Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guérin vaccination against tuberculosis.

BACKGROUND: Recent evidence suggests that the duration of protection by bacillus Calmette-Guérin (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.

A case-control study of sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of clustering.

BACKGROUND: The authors investigated whether cases of sporadic Creutzfeldt-Jakob disease (CJD) had lived closer to one another at some time in life than individuals without sporadic CJD. Such a phenomenon would be compatible with some cases resulting from transmission. METHODS: UK sporadic CJD cases occurring from 1990 to 1998 were identified. Age-, sex- and hospital-matched controls were recruited. Lifetime residential histories were obtained by interview, usually with a proxy respondent. With use of Monte Carlo simulation, the residential proximity of cases during various time periods was compared with that expected in the absence of any clustering, using the information collected on the controls. RESULTS: Two hundred twenty sporadic CJD disease cases and 220 controls were included. Cases lived closer together than might be expected in the absence of any disease-clustering mechanism. This evidence became stronger as the critical period during which residential proximity was required to have occurred extended further into the past. CONCLUSIONS: These findings are consistent with some sporadic Creutzfeldt-Jakob disease (CJD) cases resulting from exposure to a common external factor. The rarity of sporadic CJD suggests that repeated point-source outbreaks of infection are more likely to explain our observations than direct case-to-case transmission. Identifying sources of such outbreaks many years after the event will be extremely difficult.

Comparison of outcomes of acute care in short-term residential treatment and psychiatric hospital settings.

OBJECTIVE: The study compared the demographic and diagnostic characteristics of clients and the outcomes of treatment in five short-term acute residential treatment programs and two acute hospital-based psychiatric programs. METHODS: A total of 368 clients in the short-term acute residential treatment programs and 186 clients in the psychiatric hospital programs participated in an observational study. The study used a repeated-measures design and assessed participants on multiple standardized measures of symptoms and functioning at admission, discharge, and four-month follow-up. Comparisons between the two groups were conducted separately by diagnostic category. Measures included the Brief Symptom Inventory, the Behavior and Symptom Identification Scale-32, the Medical Outcomes Short-Form-36, and the Client Satisfaction Questionnaire-8. RESULTS: The two types of programs admit persons with similar levels of acute distress who have comparable levels of improvement at discharge and an equivalent degree of short-term stability of treatment gains. Costs of treatment episodes were considerably lower for the short-term residential programs, and client satisfaction with the two types of programs was comparable. CONCLUSIONS: Short-term acute residential treatment is a less costly yet similarly effective alternative to psychiatric hospitalization for many voluntary adult patients.

Risk of death from motor-vehicle injury in Brazilian steelworkers: a nested case-control study.

OBJECTIVES: In a cohort of 21,816 Brazilian steelworkers we found mortality from motor-vehicle injury was twice that in the State population. A nested case-control study was therefore undertaken to investigate possible socio-demographic, medical and occupational risk factors for this increased risk. METHODS: Cases were defined as all steelworkers in the cohort who died of motor-vehicle injury during employment in the period 1977-1992. For each case, four controls were selected at random from workers in the cohort who were employed at the time of death of the case, and who were born in the same year as the case. Data on socio-demographic factors, and medical and occupational histories were obtained from personnel, industrial hygiene and medical records, and the relation of these factors to risk of motor-vehicle injury was analysed using conditional logistic regression. RESULTS: In a multivariate analysis, the risk of death from motor-vehicle injury was independently associated with being unmarried (odds ratio [OR] compared to married = 3.21, 95% confidence interval [CI]: 1.84-5.59), having a hearing defect (OR = 2.28, 95% CI: 1.10-4.74) and exposure to moderate (OR = 1.71, 95% CI: 1.03-2.83) or high (OR = 2.00, 95% CI: 1.18-3.39) levels of noise at work. The risk of fatal motor-vehicle injury increased with intensity of occupational noise exposure (P = 0.004). CONCLUSIONS: The raised risk of motor-vehicle injury death associated with single marital status is likely to relate to selective factors in the types of individual who remain single, and behaviours associated with being unmarried. The raised risks in relation to hearing defects and exposure to occupational noise, factors that do not appear to have been examined previously, imply that occupational noise exposures might be a cause of fatal motor-vehicle accidents outside the workplace. This finding may have widespread public health consequences since high levels of noise in the workplace and occupationally acquired hearing deficits are prevalent in several occupations. Further investigation is needed to confirm the associated and its mechanisms and, if it is causal, to develop preventive strategies.

A nested case-control study of fatal work related injuries among Brazilian steel workers.

OBJECTIVES: To estimate the relative risk of death from work related injury in a steelworks, associated with exposure to various occupational hazards, sociodemographic factors, and medical history. MATERIAL AND METHODS: The study was a nested case-control design. It was based on a cohort of men employed in the steel plant of USIMINAS, Brazil between January 1977 and August 1990, who were followed up to November 1992. The cases were defined as all workers in the cohort who died from injury in the study period and whose death had been notified to the Brazilian Ministry of Labour as being related to work. Four controls per case, matched to cases on year of birth, were randomly selected from among workers employed in the plant at the time of death of the matching case. Data on potential risk factors for occupational injury were extracted from company records; for the controls these data were abstracted for the period preceding the death of the matching case. RESULTS: There were 37 deaths related to work injuries during the study period. Four surviving workers were selected as controls for each case, but for eight the personnel records were incomplete, leaving 140 controls in all. Significantly increased risk of fatal injury related to work was associated with exposure to noise, heat, dust and fumes, gases and vapours, rotating shift work, being a manual worker, and working in the steel mill, coke ovens, blast furnaces, and energy and water supply areas. Risk of fatal injury related to work increased with intensity of exposure to noise (P (trend) = 0.004) and heat (P < 0.001), and increased greatly with a hazard score that combined information on noise, heat, dust, and gas exposure (P < 0.001). Number of years of schooling (P = 0.03) and salary level (P = 0.03) were both negatively associated with risk. In a multivariate analysis including all these significant factors, only hazard score and area of work remained associated with death from injury related to work. The highest risks were for men exposed to all four environmental hazards (odds ratio (OR) 19.4; 95% confidence interval (95% CI) 1.1 to 352.1) and those working in the energy supply area (OR 18.0; 1.6 to 198.1). CONCLUSIONS: The study identified parts of the steelworks and types of hazard associated with greatly increased risk of fatal accident. Research and measures to prevent accidents need to concentrate on these areas and the people working in them. The use of a hazard score was successful in identifying high risk, and similar scoring might prove useful in other industrial situations.

Risk factors for child mortality in northern Ghana: a case-control study.

BACKGROUND: A population-based case-control study was carried out to investigate potential risk factors for post-neonatal and child mortality in northern Ghana were child survival rates are among the lowest in Africa. METHOD: Cases were post-neonatal infant and child deaths identified within a large population under continuous demographic surveillance. For each case, one living control, matched for age, sex and locality, was selected from the demographic database. Mothers of each case and control were interviewed to obtain information on social, enconomic, demographic, environmental and other possible risk factors. Matched analyses of the 317 cases and their controls were performed using discordant pairs analysis and conditional logistic regression. RESULTS: The mortality rate for children aged 6 months to 4 years was estimated as 23.9/1000 children/year. An increased risk of death was observed where the delivery was not performed by a trained person (OR = 1.8, 95% CI: 1.0-3.2), if the preceding birth interval was < 24 months (OR = 2.2, 95% CI: 1.1-3.9), if the father beat the child's mother (OR = 4.3, 95% CI: 1.2-15.6) or if the water source was unprotected (OR = 1.6, 95% CI: 1.0-2.7). No association was found between weaning practices, parental education, or any of the socioeconomic or hygiene variables considered. CONCLUSIONS: Few strong risk factors for mortality were identified, perhaps because living conditions within the study population are relatively homogeneous. While mortality rates may be reduced by targeted interventions, such as increasing deliveries by trained people, more general improvements in the socioeconomic status in the region are essential.

PIP: A population-based case-control study was conducted in the Kassena-Nankana district of the Upper East Region of Ghana to investigate potential risk factors for post-neonatal and child mortality in northern Ghana where child survival rates are among the lowest in Africa. 317 cases of post-neonatal infant and child deaths were matched with controls, with matched analyzes subsequently conducted using discordant pairs analysis and conditional logistic regression. Mothers of each case and control were interviewed to obtain information on social, economic, demographic, environmental, and other possible risk factors. The mortality rate for children aged six months to four years was estimated as 23.9/1000 children/year. An increased risk of death was observed where the delivery was not performed by a trained person, if the preceding birth interval was less than 24 months, if the father beat the child's mother, or if the water source was unprotected. No association was found between weaning practices, parental education, or any of the socioeconomic or hygiene variables considered. The authors note that few strong risk factors for mortality were identified possibly due to the relatively homogeneous living conditions within the study area. While mortality rates can be reduced by targeted interventions, general improvement in the socioeconomic status in the region is needed.

Angiographic assessment of the transverse sinus and vein of labbé to avoid complications in skull base surgery.

Advances in the field of skull base surgery have dramatically reduced the mortality and morbidity of operations on the skull base. Nevertheless, cerebral ischemic events from compromised blood supply to areas of the brain still occur. Although arterial compromise is responsible for a majority of these events, the venous side of the circulation can also play a role in producing cerebral infarctions. A key area of cerebral venous drainage is at the junction of the transverse sinus, sigmoid sinus, and vein of Labbé. Absence of the transverse sinus with the outflow of the vein of Labbé limited to the sigmoid sinus puts these patients at an increased risk for venous infarcts when this area is manipulated during skull base surgery. We have studied 100 consecutive carotid angiograms performed on 50 individuals for carotid artery disease or to rule out aneurysms. We have found that 16.7% of individuals have one atretic transverse sinus. We discuss our results and the implications that they have in skull base surgery. It is our hope that a better understanding of the cerebral venous drainage patterns will help skull base surgeons avoid complications in the future.

Cancer of the testis, socioeconomic status, and occupation.

The risk of testicular cancer in relation to lifetime histories of socioeconomic status, occupation, and occupational exposures was examined in a case-control study in England. Interviews were conducted with 259 cases, 238 control patients treated at radiotherapy and oncology centres, and 251 controls who were hospital inpatients in other departments. Risk of testicular cancer was raised in men of high socioeconomic status measured both by occupation and in other ways, and was similar in relation to status measured at birth and at various later stages of life. The occupations with highest risk of the tumour were paper and printing workers, professionals, and administrators. Exposures to various specific occupational agents that have been suggested in publications as potential risk factors were examined, but none showed an association with risk. The relative risk for occupational exposure to ionising radiation was 1.62 (95% confidence interval 0.83-3.17).

Estimated radiation doses to different organs among patients treated for ankylosing spondylitis with a single course of X rays.

A follow-up study of over 14,000 patients treated with a single course of X rays for ankylosing spondylitis demonstrated a substantial excess risk of developing cancer. Previously the excess risk of leukaemia has been related to the estimated mean radiation dose to the active bone marrow but detailed estimates were not made of the radiation doses to other organs. In the present work, data extracted from the original treatment records of a random sample of one in 15 patients have been used to make dose estimates, using Monte Carlo methods, for 30 specific organs or regions of the body and 12 bone marrow sites. Estimates of the mean and median organ doses, standard deviations and ranges have been tabulated. Detailed distributions are presented for six organs (lung, bronchi, stomach, oesophagus, active bone marrow and total body). Comparison with the earlier bone marrow estimates and more recent theoretical estimates shows good agreement.

Social and environmental factors associated with the risk of child mortality in a peri-urban community in The Gambia.

A group of 479 children born in a peri-urban West African community during a two-year period was studied in an attempt to identify social and environmental factors associated with the risk of dying in early childhood. Comparison of the characteristics of the 17 children that had died with those of the 462 survivors suggested an increased risk among the children of self-employed women, and among children living in compounds in which animals were kept. Of 500 mothers who were studied (including some whose children were born elsewhere), 145 had experienced at least one child death. When these 145 women were compared with the remaining 355, several factors related to living conditions, maternal education and health knowledge were found to be associated with the risk of child mortality.

PIP: These are the results of a study on infant and child mortality in Bakau, the Gambia. The study, carried out in 1982, concerned 479 children, 17 of whom died. Factors associated with mortality include self-employment of mother, presence of animals in the compound where the child lived, maternal education, and health knowledge.

Assessment of the protective efficacy of vaccines against common diseases using case-control and cohort studies.

Case-control and cohort studies may be employed to assess the protective efficacy of vaccines. The appropriate measure of vaccine efficacy is shown to depend upon the mode of action of the vaccination. Two models of vaccine action are considered. In the first, vaccination is assumed to reduce the instantaneous disease-rate in the total vaccinated population by a constant proportion and, in the second, vaccination is assumed to render a constant proportion of individuals totally immune from the disease. The implications of these two models on the behaviour of different measures of vaccine efficacy in cohort studies is explored. It is shown that the design of case-control studies to measure vaccine efficacy is dependent upon which model is considered appropriate. In particular, under the second model, individuals who have already had the disease under study should not be excluded from the control group.

Retrospective assessment of the effectiveness of BCG vaccination against tuberculosis using the case-control method.

It is proposed that case-control studies might be used to assess the effect on the incidence of tuberculosis of the mass BCG vaccination campaigns that were conducted in many countries in Africa and Asia from the 1950s onwards. The cost of such studies would be relatively small and they could be completed within a year or two. The results would assist countries in planning their future strategies for tuberculosis control and information on the variation in the protective effect of BCG in a number of different areas in less developed countries may give clues to the reasons for such variation. It is suggested that case-control studies should be designed to include about 200 cases and 3 or 4 times as many controls. The cases should be selected for age such that at the time of the mass vaccination campaign they will have been in an age group in which 20% or less were tuberculin positive. The same approach may be used to assess the effectiveness of giving BCG at birth, provided that this policy has been adopted for some years, coverage has been good (about 50% to 80%) and there are reasonable facilities for diagnosing tuberculosis in children.