Is nasal carriage of the main acquisition pathway for surgical-site infection in orthopaedic surgery?

International audienceThe endogenous or exogenous origin of , responsible for orthopaedic surgical-site infections (SSI), remains debated. We conducted a multicentre prospective cohort study to analyse the respective part of exogenous contamination and endogenous self-inoculation by during elective orthopaedic surgery. The nose of each consecutive patient was sampled before surgery. Strains of isolated from the nose and the wound, in the case of SSI, were compared by antibiotypes or pulsed-field gel electrophoresis (PFGE). A total of 3,908 consecutive patients undergoing orthopaedic surgery were included. Seventy-seven patients developed an SSI (2%), including 22 related to (0.6%). was isolated from the nose of 790 patients (20.2%) at the time of surgery. In the multivariate analysis, nasal carriage was found to be a risk factor for SSI in orthopaedic surgery. However, only nine subjects exhibiting SSI had been found to be carriers before surgery: when compared, three pairs of strains were considered to be different and six similar. In most cases of SSI, either an endogenous origin could not be demonstrated or pre-operative nasal colonisation retrieved a strain that was different from the one recovered from the surgical sit

Role of Sex and Early Interferon Production in the Susceptibility of Mice to Encephalomyocarditis Virus

Adult female Swiss mice showed a greater resistance to intraperitoneal (i.p.) infection with encephalomyocarditis virus (EMCV) than male mice. This difference was not observed in weanling mice, in castrated adult mice or in adult mice injected intracerebrally. Administration of antibody to mouse interferon alpha/beta enhanced the virulence of EMCV for both sexes and no difference was then observed in susceptibility between male and female mice. Six h after EMCV infection, serum interferon titres were higher in adult female mice than in male mice. There was a close correlation between the early serum interferon titre (at 6 h) and survival of EMCV-infected mice. No differences in serum interferon titres were observed between male or female weanling mice or castrated adult mice. Potent preparations of exogenous interferon provided the same degree of protection against EMCV infection in male and female mice. We conclude that the more marked early interferon response of female mice to i.p. EMCV infection is one of the important factors underlying the differential susceptibility to EMCV. It is possible that the interferon system is also involved in the reported greater prevalence of picornavirus infections of men compared with women

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

International audienceABSTRACT: The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40+ antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology

Place des microbicides vaginaux dans la prévention de l'infection par le virus de l'immunodéficience humaine

Les microbicides peuvent se définir comme des substances topiques susceptibles de réduire le risque d'infections sexuellement transmissibles. L'objet de cette revue est de présenter un état des lieux des connaissances relatives aux microbicides vaginaux susceptibles de protéger les femmes contre l'infection par le virus de l'immunodéficience humaine de type 1 (VIH-1). Les molécules microbicides à visée anti-VIH comprennent des composés non spécifiques comme les détergents, les polyanions ou les inhibiteurs d'entrée, et des molécules spécifiques de VIH-1 qui incluent principalement des inhibiteurs des étapes précoces de l'infection virale et des inhibiteurs de la réverse transcriptase. Bien que l'approche microbicide soit très séduisante sous l'angle conceptuel, aucun essai clinique contrôlé et randomisé, conduit avec des molécules de première génération n'a fait la preuve de l'efficacité préventive de ces composés contre l'infection par VIH-1. Des résultats encourageants ont été obtenus chez des primates non humains et plusieurs essais cliniques menés à travers le monde devraient livrer leur verdict assez vite. Cette revue discute ces différents aspects et encore l'évaluation préclinique de la balance bénéfices-risques des produits microbicides, les associations de composés microbicides anti-VIH-1 et la capacité de ces substances à sélectionner des mutants résistants. Une meilleure connaissance des modes de franchissement de la muqueuse cervico-vaginale par VIH-1 devrait permettre d'affiner les stratégies microbicides qui, en l'absence de vaccination préventive à moyen terme, constituent une alternative à évaluer pour protéger les femmes — et notamment les plus vulnérables d'entre elles — vis-à-vis de l'infection par VIH-1

Performance of the COVID19SEROSpeed IgM/IgG rapid test, an immunochromatographic assay for the diagnosis of SARSCoV-2 infection : A multicenter European study

This study assessed the diagnostic performance of the new COVID19-SEROSpeed IgM/IgG rapid test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders). The clinical sensitivity was evaluated on 710 sera from 564 patients whose SARS-CoV-2 infection was confirmed by quantitative reverse transcription-PCR (qRT-PCR) and whose antibody response was compared to that measured by five other commercial tests. The kinetics of the antibody response were also analyzed in seven symptomatic patients. The specificity of the test (BioS) on prepandemic specimens was 98.1% (95% confidence interval [CI], 96.2% to 99.4%). When tested on the 710 pandemic specimens, BioS showed an overall clinical sensitivity of 86.0% (95% CI, 0.83 to 0.89), with good concordance with the Euroimmun assay (overall concordance of 0.91; Cohen's kappa coefficient of 0.62). Due in part to simultaneous detection of IgM and IgG for both S1 and N proteins, BioS exhibited the highest positive percent agreement at $11days post-symptom onset (PSO). In conclusion, the BioS IgM/IgG rapid test was highly specific and demonstrated a higher positive percentage of agreement than all the enzyme-linked immunosorbent assay/chemiluminescence immunoassay (ELISA/CLIA) commercial tests considered in this study. Moreover, by detecting the presence of antibodies prior to 11days PSO in 78.2% of the patients, the BioS test increased the efficiency of the diagnosis of SARS-CoV-2 infection in the early stages of the disease

Screening a Peptide Library by DSC and SAXD: Comparison with the Biological Function of the Parent Proteins

We have recently identified the membranotropic regions of the hepatitis C virus proteins E1, E2, core and p7 proteins by observing the effect of protein-derived peptide libraries on model membrane integrity. We have studied in this work the ability of selected sequences of these proteins to modulate the Lβ-Lα and Lα-HII phospholipid phase transitions as well as check the viability of using both DSC and SAXD to screen a protein-derived peptide library. We demonstrate that it is feasible to screen a library of peptides corresponding to one or several proteins by both SAXD and DSC. This methodological combination should allow the identification of essential regions of membrane-interacting proteins which might be implicated in the molecular mechanism of membrane fusion and/or budding