Stable Cytotoxic T Cell Escape Mutation in Hepatitis C Virus Is Linked to Maintenance of Viral Fitness

Mechanisms by which hepatitis C virus (HCV) evades cellular immunity to establish persistence in chronically infected individuals are not clear. Mutations in human leukocyte antigen (HLA) class I-restricted epitopes targeted by CD8+ T cells are associated with persistence, but the extent to which these mutations affect viral fitness is not fully understood. Previous work showed that the HCV quasispecies in a persistently infected chimpanzee accumulated multiple mutations in numerous class I epitopes over a period of 7 years. During the acute phase of infection, one representative epitope in the C-terminal region of the NS3/4A helicase, NS31629-1637, displayed multiple serial amino acid substitutions in major histocompatibility complex (MHC) anchor and T cell receptor (TCR) contact residues. Only one of these amino acid substitutions at position 9 (P9) of the epitope was stable in the quasispecies. We therefore assessed the effect of each mutation observed during in vivo infection on viral fitness and T cell responses using an HCV subgenomic replicon system and a recently developed in vitro infectious virus cell culture model. Mutation of a position 7 (P7) TCR-contact residue, I1635T, expectedly ablated the T cell response without affecting viral RNA replication or virion production. In contrast, two mutations at the P9 MHC-anchor residue abrogated antigen-specific T cell responses, but additionally decreased viral RNA replication and virion production. The first escape mutation, L1637P, detected in vivo only transiently at 3 mo after infection, decreased viral production, and reverted to the parental sequence in vitro. The second P9 variant, L1637S, which was stable in vivo through 7 years of follow-up, evaded the antigen-specific T cell response and did not revert in vitro despite being less optimal in virion production compared to the parental virus. These studies suggest that HCV escape mutants emerging early in infection are not necessarily stable, but are eventually replaced with variants that achieve a balance between immune evasion and fitness for replication

Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

Background: People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed. Methods and Findings: We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade. Conclusion: Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID

Deterioration in social and economic conditions in Greece impact the health of LGBT populations: A call to action in the era of Troika

The health of the population of Greece has been severely affected because of economic crisis that occurred over the last decade. The lesbian, gay, bisexual, and transgender (LGBT) population, which in the best of economic times experiences heightened health burdens and disparities because of homophobia, which is socially produced and state sanctioned, is not immune from the effects of the economic downturn and austerity measures imposed by the European Union. To date, we have very limited knowledge about the health of LGBT people in Greece beyond HIV-related heath. Here we review the economic conditions that prevail in Greece and the limited knowledge we have regarding LGBT health. We further consider the role that discrimination plays in the lives of the LGBT population, the preponderance of homophobic attitudes within the culture, the synergy between social and economic conditions, and how these structural inequities may undermine the health of the population. We offer a set of recommendations for both research and clinical practice that will document the health of LGBT people in Greece; scientifically disentangle and delineate the culturally produced drivers that may undermine their health; and use this knowledge to inform the development of health care programs, service, and training embedded within a cultural competency framework that attends to both Greek society at large and the culture of the LGBT population within Greece. © 2018 American Psychological Association

Prevalence of intestinal parasitic infections among children in europe over the last five years

While the prevalence of intestinal parasitic infections (IPI) has been most commonly studied in African and Asian populations, less is known about the prevalence rates of IPI in European children, as well as the potential risk factors that favor the spread of parasites. We aimed to review published evidence on the prevalence rates of IPI in children residing in Europe, and to quantitatively synthesize the results of published studies. We searched Medline from 1 January 2015 to 1 April 2021 to address the most recently published prevalence patterns of IPI in European children. Randomeffects meta-analyses were performed by type of IPI infection, age group and sex, depending on data availability. Of the 967 potentially relevant articles, eight eligible cross-sectional studies were included in this analysis, yielding a sample of 3376 children (0–19 years). The overall prevalence rate was 5.9% for any IPI in children residing in European countries. Blastocystis hominis was the most commonly detected parasite yielding a prevalence rate of 10.7%. Other parasites included Entamoeba coli, Endolimax nana, and Blastocystis hominis. Studies focusing on specific types of parasites showed prevalence rates ranging from 1.3% for Cryptosporidium to 68.3% for Dientamoeba fragilis. Despite the scarce literature, the present review showed relatively low prevalence rates of IPI in Europe. Future studies accounting for proper diagnostic methods used for the detection of parasites and including information on potential sociodemographic factors, such as travelling history and history of immigration, are needed to guide clinicians about which children to test, as well as when and how to test children for IPI. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Studies of human antiviral CD8+ lymphocytes using class I peptide tetramers.

Understanding the interactions between a host and a pathogen relies crucially on quantitative measurements of immune responses. Until recently, measurements of the levels of cellular immune responses, i.e. those mediated by CD4+ and CD8+ T lymphocytes have depended largely on culture in vitro and subsequent measurement of specific functions (such as cytolysis). More recently, new technologies based around tetrameric class I peptide complexes (tetramers) have allowed immunologists to measure CD8+ T lymphocyte levels directly ex vivo and independently of function. Since CD8+ lymphocytes play a key role in a number of important human viral infections, these tools have yielded useful insights into the dynamics, phenotype and function of human antiviral lymphocyte populations. In this review we describe some of the basic aspects of the biology of virus-specific CD8+ lymphocytes, and the current methods available to detect them. The use of tetramers has, in just four years, transformed our understanding of the immune responses against HIV, HTLV-1, HBV, HCV, CMV and EBV, and holds promise in a number of areas where quantitative analysis of the antiviral response in terms of both number and function is critical

Studies of human antiviral CD8+ lymphocytes using class I peptide tetramers.

Understanding the interactions between a host and a pathogen relies crucially on quantitative measurements of immune responses. Until recently, measurements of the levels of cellular immune responses, i.e. those mediated by CD4+ and CD8+ T lymphocytes have depended largely on culture in vitro and subsequent measurement of specific functions (such as cytolysis). More recently, new technologies based around tetrameric class I peptide complexes (tetramers) have allowed immunologists to measure CD8+ T lymphocyte levels directly ex vivo and independently of function. Since CD8+ lymphocytes play a key role in a number of important human viral infections, these tools have yielded useful insights into the dynamics, phenotype and function of human antiviral lymphocyte populations. In this review we describe some of the basic aspects of the biology of virus-specific CD8+ lymphocytes, and the current methods available to detect them. The use of tetramers has, in just four years, transformed our understanding of the immune responses against HIV, HTLV-1, HBV, HCV, CMV and EBV, and holds promise in a number of areas where quantitative analysis of the antiviral response in terms of both number and function is critical

Deep Brain Stimulation-Related Surgical Site Infections: A Systematic Review and Meta-Analysis

Background: Over the last decades, the increased use of deep brain stimulation (DBS) has raised concerns about the potential adverse health effects of the treatment. Surgical site infections (SSIs) following an elective surgery remain a major challenge for neurosurgeons. Few studies have examined the prevalence and risk factors of DBS-related complications, particularly focusing on SSIs. Objectives: We systematically searched published literature, up to June 2020, with no language restrictions. Materials and Methods: Eligible were studies that examined the prevalence of DBS-related SSIs, as well as studies that examined risk and preventive factors in relation to SSIs. We extracted information on study characteristics, follow-up, exposure and outcome assessment, effect estimate and sample size. Summary odds ratios (sOR) and 95% confidence intervals (CI) were calculated from random-effects meta-analyses; heterogeneity and small-study effects were also assessed. Results: We identified 66 eligible studies that included 12,258 participants from 27 countries. The summary prevalence of SSIs was estimated at 5.0% (95% CI: 4.0%–6.0%) with higher rates for dystonia (6.5%), as well as for newer indications of DBS, such as epilepsy (9.5%), Tourette syndrome (5.9%) and OCD (4.5%). Similar prevalence rates were found between early-onset and late-onset hardware infections. Among risk and preventive factors, the perioperative implementation of intra-wound vancomycin was associated with statistically significantly lower risk of SSIs (sOR: 0.26, 95% CI: 0.09–0.74). Heterogeneity was nonsignificant in most meta-analyses. Conclusion: The present study confirms the still high prevalence of SSIs, especially for newer indications of DBS and provides evidence that preventive measures, such as the implementation of topical vancomycin, seem promising in reducing the risk of DBS-related SSIs. Large clinical trials are needed to confirm the efficacy and safety of such measures. © 2021 International Neuromodulation Societ