The current value of tuberculin testing and BCG vaccination in school children

We have examined the value of routine tuberculin testing and BCG vaccination in Edinburgh school children from 1970 to 1983. Over 89,000 children were observed for a mean period of 7 years, during which 77 new cases of tuberculosis were notified in Caucasians. The average annual incidence of tuberculosis in the 65,692 children receiving BCG vaccination at school was 7/10(5), significantly less than the 19/10(5) estimated in 12,987 Heaf negative children who missed BCG vaccination, and the 41/10(5) in 5,308 tuberculin positive children (P less than 0.001). The efficacy of BCG vaccination in this study exceeded 60%. The 5,308 tuberculin positive children were offered chest radiographs with an initial yield (new cases of tuberculosis detected/radiographs taken) of 1/555 for Heaf grade II children, 1/75 for grade III, and 1/25 for grade IV (P less than 0.001). During the period of this study approximately 700 BCG vaccinations were necessary to prevent one new case of tuberculosis and this represents considerably greater benefit than in England and Wales during the same period. There may be a case for continuing the schools' BCG programme in Scotland for a number of years longer than in England and Wales. A national BCG survey for Scotland would be valuable.     

Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence

The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination; 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin.     

Prevalence and factors associated with tuberculosis infection among new school entrants, New York City, 1991-1993.

SETTING: New York City public (or state-run) and private schools-elementary and secondary. OBJECTIVE: To describe the prevalence and determine factors associated with positive tuberculin skin tests (TSTs) in school children. DESIGN: Mandatory TST surveys among cohorts of new school entrants for the 1991, 1992 and 1993 school years, of whom birthplace was known for 81%. A positive tuberculin skin test defined as > or =10 mm induration. RESULTS: Of the 298506 new school entrants, 2.1% (6326) were tuberculin test positive. The proportion that was tuberculin test positive was 0.5% (931/199 728) among US-born and 9.2% (3794/41 346) among foreign-born students. Foreign-born (FB) students with a history of BCG vaccination were much more likely to have a positive tuberculin test than US-born students (13.6% vs. 0.5%, odds ratio [OR] = 33.6, 95% confidence interval [CI] 31.7, 35.6), and were more likely to have a positive tuberculin test than FB students with no history of BCG (13.6% vs. 4.4%, OR = 3.4, 95% CI 2.5, 4.6). Older age was independently associated with tuberculin test positivity, except among foreign-born BCG-vaccinated children, in whom the youngest were more likely to have a positive tuberculin test. CONCLUSIONS: Even in the midst of a tuberculosis resurgence such as that experienced by New York City, where tuberculosis cases nearly tripled from 1978 to 1992, the risk of tuberculosis infection among school children remained quite low. Given the reduced predictive value of the tuberculin test among low risk children and the effects of BCG vaccination, many children (especially younger children) with positive tuberculin test results are probably not infected with Mycobacterium tuberculosis. To reduce unnecessary evaluation and treatment, routine tuberculin tests should be administered only to high risk groups such as older children from countries with high rates of tuberculosis.     

Heaf status 12 years after infant BCG immunization.

Uncertainty exists over the long-term influence of Heaf status and immunity of infant BCG immunization. BCG is offered to all Leeds Asian infants with uptake estimated at 86%. We have examined the effect of this immunization policy on the Heaf status of all 12- to 13-year-old children tested in the city in 1988. 6363 children (431 Asians) were eligible for Heaf testing of whom 5379 (366 Asians) were tested. 90 (25%) Asians and 4596 (92%) non-Asians had a Heaf grade 0-1 with no definite previous BCG and were, using current UK Department of Health recommendations, eligible for BCG immunization. With an annual incidence of tuberculosis in Asian children in Leeds of only 6 per 100,000 it is probable that most of the 75% of Asian children who did not require immunization had persisting immunity from their infant BCG rather than as a result of primary infection. We conclude that infant BCG immunization is effective at providing appropriate immunity, avoiding repeat BCG, in most children at age 12 years.     

Identifying Predictors of Interferon-γ Release Assay Results in Pediatric Latent Tuberculosis: A Protective Role of Bacillus Calmette-Guerin?: A pTB-NET Collaborative Study

Rationale: Interferon-γ (IFN-γ) release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date. Objectives: To investigate factors influencing results of IFN-γ release assays in children using a large European data set. Methods: The Pediatric Tuberculosis Network European Trials group pooled and analyzed data from five sites across Europe comprising 1,128 children who were all investigated for latent tuberculosis infection by tuberculin skin test and at least one IFN-γ release assay. Multivariate analyses examined age, bacillus Calmette-Guérin (BCG) vaccination status, and sex as predictor variables of results. Subgroup analyses included children who were household contacts. Measurements and Main Results: A total of 1,093 children had a QuantiFERON-TB Gold In-Tube assay and 382 had a T-SPOT.TB IFN-γ release assay. Age was positively correlated with a positive blood result (QuantiFERON-TB Gold In-Tube: odds ratio [OR], 1.08 per year increasing age [P < 0.0001]; T-SPOT.TB: OR, 1.14 per year increasing age [P < 0.001]). A positive QuantiFERON-TB Gold In-Tube result was shown by 5.5% of children with a tuberculin skin test result less than 5 mm, by 14.8% if less than 10 mm, and by 20.2% if less than 15 mm. Prior BCG vaccination was associated with a negative IFN-γ release assay result (QuantiFERON-TB Gold In-Tube: OR, 0.41 [P < 0.001]; T-SPOT.TB: OR, 0.41 [P < 0.001]). Young age was a predictor of indeterminate IFN-γ release assay results, but indeterminate rates were low (3.6% in children < 5 yr, 1% in children > 5 yr). Conclusions: Our data show that BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of IFN-γ release assays to children with positive skin tests risks underestimating latent infection.     

The effect of bacille Calmette-Guérin vaccination at birth on tuberculin skin test reactivity in Ugandan children.

SETTING: In Uganda, bacille-Calmette Guerin (BCG) vaccination coverage at birth is between 82 and 84%. OBJECTIVE: To evaluate the effect of neonatal BCG vaccination on tuberculin skin test positivity in Ugandan children exposed to infectious cases. DESIGN: As part of an ongoing prevalence study of household contacts of new tuberculosis cases, 365 children were evaluated to determine if BCG vaccination at birth had an impact on tuberculin skin testing. The children were classified as contacts (179) and non-contacts (186) depending on the presence of a sputum acid-fast bacilli (AFB) smear-positive adult tuberculosis case in the household. RESULTS: Regardless of prior BCG vaccination, children exposed to a smear-positive adult were more likely to have a positive skin test (purified protein derivative >5mm) (68% versus 36%, P < 0.01). BCG-vaccinated children below 1 year of age without a known household contact with active tuberculosis had a lower frequency of tuberculin skin reactions (29%) compared to their counterparts in the contact households (65%, P = 0.031). CONCLUSION: BCG vaccination at birth had no important effect on the interpretation of the tuberculin skin test reactivity in this group of Ugandan children. The tuberculin skin test remains a valuable tool for the evaluation of household contacts and suspected cases of tuberculosis in BCG-vaccinated children.     

Analysis of tuberculin reaction of tuberculous children below 4 years of age]

To clarify whether the size of tuberculin reaction could be used as an useful index of the severity of tuberculosis, we analyzed the sizes of tuberculin reaction (TR) of 60 children below 4 years of age with active tuberculosis at the time of diagnosis. Of 60 patients, 53 (88.9%) had positive reactions to tuberculin. The mean size of TR of 60 patients was 24.0 +/- 13.9 mm and maximum size was 60 mm. Seven patients who had no reaction to the tuberculin skin test consisted of three primary complex and four serious tuberculosis (two miliary tuberculosis and two tuberculous meningitis). The patients without BCG vaccination showed significantly smaller TR than the patients with BCG vaccination (p < 0.05). The patients less than 1 year of age showed significantly smaller TR than the patients of 4 years of age (p < 0.05). The patients with serious tuberculosis showed significantly smaller TR than the patients with primary complex (p < 0.05). Of patients with primary complex, there were no difference of the size of TR between the patients with pulmonary tuberculosis (III) and hilar lymphadenopathy (H). Together with, it did not necessarily mean that negative TR showed no infection with tuberculosis and the sizes of TR depended on the severity of tuberculosis in infantis and young children.     

Safety and immunogenicity of Bacillus Calmette-Guerin vaccine in children born to HIV-1 infected women

This prospective cohort study was conducted to determine the complication of Bacillus Calmette-Guerin (BCG) vaccination given to newborn infants born to HIV-1 seropositive mothers and to compare the tuberculin reaction 9 months after BCG vaccination between HIV-1 infected and non infected children. Two hundred and twenty-three infants with BCG immunization at birth were examined. No BCG complication was noted. Tuberculin skin tests were performed on 126 children (56.5%). Eleven of them were excluded because of failure to have skin tests read at 48 hours. Of the 115 infants enrolled to this study, 15 (13%) had no BCG scar and 50 (43.5%) had no tuberculin reaction. Twenty-six children were classified as group 1 or HIV-1 infected children and 89 children were group 2 or HIV-1 non infected. Group 1 children had a smaller tuberculin skin response (X+SD) than group 2 (1.15 +/- 2.82 vs 4.64 +/- 4.29 mm; p < 0.0001). Mean weight + SD of group 1 children was also significantly less than those in group 2 (8,013 +/- 741 vs 8,540 +/- 984 g; p < 0.05). The proportion of children with non reactivity to the tuberculin test, a negative tuberculin test and no BCG scar in group 1 was significantly higher than that in group 2 (76.9% vs 33.7%, 92.3% vs 52.8% and 36.4% vs 6.7% respectively; p < 0.0001 for all). But, the proportion of non reactivity to the tuberculin test in children with or without BCG scar of each group was not different (p > 0.05). Positive tuberculin tests were 7.7% and 47.2% in group 1 and 2 respectively. None of the children with positive tuberculin tests had clinical evidence of tuberculosis. The findings of this study indicate that BCG vaccine given to newborn infants of HIV-1 seropositive mothers is safe. Although tuberculin skin responses of HIV-1 infected children are less than those of HIV-1 non-infected children, it is possible that BCG vaccine might protect these children from developing severe tuberculosis.     

Tuberculosis screening and prevention in new immigrants 1983-88

Although only 11 cases of active tuberculosis in new immigrants were found, 29.9% of those aged under 30 were tuberculin negative on entry and were given BCG vaccination. In addition 12.8% of children aged under 16 were strongly tuberculin positive and were given chemoprophylaxis. The defects of the official Port of Arrival system for reporting new immigrants are discussed. Entry screening of new immigrants allows worthwhile preventive action, BCG vaccination or chemoprophylaxis, in a substantial proportion of those screened.     

Effect of BCG vaccination and non-tuberculous Mycobacterium infection on interferon gamma specific assay and a tuberculin skin test among children with a tuberculosis contact in Surabaya, Indonesia

The tuberculin skin test (TST) as a diagnostic tool for tuberculosis (TB) infection is used in many countries, including Indonesia, but lacks specificity. Interferon-gamma is a highly specific assay because it is not influenced by previous BCG vaccination or non-tuberculous mycobacteria (NTM) infections. We aimed to study the effect of BCG vaccination and NTM infection on the results of the interferon-gamma specific assay and TST among children with a TB contact. We carried out a cross-sectional study of children at an outpatient clinic in Surabaya, Indonesia. We studied 37 children aged 1-15 years having a household contact with an acid-fast bacilli positive adult index case. BCG vaccination was determined by the presence of a BCG scar. A PPD RT23 2 tuberculin test was used for the TST. ESAT-6, CFP-10, and TB 7.7(p4) antigens were used for the interferon-gamma assay by ELISA. Gastric aspirates were cultured in Lowenstein-Jensen media. A comparison of the two diagnostic tools among children aged 1-5 years without a BCG scar, revealed high agreement, while children with a BCG scar it revealed disagreement. Among children aged > 5 years with or without a BCG scar the comparisons revealed disagreement. Among children aged > 5-10 years, a comparison of the two diagnostic tools among NTM positive and negative children, there was a disagreement in results. Among children aged 1-5 years, the TST was influenced by a BCG scar. Infection with NTM had no influence on the results of the TST among children aged > 5-10 years, while in children aged 1-5 years and > 10 years the results could not be determined in this study.     

Characteristics of children with positive tuberculin skin test

The aim of the study was to define the characteristics of children with latent tuberculosis diagnosed with positive tuberculin skin test (TST) and evaluate potential risk factors in children with positive TST. Children followed with the diagnosis of latent tuberculosis infection were included in the study retrospectively. Demographic characteristics of patients including history of atopy, respiratory infections, family history of tuberculosis and atopy, number of BCG vaccinations, findings of physical examination and laboratory data were extracted from patient's file. Eighty-one children (51 male, 30 female) who had positive TST were retrospectively evaluated in the study. Mean age of the patients was 8.00 ± 4.00 years. Only 13 (16%) of the children had contact with a case who had active tuberculosis. It was shown that the age of the patients, number of BCG scars and BCG vaccination significantly affected TST reaction size. TST size was not affected with time passed after last dose of BCG vaccination, family history of tuberculosis, presence of TST positive case in the family, exposure to cigarette smoke, number of household family members and presence of respiratory allergic disease. The patient's age, numbers of BCG vaccination and BCG scars significantly affect TST results in childhood. This may cause difficulty in diagnosing latent tuberculosis infection and in decision of initiating prophylactic treatment. The results of this study may show that recently developed, more accurate and convenient in vitro tests that they have higher costs and require sophisticated laboratory, can be used to diagnose latent tuberculosis.     

Effectiveness of tuberculosis vaccines

BCG revaccination in the Sverdlovsk Region is performed thrice: at the age of 5, 10 and 15 years. The percent of children covered by tuberculin diagnosis and BCG vaccination is growing. Complications of BCG vaccination remain at the same level. Tuberculosis morbidity in children rises due to minor forms of tuberculosis. However, it is 2 times less than mean tuberculosis incidence in Russia. Primary infection is registered 4.5 times less frequently.     

Results of two-step tuberculin skin test against medical and nursing school students and treatment according to the results of the test]

To assess the risk of tuberculosis infection in medical and nursing school students, tuberculin skin tests were carried out in the two-step manner. The second tuberculin skin test was repeated two weeks later excluding those who were strongly positive in the first test. BCG vaccination was done with the consent of students who showed negative reaction twice. Medical interview and revaluation of prior routine chest radiogram were made on students who were strongly positive. Prophylactic INH medication was considered to those who are at high risk of tuberculosis. Eight hundred thirty eight students underwent the two-step tuberculin skin test, and among them, 771 students showed the positive reaction on the first test (92.0%) which included 58 weakly positive (6.9%), 347 intermediately positive (41.4%) and 366 strongly positive (43.7%) and 2 not-measurable (0.2%), and 65 students were negative (7.8%). The average size of the erythema was 30.9 +/- 18.8 mm on the first test and 37.9 +/- 20.6 mm on the second test. Twenty one students were negative on the second tuberculin skin test, and among them, 15 received BCG vaccination. Out of eight students who were vaccinated with BCG in 1999 and were followed up in the next year, 6 (75.0%) converted to positive. Strongly positive reaction was seen in 28 students (3.3%) and one of them underwent prophylactic medication of INH according to her family history of exposure to tuberculosis.     

The effect of BCG vaccination on tuberculin reactivity and the booster effect among hospital employees

BACKGROUND: We estimated the effect of remote BCG vaccination on tuberculin reactivity and the booster effect among hospital employees. METHODS: Cross-sectional survey at a university hospital. All personnel employed during a 24-month period were included in the study. Employees were administered 2-step tuberculin testing, and BCG vaccination scars were verified. RESULTS: Of 665 hospital employees studied, 239 (36%) had been vaccinated with BCG in childhood. Significant tuberculin reactions (> or =5 mm) were more frequent among BCG-vaccinated (60%) than among nonvaccinated (29%) employees (odds ratio [OR], 3.6; 95% confidence interval [CI], 2.6-5.2). The predictive value of tuberculosis infection increased with increasing reaction size and greater age (from 37% in subjects 30 years or younger with indurations > or =5 mm to 100% in subjects 50 years or older with indurations > or =15 mm). Among 374 employees with a negative tuberculin test reaction who underwent a second test, 39 (43%) of 91 vaccinated subjects had a positive booster reaction in contrast to 51 (22%) of 232 nonvaccinated subjects (OR, 3.4; 95% CI, 2-5.7). Neither different size criteria nor different definitions of the booster effect had an impact on the predictive value of tuberculosis infection. CONCLUSIONS: Remote BCG vaccination largely influences the tuberculin reaction and the boosting phenomenon among hospital employees. The interpretation of the results of 2-step tuberculin testing in a BCG-vaccinated subject must take into account age, size of the reaction, and local prevalence of tuberculosis infection. No single criterion, however, can accurately separate reactions caused by true infection from those caused by BCG vaccination.     

Factors associated with tuberculin reactivity among the foreign-born in Montreal.

Because tuberculosis among the foreign-born is of increasing importance in North America, it has recently been recommended that newly arriving immigrants be tuberculin tested and preventive therapy given to all those with significant reactions. The factors affecting the prevalence of tuberculin reactions were assessed in a community-based tuberculin survey among foreign-born schoolchildren and young adults. Of 1,198 foreign-born who were tuberculin tested, 32.4% had significant tuberculin reactions. False-positive tuberculin reactions due to sensitivity to purified protein derivative (PPD)-B (for Mycobacterium avium) were uncommon and those due to BCG vaccination of importance only among immigrants from countries with low tuberculosis rates. Tuberculin reactions of 10+ mm were associated with tuberculosis rates in the country of origin (p less than or equal to 0.001), age when immigrated (p less than or equal to 0.001), bacillus Calmette-Guérin (BCG) vaccination (p less than or equal to 0.01), and residence in poorer neighborhoods in Montreal (p less than or equal to 0.001), but not with number of years resident in Canada. The booster phenomenon, seen in 16% of those undergoing two-step testing, was most strongly associated with prior BCG vaccination (p less than or equal to 0.001) and also with tuberculosis rates in the country of origin (p less than or equal to 0.08), age of immigration (p less than or equal to 0.01), and number of years resident in Canada (p less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Isoniazid resistant tuberculosis in a school outbreak: the protective effect of BCG

An outbreak of isoniazid resistant tuberculosis occurred in a large second level school. A total of 1,160 teenage pupils were at risk. Nineteen cases of tuberculosis were diagnosed, 15 were students, 9 of whom were among 251 non-vaccinated students and 6 among 909 vaccinated students. Two cases of miliary tuberculosis, one of whom also had tuberculous (TB) meningitis, occurred in the non-vaccinated group. The number of children with Heaf grade +3 or +4 was significantly greater among children who had been given Bacille Calmette-Guérin (BCG) vaccination (8 vs 4.4%). This suggests a boosting effect on the response in vaccinated children. The protective effect of neonatal BCG vaccination in this school outbreak suggests that it provides significant protection against tuberculosis lasting into adolescence.     

Tuberculin reactivity in first‐year schoolchildren in Madagascar

Objective The tuberculin skin test (TST) is an important tool in the diagnosis of tuberculosis infection in children. However, the interpretation of TST may be complicated by prior Bacillus Calmette‐Guerin (BCG) vaccination. We evaluated the effect of vaccination with BCG on TST reactivity in first‐year pupils attending state schools in Antananarivo. Methods STs were performed on 376 first‐year schoolchildren, aged 6 and 7, attending two state primary schools. The relationships between epidemiological information, BCG status (vaccination, BCG scars) and TST reactivity were assessed to compare TST sensitivity between children with and without BCG vaccination and between those with and without a BCG scar. Result The prevalence of positive TST results of ≥5, ≥10 and ≥ 15 mm was 20.2% (76/376), 18.3% (69/376) and 11.4% (43/376), respectively. BCG vaccination was not associated with TST reactivity, whatever the threshold used: ≥5 mm (odds ratio (OR, 1.2; 95% confidence interval (CI), 0.7–2.0); ≥10 mm (OR, 0.9; 95% CI, 0.6–1.7); ≥15 mm (OR, 0.6; 95% CI, 0.3–1.2). Conclusion These results suggest that in Madagascar, a positive TST result indicates TB infection (active or latent) rather than past BCG vaccination. Therefore, high BCG vaccination coverage does not appear to impair the usefulness of the TST as a tool for diagnosing tuberculosis.     

Usefulness of QuantiFERON TB-2G in contact investigation of a tuberculosis outbreak in a university

PURPOSE: This study examined the usefulness of QuantiFERON TB-2G (QFT) i.e., a novel technique for detecting tuberculosis infection based on the whole blood interferon-gamma response to specific antigens, in the investigation of a tuberculosis outbreak among university students. SUBJECTS AND METHOD: One university student was diagnosed as smear-positive pulmonary tuberculosis. In order to determine the extent of tuberculosis infection among contact students, tuberculin skin tests and QFT were performed on the close-contact group (220 people), as well as on the non-close-contact group (242 people). RESULTS: Nine students were found to be TB either clinically or on the X-ray screening in the contact investigation. In the close-contact group, the QFT-positive rate was 32.7%. The proportion of those exhibiting tuberculin reactions with erythema diameters of 30 mm or larger was 57.7%. In the non-close-contact group, the QFT-positive rate was only 0.8 %, as expected from the current healthy Japanese youths of this age. In contrast, strong tuberculin reactions with erythema of 30 mm or larger were seen in 18.2% in the latter group, most likely due to the previous history of BCG vaccination. CONCLUSION: QFT was clearly demonstrated to be a useful method for diagnosing tuberculosis infection, especially among subjects who show tuberculin reactivity due to past BCG vaccination. At the same time, the current criteria for the indication of chemoprophylaxis based on the strong tuberculin reaction were considered to be unreliable, causing many subjects with strong reactions to be given unnecessary preventive medications.     

现代结核病控制措施下结核病传染参数的研究

目的　探索现代结核病控制措施 (DOTS)下的结核病传染参数。方法 北京市顺义区自1978年开始对传染性肺结核病人采取现代结核病控制措施 (DOTS)。1988年7月全县开始停止新生儿卡介苗接种,并对儿童采取了一系列保护性预防措施。1995年按照WHO和IUATLD推荐的国际标准结核菌素试验技术并采用国际标准PPD,对1988～1989年停止卡介苗接种的12849名6～7岁小学一年级儿童进行PPD皮内试验。根据PPD试验反应硬结分布情况,以PPD反应硬结横径≥10mm为结核自然感染标准,然后,根据公式计算年结核感染率和传染参数。结果 顺义区结核自然感染率为1.35%,推算年结核感染率为0.21%。与此同时,痰涂片阳性肺结核病人的年患病率为21.7/10万～39.1/10万,由此计算传染参数约为6。结论 北京市顺义区的结核病传染参数约为6,也就是1名传染源每年平均传染6名健康人,充分说明北京市顺义区所采取的现代结核病控制措施(DOTS)对控制结核病传染源、减少结核菌传播以及保护健康人群十分有效。     

Effectiveness of BCG vaccination in England and Wales in 1983

The effectiveness of BCG vaccination, at about age 13 years, in the prevention of tuberculosis at ages 15-24 years in England and Wales in 1983, has been determined by the same method as in two previous surveys in 1973 and 1978. In 1983, the tuberculosis notification rate among those vaccinated in the schools' scheme was 3.30 per 100,000, compared with an estimated rate of 13.20 per 100,000 among those who were tuberculin negative and not vaccinated in the scheme. The protective effectiveness of BCG vaccination at ages 15-24 years in England and Wales in 1983 is thus estimated as 75%; the estimated efficacy in the white ethnic group is closely similar, namely 76%. The estimated efficacy of BCG at ages 15-19 and 20-24 years in the three surveys, both in the white ethnic group and in the entire cohort, has been compared with that found in the Medical Research Council's controlled trial of tuberculosis vaccines which began in 1950. There is no evidence of any decrease in the protective efficacy of BCG vaccination between the four cohorts of young adults, which span a total period of 29 years. However, there were steep decreases between the cohorts in the annual notification rates for the white ethnic group; these decreases occurred in the BCG vaccinated and in the tuberculin negative unvaccinated groups, as well as among those found tuberculin positive (and not vaccinated) in the schools' scheme. It is concluded that the level of protective efficacy of BCG vaccination at ages 15-24 years is high, and has remained unchanged since the start of the BCG in schools' scheme. However, as the tuberculosis notification rate in young adults has decreased steeply throughout this period, and is continuing to decrease, the benefits to be expected from the BCG in schools' scheme will decrease equally rapidly.