“Saprophytic Form” of Histoplasma capsulatum in vivo *

It is the purpose of this paper to report a unique observation concerning Histoplasma capsulatum. This diphasic fungus, according to previous reports, produces only yeast-like forms in the body of man and other animals. In culture, either the mycelial stage or the yeast-like form is obtained according to the experimental conditions. For the first time, so far as the author is aware, the mycelial stage, considered to be characteristic of the saprophytic portion of the life cycle, has been encountered in animals. If tissue containing Histoplasma capsulatum is carefully macerated in a tissue grinder and then implanted on Sabouraud's medium and incubated at room temperature, the filamentous form of this organism develops. The mycelium, at first white, gradually becomes brownish and may produce pyriform conidia, but, as the culture ages, there also will be produced many thick-walled tuberculated chlamydospores; The production of tuberculated chlamydospores makes the identification of H. capsulatum certain among the fungi pathogenic to man and animal. If, however, macerated tissue is planted on fresh, moist blood agar in tubes sealed with paraffin, and the tubes are then incubated at 370 C., the yeast-like form will develop. When the yeast form of Histoplasma capsulatunt is injected into experimental animals, the cells of the reticulo-endothelial system are induced to proliferate. The mononuclear cells are literally packed with the yeast-like organisms. In the liver such proliferation of macrophages may give rise to focal lesions which undergo necrosis and involve adjacent liver parenchyma. If the animals are injected with a saline suspension of the filamentous form of this organism, their tissues at the time of death or autopsy will contain the yeast form. While examining tissues of animals experimentally infected with the yeast form of H. capsulatum, a necrotic lesion in the liver of one of these animals was noted to contain masses of hyphae and many tuberculated chlamydospores. For reasons to be stated, however, it is not at present possible to offer any explanation for this reversion in znvo of the parasitic form of this fungus to the mycelial phase. To obtain tissue infected with H. capsulatum for teaching purposes, eight white mice of unknown strain, weighing between 16 and 20 grams, were