécessité de diriger les familles vers des ressources ou de l'information juridiques, sur demande. Des systèmes de surveillance visant à répertorier les cas de transmission par le lait maternel devraient être en place pour corriger les lacunes en matière de soins et accroître les connaissances dans ce domaine. Conclusion: Les lignes directrices consensuelles canadiennes sur l'alimentation des nourrissons sont conçues pour éclairer les soins aux MVIH et à leurs nourrissons et pour les améliorer. Il sera important d'assurer l'évaluation continue de ces lignes directrices à mesure que de nouvelles données probantes seront découvertes.

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.

SARS-CoV-2 Infection of Young Infants during the Omicron Wave: A Case Series.

We describe the clinical course of 4 infants infected with severe acute respiratory syndrome coronavirus 2. All were admitted to our tertiary care neonatal intensive care unit during the Omicron variant wave in our region. All 4 infants, who were less than 3 months of age, including three born prematurely, presented with critical illness. However, their clinical presentation varied considerably. Of them, two infants presented with apnea, one with respiratory distress, and one with gastrointestinal manifestation. Our experience with these four infants provides evidence for a severe form of disease and varied clinical presentation in neonates and young infants speculated to be infected with Omicron variant.

Utility of SARS-CoV-2 Genomic Sequencing for Understanding Transmission and School Outbreaks.

OBJECTIVE: An understanding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission in schools is important. It is often difficult, using epidemiological information alone, to determine whether cases associated with schools represent multiple introductions from the community or transmission within the school. We describe the use of whole genome sequencing (WGS) in multiple schools to investigate outbreaks of SARS-CoV-2 in the pre-Omicron period. STUDY DESIGN: School outbreaks were identified for sequencing by local public health units based on multiple cases without known epidemiological links. Cases of SARS-CoV-2 from students and staff from 4 school outbreaks in Ontario underwent WGS and phylogenetic analysis. The epidemiological clinical cohort data and genomic cluster data are described to help further characterize these outbreaks. RESULTS: A total of 132 positive SARS-CoV-2 cases among students and staff from 4 school outbreaks were identified with 65 (49%) of cases able to be sequenced with high-quality genomic data. The 4 school outbreaks consisted of 53, 37, 21 and 21 positive cases; within each outbreak there were between 8 and 28 different clinical cohorts identified. Among the sequenced cases, between 3 and 7 genetic clusters, defined as different strains, were identified in each outbreak. We found genetically different viruses within several clinical cohorts. CONCLUSIONS: WGS, together with public health investigation, is a useful tool to investigate SARS-CoV-2 transmission within schools. Its early use has the potential to better understand when transmission may have occurred, can aid in evaluating how well mitigation interventions are working and has the potential to reduce unnecessary school closures when multiple genetic clusters are identified.

Type and timing of antiretroviral therapy during pregnancy: Impact on risk of preterm delivery and small-for-gestational age births in Canada, a retrospective cohort study.

OBJECTIVE: To evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of preterm delivery (PTD) and small-for-gestational age (SGA) birth among pregnant women and people living with HIV in Canada. METHODS: Data for this retrospective cohort study were analyzed from the Canadian Perinatal HIV Surveillance Program from 1990 to 2020. The association between ART and risk of PTD (<37 weeks) and SGA birth (<10th percentile) was explored using mixed effects logistic regression and time-dependent Cox proportional hazards models. RESULTS: Overall, there were 14.9% (654 of 4379) PTD and 18.5% (732 of 3947) SGA cases. A higher risk of PTD was observed with nonnucleoside reverse transcriptase inhibitor-(adjusted hazard ratio [aHR], 1.73; P = 0.019) and boosted protease inhibitor- (aHR, 186; P = 0.007) based regimens compared with integrase strand transfer inhibitor (INSTI)-based regimens. ART initiation prior to conception was associated with a lower risk of SGA birth compared with ART initiation after conception at 1 to 14 weeks (adjusted odds ratio [aOR], 0.69; P = 0.024) and > 14 weeks (aOR, 0.70; P = 0.005). CONCLUSION: INSTI-based ART regimens were associated with lower risk of PTD compared with other regimens, and ART initiation before conception was associated with a lower risk of SGA birth. These findings, with overall safety data, should be considered when providing pregnancy counseling to people living with HIV.

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.

Invasive Pneumococcal Disease in High-risk Children: A 10-Year Retrospective Study.

BACKGROUND: Despite the availability of conjugate pneumococcal vaccines, children with high-risk conditions remain vulnerable to invasive pneumococcal disease (IPD). This study sought to describe IPD prevalence, vaccination and outcomes among high-risk children. METHODS: We used International Classification of Disease10 discharge and microbiology codes to identify patients hospitalized for IPD at a large pediatric hospital from January 1, 2009, to December 31, 2018. Patients were considered high-risk if they had: primary immunodeficiency, asplenia, transplant, active malignancy, sickle cell disease, cochlear implant, nephrotic syndrome, chronic lung disease, cerebrospinal fluid leak, HIV or used immunosuppressive therapy. RESULTS: In total 94 high-risk patients were hospitalized for IPD. The most common high-risk conditions included malignancy (n = 33, 35%), solid-organ or bone marrow transplant (n = 17, 18%) and sickle cell disease (n = 14, 15%). Bacteremia was the most common presentation (n = 81, 86%) followed by pneumonia (n = 23, 25%) and meningitis (n = 9, 10%). No deaths occurred. Of 66 patients with known pneumococcal vaccination status, 15 (23%) were unvaccinated, and 51 (77%) received at least one dose of a pneumococcal vaccine; 20 received all four recommended pneumococcal conjugate vaccine (PCV) doses. Only three children received PPSV23. Of 20 children with no or partial (<3 doses) immunization, 70% (14) of IPD episodes were due to vaccine-preventable serotypes. Of 66 known IPD serotypes, 17% (n = 11) were covered by PCV13, 39% (n = 26) were covered by PPSV23 and 39% (n = 26) were nonvaccine serotype. CONCLUSIONS: Despite the availability of effective pneumococcal vaccines, IPD persists among children with high-risk conditions. Improving PCV13 and PPSV23 vaccination could significantly reduce IPD; most episodes were due to vaccine-preventable serotypes in incompletely immunized patients.

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.

Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV.

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.