What are the diagnostic tests for histoplasmosis?

Diagnostic Testing for Histoplasmosis

The most effective approach to diagnose histoplasmosis is combining urine and serum antigen testing with antibody detection, which increases diagnostic sensitivity to 96.3%. 1, 2

Primary Diagnostic Tests

Antigen Detection

• Urine antigen testing:

  • Sensitivity: 79.5% overall, 95% in disseminated disease 1
  • First-line test due to high sensitivity and rapid results
  • More sensitive than serum testing alone 3

• Serum antigen testing:

  • Sensitivity: 83.9% overall, 85% in disseminated disease 1
  • Particularly useful when urine testing is negative

• Combined urine and serum antigen testing:

  • Significantly increases sensitivity to 93% 3, 1
  • Essential approach as 45.8% of cases may have antigenemia only 4

Antibody Detection

• Serologic testing (antibodies):
  • Sensitivity varies by immune status:
    • 80-95% in immunocompetent patients with pulmonary disease 3
    • Only 18% in transplant recipients 3, 1
    • Only 45% in HIV/AIDS patients 3, 1
  • MVista Histoplasma antibody EIA offers improved sensitivity over traditional methods 2
  • Separate IgG (87.5% sensitivity) and IgM (67.5% sensitivity) detection 2

Confirmatory and Additional Tests

Fungal Culture

• Gold standard for definitive diagnosis 1
• Specimens can be obtained from:
  • Blood (lysis-centrifugation method preferred)
  • Bone marrow
  • Respiratory secretions
  • Other involved sites
• May require up to 6 weeks for growth 3
• DNA probe can shorten identification time 3

Histopathology

• Tissue biopsy with fungal stains showing characteristic morphology 1
• Defines "proven histoplasmosis" according to IDSA and American Society of Transplantation 1

Bronchoalveolar Lavage (BAL)

• Antigen detection in BAL fluid: 93.5% sensitivity 5
• Particularly useful for pulmonary disease
• Combining BAL antigen detection with cytopathology increases sensitivity to 96.8% 5

Diagnostic Algorithm

1. Initial testing (order simultaneously):

   • Urine and serum Histoplasma antigen testing
   • Histoplasma antibody testing (preferably EIA with separate IgG/IgM)
   • Blood cultures using lysis-centrifugation method

2. If pulmonary involvement suspected:

   • Add BAL with antigen testing and cytopathology
   • Respiratory culture

3. If initial tests negative but suspicion remains high:

   • Tissue biopsy from involved sites
   • Consider additional BAL if not already performed

Important Clinical Considerations

• Antigen levels correlate with disease severity - levels >16 pg/ml have 88% PPV for moderate to severe disease requiring inpatient treatment 3

• Antigen testing has limitations:

  • Cross-reactivity with other endemic fungi (blastomycosis, coccidioidomycosis, paracoccidioidomycosis, talaromycosis) 3
  • Limited availability (few reference laboratories in the US) 3
  • May be falsely negative in 17% of acute pulmonary cases 2

• Antigen levels can be used to monitor treatment response:

  • Levels decrease with effective therapy 3
  • Rising levels predict relapse 3
  • Should be monitored during and for 12 months after therapy 1

• PCR and DNA probes for H. capsulatum in tissues and body fluids remain investigational and are not validated for clinical use 3