Clinical meaning
Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic fungus endemic to the Ohio and Mississippi River Valleys in North America and certain regions of Central America, Africa, and Southeast Asia. 'Dimorphic' means the organism exists in two forms depending on temperature: as a mould (mycelial form) in the environment at 25°C and as a yeast within human tissues at 37°C. This thermal dimorphism is a key virulence factor shared with other endemic mycoses (blastomycosis, coccidioidomycosis).
Histoplasma thrives in soil enriched with nitrogen from bird droppings (starlings, chickens, pigeons) and bat guano. Birds themselves are not infected (their body temperature is too high for the organism), but their droppings create an ideal growth medium. Bats, however, can be infected and excrete the organism in their guano. Activities that disturb contaminated soil aerosolize the infectious microconidia (2-4 micrometres), which are inhaled into the terminal bronchioles and alveoli. Risk activities include cave exploration (spelunking), cleaning chicken coops, demolishing old buildings, landscaping, and farming in endemic areas.
Once inhaled, the microconidia convert to the yeast form at body temperature. The yeasts are phagocytosed by alveolar macrophages but survive and replicate within the phagolysosome by modulating the intracellular pH and acquiring essential iron from the host cell. This intracellular survival strategy is similar to that of Mycobacterium tuberculosis, and indeed the clinical and pathological features of histoplasmosis closely resemble tuberculosis. The organisms spread via the lymphatics and bloodstream to the reticuloendothelial system (liver, spleen, bone marrow, lymph nodes) during the initial fungaemia that occurs before the adaptive immune response develops (typically 2-4 weeks post-exposure).