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

Epigenetic Regulation of Hepatitis B Virus Biosynthesis

Transcription of cellular genes occurs in the context of chromatin and is known to be regulated by DNA and histone modifications, which govern the accessibility of transcription factors and coactivators to their regulated gene promoters and enhancers to modulate transcription. For transcription to take place from a repressed chromatin template, repressive epigenetic modifications including DNA methylation have to be removed. Additionally, associated repressive histone marks have to be replaced by transcriptional activation marks deposited by means of histone modifiers to promote open chromatin conformation which provides accessibility to downstream transcription factors or nuclear receptors and their associated coactivators to get recruited and hence, transcription is activated. The transition from a repressed to a transcriptionally competent chromatin state during development is a role that has been ascribed to pioneer transcription factors which can access their binding sites in compact chromatin such as FOXA pioneer transcription factors. The current study sheds light on a potentially similar mode of regulation connecting HBV epigenome to its transcriptional activation. This study demonstrates that wildtype expression of FOXA transcription factors in the liver of HBV transgenic mouse model of chronic infection during development is required for the loss of repressive HBV transgene DNA methylation and hence, HBV transcriptional activation. The loss of viral DNA methylation presumably promotes a series of events including the formation of open chromatin conformation, the recruitment of nuclear receptors or transcription factors and their associated coactivators such as PGC1 to viral gene promoters to activate viral gene expression. Consistent with that, the current study demonstrates that PGC1 coactivators, by functioning as adaptor molecules, recruit additional coactivators with histone modifying activity such as CBP, SRC1 and PRMT1 which presumably contribute to the active chromatin structure associated with HBV genes by means of covalent histone modifications. The recruitment of PGC1 coactivators to viral gene promoters in this study leads to activation of viral transcription and hence replication. The current study also demonstrates that PGC1-dependent HBV replication seems to be governed by a critical threshold level of HBV core antigen (HBcAg) polypeptides required for the assembly of replication-competent HBV nucleocapsids. This observation highlights a potential cooperative capsid assembly process required for viral replication to occur. In conclusion, the current study provides a suggested model for the potential coupling of FOXA pioneer transcription factor-mediated loss of repressive HBV DNA methylation to viral transcriptional activation in which PGC1 transcriptional coactivators could play a role. These observations provide mechanistic insights into HBV gene regulation and also suggest potential routes for resolution of chronic HBV infection via modulating FOXA and PGC1 levels or activities

PGC1 alpha Transcriptional Adaptor Function Governs Hepatitis B Virus Replication by Controlling HBcAg/p21 Protein-Mediated Capsid Formation

PGC-1&alpha; Transkripsiyonel Adapt&ouml;r Fonksiyonu HBcAg/p21 Protein-Aracılı Kapsid Oluşumunu Kontrol Ederek Hepatit B Vir&uuml;s Replikasyonunu D&uuml;zenler &Ouml;zet: İnsan hepatoma h&uuml;cre hatlarında peroksizom proliferat&ouml;r aktive edici resept&ouml;r gama koaktivat&ouml;r1&alpha; (PGC-1&alpha;), Siklik AMP yanıt elementine bağlanan proteine bağlanan protein (CBP), steroid resept&ouml;r koaktivat&ouml;r 1 (SRC1) ve protein arjinin metil transferaz 1&rsquo;in (PRMT 1) koekspresyonu Hepatitis B vir&uuml;s (HBV) biyosentezini kısmi d&uuml;zeyde artırır. İnsan embriyonik b&ouml;brek h&uuml;cre hatları kullanılmasına rağmen PGC-1&alpha;&rsquo;nın tek başına ek koaktivat&ouml;r ve transkripsiyon fakt&ouml;rlerinin ekspresyonundan bağımsız olarak viral biyosentezi destekleyebildiğini g&ouml;stermek m&uuml;mk&uuml;n olabildi. Buna karşın PGC-1&alpha; yokluğunda ek koaktivat&ouml;rlerin varlığı HBV repikasyonunu g&uuml;&ccedil;l&uuml; bir şekilde desteklememektedir. Bu g&ouml;zlem ve veriler PGC-1&alpha;&rsquo;nın 3.5 kb&rsquo;lik pregenomik RNA&rsquo;nın sentez d&uuml;zeyinin artırılmasında HBV n&uuml;kleokapsid promotor ile ilişkili transkripsiyonel makineler i&ccedil;in gerekli yeni bir adapt&ouml;r molek&uuml;l olduğuna işaret etmektedir. Transkripsiyon d&uuml;zeyindeki bu değişim Hepatitis B vir&uuml;s kor antijen polipeptid (HBcAg/p21) sentezinin benzer şekilde kısmen artışı ile ilişkili olmasına karşın bu kısmi artış viral replikasyonun daha g&uuml;&ccedil;lenmesi ve viral kapsid sentezinde &ouml;nemli oranda artışa aracılık etmektedir. Sonu&ccedil; olarak, kritik bir d&uuml;zey &uuml;zerindeki sitoplazmik HBcAg/p21 sentezinin HBV replikasyonuna elverişli viral kapsidlerin kurgusu i&ccedil;in gerekli olduğu anlaşılmaktadır &Ouml;NEM: Hepatitis B vir&uuml;s &ouml;nemli bir İnsan patojenidir ve ek terap&ouml;tik ajanların geliştirilmesi i&ccedil;in yeni hedeflere acilen ihtiya&ccedil; bulunmaktadır. Biz burada peroksizom proliferat&ouml;r aktive edici resept&ouml;r gama koaktivat&ouml;r1&alpha;&rsquo;in (PGC-1&alpha;), HBV transkripsiyonunu daha verimli d&uuml;zenleyebilen ek koaktivat&ouml;rleri g&uuml;&ccedil;lendirici &ouml;zg&uuml;n bir adapt&ouml;r molek&uuml;l olarak g&ouml;rev yaptığını g&ouml;sterdik. PGC-1&alpha; tarafından viral RNA d&uuml;zeylerinin bu hassas d&uuml;zenlemenin &ouml;nemi dimer formasyonu y&ouml;n&uuml;ndeki dengeyi viral kapsid kurgusu lehine &ouml;nemli oranda değiştiren HBcAg/p21 polipeptid translasyonunda kritik bir artıştır. Bu bulgu ve veriler gerek PGC-1&alpha; gerekse kapsid kurgusunun kronik HBV enfeksiyonuna karşı antiviral ajanların geliştirilmesi i&ccedil;in dikkate değer hedefler olabileceğini &ouml;nermektedir. Anahtar Kelimeler: PGC-1&alpha;, kapsid kurgusu, hepatitis B vir&uuml;s, transkripsiyonel koaktivat&ouml;rle

Peroxisome proliferator-activated receptor coactivator family members competitively regulate hepatitis b virus biosynthesis

Transcriptional coactivators represent critical components of the transcriptional pre-initiation complex and are required for efficient gene activation. Members of the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family differentially regulate hepatitis b virus (HBV) biosynthesis. Whereas PGC1α has been shown to be a potent activator of HBV biosynthesis, PGC1β only very poorly activates HBV RNA and DNA synthesis in human hepatoma (HepG2) and embryonic kidney (HEK293T) cells. Furthermore, PGC1β inhibits PGC1α-mediated HBV biosynthesis. These observations suggest that a potential competition between human hepatoma (HepG2) and embryonic kidney (HEK293T) cells PGC1α and PGC1β for common transcription factor target(s) may regulate HBV transcription and replication in a context and signal transduction pathway dependent manner

Promising photocatalytic and antimicrobial activity of novel capsaicin coated cobalt ferrite nanocatalyst

Abstract In this study, CoFe2O4 nanoparticles were prepared by the co-precipitation method then surface modified with Capsaicin (Capsicum annuum ssp.). The virgin CoFe2O4 NPs and Capsaicin-coated CoFe2O4 NPs (CPCF NPs) were characterized by XRD, FTIR, SEM, and TEM. The antimicrobial potential and photocatalytic degradation efficiencies of the prepared samples via Fuchsine basic (FB) were investigated. The results revealed that CoFe2O4 NPs have spherical shapes and their diameter varied from 18.0 to 30.0 nm with an average particle size of 25.0 nm. Antimicrobial activity was tested on Gram-positive (S. aureusATCC 52923) and Gram-negative (E. coli ATCC 52922) by disk diffusion and broth dilution methods to determine the zone of inhibition (ZOI) and minimum inhibitory concentration (MIC), respectively. UV-assisted photocatalytic degradation of FB was examined. Various parameters affecting the photocatalytic efficiency such as pH, initial concentration of FB, and dose of nanocatalyst were studied. The in-vitro ZOI and MIC results verified that CPCF NPs were more active upon Gram-Positive S. aureus ATCC 52923 (23.0 mm ZOI and 0.625 μg/ml MIC) than Gram-Negative E. coli ATCC 52922 (17.0 mm ZOI and 1.250 μg/ml MIC). Results obtained from the photocatalytic activity indicated that the maximum FB removal achieving 94.6% in equilibrium was observed using 20.0 mg of CPCF NPS at pH 9.0. The synthesized CPCF NPs were effective in the removal of FB and also as potent antimicrobial agent against both Gram-positive and Gram-negative bacteria with potential medical and environmental applications

Isolation and characterization of three bacteriophages infecting Erwinia amylovora and their potential as biological control agent

Abstract Background Fire Blight, incited by Erwinia amylovora, is one of the most damaging pear and apple diseases in the world. Fire blight was introduced to Egypt in the 1960 and threatens the Egypt’s costs for pear industry. Currently, Phage therapy is considered to be secured biological method for controlling plant bacterial diseases. This investigation aimed to isolate and identify molecularly for bacteria causing fire bright disease. As well as isolation and identification bacteriophages via spot and plaque assay techniques from pear fire blight lesions and soil. On the other hand, bacteriophages were identified based on plaque morphology, virion morphology, physical characters, profile of DNA restriction and protein. Results Pathogenicity test revealed that healthy seedlings and pear fruits were responsive to fire blight E. amylovora. Considering the relatively wide host range and greatest protein and genetic variability, using restriction enzyme pattern, the three diversity phage isolates named, EAP1, EAP2 and EAP3 showed a lack of diversity out of five were fatherly characterized. The phages confirmed the close relation of EAP1, EAP2 to Siphoviridae (hexagonal head and long flexible non-contractile tail) and EAP3 to Myoviridae (icosahedral head and contractile tail). The phages retained higher lytic competence of 90.4; 92.68 and 95.25% for EAP1, EAP2 and EAP3, respectively. The phages were stable at strong alkaline (pH 10) 2% salt solution conditions and UV spectra. While EAP3 phage revealed the hexagonal head and very short tail that belongs to Myoviridae family. Bacteriophages were characterized by digestion of the phage DNA with three restriction endonucleases and were placed into three groups based on the patterns. Bacteriophages were 9 used for reducing bacterial infection populations and severity on pear. In a bioassay, the biocontrol of E. amylovora was evaluated using disks of immature pear fruit. On the pear disk surface, bacterial exudate was considerably suppressed by all phage isolates. According to measurements of the bacterial population still present on the disk surface, phage therapy could reduce it by up to 97%. Bacteriophages reduced pear fire blight disease severity on pear fruit trails. Conclusion The results indicated that bacteriophage isolates may demonstrate variable reactivity against E. amylovora. Bacteriophages reduced pear fire blight disease severity on pear fruit trials. The results indicated that bacteriophage isolates may demonstrate variable reactivity against E. amylovora

Effect of a 12-Week Dietary Intervention with Folic Acid or Folate-Enhanced Foods on Folate Status in Healthy Egyptian Women

The Egyptian government introduced wheat-flour fortification with iron and folic acid to reduce the incidence of neural tube defects, but suspended it for technical reasons. We previously developed novel legume foods with enhanced folate content. In this study, we investigated the efficacy of 12-week intervention with folate-en- hanced foods versus folic acid supplement in improving folate status in Egyptian women. A randomized, parallel intervention trial with two active groups (n = 19, n = 18) and one blinded control group (n = 20) was executed over 12 weeks. Volunteers received either germinated legume foods and orange juice (≈250 μg/d folate) or folic acid supplement (500 μg/d) or apple juice (0 μg/d folate). Folate status was assessed by erythrocyte and plasma folate and total homocysteine (tHcy) at day 0, and after 8 and 12 weeks of intervention. After 12 weeks, mean plasma folate increased by 14 (P &lt; 0.0001) and 12 (P &lt; 0.0001) nmoL in the folic acid and food group, respectively. Erythrocyte folate concentration increased in the folic acid group from 614 to 912 (P &lt; 0.0001) and in the food group from 631 to 914 nmoL (P &lt; 0.0001). After 12 weeks, 90% of subjects in the folic acid group and 70% in the food group had erythrocyte folate concentrations exceeding 906 nmol/L. tHcy concentration was decreased by 20% (P = 0.007) and 18% (P = 0.006) in the folic acid and food group, respectively, but remained unchanged in the control group during intervention. Folate-enhanced foods effectively improve folate status in women of reproductive age. These foods could be used as a complement to folic acid fortification

Hepatic deficiency of the pioneer transcription factor FoxA restricts hepatitis B virus biosynthesis by the developmental regulation of viral DNA methylation.

The FoxA family of pioneer transcription factors regulates hepatitis B virus (HBV) transcription, and hence viral replication. Hepatocyte-specific FoxA-deficiency in the HBV transgenic mouse model of chronic infection prevents the transcription of the viral DNA genome as a result of the failure of the developmentally controlled conversion of 5-methylcytosine residues to cytosine during postnatal hepatic maturation. These observations suggest that pioneer transcription factors such as FoxA, which mark genes for expression at subsequent developmental steps in the cellular differentiation program, mediate their effects by reversing the DNA methylation status of their target genes to permit their ensuing expression when the appropriate tissue-specific transcription factor combinations arise during development. Furthermore, as the FoxA-deficient HBV transgenic mice are viable, the specific developmental timing, abundance and isoform type of pioneer factor expression must permit all essential liver gene expression to occur at a level sufficient to support adequate liver function. This implies that pioneer transcription factors can recognize and mark their target genes in distinct developmental manners dependent upon, at least in part, the concentration and affinity of FoxA for its binding sites within enhancer and promoter regulatory sequence elements. This selective marking of cellular genes for expression by the FoxA pioneer factor compared to HBV may offer the opportunity for the specific silencing of HBV gene expression and hence the resolution of chronic HBV infections which are responsible for approximately one million deaths worldwide annually due to liver cirrhosis and hepatocellular carcinoma