Infectious Agent

Histoplasma capsulatum, a dimorphic fungus that grows as a mold in soil and as a yeast in animal and human hosts.


Through inhalation of spores (conidia) from soil (often soil contaminated with bat guano or bird droppings); not transmitted from person to person.


Distributed worldwide, except in Antarctica, but most often associated with river valleys. Activities that expose people to soil disruption or areas where bats live and birds roost, such as construction, excavation, demolition, farming, gardening, and caving, can increase risk of histoplasmosis. Outbreaks have been reported associated with travel to many countries in Central and South America, most often associated with visiting caves.

Clinical Presentation

Incubation period is typically 3–17 days for acute disease. Ninety percent of infections are asymptomatic or result in a mild influenzalike illness. Some infections may cause acute pulmonary histoplasmosis, manifested by high fever, headache, nonproductive cough, chills, weakness, pleuritic chest pain, and fatigue. Most people spontaneously recover 2–3 weeks after onset of symptoms, although fatigue may persist longer. High-dose exposure can lead to severe pulmonary disease. Dissemination, especially to the gastrointestinal tract and central nervous system, can occur in people who are immunocompromised.


Several methods are available to diagnose histoplasmosis.

  • Although the gold standards remain culture and histopathologic identification, antigen or antibody testing are commonly used.
  • Rapid Histoplasma antigen testing by EIA on multiple specimen types (for example, urine, serum, plasma, bronchoalveolar lavage, or cerebrospinal fluid) is available at multiple US laboratories. Antigen testing is most sensitive in severely ill patients.
  • Antibody testing by EIA, immunodiffusion (ID), and complement fixation (CF) can be used to detect subacute and chronic forms of histoplasmosis. Antibodies to Histoplasma typically become detectable in serum 4–8 weeks after infection. A small proportion (<5%) of people living in histoplasmosis-endemic areas have positive serology by CF or ID. Testing a single serum specimen can aid in diagnosis, but testing serial specimens offers greater specificity (detection of seroconversion and increases in antibody titer). An antibody response may be absent in immunocompromised people.
  • Other endemic mycoses (such as blastomycosis, paracoccidioidomycosis, and talaromycosis [formerly penicilliosis]) can lead to false-positive antigen and antibody tests for H. capsulatum .
  • Culture of H. capsulatum from bone marrow, blood, sputum, and tissue specimens is the definitive method but may take weeks to grow. DNA probe is sometimes used to confirm H. capsulatum in culture.
  • Demonstration of the typical intracellular yeast forms in tissue by microscopic examination strongly supports the diagnosis of histoplasmosis when clinical, epidemiologic, and other laboratory studies are compatible. Molecular diagnostics, such as PCR on tissue specimens, are increasingly available to support microscopic findings, although the performance of these tests may vary.


Treatment is not usually indicated for immunocompetent people with acute, localized pulmonary infection. People with more extensive disease or persistent symptoms beyond 1 month are generally treated with an azole drug such as itraconazole for mild to moderate illness or amphotericin B for severe infection. Patients with acute respiratory distress may benefit from steroids as well as antifungal treatment.


People at increased risk for severe disease should avoid high-risk areas, such as bat-inhabited caves.

CDC website: www.cdc.gov/fungal/diseases/histoplasmosis


  1. Armstrong PA, Beard JD, Bonilla L, Arboleda N, Lindsley MD, Chae S, et al. Outbreak of severe histoplasmosis among tunnel workers—Dominican Republic, 2015. Clin Infect Dis. 2018 May 2;66(10):1550–1557. doi: 10.1093/cid/cix1067.  [PMID:29211836]
  2. Azar MM, Hage CA. Laboratory diagnostics for histoplasmosis. J Clin Microbiol. 2017 Jun 1;55(6): 1612–20.  [PMID:28275076]
  3. CDC. Outbreak of histoplasmosis among travelers returning from El Salvador—Pennsylvania and Virginia, 2008. MMWR Morb Mortal Wkly Rep. 2008 Dec 19;57(50):1349–53.  [PMID:19092757]
  4. Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev. 2007 Jan;20(1):115–32.  [PMID:17223625]
  5. Morgan J, Cano MV, Feikin DR, Phelan M, Monroy OV, Morales PK, et al. A large outbreak of histoplasmosis among American travelers associated with a hotel in Acapulco, Mexico, spring 2001. Am J Trop Med Hyg. 2003 Dec;69(6):663–9.  [PMID:14740886]
  6. Weinberg M, Weeks J, Lance-Parker S, Traeger M, Wiersma S, Phan Q, et al. Severe histoplasmosis in travelers to Nicaragua. Emerg Infect Dis. 2003 Oct;9(10):1322–5.  [PMID:14609473]
  7. Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807–25.


Brendan R. Jackson, Tom M. Chiller