Evaluation of histoplasmin and yeast phase antigens derived from a single strain of Histoplasma capsulatum in the complement fixation test.

A complement fixation procedure for the serological diagnos of histoplasmosis in a human patient was attempted first in 1941 by Van Pernis, Benson, and Hollinger. The results were negative with an antigen which consisted of the undiluted filtrate (histoplasmin) from a glucose broth medium inoculated with Hidtoplasma capsulatum. Since that time other types of antigens have been developed by various investigators. Salvin (1947) found that yeast phase cells of H. capsulatum reacted with sera from rabbits infected with the same fungus, but that histoplasmin failed to give reactions. This reactivity of yeast phase antigen with rabbit sera was confirmed by Saslaw and Campbell (1948a). Tenenberg and Howell (1948), however, found that histoplasmin was a satisfactory antigen for detecting complement-fixing antibodies in guinea pigs experimentaRly inoculated with H. capsulatuum. Furcolow, Bunnell, and Tennenberg (1948), using Howell's antigen, detected 14 positive complement fixation reactors among 300 patients suspected of having histoplasmosis. On the basis of comparative tests with whole yeast phase cells, ground yeast phase cells, and histoplasmin, on sera from two proven hulman cases of histoplasmosis and hyperimmunized rabbits, Grayston (1952) favored the yeast phase antigen over histoplasmin. That histoplasmins may vary widely in their antigenic potencies was shown by Schubert et al. (1953) who compared the antigenic levels of histoplasmin produced by 10 different isolates of H. cap*ulatum. Relatively high titers were obtained with sera from culturally proven human cases of histoplasmosis with certain histoplamins and weak or negative reactions with other histoplasmin preparations. It was concluded that pretesting of several lots of antigen must be undertaken to insure the selection of potent lots of histoplasmin for use in serological tests. Recently, Martin (1953) prepared a sonic disintegrated yeast phase antigen of H. capsulatum that elicited low titers in two sera from proven cases of histoplasmosis, but no comparisons were made with other types of antigens. Although all the above antigens currently are being utilized in complement fixation tests for histoplasmosis, extensive comparative studies have not been carried out to determine the merits, if any, of one particular type of antigen over another. The present investigation was undertaken to compare the relative values of particulate yeast phase and sonic disintegrated yeast phase antigens with histoplasnin. All three types of antigens were derived from a single strain of H. capsulatum and used in complement fixation tests for histoplasmosis with sera from a series of human and animal sources.