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Histoplasmosis is an airborne infection. The spores that cause this disease are found in soil that has been contaminated with bird or bat droppings. In the United States, the disease is most common in eastern and midwestern states and is widespread in the upper Mississippi, Ohio, Missouri, and St. Lawrence river valleys. Sometimes histoplasmosis is called Ohio Valley disease, Central Mississippi River Valley disease, Appalachian Mountain disease, Darling's disease, or Histoplasma capsulatum infection.

Anyone can get histoplasmosis, but people who come in contact with bird and bat excrement are more likely to be infected. This includes farmers, gardeners, bridge inspectors and painters, roofers, chimney cleaners, demolition and construction workers, people installing or servicing heating and air conditioning units, people restoring old or abandoned buildings, and people who explore caves.

The very young and the elderly, especially if they have a pre-existing lung disease or are heavy smokers, are more likely to develop symptoms that are more severe. People who have a weakened immune system, either from diseases such as AIDS or leukemia, or as the result of medications they take (corticosteroids, chemotherapy drugs), are more likely to develop chronic or disseminated histoplasmosis.

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