A study of neonatal BCG immunization within an acute hospital trust

BACKGROUND: Tuberculosis is a re-emerging problem in the United Kingdom. BCG immunization administered in the neonatal period is protective. National guidelines and locally published standards identify infants for whom BCG immunization is recommended. The study aimed to calculate the rate of identification of infants 'at risk' by parental ethnic group and/or family history of tuberculosis, to determine subsequent immunization uptake, and to describe characteristics associated with missed BCG immunization. METHODS: A retrospective audit was conducted. Demographic data were collected from a computer database of antenatal booking data, for 2043 pregnancies delivering between 1 October 1998 and 30 April 1999. A cohort of infants 'at risk' was defined, and infants referred for BCG immunization were identified. A manual search of immunization records determined immunization uptake. RESULTS: A cohort of 247 (12 per cent pregnancies) was 'at risk'. Fifty-five per cent of the cohort 'at risk' was correctly identified and 42 per cent correctly identified and immunized. The largest subgroup of the cohort, 48 per cent, was Caucasian and at risk because of a positive family history of tuberculosis. Family history of tuberculosis was the most important risk factor, and was missed in 86 per cent of cases. CONCLUSIONS: Despite the local publication of established guidelines, 58 per cent of infants 'at risk' failed to be immunized. Family history of tuberculosis was more important than parental ethnic group in predicting risk for the cohort, and was missed in the majority of cases. Appropriate guidelines alone do not guarantee good practice. Guidelines should be introduced in conjunction with regular audit to ensure effective implementation.     

Trial of BCG vaccines in south India for tuberculosis prevention: first report: Tuberculosis Prevention Trial*1

The protective effect of BCG vaccination is being evaluated in a controlled community trial near Madras in south India. After tuberculin and sensitin testing and radiographic and bacteriological examinations, BCG vaccines and placebo were allocated randomly to about 260 000 individuals, of whom 115 000 were definitely tuberculin negative at the time of vaccination. Intensive efforts are being made, by means of regular follow-up surveys, to identify all new cases of tuberculosis occurring in the community. This report presents the findings of the first 7½ years of follow-up. Incidence of infection was high in the study population. However, incidence of bacillary disease was more frequent among initial tuberculin reactors, especially among the older persons, than among non-reactors of whom the majority were in the younger age groups. The distribution of new cases of bacillary tuberculosis among those not infected at intake did not show any evidence of a protective effect of the BCG vaccines.     

A case-control study of BCG and childhood tuberculosis in Cali, Colombia

We conducted a case-control study to evaluate the effectiveness of BCG vaccination in preventing childhood tuberculosis (TB) in Cali, Colombia. We ascertained 178 cases aged 0 to 14 years from the respiratory clinics with cough or fever for at least three weeks and a positive chest X-ray for TB, as well as 320 controls who were from the same households but had no symptoms and negative X-rays. Using matched set multiple logistic regression analysis, we found the age- and sex-adjusted relative risk (RR) of TB among vaccinees compared with non-vaccinees to be 0.84 with 95% confidence limits (CL) from 0.43 to 1.62. There was, however, a significantly lowered relative risk of TB with increasing time since vaccination (RR = 0.83 per year since time of vaccination with 95% CL from 0.74 to 0.94.)     

The effect of a policy of non-vaccination of schoolchildren on the incidence of tuberculosis in Oxfordshire

We examined the effect of the decision in 1981 in Oxfordshire to cease routine vaccination of schoolchildren for tuberculosis. All notifications, laboratory and death certificate reports of tuberculosis between 1973 and 1989 were reviewed. Results showed that the incidence of tuberculosis in Oxfordshire continued to decline with an annual 5 per cent decrease. The incidence increased with age from a mean annual rate of 6.18 per 100,000 at age 0-10 to 19.90 per 100,000 at age 71-80. There was a higher incidence in the Asian population, with a mean annual rate of 79.6 per 100,000 compared with 7.35 per 100,000 in non-Asians. Four cases had occurred since 1981 in children who had not been immunized routinely at school. All four children had other risk factors in addition to not receiving BCG vaccine. We did not find a need to resume the routine vaccination programme. However, the findings demonstrated the need to be effective in contract-tracing and in vaccinating those most at risk.     

BCG and vole bacillus vaccination in adolescence and mortality from leukaemia

In total, 28 deaths from leukaemia are known to have occurred among the 54,239 participants in the Medical Research Council tuberculosis vaccines trial (initially aged about 14 years), from its beginning in 1950 to the end of 1979. There is evidence that this total is likely to be very nearly complete. During the entire period (average 27.1 years) the leukaemia mortality per million person-years was 25 in the BCG vaccinated group, 20 in the vole-bacillus vaccinated group, and 21 in the randomly-allocated unvaccinated (control) group. Although there was neither a benefit nor a disadvantage from vaccination over the whole period, detailed figures suggested that there may have been a beneficial effect against leukaemia during the first 15 years after entry (that is between age 15 and 30 years) and a deleterious effect after longer intervals (or above the age of 30 years). Alternatively this swing may simply represent an unusual chance fluctuation. There has been no sign in recent years of any substantial decrease in leukaemia mortality in England and Wales at ages 15–29 years, although the proportion of children given BCG vaccine at about age 13 years has risen from less than 1 per cent (for the cohort aged 15–19 years in 1951–1955) to more than 70 per cent 25 years later. It has therefore been provisionally concluded that chance is the explanation for the apparent swing from prevention to enhancement, and that BCG vaccination at age 13–14 years in Great Britain does not affect subsequent mortality from leukaemia.     

The risk of hip fracture in postmenopausal females with or without estrogen drug exposure.

This study estimated the risk of hip fracture among postmenopausal females with and without estrogen drug exposure. The Kaiser-Permanente Medical Care Program in Portland, Oregon served as the setting and medical records the source of data. A retrospective case-control method that matched each female member hospitalized with a hip fracture (N = 168) between 1965-1975 with two control female members hospitalized for reasons other than a hip fracture was used. The estrogen exposure rate of cases was 29.2 per cent and of controls 36.0 per cent. The risk of hip fracture was reduced with postmenopausal and prefracture estrogen exposure (RML = 0.72, 95 per cent CL: 0.48-1.09). However, the number of cases was sufficient only to detect a reduction in risk of about 50 per cent or greater. A possible protective effect from estrogens was also suggested with oral estrogen exposure and with longer lengths of estrogen exposure.     

Smallpox and BCG vaccination in childhood and cutaneous malignant melanoma in Danish adults followed from 18 to 49 years

BackgroundEarly smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with reduced risk of cutaneous malignant melanoma (CMM). We assessed the association between pre-school smallpox vaccination and early-school BCG vaccination and CMM in a young Danish population.MethodsWe conducted a register-based case-cohort study of individuals growing up during the phase-out period of smallpox and BCG vaccination in Denmark (born 1965–1976) utilising the decrease in vaccination during this period. Information on childhood vaccinations and potential confounders from Copenhagen school health records were linked with nationwide registers on cancer (CMM diagnoses), migrations and deaths by personal identification numbers.ResultsThe individuals were followed from age 18 until 31/12/2014 (maximum age at end of follow-up, 49 years). 188 cases of CMM occurred in the background population of 46,239 individuals; 172 CMM cases (91%) had full information and were analysed. The adjusted hazard ratio (HR) for CMM by BCG and/or smallpox vaccination compared with neither vaccine was 1.29 (95% confidence interval (CI) 0.72–2.31). For smallpox vaccination only, HR = 1.23 (95% CI 0.53–2.86) for BCG vaccination only, HR = 1.13 (95% CI 0.61–2.09) and for both smallpox and BCG vaccination, HR = 1.75 (95% CI 0.87–3.48) compared with none of these. Vaccination below the age of one year gave similar results.ConclusionsWe found no strong beneficial effect of smallpox and BCG vaccination against CMM among young adult Danes and with broad confidence intervals our data alone could be compatible with both modest preventive effects, no effects, and modest harmful effects. Our estimates do not contradict a potential modest beneficial effect of neonatal vaccination.     

BCG vaccination of children against leprosy: fourteen-year findings of the trial in Burma

The value of BCG vaccination in preventing leprosy among children was studied in an area of high leprosy endemicity in Burma through a controlled trial; one group of 13 066 children received BCG and another group of 13 176 served as controls. The overall protective effect of BCG, which was only about 20% over the 14-year period, was found to vary with the batch of vaccine, as well as age, sex, and contact status of the children. BCG protection was found to be independent of the initial tuberculin status of the children. The protective effect of BCG against the lepromatous type of leprosy could not be measured because of the low incidence. Protection was observed throughout the fourteen years of the study except for the first year. The results are compared with those of three other major BCG trials in leprosy. The trial has shown that BCG provides only a very modest level of protection and that BCG vaccination is not likely to be an important solution for leprosy control.     

BCG vaccination reduces risk of infection with Mycobacterium tuberculosis as detected by gamma interferon release assay

Aims

To investigate whether BCG vaccination, in addition to a reduction of active tuberculosis, leads to a reduction of Mycobacterium tuberculosis infection during an outbreak of tuberculosis.

Methods

Pupils (n = 199) of a Junior School exposed to a pupil with active pulmonary tuberculosis were screened using a gamma interferon release assay for detection of M. tuberculosis infection (ex vivo ELISPOT assay). Relative risk of M. tuberculosis infection and pulmonary tuberculosis associated with BCG vaccination were calculated and adjusted for exposure risk.

Results

Twenty-nine percent of children with previous BCG vaccination had a reactive gamma interferon release assay compared with 47% of unvaccinated children (unadjusted RR 0.61, 95%CI 0.39, 0.96). The protective effect of BCG vaccination persisted following adjustment for other risk factors for infection like ethnicity and proximity to the source case reflected in membership of class and activity groups (corrected relative risk 0.26, 95%CI 0.09, 0.69 and risk reduction of 74%, 95%CI 31%, 91%). A higher proportion of unvaccinated children (11%) were diagnosed with active pulmonary tuberculosis compared with 5% of vaccinated children (RR 0.51 95%CI 0.15, 1.70).

Conclusion

BCG vaccination was associated with a reduction of M. tuberculosis infection diagnosed by gamma interferon release assay testing in school children during a point source outbreak.     

BCG vaccination in the first year of life protects children of Indian subcontinent ethnic origin against tuberculosis in England.

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.     

BCG vaccination practices in Victoria

Abstract: To determine the patterns of usage of bacille Calmette-Guérin (BCG) vaccine in Victoria and assess whether the vaccine was being administered to those in high-risk groups, as identified by the National Health and Medical Research Council, an audit of BCG vaccine unit sales and expenditure, over the past four years was conducted. A postal survey covering all registered Victorian BCG vaccinators inquired about BCG vaccination practices during 1993. Vaccine sales and expenditure had nearly doubled since 1991. The number of registered vaccinators had also increased. The survey response rate was 77 per cent, (228 of 295). Half of the vaccinators were working in general practice, 11 per cent of vaccinators used no set guideline for client selection, 69 per cent vaccinated fewer than 25 people in 1993, 26 per cent had vaccinated neonates (mainly southeast Asian), with few of these vaccinations being carried out in maternity hospitals. Tertiary students and ethnic groups were the most commonly vaccinated groups. Only small amounts of BCG were being given to people outside risk groups, mainly travellers and anxious public. There has been significant increase in numbers of registered vaccinators and use of BCG with much wastage. Application of guidelines was inconsistent and coverage of high-risk groups varied. Despite some selection for vaccination by personal choice, little vaccine appeared to be used in nonrecommended groups. Subsequent changes in practice have resulted, including publicising and clarifying guidelines, reduction in the number of vaccinators, vaccinator upgrading courses, and restructuring of the vaccine ordering system.     

Measles outbreak in a vaccinated school population: epidemiology, chains of transmission and the role of vaccine failures

An outbreak of measles occurred in a high school with a documented vaccination level of 98 per cent. Nineteen (70 per cent) of the cases were students who had histories of measles vaccination at 12 months of age or older and are therefore considered vaccine failures. Persons who were unimmunized or immunized at less than 12 months of age had substantially higher attack rates compared to those immunized on or after 12 months of age. Vaccine failures among apparently adequately vaccinated individuals were sources of infection for at least 48 per cent of the cases in the outbreak. There was no evidence to suggest that waning immunity was a contributing factor among the vaccine failures. Close contact with cases of measles in the high school, source or provider of vaccine, sharing common activities or classes with cases, and verification of the vaccination history were not significant risk factors in the outbreak. The outbreak subsided spontaneously after four generations of illness in the school and demonstrates that when measles is introduced in a highly vaccinated population, vaccine failures may play some role in transmission but that such transmission is not usually sustained.     

Resource Needs of an Occupational Health Service to Accommodate a Hepatitis B Vaccination Programme

The administrative, organizational and clinical commitment ofan occupational health department to implement the DHSS recommendation¹for a hepatitis B vaccination programme for the health careworkers in a District General Hospital was reviewed to evaluatethe resource implications needed to accommodate the additionalworkload. The deficiencies observed in the existing DHSS guidance in implementingthe plan are described. It is suggested that the Departmentof Health, while making future recommendations for vaccination,should be more precise in identifying those at risk, in describingthe desired titre to be achieved after vaccination, and in describingthe follow-up plan for those who accept the vaccination, thosewho refuse and those who do not seroconvert. The recommendationshould describe the commitment of the Health Authorities andmust include recommendations for appropriate and adequate resourcesto support such a programme. Vaccination for 1000 employees at risk required 4000 additionalconsultations necessitating 16 additional hours of occupationalhealth commitment per week. Eighteen months after initiatingthe vaccination programme. 677 employees had accepted the vaccine.After receiving 3 vaccines 508 (75 per cent) recipients hadprotective seroconversion (anti-Hbs greater than 100 I.U.) anda further 61(9 per cent) converted after the 4th injection,thereby offering protective immunity to 84 per cent of the recipients.During the period 84(12.4 per cent) were lost to follow-up. Recommendations have been made to accommodate the additionalcommitment through the vaccination programme to standardizeour care and prevent disruption of the existing service. Requests for reprints should be addressed to: Dr S. J. Jachuck, Occupational Health Department, Newcastle General Hospital, Westgate Road, Newcastle Upon Tyne NE4 6BE, UK     

某院新生儿卡介苗接种及安全性监测分析

[目的]分析国际和平妇幼保健院新生儿卡介苗(BCG)疑似预防接种异常反应(AEFI)的发病流行特征,评价本院新生儿BCG预防接种安全性。[方法]通过疑似预防接种异常反应信息管理系统,收集2010-2013年报告的接种BCG后AEFI个案数据,对相关指标进行描述性流行病学分析。[结果]2010-2013年本院新生儿BCG接种率为94.54%~95.36%,新生儿BCG合计接种率为95.19%。4年间,共监测到21例,报告发生率为430.86/100万剂。BCG AEFI中,以BCG淋巴结炎为主,占95.24%,报告发生率为410.34/100万剂。[结论]本院新生儿BCG接种率维持在较高水平,新生儿接种BCG后发生AEFI以BCG淋巴结炎为主,报告发生率相对较高,在WHO估算发生率范围之内,BCG安全性尚可。     

不同等级2所医院新生儿卡介苗接种效果及影响因素研究

目的了解常州市不同等级的2所医院新生儿卡介苗接种效果及其影响因素,为提高接种质量和人群免疫水平提供依据.方法 选择1个市级医院,1个县级医院作为哨点,监测2013年1~12月不同批次菌苗对符合条件新生儿的接种情况,3个月后进行结核菌素试验试验(PPD),观察硬结纵横径和直径,评价接种效果;采用Logistic回归模型,对接种效果进行多因素回归分析. 结果共接种卡介苗新生儿2254例,接种成功2090人,接种成功率92.7%.单因素分析显示,不同单位,季节,疫苗批次卡介苗接种成功率差异有统计学意义(P<0.05);金坛市人民医院接种成功率为95.15%,明显大于市妇幼保健院90.17%,差异有统计学意义(P < 0.05); 经组间比较,秋季接种成功率明显高于冬季(χ²=14.080, P = 0.000).疫苗批号201003a015-1接种成功率明显低于其他各批号,批号201003a012-2接种成功率明显低于批号201101a004-1和201012a083-2,差异均有统计学意义(均P = 0.000).多因素logistic回归分析,疫苗批号(OR=1.754,95%CI:1.477~2.084)是卡介苗接种成功的影响因素. 结论常州市市县不同等级医院新生儿卡介苗接种成功率均较高,疫苗不同批次是影响接种成功的影响因素.     

Tuberculosis prevention: where do we go from here?

The Karonga (Malawi) Prevention Trial revealed that repeat BCG vaccinations did not protect against pulmonary tuberculosis (TB) but appeared to provide some protection against glandular TB. They increased protection against leprosy. In fact, a single BCG vaccination conferred 50% protection against leprosy and a repeat BCG vaccination increased protection by another 50%. This trial's findings confirm the need for maintaining BCG vaccination programs in countries where leprosy is a public health problem, for individuals at high risk of leprosy (i.e., contacts of leprosy cases), and because BCG provides some protection against severe forms of TB (i.e., miliary disease and TB meningitis). An alternative TB vaccine needs to be developed, however. The protective efficacy of BCG against pulmonary TB is higher at latitudes far from the equator (80% in northern Europe vs. 0% in India and Malawi). It appears that the immunologic effects of environmental mycobacteria compromise BCG's protective effect against pulmonary TB. There is heterologous immunity between various mycobacterial infections. Low-level delayed-type hypersensitivity (DTH) to tuberculin in non-BCG vaccinated people reflects exposure to environmental mycobacteria. These people are at lower risk of TB than are people with either no DTH or strong DTH to tuberculin. Intradermal exposure to different mycobacteria provides varying degrees of protection against TB in guinea pigs. The warmer and the wetter the environment, the more widespread is colonization by mycobacteria. An area of future research is mapping the distribution of environmental mycobacteria, correlating it with the pattern of DTH responses to tuberculin, and then laboratory work to isolate relevant antigens of the mycobacteria. Another approach is identifying mycobacterial antigens that elicit protective immune responses in vitro so researchers can then identify which antigens and responses are associated with patterns of DTH known to reflect low risk of TB and which response patterns are elicited by BCG against leprosy but not TB antigens. New vaccines are not on the imminent horizon, however.     

BCG-induced immunity profiles in household contacts of leprosy patients differentiate between protection and disease

Leprosy is an infectious disease caused by Mycobacterium leprae leading to irreversible disabilities along with social exclusion. Leprosy is a spectral disease for which the clinical outcome after M. leprae infection is determined by host factors. The spectrum spans from anti-inflammatory T helper-2 (Th2) immunity concomitant with large numbers of bacteria as well as antibodies against M. leprae antigens in multibacillary (MB) leprosy, to paucibacillary (PB) leprosy characterised by strong pro-inflammatory, Th1 as well as Th17 immunity. Despite decades of availability of adequate antibiotic treatment, transmission of M. leprae is unabated. Since individuals with close and frequent contact with untreated leprosy patients are particularly at risk to develop the disease themselves, prophylactic strategies currently focus on household contacts of newly diagnosed patients.It has been shown that BCG (re)vaccination can reduce the risk of leprosy. However, BCG immunoprophylaxis in contacts of leprosy patients has also been reported to induce PB leprosy, indicating that BCG (re)vaccination may tip the balance between protective immunity and overactivation immunity causing skin/nerve tissue damage.In order to identify who is at risk of developing PB leprosy after BCG vaccination, amongst individuals who are chronically exposed to M. leprae, we analyzed innate and adaptive immune markers in whole blood of household contacts of newly diagnosed leprosy patients in Bangladesh, some of which received BCG vaccination. As controls, individuals from the same area without known contact with leprosy patients were similarly assessed.Our data show the added effect of BCG vaccination on immune markers on top of the effect already induced by M. leprae exposure. Moreover, we identified BCG-induced markers that differentiate between protective and disease prone immunity in those contacts.     

Effectiveness of Bacillus Calmette Guerin (BCG) vaccination in the prevention of leprosy: a population-based case-control study in Yavatmal District, India

OBJECTIVE: To estimate the effectiveness of Bacillus Calmette Guerin (BCG) vaccination in the prevention of leprosy. Study design. Population-based case-control study. METHODS: The study was carried out in Yavatmal District, Maharashtra, India. It included 364 cases of leprosy (diagnosed by the World Health Organization's criteria), born since 1962, that were detected during a leprosy survey conducted by the Government of Maharashtra in 2,175,514 people. Each case was pair-matched with one neighbourhood control for age, sex and socio-economic status. Exclusion criteria for controls included past or current history of tuberculosis or leprosy. BCG vaccination status was assessed by examination for the presence of a BCG scar, immunization records if available and information from subjects/parents of children. Subjects who were uncertain about BCG vaccination were not included. RESULTS: A significant protective association between BCG and leprosy was observed [odds ratio=0.46, 95% confidence intervals (CI) 0.34-0.61]. Overall vaccine effectiveness (VE) was 54% (95% CI 39-66). BCG effectiveness against multibacillary, paucibacillary and single skin lesion leprosy was 68% (95% CI 26-86), 57% (95% CI 29-74) and 48% (95% CI 22-65), respectively. Analysis of linear trend revealed a significant linear association between the protective effect of BCG and the type of leprosy. The BCG vaccine was more effective in those aged < or =20 years compared with those aged >20 years (VE 61%, 95% CI), among females compared with males (VE 60%, 95% CI), in lower socio-economic strata compared with upper and middle strata (VE 57%, 95% CI), and in subjects who had a BCG scar size < or =5 mm compared with those with a BCG scar size >5 mm (VE 61%, 95% CI). However, these differences were not statistically significant, as reflected by the overlapping 95% CIs. The overall prevented fraction was 35% (95% CI 22-46). CONCLUSION: The current study identified a beneficial role of BCG vaccination in the prevention of leprosy in the study population.     

The BCG controversy: a reappraisal of the protective effect against tuberculosis and leprosy

BCG (Bacillus Calmette Guerin) vaccine remains a highly controversial method of preventing tuberculosis and leprosy despite more than eighty years of use. The protective effect against tuberculosis observed in various studies ranged from -56% to 98%. Case-control studies carried out at Nagpur reported moderate effectiveness of BCG vaccination in prevention of tuberculosis. Its effectiveness was higher against extra-pulmonary tuberculosis. The summary protective effects obtained from meta-analysis of trials, cohort studies and case-control studies of BCG vaccination and tuberculosis were 51 (33-64), 76 (63-85), and 65 (57-72) percent respectively. The case-control studies carried out at Nagpur also demonstrated a significant protective association between BCG vaccination and leprosy. The summary protective effects obtained from meta-analysis of trials, cohort studies and case-control studies of BCG vaccination and leprosy were 43 (27-55), 62 (53-69), and 59 (46-68) percent respectively. The results of the current study and systematic review thus supported arguments favoring use of BCG vaccine for prevention of tuberculosis and leprosy.     

Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: A Danish case-cohort study

Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines. In a background cohort (N = 47,622) from the Copenhagen School Health Records Register, cases of leukaemia (N = 20) and lymphoma (N = 51) were identified through the Danish Cancer Registry. The vaccination status of the cases was compared with the vaccination status of a 5% random sample (N = 2073) of the background cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR = 0.49 (95% CI: 0.26–0.93)), whereas smallpox vaccination did not (HR = 1.32 (0.56–3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR = 0.81 (0.31–2.16); smallpox vaccination HR=1.32 (0.49–3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas.