Refugee and Immigrant Community Health Champions:a Qualitative Study of Perceived Barriers to Service Access and Utilisation of the National Health Service (NHS) in the West Midlands, UK

There has been much discussion recently that better healthcare systems lead to increased service access and utilisation. However, there are still concerns raised among the refugee and immigrant communities about barriers to access and utilisation of primary healthcare services in the UK. This study aimed to explore with refugee and immigrant community health champions (CHCs) their perceptions about such barriers based on feedback in their own discussions with fellow refugees, asylum-seekers and immigrants in the West Midlands, UK. A total of 42 refugees and immigrants were recruited. Qualitative design-focused group discussions were conducted among purposively selected participants. These discussions were conducted between May and September 2019, and data were analysed using thematic analysis. The barriers to service access and utilisation are categorised into four themes: (i) knowledge about health issues that most affected refugees and immigrants; (ii) community indications of factors that obstructed service access; (iii) challenges in identifying local teams involved in service provision; and (iv) accurate knowledge about the different teams and their roles in facilitating access. This study higlighted that the levels of service access and utilisation would depend on the competence and effectiveness of the health system. Urgency and seriousness of individuals’ healthcare needs were the factors that were perceived to strongly influence refugees and immigrants to seek and utilise local services. We identified a number of potential barriers and challenges to service access and utilisation that should be overcome if primary healthcare service is to be planned and delivered effectively, efficiently and equitably in the West Midlands

Human cytomegalovirus evades ZAP detection by suppressing CpG dinucleotides in the major immediate early 1 gene

The genomes of RNA and small DNA viruses of vertebrates display significant suppression of CpG dinucleotide frequencies. Artificially increasing dinucleotide frequencies results in substantial attenuation of virus replication, suggesting that these compositional changes may facilitate recognition of non-self RNA sequences. Recently, the interferon inducible protein ZAP, was identified as the host factor responsible for sensing CpG in viral RNA, through direct binding and possibly downstream targeting for degradation. Using an arrayed interferon stimulated gene expression library screen, we identified ZAPS, and its associated factor TRIM25, as inhibitors of human cytomegalovirus (HCMV) replication. Exogenous expression of ZAPS and TRIM25 significantly reduced virus replication while knockdown resulted in increased virus replication. HCMV displays a strikingly heterogeneous pattern of CpG representation with specific suppression of CpG motifs within the IE1 major immediate early transcript which is absent in subsequently expressed genes. We demonstrated that suppression of CpG dinucleotides in the IE1 gene allows evasion of inhibitory effects of ZAP. We show that acute virus replication is mutually exclusive with high levels of cellular ZAP, potentially explaining the higher levels of CpG in viral genes expressed subsequent to IE1 due to the loss of pressure from ZAP in infected cells. Finally, we show that TRIM25 regulates alternative splicing between the ZAP short and long isoforms during HCMV infection and interferon induction, with knockdown of TRIM25 resulting in decreased ZAPS and corresponding increased ZAPL expression. These results demonstrate for the first time that ZAP is a potent host restriction factor against large DNA viruses and that HCMV evades ZAP detection through suppression of CpG dinucleotides within the major immediate early 1 transcript. Furthermore, TRIM25 is required for efficient upregulation of the interferon inducible short isoform of ZAP through regulation of alternative splicing

Depression, anxiety, pain and quality of life in people living with chronic hepatitis C: A systematic review and meta-analysis

Objectives: Individuals infected with hepatitis C virus (HCV) can develop extrahepatic conditions which may have a significant impact on life expectancy and quality of life. We conducted a systematic review to assess the causal relationship between HCV and extrahepatic conditions and the impact of HCV upon health-related quality of life of people in the UK. / Methods: HCV advocacy groups identified conditions that they thought most important to research, and the perspectives of various stakeholders informed the scope of the review. A comprehensive literature search of a range of electronic databases and websites was undertaken. Screening, quality assessment and data extraction were conducted using specialist software. The key criterion for inclusion in a synthesis was a study’s testing of the association between HCV and either quality of life or conditions specified as important by advocacy groups: depression, anxiety or painful conditions. Other criteria relating to study populations, measures and matching of study groups were also applied. Two reviewers assessed included studies, with disagreements resolved by a third reviewer where necessary. Studies were assessed for methodological quality using standardised appraisal tools. Metaanalyses were performed. Based on the consistency and sufficiency of research evidence, the findings were graded as strong, promising, tentative or inconclusive. / Results: 71 studies were included in the review’s syntheses. All studies were judged to be at a moderate or high risk of bias. Only two UK studies met our inclusion criteria. / Quality of life: Evidence from 22 studies indicates that people with HCV have worse quality of life than ‘general’ or ‘healthy’ populations; meta-analysis of nine studies indicated\ud that the physical (PCS) and mental health (MCS) domains of quality of life on the Health-Related Quality of Life Scale were both statistically and clinically worse among HCV-infected people (PCS: MD 5.54, 95% CI 3.73-7.35, MCS: MD 3.81, 95% CI 1.97-5.64). Evidence from seven included studies suggests that people co-infected with HCV and HIV have worse quality of life than individuals with HIV only; metaanalysis of five studies indicated that both the physical and mental health domains of quality of life were significantly worse among people who were co-infected (PCS: MD 2.57, 95% CI 1.08-4.06, MCS: MD 1.88, 95% CI 0.06-3.69). / Depression and anxiety: Evidence from 22 studies indicates that depression and anxiety are more severe, and depression is more common among people with HCV compared to those without it. Meta-analysis of 12 studies identified the severity of depression in people with HCV to be significantly greater than in those without HCV (Mean difference 0.98, 95% CI 0.43-1.53). Meta-analysis of nine studies identified the severity of clinical anxiety to be significantly greater among people with HCV (Mean difference 0.47, 95% CI 0.09-0.86). Meta-analysis of seven studies identified participants with HCV to be approximately three times more likely to be depressed compared to those without HCV (OR 2.77, 95% CI 1.62-4.74). No statistically significant evidence that anxiety is more common among people with HCV was found. / Pain: Evidence was appraised from 26 studies on painful conditions. A meta-analysis of four studies indicates that people with HCV are 17% more likely to suffer from arthralgia than those without HCV (RR 1.17, 95% CI 1.04-1.31). A meta-analysis of five studies suggested that people with HCV are significantly more likely to suffer from fibromyalgia; key differences across the studies in terms of the health status (co-morbidities) of HCV patients and comparison groups mean it is not possible to quantify the increased risk attributable to HCV. Other studies, including those on arthritis, were not amenable to meta-analysis. / Conclusions: Evidence suggests an association between HCV infection and depression, anxiety, fibromyalgia, arthralgia and health-related quality of life. However, the evidence was graded as ‘promising’ or ‘tentative’ rather than ‘strong’. More high-quality research on the association between HCV and these conditions is needed

Epidemiology of Human Parvovirus 4 Infection in Sub-Saharan Africa

Human parvovirus 4 infections are primarily associated with parenteral exposure in western countries. By ELISA, we demonstrate frequent seropositivity for antibody to parvovirus 4 viral protein 2 among adult populations throughout sub-Saharan Africa (Burkina Faso, 37%; Cameroon, 25%; Democratic Republic of the Congo, 35%; South Africa, 20%), which implies existence of alternative transmission routes

Thyroid Stimulating Hormone Receptor (TSHR) Intron 1 Variants Are Major Risk Factors for Graves' Disease in Three European Caucasian Cohorts

BACKGROUND: The thyroid stimulating hormone receptor (TSHR) gene is an established susceptibility locus for Graves' disease (GD), with recent studies refining association to two single nucleotide polymorphisms (SNPs), rs179247 and rs12101255, within TSHR intron 1. METHODOLOGY AND PRINCIPAL FINDINGS: We aimed to validate association of rs179247 and rs12101255 in Polish and UK Caucasian GD case-control subjects, determine the mode of inheritance and to see if association correlates with specific GD clinical manifestations. We investigated three case-control populations; 558 GD patients and 520 controls from Warsaw, Poland, 196 GD patients and 198 controls from Gliwice, Poland and 2504 GD patients from the UK National collection and 2784 controls from the 1958 British Birth cohort. Both rs179247 (P = 1.2×10(-2)-6.2×10(-15), OR = 1.38-1.45) and rs12101255 (P = 1.0×10(-4)-3.68×10(-21), OR = 1.47-1.87) exhibited strong association with GD in all three cohorts. Logistic regression suggested association of rs179247 is secondary to rs12101255 in all cohorts. Inheritance modeling suggested a co-dominant mode of inheritance in all cohorts. Genotype-phenotype correlations provided no clear evidence of association with any specific clinical characteristics. CONCLUSIONS: We have validated association of TSHR intron 1 SNPs with GD in three independent European cohorts and have demonstrated that the aetiological variant within the TSHR is likely to be in strong linkage disequilibrium with rs12101255. Fine mapping is now required to determine the exact location of the aetiological DNA variants within the TSHR

Data integration for large-scale models of species distributions

With the expansion in the quantity and types of biodiversity data being collected, there is a need to find ways to combine these different sources to provide cohesive summaries of species’ potential and realized distributions in space and time. Recently, model-based data integration has emerged as a means to achieve this by combining datasets in ways that retain the strengths of each. We describe a flexible approach to data integration using point process models, which provide a convenient way to translate across ecological currencies. We highlight recent examples of large-scale ecological models based on data integration and outline the conceptual and technical challenges and opportunities that arise

Seasonal dynamics of the wild rodent faecal virome

Viral discovery studies in wild animals often rely on cross-sectional surveys at a single time point. As a result, our understanding of the temporal stability of wild animal viromes remains poorly resolved. While studies of single host–virus systems indicate that host and environmental factors influence seasonal virus transmission dynamics, comparable insights for whole viral communities in multiple hosts are lacking. Utilizing noninvasive faecal samples from a long-term wild rodent study, we characterized viral communities of three common European rodent species (Apodemus sylvaticus, A. flavicollis and Myodes glareolus) living in temperate woodland over a single year. Our findings indicate that a substantial fraction of the rodent virome is seasonally transient and associated with vertebrate or bacteria hosts. Further analyses of one of the most common virus families, Picornaviridae, show pronounced temporal changes in viral richness and evenness, which were associated with concurrent and up to ~3-month lags in host density, ambient temperature, rainfall and humidity, suggesting complex feedbacks from the host and environmental factors on virus transmission and shedding in seasonal habitats. Overall, this study emphasizes the importance of understanding the seasonal dynamics of wild animal viromes in order to better predict and mitigate zoonotic risks

The Global Spread of Hepatitis C Virus 1a and 1b: A Phylodynamic and Phylogeographic Analysis

Using phylodynamic and phylogeographic methods, Angelos Hatzakis and colleagues find that the global spread of Hepatitis C virus coincided with widespread use of transfused blood and with the expansion of intravenous drug use