A fungus. Histoplasma capsulatum and H. capsulatum var. duboisii (Africa).

Culture, serology and a urine Histoplasma antigen are used for diagnosis.

Of these, the urine antigen is the best test and the level parallels disease progression or response to treatment. A low positive (< 0.6 ng/ml) has a 50% chance of false positive (PubMed). If ordering a urine antigen you do NOT need to also order a serum antigen.

Testing CSF for anti-Histoplasma IgG, IgM antibody and antigen increases the sensitivity for the diagnosis of meningitis (PubMed).

Epidemiologic Risks

World wide. Histoplasma capsulatum var. capsulatum (Western hemisphere. Mississippi River valley up into Ontario, caves in the Caribbean, Central Mexico, Mexico, and Brazil (PubMed). There are also cases in Asia and Africa. In China along the Yangtze River and in India.

As with all infections, the range is moving with climate change, a 2018 map of risk/distribution for Histoplasmosis (PubMed).

H. capsulatum var. duboisii (Africa)(PubMed).

H. capsulatum var. farciminosum: epizootic lymphangitis in horses in North Africa and the Middle East.

Found in the soils of the Mississippi and Ohio River Valleys of N. America and a smattering of cases in Montana (PubMed) and Idaho, as well as SE Asia. Often with decaying bat guano (if that really is the name) or bird droppings.

Usually acquired by inhaling dust and dirt, especially from rotting organic material. As an example, disease rates kicked up in Illinois when they did extensive road work. But in Arkansas, there was an outbreak from bamboo bonfires (PubMed) and it was suggested that it was blackbird roosts in the bamboo that was the source.

There are indoor outbreaks associated with cleaning air vents (PubMed).

Also strains in Mexico, Central and South America, parts of eastern and southern Europe, and Australia. These strains may not react with the US antigen test. There was an outbreak in the Dominican Republic in workers removing bat guano (Dr. Strangeglove) from a tunnel with no protection (PubMed).

There is an African (H. capsulatum var. duboisii) strain found in the Democratic Republic of Congo, Nigeria, Senegal, and Uganda.

Immunosuppression can cause reactivation, HIV and the TNF inhibitors are most commonly reported but do not underestimate methotrexate and steroids.

Auto-antibodies to gamma interferon is a risk (Pubmed); patients act like HIV.

Bendamustine when used for non-Hodgkins lymphoma (PubMed).


Asymptomatic diseases: lots of calcified granuloma on CXR in an old Midwest farmer.

Pneumonia, both acute and chronic.

Acute pneumonia. Make the diagnosis with both antigen AND antibody (Pubmed). The antigen alone may be negative in a fifth of patients.

Can, rarely, cause a chronic pneumonia that mimics TB (Pubmed) Treatment is a year of itraconazole.

Acute disseminated disease. One of the few diseases to cause a sky-high LDH (the others being PJP and miliary TB)

Chronic progressive disseminated disease.

Reactivation disseminated disease in AIDS and in patients on TNF inhibitors (PubMed).

Various focal infections: meningitis etc.

African histoplasmosis mostly infects skin and bones. It has reactivated 40 years after leaving an endemic area (PubMed).


Amphotericin B > itraconazole at a minimum of 400 mg po qd. In disseminated disease in HIV, lipid-based amphotericin for 2 weeks followed by itraconazole has better outcomes than regular amphotericin followed by itraconazole. Type and duration depend on the severity of disease; meningitis and disseminated disease should get high dose (1 mg/kg/d) of amphotericin.

For HIV patients, "discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis (PubMed)."

For those on TNF inhibitors plan on stopping it and at least 12 months of antifungal therapy (PubMed).


Curious complications include oral (especially tongue. So few infections involve the tongue) ulcers, adrenal involvement, and mediastinal fibrosis (a question I missed on my boards, I am bitter to this day). Many a Midwesterner will have TNTC calcified granuloma on CXR and in the spleen.

While serologies are nice and culture the gold standard, they can be slow and the best diagnostic test to treat and follow the disease is the urine Histoplasma antigen.

Curious Cases

Relevant links to my Medscape blog




I Just Want to Giggle

Bad Old Days Return Part 2


Last Update: 03/31/21.