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

Coumarin derivatives as acetyl- and butyrylcholinestrase inhibitors: An in vitro, molecular docking, and molecular dynamics simulations study

Alzheimer's disease is an irreversible and progressive brain disease that can cause problems with memory and thinking skills. It is characterized by loss of cognitive ability and severe behavioral abnormalities, and could lead to death. Cholinesterases (ChEs) play a crucial role in the control of cholinergic transmission, and subsequently, the acetylcholine level in the brain is upgraded by inhibition of ChEs. Coumarins have been shown to display potential cholinesterase inhibitory action, where the aromatic moiety has led to the design of new candidates that could inhibit Aβ aggregation. Accordingly, the present work is an in vitro activity, along with docking and molecular dynamics (MD) simulation studies of synthesized coumarin derivatives, to explore the plausible binding mode of these compounds inside the cholinesterase enzymes. For this purpose, a series of previously prepared N1-(coumarin-7-yl) derivatives were screened in vitro for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. The assayed compounds exhibited moderate inhibitory activity against AChE, with IC50 values ranging from 42.5 ± 2.68 to 442 ± 3.30 μM. On the other hand, the studied compounds showed remarkable activity against BChE with IC50 values ranging from 2.0 ± 1.4 nM to 442 ± 3.30 μM. In order to better understand the ligand binding site interaction of compounds and the stability of protein-ligand complexes, a molecular docking with molecular dynamics simulation of 5000 ps in an explicit solvent system was carried out for both cholinesterases. We concluded that the tested coumarin derivatives are potential candidates as leads for potent and efficacious ChEs inhibitors

Molecular characterization and pathogenicity of Streptococcus agalactiae serotypes Ia ST7 and III ST283 isolated from cultured red hybrid tilapia in Malaysia

Streptococcus agalactiae is one of the most important pathogens infecting tilapia worldwide. In this study, we determined the serotype, sequence type (ST), virulence gene profile and pathogenicity of S. agalactiae isolated from cultured fish. A collection of 256 S. agalactiae that were previously isolated from outbreaks of streptococcosis in red hybrid tilapia in Peninsular Malaysia were studied. The genotype and ST of the isolates were determined by molecular serotyping of the capsular polysaccharide (cps) gene clusters, and multi-locus sequence typing (MLST). The virulence gene profiles were constructed using m-PCR for 14 standard virulence genes with published primers. Two serotypes, with different associated STs, were identified in this study: serotypes Ia ST7 and III ST283. Serotype Ia ST7 lacks lmb, scpB, pavA, fbsB, cyl, bca, cspA and bac genes, which were present in serotype III ST283. The LD50–240h of S. agalactiae in red hybrid tilapia for serotypes Ia ST7 and III ST283 were 8.7 × 103 CFU/mL and 6.3 × 103 CFU/mL, respectively. The histopathological findings were consistent with meningitis, necrosis of hepatocytes, coagulative tubular necrosis and hypocellular of the spleen. Histopathological scores revealed significant differences (p < 0.05) between the two serotypes in all lesions in the brain, liver (except hepato-necrosis) and spleen, but not the kidney. This study revealed that S. agalactiae serotypes Ia ST7 and III ST283 currently exist in cultured tilapia in Malaysia. This molecular epidemiology study could be useful for the future development of cross protective vaccines against streptococcosis in the region

Optimal BMI cut-off values for predicting diabetes, hypertension and hypercholesterolaemia in a multi-ethnic population

Objective To determine the optimal cut-offs of BMI for Malaysian adults. Design Population-based, cross-sectional study. Receiver operating characteristic curves were used to determine the cut-off values of BMI with optimum sensitivity and specificity for the detection of three cardiovascular risk factors: diabetes mellitus, hypertension and hypercholesterolaemia. Gender-specific logistic regression analyses were used to examine the association between BMI and these cardiovascular risk factors. Setting All fourteen states in Malaysia. Subjects Malaysian adults aged ≥18 years (n 32 703) who participated in the Third National Health and Morbidity Survey in 2006. Results The optimal BMI cut-off value for predicting the presence of diabetes mellitus, hypertension, hypercholesterolaemia or at least one of these cardiovascular risk factors varied from 23·3 to 24·1 kg/m 2 for men and from 24·0 to 25·4 kg/m2 for women. In men and women, the odds ratio for having diabetes mellitus, hypertension, hypercholesterolaemia or at least one cardiovascular risk factor increased significantly as BMI cut-off point increased. Conclusions Our findings indicate that BMI cut-offs of 23·0 kg/m2 in men and 24·0 kg/m2 in women are appropriate for classification of overweight. We suggest that these cut-offs can be used by health professionals to identify individuals for cardiovascular risk screening and weight management programmes. © 2012 The Authors

Humic Acid-Coated Fe₃O₄ Nanoparticles Confer Resistance to Acremonium Wilt Disease and Improve Physiological and Morphological Attributes of Grain Sorghum

Acremonium wilt disease affects grain quality and reduces sorghum yield around the globe. The present study aimed to assess the efficacy of humic acid (HA)-coated Fe3O4 (Fe3O4/HA) nanoparticles (NPs) in controlling acremonium wilt disease and improving sorghum growth and yields. During the season 2019, twenty-one sorghum genotypes were screened to assess their response to Acremonium striticum via artificial infection under field conditions and each genotype was assigned to one of six groups, ranging from highly susceptible to highly resistant. Subsequently, over the two successive seasons 2020 and 2021, three different concentrations of 10, 40 and 80 mg L−1 of Fe3O4/HA NPs were tested against A. striticum. The concentrations of 40 and 80 mg L−1 were found to be highly effective in controlling acremonium wilt disease on different sorghum genotypes: LG1 (highly susceptible), Giza-3 (susceptible), and Local 119 (resistant) genotypes. After harvest, the physiological (growth and yield) and biochemical (peroxidase, catalase, and gibberellic acid) attributes of sorghum plants were determined, and the results demonstrated that concentrations of 40 and 80 mg L−1 increased peroxidase and catalase activities in healthy (uninoculated) sorghum genotypes compared to inoculated sorghum genotypes. Additionally, the toxicity of Fe3O4/HA NPs on male albino rats was investigated via hematological (CBC), chemical (ALT and AST) and histopathological analyses. The concentration 80 mg L−1 of Fe3O4/HA NPs caused a marked increase in ALT and creatinine level after 51 days of feeding. Severe pathological alterations were also observed in liver and kidney tissues of rats administered with grain sorghums treated with 80 mg L−1. In comparison with the untreated control plants, a concentration of 40 mg L−1 significantly increased the growth, yield and gibberellic acid levels (p ≤ 0.05) and was found to be safe in male albino rats. Conclusively, a concentration of 40 mg L−1 of Fe3O4/HA NPs showed promising results in curtailing A. striticum infections in sorghum, indicating its great potential to substitute harmful fertilizers and fungicides as a smart agriculture strategy

Optimal waist circumference cut-off values for predicting cardiovascular risk factors in a multi-ethnic Malaysian population

Introduction: Previous studies have proposed the lower waist circumference (WC) cutoffs be used for defining abdominal obesity in Asian populations. Objective: To determine the optimal cut-offs of waist circumference (WC) in predicting cardiovascular (CV) risk factors in the multi-ethnic Malaysian population. Methods: We analysed data from 32,703 respondents (14,980 men and 17,723 women) aged 18 years and above who participated in the Third National Health and Morbidity Survey in 2006. Gender-specific logistic regression analyses were used to examine associations between WC and three CV risk factors (diabetes mellitus, hypertension, and hypercholesterolemia). The Receiver Operating Characteristic (ROC) curves were used to determine the cut-off values of WC with optimum sensitivity and specificity for detecting these CV risk factors. Results: The odds ratio for having diabetes mellitus, hypertension, and hypercholesterolemia, or at least one of these risks, increased significantly as the WC cut-off point increased. Optimal WC cut-off values for predicting the presence of diabetes mellitus, hypertension, hypercholesterolemia and at least one of the three CV risk factors varied from 81.4 to 85.5 cm for men and 79.8 to 80.7 cm for women. Conclusions: Our findings indicate that WC cut-offs of 81 cm for men and 80 cm for women are appropriate for defining abdominal obesity and for recommendation to undergo cardiovascular risk screening and weight management in the Malaysian adult population

Accelerating Novel Candidate Gene Discovery in Neurogenetic Disorders via Whole-Exome Sequencing of Prescreened Multiplex Consanguineous Families

Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function