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

Risk of Vaccine-Preventable Infections in Swiss Adults with Inflammatory Bowel Disease.

BACKGROUND Patients with inflammatory bowel disease (IBD) have a higher risk of infection and are frequently not up to date with their immunizations. OBJECTIVES This study aims to review vaccination status and evaluate whether age, disease type, or treatment regimen could predict the absence of seroprotection against selected vaccine-preventable infection in adults with IBD. METHODS Cross-sectional study using questionnaire, immunization records review, and assessment of tetanus-specific, varicella-specific, and measles-specific immunoglobulin G concentrations. ClinicalTrials.gov: NCT01908283. RESULTS Among the 306 adults assessed (median age 42.7 years old, 70% with Crohn's disease, 78% receiving immunosuppressive treatment), only 33% had an immunization record available. Absence of seroprotection against tetanus (6%) was associated with increasing age and absence of booster dose; absence of seroprotection against varicella (1%) or measles (3%) was exclusively observed in younger patients with Crohn's disease. There was no statistically significant difference in immunoglobulin concentrations among treatment groups. Although vaccinations are strongly recommended in IBD patients, the frequencies of participants with at least 1 dose of vaccine recorded were low for nearly all antigens: tetanus 94%, diphtheria 87%, pertussis 54%, poliovirus 22%, measles-mumps-rubella 47%, varicella-zoster 0%, Streptococcus pneumoniae 5%, Neisseria meningitidis 12%, hepatitis A 41%, hepatitis B 48%, human papillomavirus 5%, and tick-borne encephalitis 6%. CONCLUSIONS Although many guidelines recommend the vaccination of IBD patients, disease prevention through immunization is still often overlooked, including in Switzerland, increasing their risk of vaccine-preventable diseases. Serological testing should be standardized to monitor patients' protection during follow-up as immunity may wane faster in this population

Beyond specific effects of vaccines

Whereas the paradigm of vaccine is to provide protection of the vaccinee against the targeted disease (the specific effect of vaccine), many other effects may emanate from vaccination. These include: populational protection acquired through induction of herd immunity; individual protection of nonvaccinated persons acquired through third-party strategies such as maternal, toddler and caregiver immunisation; cross-protective effects against closely related pathogen; downstream effects by indirectly protecting against diseases that would have been predisposed by the prevented infection; adverse effects, that may also indirectly inform on vaccine responses or on the vaccinee’s underlying immunity; and non-specific effects. The study of non-specific effects of vaccines is a research topic of growing importance in vaccinology. Non-specific effects of vaccines are proposed to explain observations that certain vaccines can provide “unplanned” benefits against unrelated infections, allergic diseases, autoimmune diseases, and malignancies, through the induction of broader changes to immune cells, and therefore have an impact beyond the protection against the specific pathogens for which the vaccines were designed. In this Privat Docent thesis I have tried to illustrate these different facets of vaccination with some of the papers I have published in the past three years. After a general introduction setting up the context, the publications are introduced sequentially, followed by a general discussion giving future perspectives

Vaccination des sujets immunosupprimés

Les sujets immunosupprimés sont menacés par un risque d'infections sévères, potentiellement mortelles, et bénéficieraient d'être adéquatement vaccinés. Bien que les vaccins vivant-atténués soit contre-indiqués en cas d'immunosuppression, dans le contexte d'une première étude nous avons vacciné contre la rougeole 44 enfants transplantés hépatiques et avons démontré une réponse immunitaire adéquate, sans réplication incontrôlée du virus vaccinal. Grâce à cette étude, nous avons permis le changement des recommandations de vaccination après transplantation. Notre deuxième étude s'intéresse aux effets des traitements immunomodulateurs sur les réponses vaccinales, chez 306 adultes atteints de maladies inflammatoires chroniques de l'intestin, auxquels nous avons administré le vaccin 13-valent conjugué contre le pneumocoque. L'excellente réponse vaccinale observée n'était que légèrement diminuée chez les patients sous traitement anti-TNF et aucun effet négatif sur la maladie sous-jacente n'a été remarqué. Nous espérons que les résultats de cette étude aideront à promouvoir recommandation et remboursement de ce vaccin dans cette indication

Bordetella holmesii, une bactérie méconnue, potentiellement invasive et préjudiciable à l'évaluation de l'efficacité du vaccin contre la coqueluche

Découverte en 1995, Bordetella holmesii est une bactérie méconnue qui s'apparente à celle qui cause la coqueluche, Bordetella pertussis. A l'inverse de cette dernière, B. holmesii ne cause pas uniquement des infections respiratoires mais également des infections invasives, comme des méningites, endocardites ou arthrites. Sa non-identification est problématique, notamment lors d'infections respiratoires. En effet, en cas de coqueluche, les outils diagnostiques utilisés ne permettent pas de distinguer B. holmesii de B. pertussis. Cette erreur systématique biaise les analyse d'efficacité du vaccin contre la coqueluche, car celui-ci ne protège pas contre B. holmesii. Puisque toutes les infections respiratoires à B. holmesii sont actuellement diagnostiquées comme dues à B. pertussis, elles peuvent potentiellement être interprétées comme un échec vaccinal. Ce travail de thèse a donc pour but de résumer la littérature disponible sur B. holmesii afin de sensibiliser à sa problématique et de chercher si B. holmesii circule également en Suisse

Bronchiolitis retrospective study 2010-2018

AbstractDatabase of the publication "Factors associated with nonadherence to the American Academy of Pediatrics 2014 bronchiolitis guidelines: a retrospective study" Abstract: 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

Does bacillus Calmette-Guérin vaccine prevent herpes simplex virus recurrences? A systematic review

Recurrent infections with herpes simplex virus (HSV) in the orofacial (cold sores), ocular or genital region are common and sometimes disabling, calling for an effective preventive intervention. The bacillus Calmette-Guérin (BCG) vaccine has beneficial off-target effects that might impact recurrence of HSV infections. In this systematic review, Medline, EMBASE, and PubMed were searched in June 2020; 16 articles were deemed relevant comprising eight animal and eight human studies (301 patients). In animals, BCG administration led to a 1.9 to 5.5-fold increase in survival rate following HSV challenge (vaginal, corneal, or intraperitoneal inoculation). This beneficial effect was influenced by the dose of BCG (higher better), mode of administration (intradermal better than intraperitoneal), and the interval between vaccination and viral challenge (at least 6 days required). In nonrandomized human studies (that failed to control for a placebo effect), BCG vaccination appeared beneficial in 78% of adults with recurrent herpes genitalis or labialis, with 37% being recurrence-free for an extended period, 41% experiencing less frequent or severe episodes, and only 22% reporting no change. This clinical benefit is consistent with the findings of immunological sub-studies. In the two studies restricted to recurrent herpes labialis, 94% appeared to benefit from BCG. The one randomized controlled trial used an intervention in the control group that has immunomodulatory effects thus limiting interpretation. In conclusion, BCG vaccine is a potential, safe, affordable and readily available candidate intervention to decrease the high burden of disease associated with HSV infection and recurrences, but properly controlled randomized trials are required