Factors Influencing Histoplasmin Formation.

Histoplasmin was originally defined by Zarafonetis and Lindberg (1941) as "the antigenic substance or substances of Histoplasma capsulatum" Darling. The term, however, is now used generally to indicate the filtrate derived from the growth of the mycelial phase of Histoplasma in a liquid synthetic medium and capable of producting a positive skin reaction in sensitized animals and man. The histoplasmin that was prepared by Zarafonetis and Lindberg and that produced cutaneous reactions in experimentally infected rabbits was a filtrate from a 7 weeks' growth of the mycelial phase in Williams' synthetic medium (Williams and Saunders, 1934). Van Pernis, Benson, and Holinger (1941) used a filtrate from about 1 month's growth of the mycelial phase in a glucose broth and obtained cutaneous reactions in an infected human patient and in experimentally infected mice. Emmons, Olson, and Eldridge (1945) reported the preparation of histoplasmin in the synthetic broth medium used by Smith (1943) for the preparation of coccidioidin. The particular lot of histoplasmin used most extensively by Emmons et al. (1945) and by Palmer (1945) was grown in a dark cupboard at room temperature for 7 months. A similar preparation was used by Christie and Peterson (1945) in their studies on histoplasmosis. Although histoplasmin has been used extensively for intradermal testing, little is known about the process by which the antigen is produced and what factors are most influential in its formation. Accordingly, a study was initiated to determine what factors play important roles in the development of histoplasmin. This paper reports experiments on the influence of the environment and of nutritive substances in the medium on the formation of histoplasmin.