Community-based symptom reporting among agro-pastoralists and their livestock in Chad in a One Health approach.

One Health Syndromic Surveillance has a high potential for detecting early epidemiological events in remote and hard-to-reach populations. Chadian pastoralists living close to their animals and being socio-economically unprivileged have an increased risk for zoonosis exposure. Engaging communities in disease surveillance could also strengthen preparedness capacities for outbreaks in rural Chad. This study describes a retrospective cross-sectional survey that collected data on clinical symptoms reported in people and livestock in Chadian agro-pastoral communities. In January-February 2018, interviews were conducted in rural households living in nomadic camps or settled villages in the Yao and Danamadji health districts. The questionnaire covered demographic data and symptoms reported in humans and animals for the hot, wet, and cold seasons over the last 12 months. Incidence rates of human and animal symptoms were comparatively analyzed at the household level. Ninety-two households with a homogeneous socio-demographic distribution were included. We observed cough and diarrhea as the most frequent symptoms reported simultaneously in humans and animals. In all species, the incidence rate of cough was significantly higher during the cold season, and diarrhea tended to occur more frequently during the wet season. However, the incidence rate of cough and diarrhea in animals did not predict the incidence rate of these symptoms in humans. Overall, the variations in reported symptoms were consistent with known seasonal, regional, and sociological influences on endemic diseases. Our retrospective study demonstrated the feasibility of collecting relevant health data in humans and animals in remote regions with low access to health services by actively involving community members. This encourages establishing real-time community-based syndromic surveillance in areas such as rural Chad.

Inflammatory biomarker concentrations in dogs with gastric dilatation volvulus with and without 24-h intravenous lidocaine.

Background: Canine gastric dilatation volvulus (GDV) is characterized by tissue ischemia, reperfusion, and systemic inflammation. Evidence exists that lidocaine exerts anti-inflammatory properties and potentially improves outcome. Design and setting: Prospective, randomized observational cohort study in client-owned dogs with GDV. Objective: The primary objective of the study was the determination of pro- and anti-inflammatory biomarker concentrations in dogs with GDV with and without intravenous (IV) lidocaine therapy. The second objective was the evaluation of side effects of lidocaine. Methods: Of 35 dogs included in the study, 20 dogs were assigned to receive lidocaine (LIDO) (2 mg/kg initially, followed by a continuous infusion at a rate of 50 µg/kg/min over 24 h) and 15 dogs not to receive lidocaine (NO-LIDO). Plasma concentrations of cytokines interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma, keratinocyte chemotactic-like, monocyte chemotactic protein, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, T0), immediately after surgery (T1), at 24 h (T24), and at 48 h (T48) post-surgery. Results: No significant differences in concentrations of any cytokines were found between the LIDO- and the NO-LIDO group. Significant lower CRP concentrations (median [range]) were found in dogs with lidocaine compared to dogs without at T24 (97.5 pg/mL [46.3-161.7] vs. 127.9 pg/mL [26.9-182.0]; p = 0.046) and T48 (73.7 pg/mL [18.4-169.4] vs. 116.3 pg/mL [71.4-176.8]; p = 0.002). Dogs receiving lidocaine exhibited significantly impaired mentation, a prolonged period of anorexia, and longer hospitalization compared to dogs without lidocaine. Conclusion: Lidocaine administration had no impact on the plasma levels of cytokines during the 48-h study period, but significantly lower CRP concentrations were found at T24 and T48. Lidocaine's potential side effects require careful decision making regarding its use.

Blockade of the cholinergic system during sensitization enhances lung responsiveness to allergen in rats.

Although acute prophylactic administration of atropine modulates airway responsiveness, the role of the parasympathetic nervous system in the pathogenesis of sensitization and in antigen-induced bronchoconstriction remains unclear. The aim of the present study is to determine whether blocking muscarinic receptors during chronic allergen exposure modulates lung responsiveness to the specific allergen. Forty rats were randomly assigned to one of the following five treatment groups: sensitization with saline vehicle, intraperitoneal injection of ovalbumin (1 mg) with or without atropine treatment (10 mg/kg per day) and repeated ovalbumin aerosol (1.25 mg/mL for 20 minutes) either alone or combined with atropine. Lung responsiveness to methacholine (4-16 µg/kg per minute) and intravenous ovalbumin (2 mg) was established before and 21 days after treatment with forced oscillations following bilateral vagotomy. Lung cellularity was determined by analysis of bronchoalveolar lavage fluid (BALF). A lung inflammatory response in all sensitized animals was defined as an increase in the number of inflammatory cells in the BALF. Baseline respiratory mechanics and methacholine responsiveness on Days 0 and 21 were comparable in all groups. However, increases in airway resistance following intravenous allergen challenge were significantly exacerbated in rats that received atropine. Inhibition of the cholinergic nervous system during allergic sensitization potentiates bronchoconstriction following exposure to the specific allergen. These findings highlight the role of the cholinergic neuronal pathway in airway sensitization to a specific allergen.

Lung responses in murine models of experimental asthma: Value of house dust mite over ovalbumin sensitization.

Ovalbumin (OVA) sensitization has limitations in modelling asthma. Thus, we examined the value of allergic sensitization using a purified natural allergen, house dust mite (HDM), over the sensitization performed with OVA. Mice were sham-treated, or sensitized with OVA- or HDM with identical chronology. Airway resistance, tissue damping and elastance were assessed under control conditions and after challenging the animals with methacholine (MCh) and the specific allergen. Inflammatory profile of the bronchoalveolar lavage fluid was characterized and lung histology was performed. While no difference in the lung responsiveness to the specific allergen was noted, hyperresponsiveness to MCh was observed only in the HDM-sensitized animals in the lung peripheral parameters. Lung inflammation differed between the models, but excessive bronchial smooth muscle remodelling occurred only with OVA. In conclusion, we demonstrate that a purified natural allergen offers a more relevant murine model of human allergic asthma by expressing the key features of this chronic inflammatory disease both in the lung function and structure.

Interferon-γ-Driven iNOS: A Molecular Pathway to Terminal Shock in Arenavirus Hemorrhagic Fever.

Arenaviruses such as Lassa virus (LASV) cause hemorrhagic fever. Terminal shock is associated with a systemic cytokine storm, but the mechanisms are ill defined. Here we used HLA-A2-expressing mice infected with a monkey-pathogenic strain of lymphocytic choriomeningitis virus (LCMV-WE), a close relative of LASV, to investigate the pathophysiology of arenavirus hemorrhagic fever (AHF). AHF manifested as pleural effusions, edematous skin swelling, and serum albumin loss, culminating in hypovolemic shock. A characteristic cytokine storm included numerous pro-inflammatory cytokines and nitric oxide (NO) metabolites. Edema formation and terminal shock were abrogated in mice lacking inducible nitric oxide synthase (iNOS), although the cytokine storm persisted. iNOS was upregulated in the liver in a T cell- and interferon-γ (IFN-γ)-dependent fashion. Accordingly, blockade of IFN-γ or depletion of T cells repressed hepatic iNOS and prevented disease despite unchecked high-level viremia. We identify the IFN-γ-iNOS axis as an essential and potentially druggable molecular pathway to AHF-induced shock.

Synchrotron Imaging Shows Effect of Ventilator Settings on Intrabreath Cyclic Changes in Pulmonary Blood Volume.

Despite the importance of dynamic changes in the regional distributions of gas and blood during the breathing cycle for lung function in the mechanically ventilated patient, no quantitative data on such cyclic changes are currently available. We used a novel gated synchrotron computed tomography imaging to quantitatively image regional lung gas volume (Vg), tissue density, and blood volume (Vb) in six anesthetized, paralyzed, and mechanically ventilated rabbits with normal lungs. Images were repeatedly collected during ventilation and steady-state inhalation of 50% xenon, or iodine infusion. Data were acquired in a dependent and nondependent image level, at zero end-expiratory pressure (ZEEP) and 9 cm H2O (positive end-expiratory pressure), and a tidal volume (Vt) of 6 ml/kg (Vt1) or 9 ml/kg (Vt2) at an Inspiratory:Expiratory ratio of 0.5 or 1.7 by applying an end-inspiratory pause. A video showing dynamic decreases in Vb during inspiration is presented. Vb decreased with positive end-expiratory pressure (P = 0.006; P = 0.036 versus Vt1-ZEEP and Vt2-ZEEP, respectively), and showed larger oscillations at the dependent image level, whereas a 45% increase in Vt did not have a significant effect. End-inspiratory Vb minima were reduced by an end-inspiratory pause (P = 0.042, P = 0.006 at nondependent and dependent levels, respectively). Normalized regional Vg:Vb ratio increased upon inspiration. Our data demonstrate, for the first time, within-tidal cyclic variations in regional pulmonary Vb. The quantitative matching of regional Vg and Vb improved upon inspiration under ZEEP. Further study is underway to determine whether these phenomena affect intratidal gas exchange.

Pressure-regulated volume control vs. volume control ventilation in healthy and injured rabbit lung: An experimental study.

BACKGROUND: It is not well understood how different ventilation modes affect the regional distribution of ventilation, particularly within the injured lung. OBJECTIVES: We compared respiratory mechanics, lung aeration and regional specific ventilation ((Equation is included in full-text article.)) distributions in healthy and surfactant-depleted rabbits ventilated with pressure-regulated volume control (PRVC) mode with a decelerating inspiratory flow or with volume control (VC) mode. DESIGN: Randomised experimental study. ANIMALS AND INTERVENTIONS: New Zealand white rabbits (n = 8) were anaesthetised, paralysed and mechanically ventilated either with VC or PRVC mode (tidal volume: 7 ml kg; rate: 40 min; positive end-expiratory pressure (PEEP): 3 cmH2O), at baseline and after lung injury induced by lung lavage. MAIN OUTCOME MEASURES: Airway resistance (Raw), respiratory tissue damping (G) and elastance (H) were measured by low-frequency forced oscillations. Synchrotron radiation computed tomography during stable xenon wash-in was used to measure regional lung aeration and specific ventilation and the relative fraction of nonaerated, trapped, normally, poorly and hyperinflated lung regions. RESULTS: Lung lavage significantly elevated peak inspiratory pressure (PIP) (P < 0.001). PIP was lower on PRVC compared with VC mode (-12.7 ±â€Š1.7%, P < 0.001). No significant differences in respiratory mechanics, regional ventilation distribution, strain or blood oxygenation could be detected between the two ventilation modes. CONCLUSION: A decelerating flow pattern (PRVC) resulted in equivalent regional ventilation distribution, respiratory mechanics and gas exchange, in both normal and mechanically heterogeneous lungs with, however, a significantly lower peak pressure. Our data suggest that the lower PIP on PRVC ventilation was because of the decelerating flow pattern rather than the ventilation distribution.

Fluid replacement and respiratory function: comparison of whole blood with colloid and crystalloid: A randomised animal study.

BACKGROUND: Fluid replacement with blood products, colloids and crystalloids is associated with morbidity and mortality. Despite this, the consequences of fluid administration on airway and respiratory tissue properties are not fully understood. OBJECTIVE: Comparison of respiratory effects of fluid replacement with autologous blood (Group B), colloid (HES 6% 130/0.4, Group CO) or crystalloid solution (NaCl 0.9%, Group CR) after haemorrhage with separate assessments of airway resistance and respiratory tissue mechanics. DESIGN: A randomised study. SETTING: An experimental model of surgical haemorrhage and fluid replacement in rats. PARTICIPANTS: Anaesthetised, ventilated rats randomly allocated into three groups (Group B: n = 8, Group CO: n = 8, Group CR: n = 9). INTERVENTION: Animals were bled in six sequential steps, each manoeuvre targeting a loss of 5% of total blood volume. The blood loss was then replaced stepwise in a 1 : 1 ratio with one of the three fluids. MAIN OUTCOME MEASURE: After each step, airway resistance (Raw), tissue damping and elastance (H) were determined by forced oscillations. Oedema indices from lung weights and histology were also measured. RESULTS: Raw (mean ±â€ŠSD) decreased in all groups following blood loss (-20.3 ±â€Š9.5% vs. baseline, P < 0.05), and remained low following blood replacement (-21.7 ±â€Š14.5% vs. baseline, P < 0.05), but was normalised by colloid (5.5 ±â€Š10.7%, NS). Crystalloid administration exhibited an intermediate reversal effect (-8.4 ±â€Š14.7%, NS). Tissue viscoelasticity increased following both blood loss and replacement, with no evidence of a significant difference in H between Groups CO and CR. More severe oedema was observed in Groups CR and CO than in Group B (P < 0.05), with no difference between the colloid and crystalloid solutions. CONCLUSION: This model, which mimics surgical haemorrhage, yields no evidence of a difference between colloids and crystalloids with regard to the pulmonary consequences of blood volume restoration. Functional changes in the lung should not be a key concern when choosing fluid replacement therapy with these solutions.

Cardiorespiratory effects of recruitment maneuvers and positive end expiratory pressure in an experimental context of acute lung injury and pulmonary hypertension.

BACKGROUND: Recruitment maneuvers (RM) and positive end expiratory pressure (PEEP) are the cornerstone of the open lung strategy during ventilation, particularly during acute lung injury (ALI). However, these interventions may impact the pulmonary circulation and induce hemodynamic and respiratory effects, which in turn may be critical in case of pulmonary hypertension (PHT). We aimed to establish how ALI and PHT influence the cardiorespiratory effects of RM and PEEP. METHODS: Rabbits control or with monocrotaline-induced PHT were used. Forced oscillatory airway and tissue mechanics, effective lung volume (ELV), systemic and right ventricular hemodynamics and blood gas were assessed before and after RM, during baseline and following surfactant depletion by whole lung lavage. RESULTS: RM was more efficient in improving respiratory elastance and ELV in the surfactant-depleted lungs when PHT was concomitantly present. Moreover, the adverse changes in respiratory mechanics and ELV following ALI were lessened in the animals suffering from PHT. CONCLUSIONS: During ventilation with open lung strategy, the role of PHT in conferring protection from the adverse respiratory consequences of ALI was evidenced. This finding advocates the safety of RM and PEEP in improving elastance and advancing lung reopening in the simultaneous presence of PHT and ALI.

Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (sV̇) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on sV̇ distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased sV̇ (P < 0.001) and sV̇ heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants.

Polarization state studies in second harmonic generation signals to trace atherosclerosis lesions.

We have performed multi-photon image reconstructions as well as polarization state analyses inside an artery wall affected by atherosclerosis to investigate the changes in collagen structure. Mice, either healthy or affected by spontaneous atherosclerosis, have been used for this purpose. A two-photon imaging system has been used to investigate atherosclerotic lesions in the ascending aorta of mice. Second harmonic imaging has been performed alternatively on healthy samples and on affected region. The reconstructed images show that the spatial distribution of the collagen network seems disorganized by the disease. The polarization state studies reveal however that the apparent disorganization of the collagen is related to its spatially diffuse distribution and that the internal structure of the collagen fibers is not affected by the disease. In addition, a theoretical simulation of the second harmonic polarization states shows that they are consistent with the known 3D structure of the collagen network.