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

Control of Metabolic Homeostasis by Stress Signaling Is Mediated by the Lipocalin NLaz

Metabolic homeostasis in metazoans is regulated by endocrine control of insulin/IGF signaling (IIS) activity. Stress and inflammatory signaling pathways—such as Jun-N-terminal Kinase (JNK) signaling—repress IIS, curtailing anabolic processes to promote stress tolerance and extend lifespan. While this interaction constitutes an adaptive response that allows managing energy resources under stress conditions, excessive JNK activity in adipose tissue of vertebrates has been found to cause insulin resistance, promoting type II diabetes. Thus, the interaction between JNK and IIS has to be tightly regulated to ensure proper metabolic adaptation to environmental challenges. Here, we identify a new regulatory mechanism by which JNK influences metabolism systemically. We show that JNK signaling is required for metabolic homeostasis in flies and that this function is mediated by the Drosophila Lipocalin family member Neural Lazarillo (NLaz), a homologue of vertebrate Apolipoprotein D (ApoD) and Retinol Binding Protein 4 (RBP4). Lipocalins are emerging as central regulators of peripheral insulin sensitivity and have been implicated in metabolic diseases. NLaz is transcriptionally regulated by JNK signaling and is required for JNK-mediated stress and starvation tolerance. Loss of NLaz function reduces stress resistance and lifespan, while its over-expression represses growth, promotes stress tolerance and extends lifespan—phenotypes that are consistent with reduced IIS activity. Accordingly, we find that NLaz represses IIS activity in larvae and adult flies. Our results show that JNK-NLaz signaling antagonizes IIS and is critical for metabolic adaptation of the organism to environmental challenges. The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting that similar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis

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

Effets de la nutrition sur le contrôle de la croissance chez Drosophila melanogaster

Tous les organismes vivants croissent. Ils puisent dans leur environnement des substances nutritives, les ingèrent, et se développent. Mais la qualité nutritive de l'environnement peut varier, obligeant les organismes à percevoir et à répondre à ces variations. Ainsi, les levures, par exemple, règlent leur croissance en fonction de la disponibilité en nutriments dans le milieu extracellulaire, via un module de signalisation faisant intervenir la protéine kinase TOR. Ces mécanismes de régulation intrinsèques à la cellule sont remarquablement conservés au cours de l'évolution. De plus, chez les métazoaires, des circuits de régulations humorales, contrôlés par des molécules circulantes comme l'insuline ou les IGF permettent d'harmoniser le métabolisme et la croissance des tissus d'un organisme. Mes travaux de thèse effectués chez la drosophile étudient comment la croissance globale est contrôlée par le niveau des nutriments. Chez la drosophile, la taille de l'adulte ne varie pas et est déterminée par une période de croissance qui prend place au cours des stades larvaires. De fait, le développement de la larve de drosophile constitue un excellent modèle d'étude de la croissance. Le corps gras est un tissu endoréplicatif de la larve particulièrement sensible aux variations nutritionnelles. Ce tissu dispersé remplit des fonctions équivalentes à celles du foie des mammifères, comme le stockage des protéines, des glucides et des lipides, mais il a aussi des fonctions endocrines. Nos expériences démontrent que le corps gras agit comme un senseur qui orchestre la croissance des autres tissus en fonction des conditions nutritionnelles. L'inhibition de la voie de signalisation dTOR dans ce tissu en réponse à une carence en acides aminés est à l'origine d'un arrêt systémique de la croissance dans les tissus périphériques. Plusieurs molécules de type insuline/IGF, les Dilps (Drosophila insulin-like peptides) sont sécrétées par des cellules neurosécrétrices et agissent via dInr, l'unique récepteur à l'insuline chez la drosophile. La mise en carence nutritionnelle du corps gras induit une forte réduction de l'activité de la voie Dilp dans les tissus périphériques de la larve. Une possibilité est qu'en l'absence de nutriments, le corps gras cesse d'émettre un signal qui normalement potentialise la sécrétion et/ou l'activité des Dilps circulants. J'ai récemment identifié une molécule pouvant remplir ce rôle: il s'agit de l'orthologue chez la drosophile de la glycoprotéine ALS (acid-labile subunit). Chez les mammifères, ALS lie l'IGF-BP (binding protein) et l'IGF-I dans un complexe ternaire, ce qui entraîne une stabilisation de l'IGF-I circulant. Chez la drosophile, dALS pourrait avoir le même effet sur les Dilps. Le gène dALS est exprimé à des niveaux élevés dans le corps gras et son expression est abaissée par la carence nutritionnelle dans ce tissu. De façon remarquable, dALS est aussi exprimée dans les cellules neurosécrétrices exprimant les Dilps, renforçant l'hypothèse selon laquelle cette protéine joue le rôle de partenaire des Dilps circulants. Mes travaux permettent donc d'établir un nouveau modèle pour le contrôle de la croissance larvaire. Je démontre que la nutrition contrôle de façon systémique la croissance et la taille de l'organisme par un senseur des niveaux d'acides aminés opérant dans le corps gras. Je propose donc le modèle selon lequel, le senseur nutritionnel du corps gras est modulé par la voie de signalisation conservée dTOR, et que l'activation de ce senseur est relayée dans les tissus périphériques au travers d'un mécanisme humoral régulant la voie de signalisation Dilp/dInr.NICE-BU Sciences (060882101) / SudocSudocFranceF

[Targeting the appropriate body size].

International audienc

The Hippo signalling pathway coordinates organ growth and limits developmental variability by controlling dilp8 expression

International audienc