Infectious Disease Compendium



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 postive (PubMed).

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

Epidemiologic Risks

Histoplasma capsulatum var. capsulatum (Western hemisphere. Missisippi River valley up into Ontario, caves in the Caribbean, Central Mexico, and Mexico. There is also cases in Asia and Africa.

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 is was suggested that it was blackbird roosts in the bamboo that were the source.

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 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 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.

Autoantibodies to gamma interferon is a risk (Pubmed); patients act like HIV.


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.

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).


see IDSA guidelines.

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 depends 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 spleen.

While serologies are nice and cultures 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




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Last Update: 05/16/18.