Released July 1, 2026

About the Episode

In this installment, Dr. Auwaerter provides a practical framework for diagnosing histoplasmosis, focusing on when to use antigen versus antibody testing based on immune status, clinical presentation, and fungal burden.

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Episode Summary

In this episode, Dr. Auwaerter addresses a scenario that frequently comes up in clinical management conferences and on consultation rounds: sorting through someone with a lung condition or granulomatous disease on a lymph node or other tissue, and how to use either direct or indirect tests for histoplasmosis.

He emphasizes that host immune status, clinical syndrome, and fungal burden are all very important when trying to secure a diagnosis. The direct histoplasma urine antigen test works extraordinarily well in disseminated infection, especially in significantly immunocompromised patients. In advanced HIV, sensitivity can exceed 95% with specificity in the 97–99% range. In other forms of immune compromise, sensitivity is 85–95%. However, in chronic pulmonary disease, it can fall as low as 10–40%, or perhaps 60–80% in acute infection. When dealing with disease that’s been going on for months in an otherwise immunocompetent patient, he doesn’t hold out hope for the urine antigen.

For chronic disease, antibody-based testing works best. In chronic pulmonary disease, sensitivity is typically 80–90+ percent with specificity in the upper 90s. But antibody testing falls short in the immunocompromised—exactly where antigen testing excels—with sensitivity of only 20–60%. Complement fixation antibody has reasonable specificity and titers over 1:32 often favor active disease. The complement fixation isn’t quite as specific and can cross-react with other endemic fungi. Immunodiffusion antibody has lower sensitivity but is more specific. Dr. Auwaerter often orders both in combination.

Histopathology and culture remain the gold standard, though culture takes two to eight weeks. His shorthand approach: in immunocompetent states with chronic lung disease, rest more on serological testing. In sicker, immunocompromised patients, start with urine antigen testing, perhaps combined with serum—though negatives never rule out the condition.

About the Presenter

Paul Auwaerter, MD, MBA

Paul G. Auwaerter is the Sherrilyn and Ken Fisher Professor of Medicine at the Johns Hopkins University School of Medicine serving as the Clinical Director for the Division of Infectious Diseases and Director of the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases.

He serves as the Executive Director of the Johns Hopkins Point of Care-Information Technology (POC-IT) Center producing the Johns Hopkins Guides – Antibiotic (ABX) (Antibiotic), HIV, Osler, Psychiatry, and Diabetes Guides. In 2018, Dr. Auwaerter served as President for the Infectious Diseases Society of America, the largest professional society worldwide related to infectious diseases.

For More Information

Johns Hopkins Antibiotic (ABX) Guide: https://www.hopkinsguides.com​

Unbound Medicine: https://www.unboundmedicine.com