Setting The LTBI programme offers testing and treatment to new entrant migrants from high incidence countries in England. However, the rates of LTBI testing, treatment acceptance and completion are suboptimal and appropriate access must be improved. Objective: To gain insights from the community, community-based organisations (CBOs), and public sector stakeholders on interventions that facilitate collaboration to improve health care outreach and delivery. Design Three stakeholder meetings and five focus group discussions were held using thematic analysis to identify themes arising from the participants' perspectives. Results Four overarching themes emerged from the discussions. These were capacity, collaboration, culture and trust. These highlighted the complementary skills sets different sectors bring to collaboration, as well as the barriers that need surmounting. Stigma could be reduced by making LTBI testing routine, and community members could act as champions for health promotion raising awareness on LTBI testing, and providing a bridge between communities and primary care services. Conclusion Public service providers, community members and CBOs have a willingness to collaborate to support primary care delivery of testing for LTBI and other communicable and non-communicable diseases. Policy and commissioning support are needed to facilitate such workings.
Lower respiratory tract bacterial infections are characterized by neutrophilic inflammation in the airways. The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 8 is expressed in and released by human granulocytes. Our study demonstrates that human granulocytes release CEACAM8 in response to bacterial DNA in a TLR9-dependent manner. Individuals with a high percentage of bronchial lavage fluid (BALF) granulocytes were more likely to have detectable levels of released CEACAM8 in the BALF than those with a normal granulocyte count. Soluble, recombinant CEACAM8-Fc binds to CEACAM1 expressed on human airway epithelium. Application of CEACAM8-Fc to CEACAM1-positive human pulmonary epithelial cells resulted in reduced TLR2-dependent inflammatory responses. These inhibitory effects were accompanied by tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) of CEACAM1 and by recruitment of the phosphatase SHP-1, which could negatively regulate Toll-like receptor 2-dependent activation of the phosphatidylinositol 3-OH kinase-Akt kinase pathway. Our results suggest a new mechanism by which granulocytes reduce pro-inflammatory immune responses in human airways via secretion of CEACAM8 in neutrophil-driven bacterial infections.
Background Evaluating interventions that may lead to a reduction in people diagnosed with tuberculosis (TB) in high-income low incidence countries is key to accelerate progress towards elimination. We assessed the effectiveness of pre-entry active TB and post-entry latent TB infection (LTBI) screening to reduce TB incidence and the effect of primary care access on TB incidence in new-entrant migrants to the UK. Methods We performed a population-based cohort study of migrants from 66 countries, who were negative for active TB at pre-entry screening between January 1, 2011 and December 31, 2014 and were eligible for LTBI screening. We used record linkage to track their first contact with primary care, uptake of LTBI screening and development of active TB in England, Wales or Northern Ireland. To assess the effectiveness of the pre-entry screening programme we identified a control group of migrants not screened for active TB using the specific code for new-entrants registering in primary care within the NHS patient registration data system. Our primary outcome was development of active TB notified to the National Enhanced Surveillance System (ETS). in this population. The pre-entry and LTBI screening programmes are likely to be responsible for the reduction in TB incidence in the UK. However, the LTBI programme will only succeed by securing early access to health services, because its effectiveness may be compromised by low attendance to primary care. The pre-entry screening programme provides an opportunity to actively deliver health promotion to inform its participants about the LTBI screening and primary care registration upon UK arrival. Likewise, the compulsory payment of an immigration health surcharge must be coupled with information on entitlements and the importance of primary care registration as entry point to the health system in the UK. Conroy, without their support this study would have not been possible. Authors' contributions: DZ, LCBA, and AL conceptualised the initial hypothesis, conceived and designed the study. LCBA and RH analysed the data. LCBA wrote the first draft of the manuscript. LCBA, AMO and AM performed the record linkage. All authors contributed substantially to data acquisition and interpretation, and revision and editing of the manuscript. Conflict of interest statement: AL is named inventor on patents pertaining to T cell-based diagnosis, including IGRA technologies. Some of these patents were assigned by the University of Oxford to Oxford Immunotec plc resulting in royalty entitlements for the University of Oxford and AL. All other authors declare no competing interests.
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