A standardised tuberculin (purified protein derivative) for uniformity in diagnosis and epidemiology

Summary o (1) The use of tuberculin as a diagnostic agent in epidemiology and clinical practice has increased considerably in recent years. With the further drop in infection incidence that may be expected, a still greater diagnostic value is to be anticipated. (2) In view of this probable increase in the use of tuberculin, standardisation permitting more accurate comparison of data than is at present possible with the variable preparations on the market, seems timely. (3) Old Tuberculin, a sample of which has been arbitrarily selected as an International Standard, logically might receive first consideration as a basic substance for a standard tuberculin, because of its proven specificity and long history of successful application in epidemiology. (4) Old Tuberculin, however, cannot be made uniformly, because of inherent inconstancies in its manufacture. The various preparations of Old Tuberculin are inevitably solutions of unknown strength of an active principle. Therefore it is logical to separate the active principle from Old Tuberculin and use this substance in solutions of known strength. (5) The active principle of Old Tuberculin can be isolated by a method outlined in the text of the is article, and put up in dry form such that the essential requirements of a standard, viz., specificity, high potency, constancy in strength and stability, are ensured. The active principle as it exists in Old Tuberculin is a protein derivative, the exact chemical composition of which is under investigation. In its present refined form it has been designated simply Purified Protein Derivative from tuberculin. (6) Optimum dosages of this substance for epidemiological work and testing of child and adult tuberculous patients, have been established on the basis of several thousand tests. The doses selected are 0·00002 mg. by weight of the Purified Protein Derivative for the initial test, and 0·005 mg, for injection of those failing to react to the first dose. Experience has shown that the small first dose detects all the highly sensitive cases, without danger of excessively severe reactions, while the second dose defects the remainder of positive cases, that is, those whose sensitiveness is such that they would respond to the conventional doses of preparations of tuberculin of strength equal or superior to that of the International Standard. (7) Several series of tests in the United States, England and Wales, are here reported, in some of which comparison with Old Tuberculin and X-ray findings is recorded. The X-ray examinations indicate that the Purified Protein Derivative, like other tuberculins, may fail to defect an occasional case of healed primary tuberculosis with calcified foci, but that cases of clinical significance are not missed. (8) The incidence of positive tuberculin reactions to the Purified Protein Derivative in surveys in England and Wales varied from 38 per cent. in children 16 years of age or less in an orphan asylum, to 100 per cent. in a tuberculosis sanatorium for adults. Almost all adult patients with tuberculosis reacted to the small first dose. (9) In the United States during the fall of 1934 the Purified Protein Derivative was used in testing about eight thousand college students in various parts of the country. The results are significant, because, for the first time, the tuberculin used on various groups of college students was uniform. In the east about 50 per cent, of the students reacted positively in the middle-west 25 to 30 per cent, and on the west coast about 50 per cent.