Objectives To determine whether BCG vaccination protects against Mycobacterium tuberculosis infection as assessed by interferon γ release assays (IGRA) in children.Design Systematic review and meta-analysis. Searches of electronic databases 1950 to November 2013, checking of reference lists, hand searching of journals, and contact with experts. Setting Community congregate settings and households.Inclusion criteria Vaccinated and unvaccinated children aged under 16 with known recent exposure to patients with pulmonary tuberculosis. Children were screened for infection with M tuberculosis with interferon γ release assays. Data extractionStudy results relating to diagnostic accuracy were extracted and risk estimates were combined with random effects meta-analysis. ResultsThe primary analysis included 14 studies and 3855 participants. The estimated overall risk ratio was 0.81 (95% confidence interval 0.71 to 0.92), indicating a protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children. The observed protection was similar when estimated with the two types of interferon γ release assays (ELISpot or QuantiFERON). Restriction of the analysis to the six studies (n=1745) with information on progression to active tuberculosis at the time of screening showed protection against infection of 27% (risk ratio 0.73, 0.61 to 0.87) compared with 71% (0.29, 0.15 to 0.58) against active tuberculosis. Among those infected, protection against progression to disease was 58% (0.42, 0.23 to 0.77). Conclusions BCG protects against M tuberculosis infection as well as progression from infection to disease.Trial registration PROSPERO registration No CRD42011001698 (www. crd.york.ac.uk/prospero/). IntroductionBCG vaccine has been the subject of numerous efficacy trials and epidemiological studies conducted over several decades. These trials indicate that BCG has 60-80% protective efficacy against severe forms of tuberculosis in children, particularly meningitis, 1 2 and its efficacy against pulmonary diseases varies geographically.3-5 BCG does not seem to protect against disease when it is given to people already infected or sensitised to environmental mycobacteria, which could explain the geographical variation.6-8 Until recently it was not possible to establish whether the protective effect of BCG vaccination against disease was from its action in preventing acquisition of infection or limited to prevention of progression from infection to clinical disease.The scarcity of evidence on whether the vaccine is effective against Mycobacterium tuberculosis infection was because of limitations of the tuberculin skin test. This test cannot distinguish a positive response caused by M tuberculosis infection from that caused by BCG vaccination or non-tuberculous In this systematic review we examined the evidence for the protective effect of BCG against M tuberculosis infection, as opposed to against disease, in settings where children can be presumed to have been exposed to M tu...

The implementation of bacterial screening of PLT components with the NHSBT BacT/ALERT protocol was an effective risk reduction measure and increased the safety of the blood supply.

The study validates diversion and an improved donor-arm disinfection procedure. In combination, these two interventions produced a substantial reduction in contamination. These procedures are to be introduced by the English National Blood Service to enhance the safety of the blood supply.

The Medi-Flex disinfection method offers the English National Blood Service a validated, optimal 'best practice' disinfection technique and should contribute significantly to the reduction in risk of transmission of bacteria by transfusion.

BackgroundThree arguments are usually invoked in favour of stepped wedge cluster randomised controlled trials: the logistic convenience of implementing an intervention in phases, the ethical benefit of providing the intervention to all clusters, and the potential to enhance the social acceptability of cluster randomised controlled trials. Are these alleged benefits real? We explored the logistic, ethical, and political dimensions of stepped wedge trials using case studies of six recent evaluations.MethodsWe identified completed or ongoing stepped wedge evaluations using two systematic reviews. We then purposively selected six with a focus on public health in high, middle, and low-income settings. We interviewed their authors about the logistic, ethical, and social issues faced by their teams. Two authors reviewed interview transcripts, identified emerging issues through qualitative thematic analysis, reflected upon them in the context of the literature, and invited all participants to co-author the manuscript.ResultsOur analysis raises three main points. First, the phased implementation of interventions can alleviate problems linked to simultaneous roll-out, but also brings new challenges. Issues to consider include the feasibility of organising intervention activities according to a randomised sequence, estimating time lags in implementation and effects, and accommodating policy changes during the trial period. Second, stepped wedge trials, like parallel cluster trials, require equipoise: without it, randomising participants to a control condition, even for a short time, remains problematic. In stepped wedge trials, equipoise is likely to lie in the degree of effect, effectiveness in a specific operational milieu, and the balance of benefit and harm, including the social value of better evaluation. Third, the strongest arguments for a stepped wedge design are logistic and political rather than ethical. The design is advantageous when simultaneous roll-out is impractical and when it increases the acceptability of using counterfactuals.ConclusionsThe logistic convenience of phased implementation is context-dependent, and may be vitiated by the additional requirements of phasing. The potential for stepped wedge trials to enhance the social acceptability of cluster randomised trials is real, but their ethical legitimacy still rests on demonstrating equipoise and its configuration for each research question and setting.