Estimates of the transmissibility of the 1968 (Hong Kong) influenza pandemic: evidence of increased transmissibility between successive waves.

The transmissibility of the strain of influenza virus which caused the 1968 influenza pandemic is poorly understood. Increases in outbreak size between the first and second waves suggest that it may even have increased between successive waves. The authors estimated basic and effective reproduction numbers for both waves of the 1968 influenza pandemic. Epidemic curves and overall attack rates for the 1968 pandemic, based on clinical and serologic data, were retrieved from published literature. The basic and effective reproduction numbers were estimated from 46 and 17 data sets for the first and second waves, respectively, based on the growth rate and/or final size of the epidemic. Estimates of the basic reproduction number (R(0)) were in the range of 1.06-2.06 for the first wave and, assuming cross-protection, 1.21-3.58 in the second. Within each wave, there was little geographic variation in transmissibility. In the 10 settings for which data were available for both waves, R(0) was estimated to be higher during the second wave than during the first. This might partly explain the larger outbreaks in the second wave as compared with the first. This potential for change in viral behavior may have consequences for future pandemic mitigation strategies

An economic analysis of a pneumococcal vaccine programme in people aged over 64 years in a developed country setting.

BACKGROUND: Polysaccharide pneumococcal vaccination for older adults is being introduced in developed country settings. Evidence of protection by this vaccine against pneumococcal pneumonia, or confirmation that illness and death from bacteraemia are prevented, is currently limited. Decisions are often made based on partial information. We examined the policy implications by exploring the potential economic benefit to society and the health sector of pneumococcal vaccination in older adults. METHODS: A model to estimate the potential cost savings and cost-effectiveness of a polysaccharide pneumococcal vaccine programme was based on costs collected from patients, the literature, and routine health-services data. The effect of a pneumococcal vaccine (compared with no vaccination) was examined in a hypothetical cohort aged over 64 years. The duration of protection was assumed to be 10 years, with or without a booster at 5 years. RESULTS: If it were effective against morbidity from pneumococcal pneumonia, the main burden from pneumococcal disease, the vaccine could be cost-neutral to society or the health sector at low efficacy (28 and 37.5%, respectively, without boosting and with 70% coverage). If it were effective against morbidity from bacteraemia only, the vaccine's efficacy would need to be 75 and 89%, respectively. If protection against both morbidity and mortality from pneumococcal bacteraemia was 50%, the net cost to society would be 2500 pounds per year of life saved ( 3365 pounds from the health-sector perspective). Results were sensitive to incidence, case-fatality rates, and costs of illness. CONCLUSIONS: A vaccine with moderate efficacy against bacteraemic illness and death would be cost-effective. If it also protected against pneumonia, it would be cost-effective even if its efficacy were low

Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses.

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

Formative research on the feasibility of hygiene interventions for influenza control in UK primary schools

<p>Abstract</p> <p>Background</p> <p>Interventions to increase hand washing in schools have been advocated as a means to reduce the transmission of pandemic influenza and other infections. However, the feasibility and acceptability of effective school-based hygiene interventions is not clear.</p> <p>Methods</p> <p>A pilot study in four primary schools in East London was conducted to establish the current need for enhanced hand hygiene interventions, identify barriers to their implementation and to test their acceptability and feasibility. The pilot study included key informant interviews with teachers and school nurses, interviews, group discussions and essay questions with the children, and testing of organised classroom hand hygiene activities.</p> <p>Results</p> <p>In all schools, basic issues of personal hygiene were taught especially in the younger age groups. However, we identified many barriers to implementing intensive hygiene interventions, in particular time constraints and competing health issues. Teachers' motivation to teach hygiene and enforce hygienic behaviour was primarily educational rather than immediate infection control. Children of all age groups had good knowledge of hygiene practices and germ transmission.</p> <p>Conclusion</p> <p>The pilot study showed that intensive hand hygiene interventions are feasible and acceptable but only temporarily during a period of a particular health threat such as an influenza pandemic, and only if rinse-free hand sanitisers are used. However, in many settings there may be logistical issues in providing all schools with an adequate supply. In the absence of evidence on effectiveness, the scope for enhanced hygiene interventions in schools in high income countries aiming at infection control appears to be limited in the absence of a severe public health threat.</p

Small-area level socio-economic deprivation and tuberculosis rates in England: An ecological analysis of tuberculosis notifications between 2008 and 2012.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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

The impact of targeting all elderly persons in England and Wales for yearly influenza vaccination: excess mortality due to pneumonia or influenza and time trend study.

OBJECTIVE: To investigate the impact on mortality due to pneumonia or influenza of the change from risk-based to age group-based targeting of the elderly for yearly influenza vaccination in England and Wales. DESIGN: Excess mortality estimated using time series of deaths registered to pneumonia or influenza, accounting for seasonality, trend and artefacts. Non-excess mortality plotted as proxy for long-term trend in mortality. SETTING: England and Wales. PARTICIPANTS: Persons aged 65-74 and 75+ years whose deaths were registered to underlying pneumonia or influenza between 1975/1976 and 2004/2005. OUTCOME MEASURES: Multiplicative effect on average excess pneumonia and influenza deaths each winter in the 4-6 winters since age group-based targeting of vaccination was introduced (in persons aged 75+ years from 1998/1999; in persons aged 65+ years from 2000/2001), estimated using multivariable regression adjusted for temperature, antigenic drift and vaccine mismatch, and stratified by dominant circulating influenza subtype. Trend in baseline weekly pneumonia and influenza death rates. RESULTS: There is a suggestion of lower average excess mortality in the six winters after age group-based targeting began compared to before, but the CI for the 65-74 years age group includes no difference. Trend in baseline pneumonia and influenza mortality shows an apparent downward turning point around 2000 for the 65-74 years age group and from the mid-1990s in the 75+ years age group. CONCLUSIONS: There is weakly supportive evidence that the marked increases in vaccine coverage accompanying the switch from risk-based to age group-based targeting of the elderly for yearly influenza vaccination in England and Wales were associated with lower levels of pneumonia and influenza mortality in older people in the first 6 years after age group-based targeting began. The possible impact of these policy changes is observed as weak evidence for lower average excess mortality as well as a turning point in baseline mortality coincident with the changes

A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom general practice research database.

BACKGROUND: The effectiveness of influenza vaccination against hospitalization and death can only ethically be assessed in observational studies. A concern is that individuals who are vaccinated are healthier than individuals who are not vaccinated, potentially biasing estimates of effectiveness upward. METHODS: We conducted a historical cohort study of individuals >64 years of age, for whom there were data available in the General Practice Research Database for 1989 to 1999 in England and Wales. Rates of admissions for acute respiratory diseases and rates of death due to respiratory disease were compared over 692,819 person-years in vaccine recipients and 1,534,280 person-years in vaccine nonrecipients. RESULTS: The pooled effectiveness of vaccine against hospitalizations for acute respiratory disease was 21% (95% confidence interval [CI], 17%-26%). The rate reduction attributable to vaccination was 4.15 hospitalizations/100,000 person-weeks in the influenza season. Among vaccine recipients, no important reduction in the number of admissions to the hospital was seen outside influenza seasons. The pooled effectiveness of vaccine against deaths due to respiratory disease was 12% (95% CI, 8%-16%). A greater proportionate reduction was seen among people without medical disorders, but absolute rate reduction was higher in individuals with medical disorders, compared with individuals without such disorders (6.14 deaths due to respiratory disease/100,000 person-weeks vs. 3.12 deaths due to respiratory disease/100,000 person-weeks). Clear protection against death due to all causes was not seen. CONCLUSIONS: Influenza vaccination reduces the number of hospitalizations and deaths due to respiratory disease, after correction for confounding in individuals >64 years of age who had a high risk or a low risk for influenza. For elderly people, untargeted influenza vaccination is of confirmed benefit against serious outcomes

Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study.

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

Drug misuse, tobacco smoking, alcohol and other social determinants of tuberculosis in UK-born adults in England: a community-based case-control study.

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

The identification and validity of congenital malformation diagnoses in UK electronic health records: A systematic review

PURPOSE: To describe the methods used to identify and validate congenital malformation diagnoses recorded in UK electronic health records, and the results of validation studies. METHODS: Medline and Embase were searched for publications between 1987 and 2019 that involved identifying congenital malformations from UK electronic health records using diagnostic codes. The methods and code-lists used to identify congenital malformations, and the methods and results of validations, were examined. RESULTS: We retrieved 54 eligible studies; 36 identified congenital malformations from primary care data and 18 from secondary care data alone or in combination with birth and/or death records. Identification in secondary care data relied on codes from the 'Q' chapter for congenital malformations in ICD-10. In contrast, studies using primary care data frequently used additional codes outside of the 'P' chapter for congenital malformation diagnoses in Read, although the exact codes used were not always clear. Eight studies validated diagnoses identified in primary care data. The positive predictive value was highest (80%-100%) for congenital malformations overall, major malformations, and heart defects although the validity of the reference standard used was often uncertain. It was lowest for neural tube defects (71%) and developmental hip dysplasia (56%). CONCLUSIONS: Studies identifying congenital malformations from primary care data provided limited details about the methods used. The few validation studies were limited to diagnoses recorded in primary care. Further assessments of all measures of validity in both data sources and of other malformation subgroups are needed, using robust reference standards and adhering to reporting guidelines