A systematic review of the impact of psychosocial factors on immunity: Implications for enhancing BCG response against tuberculosis.

Background: Tuberculosis (TB) remains an urgent global public health priority, causing 1.5 million deaths worldwide in 2018. There is evidence that psychosocial factors modulate immune function; however, how this may influence TB risk or BCG vaccine response, and whether this pathway can be modified through social protection, has not been investigated. This paper aims to: a) systematically review evidence of how psychosocial factors influence the expression of biomarkers of immunity, and b) apply this general evidence to propose plausible TB-specific pathways for future study. Methods: Papers reporting on the impact of psychosocial stressors on immune biomarkers in relation to infectious disease risk were identified through a search of the databases MEDLINE, PsycINFO, Global Health and PsycEXTRA alongside reference list and citation searching of key papers. Data extraction and critical appraisal were carried out using a standardised form. The findings were tabulated and synthesised narratively by infectious disease category, and used to propose plausible mechanisms for how psychosocial exposures might influence immune outcomes relevant to TB and BCG response. Results: 27,026 citations were identified, of which 51 met the inclusion criteria. The literature provides evidence of a relationship between psychosocial factors and immune biomarkers. While the direction and strength of associations is heterogenous, some overarching patterns emerged: adverse psychosocial factors (e.g. stress) were generally associated with compromised vaccine response and higher antibody titres to herpesviruses, and vice versa for positive psychosocial factors (e.g. social support). Conclusions: The evidence identifies pathways linking psychosocial factors and immune response: co-viral infection and immune suppression, both of which are potentially relevant to TB and BCG response. However, the heterogeneity in the strength and nature of the impact of psychosocial factors on immune function, and lack of research on the implications of this relationship for TB, underscore the need for TB-specific research

Access to healthcare for people seeking and refused asylum in Great Britain: a review of evidence

This research report is a review of evidence looking at the barriers people seeking or refused asylum face in trying to access healthcare services in the UK, and what may help them to do so more easily. This report, and the partner report on lived experiences (https://www.equalityhumanrights.com/en/publication-download/lived-experiences-access-healthcare-people-seeking-and-refused-asylum), will be of interest to people who play an important role in delivering healthcare and related support services to people seeking or refused asylum. We have also made recommendations for what changes are needed (https://www.equalityhumanrights.com/en/publication-download/making-sure-people-seeking-and-refused-asylum-can-access-healthcare-what-needs) to make sure that people seeking and refused asylum have full enjoyment of their right to health. This review was carried out by Imperial College London, with primary data provided by Doctors of the World UK

The lived experiences of access to healthcare for people seeking and refused asylum

This research aims to explore the lived experiences of accessing healthcare among people currently seeking asylum and those who have had their claim for asylum refused, as well as the experiences of health service providers working with these communities. It examines the extent to which people are able to exercise their rights to access healthcare. It looks at the differences between those currently in the asylum system and those who have had their claim refused in England, Scotland and Wales. This report, and the partner report providing a review of evidence (https://www.equalityhumanrights.com/en/publication-download/access-healthcare-people-seeking-and-refused-asylum-great-britain-review), will be of interest to people who play an important role in delivering healthcare and related support services to people seeking or refused asylum. We have also made recommendations for what changes are needed (https://www.equalityhumanrights.com/en/publication-download/making-sure-people-seeking-and-refused-asylum-can-access-healthcare-what-needs) to make sure that people seeking and refused asylum have full enjoyment of their right to health. This report was produced in collaboration with Imperial College London and Doctors of the World UK

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

Identifying research questions for HIV, tuberculosis, tuberculosis-HIV, malaria, and neglected tropical diseases through the World Health Organization guideline development process: a retrospective analysis, 2008-2018.

OBJECTIVES: World Health Organization (WHO) guidelines for health programmes and healthcare delivery are the foundation of its technical leadership in public health and essential to decision-making globally. A key function of guideline development is to identify areas in which further evidence is needed because filling these gaps will lead to future improvements in population health. The objective of this study was to examine the knowledge gaps and research questions for addressing those gaps generated through the WHO guideline development process, with the goal of informing future strategies for improving and strengthening the guideline development process. STUDY DESIGN: We did a systematic, retrospective analysis of research questions identified in the published guidelines. METHODS: We analyzed guidelines published between January 1, 2008, and December 31, 2018, by the Communicable Diseases Cluster in five disease areas: tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases (NTDs). Research questions were extracted independently by two researchers. We analyzed the distribution of research questions by disease and by topic category and did a qualitative assessment of optimum practice for research question generation during the guideline development process. RESULTS: A total of 48 guidelines were included: 26 on HIV, 1 on malaria, 11 on TB, 5 on TB/HIV, and 5 on NTDs. Overall, 36 (75%) guidelines encompassed a total of 360 explicit research questions; the remainder did not contain specific research questions. The number of research questions that focused on TB was 49, TB/HIV was 38, HIV was 250, and NTDs was 23. The number of research questions that focused on diagnosis was 43 (11.9%) of 360, prevention was 62 (17.2%), treatment was 103 (28.6%), good practice was 12 (3.3%), service delivery was 86 (23.8%), and other areas was 54 (15%). Research questions were often not formulated in a specific or actionable way and were hard to identify in the guideline. Examples of good practice identified by the review team involved the generation of specific and narrowly defined research questions, with accompanying recommendations for appropriate study design. CONCLUSIONS: The WHO must strengthen its approach to identifying and presenting research questions during the guideline development process. Ensuring access to research questions is a key next step in adding value to the guideline development process

Global patterns of mortality in international migrants: a systematic review and meta-analysis.

BACKGROUND: 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. FINDINGS: Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15·2 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0·70 [95% CI 0·65-0·76]; I2=99·8%). All-cause SMR was lower in both male migrants (0·72 [0·63-0·81]; I2=99·8%) and female migrants (0·75 [0·67-0·84]; I2=99·8%) compared with the general population. A mortality advantage was evident for refugees (SMR 0·50 [0·46-0·54]; I2=89·8%), but not for asylum seekers (1·05 [0·89-1·24]; I2=54·4%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. INTERPRETATION: Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. FUNDING: Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants

Delivering multi-disease screening to migrants for latent TB and blood-borne viruses in an emergency department setting: A feasibility study.

BACKGROUND: Screening for latent tuberculosis infection (LTBI) in migrants is important for elimination of tuberculosis in low-incidence countries, alongside the need to detect blood-borne infections to align with new guidelines on migrant screening for multiple infections in European countries. However, feasibility needs to be better understood. METHODS: We did a feasibility study to test an innovative screening model offering combined testing for LTBI (QuantiFERON), HIV, hepatitis B/C in a UK emergency department, with two year follow-up. RESULTS: 96 economic migrants, asylum seekers and refugees from 43 countries were screened (46 [47.9%] women; mean age 35.2 years [SD 11.7; range 18-73]; mean time in the UK 4.8 years [SD 3.2; range 0-10]). 14 migrants (14.6%) tested positive for LTBI alongside HIV [1], hepatitis B [2], and hepatitis C [1] Of migrants with LTBI, 5 (35.7%) were successfully engaged in treatment. 74 (77.1%) migrants reported no previous screening since migrating to the UK. CONCLUSION: Multi-disease screening in this setting is feasible and merits being further tested in larger-scale studies. However, greater emphasis must be placed on ensuring successful treatment outcomes. We identified major gaps in current screening provision; most migrants had been offered no prior screening despite several years since migration, which holds relevance to policy and practice in the UK and other European countries

Do Quality Improvement Initiatives Improve Outcomes for Patients in Antiretroviral Programs in Low- and Middle-Income Countries? A Systematic Review.

BACKGROUND: There have been a range of quality improvement (QI) and quality assurance initiatives in low- and middle-income countries to improve antiretroviral therapy (ART) treatment outcomes for people living with HIV. To date, these initiatives have not been systematically assessed and little is known about how effective, cost-effective, or sustainable these strategies are in improving clinical outcomes. METHODS: We conducted a systematic review adhering to PRISMA guidelines (PROSPERO ID: CRD42017071848), searching PubMed, MEDLINE, Embase, Web of Science, and the Cochrane database of controlled trials for articles reporting on the effectiveness of QI and quality assurance initiatives in HIV programs in low- and middle-income countries in relation to ART uptake, retention in care, adherence, viral load suppression, mortality, and other outcomes including cost-effectiveness and long-term sustainability. RESULTS: One thousand eight hundred sixty articles were found, of which 29 were included. QI approaches were categorized as follows: (1) health system approaches using QI methods; (2) QI learning networks including collaboratives; (3) standard-based methods that use QI tools to improve performance gaps; and (4) campaigns using QI methods. The greatest improvements were seen in ART uptake [median increase of 14.0%; interquartile range (IQR) -9.0 to 29.3], adherence [median increase of 22.0% (IQR -7.0 to 25.0)], and viral load suppression [median increase 26.0% (IQR -8.0 to 26.0)]. CONCLUSIONS: QI interventions can be effective in improving clinical outcomes; however, there was significant variability, making it challenging to identify which aspects of interventions lead to clinical improvements. Standardizing reporting and assessment of QI initiatives is needed, supported by national quality policies and directorates, and robust research