FEATURE: Diagnosing Histoplasmosis by Antigen Detection

Lawrence Joseph Wheat, MD
Medical Director, Founder & President of MiraVista Diagnostics

Here is an important patient case report I’d like to share with colleagues about diagnosing histoplasmosis by antigen detection. I welcome your questions and appreciate your feedback. You can reach me at 317-856-2681 or jwheat@miravistalabs.com.

CASE REPORT: Diagnosing Histoplasmosis by Antigen Detection

A patient with ulcerative colitis who was treated with a TNF blocker presented with respiratory symptoms but denied fever or weight loss. CT chest showed numerous parenchymal and pleural-based nodules and extensive mediastinal and bilateral hilar adenopathy. The patient underwent bronchoalveolar lavage and bacterial, fungal and mycobacterial stains were negative.

Subsequently a needle aspirate of a mediastinal lymph node revealed necrotizing granuloma and the GMS stain showed yeast suggestive of Histoplasma capsulatum. The urine antigen was negative but the serum antigen was 3.0 ng/ml.

Most physicians are familiar with the useful role of antigen detection for diagnosis of disseminated histoplasmosis[1] but are not aware that both the urine and serum must be tested for optimal sensitivity. In an earlier review of histoplasmosis complicating TNF blocker therapy the serum antigen was positive but the urine antigen was negative in one case[2]. In acute pulmonary histoplasmosis, the sensitivity for antigen detection was 83%, but 38% were positive only in the serum and would have been missed by testing only the urine[3].

NOTE: These observations apply only to the MVista® Histoplasma Quantitative Antigen EIA performed at MiraVista Diagnostics.


Is There Value in Testing Serum AND Urine for Histoplasma Antigen?

While many physicians are aware of testing urinary antigen to diagnose histoplasmosis, the practice of testing serum antigen for diagnosis is not as well-known. In fact, many physicians are surprised when they receive negative urine in a patient with disseminated disease. Testing performed at MiraVista Diagnostics’ laboratory using the MVista® Histoplasma Quantitative Antigen EIA show:

  • Testing both urine AND serum consistently provides the highest sensitivity for Histoplasma antigen
  • 38% of acute pulmonary histoplasmosis cases may not be properly diagnosed if only urine is tested
  • 5-10% of progressive disseminated histoplasmosis cases may not be properly diagnosed if only urine is tested

Consequences of Missed Diagnosis of Acute Pulmonary Histoplasmosis

  • 27% hospitalization
  • 6% acute respiratory failure
  • 4% death
  • 3% progressive disseminated histoplasmosis

Outcomes of Delayed Diagnosis of Progressive Disseminated Histoplasmosis

  • Transplant (N = 152): 32% ICU and 10% death
  • TNF Blocker (N = 98): 17% ICU and 1% death
  • AIDS (N = 141): 8% ICU and 4% death


(1)    Hage CA, Ribes JA, Wengenack NL, et al. A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis 2011 Sep; 53(5):448-54.

(2)    Hage CA, Bowyer S, Tarvin SE, Helper D, Kleiman MB, Joseph WL. Recognition, diagnosis, and treatment of histoplasmosis complicating tumor necrosis factor blocker therapy. Clin Infect Dis 2010 Jan 1; 50(1):85-92.

(3)    Swartzentruber S, Rhodes L, Kurkjian K, et al. Diagnosis of acute pulmonary histoplasmosis by antigen detection. Clin Infect Dis 2009 Dec 15; 49(12):1878-82.


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