Information for Healthcare Professionals about Histoplasmosis

Clinical features
Healthcare professionals can use the Clinical Testing Algorithm for Histoplasmosis to help guide diagnoses.

Severity of illness depends on host immunity and the intensity of the exposure. Symptomatic infections (1%) usually present 3 to 17 days after exposure. Acute pulmonary histoplasmosis is often self-limiting; symptoms include fever, malaise, cough, headache, chest pain, chills, and myalgias. Persons with a history of pulmonary disease can develop chronic pulmonary histoplasmosis. Immunosuppressed persons are at risk for developing disseminated histoplasmosis.

Etiologic agent

Histoplasma capsulatum var. capsulatum (near-worldwide distribution) and Histoplasma capsulatum var. duboisii (in Africa). 1

Reservoir and endemic areas

Soil, particularly when heavily contaminated with bird or bat droppings. Endemic areas include the central and eastern United States, particularly areas around the Ohio and Mississippi River Valleys, 2 as well as parts of Central and South America, 3 Africa, 4 Asia, 5 and Australia. 6


Histoplasmosis is typically acquired via inhalation of airborne microconidia, often after disturbance of contaminated material (e.g., activities such as spelunking, cleaning chicken coops, or construction). Primary cutaneous histoplasmosis and solid organ donor-derived histoplasmosis are extremely uncommon. 7,8


Can include pericarditis, broncholithiasis, pulmonary nodules, mediastinal granuloma, or mediastinal fibrosis. 1,9 In persons who develop progressive, chronic, or disseminated disease, symptoms may persist for months or longer. Mortality is high in HIV-infected persons who develop disseminated histoplasmosis.


Histoplasma antigen detection in urine and/or serum is the most widely used and most sensitive method for diagnosing disseminated histoplasmosis and acute pulmonary histoplasmosis following exposure to a large inoculum. 1 Other methods include antibody tests, culture, and microscopy. 1

  • Antigen detection: Enzyme immunoassay (EIA) is typically performed on urine and/or serum, but can also be used on cerebrospinal fluid or bronchoalveolar lavage fluid.
  • Antibody tests: Because development of antibodies to Histoplasma can take two to six weeks, antibody tests are not as useful as antigen detection tests in diagnosing acute histoplasmosis or in immunosuppressed persons, who may not mount a strong immune response.
    • Immunodiffusion (ID): Tests for the presence of H (indicates chronic or severe acute infection) and M (develops within weeks of acute infection and can persist for months to years after the infection has resolved) precipitin bands; ~80% sensitivity.
    • Complement Fixation (CF): Complement-fixing antibodies may take up to 6 weeks to appear after infection. CF is more sensitive but less specific than immunodiffusion.
  • Culture: can be performed on tissue, blood, and other body fluids, but may take up to 6 weeks to become positive; most useful in the diagnosis of the severe forms of histoplasmosis. A commercially available DNA probe (AccuProbe, GenProbe Inc.) can be used to confirm.
  • Microscopy: for detection of budding yeast in tissue or body fluids, low sensitivity, but can provide a quick proven diagnosis if positive.
  • Polymerase Chain Reaction (PCR): PCR for detection of Histoplasma directly from clinical specimens is still experimental, but promising.

Mild to moderate cases of acute pulmonary histoplasmosis will often resolve without treatment; however, treatment is indicated for moderate to severe acute pulmonary, chronic pulmonary, disseminated, and central nervous system (CNS) histoplasmosis. Antifungal agents proven to be effective are amphotericin B (including liposomal and lipid formulations) and itraconazole (for mild-to-moderate infections and step-down therapy).

For detailed treatment guidelines, please refer to the Infectious Diseases Society of America’s Clinical Practice Guidelines for the Management of Patients with Histoplasmosis.

Risk groups

People in endemic areas, particularly those who have occupations or participate in activities exposing them to soil that contains bird or bat droppings. Disseminated histoplasmosis is more likely to occur in immunosuppressed persons (HIV/AIDS, 10 organ transplant, 11 or use of immunosuppressive medications 13), infants, 13 or adults age 55 years and older. 14

Surveillance and statistics

Histoplasmosis is reportable in certain states. Check with your local, state, or territorial public health department for more information about disease reporting requirements and procedures in your area. Click here for histoplasmosis statistics.

Areas for further research
  • Developing and validating improved diagnostic tests
  • Developing improved methods for detection of Histoplasma in environmental samples
  • Identifying safe and effective environmental remediation measures
  • Determining trends in histoplasmosis incidence and the global burden of infection
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  2. Manos NE, Ferebee SH, Kerschbaum WF. Geographic variation in the prevalence of histoplasmin sensitivity. Dis Chest. 1956 Jun;29(6):649-68.
  3. Colombo AL, Tobon A, Restrepo A, Queiroz-Telles F, Nucci M. Epidemiology of endemic systemic fungal infections in Latin America. Med Mycol. 2011 Nov;49(8):785-98.
  4. Loulergue P, Bastides F, Baudouin V, Chandenier J, Mariani-Kurkdjian P, Dupont B, et al. Literature review and case histories of Histoplasma capsulatum duboisii infections in HIV-infected patients. Emerg Infect Dis. 2007 Nov;13(11):1647-52.
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  11. Cuellar-Rodriguez J, Avery RK, Lard M, Budev M, Gordon SM, Shrestha NK, et al. Histoplasmosis in solid organ transplant recipients: 10 years of experience at a large transplant center in an endemic area. Clin Infect Dis. 2009 Sep 1;49(5):710-6.
  12. Smith JA, Kauffman CA. Endemic fungal infections in patients receiving tumour necrosis factor-alpha inhibitor therapy. Drugs. 2009 Jul 30;69(11):1403-15.
  13. Odio CM, Navarrete M, Carrillo JM, Mora L, Carranza A. Disseminated histoplasmosis in infants. Ped Infect Dis J. 1999 Dec;18(12):1065-8.
  14. Wheat LJ, Slama TG, Norton JA, Kohler RB, Eitzen HE, French ML, et al. Risk factors for disseminated or fatal histoplasmosis. Analysis of a large urban outbreak. Ann Intern Med. 1982 Feb;96(2):159-63.