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Background: Ensuring vaccination coverage reaches established herd immunity thresholds (HITs) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPDs) and outbreaks, yet it is not clear to what extent they are an under-immunized group., Methods: We did a systematic review and meta-analysis to synthesize peer-reviewed published primary research reporting data on the immune status of migrants in EU/EEA countries, the UK and Switzerland, calculating their pooled immunity coverage for measles, mumps, rubella and diphtheria using random-effects models. We searched on Web of Science, Embase, Global Health and MEDLINE (1 January 2000 to 10 June 2022), with no language restrictions. The protocol is registered with PROSPERO (CRD42018103666)., Findings: Of 1103 abstracts screened, 62 met eligibility criteria, of which 39 were included in the meta-analysis. The meta-analysis included 75 089 migrants, predominantly from outside Europe. Pooled immunity coverage among migrant populations was well below the recommended HIT for diphtheria (n = 7, 57.4% [95% confidence interval (CI): 43.1-71.7%] I2 = 99% vs HIT 83-86%), measles (n = 21, 83.7% [95% CI: 79.2-88.2] I2 = 99% vs HIT 93-95%) and mumps (n = 8, 67.1% [95% CI: 50.6-83.6] I2 = 99% vs HIT 88-93%) and midway for rubella (n = 29, 85.6% [95% CI: 83.1-88.1%] I2 = 99% vs HIT 83-94%), with high heterogeneity across studies., Interpretation: Migrants in Europe are an under-immunized group for a range of important VPDs, with this study reinforcing the importance of engaging children, adolescents and adults in 'catch-up' vaccination initiatives on arrival for vaccines, doses and boosters they may have missed in their home countries. Co-designing strategies to strengthen catch-up vaccination across the life course in under-immunized groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity., (© International Society of Travel Medicine 2024. Published by Oxford University Press.)

Introduction: The Middle East and North African (MENA) region is characterised by high and complex migration flows, yet little is known about the health of migrant populations, their levels of underimmunisation and access to healthcare provision. Data are needed to support regional elimination and control targets for key diseases and the design and delivery of programmes to improve health outcomes in these groups. This protocol describes a suite of seven systematic reviews that aim to identify, appraise and synthesise the available evidence on the burden and health outcomes, policies and access (barriers and facilitators) related to these mobile populations in the region., Methods: Seven systematic reviews will cover three questions to explore the: (1) burden and health outcomes, (2) policies and (3) healthcare barriers and facilitators for the following seven disease areas in migrants in the MENA region: tuberculosis, HIV and hepatitis B and C, malaria and neglected tropical diseases, diabetes, mental health, maternal and neonatal health, and vaccine-preventable diseases. We will search electronic databases for studies in any language (year 2000-2023), reference-check relevant publications and cross-check included studies with experts. We will search for grey literature by hand searching key databases and websites (including regional organisations and MoH websites) for country-specific guidelines and talking to our network of experts for local and regional reports and key datasets. We will assess the studies and policies for their quality using appropriate tools. We will meta-analyse the data by disease outcome if they are of sufficient volume and similarity. Where meta-analysis is not possible and where data are on policy or access, we will narratively synthesise the evidence using summary tables, figures and text., Dissemination: We anticipate disseminating the findings through peer-reviewed publications, conferences and other formats relevant to all stakeholders. We are following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and protocols will be registered on International Prospective Register of Systematic Reviews., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Double malnutrition (co-existing overnutrition and undernutrition) is increasingly prevalent in sub-Saharan Africa due to rapid epidemiological and nutritional transitions. In this region, studies of double malnutrition have largely been conducted at country and household level, with individual-level studies primarily limited to children and women of reproductive age. We investigated the prevalence and determinants of individual-level double malnutrition in middle-aged and older adults who constitute an increasing proportion of the sub-Saharan African population., Methods: 250 individuals aged 40-70 years (50% women) and resident in the Agincourt Health and socio-Demographic Surveillance System in rural Mpumalanga province, South Africa, were randomly selected. Double malnutrition was defined as overweight/obesity and anaemia only, overweight/obesity and iodine insufficiency, or overweight/obesity and any micronutrient deficiency (anaemia and/or iodine insufficiency). The Chi-squared goodness of fit test was used to compare the expected and observed numbers of individuals with the type of double malnutrition. Logistic regression was used to investigate determinants of each type of double malnutrition., Results: Double malnutrition was present in 22-36% of participants, depending on the definition used. All types of double malnutrition were more common in women than in men (overweight/obesity and anaemia: 34% vs. 10.2%, p < 0.01; overweight/obesity and iodine insufficiency: 32% vs. 12.2%, p < 0.01 and overweight/obesity and any micronutrient deficiency: 50.5% vs. 20.4%, p < 0.01). There were no differences between the overall expected and observed numbers of individuals with combinations of overweight and micronutrient deficiencies [overweight/obesity and anaemia (p = 0.28), overweight/obesity and iodine insufficiency (p = 0.27) or overweight/obesity and any micronutrient deficiency (p = 0.99)]. In models adjusted for socio-demographic factors, HIV and antiretroviral drug status, and food security or dietary diversity, men were 84-85% less likely than women to have overweight/obesity and anaemia, 65% less likely to have overweight/obesity and iodine insufficiency and 74% less likely to have overweight/obesity and any micronutrient deficiency., Conclusions: Individual-level double malnutrition is prevalent in middle-aged and older adults in a rural sub-Saharan African community. Interventions to improve nutrition in similar settings should target individuals throughout the life course and a focus on women may be warranted., (© 2024. The Author(s).)

Adult and adolescent migrants worldwide, and those arriving in Europe, are an under-immunised group for routine vaccinations due to missed childhood vaccines and doses in their countries of origin, and their subsequent marginalisation from health and vaccination systems. Declining population-level coverage for routine vaccines across Europe, which has accelerated post-pandemic, places these and other under-immunised populations at even greater risk of vaccine-preventable diseases. However, despite clear guidelines around the importance of delivering 'catch-up' vaccination throughout the life-course, migrants are rarely effectively incorporated into routine vaccination programmes on arrival to Europe. These populations have subsequently been involved in outbreaks, including measles and diphtheria, and are missing opportunities to receive more recently introduced vaccines such as HPV to align them with European vaccine schedules. WHO's new Immunization Agenda 2030 places a renewed emphasis on equitable access to vaccine systems and integrating catch-up vaccination for missed vaccines and doses throughout the life-course. In addition, lessons learned and innovations from the COVID-19 pandemic merit further consideration in the design and delivery of more inclusive vaccination programmes. We describe current gaps in policy and practice around life-course vaccination in migrant populations, key factors that drive low vaccine uptake and coverage, and explore the benefits of participatory approaches to designing and delivering interventions with impacted communities, to define new strategies to advance vaccine equity across the Region., Competing Interests: All authors declare no conflicts of interest., (© 2023 The Author(s).)

Antibodies are essential research tools whose performance directly impacts research conclusions and reproducibility. Owing to its central role in Alzheimer's disease and other dementias, hundreds of distinct antibody clones have been developed against the microtubule-associated protein Tau and its multiple proteoforms. Despite this breadth of offer, limited understanding of their performance and poor antibody selectivity have hindered research progress. Here, we validate a large panel of Tau antibodies by Western blot (79 reagents) and immunohistochemistry (35 reagents). We address the reagents' ability to detect the target proteoform, selectivity, the impact of protein phosphorylation on antibody binding and performance in human brain samples. While most antibodies detected Tau at high levels, many failed to detect it at lower, endogenous levels. By WB, non-selective binding to other proteins affected over half of the antibodies tested, with several cross-reacting with the related MAP2 protein, whereas the "oligomeric Tau" T22 antibody reacted with monomeric Tau by WB, thus calling into question its specificity to Tau oligomers. Despite the presumption that "total" Tau antibodies are agnostic to post-translational modifications, we found that phosphorylation partially inhibits binding for many such antibodies, including the popular Tau-5 clone. We further combine high-sensitivity reagents, mass-spectrometry proteomics and cDNA sequencing to demonstrate that presumptive Tau "knockout" human cells continue to express residual protein arising through exon skipping, providing evidence of previously unappreciated gene plasticity. Finally, probing of human brain samples with a large panel of antibodies revealed the presence of C-term-truncated versions of all main Tau brain isoforms in both control and tauopathy donors. Ultimately, we identify a validated panel of Tau antibodies that can be employed in Western blotting and/or immunohistochemistry to reliably detect even low levels of Tau expression with high selectivity. This work represents an extensive resource that will enable the re-interpretation of published data, improve reproducibility in Tau research, and overall accelerate scientific progress., (© 2024. The Author(s).)

Introduction: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa., Methods: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data., Results: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10)., Conclusion: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The World Health Organization's (WHO) Immunization Agenda 2030 emphasises ensuring equitable access to vaccination across the life course. This includes placing an emphasis on migrant populations who may have missed key childhood vaccines, doses, and boosters due to disrupted healthcare systems and the migration process, or differing vaccination schedules in home countries. Guidelines exist in the UK for offering catch-up vaccinations to adolscent and adult migrants with incomplete or uncertain vaccination status (including MMR, Td-IPV, MenACWY, HPV), but emerging evidence suggests awareness and implementation in primary care is poor. It is unclear whether patient-level barriers to uptake of catch-up vaccinations also exist. We explored experiences and views around catch-up vaccination among adult migrants from a range of backgrounds, to define strategies for improving catch-up vaccination policy and practice., Methods: In-depth semi-structured interviews were carried out in two phases with adult migrant populations (refugees, asylum seekers, undocumented migrants, those with no recourse to public funds) on views and experiences around vaccination, involving a team of peer researchers from specific migrant communities trained through the study. In Phase 1, we conducted remote interviews with migrants resident in the UK for < 10 years, from diverse backgrounds. In Phase 2, we engaged specifically Congolese and Angolan migrants as part of a community-based participatory study. Topic guides were developed iteratively and piloted. Participants were recruited using purposive, opportunistic and snowball sampling methods. Interviews were conducted in English (interpreters offered), Lingala or French and were audio-recorded, transcribed and analysed using a thematic framework approach in NVivo 12., Results: 71 participants (39 in Phase 1, 32 in Phase 2) were interviewed (Mean age 43.6 [SD:12.4] years, 69% female, mean 9.5 [SD:7] years in the UK). Aside from COVID-19 vaccines, most participants reported never having been offered vaccinations or asked about their vaccination history since arriving in the UK as adults. Few participants mentioned being offered specific catch-up vaccines (e.g. MMR/Td-IPV) when attending a healthcare facility on arrival in the UK. Vaccines such as flu vaccines, pregnancy-related or pre-travel vaccination were more commonly mentioned. In general, participants were not aware of adult catch-up vaccination but regarded it positively when it was explained. A few participants expressed concerns about side-effects, risks/inconveniences associated with access (e.g. links to immigration authorities, travel costs), preference for natural remedies, and hesitancy to engage in further vaccination campaigns due to the intensity of COVID-19 vaccination campaigns. Trust was a major factor in vaccination decisions, with distinctions noted within and between groups; some held a healthcare professional's recommendation in high regard, while others were less trusting towards the healthcare system because of negative experiences of the NHS and past experiences of discrimination, injustice and marginalisation by wider authorities., Conclusions: The major barrier to adult catch-up vaccination for missed routine immunisations and doses in migrant communities in the UK is the limited opportunities, recommendations or tailored vaccination information presented to migrants by health services. This could be improved with financial incentives for provision of catch-up vaccination in UK primary care, alongside training of healthcare professionals to support catch-up immunisation and raise awareness of existing guidelines. It will also be essential to address root causes of mistrust around vaccination, where it exists among migrants, by working closely with communities to understand their needs and meaningfully involving migrant populations in co-producing tailored information campaigns and culturally relevant interventions to improve coverage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sally Hargreaves, Alison Crawshaw reports financial support was provided by National Institute of Health Research (NIHR). Anna Deal, Sally Hayward reports financial support was provided by UKRI Medical Research Council. Sally Hargreaves reports financial support was provided by Academy of Medical Sciences. Sandra Mounier-Jack reports financial support was provided by National Institute for Health Research Health Protection Research Unit in Vaccines and Immunisation. Azeem Majeed reports financial support was provided by NIHR Applied Research Collaboration NW London. Azeem Majeed reports financial support was provided by NIHR Biomedical Research Centre. Oumnia Bouaddi reports financial support was provided by La Caixa., (Copyright © 2024 The Authors. Published by Elsevier India Pvt Ltd. All rights reserved.)

Background: Migrants in the UK and Europe face vulnerability to vaccine-preventable diseases (VPDs) due to missed childhood vaccines and doses and marginalisation from health systems. Ensuring migrants receive catch-up vaccinations, including MMR, Td/IPV, MenACWY, and HPV, is essential to align them with UK and European vaccination schedules and ultimately reduce morbidity and mortality. However, recent evidence highlights poor awareness and implementation of catch-up vaccination guidelines by UK primary care staff, requiring novel approaches to strengthen the primary care pathway., Methods: The 'Vacc on Track' study (May 2021-September 2022) aimed to measure under-vaccination rates among migrants in UK primary care and establish new referral pathways for catch-up vaccination. Participants included migrants aged 16 or older, born outside of Western Europe, North America, Australia, or New Zealand, in two London boroughs. Quantitative data on vaccination history, referral, uptake, and sociodemographic factors were collected, with practice nurses prompted to deliver catch-up vaccinations following UK guidelines. Focus group discussions and in-depth interviews with staff and migrants explored views on delivering catch-up vaccination, including barriers, facilitators, and opportunities. Data were analysed using STATA12 and NVivo 12., Results: Results from 57 migrants presenting to study sites from 18 countries (mean age 41 [SD 7.2] years; 62% female; mean 11.3 [SD 9.1] years in UK) over a minimum of 6 months of follow-up revealed significant catch-up vaccination needs, particularly for MMR (49 [86%] required catch-up vaccination) and Td/IPV (50 [88%]). Fifty-three (93%) participants were referred for any catch-up vaccination, but completion of courses was low (6 [12%] for Td/IPV and 33 [64%] for MMR), suggesting individual and systemic barriers. Qualitative in-depth interviews (n = 39) with adult migrants highlighted the lack of systems currently in place in the UK to offer catch-up vaccination to migrants on arrival and the need for health-care provider skills and knowledge of catch-up vaccination to be improved. Focus group discussions and interviews with practice staff (n = 32) identified limited appointment/follow-up time, staff knowledge gaps, inadequate engagement routes, and low incentivisation as challenges that will need to be addressed. However, they underscored the potential of staff champions, trust-building mechanisms, and community-based approaches to strengthen catch-up vaccination uptake among migrants., Conclusions: Given the significant catch-up vaccination needs of migrants in our sample, and the current barriers to driving uptake identified, our findings suggest it will be important to explore this public health issue further, potentially through a larger study or trial. Strengthening existing pathways, staff capacity and knowledge in primary care, alongside implementing new strategies centred on cultural competence and building trust with migrant communities will be important focus areas., (© 2024. The Author(s).)

Throughout pregnancy, some degree of insulin resistance is necessary to divert glucose towards the developing foetus. In gestational diabetes mellitus (GDM), insulin resistance is exacerbated in combination with insulin deficiency, causing new-onset maternal hyperglycaemia. The rapid reversal of insulin resistance following delivery strongly implicates the placenta in GDM pathogenesis. In this case-control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal-fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38-40 weeks. Medium/large (m/l) and small (s) STBEVs were isolated from GDM (n = 4) and normal (n = 5) placentae using ex vivo dual-lobe perfusion and subjected to mass spectrometry. Bioinformatics were used to identify differentially carried proteins and mechanistic pathways. In m/lSTBEVs, 56 proteins were differently expressed while in sSTBEVs, no proteins reached statistical difference. Differences were also observed in the proteomic cargo between m/lSTBEVs and sSTBEVs, indicating that the two subtypes of STBEVs may have divergent modes of action and downstream effects. In silico functional enrichment analysis of differentially expressed proteins in m/lSTBEVs from GDM and normal pregnancy found positive regulation of cytoskeleton organisation as the most significantly enriched biological process. This work presents the first comparison of two populations of STBEVs' protein cargos (m/l and sSTBEVs) from GDM and normal pregnancy isolated using placenta perfusion. Further investigation of differentially expressed proteins may contribute to an understanding of GDM pathogenesis and the development of novel diagnostic and therapeutic tools.

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). In addition, CKD itself is a coronary artery disease equivalent due to its atherogenic potential. Despite the role of CKD in ASCVD and recommendations to control lipid levels aggressively, landmark lipid studies have often excluded patients with advanced CKD. Furthermore, there is a scarcity of data on the use and efficacy of lipid-lowering therapy (LLT) in those with CKD in South Africa (SA)., Objectives: To determine the prevalence and control of dyslipidaemia in a cohort of SA patients with CKD., Methods: A retrospective, cross-sectional observational study of 250 patients with CKD attending the Charlotte Maxeke Johannesburg Academic Hospital renal clinic from 1 July 2019 to 31 July 2020 was carried out. Lipograms, the use of LLT and achievement of target lipid levels were examined., Results: The median (interquartile range) age of this cohort was 58 (46 - 69) years; 50.4% were males and 64.4% black African. Dyslipidaemia was prevalent in 83.6% (n=209) of patients. A total of 169 (67.6%) patients were on LLT, and of these only 28 (16.6%) achieved the recommended low-density lipoprotein cholesterol (LDL-C) target. Of those not on LLT, 51 (63%) were eligible for LLT and almost all were classified as either very high risk (64.2%) or high risk (28.4%) for ASCVD. Of those on LLT, all were on statin therapy, of which simvastatin at a mean dose of 20 mg daily was the most commonly prescribed LLT., Conclusion: This cohort comprised a large proportion of patients classified as high or very high risk for ASCVD. Despite this, the use of LLT was inadequate, and <20% of patients were at target LDL-C levels. These data suggest a greater need for awareness of initiating LLT to achieve recommended target LDL-C levels in patients with CKD.

Background: Migrants in Europe face a disproportionate burden of undiagnosed infection, including tuberculosis, blood-borne viruses, and parasitic infections and many belong to an under-immunised group. The European Centre for Disease Control (ECDC) has called for innovative strategies to deliver integrated multi-disease screening to migrants within primary care, yet this is poorly implemented in the UK. We did an in-depth qualitative study to understand current practice, barriers and solutions to infectious disease screening in primary care, and to seek feedback on a collaboratively developed digitalised integrated clinical decision-making tool called Health Catch UP!, which supports multi-infection screening for migrant patients., Methods: Two-phase qualitative study of UK primary healthcare professionals, in-depth semi-structured telephone-interviews were conducted. In Phase A, we conducted interviews with clinical staff (general practitioners (GPs), nurses, health-care-assistants (HCAs)); these informed data collection and analysis for phase B (administrative staff). Data were analysed iteratively, using thematic analysis., Results: In phase A, 48 clinicians were recruited (25 GPs, 15 nurses, seven HCAs, one pharmacist) and 16 administrative staff (11 Practice-Managers, five receptionists) in phase B. Respondents were positive about primary care's ability to effectively deliver infectious disease screening. However, we found current infectious disease screening lacks a standardised approach and many practices have no system for screening meaning migrant patients are not always receiving evidence-based care (i.e., NICE/ECDC/UKHSA screening guidelines). Barriers to screening were reported at patient, staff, and system-levels. Respondents reported poor implementation of existing screening initiatives (e.g., regional latent TB screening) citing overly complex pathways that required extensive administrative/clinical time and lacked financial/expert support. Solutions included patient/staff infectious disease champions, targeted training and specialist support, simplified care pathways for screening and management of positive results, and financial incentivisation. Participants responded positively to Health Catch-UP!, stating it would systematically integrate data and support clinical decision-making, increase knowledge, reduce missed screening opportunities, and normalisation of primary care-based infectious disease screening for migrants., Conclusions: Our results suggest that implementation of infectious disease screening in migrant populations is not comprehensively done in UK primary care. Primary health care professionals support the concept of innovative digital tools like Health Catch-UP! and that they could significantly improve disease detection and effective implementation of screening guidance but that they require robust testing and resourcing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Objectives: To systematically review the accuracy of artificial intelligence (AI)-based systems for grading of fundus images in diabetic retinopathy (DR) screening., Methods: We searched MEDLINE, EMBASE, the Cochrane Library and the ClinicalTrials.gov from 1st January 2000 to 27th August 2021. Accuracy studies published in English were included if they met the pre-specified inclusion criteria. Selection of studies for inclusion, data extraction and quality assessment were conducted by one author with a second reviewer independently screening and checking 20% of titles. Results were analysed narratively., Results: Forty-three studies evaluating 15 deep learning (DL) and 4 machine learning (ML) systems were included. Nine systems were evaluated in a single study each. Most studies were judged to be at high or unclear risk of bias in at least one QUADAS-2 domain. Sensitivity for referable DR and higher grades was ≥85% while specificity varied and was <80% for all ML systems and in 6/31 studies evaluating DL systems. Studies reported high accuracy for detection of ungradable images, but the latter were analysed and reported inconsistently. Seven studies reported that AI was more sensitive but less specific than human graders., Conclusions: AI-based systems are more sensitive than human graders and could be safe to use in clinical practice but have variable specificity. However, for many systems evidence is limited, at high risk of bias and may not generalise across settings. Therefore, pre-implementation assessment in the target clinical pathway is essential to obtain reliable and applicable accuracy estimates.

Newborn bloodspot screening (NBS) policy is a contentious area in Europe. Variation in the screening panels on offer, in the approach to evidence assessment and in the use of health economic modelling are some of the issues which are debated on the topic. In this paper we focus on a set of patient-driven principles for newborn screening published by EURORDIS and use these as a reference point for exploration and comparison with NBS policy development and screening practice in the UK. In doing so, we share UK practice; we note the UK is generally well aligned with many of the recommended principles, but we also discuss areas of controversy and challenges. Some of these, like 'actionability', will undoubtedly continue to be debated and may never reach consensus. For others, such as patient and public voice participation in newborn screening systems, there are opportunities to continue improving existing processes and developing new mechanisms for stakeholder participation. Screening bodies in other European countries should also compare their policy-making and implementation practices with the EURORDIS principles to stimulate further discussion on the challenges and opportunities of newborn screening and provide a cross-European baseline., Competing Interests: All authors have completed the ICMJE disclosure form at https://www.thelancet.com/for-authors/forms?section=icmje-coi and declare: SL and JM are employed by the UK National Screening Committee (UKNSC), hosted at the Department of Health and Social Care (DHSC); FS was employed by the UKNSC until October 2022 and she is currently employed by St George's University of London (SGUL); DE is employed by Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH), he has also honorary contracts with NHS England (NHSE) and DHSC to provide advice on matters relating to newborn screening and he is currently the Chair of the UKNSC Bloodspot Task Group; no other relationships or activities that could appear to have influenced the submitted work. The views expressed are those of the author(s) and not necessarily those of the UKNSC, DHSC, SGUL, NHSE or GOSH., (© 2023 The Authors.)

Background: Group B Streptococcus (GBS) can cause invasive disease (iGBS) in young infants, typically presenting as sepsis or meningitis, and is also associated with stillbirth and preterm birth. GBS vaccines are under development, but their potential health impact and cost-effectiveness have not been assessed globally., Methods and Findings: We assessed the health impact and value (using net monetary benefit (NMB), which measures both health and economic effects of vaccination into monetary units) of GBS maternal vaccination in an annual cohort of 140 million pregnant women across 183 countries in 2020. Our analysis uses a decision tree model, incorporating risks of GBS-related health outcomes from an existing Bayesian disease burden model. We extrapolated country-specific GBS-related healthcare costs using data from a previous systematic review and calculated quality-adjusted life years (QALYs) lost due to infant mortality and long-term disability. We assumed 80% vaccine efficacy against iGBS and stillbirth, following the WHO Preferred Product Characteristics, and coverage based on the proportion of pregnant women receiving at least 4 antenatal visits. One dose was assumed to cost $50 in high-income countries, $15 in upper-middle income countries, and $3.50 in low-/lower-middle-income countries. We estimated NMB using alternative normative assumptions that may be adopted by policymakers. Vaccinating pregnant women could avert 127,000 (95% uncertainty range 63,300 to 248,000) early-onset and 87,300 (38,100 to 209,000) late-onset infant iGBS cases, 31,100 deaths (14,400 to 66,400), 17,900 (6,380 to 49,900) cases of moderate and severe neurodevelopmental impairment, and 23,000 (10,000 to 56,400) stillbirths. A vaccine effective against GBS-associated prematurity might also avert 185,000 (13,500 to 407,000) preterm births. Globally, a 1-dose vaccine programme could cost $1.7 billion but save $385 million in healthcare costs. Estimated global NMB ranged from $1.1 billion ($-0.2 to 3.8 billion) under the least favourable normative assumptions to $17 billion ($9.1 to 31 billion) under the most favourable normative assumptions. The main limitation of our analysis was the scarcity of data to inform some of the model parameters such as those governing health-related quality of life and long-term costs from disability, and how these parameters may vary across country contexts., Conclusions: In this study, we found that maternal GBS vaccination could have a large impact on infant morbidity and mortality. Globally, a GBS maternal vaccine at reasonable prices is likely to be a cost-effective intervention., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: FS is employed by the UK NSC which developed the policy recommendation for maternal GBS screening. RH is member of the World Health Organisation., (Copyright: © 2023 Procter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rigorous evaluation of artificial intelligence (AI) systems for image classification is essential before deployment into health-care settings, such as screening programmes, so that adoption is effective and safe. A key step in the evaluation process is the external validation of diagnostic performance using a test set of images. We conducted a rapid literature review on methods to develop test sets, published from 2012 to 2020, in English. Using thematic analysis, we mapped themes and coded the principles using the Population, Intervention, and Comparator or Reference standard, Outcome, and Study design framework. A group of screening and AI experts assessed the evidence-based principles for completeness and provided further considerations. From the final 15 principles recommended here, five affect population, one intervention, two comparator, one reference standard, and one both reference standard and comparator. Finally, four are appliable to outcome and one to study design. Principles from the literature were useful to address biases from AI; however, they did not account for screening specific biases, which we now incorporate. The principles set out here should be used to support the development and use of test sets for studies that assess the accuracy of AI within screening programmes, to ensure they are fit for purpose and minimise bias., Competing Interests: Declaration of interests BG reports receiving stock options given for a role as scientific adviser for Kheiron Medical Technologies outside the submitted work. FSe and GK were employed by the UK National Screening Committee, that was hosted by Public Health England, during the conduct of this study. ST-P has received funding from the UK National Institute for Health Research in the form of a development fellowship payment to her institution for a broad group of work in evaluating screening tests. SH is the Chair of the UK National Screening Committee Artificial Intelligence Task Group, which received institutional funding from the National Institute for Health and Care Research biomedical research centre. LW is a member of the Optimam Steering Group. AC declares reimbursement for paid consultancy from Paige AI outside the submitted work. AC and FSh report that as employees of King's Technology Evaluation Centre they received funding from the UK National Screening Committee to complete this study. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Artificial intelligence (AI) could have the potential to accurately classify mammograms according to the presence or absence of radiological signs of breast cancer, replacing or supplementing human readers (radiologists). The UK National Screening Committee's assessments of the use of AI systems to examine screening mammograms continues to focus on maximising benefits and minimising harms to women screened, when deciding whether to recommend the implementation of AI into the Breast Screening Programme in the UK. Maintaining or improving programme specificity is important to minimise anxiety from false positive results. When considering cancer detection, AI test sensitivity alone is not sufficiently informative, and additional information on the spectrum of disease detected and interval cancers is crucial to better understand the benefits and harms of screening. Although large retrospective studies might provide useful evidence by directly comparing test accuracy and spectrum of disease detected between different AI systems and by population subgroup, most retrospective studies are biased due to differential verification (ie, the use of different reference standards to verify the target condition among study participants). Enriched, multiple-reader, multiple-case, test set laboratory studies are also biased due to the laboratory effect (ie, radiologists' performance in retrospective, laboratory, observer studies is substantially different to their performance in a clinical environment). Therefore, assessment of the effect of incorporating any AI system into the breast screening pathway in prospective studies is required as it will provide key evidence for the effect of the interaction of medical staff with AI, and the impact on women's outcomes., Competing Interests: Declaration of interests This Health Policy paper was sent to all members of the UK NSC and the AI Task Group of the UK NSC for comment, before submission. BG is a part-time employee of HeartFlow and Kheiron Medical Technologies and holds stock options as part of the standard compensation package for both companies. BG had an advisory role with stock options for Khieron Medical Technologies (from January, 2018, to September, 2021). BG was a Visiting Researcher and part-time employee of Microsoft Research until May, 2021. BG has received grants from Innovate UK, the EU Commission, and jointly from the National Institute for Health and Care Research (NIHR) and the Medical Research Council. Kheiron Medical Technologies currently has a breast screening AI product available. As such, BG contributed to the text as an expert in AI, focusing on the accuracy of the technical descriptions of the AI method. BG did not comment on or suggest changes to the described requirements of evidence. LW declares that she is a member of the Optimam Steering Group, a collaboration between research scientists at the University of Surrey and Cancer Research UK, which, among other activities, is collating a database of mammography images to be used for research and assessment of AI. AM, JM, GK, and FS declare that they are employed by the UK NSC. SH is Chair of the AI Task Group of the UK NSC. RG-W is Chair of the Adult Reference Group of the UK NSC. RJS was the Chair of the UK NSC at the time of writing this paper. ST-P has previously received funds from the UK NSC to undertake evidence reviews for the UK NSC, including for Breast AI, and is a member of the Adult Reference Group and AI Task Group of the UK NSC. The opinions are those of the authors and not the NIHR, the NHS, or the Department of Health and Social Care. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets., Methods: We collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates., Findings: Data from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9-21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100-455 000) early-onset and 162 200 (70 200-394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800-187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500-125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600-96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500-66 200) maternal iGBS cases and 46 200 (20 300-111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births., Interpretation: Our analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests The Department of Clinical Epidemiology of Aarhus University receives funding from private and public institutions in the form of institutional research grants to (and administered by) Aarhus University; none of these grants has any relation to the present study. SAM declares funding from Astrazeneca, the Bill & Melinda Gates Foundation, GlaxoSmithKline, Minervax, Novavax, Pfizer, and the South Africa Medical Research Council; in particular, SAM delares funding to his institution from Pfizer for epidemiology studies on group B streptococcus (GBS) and a clinical trial on the GBS vaccine, and from the Bill & Melinda Gates Foundation on GBS epidemiology. FS declares employment by the UK National Screening Committee, which developed the policy recommendation for maternal GBS screening. CT declares a consulting fee from WHO for drafting a report on the Full Value of Vaccine Assessment for GBS vaccines, which is related to the current manuscript. RL declares participation on an advisory board for Janssen and Pfizer; payment for lectures from Reckitt; and grants to Fundación INFANT from the Bill & Melinda Gates Foundation and PATH. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Population breast screening services in England were suspended in March 2020 due to the COVID-19 pandemic. Here, we estimate the number of breast cancers whose detection may be delayed because of the suspension, and the potential impact on cancer deaths over 10 years., Methods: We estimated the number and length of screening delays from observed NHS Breast Screening System data. We then estimated additional breast cancer deaths from three routes: asymptomatic tumours progressing to symptomatically diagnosed disease, invasive tumours which remain screen-detected but at a later date, and ductal carcinoma in situ (DCIS) progressing to invasive disease by detection. We took progression rates, prognostic characteristics, and survival rates from published sources., Results: We estimated that 1,489,237 women had screening delayed by around 2-7 months between July 2020 and June 2021, leaving 745,277 outstanding screens. Depending on how quickly this backlog is cleared, around 2500-4100 cancers would shift from screen-detected to symptomatic cancers, resulting in 148-452 additional breast cancer deaths. There would be an additional 164-222 screen-detected tumour deaths, and 71-97 deaths from DCIS that progresses to invasive cancer., Conclusions: An estimated 148-687 additional breast cancer deaths may occur as a result of the pandemic-related disruptions. The impact depends on how quickly screening services catch up with delays., (© 2022. The Author(s).)

Background: Data are limited regarding long-term consequences of invasive GBS (iGBS) disease in early infancy, especially from low- and middle-income countries (LMIC) where most cases occur. We aimed to estimate risk of neurodevelopmental impairment (NDI) in children with a history of iGBS disease., Methods: A multi-country matched cohort study was undertaken in South Africa, India, Mozambique, Kenya, and Argentina from October 2019 to April 2021. The exposure of interest was defined as a history of iGBS disease (sepsis or meningitis) before 90 days of age, amongst children now aged 1·5-18 years. Age and sex-matched, children without history of GBS were also recruited. Age-appropriate, culturally-adapted assessments were used to define NDI across multiple domains (cognitive, motor, hearing, vision, emotional-behaviour, growth). Pooled NDI risk was meta-analysed across sites. Association of iGBS exposure and NDI outcome was estimated using modified Poisson regression with robust variance estimator., Findings: Amongst 138 iGBS survivors and 390 non-iGBS children, 38·1% (95% confidence interval [CI]: 30·0% - 46·6%) of iGBS children had any NDI, compared to 21·7% (95% CI: 17·7% - 26·0%) of non- iGBS children, with notable between-site heterogeneity. Risk of moderate/severe NDI was 15·0% (95% CI: 3·4% - 30·8%) among GBS-meningitis, 5·6% (95% CI: 1·5% - 13·7%) for GBS-sepsis survivors. The adjusted risk ratio (aRR) for moderate/severe NDI among iGBS survivors was 1.27 (95% CI: 0.65, 2.45), when compared to non-GBS children. Mild impairment was more frequent in iGBS (27.6% (95% CI: 20.3 - 35.5%)) compared to non-GBS children (12.9% (95% CI: 9.7% - 16.4%)). The risk of emotional-behavioural problems was similar irrespective of iGBS exposure (aRR=0.98 (95% CI: 0.55, 1.77))., Interpretation: Our findings suggest that iGBS disease is on average associated with a higher risk of moderate/severe NDI, however substantial variation in risk was observed between sites and data are consistent with a wide range of values. Our study underlines the importance of long-term follow-up for at-risk neonates and more feasible, standardised assessments to facilitate diagnosis in research and clinical practice., Funding: This work was supported by a grant (INV-009018) from the Bill & Melinda Gates Foundation to the London School of Hygiene &Tropical Medicine., Competing Interests: SRP reports additional finding from Bill & Melinda Gates Foundation on Covid-19 related projects.  ZD and SL report subawards from the London School of Hygiene & Tropical Medicine (LSHTM) to the Wits Health Consortium. SS and HBJ report subawards from LSHTM to Christian Medical College. QB and AB reports subawards from LSHTM to ISGlobal and Centro de Investigação em Saúde de Manhiça. AA and CN reports subawards from the LSHTM to the University of Oxford. CRN. reports subawards from LSHTM to Kenya Medical Research Institute, Kilifi, Kenya. CSY reports subawards from LSHTM to Fundación INFANT. RL reports subawards from LSHTM to Fundación INFANT. a grant from Program for Appropriate Technology in Health for a respiratory syncytial virus (RSV) costing study, grants to Fernando Polack from the Bill & Melinda Gates Foundation for estimating the RSV burden of disease, consulting fees and participating for serving on Pfizer’s GBS advisory board and Janssen’s RSV advisory board, payment or honoraria for Janssen’s RSV lecture and Merck’s human papillomavirus lecture, and stock or stock options from iTRIALS. FS reports non-financial support from The Federal University of São Paulo for submitted work and employment by the UK NSC hosted by the Department of Health, who developed the maternal GBS screening policy recommendation in the UK.  All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© 2022 The Author(s).)

Background: Invasive group B Streptococcus disease (iGBS) in infancy, including meningitis or sepsis, carries a high risk of mortality and neurodevelopmental impairment (NDI). We present data on iGBS from 2 decades of surveillance in Manhiça, Mozambique, with a focus on NDI., Methods: Morbidity surveillance databases in a rural Mozambican district hospital were screened for iGBS cases. From February 2020 to March 2021, surviving iGBS patients (n = 39) plus age- and sex-matched children without iGBS (n = 119) were assessed for neurocognitive development, vision, and hearing. The role of GBS in stillbirths and infant deaths was investigated using minimally invasive tissue sampling (MITS)., Results: Ninety iGBS cases were included, with most children being <3 months of age (85/90). The in-hospital case fatality rate was 14.4% (13/90), increasing to 17.8% (3 additional deaths) when considering mortality during the 6 months postdiagnosis. Fifty percent of the iGBS exposed infants and 10% of those unexposed showed any NDI. Surviving GBS conferred a 11-fold increased adjusted odds of moderate/severe NDI (odds ratio, 2.8 [95% confidence interval, .92-129.74]; P = .06) in children aged 0-5 years. For older children (6-18 years), no differences in NDI were found between exposed and unexposed. Motor domain was the most affected among young GBS survivors. Three stillbirths and 4 early neonatal deaths (of the 179 MITS performed) were attributed to iGBS., Conclusions: In absence of preventive strategies, such as intrapartum antibiotics, iGBS remains a significant cause of perinatal and infant disease and death. GBS also causes major longer-term neurodevelopmental sequelae, altogether justifying the need for maternal GBS vaccination strategies to increase perinatal and infant survival., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Dysbetalipoproteinemia (DBL) is an uncommon condition characterized by a mixed hyperlipidemia due to accumulation of remnant lipoproteins and is highly atherogenic. Typically, DBL is an autosomal recessive condition requiring an additional metabolic stress with reduced apolipoprotein E (apoE) function. However, DBL is also described in patients with multiple myeloma without the characteristic apoE2/E2 mutation seen in familial DBL. Although the underlying pathogenesis in these cases is not fully characterized, it is thought to occur due to interference with apoE function by antibodies produced from clonal plasma cells. Such cases are referred to as hyperlipidemic myeloma (HLM) and have rarely been described in the literature. To our knowledge there is no prior description of HLM in HIV positive patients in Africa. We describe a case of HLM in an African woman with underlying HIV infection who presented with phenotypic and biochemical features of DBL that responded poorly to lipid lowering therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Most cases of hypertension are because of essential hypertension, however 5% - 15% of cases can be a result of a secondary cause. In this article, we focus on the endocrine causes of secondary hypertension with a particular focus on pheochromocytomas (PCCs) and paragangliomas (PGLs). Around 15 endocrine disorders can initially present with hypertension. Amongst those PCCs and PGLs are rare but potentially life-threatening causes. An early diagnosis and timely referral can be life-saving. Herein, we present an approach for screening and diagnosis of these patients and focus on the importance of genetic testing.

Summary: Acromegaly is a rare, chronic progressive disorder with characteristic clinical features caused by persistent hypersecretion of growth hormone (GH), mostly from a pituitary adenoma (95%). Occasionally, ectopic production of GH or growth hormone-releasing hormone (GHRH) with resultant GH hypersecretion may lead to acromegaly. Sometimes localizing the source of GH hypersecretion may prove difficult. Rarely, acromegaly has been found in patients with an empty sella (ES) secondary to prior pituitary radiation and/or surgery. However, acromegaly in patients with primary empty sella (PES) is exceeding rarely and has only been described in a few cases. We describe a 47-year-old male who presented with overt features of acromegaly (macroglossia, prognathism, increased hand and feet size). Biochemically, both the serum GH (21.6 μg/L) and insulin-like growth factor 1 (635 μg/L) were elevated. In addition, there was a paradoxical elevation of GH following a 75 g oral glucose load. Pituitary MRI demonstrated an ES. In order to exclude an ectopic source of GH hypersecretion, further biochemical tests and imaging were done, which were unremarkable. Notably, increased uptake in the sella turcica on the 68Gallium DOTATATE PET/CT confirmed the ES as the likely source of GH secretion. As no overt lesion was noted, medical treatment (octreotide acetate) was initiated with a good clinical and biochemical response. At his 3 month follow-up, he reported an improvement in symptoms (fatigue and headache), however he still complained of low libido. Due to a persistently low testosterone level at follow-up, a long-acting testosterone was initiated. His GH level normalised, and IGF-1 has significantly reduced., Learning Points: The commonest cause of acromegaly is due to GH hypersecretion from pituitary adenomas (95%). Acromegaly has rarely been found in patients with ES. It is important to exclude a past history suggestive of pituitary apoplexy. Extra-pituitary source of GH such as ectopic production of GHRH with resultant GH hypersecretion needs to be excluded. In such cases, since there is no resectable mass, medical therapy is the primary treatment option.

Purpose of Review: Familial hypercholesterolemia is a genetic disorder of defective clearance and subsequent increase in serum LDL cholesterol (LDL-C) with a resultant increased risk of premature atherosclerotic cardiovascular disease. Despite treatment with traditional lipid-lowering therapies (LLT), most patients with familial hypercholesterolemia are unable to achieve target LDL-C. We review current and future novel therapeutic options available for familial hypercholesterolemia., Recent Findings: The use of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are effective in lowering LDL-C in patients with familial hypercholesterolemia, with a reduction in LDL-C of 60% in heterozygous familial hypercholesterolemia (HeFH) and up to 35% in homozygous familial hypercholesterolemia (HoFH). Inclisiran, another novel agent, is a small-interfering ribonucleic acid that reduces hepatic production of PCSK9 to provide a prolonged and sustained reduction in LDL-C of nearly 50% in HeFH. However, both agents require LDL receptor (LDLR) activity. Evinacumab, a novel monoclonal antibody against angiopoetin-like 3 (ANGPTL3), reduces LDL-C by 50% independent of LDLR activity., Summary: Achieving a target LDL-C in familial hypercholesterolemia can be challenging with standard LLT; however, novel therapeutic modalities show remarkable reductions in LDL-C allowing nearly all patients with HeFH and a significant proportion of patients with HoFH to achieve acceptable LDL-C levels., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Migrants in high-income countries may be at increased risk of COVID-19 due to their health and social circumstances, yet the extent to which they are affected and their predisposing risk factors are not clearly understood. We did a systematic review to assess clinical outcomes of COVID-19 in migrant populations, indirect health and social impacts, and to determine key risk factors., Methods: We did a systematic review following PRISMA guidelines (PROSPERO CRD42020222135). We searched multiple databases to 18/11/2020 for peer-reviewed and grey literature on migrants (foreign-born) and COVID-19 in 82 high-income countries. We used our international networks to source national datasets and grey literature. Data were extracted on primary outcomes (cases, hospitalisations, deaths) and we evaluated secondary outcomes on indirect health and social impacts and risk factors using narrative synthesis., Results: 3016 data sources were screened with 158 from 15 countries included in the analysis (35 data sources for primary outcomes: cases [21], hospitalisations [4]; deaths [15]; 123 for secondary outcomes). We found that migrants are at increased risk of infection and are disproportionately represented among COVID-19 cases. Available datasets suggest a similarly disproportionate representation of migrants in reported COVID-19 deaths, as well as increased all-cause mortality in migrants in some countries in 2020. Undocumented migrants, migrant health and care workers, and migrants housed in camps have been especially affected. Migrants experience risk factors including high-risk occupations, overcrowded accommodation, and barriers to healthcare including inadequate information, language barriers, and reduced entitlement., Conclusions: Migrants in high-income countries are at high risk of exposure to, and infection with, COVID-19. These data are of immediate relevance to national public health and policy responses to the pandemic. Robust data on testing uptake and clinical outcomes in migrants, and barriers and facilitators to COVID-19 vaccination, are urgently needed, alongside strengthening engagement with diverse migrant groups., Competing Interests: The authors report no conflicts of interest to declare, (© 2021 The Author(s). Published by Elsevier Ltd.)

Background: To determine the association of human leukocyte antigen (HLA) alleles as correlates of risk for and protection against tuberculin skin test (TST) positivity and active TB disease amongst HIV-infected adults., Methods: Genomic DNA was extracted from 754 HIV-infected adults whole-blood. HLA-A, -B, -C and -DRB1 loci were genotyped by next generation sequencing methods. HLA alleles were analysed by the presence/absence of TST immune conversion and active TB disease and further stratified by exposure to a household TB contact, CD4 + T-cell count and, for active TB disease, TST-positivity., Results: HLA-A*29:11 and - B*45:01/07 were associated with TST-positivity, while HLA-A*24:02, -A*29:02 and -B*15:16 with TST-negativity. In participants with a household TB contact, HLA-A*66:01, -A*68:02 and -B*49:01 were associated with TST-negativity. For TB disease, HLA-B*41:01, -C*06:02, -DRB1*04:01 and -DRB1*15:01 were associated with susceptibility, while HLA-B*07:02 and -DRB1*11:01 were protective, even for CD4 + T-cell count <350 cells/mm 3 . For initial TST-positivity and subsequent TB disease, HLA-A*01:01 and -DRB1*11:01 conveyed protection including for those with CD4 + T-cell count <350 cells/mm 3 ., Conclusion: Several HLA alleles are noted as correlates of TB infection, risk and natural protection in HIV-infected individuals. HLA associations may enable risk stratification of those with HIV infection. Protective alleles may assist in future TB vaccine development., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess the cost-effectiveness of universal repeat screening for syphilis in late pregnancy, compared with the current strategy of single screening in early pregnancy with repeat screening offered only to high-risk women., Design: A decision tree model was developed to assess the incremental costs and health benefits of the two screening strategies. The base case analysis considered short-term costs during the pregnancy and the initial weeks after delivery. Deterministic and probabilistic sensitivity analyses and scenario analyses were conducted to assess the robustness of the results., Setting: UK antenatal screening programme., Population: Hypothetical cohort of pregnant women who access antenatal care and receive a syphilis screen in 1 year., Primary and Secondary Outcome Measures: The primary outcome was the cost to avoid one case of congenital syphilis (CS). Secondary outcomes were the cost to avoid one case of intrauterine fetal demise (IUFD) or neonatal death and the number of women needing to be screened/treated to avoid one case of CS, IUFD or neonatal death. The cost per quality-adjusted life year gained was assessed in scenario analyses., Results: Base case results indicated that for pregnant women in the UK (n=725 891), the repeat screening strategy would result in 5.5 fewer cases of CS (from 8.8 to 3.3), 0.1 fewer cases of neonatal death and 0.3 fewer cases of IUFD annually compared with the single screening strategy. This equates to an additional £1.8 million per case of CS prevented. When lifetime horizon was considered, the incremental cost-effectiveness ratio for the repeat screening strategy was £120 494., Conclusions: Universal repeat screening for syphilis in pregnancy is unlikely to be cost-effective in the current UK setting where syphilis prevalence is low. Repeat screening may be cost-effective in countries with a higher syphilis incidence in pregnancy, particularly if the cost per screen is low., Competing Interests: Competing interests: SH, GW and EA work at Aquarius Population Health and have received consultancy fees from the following companies on projects related to STIs: Abbott, Cepheid, Binx Health, Hologic and St. Georges University of London. IA, KT and MT were funded as consultants on the project through Aquarius Population Health. MT has received support from Cepheid for conference attendance. KT is in receipt of funding to University of Bristol from GlaxoSmithKline for work unrelated to this work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In acute sepsis, reduced lipid and lipoprotein levels occur in HIV negative patients, in particular, low high-density lipoprotein cholesterol (HDL-c) levels are inversely correlated with sepsis severity and increased mortality. However, due to the limited data describing lipid and lipoprotein levels in septic HIV-infected individuals we aimed to investigate the changes in this subgroup., Materials and Methods: A prospective cross-sectional observational study of HIV-infected patients comparing admitted HIV - infected patients with sepsis to healthy controls from the antiretroviral therapy (ART) clinic. Non fasting - lipograms, ART use, diagnosis of tuberculosis (TB), markers of infection, renal function and mortality outcome to 3 months post discharge were reviewed., Results: Total cholesterol (TC), low-density lipoprotein (LDL-c) and HDL-c were all significantly lower in the sepsis group (p < 0.001). HDL-c was significantly associated with a higher white cell count (p = 0.018), higher C- reactive protein (p = 0.036) and low serum albumin (p < 0.001). In those with active TB (55%) HDL-c was reduced even further (0.55 vs. 0.72mmol/L, p = 0.013). Acute kidney injury (p = 0.560) and mortality at discharge (p = 0.097) or 3 months follow up (p = 0.953) was not associated with reduced HDL-c., Conclusion: Septic HIV-infected patients had significantly reduced lipid and lipoprotein levels at admission. Of note however, a low HDL-c was associated with markers of infection and reductions in HDL-c was more marked in those with active TB., (Copyright: © 2020 Afr. J. Infect. Diseases.)