Phyllis Q. Edwards

Experimental and epidemiologic basis for the interpretation of tuberculin sensitivity

Summary 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.

Nationwide histoplasmin sensitivity and histoplasmal infection

RESULTS of skin testing with histoplasmin and the diagnosis of clinical cases of histoplasmosis have made it clear that where people live is of prime significance in the risk of beicoming infected with the fungus Histopla8ma capsulatum. The purpose of this paper is twofold: to depict State-to-State variations in indigenous sources of sensitivity to histoplasmin, as measured by the prevalence of reactions among young men who have lived all their lives in one State, and to distinguish, in some regions, between the reactions caused by infection with Histoplasima and cross-reactions attributable to infection with other agents. In dealing with geographic units as large as States, the presence of small and perhaps isolated areas of both high and low prevalence will be obscured. State figures, on the other hand, can provide a broad picture of geographic variations across the 3,000 miles from the Atlantic to the Pacific coasts. Several earlier reports from this office have described nationwide variations in the prevalence of histoplasmin sensitivity and variations in the sizes of reactions observed in different geographic areas (1-4). These reports were based on material collected in several studies of young adults during 1945-52. More recently, it has been possible to obtain material in a single study, in which the same histoplasmin, techniques, and procedures were used for giving skin tests, at the same time and place, to large numbers of young men (Navy recruits) from all parts of the country. Results of this newer study confirm and extend the conclusions drawn from the previous material, which was collected, on the average, about 10 years earlier.

Skin sensitivity of healthy young Adults to the fungus antigen, haplosporangin.

The fungus isolated and named Haplosporangium parvum by EMIVIONS & ASHBURN in 1942 (8), and recently renamed Emmonsia parva (3,9), has been found in the lungs of wild rodents and small mammals in the northern and western parts of the United States and Canada by numerous investigators (1, 4, 9, 11, 12), in Italy by CIrERRI (3), in England by MCDIARMID & AUSTWlCK (20) and TEVlS (23), and in such scattered areas as Africa, Ecuador, Finland, France, Japan, Korea, Norway, Sweden, and Yugoslavia by JELLISON and associates (9, 13-18). Whether or not the animals can be considered infected is debatable because the organism seemingly does not multiply in the natural host--i t simply becomes enlarged. As far as is known, no case of haplomycosis has yet been reported in a human being. The question of whether man, too, may unknowingly share the role of host to this curious invader thus remains unanswered. Several years ago, we found what appeared to be histoplasmin cross reactions in a fairly large percentage of the young men, Navy recruits, coming from the eastern part of Texas and the adjacent states (5, 22). Coccidioidomycosis could not be incriminated as a significant source of the cross sensitivity because very few recruits from that area react to coccidioidin. And results of subsequent skin test studies in Navy recruits with a blastomyces antigen speak against blastomycosis as the causative agent (7). Our interest in this problem was one of the reasons for including haplosporangin in our studies of skin sensitivity to antigens prepared from a number of different pathogenic and possibly pathogenic fungi. Results of tests with haplosporangin in several thousand Navy recruits coming from all parts of the United States, and in several smaller groups of persons in this country and in Egypt, are