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

Persistence of IgE-associated allergy and allergen-specific IgE despite CD4+ T cell loss in AIDS

The infection of CD4+ cells by HIV leads to the progressive destruction of CD4+ T lymphocytes and, after a severe reduction of CD4+ cells, to AIDS. The aim of the study was to investigate whether HIV-infected patients with CD4 cell counts <200 cells/µl can suffer from symptoms of IgE-mediated allergy, produce allergen-specific IgE antibody responses and show boosts of allergen-specific IgE production. HIV-infected patients with CD4 counts ≤ 200 cells/µl suffering from AIDS and from IgE-mediated allergy were studied. Allergy was diagnosed according to case history, physical examination, skin prick testing (SPT), and serological analyses including allergen microarrays. HIV infection was confirmed serologically and the disease was staged clinically. The predominant allergic symptoms in the studied patients were acute allergic rhinitis (73%) followed by asthma (27%) due to IgE-mediated mast cell activation whereas no late phase allergic symptoms such as atopic dermatitis, a mainly T cell-mediated skin manifestation, were found in patients suffering from AIDS. According to IgE serology allergies to house dust mites and grass pollen were most common besides IgE sensitizations to various food allergens. Interestingly, pollen allergen-specific IgE antibody levels in the patients with AIDS and in additional ten IgE-sensitized patients with HIV infections and low CD4 counts appeared to be boosted by seasonal allergen exposure and were not associated with CD4 counts. Our results indicate that secondary allergen-specific IgE production and IgE-mediated allergic inflammation do not require a fully functional CD4+ T lymphocyte repertoire

Allergen-specific IgE antibody levels (kUA/L) and CD4 counts in HIV-positive patients with AIDS (#8–11) and in HIV-positive patients with CD4 counts below 200/µl (#12–13).

<p>CD4 counts (right y-axes) and allergen-specific IgE levels (left y-axes) measured in serum samples obtained at different points of time (x-axes) are shown. The usual periods of the grass and tree pollen season is indicated in green and brown, respectively.</p

Allergen-specific IgE antibody levels (kUA/L) and CD4 counts in HIV-positive patients with low CD4 counts (#14–21) for whom sequential serum samples were available.

<p>CD4 counts (right y-axes) and allergen-specific IgE levels (left y-axes) measured in serum samples obtained at different points of time (x-axes) are shown. The usual periods of the grass and tree pollen season is indicated in green and brown, respectively.</p

Demographic, clinical and immunological characterization of ten HIV infected patients with low CD4 counts.

<p>Displayed are age, sex and ranges of CD4 counts for follow-up sera. Allergic symptoms and positive results obtained by skin prick testing and determination of allergen-specific IgE are summarized.</p><p>Abbreviations: F: female; M: male; R: rhinitis; RC: rhinoconjunctivitis; U: urticaria; AB: asthma bronchiale; AP: allergic pharyngitis; SPT: skin prick test; Der p: <i>Dermatophagoides pteronyssinus</i>; n.k.: not known;</p

Monitoring of CD4+ and CD8+ T-cell counts, viral loads and IgG reactivity profiles to HIV-1 clade C-derived proteins and peptides during infection and treatment.

<p>Displayed are percentages of CD4+ T-cells, CD4+ and CD8+ T-cell counts, viral loads and levels of IgG antibodies to HIV-1 clade C-derived proteins and peptides (the box shows color codes of antigens and peptides) over time (top line) for patients with variable antibody reactivity profiles (A: patient #3; B: patient #10; C: patient #12; D: patient #9). Abbreviations: 0, 1^st positive test / 1^st visit; ART, antiretroviral therapy; ART1, ART2 and ART3 denote different ART regimens; y, years; m, months; VL, viral load; n.a., not available; n.d., not done; OD, optical density; Prot., Proteins; MA, matrix; CA, capsid; NC, nucleocapsid; PR, protease; RR, reverse transcriptase+RNAseH; IN, integrase; HSA, human serum albumin.</p

Purity and immunoreactivity of recombinant HIV-1 clade C structural, accessory and <i>pol</i>-derived proteins.

<p>(A) Coomassie-stained SDS-PAGE containing recombinant matrix (MA), capsid (CA), nucleocapsid (NC), NEF, TAT, VIF, protease (PR), reverse transcriptase+RNAseH (RR), integrase (IN) and molecular weight markers (M). Molecular weights (kDa) are indicated on the left. SDS-PAGE analysis of NEF was performed on a separate gel with identical molecular weight marker as for structural and accessory proteins. (B) Frequencies and intensities (y-axes: number of reactive sera; <i>OD</i> levels color-coded) of IgG, IgG subclass, IgA and IgM responses of African (left) and European (right) patients to structural, accessory and <i>pol</i>-derived proteins (x-axes).</p

Surgical site infection after gastrointestinal surgery in children : an international, multicentre, prospective cohort study

Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings. Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI). Results Of 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI. Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.Peer reviewe