Search

In response to unusual crow die‐offs from avian influenza A(H5N1) virus infection during January‐February 2017 in Dhaka, Bangladesh, a One Health team assessed potential infection risks in live bird markets (LBMs). Evidence of aerosolized avian influenza A viruses was detected in LBMs and in the respiratory tracts of market workers, indicating exposure and potential for infection. This study highlighted the importance of surveillance platforms with a coordinated One Health strategy to investigate and mitigate zoonotic risk.

Highlights • Applicability of GAIA definitions were assessed using medical records in LMICs. • LBW, preterm birth and neonatal death definitions were applicable in the field. • SGA, stillbirth, neonatal infection, congenital microcephaly definitions were less applicable. • Suggestions to the improvement in GAIA definitions were made. • Better documentation of maternal immunization is suggested for vaccine-safety studies., Standardized case definitions strengthen post-marketing safety surveillance of new vaccines by improving generated data, interpretation and comparability across surveillance systems. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project developed standardized case definitions for 21 key obstetric and neonatal terms following the Brighton Collaboration (BC) methodology. In this prospective cohort study, we assessed the applicability of GAIA definitions for maternal immunization exposure and for low birth weight (LBW), preterm birth, small for gestational age (SGA), stillbirth, neonatal death, neonatal infection, and congenital microcephaly. We identified the missing data elements that prevented identified cases and exposures from meeting the case definition (level 1–3 of BC diagnostic certainty). Over a one-year period (2019–2020), all births occurring in 21 sites (mostly secondary and tertiary hospitals) in 6 Low Middle Income Countries and 1 High Income Country were recorded and the 7 perinatal and neonatal outcome cases were identified from routine medical records. Up to 100 cases per outcome were recruited sequentially from each site. Most cases recruited for LBW, preterm birth and neonatal death met the GAIA case definitions. Birth weight, a key parameter for all three outcomes, was routinely recorded at all sites. The definitions for SGA, stillbirth, neonatal infection (particularly meningitis and respiratory infection) and congenital microcephaly were found to be less applicable. The main barrier to obtaining higher levels of diagnostic certainty was the lack of sonographic documentation of gestational age in first or second trimester. The definition for maternal immunization exposure was applicable, however, the highest level of diagnostic certainty was only reached at two sites. Improved documentation of maternal immunization will be important for vaccine safety studies. Following the field-testing of these 8 GAIA definitions, several improvements are suggested that may lead to their easier implementation, increased standardization and hence comparison across studies.

Brucellosis is a zoonotic disease imposing significant impacts on livestock production and public health worldwide. India is the world’s leading milk producer and Punjab is the state which produces the most cattle and buffalo milk per capita. The aim of this study was to investigate the epidemiology of bovine brucellosis to provide evidence for control of the disease in Punjab State, India. A cross-sectional study of dairy farms was conducted in humans and livestock in rural Ludhiana district using a multi-stage sampling strategy. The study suggests that brucellosis is endemic at high levels in cattle and buffalo in the study area with 15.1% of large ruminants testing seropositive and approximately a third of dairy farms having at least one animal test seropositive. In total, 9.7% of those in direct contact with livestock tested seropositive for Brucella spp. Persons that assisted with calving and/or abortion within the last year on a farm with seronegative livestock and people which did not assist with calving/abortion had 0.35 (95% CI: 0.17 to 7.1) and 0.21 (0.09 to 0.46) times the odds of testing seropositive compared to persons assisting with calving/abortion in a seropositive farm, respectively. The study demonstrated that persons in direct contact with cattle and buffalo in the study area have high risk of exposure to Brucella spp. Control of the disease in livestock is likely to result in benefits to both animal and public health sectors., Author summary Brucellosis is a bacterial disease that causes production losses in livestock due to abortions, increased calving intervals and reduced milk production. The disease can also be transmitted to humans via direct contact with livestock when they give birth or abort or via consumption of unpasteurised dairy products. This study aimed to estimate the frequency of exposure to the bacteria (Brucella spp.) in cattle and buffalo in Ludhiana district, Punjab State, India. In addition, persons in contact with these livestock, either through their occupation or household, were also tested for Brucella spp. antibodies and the data used to identify factors increasing their risk of exposure. The study found high levels of exposure in cattle and buffalo in the study area with 15.1% of large ruminants testing positive for antibodies to Brucella spp. (seropositive) and approximately a third of dairy farms having at least one animal test seropositive. Around 10% of people tested seropositive for the bacteria and those that assisted with calving and/or abortion on a farm where at least one animal tested seropositive had a high risk of infection. Control of brucellosis could reduce production losses in livestock and protect humans in contact with livestock from becoming infected.

International audience; BackgroundInfluenza surveillance helps time prevention and control interventions especially where complex seasonal patterns exist. We assessed influenza surveillance sustainability in Africa where influenza activity varies and external funds for surveillance have decreased.MethodsWe surveyed African Network for Influenza Surveillance and Epidemiology (ANISE) countries about 2011-2017 surveillance system characteristics. Data were summarized with descriptive statistics and analyzed with univariate and multivariable analyses to quantify sustained or expanded influenza surveillance capacity in Africa.ResultsEighteen (75%) of 24 ANISE members participated in the survey; their cumulative population of 710 751 471 represent 56% of Africa's total population. All 18 countries scored a mean 95% on WHO laboratory quality assurance panels. The number of samples collected from severe acute respiratory infection case-patients remained consistent between 2011 and 2017 (13 823 vs 13 674 respectively) but decreased by 12% for influenza-like illness case-patients (16 210 vs 14 477). Nine (50%) gained capacity to lineage-type influenza B. The number of countries reporting each week to WHO FluNet increased from 15 (83%) in 2011 to 17 (94%) in 2017.ConclusionsDespite declines in external surveillance funding, ANISE countries gained additional laboratory testing capacity and continued influenza testing and reporting to WHO. These gains represent important achievements toward sustainable surveillance and epidemic/pandemic preparedness.

BackgroundTuberculosis (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.ObjectivesTo 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.MethodsEcological 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.ResultsThere 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).ConclusionsSocio-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.

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 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.

Addressing social determinants of tuberculosis (TB) is essential to achieve elimination, including in low-incidence settings. We measured the association between socio-economic status and intermediate social determinants of health (SDHs, including drug misuse, tobacco smoking and alcohol), and TB, taking into account their clustering in individuals. We conducted a case-control study in 23–38 years old UK-born White adults with first tuberculosis episode, and randomly selected age and sex frequency-matched community controls. Data was collected on education, household overcrowding, tobacco smoking, alcohol and drugs use, and history of homelessness and prison. Analyses were done using logistic regression models, informed by a formal theoretical causal framework (Directed Acyclic Graph). 681 TB cases and 1183 controls were recruited. Tuberculosis odds were four times higher in subjects with education below GCSE O-levels, compared to higher education (OR = 3.94; 95%CI: 2.74, 5.67), after adjusting for other TB risk factors (age, sex, BCG-vaccination and stays ≥3 months in Africa/Asia). When simultaneously accounting for respective SDHs, higher tuberculosis risk was independently associated with tobacco smoking, drugs use (especially injectable drugs OR = 5.67; 95%CI: 2.68, 11.98), homelessness and area-level deprivation. Population Attributable Fraction estimates suggested that tobacco and class-A drug use were, respectively, responsible for 18% and 15% of TB cases in this group. Our findings suggest that socio-economic deprivation remains a driver of tuberculosis in England, including through drugs misuse, tobacco smoking, and homelessness. These findings further support the integration of health and social services in high-risk young adults to improve TB control efforts.

Background The roll-out of anti-retroviral therapy (ART) has changed contexts of human immunodeficiency virus (HIV) risk. Here, we summarise direct estimates of HIV incidence among adolescent girls and young women (AGYW) since ART and before large investments in targeted prevention for AGYW in sub-Saharan Africa. Methods Database searches identified studies reporting HIV incident data from serological samples collected among 15-24 year-old females in 10 countries selected for PEPFAR investment in 2015. Estimates collected between 2005-2015, published or received from authors, were summarised by age and sex, and pooled by region. Findings Fifty-one analyses were identified from nine of the eligible countries (save Lesotho). Directly-observed incidence rates were lowest among AGYW in Kumi, Uganda (0.38%) and highest in KwaZulu-Natal, South Africa (7.8% among 15-19y; 8.6% in 20-24y); fishing communities in Uganda (12.4% and 4.7% among 15-19y and 20-24y females); and among sex workers aged 18-24y in South Africa (13.2%) and Zimbabwe (10.8%). In pooled rates from general population studies, the greatest sex differentials were in the youngest age groups, i.e., 15-19y females compared to males in both Southern African (relative risk=5.94; 95% CI:3.39-10.44) and Eastern African countries (3.22; 95% CI:1.51-6.87), and not significantly different among the oldest (25-29y) in either region. Incidence often peaked earlier (during teenage years) among high-risk compared to general populations. Since 2005, AGYW incidence declined in Rakai (Uganda), Manicaland (Zimbabwe), and among sex workers in Kenya, but not in the highest-risk communities in South Africa. Interpretation Few sources of direct estimates of HIV incidence exist in high-burden countries and trend analyses with age/sex disaggregated data are rare but indicate recent declines among AGYW. In some of the highest-risk settings, however, little evidence exists to suggest ART availability and other efforts slowed transmission by 2016. Despite wide geographic diversity in absolute levels of AGYW incidence, risk relative to males persisted in all settings, with the greatest sex differentials in the youngest age groups. To end new infections among the growing population of adolescents in sub-Saharan Africa, prevention programs must address gender inequalities driving excessive risk among adolescent girls.

Background Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Methods Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. Results The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Conclusions Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

BackgroundEvidence of protection from childhood BCG against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation.MethodsWe conducted a population-based case-control study of protection by BCG given to children aged 12 to 13 years against tuberculosis occurring 10 to 29 years later. We recruited UK-born white subjects with tuberculosis and randomly sampled white community controls. Hazard ratios and 95% confidence intervals were estimated using case-cohort Cox regression, adjusting for potential confounding factors, including socio-economic status, smoking, drug use, prison and homelessness. Vaccine effectiveness (VE=1-hazard ratio) was assessed at successive intervals more than 10 years following vaccinationResultsWe obtained 677 cases and 1170 controls after a 65% response rate in both groups. Confounding by deprivation, education and lifestyle factors was slight 10-20 years after vaccination, more evident after 20 years. VE 10 -15 years after vaccination was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15-20 years. Subsequently BCG protection appeared to wane; 20-25 years VE=25% (CI -14%, 51%) and 25-29 years VE= 1% (CI -84%, 47%). Based on multiple imputation of missing data (in 17% subjects) VE estimated in the same intervals after vaccination were similar (56% (CI 33, 72%), 57% (CI 36, 71%), 25% (-10, 48%), 21% (-39, 55%).ConclusionsSchool-age BCG vaccination offered moderate protection against tuberculosis for at least 20 years which is longer than previously thought. This has implications for assessing the costeffectiveness of BCG vaccination and when evaluating new TB vaccines.

Time series regression has been developed and long used to evaluate the short-term associations of air pollution and weather with mortality or morbidity of non-infectious diseases. The application of the regression approaches from this tradition to infectious diseases, however, is less well explored and raises some new issues.We discuss and present potential solutions for five issues often arising in such analyses: changes in immune population, strong autocorrelations, a wide range of plausible lag structures and association patterns, seasonality adjustments, and large overdispersion.The potential approaches are illustrated with datasets of cholera cases and rainfall from Bangladesh and influenza and temperature in Tokyo. Though this article focuses on the application of the traditional time series regression to infectious diseases and weather factors, we also briefly introduce alternative approaches, including mathematical modeling, wavelet analysis, and autoregressive integrated moving average (ARIMA) models.Modifications proposed to standard time series regression practice include using sums of past cases as proxies for the immune population, and using the logarithm of lagged disease counts to control autocorrelation due to true contagion, both of which are motivated from "susceptible-infectious-recovered" (SIR) models. The complexity of lag structures and association patterns can often be informed by biological mechanisms and explored by using distributed lag non-linear models. For overdispersed models, alternative distribution models such as quasi-Poisson and negative binomial should be considered. Time series regression can be used to investigate dependence of infectious diseases on weather, but may need modifying to allow for features specific to this context., Environmental Research, 142, pp.319-327; 2015

BackgroundUntil recently, evidence that protection from the bacillus Calmette–Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK’s universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced.ObjectivesTo assess the duration of protection of infant and school-age BCG vaccination against TB in the UK.MethodsTwo case–control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0–19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10–29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case–cohort analysis based on Cox regression.ResultsIn the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10–15 years after vaccination and 57% (95% CI 33% to 72%) 15–20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading.LimitationsThe difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination.ConclusionsInfant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading.FundingThe National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.

Almost all human infections by avian influenza viruses (AIVs) are transmitted from poultry. A systematic review was conducted to identify practices associated with human infections, their prevalence, and rationale. Observational studies were identified through database searches. Meta-analysis produced combined odds ratio estimates. The prevalence of practices and rationales for their adoptions were reported. Of the 48,217 records initially identified, 65 articles were included. Direct and indirect exposures to poultry were associated with infection for all investigated viral subtypes and settings. For the most frequently reported practices, association with infection seemed stronger in markets than households, for sick and dead than healthy poultry, and for H7N9 than H5N1. Practices were often described in general terms and their frequency and intensity of contact were not provided. The prevalence of practices was highly variable across studies, and no studies comprehensively explored reasons behind the adoption of practices. Combining epidemiological and targeted anthropological studies would increase the spectrum and detail of practices that could be investigated and should aim to provide insights into the rationale(s) for their existence. A better understanding of these rationales may help to design more realistic and acceptable preventive public health measures and messages.

School closure is often considered as an influenza control measure, but its effects on transmission are poorly understood. We used 2 approaches to estimate how school holidays affect the contact parameter (the per capita rate of contact sufficient for infection transmission) for influenza using primary care data from England and Wales (1967–2000). Firstly, we fitted an age-structured susceptible-infectious-recovered model to each year's data to estimate the proportional change in the contact parameter during school holidays as compared with termtime. Secondly, we calculated the percentage difference in the contact parameter between holidays and termtime from weekly values of the contact parameter, estimated directly from simple mass-action models. Estimates were combined using random-effects meta-analysis, where appropriate. From fitting to the data, the difference in the contact parameter among children aged 5–14 years during holidays as compared with termtime ranged from a 36% reduction to a 17% increase; estimates were too heterogeneous for meta-analysis. Based on the simple mass-action model, the contact parameter was 17% (95% confidence interval: 10, 25) lower during holidays than during termtime. Results were robust to the assumed proportions of infections that were reported and individuals who were susceptible when the influenza season started. We conclude that school closure may reduce transmission during influenza outbreaks.

Summary Background Little is known about how long the BCG vaccine protects against tuberculosis. We assessed the long-term vaccine effectiveness (VE) in Norwegian-born individuals. Methods 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. Findings 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). Interpretation 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 Funding Norwegian Institute of Public Health and London School of Hygiene & Tropical Medicine.

Background: South Asian migrants show lower cancer incidence than their host population in England for most major cancers. We seek to study the ethnic differences in survival from cancer. Methods: We described and modelled the effect of ethnicity, time, age and deprivation on survival for the five most incident cancers in each sex in South Asians in England between 1986 and 2004 using national cancer registry data. South Asian ethnicity was flagged using the validated name-recognition algorithm SANGRA (South Asian Names and Group Recognition Algorithm). Results: We observed survival advantage in South Asians in earlier periods. This ethnic gap either remained constant or narrowed over time. By 2004, age-standardised net survival was comparable for all cancers except three in men, where South Asians had higher survival 5 years after diagnosis: colorectal (58.9% vs 53.6%), liver (15.0% vs 9.4%) and lung (15.9% vs 9.3%). Compared with non-South Asians, South Asians experienced a slower increase in breast and prostate cancer survival, both cancers associated with either a screening programme or an early diagnosis test. We did not find differential patterns in survival by deprivation between both ethnicities. Conclusions: Considering recent survival trends, appropriate action is required to avoid deficits in cancer survival among South Asians in the near future.

South Asian women in England have a lower breast cancer risk than their English-native counterparts, but less is known about variations in risk between distinct South Asian ethnic subgroups. We used the data from a population-based case-control study of first-generation South Asian migrants to assess risks by ethnic subgroup. In all, 240 breast cancer cases, identified through cancer registries, were individually matched on age and general practitioner to two controls. Information on the region of origin, religious and linguistic background, and on breast cancer risk factors was obtained from participants. Breast cancer odds varied significantly between the ethnic subgroups (P=0.008), with risk increasing in the following order: Bangladeshi Muslims (odds ratio (OR) 0.33, 95% confidence interval (CI): 0.10, 1.06), Punjabi Hindu (OR 0.59, 95% CI: 0.33, 1.27), Gujarati Hindu (1=reference group), Punjabi Sikh (OR 1.23, 95% CI: 0.72, 2.11) and Pakistani/Indian Muslims (OR 1.76, 95% CI: 1.10, 2.81). The statistically significant raised risk in Pakistani/Indian Muslims increased with adjustment for socioeconomic and reproductive risk factors (OR 2.12, 95% CI: 1.25, 3.58), but was attenuated, and no longer significant, with further adjustment for waist circumference and intake of nonstarch polysaccharides and fat (OR 1.49, 95% CI: 0.85, 2.63). These findings reveal differences in breast cancer risk between South Asian ethnic subgroups, which were not fully explained by reproductive differences, but were partly accounted for by diet and body size.

BACKGROUND: Recent evidence suggests that the duration of protection by bacillus Calmette-Guerin (BCG) may exceed previous estimates with potential implications for estimating clinical and cost-efficacy. OBJECTIVES: To estimate the protection and duration of protection provided by BCG vaccination against tuberculosis, explore how this protection changes with time since vaccination, and examine the reasons behind the variation in protection and the rate of waning of protection. DATA SOURCES: Electronic databases including MEDLINE, Excerpta Medica Database (EMBASE), Cochrane Databases, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE), Web of Knowledge, Biosciences Information Service (BIOSIS), Latin American and Caribbean Health Sciences Literature (LILACs), MEDCARIB Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from inception to May 2009. Index to Theses, System for Information on Grey Literature in Europe (SIGLE), Centre for Agricultural Bioscience International (CABI) Abstracts, Scopus, Article First, Academic Complete, Africa-Wide Information, Google Scholar, Global Health, British National Bibliography for Report Literature, and clinical trial registration websites were searched from inception to October 2009. REVIEW METHODS: Electronic databases searches, screening of identified studies, data extraction and analysis were undertaken. Meta-analysis was used to present numerical and graphical summaries of clinical efficacy and efficacy by time since vaccination. Evidence of heterogeneity was assessed using the tau-squared statistic. Meta-regression allowed the investigation of observed heterogeneity. Factors investigated included BCG strain, latitude, stringency of pre-BCG vaccination tuberculin testing, age at vaccination, site of disease, study design and vulnerability to biases. Rate of waning of protection was estimated using the ratio of the measure of efficacy after 10 years compared with the efficacy in the first 10 years of a study. RESULTS: Study selection. A total of 21,030 references were identified, providing data on 132 studies after abstract and full-text review. Efficacy. Protection against pulmonary tuberculosis in adults is variable, ranging from substantial protection in the UK MRC trial {rate ratio 0.22 [95% confidence interval (CI) 0.16 to 0.31]}, to absence of clinically important benefit, as in the large Chingleput trial [rate ratio 1.05 (95% CI 0.88 to 1.25)] and greater in latitudes further away from the equator. BCG vaccination efficacy was usually high, and varied little by form of disease (with higher protection against meningeal and miliary tuberculosis) or study design when BCG vaccination was given only to infants or to children after strict screening for tuberculin sensitivity. High levels of protection against death were observed from both trials and observational studies. The observed protective effect of BCG vaccination did not differ by the strain of BCG vaccine used in trials. DURATION: Reviewed studies showed that BCG vaccination protects against pulmonary and extrapulmonary tuberculosis for up to 10 years. Most studies either did not follow up participants for long enough or had very few cases after 15 years. This should not be taken to indicate an absence of effect: five studies (one trial and four observational studies) provided evidence of measurable protection at least 15 years after vaccination. Efficacy declined with time. The rate of decline was variable, with faster decline in latitudes further from the equator and in situations where BCG vaccination was given to tuberculin-sensitive participants after stringent tuberculin testing. LIMITATIONS: The main limitation of this review relates to quality of included trials, most of which were conducted before current standards for reporting were formulated. In addition, data were lacking in some areas and the review had to rely on evidence from observational studies. CONCLUSIONS: BCG vaccination protection against tuberculosis varies between populations, to an extent that cannot be attributed to chance alone. Failure to exclude those already sensitised to mycobacteria and study latitude closer to the equator were associated with lower efficacy. These factors explained most of the observed variation. There is good evidence that BCG vaccination protection declines with time and that protection can last for up to 10 years. Data on protection beyond 15 years are limited; however, a small number of trials and observational studies suggest that BCG vaccination may protect for longer. Further studies are required to investigate the duration of protection by BCG vaccination. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

SUMMARYCompletion of treatment is key to tuberculosis control. Using national surveillance data we assessed factors associated with tuberculosis patients being lost to follow-up before completing treatment (‘lost’). Patients reported in England, Wales and Northern Ireland between 2001 and 2007 who were lost 12 months after beginning treatment were compared to those who completed, or were still on treatment, using univariable and multivariable logistic regression. Of 41 120 patients, men [adjusted odds ratio (aOR) 1·29; 95% confidence interval (CI) 1·23–1·35], 15- to 44-year-olds (P

To determine how school closure for pandemic (H1N1) 2009 affected students’ contact patterns, we conducted a retrospective questionnaire survey at a UK school 2 weeks after the school reopened. School closure was associated with a 65% reduction in the mean total number of contacts for each student.

Background Since 2004, 21 highly pathogenic avian influenza H5N1 outbreaks in domestic poultry and eight human cases have been confirmed in Cambodia. As a result, a large number of avian influenza education campaigns have been ongoing in provinces in which H5N1outbreaks have occurred in humans and/or domestic poultry. Methodology/Principal Findings Data were collected from 1,252 adults >15 years old living in two southern provinces in Cambodia where H5N1 has been confirmed in domestic poultry and human populations using two cross-sectional surveys conducted in January 2006 and in November/December 2007. Poultry handling behaviors, poultry mortality occurrence and self-reported notification of suspect H5N1 poultry cases to animal health officials in these two surveys were evaluated. Our results demonstrate that although some at risk practices have declined since the first study, risky contact with poultry is still frequent. Improved rates of reporting poultry mortality were observed overall, but reporting to trained village animal health workers decreased by approximately 50%. Conclusions/Significance Although some improvements in human behavior have occurred, there are still areas—particularly with respect to the handling of poultry among children and the proper treatment of poultry and the surrounding household environment—that need to be addressed in public health campaigns. Though there were some differences in the sampling methods of the 2006 and 2007 surveys, our results illustrate the potential to induce considerable, potentially very relevant, behavioral changes over a short period of time.

Objective To estimate the protection against death provided by vaccination against influenza. Design Prospective cohort follow up supplemented by weekly national counts of influenza confirmed in the community. Setting Primary care. Participants 24 535 patients aged over 75 years from 73 general practices in Great Britain. Main outcome measure Death. Results In unvaccinated members of the cohort daily all cause mortality was strongly associated with an index of influenza circulating in the population (mortality ratio 1.16, 95% confidence interval 1.04 to 1.29 at 90th centile of circulating influenza). The association was strongest for respiratory deaths but was also present for cardiovascular deaths. In contrast, in vaccinated people mortality from any cause was not associated with circulating influenza. The difference in patterns between vaccinated and unvaccinated people could not easily be due to chance (P = 0.02, all causes). Conclusions This study, using a novel and robust approach to control for confounding, provides robust evidence of a protective effect on mortality of vaccination against influenza.

Background Influenza vaccination policy for elderly people in Britain has changed twice since 1997 to increase protection against influenza but there is no information available on how this has affected vaccine uptake, and socioeconomic variation therein, among people aged over 74 years. Methods Vaccination information for 1997–2000 was collected directly from general practices taking part in a MRC-funded Trial of the Assessment and Management of Older People in the Community. This was linked to information collected during assessments carried out as part of the Trial. Regression modelling was used to assess relative probabilities (as relative risks, RR) of having vaccination according to year, gender, age, area and individual socioeconomic characteristics. Results Out of 106 potential practices, 73 provided sufficient information to be included in the analysis. Uptake was 48% (95% CI 45%, 55%) in 1997 and did not increase substantially until 2000 when the uptake was a third higher at 63% (50%, 66%). Vaccination uptake was lower among women than men (RR 0.9), people aged 85 or more compared to people aged under 80 (RR 0.9), those in the most deprived areas (RR 0.8) compared to the least deprived, and was relatively high for those in owner-occupied homes with central heating compared to other non-supported housing (RR for remainder = 0.9). This pattern did not change over the years studied. Conclusions Increased uptake in 2000 may have resulted from the additional financial resources given to practices; it was not at the expense of more disadvantaged socioeconomic groups but nor did they benefit disproportionately.

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 > or = 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.

Ethnic differences in breast cancer survival have been observed in the USA but have not been examined in Britain. We aimed to investigate such differences between South Asian (i.e. those with family roots in the Indian subcontinent) and non-South Asian (essentially British-native) women in England. Primary breast cancer cases incident in 1986 -1993 and resident in South East England were ascertained through the Thames Cancer and Registry and followed up to the end of 1997. Cases of South Asian ethnicity were identified on the basis of their names by using a previously validated computer algorithm. A total of 1037 South Asian and 50 201 non-South Asian breast cancer cases were included in the analysis; 30% of the South Asian (n=312) and 44% (n=22 201) of the non-South Asian cases died during follow-up. South Asian cases had a higher relative survival than non-South Asians throughout the follow-up period. The 10-year relative survival rates were 72.6% (95% confidence interval: 69.0, 75.9%) and 65.2% (64.5, 65.8%) for South Asians and non-South Asians, respectively. The excess mortality rates experienced by South Asians were 82% (72, 94%) of those experienced by non-South Asians (P=0.004). The magnitude of this effect was slightly reduced with adjustment for differences in age at diagnosis, but was strengthened with further adjustment for differences in stage at presentation and socioeconomic deprivation (excess mortality rates in South Asians relative to non-South Asians=72% (63, 82%), P&