Associations Between Kveim Test Results, Previous B.C.G. Vaccination, and Tuberculin Sensitivity in Healthy Young Adults

A trial of tuberculosis vaccines in more than 54,000 adolescents, nearly all aged 14 to 5l years and attending school in urban or suburban areas, was started in England in 1950-2 (Medical Research Council, 1956, 1959, 1963).Those found to be tuberculin-negative on entry to the trial-that is, with no induration, or one of less than 5 mm., both to 3 and to 100 tuberculin units (T.U.) of Old Tuberculin-were vaccinated with B.C.G. or vole-bacillus vaccine or left unvaccinated, according to a method of random allocation.All the participants, including those who were tuberculin-positive to 3 or to 100 T.U.initially, were followed up intensively, with annual postal inquiries, home visits, radiographic examinations, and tuberculin tests, until September 1960 (which represented an average period of 8.8 years).Of the tuberculin-negative participants, 13,598 were allocated to the B.C.G.-vaccinated group.All had had a clear chest radiograph immediately before vaccination, and just over half, not selected in any special way, had further tuberculin tests within a year after vaccination (nearly all within six months) ; of these, 17 (0.23%) were still negative to 100 T.U. ; the remainder were positive either to 3 T.LJ.(85.3%/0) or to 100 T.U.(14.4%').It was expected that some of the small number who were still tuberculin-negative would represent failures of the vac- cination (or of the tuberculin tests) for technical reasons, but it seemed likely that others had a temporary or lasting tuberculin anergy, a condition recognized by previous workers-for example, Ustvedt (1951), Borrie (1952), Stewart and Beckwith (1960), and Sparrow and Carr6 (1960).We considered such individuals to be of particular immunological interest, not merely as regards their subsequent susceptibility to tuberculosis, but also because they might include some occult cases of sarcoidosis, in which disease a depression of tuberculin sensitivity and little or no enhancement thereof after B.C.G. vaccination are common (see Israel and Sones, 1961).During the follow-up no case of sarcoidosis (nor any case of tuberculosis) was discovered either among the above 17 participants, who were known to have been negative to 100 T.U.soon after B.C.G. vaccination, or among any of the 35 additional participants in whom evidence that they had not become positive to 100 T.U.following B.C.G. vaccination was based on tests only made later (the possibility that some of these 35 had become positive and then reverted to negativity can therefore not be excluded).(In the total of 54,239 participants in the vaccines trial, 38 cases of definite or possible sarcoidosis and 504 cases of tuberculosis are known to have developed during the intensive follow-up; as just implied, none of these cases conformed to the criteria of the above 52 participants.)Despite these negative findings for sarcoidosis in the vaccines trial records for the 52, it was decided in 1960 to make a special * From the Medical Research Council's Tuberculosis and Statistical Re- search Units, M.R.