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School closure is a potential intervention during an influenza pandemic and has been investigated in many modelling studies. To systematically review the effects of school closure on influenza outbreaks as predicted by simulation studies. We 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. School 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. Simulation 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.

Little is known about how long the BCG vaccine protects against tuberculosis. We assessed the long-term vaccine effectiveness (VE) in Norwegian-born individuals. In this retrospective population-based cohort study, we studied Norwegian-born individuals aged 12–50 years who were tuberculin skin test (TST) negative and eligible for BCG vaccination as part of the last round of Norway's mandatory mass tuberculosis screening and BCG vaccination programme between 1962 and 1975. We excluded individuals who had tuberculosis before or in the year of screening and those with unknown TST and BCG status. We obtained TST and BCG information and linked it to the National Tuberculosis Register, population and housing censuses, and the population register for emigrations and deaths. We followed individuals up to their first tuberculosis episode, emigration, death, or Dec 31, 2011. We used Cox regressions to estimate VE against all tuberculosis and just pulmonary tuberculosis by time since vaccination, adjusted for age, time, county-level tuberculosis rates, and demographic and socioeconomic indicators. Median follow-up was 41 years (IQR 32–49) for 83 421 BCG-unvaccinated and 44 years (41–46) for 297 905 vaccinated individuals, with 260 tuberculosis episodes. Tuberculosis rates were 3·3 per 100 000 person-years in unvaccinated and 1·3 per 100 000 person-years in vaccinated individuals. The adjusted average VE during 40 year follow-up was 49% (95% CI 26–65), although after 20 years, the VE was not significant (up to 9 years VE [excluding tuberculosis episodes in the first 2 years] 61% [95% CI 24–80]; 10–19 years 58% [27–76]; 20–29 years 38% [–32 to 71]; 30–40 years 42% [–24 to 73]). VE against pulmonary tuberculosis up to 9 years (excluding tuberculosis episodes in the first 2 years) was 67% (95% CI 27–85), 10–19 years was 63% (32–80), 20–29 years was 50% (−19 to 79), and 30–40 years was 40% (−46 to 76). Findings are consistent with long-lasting BCG protection, but waning of VE with time. The vaccine could be more cost effective than has been previously estimated Norwegian Institute of Public Health and London School of Hygiene & Tropical Medicine.

Background. Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood. Methods. We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression. Results. We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18–.37), or infants (RR, 0.41; 95% CI, .29–.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35–1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59–1.31 and RR, 0.81; 95% CI, .55–1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01–.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03–.25). Conclusions. 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.

Live animal markets are known hotspots of zoonotic disease emergence. To mitigate those risks, we need to understand how networks shaped by trading practices influence disease spread. Yet, those practices are rarely recorded in high-risk settings. Through a large cross-sectional study, we assessed the potential impact of live poultry trading networks’ structures on avian influenza transmission dynamics in Bangladesh. Networks promoted mixing between chickens sourced from different farming systems and geographical locations, fostering co-circulation of viral strains of diverse origins in markets. Viral transmission models suggested that the observed rise in viral prevalence from farms to markets was unlikely explained by intra-market transmission alone, but substantially influenced by transmission occurring in upstream network nodes. Disease control interventions should therefore alter the entire network structures. However, as networks differed between chicken types and city supplied, standardised interventions are unlikely to be effective, and should be tailored to local structural characteristics.

Objective To review the effects of school closures on pandemic and seasonal influenza outbreaks. Design Systematic review. Data sources MEDLINE and EMBASE, reference lists of identified articles, hand searches of key journals and additional papers from the authors' collections. Study selection Studies were included if they reported on a seasonal or pandemic influenza outbreak coinciding with a planned or unplanned school closure. Results Of 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. Conclusions School 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.

Tuberculosis (TB) rates in England are among the highest in high-income countries. Poverty and historic and current immigration from high TB incidence parts of the world are two major drivers of tuberculosis in England. However, little has been done in recent years to examine socio-economic trends in TB rates in England, and to disentangle the role of deprivation from that of place of birth in the current TB epidemiology. To assess the association between England's 2008-2012 TB notification rates and small area-level deprivation, together and separately in the UK-born and foreign-born populations. Ecological analysis of the association between quintiles of England's 2010 Index of Multiple Deprivation (IMD) and TB rates at the Lower-layer Super Output Area (LSOA; average population ~1500) level, using negative binomial and zero-inflated negative binomial regression models, adjusting for age, sex, urban/rural area classification, and area-level percentage of non-White residents. There was a log-linear gradient between area-deprivation levels and TB rates, with overall TB rates in the most deprived quintile areas three times higher than the least deprived quintile after adjustment for age and sex (IRR = 3.35; 95%CI: 3.16 to 3.55). The association and gradient were stronger in the UK-born than the foreign-born population, with UK-born TB rates in the most deprived quintiles about two-and-a-half times higher than the least deprived quintile (IRR = 2.39; 95%CI: 2.19 to 2.61) after controlling for age, sex, urban/rural classification and percentage of non-White residents; whereas the comparable figure for foreign-born persons was 80% higher (IRR = 1.78; 95%CI: 1.66 to 1.91). Socio-economic deprivation continues to play a substantial role in sustaining the TB epidemic in England, especially in the UK-born population. This supports the case for further investigations of the underlying social- determinants of TB.

Highly pathogenic avian influenza virus subtype H5N1 is endemic in Asia, with live bird trade as a major disease transmission pathway. A cross-sectional survey was undertaken in northern Vietnam to investigate the structure of the live bird market (LBM) contact network and the implications for virus spread. Based on the movements of traders between LBMs, weighted and directed networks were constructed and used for social network analysis and individual-based modeling. Most LBMs were connected to one another, suggesting that the LBM network may support large-scale disease spread. Because of cross-border trade, it also may promote transboundary virus circulation. However, opportunities for disease control do exist. The implementation of thorough, daily disinfection of the market environment as well as of traders’ vehicles and equipment in only a small number of hubs can disconnect the network dramatically, preventing disease spread. These targeted interventions would be an effective alternative to the current policy of a complete ban of LBMs in some areas. Some LBMs that have been banned still are very active, and they likely have a substantial impact on disease dynamics, exhibiting the highest levels of susceptibility and infectiousness. The number of trader visits to markets, information that can be collected quickly and easily, may be used to identify LBMs suitable for implementing interventions. This would not require prior knowledge of the force of infection, for which laboratory-confirmed surveillance would be necessary. These findings are of particular relevance for policy development in resource-scarce settings.

Background People with end-stage kidney disease have an increased risk of active tuberculosis (TB). Previous systematic reviews have demonstrated that patients with chronic kidney disease (CKD) have increased risk of severe community-acquired infections. We investigated the association between CKD (prior to renal replacement therapy) and incidence of TB in UK General Practice. Methods Using the UK Clinical Practice Research Datalink, 242,349 patients with CKD (stages 3-5) (estimated glomerular filtration rate < 60 mL/min/1.73 m 2 for ≥3 months) between April 2004 and March 2014 were identified and individually matched (by age, gender, general practice and calendar time) to a control from the general population without known CKD. The association between CKD (overall and by stage) and incident TB was investigated using a Poisson regression analysis adjusted for age, gender, ethnicity, socio-economic status, chronic obstructive pulmonary disease (COPD) and diabetes. Results The incidence of TB was higher amongst patients with CKD compared to those without CKD: 14.63 and 9.89 cases per 100,000 person-years. After adjusting for age, gender, ethnicity, socio-economic status, diabetes and COPD, the association between CKD and TB remained (adjusted rate ratio [RR] 1.42, 95% confidence interval [CI] 1.01–1.85). The association may be stronger amongst those from non-white ethnic minorities (adjusted RR 2.83, 95%CI 1.32–6.03, p -value for interaction with ethnicity = 0.061). Amongst those with CKD stages 3–5, there was no evidence of a trend with CKD severity. Conclusions CKD is associated with an increased risk of TB diagnosis in a UK General Practice cohort. This group of patients should be considered for testing and treating for latent TB.

Avian influenza is endemic in Bangladesh, where greater than 90% of poultry are marketed through live poultry markets (LPMs). We conducted a population-based cross-sectional mobile telephone survey in urban Dhaka, Bangladesh to investigate the frequency and patterns of human exposure to live poultry in LPMs and at home. Among 1047 urban residents surveyed, 74.2% (95% CI 70.9–77.2) reported exposure to live poultry in the past year, with the majority of exposure occurring on a weekly basis. While visiting LPMs was less common amongst females (40.3%, 95% CI 35.0–45.8) than males (58.9%, 95% CI 54.0–63.5), females reported greater poultry exposure through food preparation, including defeathering (13.2%, 95% CI 9.5–17.9) and eviscerating (14.8%, 95% CI 11.2–19.4) (p < 0.001). A large proportion of the urban population is frequently exposed to live poultry in a setting where avian influenza viruses are endemic in LPMs. There is thus not only ample opportunity for spillover of avian influenza infections into humans in Dhaka, Bangladesh, but also greater potential for viral reassortment which could generate novel strains with pandemic potential.

Changes in children's contact patterns between termtime and school holidays affect the transmission of several respiratory-spread infections. Transmission of varicella zoster virus (VZV), the causative agent of chickenpox, has also been linked to the school calendar in several settings, but temporal changes in the proportion of young children attending childcare centres may have influenced this relationship. We used two modelling methods (a simple difference equations model and a Time series Susceptible Infectious Recovered (TSIR) model) to estimate fortnightly values of a contact parameter (the per capita rate of effective contact between two specific individuals), using GP consultation data for chickenpox in England and Wales from 1967-2008. The estimated contact parameters were 22-31% lower during the summer holiday than during termtime. The relationship between the contact parameter and the school calendar did not change markedly over the years analysed. In England and Wales, reductions in contact between children during the school summer holiday lead to a reduction in the transmission of VZV. These estimates are relevant for predicting how closing schools and nurseries may affect an outbreak of an emerging respiratory-spread pathogen.