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

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 optimization of voltage parameter for tissue electroporation in somatic embryos of Astragalus chrysochlorus (Leguminosae)

Somatic embryo tissues of Astragalus chrysochlorus were transformed with the beta-glucuronidase (GUS) and neomycin phosphotransferase II (npt II) genes by electroporation. The effect of electric field strength was tested for transient expression. It was found that 1000 V/cm and 200 mu s and 1 pulse was the optimum combination to transform embryo tissues (expression level was 61.5%). Electroporated somatic embryo tissues were positive for GUS expression and PCR analysis for the genes GUS and npt II. After PCR analysis, we found that the efficiency of the somatic embryos with transient GUS expression by electroporation was 48%

Analysis of elicitor inducible cytochrome P450 induction in Astragalus chrysochlorus cells

Abstract In this study, elicitor-inducible cytochrome P450 biosynthesis in Astragalus chrysochlorus was investigated for further analysis on phenylpropanoid metabolism. In order to analyse cytochrome P450s under yeast extract elicited conditions, we used non-radioactive P450 targeted differential display method. The P450 targeted differential display of mRNA technique was performed with upstream primers based on the conserved heme-binding region [PFG] of P450s, as a result 56 clearly differential bands were revealed; 37 of the bands were correctly analysed, and one of the PCR products was contained the P450 fingerprint. This sequence has been confirmed to be up-regulated and subsequently cloned and sequenced. Homology analysis of the 400 bp long sequence revealed that 81 % similarity with cinnamate 4-hydroxylase in the manner of amino acid. Quantitative real-time-PCR analysis showed that putative C4H gene was up-regulated 13,24-fold by 6h yeast extract treatment unlike untreated control. 1338 bp long cDNA fragment (Accession no: GQ844863) of A. chrysochlorus C4H (AcC4H) has been obtained by PCR with degenerate primers. Bioinformatics analyses revealed that putative AcC4H (1338 bp) was highly similar (95 %) to trans-cinnamate 4-monooxygenase (EC 1.14.13.11). As a result, we have isolated a putative C4H fragment from A. chrysochlorus suspension cells under yeast extract elicited conditions. This knowledge will use for obtaining whole C4H sequence, and to manupulate phenylpropanoid metabolic pathway of this medicinal plant

Analysis of elicitor inducible cytochrome P450 induction in Astragalus chrysochlorus cells

In this study, elicitor-inducible cytochrome P450 biosynthesis in Astragalus chrysochlorus was investigated for further analysis on phenylpropanoid metabolism. In order to analyse cytochrome P450s under yeast extract elicited conditions, we used non-radioactive P450 targeted differential display method. The P450 targeted differential display of mRNA technique was performed with upstream primers based on the conserved heme-binding region [PFG] of P450s, as a result 56 clearly differential bands were revealed; 37 of the bands were correctly analysed, and one of the PCR products was contained the P450 fingerprint. This sequence has been confirmed to be up-regulated and subsequently cloned and sequenced. Homology analysis of the 400 bp long sequence revealed that 81 % similarity with cinnamate 4-hydroxylase in the manner of amino acid. Quantitative real-time-PCR analysis showed that putative C4H gene was up-regulated 13,24-fold by 6h yeast extract treatment unlike untreated control. 1338 bp long cDNA fragment (Accession no: GQ844863) of A. chrysochlorus C4H (AcC4H) has been obtained by PCR with degenerate primers. Bioinformatics analyses revealed that putative AcC4H (1338 bp) was highly similar (95 %) to trans-cinnamate 4-monooxygenase (EC 1.14.13.11). As a result, we have isolated a putative C4H fragment from A. chrysochlorus suspension cells under yeast extract elicited conditions. This knowledge will use for obtaining whole C4H sequence, and to manupulate phenylpropanoid metabolic pathway of this medicinal plant

Selenium tolerance in Astragalus chrysochlorus: identification of a cDNA fragment encoding a putative Selenocysteine methyltransferase

Selenium (Se) plays an indispensable role in human nutrition and has been implicated to have important health benefits, including being a cancer preventative agent. Selected members of the genus Astragalus (Fabaceae) are known for their ability to accumulate high levels of selenium, mainly in the form of methyl-selenocysteine (MeSeCys). The Se-hyperaccumulator Astragalus bisulcatus metabolizes > 90% of the accumulated Se into MeSeCys in young shoot tissue. Selenocysteine methyltransferase (SMT) catalyzes the methylation of SeCys to yield MeSeCys. In this study, we aimed to investigate selenium accumulation ability of Astragalus chrysochlorus. For this reason, A. chrysochlorus plants were cultured in Murashige and Skoog medium containing 1, 5, 25 or 75 ppm sodium selenate. Both shoot and root length decreased significantly when plants exposed more than 5 ppm sodium selenate. Dried plant materials were analysed with ICP-MS in the terms of Se and S accumulation. Regarding the calculated discrimination coefficients (DC (i) ) value (0.95) A. chrysochlorus was evaluated as a secondary Se accumulator plant. Putative SMT fragments were amplified by using the primers which were designed according to conserved region of Astragalus bisulcatus, Camelia sinensis and Brassica oleracea SMT genes. Reverse transcription PCR demonstrated that 595 bp fragment was expressed (Accession no: GQ844862), and a database search indicated that the similarity between A. bisulcatus SMT nucleotide sequence and the putative AcSMT fragment was 92%. The putative AcSMT gene represents a single copy sequence in Astragalus chrysoclorus genome

Molecular cloning and biotic elicitation response of phenylalanine ammonia-lyase gene of Astragalus chrysochlorus.

Phenylalanine ammonia lyase (PAL) is the first enzyme of the phenylpropanoid pathway, and it is necessary to upregulate flavonoid biosynthesis in most of the plant species. In this study, we have cloned PAL gene from endemic Astragalus chrysochlorus which is a producer of phenolic nicotiflorin (kaempferol-3-O-rutinoside). The cDNA encoding PAL was cloned from A. chrysochlorus using RT-PCR (reverse transcription-polymerase chain reaction) with conserved primer pairs. Amino acid sequence alignments showed that AcPAL (2160 bp, Accession number: KM189182) has more than 95% amino acid identity with their homologues in other Astragalus species. The coding sequence for the protein of AcPAL is 720 amino acids with a calculated molecular weight of 78.53 kDa. Full length AcPAL was cloned and expressed in Escherichia coli. qPCR (quantitative real-time PCR) analysis of the expression of PAL gene of A. chrysochlorus suggested that maximum transcript level was observed in 3 h yeast extract elicited suspension cells. Our findings suggest that AcPAL plays role in early response for yeast extract treatment. The isolation of AcPAL gene could be result in further studies for overproduction of secondary metabolite, nicotiflorin