Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Glucose Transporter 1 and Monocarboxylate Transporters 1, 2, and 4 Localization within the Glial Cells of Shark Blood-Brain-Barriers

Although previous studies showed that glucose is used to support the metabolic activity of the cartilaginous fish brain, the distribution and expression levels of glucose transporter (GLUT) isoforms remained undetermined. Optic/ultrastructural immunohistochemistry approaches were used to determine the expression of GLUT1 in the glial blood-brain barrier (gBBB). GLUT1 was observed solely in glial cells; it was primarily located in end-feet processes of the gBBB. Western blot analysis showed a protein with a molecular mass of 50 kDa, and partial sequencing confirmed GLUT1 identity. Similar approaches were used to demonstrate increased GLUT1 polarization to both apical and basolateral membranes in choroid plexus epithelial cells. To explore monocarboxylate transporter (MCT) involvement in shark brain metabolism, the expression of MCTs was analyzed. MCT1, 2 and 4 were expressed in endothelial cells; however, only MCT1 and MCT4 were present in glial cells. In neurons, MCT2 was localized at the cell membrane whereas MCT1 was detected within mitochondria. Previous studies demonstrated that hypoxia modified GLUT and MCT expression in mammalian brain cells, which was mediated by the transcription factor, hypoxia inducible factor-1. Similarly, we observed that hypoxia modified MCT1 cellular distribution and MCT4 expression in shark telencephalic area and brain stem, confirming the role of these transporters in hypoxia adaptation. Finally, using three-dimensional ultrastructural microscopy, the interaction between glial end-feet and leaky blood vessels of shark brain was assessed in the present study. These data suggested that the brains of shark may take up glucose from blood using a different mechanism than that used by mammalian brains, which may induce astrocyte-neuron lactate shuttling and metabolic coupling as observed in mammalian brain. Our data suggested that the structural conditions and expression patterns of GLUT1, MCT1, MCT2 and MCT4 in shark brain may establish the molecular foundation of metabolic coupling between glia and neurons

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Cloning and effects of osmotic acclimation on GLUT1 expression in the euryhaline fish, gilthead sea bream (Sparus aurata)

8º Congreso Asociación Ibérica de Endocrinología Comparada (AIEC), Madrid, 5-7 septiembre, 2011.Gilthead sea bream (S. aurata) is a eurihaline fish, and therefore presents the capacity to live under different environmental salinities, expending extra energy for maintaining the homeostasis when there are osmotic differences between the internal medium and the external environment. In fish, glucose has a relevant role in osmotic stress, supplying the necessary extra energy to the osmoregulatory organs. This metabolite is a hydrophilic molecule that needs a specific transporter (GLUT) to cross plasma membrane. Several members of the GLUT family have been cloned in various fish species, but not in S. aurata. In this study we have cloned the S. aurata GLUT1 (saGLUT1). The cDNA is composed by 4483 bp, with a 5¿UTR of 173 bp, ORF 1476 bp and 3¿UTR which has 2616 bp, presenting high similarity to GLUT1 in other fish species (between 79 to 95 % identity). In addition, saGLUT1 mRNA expression changes in gills, kidney, liver and brain were determined by real time PCR analysis in specimens of 100-150 g body weight, acclimated to four different salinities (5, 12, 40 and 55 ppt) during 15 days. The major levels of expression were found in brain and gills (5000 and 8000 copies/10 ng RNA). Statistical differences in gills (highest expression at 40 ppt) and kidney (highest expression at 5 ppt) were detected, without any significant changes in brain and liver. Our results show that saGLUT1 mRNA expression is regulated in osmoregulatory organs in response to different environmental salinitiesCB-A is supported by a postdoctoral fellowship "Becas Chile" from Chile Government. JAM-S is supported by a Ph.D. fellowship (FPU) from (he Spanish Ministry of Education.Peer Reviewe

Cloning and expression pattern of facilitative glucose transporter 1 (GLUT1) in gilthead sea bream Sparus aurata in response to salinity acclimation

Facilitative glucose transporters (GLUT) are transmembrane transporter proteins involved in glucose transport across the plasma membrane. In fish, several GLUT mRNAs have been cloned, but to date there is no information about these transporters in the marine euryhaline teleost Sparus aurata. In the present study we obtained the complete coding sequence from S. aurata GLUT1 (saGLUT1), composed by 4483 bases, presenting a 79 to 95% identity with respect to other fish GLUT1 mRNAs. The analysis of the 5′ and 3′ UTRs showed the presence of several post-transcriptional regulatory elements. In addition, the effect on saGLUT1 mRNA expression of the osmotic acclimation to four different environmental salinities (5, 12, 40 and 55 ppt), in gills, kidney, liver and brain, was studied. Changes in mRNA expression levels were detected in gills and brain, indicating that GLUT1 has an important role in these organs for osmotic acclimation in S. aurata.This study was funded by project AGL2010-14876 from MICINN to JMM.Peer reviewe

Clinical and experimental approaches to knee cartilage lesion repair and mesenchymal stem cell chondrocyte differentiation

Cartilage has poor regeneration capacity due to the scarcity of endogenous stem cells, its low metabolic activity and the avascular environment. Repair strategies vary widely, including microfracture, autologous or allogenic tissue implantation, and in vitro engineered tissues of autologous origin. However, unlike the advances that have been made over more than two decades with more complex organs, including vascular, cardiac or bone tissues, similar advances in tissue engineering for cartilage repair are lacking. Although the inherent characteristics of cartilage tissue, such as the lack of vascularity and low cellular diversity, suggest that it would be one of the more simple tissues to be engineered, its functional weight-bearing role and implant viability and adaptation make this type of repair more complex. Over the last decade several therapeutic approaches and innovative techniques show promise for lasting and functional regeneration of hyaline cartilage. Here we will analyze the main strategies for cartilage regeneration and discuss our experience

Isosmotic enviroment improves growth rates through a more efficient intestine and a metabolic orchestration in the gilthead sea bream (Sparus Aurata)

Trabajo presentado en en la Society for Experimental Biologia(SEB) 2019 Annual Meeting, celebrado en Sevilla (España), del 2 al 5 de julio de 2019The gilthead sea bream (Sparus aurata) is an euryhaline teleost species with an unmatched capacity for osmoregulatory adaptation. Moreover, environmental salinities that differ from the internal milieu produce a great energetic cost to regulate active ion transport. The present study evaluates, in an 11-weeks feeding trial using a RAS system, the effect of three different environmental salinities (brackish water, BW: 18 ppt; seawater, SW: 37 ppt; and high salinity water, HSW: 55 ppt) on osmoregulatory capacity, growth performance, stress processes and metabolism in S. aurata juveniles (~7 g initial mean body mass). Plasma osmolality did not show significant differences among the three experimental groups, demonstrating the good osmoregulatory acclimation of fish despite the wide range of environmental osmolalities assayed (500-1720 mOsm/kg). Even so, the metabolic orchestration related to glucose, triglycerides and lactate confirms a clear energy repartitioning at hepatic and muscular levels, indicating that the higher energy budget invested for osmoregulatory function produces a salinity-dependent reduction in growth-related parameters. In this regard, BW-acclimated fish enhanced feed intake and feed efficiency when compared to fish kept under hyperosmotic (SW and HSW) environments, which is translated into better growth rates. All these features can be attributed to a shorter (BW < SW ¿ HSW) but more specific intestine for nutritional purposes. Finally, important stress-related markers at hypothalamic (corticotrophin releasing hormone, crh binding protein), hypophyseal (proopiomelanocortin a and b) and plasma (cortisol) levels will be unraveled as putative endocrine mediators of the metabolic and osmoregulatory capacity of acclimated fis

MCT2 and MCT4 are also expressed in shark brain cells.

<p>A–B, Western blot analysis of MCT2 and MCT4 expression in total protein extracts prepared from rat brain (A, lane 1), <i>S. chilensis</i> shark brain (A, B; lanes 2 and 4) and rat muscle (B, lane 3). C–K, Immunohistochemistry of MCT1, 2, 4, and GLUT1 in the telencephalic area. MCT2 is observed in endothelial cells and neurons (C) without co-localization with GLUT1 (C–E). MCT4 is observed in endothelial cells (F) and perivascular structures in telencephalic cortex vessels (I). MCT4 co-localized with MCT1 (H, K). BV: blood vessel, N: neurons. Scale bar: C–H, 15 µm; I–K, 50 µm.</p

Cellular characteristics and distribution of glial cells in the shark brain.

<p>A–B, Scanning electron microscopy of glial cells contacting the CSF (arrow). C–H, Shark (<i>S. chilensis</i>) sagittal brain sections using anti-S100 antibody in the telencephalic area (C–D), cerebellar cortex (E–F) and auricula cerebelli (G–H). I, Schematic representation of radial glial cells, neurons and endothelial cells present in the shark brain. Glial end-feet are in contact with blood vessel endothelial cells. J–K, Ultrastructural analysis of blood vessels and radial glia end-feet. The basal membrane of the blood vessel is shown with arrows. BV: blood vessel, N: neuron, RG: radial glia processes, V: ventricle. Scale bar: A and B, 10 µm; C–H, 20 αm; J–K, 2 αm.</p