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Objectives: (i) To evaluate the relationship between the levels of vitamin A, folate and iron in maternal blood and cord blood from mother-baby pairs who had intra-uterine growth retardation (IUGR) and appropriate birth weight (ABW) for gestational age. (ii) To assess low or marginal levels of vitamin A, folate and iron as risk factors for IUGR., Design: Retrospective unmatched case-control study., Setting: Maternidade de Campinas, Universidade Estadual de Campinas, Pontificia Universidade Catolica de Campinas, Hospital Albert Sabin., Subjects: 356 mother-baby pairs who had IUGR and 356 mother-baby pairs who had ABW for gestational age., Interventions: Newborns were classified as being IUGR according to the Lubchenco classification. Gestational age of the newborns was evaluated by the Capurro method. Vitamin A, folate, ferritin, and haemoglobin were measured respectively by high performance liquid chromatography (HPLC), radioimmunoassay, immunoenzymetric assay and by the cyanmethaemoglobin method., Results: The percentages of IUGR babies with abnormal levels of nutritional indices compared with ABW babies were 33.1 vs 14.6 for vitamin A, 25.7 vs 19.9 for red blood cell (RBC) folate, 37.0 vs 21.4 for haemoglobin, but similar for ferritin. The percentages of IUGR mothers with abnormal levels of nutritional indices compared to ABW mothers were similar (1.1 vs 1.4) for vitamin A, and 36.8 vs 32.1 for RBC folate. IUGR mothers were less often anaemic (43.2 vs 50.8), but tended to have higher levels of ferritin (37.6 vs 23.9) compared to ABW mothers., Conclusions: These results indicate marked differences in cord blood between IUGR and ABW with small differences in maternal levels. They suggest that micronutrient deficiency is the result of being born small rather than vice versa. The high levels of ferritin in IUGR mothers may reflect subclinical maternal infection contributing to IUGR. Maternal micronutrient deficiency is unlikely to be a causative factor for IUGR in this population., Sponsorship: ODA (Overseas Development Agency), United Kingdom; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico), Brazil.

Objectives: To investigate the association between four sociodemographic measures (unemployment, overcrowding, low social class, and the proportion of migrants from areas of high prevalence of tuberculosis) and average level and rate of change of notification rates for tuberculosis., Design: Ecological analysis of both the average and the rate of change of standardised annual notification rates for tuberculosis from 1982-91 and sociodemographic measures from the 1981 and 1991 censuses., Setting: 32 London boroughs. SUBJECTS AND DATA: Sociodemographic measures from the 1981 and 1991 censuses and tuberculosis notification rates for 1982-91., Main Outcome Measures: A measure of the association between average levels and rate of change in tuberculosis notification rates and four sociodemographic measures in 1981 and between the rate of change in tuberculosis notification rates between 1981 and 1991 and changes in sociodemographic measures between 1981 and 1991., Results: The average level of notifications was correlated with overcrowding and the proportion of migrants but not with unemployment or social class. No significant association was found between the rate of change in notification rates and sociodemographic measures in 1981. An association was found between increases in unemployment and the rate of change in notification rates, but the effect was small. Changes in the levels of unemployment explained 23% of the variation between boroughs in the rate of change in their notification rates., Conclusion: The average tuberculosis notification rates were related to overcrowding and the proportion of migrants in 1981. Only increases in unemployment from 1981 to 1991, however, were significantly associated with the rate of change in notifications over the same period.

Background: The verbal autopsy appears to be an attractive technique for the assessment of causes of adult death in settings where the proportion of people who die while under medical care is low. Verbal autopsies have been used extensively to assess causes of childhood deaths. The existing experience in verbal autopsies for adult deaths is limited mainly to maternal deaths. This paper aims to highlight the critical issues in verbal autopsies to assess causes of adult death which need further research., Methods: This paper reviews the methods of verbal autopsy used in 35 published studies and discusses issues in the development of verbal autopsies, including mortality classification, design of questionnaires, interviewers, respondents, recall periods, procedures for deriving a diagnosis and the recording of single versus multiple causes of death. It also discusses issues in the validation of verbal autopsies, including the choice of reference diagnosis and the required sample size., Results: The methodological approaches used in verbal autopsy studies have varied widely. Very few studies of the validity of verbal autopsies have been conducted. In these studies, the reported sensitivity and specificity varied widely between different causes of death and between studies., Conclusions: The information available is inadequate to draw firm conclusions on preferred methodological approaches for verbal autopsies for adult deaths. Before these tools are used more widely for adult deaths, further research is required to compare alternative methods and to evaluate the validity of this tool in a range of settings.

The protective effect of BCG against tuberculosis (TB) estimated in randomized controlled trials and observational studies ranges from negative to close to a 100%. One of the many explanations offered for this is that different immunological mechanisms may be associated with protective effect against different forms and sites of disease. In this investigation, we recalculated vaccine protective effect separately for pulmonary disease and for meningeal/miliary disease in randomized controlled trials and case-control studies, tested for heterogeneity in site-specific estimates of protective effect and calculated a summary measure when appropriate. We found protective effect against pulmonary disease to be heterogeneous to a statistically significant degree, and thus we did not calculate a summary measure of protection. Protective effect against meningeal and miliary TB was higher than against pulmonary disease and, except for a single study with two cases only, appeared to be homogenous. Summary BCG protective effect against miliary or meningeal TB in randomized controlled trials was 86% (95% confidence interval [CI] 65, 95) and in case-control studies 75% (95% CI: 61, 84). The fact that protective effect appeared to be homogeneous against meningitis and miliary TB but not against pulmonary disease may result from the fact that patients with meningitis are on average younger and thus less likely to have been exposed to atypical bacteria; to a waning of the protective effect of BCG; or from the diversity of mechanisms of pathogenesis of pulmonary disease, which can originate from reinfection, reactivation or primary progression.

Two different measures of hospital-acquired infection (HAI), risk per discharge and incidence rate, were used to analyse the incidence of 225 primary HAIs detected in 3,090 patients in an 11-month survey. Longer hospital stay was associated with a greater risk of developing HAI, but the strength of the association was different for the two measures used. Day-specific incidence rates were found to vary, with a peak between the 14th and 19th days of hospitalisation. Similar patterns were observed when the data were stratified by age, sex and operation. Methods for calculating HAI should control for the length of hospital stay. Further studies are required to clarify the mechanisms that affect the temporal pattern of incidence of HAI observed with length of hospitalisation.

Study Objective: The aim was to investigate whether the winter increase in risk of sudden infant death was similar across social classes., Design: This was an unmatched case-control study using routine data., Setting: Cases and controls were selected from files holding routine birth and death certificate data for England and Wales for 1986., Subjects: Cases were deaths in the first year of life occurring in the summer or the winter of 1986 with mention of sudden infant death or SIDS in the death certificate. Controls were a 1% random sample of all children born in the same year. Only children whose parents were married or living together at the time of birth registration were included., Main Results: Data on age and season of death for cases, and on date of birth, social class of father, and birth weight were abstracted from the file. Season of birth and birth weight were treated as confounding variables. The increase in risk of SIDS in winter was calculated for each age group and social class. The winter increase in SIDS was more marked among the higher social classes for all ages, but not to a statistically significant degree: the p values for heterogeneity were 0.26 for age 0-3 months, 0.42 for 4-7 months, and 0.41 for 8-12 months., Conclusions: There is no direct association between seasonal variation in sudden infant death and social class.

The aetiology of sudden infant death syndrome (SIDS) remains uncertain; many causal pathways have been proposed. In this paper we have examined firstly the variation in the risk of SIDS with age, month of death and month of birth; and secondly the space time clustering of SIDS deaths, and, separately, space time clustering of their births. Data were obtained from the Office of Populations, Censuses and Surveys on all certified SIDS deaths in the period; children were assigned grid references for the address of birth and of death. Data on number of births were abstracted from published material. A log-linear modelling technique was used to investigate the separate effects of age, month of death and month of birth on the risk of SIDS. The Knox method was used to investigate space time clustering of deaths and of births of children who died of SIDS. Separate, statistically significant effects were found for age, month of death and month of birth. There was minor space time clustering of SIDS births and deaths at large time and space intervals, and a marked space time clustering of births in short space time intervals in the first quarter of the year. The finding of an effect of month of birth on the risk of SIDS, and of space time clustering of births suggest that a perinatal hazard--possibly of infectious origin--may play a role in the aetiology of SIDS.

Study Objective: The aim was to examine the factors associated with incomplete vaccination in an urban area in Sao Paulo, Brazil; and to explore whether differences in vaccine coverage in the catchment area of health centres remain after the demographic constitution of the population in these areas is controlled for., Design: The children were selected as controls for a case-control study. 455 children were selected at random (but age matched) from the health centre registries. Data was collected from the health centre records and from home interviews., Setting: All children were registered in FAISA, a municipal health service comprising a large network of health centres and hospitals. FAISA's services are free at the point of delivery, and over 85% of the city's children are registered., Participants: Participants were selected to represent, except in their age distribution, all children registered in the municipal health service., Measurements and Main Results: Information was collected on subjects' vaccine history, year of birth, sex, birth order and birth weight, and health centre of registration; their mothers' age, education, and marital status; and the family's income per capita and history of migration. Analysis was undertaken to identify risk factors for vaccination and whether the differential coverage in health centres' catchment areas remained after demographic characteristics of the population were controlled for. The high coverage for DPT and polio vaccines suggests that low overall coverage was not simply a result of mothers failing to bring children for vaccination. The variable that best predicted vaccine coverage was year of birth. Children born to immigrant mothers or into large families had lower vaccine uptake. The characteristics of children and their mothers did not account for the variation in vaccination coverage in catchment areas of different health centres., Conclusions: It is likely that in this area vaccination completeness was associated mainly with the health centre's ability to deliver vaccination to the target population.

Study Objective: The aim was to assess the protection conferred by BCG given during the first year of life against tuberculosis among children of Asian ethnic origin born in England., Design: This was a matched case-control study., Setting: Cases were selected from notifications of tuberculosis and controls were selected from child health or school health records in 14 English health districts., Participants: 111 cases of childhood tuberculosis with Asian names were selected. For each case there were five controls with Asian names, matched for age, sex and district of birth., Measurements and Main Results: Child health or school health records were searched to determine the proportions of cases and controls who had been vaccinated with BCG. Overall, BCG vaccination given in the first year of life was estimated to confer 49% protection against tuberculosis with 95% confidence interval 14-62%., Conclusions: BCG vaccination in infancy was found to be associated with a lower protective efficacy than has been found for the secondary school age BCG programme (80%) but nevertheless the protection is substantial and, in the United Kingdom, BCG vaccination of infants considered to be at relatively higher risk of tuberculosis is likely to reduce the incidence of childhood tuberculosis.

Tuberculosis is a major cause of morbidity and mortality in developing countries. It is estimated that one-fifth of the world population is infected, 12-16 million people have the disease, every year 6-8 million develop tuberculosis and 2-3 million die from it. Four methods for the prevention of tuberculosis are available: improvement of socio-economic conditions, case-finding and treatment, chemoprophylaxis, and vaccination. Each of these methods is examined in relation to a model of the chain of transmission and development of disease. Improvement of socio-economic conditions, responsible for the decline of tuberculosis in the developed world, must be seen as a long-term solution. Case-finding and treatment is the only method expected to have an important short-term impact on transmission. A summary of the results of 35 studies shows the estimated efficacy of bacillus Calmette-Guérin (BCG) vaccination ranging from 96% to none. Follow-up results from 10 controlled trials are consistent with waning of BCG protective efficacy with time since vaccination. Chemoprophylaxis and vaccination are expected to protect the individual but not to have a significant short-term impact on transmission.

A case-control study was carried out in the Metropolitan Region of São Paulo, Brazil, to determine the protection against tuberculous meningitis conferred by BCG vaccination to children aged less than 5 years. The BCG vaccination coverage in the study area was about 88%. A total of 72 tuberculous meningitis patients were studied as well as 505 neighbourhood and 81 hospital controls. Analysis of the data using a conditional logistic regression for matched case-control studies indicated that the efficacy of BCG was similar for both groups of controls, that for neighbourhood controls (84.5%) being slightly greater than that for hospital controls (80.2%). No significant interactions were found between vaccination status and sex, age, or socioeconomic status.

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.

A pulse immunization project was started in Mozambique to compensate for the decrease in routine immunization caused by destabilization. A study was conducted to evaluate the project and identify determinants of vaccination in urban and rural areas of Mozambique. Vaccine coverage based on a documented record, the 'Road to Health' card, was 53% in urban and 60% in rural project areas, and 12% higher if a verbal history of vaccination was considered. A further 17% of children would have received effective vaccination if the correct schedule had been followed for all vaccines given and all preventive health services contacts had been used for vaccination. Factors relating to the individual mother and child and factors relating to the clusters were investigated for their association with vaccine uptake. Those which showed a strong negative association included vaccination on offer at the nearest vaccination post for only a small number of days per week; cancellation of an outreach session; knowing a child with a post-vaccination abscess; child born at home; at least five children in the family; mother's inability to speak Portuguese and her inability to name at least two target diseases. Improving the supervision of health services and immunizing at least three days per week at permanent immunization clinic sites may be the most important measures to improve coverage further.