From the Guidelines
False positive urine histoplasma antigen tests are most commonly caused by cross-reactivity with other fungal infections, such as blastomycosis, coccidioidomycosis, paracoccidioidomycosis, and talaromycosis, as noted in a 2019 study by the American Thoracic Society 1. The causes of false positive urine histoplasma antigen results can be multifactorial, including:
- Cross-reactivity with other fungal infections: The test may react with antigens from other fungi like Blastomyces, Paracoccidioides, or Penicillium, as seen in studies examining the diagnostic yield of Histoplasma antigen 1.
- Recent antifungal therapy: Patients who have recently received antifungal treatment may still have detectable antigen levels even if the infection has cleared.
- Contamination: Improper sample collection or handling can introduce contaminants that interfere with the test.
- Certain medications: Some antibiotics or immunosuppressants can affect test results.
- Immune complex formation: In some cases, antibodies to histoplasma can form complexes with antigens, leading to false positives.
- Renal insufficiency: Patients with kidney problems may have delayed clearance of antigens, causing persistent positive results. To minimize false positives, it is essential to ensure proper sample collection, consider the patient's medical history and current medications, and interpret results in conjunction with clinical symptoms and other diagnostic tests, as recommended by the American Thoracic Society 1. If a false positive is suspected, repeat testing or use alternative diagnostic methods may be necessary.
From the Research
Causes of False Positive Urine Histoplasma Antigen Results
- Cross-reactivity with other fungal infections, such as blastomycosis, paracoccidioidomycosis, and penicilliosis 2
- Cross-reactivity with Emergomyces africanus infection, a closely-related pathogen that causes a multi-system disease among HIV-seropositive persons with a low CD4 cell count 3
- Presence of human anti-rabbit antibody, produced in response to rabbit antithymocyte globulin (ATG) administration in solid organ transplant patients 4
- Cross-reactivity with coccidioidomycosis, a fungal infection caused by Coccidioides species, particularly in patients with acute or chronic coccidioidomycosis 5
- Other endemic mycoses, such as sporotrichosis, cryptococcosis, and talaromycosis, may also cause cross-reactivity, although this has not been extensively studied 2, 3
Specific Fungal Infections Causing Cross-Reactivity
- Blastomyces dermatitidis: cross-reactivity observed in 12 of 19 patients with blastomycosis 2
- Paracoccidioides brasiliensis: cross-reactivity observed in 8 of 9 patients with paracoccidioidomycosis 2
- Penicillium marneffei: cross-reactivity observed in 17 of 18 patients with P. marneffei infection 2
- Emergomyces africanus: cross-reactivity observed in urine specimens from patients with E. africanus infection and in culture filtrates of E. africanus and related fungi 3
- Coccidioides species: cross-reactivity observed in 11 of 19 patients with acute or chronic coccidioidomycosis 5