Tuberculin Tests in Guinea Pigs With Purified Protein Derivative

Abstract

Increased purification and the avoidance of denaturization of an antigen would appear to have obvious advantages. Accordingly the purified protein derivative, PPD, has been recommended unreservedly to replace the crude concentration of heterogeneous substances in glycerol broth cultures of the tubercle bacillus, introduced by Koch more than half a century ago under the name of Old Tuberculin. The discovery of the occurrence of non-specific reactions with large doses of PPD 1 seemed only to indicate that smaller doses of this potent material be used. A report that PPD did not give as good reactions in the skin of guinea pigs as did O.T. seemed to be attributable to the low doses of PPD used in that study. 2

In June, 1941, Dr. F. B. Seibert kindly donated a generous amount of her new potent preparation of PPD 3 for further study. Comparison of this material with a commercial Old Tuberculin (Cutter) has yielded results which are quite disconcerting.

In general, the local reaction to PPD was less distinct and characteristic than that to O.T. In known tuberculous animals, the injection of 0.1 mg of PPD, which according to Dr. Seibert corresponds to from 10 to 20 mg O.T., resulted only in 2 or 3 plus reactions in the skin, with erythema and edema of varying extent, disappearing in 3 or 4 days, without the persisting necrosis or ulceration characteristic of the reaction to 5 mg O.T.

The systemic or lethal effect of the PPD, however, was much greater than that of the O.T. Although death from 5 mg O.T. in tuberculous animals is exceedingly rare, the injection of PPD in doses as low as .005 mg which correspond to less than a milligram of O.T. resulted in death of some of the animals.