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Kirtsman et al discuss the probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection. They present a case study of a 40-year-old woman who was admitted to a tertiary hospital in Toronto, Ontario. She had familial neutropenia, gestational diabetes and a history of frequent bacterial infections during pregnancy, which resolved with antibiotic treatment. Details of the maternal course and outcome have been published separately because of her hematologic condition. A nasopharyngeal swab was positive for suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gene targets via reverse transcription polymerase chain reaction (RT-PCR) testing. There were no fetal concerns during the pregnancy or following admission. A semiurgent cesarean delivery was done under regional anesthesia, with airborne, droplet and contact precautions, owing to worsening coagulopathy and reducing platelet count at 35 weeks. Artificial rupture of membranes was performed at operation. The male neonate was vigorous and did not require resuscitation. His Apgar scores were 9 at 1 minute and 9 at 5 minutes, but all 3 of the neonate's nasopharyngeal swabs were positive for SARS-CoV-2 gene targets via RT-PCR testing.

According to WHO Global Health Estimates, tuberculosis (TB) is among the top ten causes of global mortality and ranks second after cardiovascular disease in most high-burden regions. In this systematic review and meta-analysis, we investigated the role of second-hand smoke (SHS) exposure as a risk factor for TB among children and adults. We performed a systematic literature search of PubMed, Embase, Scopus, Web of Science, and Google Scholar up to August 31, 2014. Our a priori inclusion criteria encompassed only original studies where latent TB infection (LTBI) and active TB disease were diagnosed microbiologically, clinically, histologically, or radiologically. Effect estimates were pooled using fixed- and random-effects models. We identified 18 eligible studies, with 30,757 children and 44,432 adult non-smokers, containing SHS exposure and TB outcome data for inclusion in the meta-analysis. Twelve studies assessed children and eight studies assessed adult non-smokers; two studies assessed both populations. Summary relative risk (RR) of LTBI associated with SHS exposure in children was similar to the overall effect size, with high heterogeneity (pooled RR 1.64, 95% CI 1.00-2.83). Children showed a more than 3-fold increased risk of SHS-associated active TB (pooled RR 3.41, 95% CI 1.81-6.45), which was higher than the risk in adults exposed to SHS (summary RR 1.32, 95% CI 1.04-1.68). Positive and significant exposure-response relationships were observed among children under 5 y (RR 5.88, 95% CI 2.09-16.54), children exposed to SHS through any parent (RR 4.20, 95% CI 1.92-9.20), and children living under the most crowded household conditions (RR 5.53, 95% CI 2.36-12.98). Associations for LTBI and active TB disease remained significant after adjustment for age, biomass fuel (BMF) use, and presence of a TB patient in the household, although the meta-analysis was limited to a subset of studies that adjusted for these variables. There was a loss of association with increased risk of LTBI (but not active TB) after adjustment for socioeconomic status (SES) and study quality. The major limitation of this analysis is the high heterogeneity in outcomes among studies of pediatric cases of LTBI and TB disease. We found that SHS exposure is associated with an increase in the relative risk of LTBI and active TB after controlling for age, BMF use, and contact with a TB patient, and there was no significant association of SHS exposure with LTBI after adjustment for SES and study quality. Given the high heterogeneity among the primary studies, our analysis may not show sufficient evidence to confirm an association. In addition, considering that the TB burden is highest in countries with increasing SHS exposure, it is important to confirm these results with higher quality studies. Research in this area may have important implications for TB and tobacco control programs, especially for children in settings with high SHS exposure and TB burden.

The overall global impact of COVID-19 in children and regional variability in pediatric outcomes are presently unknown. To evaluate the magnitude of global COVID-19 death and intensive care unit (ICU) admission in children aged 0-19 years, a systematic review was conducted for articles and national reports as of December 7, 2020. This systematic review is registered with PROSPERO (registration number: CRD42020179696). We reviewed 16,027 articles as well as 225 national reports from 216 countries. Among the 3,788 global pediatric COVID-19 deaths, 3,394 (91.5%) deaths were reported from low- and middle-income countries (LMIC), while 83.5% of pediatric population from all included countries were from LMIC. The pediatric deaths/1,000,000 children and case fatality rate (CFR) were significantly higher in LMIC than in high-income countries (HIC) (2.77 in LMIC vs 1.32 in HIC; p < 0.001 and 0.24% in LMIC vs 0.01% in HIC; p < 0.001, respectively). The ICU admission/1,000,000 children was 18.80 and 1.48 in HIC and LMIC, respectively (p < 0.001). The highest deaths/1,000,000 children and CFR were in infants < 1 year old (10.03 and 0.58% in the world, 5.39 and 0.07% in HIC and 10.98 and 1.30% in LMIC, respectively). The study highlights that there may be a larger impact of pediatric COVID-19 fatality in LMICs compared to HICs.

Purpose of ReviewThe rise in antimicrobial resistance is an urgent public health threat which, in the absence of intervention, may result in a post-antibiotic era limiting the effectiveness of antibiotics to treat both common and serious infections. Globalization and human migration have profoundly contributed to the spread of drug-resistant bacteria. In this review, we summarize the recent literature on the importance of travelers in the spread of drug-resistant bacterial organisms. Our goal was to describe the importance of travel on a variety of clinically relevant drug-resistant bacterial organisms including extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus, Salmonella species, as well as other enteric infections.Recent FindingsTravelers from high income countries, visiting low and middle income countries, frequently acquire drug-resistant bacteria, particularly extended-spectrum β-lactamase-producing Enterobacteriaceae. The highest risk is associated with travel to the Indian subcontinent. Multidrug-resistant enteric infections in travelers from Salmonella spp., Campylobacter spp., and Shigella spp. are increasing. Refugees, pilgrimages, and medical tourists are associated with considerable risk of multiple forms of drug resistance.SummaryThis review highlights the importance of antimicrobial stewardship, infection control, and surveillance; particularly in low and middle income countries. International leadership with global coordination is vital in the battle against antimicrobial resistance.

There are limited data on outcomes of SARS-CoV-2 infection among infants (<1 year of age). In the absence of approved vaccines for infants, understanding characteristics associated with hospitalization and severe disease from COVID-19 in this age group will help inform clinical management and public health interventions. The objective of this study was to describe the clinical manifestations, disease severity, and characteristics associated with hospitalization among infants infected with the initial strains of SARS-CoV-2. This is a national, prospective study of infants with SARS-CoV-2 from April 8.sup.th 2020 to May 31.sup.st 2021 using the infrastructure of the Canadian Paediatric Surveillance Program. Infants <1 year of age with microbiologically confirmed SARS-CoV-2 infection from both inpatients and outpatients seen in clinics and emergency departments were included. Cases were classified as either: 1) Non-hospitalized patient with SARS-CoV-2 infection; 2) COVID-19-related hospitalization; or 3) non-COVID-19-related hospitalization (e.g., incidentally detected SARS-CoV-2). Case severity was defined as asymptomatic, outpatient care, mild (inpatient care), moderate or severe disease. Multivariable logistic regression was performed to identify characteristics associated with hospitalization. A total of 531 cases were reported, including 332 (62.5%) non-hospitalized and 199 (37.5%) hospitalized infants. Among hospitalized infants, 141 of 199 infants (70.9%) were admitted because of COVID-19-related illness, and 58 (29.1%) were admitted for reasons other than acute COVID-19. Amongst all cases with SARS-CoV-2 infection, the most common presenting symptoms included fever (66.5%), coryza (47.1%), cough (37.3%) and decreased oral intake (25.0%). In our main analysis, infants with a comorbid condition had higher odds of hospitalization compared to infants with no comorbid conditions (aOR = 4.53, 2.06-9.97), and infants <1 month had higher odds of hospitalization then infants aged 1-3 months (aOR = 3.78, 1.97-7.26). In total, 20 infants (3.8%) met criteria for severe disease. We describe one of the largest cohorts of infants with SARS-CoV-2 infection. Overall, severe COVID-19 in this age group was found to be uncommon. Comorbid conditions and younger age were associated with COVID-19-related hospitalization amongst infants.

Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.

Paediatric randomised controlled trials (RCTs) are key to evaluating new and existing interventions that can improve health outcomes in newborns, infants, children, and adolescents (aged 0-19 years). Well reported RCT protocols facilitate the planning and implementation of trials that generate high quality, reproducible evidence, and strengthen the foundations of paediatric healthcare decisions and ultimately improve patient outcomes. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025 statement contains a checklist of essential reporting items and an explanation and elaboration paper. However, SPIRIT 2025 does not consider important elements that are unique to paediatric RCT protocols. As a paediatric extension to SPIRIT, we developed the SPIRIT-Children and Adolescents (SPIRIT-C) 2026 checklist, which this explanation and elaboration paper accompanies. We adopted a group writing approach to prepare this explanation and elaboration paper, and involved key partners with lived experience relevant to paediatric clinical trials, including family caregivers, trialists, child health researchers, clinicians, journal editors, and methodologists. This explanation and elaboration paper presents examples, explanations, and key elements for the 17 new SPIRIT-C 2026 reporting items; paediatric considerations with good reporting examples for six SPIRIT 2025 items; and a glossary. This paper also promotes the reporting of methodological rigor, patient safety, promotes a patient oriented approach, and facilitates the generation of high quality, reproducible trial evidence that will strengthen paediatric practice and policy decisions and ultimately improve patient outcomes.

Paediatric randomised controlled trials (RCTs) generate critical evidence on the effects of interventions aimed at improving health outcomes in children and adolescents (aged 0-19 years). Evidence from appropriately designed, conducted, and reported RCTs is key to the evaluation and implementation of safe and effective interventions. Clear and comprehensive reporting of paediatric specific trial methods implemented in the trial and of its results facilitates a proper evaluation, including generalisability and applicability considerations and critical appraisal of trial methods and findings. The Consolidated Standards of Reporting Trials (CONSORT) 2025 statement provides general guidance for authors when reporting RCTs but contains no detail specific to paediatric trials. To overcome existing deficiencies in the reporting of paediatric clinical trials, we developed CONSORT-Children and Adolescents (CONSORT-C) 2026 as an extension of CONSORT 2025. A group writing approach was implemented and involved key partners with lived experience relevant to paediatric clinical trials, including family caregivers, trialists, child health researchers, clinicians, journal editors, and methodologists to contribute to this explanation and elaboration paper. This paper was prepared to provide explanations and good reporting examples for the 13 new CONSORT-C 2026 reporting items, paediatric considerations with good reporting examples for eight CONSORT 2025 items, and a glossary. It is recommended to use this explanation and elaboration paper as a resource together with the CONSORT-C 2026 checklist. Widespread implementation of CONSORT-C 2026 should improve reporting quality, enhance critical appraisal of key methodological aspects of paediatric RCTs, facilitate the peer review processes, and foster better understanding and interpretation of study findings by end users. Consequently, effective interventions may be translated to paediatric practice and policy decisions more efficiently, and ultimately improve patient outcomes.

Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

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. 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. 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%). 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.