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

The Myeloid Receptor PILRβ Mediates the Balance of Inflammatory Responses through Regulation of IL-27 Production

Paired immunoglobulin-like receptors beta, PILRβ, and alpha, PILRα, are related to the Siglec family of receptors and are expressed primarily on cells of the myeloid lineage. PILRβ is a DAP12 binding partner expressed on both human and mouse myeloid cells. The potential ligand, CD99, is found on many cell types, such as epithelial cells where it plays a role in migration of immune cells to sites of inflammation. Pilrb deficient mice were challenged with the parasite Toxoplasma gondii in two different models of infection induced inflammation; one involving the establishment of chronic encephalitis and a second mimicking inflammatory bowel disease in order to understand the potential role of this receptor in persistent inflammatory responses. It was found that in the absence of activating signals from PILRβ, antigen-presenting cells (APCs) produced increased amounts of IL-27, p28 and promoted IL-10 production in effector T cells. The sustained production of IL-27 led ultimately to enhanced survival after challenge due to dampened immune pathology in the gut. Similar protection was also observed in the CNS during chronic T. gondii infection after i.p. challenge again providing evidence that PILRβ is important for regulating aberrant inflammatory responses

Cadmium-Induced Oxidative Stress and Apoptotic Changes in the Testis of Freshwater Crab, Sinopotamon henanense

Cadmium (Cd), one of the most toxic environmental and industrial pollutants, is known to exert gonadotoxic and spermiotoxic effects. In the present study, we examined the toxic effect of Cd on the testis of freshwater crab, Sinopotamon henanense. Crabs were exposed to different Cd concentrations (from 0 to 116.00 mg·L−1) for 7 d. Oxidative stress and apoptotic changes in the testes were detected. The activities of SOD, GPx and CAT initially increased and subsequently decreased with increasing Cd concentrations, which was accompanied with the increase in malondialdehyde (MDA) and H2O2 content in a concentration-dependent manner. Typical morphological characteristic and physiological changes of apoptosis were observed using a variety of methods (HE staining, AO/EB double fluorescent staining, Transmission Electron Microscope observation and DNA fragmentation analysis), and the activities of caspase-3 and caspase-9 were increased in a concentration-dependent manner after Cd exposure. These results led to the conclusion that Cd could induced oxidative damage as well as apoptosis in the testis, and the apoptotic processes may be mediated via mitochondria-dependent apoptosis pathway by regulating the activities of caspase-3 and caspase-9

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

The impact of synthetic text generation for sentiment analysis using GAN based models

Data imbalance in datasets is a common issue where the number of instances in one or more categories far exceeds the others, so is the case with the educational domain. Collecting feedback on a course on a large scale and the lack of publicly available datasets in this domain limits models' performance, especially for deep neural network based models which are data hungry. A model trained on such an imbalanced dataset would naturally favor the majority class. However, the minority class could be critical for decision-making in prediction systems, and therefore it is usually desirable to train a model with equally high class-level accuracy. This paper addresses the data imbalance issue for the sentiment analysis of users' opinions task on two educational feedback datasets utilizing synthetic text generation deep learning models. Two state-of-the-art text generation GAN models namely CatGAN and SentiGAN, are employed for synthesizing text used to balance the highly imbalanced datasets in this study. Particular emphasis is given to the diversity of synthetically generated samples for populating minority classes. Experimental results on highly imbalanced datasets show significant improvement in models' performance on CR23K and CR100K after balancing with synthetic data for the sentiment classification task

Systemic cytokine response in WT and <i>Pilrb</i> −/− mice after acute and chronic i.p infection.

<p>WT and <i>Pilrb</i> −/− mice were challenged i.p. with either PBS or <i>T.gondii</i> and serum cytokine protein levels were determined by ELISA during acute infection; IL-12p70 (a), IFNγ (b), IL-10 (c), and IL-27p28 (d) all on day 5. Alternatively, IL-27p28 was analyzed on day 60–90 after challenge (e). Pooled data from 2–3 experiments is shown for all graphs. For panel b, p<0.043; for panel d, p = 0.0007 and for panel e, p<0.01.</p

Host survival is characterized by increased capacity to produce IL-27p28.

<p>Recall assays using MLNs at day 5 (a); and splenocytes at day 7 (b and c, left panels) or day 10 (b and c, right panels) after peroral challenge. Amount of IFNγ (a, top graph; and b, left and right) or IL-10 (a, bottom graph; and c, left and right) detectable in supernatants of WT (grey bars) and <i>Pilrb−/−</i> (black bars) after 3 days of culture in media alone, with STAg, or with αCD3. For panel a, one representative experiment of two shown; for panels b and c, combined data from 3 independent experiments shown. Time course of IL-27p28 protein in serum from infected WT (grey bars) and <i>Pilrb</i> −/− (black bars) mice as detected by ELISA, mean ± SD is shown (d). Values between strains on days 5, p = 0.0219 and 7, p = 0.0318 are all significantly different. Recall assay using MLNs at day 5 post-peroral infection and cultured as above. Amount of IL-27p28 detectable in supernatants after 3 days of culture (e). Mean ± SD are shown. For STAg, p = 0.0143; for αCD3, p = 0.0371.</p

Cytokine mRNA expression in dendritic cells and macrophages from infected mice.

<p>Populations of DCs and macrophages were enriched from the spleens of WT and <i>Pilrb</i> −/− mice 5 days after i.p. challenge. Cells were then analyzed by RT-PCR for mRNA levels of IL27p28 (a) EBi3 (b) and IL-10 (c). Pooled data from one of two representative experiments is shown.</p

IL-27 can mediate resistance to parasite induced immunopathology.

<p>Expression of p28, EBi3, IL27 hyperkine, or GFP control were induced in vivo using minicircle DNA for systemic expression prior to high dose peroral infection with <i>T. gondii</i>. Survival curve of all groups 14 days post infection (a), p<0.02 for IL-27 vs. eGFP treatment groups. Serum cytokine levels for each treatment group at day 0 (white bars) and day 7 (black bars) post infection showing IL-27p28 (b), IL-10 (c), p<0.004, and IFNγ (d). For all panels means ± SD are shown. For panel a, n = 5 or 10 mice/group for each of 3 experiments performed. For panels b, c and d, n = 10 mice/group for the experiment shown, 2 total experiments performed.</p

Characterization of the local inflammatory response during chronic i.p. infection.

<p>WT and <i>Pilrb</i> −/− mice were challenged i.p. with 20 cysts <i>T.gondii</i> and followed over time. Survival of WT and <i>Pilrb−/−</i> mice through 100 days post infection (a). H&E of brain sections reveal larger inflammatory foci in WT mice compared to <i>Pilrb−/−</i>, shown at 10× magnification (b). Total number of cysts present in the CNS of mice 60–90 days post infection (c). Actual numbers of BMNCs isolated from the CNS of mice (d). Recall assays using BMNCs isolated from WT and <i>Pilrb−/−</i> mice and cultured for 72 hrs in the presence of Media alone, STAg, or αCD3. Levels of protein are shown as detected by ELISA for TNFα (e), IFNγ (f), NO (g), and IL-10 (h). For panel a, n = 5–15 mice/group for each of 3 experiments performed. For panel c, pooled data from 2 experiments are shown, p<0.004. For panel d, one representative experiment of 2 is shown, p<0.05. For panels e,f, and h, pooled data from 2–3 experiments are shown, *p<0.005; **p<0.002.</p