Histoplasma

Histoplasma is an endemic fungus prevalent throughout the Mississippi, Ohio, and St. Lawrence River valleys as well as parts of Central and South America, the Caribbean, Africa and Asia. Disease due to Histoplasma is termed histoplasmosis. The fungus is thermally dimorphic as it typically exists as a mold in the environment, which transitions to a yeast form during histoplasmosis in warm-blooded animals. Among the endemic dimorphic MYCO-Sses, histoplasmosis is one of the most frequently clinically encountered. Significantly, those in endemic areas are at extremely high risk for acquiring the fungus, but clinical disease remains uncommon. Nevertheless, there are ~1500 hospitalizations per year in the USA. Severity of disease is correlated with the infectious inoculum, with high dose acquisition leading to more frequent disease. Disease severity is also linked to the virulence of individual strains as well as the immunological state of the acutely or latently infected individual, with serious disease being more common in individuals with advanced HIV infection or on drugs that suppress immune functions, such as inhibitors of tumor necrosis factor-α. Moreover, reactivation of latent infection is a major risk in immunosuppressed individuals. Gold-standard techniques for histoplasmosis diagnosis include direct visualization of the fungus or culture isolation from clinical samples. Immunodiagnostic techniques, including immunodiffusion, complement fixation, and new lateral flow tests, assist with the presumptive diagnosis. Treatment depends on the severity of disease, with itraconazole being used in moderate and amphotericin B in more serious manifestations of histoplasmosis. Histoplasmosis remains an understudied and neglected pathogen that merits ongoing study to more fully understand the pathobiology of the fungus, to develop sensitive, rapid and specific diagnostics and more effective therapeutic strategies.