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Histoplasmosis, the most common endemic fungal infection in the United States, is caused by a thermal dimorphic fungus, Histoplasma capsulatum. The extent and degree of environmental contamination with the mold are augmented by bird and bat droppings; the latter may contain fungal spores as well as provide factors that stimulate mold growth.


Infection begins following inhalation of conidia (spores). These convert in the alveoli to the yeast-like invasive forms of the fungus, which are 2 to 4 μm in diameter and ovoid with narrow-based budding. This results in a focus of acute pneumonitis and regional hilar adenitis. In addition to this primary focus, yeast forms also disseminate lymphohematogenously to the reticuloendothelial organs. The host immune response aborts further progression in the vast majority of cases. Inhalation of a large inoculum can lead to acute diffuse lung infection that is severe and sometimes fatal.

Neutrophils arrive early in response but are unable to kill H capsulatum cells. Macrophages are able to control infection after stimulation by tumor necrosis factor-α and interferon-γ produced by responding CD4+ Th1 lymphocytes once these arrive. Dendritic cells also may play a fungicidal role via lysosomal hydrolases. Antibodies are produced against multiple H capsulatum antigens but do not play a significant role in controlling or preventing infection. The inflammatory infiltrate changes become granulomatous with typical Langhans-type giant cells; caseating necrosis, fibrosis, and calcification may ultimately ensue. Calcification may be evident within a few months after initial infection in children.

The spore-bearing mold form grows in the environment at temperatures less than 35°C, occurs worldwide, and is most commonly found in the United States in the Mississippi River and Ohio River basins (Fig. 295-1). Epidemiologic surveys using histoplasmin skin test reactivity in endemic areas show progressive increases with age. Infections occur as sporadic cases in communitywide outbreaks when dry, windy conditions facilitate aerosolization of spores and as localized clusters caused by disturbance of heavily contaminated microenvironments. Such hyperendemic foci include soil in sites of bird roosts, including stream banks; bat-infested caves; rotting logs; and the attics, wall insulation, and fireplaces of old structures (Table 295-1). The rate of hospitalization among children due to histoplasmosis has historically been approximately 2.5 per million population in the Midwest and South regions of the United States.

Figure 295-1

Geographic variation in the frequency of reactors to histoplasmin. Darker color indicates higher frequency. (Reproduced with permission from Edwards LB, Acquaviva FA, Livesay VT, et al. An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States, Am Rev Respir Dis. 1969 Apr;99(4):Suppl:1-132.)


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