Detection of Histoplasma capsulatum Antigen in Urine


Histoplasma capsulatum, which is localized largely along the Ohio and Mississippi River valleys, is a significant cause of morbidity and mortality among individuals with weakened cellular immunity and older people over the age of 65. While healthy individuals are able to control the infection with minimal disease manifestations, immunocompromised patients exposed to H. capsulatum typically present with a non-specific febrile illness, which can rapidly progress to pneumonia, respiratory insufficiency, disseminated disease and death. With proper antifungal management histoplasmosis can be treated effectively, though timely diagnosis is essential.

Detection of Histoplasma capsulatum urine antigen (UAg) is among the most sensitive and rapid means to diagnose histoplasmosis. In previous studies, Mayo Clinic researchers evaluated analyte specific reagents (ASR) manufactured by IMMY (Norman, OK) for detection of Histoplasma galactomannan (GM) in urine using an enzyme immunoassay (EIA), and showed low positive agreement (64.5%) with the MiraVista (MVista) Histoplasma Ag Quantitative EIA (MiraVista Diagnostics, Indianapolis, IN).

Elitza Theel, Ph.D.
Elitza Theel, Ph.D.

In a recent study published in the Journal of Clinical Microbiology, Mayo Clinic researchers, first author Elitza Theel, Ph.D., Director of Infectious Diseases Serology Laboratory at Mayo Clinic, re-evaluated the IMMY GM ASR following modification of the original assay protocol and introduction of an indeterminate range. During the study, 150 prospectively collected urine samples were tested by both the IMMY and the MVista EIAs, and clinical histories were recorded for all study subjects.

In summary, Mayo Clinic researchers demonstrated that following modification of the original protocol and interpretive criteria, the IMMY GM ASR can be used as a reliable and, when implemented on-site, timely assay for detection of Histoplasma UAg. Alongside routine diagnostic testing including culture, serology and NAAT, the IMMY GM ASR can be used to both diagnose histoplasmosis and to monitor UAg levels as a marker of disease progression. While introduction of an indeterminate range may be viewed as a limitation, use of a single cut-off value would have led to an additional six false negative results (compared to the MVista EIA), one of which would have occurred in a patient with a first time diagnosis of H. capsulatum infection.

Excluding indeterminate results, Mayo Clinic achieved 100% negative agreement and 82.3% positive agreement with the MVista EIA. Among the three IMMY GM ASR negative/MVista EIA positive subjects, the IMMY result should be considered falsely negative for only one patient. For the remaining two discordant patients, the clinical significance of persistently low-level antigenuria as detected by the MVista EIA was not entirely clear and therefore consideration of the IMMY GM ASR results as inaccurate in these cases cannot be determined with certainty.

“Modification of the assay methodology and interpretive criteria significantly improved the clinical sensitivity of the Histoplasma urine antigen assay that is currently performed at Mayo Medical Laboratories,” said Dr. Theel.

For more information about Mayo Medical Laboratories' Histoplasma urine antigen assay, view Dr. Theel's Test in Focus.

Additional Mayo Clinic authors include: Julie Harring, Ala Dababneh, M.D., Leonard Rollins, Jeannie Bestrom, and Deborah Jespersen.

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Kelley Luedke (@kschrib)

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.