Histoplasmosis is a non-contagious infection caused by the fungus Histoplasma capsulatum. The organism responsible for the disorder is a soil fungus that is widely distributed in the Midwestern and southern United States, especially in river valleys and plains. Within these endemic areas, some locales are more heavily contaminated with Histoplasma organisms than others.

In many instances, these variations have been correlated with proximity to bird habitats, which are often heavily contaminated because bird droppings serve as a good medium for the organism. Birds are not infected by the Histoplasma organism, although they can carry the organism on their feathers and spread the disease in this manner. Bat habitats can also be heavily contaminated with the organism, as bat guano is an excellent medium for Histoplasma growth. Unlike birds, bats can become infected with the organism.

Infection occurs when spores in the air are inhaled. The spores go to the lungs and cause infection of cells deep in the lungs. Most dogs show a clinically unapparent pulmonary infection; the organism has infected the lungs, yet the dog shows no signs of being ill.

Occasionally, dogs with pulmonary histoplasmosis shows signs of lung infection, such as fever, labored breathing, and coughing. The lung infection usually turns out to be benign and self limiting. If the unapparent respiratory infection extends and persists beyond the lungs and becomes systemic, a clinically apparent, often devastating form of the disease may develop. This has been referred to as "disseminated histoplasmosis," and it carries a guarded or even grave prognosis.

It is uncommon for a clinically unapparent Histoplasma infection to disseminate from the lungs. When this happens, a large number of organs and body systems may be affected. In dogs, the organs most often involved are the lungs, intestine, lymph nodes, liver, spleen and bone marrow. Systemic signs of illness such as depression, fever, and anorexia are common. The disseminated infection in dogs most often results in chronic diarrhea, intestinal blood loss, anemia, and weight loss. In a few dogs, infection of the bones, eyes, skin, and central nervous system may occur.        

The factors that predispose particular dogs to histoplasmosis are not fully understood. In people, exposure to a large amount of the organism, a suppressed immune system, as in chemotherapy or HIV infection, or exposure at a young age or old age are believed to predispose individuals to disseminated infection. There is evidence suggesting that prolonged exposure to high levels of the organism may increase the risk of disease.

Administration of immunosuppressive drugs has been correlated with a worsening of disease in dogs. Exposure to the organism at a young age is a predisposing factor; most affected dogs are less than three years old. Breed and sex are considered as possible predisposing factors in dogs, with pointers, Weimaraners, and Brittanys reported to be more susceptible, and male dogs being 1.2 times as likely to become infected as females.