Metagenomics analysis of the neonatal intestinal resistome

IntroductionThe intestinal microbiome forms a major reservoir for antibiotic resistance genes (ARGs). Little is known about the neonatal intestinal resistome.ObjectiveThe objective of this study was to investigate the intestinal resistome and factors that influence the abundance of ARGs in a large cohort of neonates.MethodsShotgun metagenomics was used to analyse the resistome in stool samples collected at 1 week of age from 390 healthy, term-born neonates who did not receive antibiotics.ResultsOverall, 913 ARGs belonging to 27 classes were identified. The most abundant ARGs were those conferring resistance to tetracyclines, quaternary ammonium compounds, and macrolide-lincosamide-streptogramin-B. Phylogenetic composition was strongly associated with the resistome composition. Other factors that were associated with the abundance of ARGs were delivery mode, gestational age, birth weight, feeding method, and antibiotics in the last trimester of pregnancy. Sex, ethnicity, probiotic use during pregnancy, and intrapartum antibiotics had little effect on the abundance of ARGs.ConclusionEven in the absence of direct antibiotic exposure, the neonatal intestine harbours a high abundance and a variety of ARGs

Should children be vaccinated against COVID-19?

Whether all children under 12 years of age should be vaccinated against COVID-19 remains an ongoing debate. The relatively low risk posed by acute COVID-19 in children, and uncertainty about the relative harms from vaccination and disease mean that the balance of risk and benefit of vaccination in this age group is more complex. One of the key arguments for vaccinating healthy children is to protect them from long-term consequences. Other considerations include population-level factors, such as reducing community transmission, vaccine supply, cost, and the avoidance of quarantine, school closures and other lockdown measures. The emergence of new variants of concern necessitates continual re-evaluation of the risks and benefits. In this review, we do not argue for or against vaccinating children against COVID-19 but rather outline the points to consider and highlight the complexity of policy decisions on COVID-19 vaccination in this age group

Metagenomics analysis of the neonatal intestinal resistome

Introduction: The intestinal microbiome forms a major reservoir for antibiotic resistance genes (ARGs). Little is known about the neonatal intestinal resistome. Objective: The objective of this study was to investigate the intestinal resistome and factors that influence the abundance of ARGs in a large cohort of neonates. Methods: Shotgun metagenomics was used to analyse the resistome in stool samples collected at 1 week of age from 390 healthy, term-born neonates who did not receive antibiotics. Results: Overall, 913 ARGs belonging to 27 classes were identified. The most abundant ARGs were those conferring resistance to tetracyclines, quaternary ammonium compounds, and macrolide-lincosamide-streptogramin-B. Phylogenetic composition was strongly associated with the resistome composition. Other factors that were associated with the abundance of ARGs were delivery mode, gestational age, birth weight, feeding method, and antibiotics in the last trimester of pregnancy. Sex, ethnicity, probiotic use during pregnancy, and intrapartum antibiotics had little effect on the abundance of ARGs. Conclusion: Even in the absence of direct antibiotic exposure, the neonatal intestine harbours a high abundance and a variety of ARGs.</p

Factors associated with nonadherence to the American Academy of Pediatrics 2014 bronchiolitis guidelines: A retrospective study.

The latest guideline from the American Academy of Pediatrics for the management of bronchiolitis has helped reduce unnecessary interventions and costs. However, data on patients still receiving interventions are missing. In patients with acute bronchiolitis whose management was assessed and compared with current achievable benchmarks of care, we aimed to identify factors associated with nonadherence to guideline recommendations. In this single-centre retrospective study the management of bronchiolitis pre-guideline (Period 1: 2010 to 2012) was compared with two periods post-guideline (Period 2: 2015 to 2016, early post-guideline; and Period 3: 2017 to 2018, late post-guideline) in otherwise healthy infants aged less than 1 year presenting at the Children's University Hospitals of Geneva (Switzerland). Post-guideline, bronchodilators were more frequently administered to older (>6 months; OR 25.8, 95%CI 12.6-52.6), and atopic (OR 3.5, 95%CI 1.5-7.5) children with wheezing (OR 5.4, 95%CI 3.3-8.7). Oral corticosteroids were prescribed more frequently to older (>6 months; OR 5.2, 95%CI 1.4-18.7) infants with wheezing (OR 4.9, 95% CI 1.3-17.8). Antibiotics and chest X-ray were more frequently prescribed to children admitted to the intensive care unit (antibiotics: OR 4.2, 95%CI 1.3-13.5; chest X-ray: OR 19.4, 95%CI 7.4-50.6). Latest prescription rates were all below the achievable benchmarks of care. In summary, following the latest American Academy of Pediatrics guideline, older, atopic children with wheezing and infants admitted to the intensive care unit were more likely to receive nonevidence-based interventions during an episode of bronchiolitis. These patient profiles are generally excluded from bronchiolitis trials, and therefore not specifically covered by the current guideline. Further research should focus on the benefit of bronchiolitis interventions in these particular populations

Diagnosis of whooping cough in Switzerland: differentiating Bordetella pertussis from Bordetella holmesii by polymerase chain reaction.

Bordetella holmesii, an emerging pathogen, can be misidentified as Bordetella pertussis by routine polymerase chain reaction (PCR). In some reports, up to 29% of the patients diagnosed with pertussis have in fact B. holmesii infection and invasive, non-respiratory B. holmesii infections have been reported worldwide. This misdiagnosis undermines the knowledge of pertussis' epidemiology, and may lead to misconceptions on pertussis vaccine's efficacy. Recently, the number of whooping cough cases has increased significantly in several countries. The aim of this retrospective study was to determine whether B. holmesii was contributing to the increase in laboratory-confirmed cases of B. pertussis in Switzerland. A multiplex species-specific quantitative PCR assay was performed on 196 nasopharyngeal samples from Swiss patients with PCR-confirmed Bordetella infection (median age: 6 years-old, minimum 21 days-old, maximum 86 years-old), formerly diagnosed as Bordetella pertussis (IS481+). No B. holmesii (IS481+, IS1001-, hIS1001+) was identified. We discuss whether laboratories should implement specific PCR to recognize different Bordetella species. We conclude that in Switzerland B. holmesii seems to be circulating less than in neighboring countries and that specific diagnostic procedures are not necessary routinely. However, as the epidemiological situation may change rapidly, periodic reevaluation is suggested

Fusion of the BCL9 HD2 domain to E1A increases the cytopathic effect of an oncolytic adenovirus that targets colon cancer cells

Swiss Cancer League, Swiss National Science Foundation and SNSF NCCR Molecular Oncology ProgrammeBackground: The Wnt signaling pathway is activated by mutations in the APC and beta-catenin genes in many types of human cancer. beta-catenin is stabilized by these mutations and activates transcription in part by acting as a bridge between Tcf/LEF proteins and the HD2 domain of the BCL9 coactivator. We have previously described oncolytic adenoviruses with binding sites for Tcf/LEF transcription factors inserted into the early viral promoters. These viruses replicate selectively in cells with activation of the Wnt pathway. To increase the activity of these viruses we have fused the viral transactivator E1A to the BCL9 HD2 domain. Methods: Luciferase assays, co-immunoprecipitation and Western blotting, immunofluorescent cell staining and cytopathic effect assays were used to characterize the E1A-HD2 fusion protein and virus in vitro. Growth curves of subcutaneous SW620 colon cancer xenografts were used to characterize the virus in vivo. Results: The E1A-HD2 fusion protein binds to beta-catenin in vivo and activates a Tcf-regulated luciferase reporter better than wild-type E1A in cells with activated Wnt signaling. Expression of the E1A-HD2 protein promotes nuclear import of beta-catenin, mediated by the strong nuclear localization signal in E1A. Tcf-regulated viruses expressing the fusion protein show increased expression of viral proteins and a five-fold increase in cytopathic effect (CPE) in colorectal cancer cell lines. There was no change in viral protein expression or CPE in HeLa cells, indicating that E1A-HD2 viruses retain selectivity for cells with activation of the Wnt signaling pathway. Despite increasing the cytopathic effect of the virus in vitro, fusion of the HD2 domain to E1A did not increase the burst size of the virus in vitro or the anti-tumor effect of the virus in an SW620 xenograft model in vivo. Conclusion: Despite an increase in the nuclear pool of beta-catenin, the effects on viral activity in colon cancer cells were small, suggesting that factors acting downstream of beta-catenin are limiting for viral replication and toxicity in these cells. The approach of fusing E1A to a protein domain implicated in oncogenic signaling could be used to selectively increase the activity of oncolytic viruses targeting several other pathways defective in cancer.Publisher PDFPeer reviewe

Management and prevention of varicella and measles infections in pediatric solid organ transplant candidates and recipients: An IPTA survey of current practice

Abstract Background: Varicella and measles infections can be life-threatening after solid organ transplantation (SOT) but may be preventable with live-attenuated vaccines (LAV). Methods: This survey conducted in January 2019 among subscribers of the International Pediatric Transplantation Association listserv aimed to explore the current strategies to prevent and manage both infections in the pediatric SOT population, including recommending LAV after SOT. Results: The answers given by 95 pediatric SOT healthcare workers show that these strategies are not yet optimal and call for further education. In particular, 59% of respondents are unnecessarily waiting for a SOT candidate to be >1 year of age to start administrating LAV before SOT. Interestingly, most respondents are willing to administer LAV after SOT (57%), and a fifth (21%) are already doing so, off-label. The survey queried the precautions taken to improve safety evaluations after LAV, and identified knowledge gaps and practitioners’ concerns. Conclusion: The results of this survey could be used as a starting point for education and promotion of the safe administration of LAV in carefully selected SOT recipients; in turn, this would increase available data that would contribute to the development of evidence-based guidelines by the transplant societies and ultimately prevent these infections after SOT

Patient characteristics.

<p>F: female, M: male, n: number, y: years-old.</p><p>* One sample was negative for all tested targets whereas volume of remaining material for two other samples was not sufficient to perform the assays.</p

Sequence and characteristics of oligonucleotides used in the qPCR assay.

<p>qPCR: quantitative polymerase chain reaction.</p