Experimental and epidemiologic basis for the interpretation of tuberculin sensitivity

Abstract

Epidemiologic evidence that nontuberculous infections cause many of the positive tuberculin reactions observed in human beings is corroborated by results of experimental studies of guinea pigs reported in the present paper. Some of the animals were infected with virulent tubercle bacilli, some with the nonphotochromogenic mycobacterium of the “Battey” type, and some were not infected. Intracutaneous tests with standard mammalian tuberculin (PPD-S) and the PPD antigen prepared from the Battey organism (PPD-B) showed that although cross-reactions occur with both types of infection, the homologous antigen usually produced a larger reaction than the heterologous antigen. Frequency histograms of the sizes of reactions to PPD-S for theoretical populations containing various proportions of tuberculous infected, Battey infected, and uninfected guinea pigs, revealed patterns of sensitivity similar to those observed in human populations. Parallel studies of patients in tuberculosis hospitals from whom only typical tubercle bacilli or Battey-type organisms had been recovered gave results like those found in the guinea pigs. Studies of healthy U.S. Navy recruits from different parts of the country, and of general population groups in this country and abroad, indicate that cross-reactions to tuberculin are highly prevalent in some geographic areas and much less prevalent in others; moreover, the frequency of cross-reactions varies with the prevalence of sensitivity to PPD-B. Whether the organism chiefly responsible for these cross-reactions is the Battey organism, or some other related organism (or organisms), is still undetermined. It is clear, however, that when the frequency of tuberculin cross-reactions is high and of specific tuberculous reactions is low, few of the tuberculous infected can be identified by the size of the tuberculin reaction alone. Simultaneous testing with PPD-S and other PPD antigens can then be expected to help determine the source of the tuberculin sensitivity, just as simultaneous testing with histoplasmin and coccidioidin helps to distinguish between the two fungus infections. Epidemiologic evidence that nontuberculous infections cause many of the positive tuberculin reactions observed in human beings is corroborated by results of experimental studies of guinea pigs reported in the present paper. Some of the animals were infected with virulent tubercle bacilli, some with the nonphotochromogenic mycobacterium of the “Battey” type, and some were not infected. Intracutaneous tests with standard mammalian tuberculin (PPD-S) and the PPD antigen prepared from the Battey organism (PPD-B) showed that although cross-reactions occur with both types of infection, the homologous antigen usually produced a larger reaction than the heterologous antigen. Frequency histograms of the sizes of reactions to PPD-S for theoretical populations containing various proportions of tuberculous infected, Battey infected, and uninfected guinea pigs, revealed patterns of sensitivity similar to those observed in human populations. Parallel studies of patients in tuberculosis hospitals from whom only typical tubercle bacilli or Battey-type organisms had been recovered gave results like those found in the guinea pigs. Studies of healthy U.S. Navy recruits from different parts of the country, and of general population groups in this country and abroad, indicate that cross-reactions to tuberculin are highly prevalent in some geographic areas and much less prevalent in others; moreover, the frequency of cross-reactions varies with the prevalence of sensitivity to PPD-B. Whether the organism chiefly responsible for these cross-reactions is the Battey organism, or some other related organism (or organisms), is still undetermined. It is clear, however, that when the frequency of tuberculin cross-reactions is high and of specific tuberculous reactions is low, few of the tuberculous infected can be identified by the size of the tuberculin reaction alone. Simultaneous testing with PPD-S and other PPD antigens can then be expected to help determine the source of the tuberculin sensitivity, just as simultaneous testing with histoplasmin and coccidioidin helps to distinguish between the two fungus infections.