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

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Pilot investigation of the circadian plasma melatonin rhythm across the menstrual cycle in a small group of women with premenstrual dysphoric disorder.

Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed

Circadian melatonin profile in controls and PMDD women.

<p>PMDD: premenstrual dysphoric disorder; FP: follicular phase; LP: luteal phase; DLMOn, dim light melatonin onset; DLMOff, dim light melatonin offset; AUC, area under the curve.</p><p>Values are mean ± SEM.</p>a<p>indicates different than controls at the level of P = .05 when LP values compared.</p>b<p>indicates different than PMDD FP at level of P = .03.</p

Circadian melatonin profile during the follicular phase in PMDD women and an expanded group of controls.^†

<p>PMDD: premenstrual dysphoric disorder; FP: follicular phase; DLMOn: dim light melatonin onset; DLMOff: dim light melatonin offset; AUC: area under the curve values are mean ± SEM.</p>†<p>This table presents FP data from the 5 control participants and 5 PMDD participants included in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051929#pone-0051929-t001" target="_blank">Table 1</a>, but the control group is supplemented by data from 3 other young healthy women who were studied under constant conditions in unrelated experiments. This larger group of 8 controls was compared to the 5 PMDD women of the current study during the FP in an attempt to increase sample size and further confirm results from our baseline group comparisons.</p

Circadian variation of plasma melatonin during the follicular and luteal phases in PMDD women and controls.

<p>* indicates significant differences between controls and PMDD women (P<.05). Data are double-plotted for illustration purposes. Values are mean ± SEM.</p

Circadian variation of plasma melatonin during the follicular phase in PMDD women and an expanded group of controls.^†

<p>* indicates significant differences between controls and PMDD women (P<.05). Data are double-plotted for illustration purposes. Values are mean ± SEM. ^† This figure presents FP data from the 5 control participants and 5 PMDD participants included in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051929#pone-0051929-g001" target="_blank">Figure 1</a>, but the control group is supplemented by data from 3 other young healthy women who were studied under constant conditions in unrelated experiments. This larger group of 8 controls was compared to the 5 PMDD women of the current study during the FP in an attempt to increase sample size and further confirm results from our baseline group comparisons.</p

Characteristics of controls and PMDD participants^†.

<p>PMDD: premenstrual dysphoric disorder; BMI: body mass index; FP: follicular phase; LP: luteal phase; VAS-core: mean score of visual analogue scale measures for depression, tension, affective lability and irritability values are mean ± SEM.</p>†<p>Participant characteristics were also included in a related manuscript <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051929#pone.0051929-Shechter3" target="_blank">[26]</a>.</p>a<p>indicates PMDD late-LP value is significantly (P≤.03) different than PMDD FP value and pone.0051929.g003.tifcontrol values in both menstrual phases.</p>b<p>indicates LP values are significantly (P = .025) different than FP values.</p