Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.

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 National Institute for Health Research Health Technology Assessment programme.

ObjectiveTo review the effects of school closures on pandemic and seasonal influenza outbreaks.DesignSystematic review.Data sourcesMEDLINE and EMBASE, reference lists of identified articles, hand searches of key journals and additional papers from the authors' collections.Study selectionStudies were included if they reported on a seasonal or pandemic influenza outbreak coinciding with a planned or unplanned school closure.ResultsOf 2579 papers identified through MEDLINE and EMBASE, 65 were eligible for inclusion in the review along with 14 identified from other sources. Influenza incidence frequently declined after school closure. The effect was sometimes reversed when schools reopened, supporting a causal role for school closure in reducing incidence. Any benefits associated with school closure appeared to be greatest among school-aged children. However, as schools often closed late in the outbreak or other interventions were used concurrently, it was sometimes unclear how much school closure contributed to the reductions in incidence.ConclusionsSchool closures appear to have the potential to reduce influenza transmission, but the heterogeneity in the data available means that the optimum strategy (eg, the ideal length and timing of closure) remains unclear.

Objective To examine the determinants of vulnerability to winter mortality in elderly British people. Design Population based cohort study (119 389 person years of follow up). Setting 106 general practices from the Medical Research Council trial of assessment and management of older people in Britain. Participants People aged ≥ 75 years. Main outcome measures Mortality (10 123 deaths) determined by follow up through the Office for National Statistics. Results Month to month variation accounted for 17% of annual all cause mortality, but only 7.8% after adjustment for temperature. The overall winter:non-winter rate ratio was 1.31 (95% confidence interval 1.26 to 1.36). There was little evidence that this ratio varied by geographical region, age, or any of the personal, socioeconomic, or clinical factors examined, with two exceptions: after adjustment for all major covariates the winter:non-winter ratio in women compared with men was 1.11 (1.00 to 1.23), and those with a self reported history of respiratory illness had a winter:non-winter ratio of 1.20 (1.08 to 1.34) times that of people without a history of respiratory illness. There was no evidence that socioeconomic deprivation or self reported financial worries were predictive of winter death. Conclusion Except for female sex and pre-existing respiratory illness, there was little evidence for vulnerability to winter death associated with factors thought to lead to vulnerability. The lack of socioeconomic gradient suggests that policies aimed at relief of fuel poverty may need to be supplemented by additional measures to tackle the burden of excess winter deaths in elderly people.

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BackgroundSchool closure is a potential intervention during an influenza pandemic and has been investigated in many modelling studies.ObjectivesTo systematically review the effects of school closure on influenza outbreaks as predicted by simulation studies.MethodsWe searched Medline and Embase for relevant modelling studies published by the end of October 2012, and handsearched key journals. We summarised the predicted effects of school closure on the peak and cumulative attack rates and the duration of the epidemic. We investigated how these predictions depended on the basic reproduction number, the timing and duration of closure and the assumed effects of school closures on contact patterns.ResultsSchool closures were usually predicted to be most effective if they caused large reductions in contact, if transmissibility was low (e.g. a basic reproduction number <2), and if attack rates were higher in children than in adults. The cumulative attack rate was expected to change less than the peak, but quantitative predictions varied (e.g. reductions in the peak were frequently 20–60% but some studies predicted >90% reductions or even increases under certain assumptions). This partly reflected differences in model assumptions, such as those regarding population contact patterns.ConclusionsSimulation studies suggest that school closure can be a useful control measure during an influenza pandemic, particularly for reducing peak demand on health services. However, it is difficult to accurately quantify the likely benefits. Further studies of the effects of reactive school closures on contact patterns are needed to improve the accuracy of model predictions.

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