Infectious Disease Compendium



A fungus. Histoplasma capsulatum (Western hemisphere. Missisippi River valley, caves in the Caribean and Mexico) 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).

Epidemiologic Risks

Histoplasma capsulatum (Western hemisphere. Missisippi River valley, caves in the Caribean and Mexico) and H. capsulatum var. duboisii (Africa).

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.

Usually acquired by inhaling dust and dirt, esp from rotting organic material. As an example, 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.

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.

Chronic progressive disseminated disease.

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

Various focal infections: meningitis etc.

African histoplasmosis 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 itraconzole. 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 (esp 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.