Table 3:

Diagnostic Tests for Endemic Fungi

Organism	Clinical Manifestations	Gold Standard	Culture	Antigen Testing	Antibody Testing	Comments
Histoplasma	Chronic pulmonary infection Acute pulmonary infection Disseminated infection	Blood, respiratory specimen, or deep tissue culture [6]	Blood Urine Sputum/ BAL Tissue	Serum antigen Urine antigen BAL antigen	CF Immunodiffusion EIA	For isolated pulmonary disease, multiple testing methods are used to aide in diagnosis. Antigen testing is most helpful in disseminated disease. This has improved sensitivity over PCR based testing.
		Limitations Time consuming; low sensitivity even in disseminated disease		Limitations Serum/urine sensitivity around 80% in disseminated disease [60] Low serum/urine sensitivity in isolated pulmonary disease [61] High BAL sensitivity [62] Cross reactivity with other endemic fungi	Limitations Antibody testing has modest sensitivity and potential to cross react with other endemic fungi [58]
Blastomyces	Subacute pulmonary infection Necrotizing pneumonia ARDS Disseminated infection	Blood, respiratory specimen, or deep tissue culture [6]	Blood Urine Sputum/ BAL Tissue	Urine antigen Serum antigen BAL antigen	CF Immunodiffusion EIA EIA to BAD-1	Cultures have a high sensitivity and are very useful in diagnosis. Antibody testing useful in the setting of sub-acute infection manifesting as pulmonary nodules.
		Limitations High sensitivity but delayed time to positivity		Limitations High sensitivity for urine but significant cross reactivity with other endemic fungi [70–72] Lower sensitivity for serum and BAL	Limitations Antibody testing has modest sensitivity and potential to cross react with other endemic fungi [73] EIA to BAD-1 has improved sensitivity and specificity [74]
Coccidioides	Asymptomatic infection Pneumonia Disseminated infection	Culture or direct visualization (spherules filled with endospores	Blood Urine Sputum/ BAL Tissue	Serum antigen Urine antigen	CF Immunodiffusion EIA	EIA is generally used as screening test with CF or immunodiffusion used for confirmatory testing
		Limitations Low sensitivity for both culture and direct visualization		Limitations Modest sensitivity and high cross reactivity [76]	Limitations EIA has high sensitivity but sensitivity may be slightly reduced immunocompromised populations [81]

Abbreviations: ARDS- Acute Respiratory Distress Syndrome, CF- Complement Fixation, EIA- Enzyme Immunoassay

¹Tests are referring to the diagnostic tests used for IC, which includes candidemia and deep-seated tissue infections