Escherichia coli population structure and antibiotic resistance at a buffalo/cattle interface in Southern Africa

At a human/livestock/wildlife interface, Escherichia coli populations were used to assess the risk of bacterial and antibiotic resistance dissemination between hosts. We used phenotypic and genotypic characterization techniques to describe the structure and the level of antibiotic resistance of E. coli commensal populations and the resistant Enterobacteriaceae carriage of sympatric African buffalo (Syncerus caffer caffer) and cattle populations characterized by their contact patterns in the southern part of Hwange ecosystem in Zimbabwe. Our results (i) confirmed our assumption that buffalo and cattle share similar phylogroup profiles, dominated by B1 (44.5%) and E (29.0%) phylogroups, with some variability in A phylogroup presence (from 1.9 to 12%); (ii) identified a significant gradient of antibiotic resistance from isolated buffalo to buffalo in contact with cattle and cattle populations expressed as the Murray score among Enterobacteriaceae (0.146, 0.258, and 0.340, respectively) and as the presence of tetracycline-, trimethoprim-, and amoxicillin-resistant subdominant E. coli strains (0, 5.7, and 38%, respectively); (iii) evidenced the dissemination of tetracycline, trimethoprim, and amoxicillin resistance genes (tet, dfrA, and blaTEM-1) in 26 isolated subdominant E. coli strains between nearby buffalo and cattle populations, that led us (iv) to hypothesize the role of the human/animal interface in the dissemination of genetic material from human to cattle and toward wildlife. The study of antibiotic resistance dissemination in multihost systems and at anthropized/natural interface is necessary to better understand and mitigate its multiple threats. These results also contribute to attempts aiming at using E. coli as a tool for the identification of pathogen transmission pathway in multihost systems. (Résumé d'auteur

Renal macro- and microcirculation autoregulatory capacity during early sepsis and norepinephrine infusion in rats

INTRODUCTION: The relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity. METHODS: Ventilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions. RESULTS: Positive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion. CONCLUSION: In our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion

Escherichia coli population structure and antibioresistance at a buffalo/cattle interface in Southern Africa

At a human/livestock/wildlife interface, Escherichia coli populations were used to assess the risk of bacteria and antibioresistance dissemination between hosts. We used phenotypic and genotypic characterization techniques to describe the structure and the level of antibioresistance of E. coli commensal populations and the resistant Enterobacteriaceae carriage of sympatric African buffalo (Syncerus caffer) and cattle populations characterized by their contact patterns in the southern part of Hwange ecosystem in Zimbabwe. Our results 1) confirmed our assumption that buffalo and cattle share similar phylogroup profiles, 2) identified a significant gradient of antibioresistance from isolated buffalo to buffalo in contact with cattle and cattle populations; 3) evidenced the dissemination of tetracycline, trimethoprim and amoxicillin resistance genes (tet, dfrA, blaTEM-1in 26 isolated sub-dominant E. coli strains between nearby buffalo and cattle populations that led us 4) to hypothesize the role of the human/animal interface in the dissemination of genetic material from human to cattle and towards wildlife. The study of antibiotic resistance dissemination in multi-host systems and at anthropised/natural interface is necessary to better understand and mitigate its multiple threats. These results also contribute to attempts aiming at using E. coli as a tool for the identification of pathogen transmission pathway in multi-host systems. (Texte intégral

Escherichia coli population structure and antibiotic resistance at a buffalo/cattle interface in southern Africa

At a human/livestock/wildlife interface, Escherichia coli populations were used to assess the risk of bacterial and antibiotic resistance dissemination between hosts. We used phenotypic and genotypic characterization techniques to describe the structure and the level of antibiotic resistance of E. coli commensal populations and the resistant Enterobacteriaceae carriage of sympatric African buffalo (Syncerus caffer caffer) and cattle populations characterized by their contact patterns in the southern part of Hwange ecosystem in Zimbabwe. Our results (i) confirmed our assumption that buffalo and cattle share similar phylogroup profiles, dominated by B1 (44.5%) and E (29.0%) phylogroups, with some variability in A phylogroup presence (from 1.9 to 12%); (ii) identified a significant gradient of antibiotic resistance from isolated buffalo to buffalo in contact with cattle and cattle populations expressed as the Murray score among Enterobacteriaceae (0.146, 0.258, and 0.340, respectively) and as the presence of tetracycline-, trimethoprim-, and amoxicillin-resistant subdominant E. coli strains (0, 5.7, and 38%, respectively); (iii) evidenced the dissemination of tetracycline, trimethoprim, and amoxicillin resistance genes (tet, dfrA, and blaTEM-1) in 26 isolated subdominant E. coli strains between nearby buffalo and cattle populations, that led us (iv) to hypothesize the role of the human/animal interface in the dissemination of genetic material from human to cattle and toward wildlife. The study of antibiotic resistance dissemination in multihost systems and at anthropized/natural interface is necessary to better understand and mitigate its multiple threats. These results also contribute to attempts aiming at using E. coli as a tool for the identification of pathogen transmission pathway in multihost systems.This study was implemented within the framework of the research Platform Conservation and Production in Partnership (www.rp-pcp.org) and in collaboration with CNRS within the framework of the Zone Atelier in the Hwange area.Agence Nationale de la Recherche (ANR) http://dx.doi.org/10.13039/501100001665ANR-11-CEPL-003.http://aem.asm.org2017-06-30Mammal Research Institut

A modelling framework for the prediction of the herd-level probability of infection from longitudinal data

International audienceThe collective control programmes (CPs) that exist for many infectious diseases of farm animals rely on the application of diagnostic testing at regular time intervals for the identification of infected animals or herds. The diversity of these CPs complicates the trade of animals between regions or countries because the definition of freedom from infection differs from one CP to another. In this paper, we describe a statistical model for the prediction of herd-level probabilities of infection from longitudinal data collected as part of CPs against infectious diseases of cattle. The model was applied to data collected as part of a CP against bovine viral diarrhoea virus (BVDV) infection in Loire-Atlantique, France. The model represents infection as a herd latent status with a monthly dynamics. This latent status determines test results through test sensitivity and test specificity. The probability of becoming status positive between consecutive months is modelled as a function of risk factors (when available) using logistic regression. Modelling is performed in a Bayesian framework, using either Stan or JAGS. Prior distributions need to be provided for the sensitivities and specificities of the different tests used, for the probability of remaining status positive between months as well as for the probability of becoming positive between months. When risk factors are available, prior distributions need to be provided for the coefficients of the logistic regression, replacing the prior for the probability of becoming positive. From these prior distributions and from the longitudinal data, the model returns posterior probability distributions for being status positive for all herds on the current month. Data from the previous months are used for parameter estimation. The impact of using different prior distributions and model implementations on parameter estimation was evaluated. The main advantage of this model is its ability to predict a probability of being status positive in a month from inputs that can vary in terms of nature of test, frequency of testing and risk factor availability/presence. The main challenge in applying the model to the BVDV CP data was in identifying prior distributions, especially for test characteristics, that corresponded to the latent status of interest, i.e. herds with at least one persistently infected (PI) animal. The model is available on Github as an R package (https://github.com/AurMad/STOCfree) and can be used to carry out output-based evaluation of disease CPs

Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats

Introduction Hydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses. Methods Thirty-two rats were mechanically ventilated and instrumented to measure mean arterial pressure (MAP) and carotid blood flow (CBF). Animals were bled during 60 minutes in order to maintain MAP at 40 ± 2 mm Hg. Ten minutes prior to retransfusion of shed blood, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl). At the end of the experiment (T = 300 minutes), blood, aorta and heart were harvested for Western blot (inductible Nitric Oxyde Synthase (iNOS), Nuclear factor-κB (NF-κB), phosphorylated Inhibitor κB (P-IκB), Inter-Cellular Adhesion Molecule (I-CAM), Heme oxygenase 1(HO-1), Heme oxygenase 2(HO-2), as well as nuclear respiratory factor 2 (Nrf2)). Nitric oxide (NO) and superoxide anion (O2 -) were also measured by electron paramagnetic resonance. Results At the end of the experiment, control rats exhibited a decrease in MAP which was attenuated by NaHS (65 ± 32 versus 101 ± 17 mmHg, P < 0.05). CBF was better maintained in NaHS-treated rats (1.9 ± 1.6 versus 4.4 ± 1.9 ml/minute P < 0.05). NaHS significantly limited shock-induced metabolic acidosis. NaHS also prevented iNOS expression and NO production in the heart and aorta while significantly reducing NF-kB, P-IκB and I-CAM in the aorta. Compared to the control group, NaHS significantly increased Nrf2, HO-1 and HO-2 and limited O2 - release in both aorta and heart (P < 0.05). Conclusions NaHS is protective against the effects of ischemia reperfusion induced by controlled hemorrhage in rats. NaHS also improves hemodynamics in the early resuscitation phase after hemorrhagic shock, most likely as a result of attenuated oxidative stress. The use of NaHS hence appears promising in limiting the consequences of ischemia reperfusion (IR)

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Design and evaluation of a method for the estimation of a herd-level probability of infection from heterogeneous data : contribution to the development of output-based surveillance

A l'échelle de territoires, les programmes collectifs de maîtrise des maladies infectieuses non règlementées des bovins présentent de multiples bénéfices. Ils créent aussi des difficultés dans les échanges entre territoires car leurs définitions du statut « indemne d'infection » diffèrent. Estimer une probabilité (d'absence) d'infection pour chaque troupeau, calculée indépendamment des modalités de surveillance, permettrait de sécuriser le commerce d'animaux entre territoires. Ce type d'estimation pourrait servir à une surveillance dite output-based, basée sur un résultat à atteindre et non sur les moyens mis en œuvre. Les objectifs de cette thèse étaient de contribuer à l'élaboration puis d'évaluer une méthode d'estimation de probabilité d'infection à l'échelle du troupeau, à partir de données de surveillance hétérogènes. En prenant l'exemple de l'infection par le virus de la diarrhée virale bovine, les informations pertinentes et disponibles ont été identifiées et organisées. Le modèle développé est un modèle de Markov caché estimant une probabilité d'infection à l'échelle du troupeau à partir de résultats de test et de facteurs de risque d'infection. Ses performances ont été évaluées sur des données simulées, représentant une diversité de dynamiques d'infection et de programmes de maîtrise. Il ressort de l'évaluation que la valeur ajoutée du modèle est d'autant plus importante que la sensibilité du test de diagnostic est faible. La valeur ajoutée des facteurs de risque semble limitée. L'utilisation de ce modèle requiert des développements supplémentaires pour la classification des troupeaux en indemne/ infecté à partir des probabilités d'infection prédites.On a territorial scale, programmes to contrai non-regulated infectious diseases of cattle have multiple benefits. They also create difficulties in exchanges between territories because the definitions of 'infection-free' status differ between programmes. Estimating a probability (of absence) of infection for each herd calculated independently of the surveillance modalities would make it possible to secure trade in animais between territories. This type of estimate could be used for output-based surveillance, a type of surveillance based on a result to be achieved and not on the means implemented. The objectives of this thesis work were to contribute to the development and evaluation of a method for estimating infection probabilities at the herd level, based on heterogeneous surveillance data. Using the example of bovine viral diarrhea virus infection, relevant and available information was identified and organised. The model developed is a hidden Markov model estimating a probability of infection at the herd level from repeated test results and risk factors for infection. lts performance was evaluated on simulated data representing a variety of infection dynamics and contrai programmes. The evaluation showed that the added value of the model was greater the lower the sensitivity of the diagnostic test. The added value of the risk factors was moderate in the range of situations evaluated. The use of this model requires further development for the classification of herds as free/infected based on predicted infection probabilities