Gene Deletions in Mycobacterium bovis BCG Stimulate Increased CD8+ T Cell Responses

Mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host''s immune response. It has been suggested that mycobacteria may contain genes that reduce the host''s ability to elicit CD8⁺ T cell responses. We screened 3,290 mutant Mycobacterium bovis bacillus Calmette Guerin (BCG) strains to identify genes that decrease major histocompatibility complex (MHC) class I presentation of mycobacterium-encoded epitope peptides. Through our analysis, we identified 16 mutant BCG strains that generated increased transgene product-specific CD8⁺ T cell responses. The genes disrupted in these mutant strains had disparate predicted functions. Reconstruction of strains via targeted deletion of genes identified in the screen recapitulated the enhanced immunogenicity phenotype of the original mutant strains. When we introduced the simian immunodeficiency virus (SIV) gag gene into several of these novel BCG strains, we observed enhanced SIV Gag-specific CD8⁺ T cell responses in vivo. This study demonstrates that mycobacteria carry numerous genes that act to dampen CD8⁺ T cell responses and suggests that genetic modification of these genes may generate a novel group of recombinant BCG strains capable of serving as more effective and immunogenic vaccine vectors.     

Mycoplasma hominis impacts gene expression in Trichomonas vaginalis

Parasitology Research - In Europe, up to 90% of isolated Trichomonas vaginalis strains are naturally infected with Mycoplasma hominis, a facultative pathogen of the human genital tract. The...     

Migration and Maternity: Insights of Context,Health Policy,and Research Evidence on Experiences and Outcomes From a Three Country Preliminary Study Across Germany,Canada, and the United Kingdom

A group from Germany, Canada, and the United Kingdom undertook country-specific scoping reviews and stakeholder consultations before joining to holistically compare migration and maternity in all three countries. We examined four interlinking dimensions to understand how international migrant/minority maternal health might be improved upon using transnational research: (a) wider sociopolitical context, (b) health policy arena, (c) constellation, outcomes, and experiences of maternity services, and (d) existing research contexts. There was clear evidence that the constellation and delivery of services may undermine good experiences and outcomes. Interventions to improve access and quality of care remain small scale, short term, and lacking in rigorous evaluation.     

Analyses of welfare-state reform policies towards long-term senior care in a cross-European perspective

The aim of this article is to introduce a systematic, structured conceptual framework for the comparative analysis of welfare-state reform policies towards long-term senior care and the care structures in a cross-European perspective. A welfare state’s policies on the long-term care of senior citizens frame the different aspects of their care: the care options of the older people, the employment situation of the different types of caregivers and the care quality. The actual structure of senior care is mainly based on the specific care-provision mix in a welfare state and on the main types of care employment. It is should not, however, be treated as a direct outcome of care policies in analyses of welfare-state policies, since the care recipients and care givers all act within the broader framework of the complex and often contradictory cultural, institutional, social and economic context—the specific ‘care arrangement’ of a country.     

Familial acquired thrombotic thrombocytopenic purpura in siblings – no immunogenetic link with associated human leucocyte antigens

Acquired immunoglobulin G (IgG)‐mediated thrombotic thrombocytopenic purpura (TTP) has not yet been described in non‐twin siblings. We report two cases of acquired TTP in Caucasian sisters with inactive ADAMTS13 metalloprotease due to ADAMTS13 autoantibodies suggesting a role of genetic determinants in this life‐threatening disease. However, human leucocyte antigen (HLA) class II types presumably associated with acquired TTP were not identified in the patients, indicating that HLA class II typing may not be useful in acquired TTP risk assessment of family members.     

Hepatitis C-associated autoimmunity in patients coinfected with HIV.

Background: Hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations. It is unclear to what extent extrahepatic manifestations occur in HIV/HCV coinfection. Methods: We prospectively assessed cross-sectional frequencies of autoimmune manifestations in HIV/HCV-coinfected patients (n=98), HIV-mono-infected (n=45) and HCV-mono-infected patients (n=78). Diagnostic vasculitis scores, HCV and HIV loads, CD4 cell counts, thyroid-, cardiolipin-, non-organ-specific tissue antibodies (nuclear, smooth muscle, anti-liver-kidney-microsome, neutrophil-cytoplasmic) and cryoglobulins were determined. Results: Synergistic effects of HCV and HIV infection were observed with respect to the prevalence of antibodies against thyroglobulin (HCV infection 15.4%, HIV infection 8.8%, HIV/HCV coinfection 30.6%; P<0.001) and cardiolipin antibodies (HCV infection 9.0%, HIV infection 31%, HIV/HCV coinfection 46%; P<0.001). Cryoglobulinemia type III, was significantly associated with HCV infection (HCV, 25.6%; HIV/HCV, 20.4%) but not with HIV infection (4.4%, P<0.05). Rheumatoid factor was commonly detected in patients with HCV infection (48%), but occurred considerably less frequently in patients with HIV infection (4.4%) or HIV/HCV coinfection (9.5%, P<0.01). Conclusion: HIV coinfection appears to differentially modulate the frequency of HCV-related autoimmunity. However, autoimmunity is rarely accompanied by clinical manifestations.