Table 5.
Comparison of Diagnostic Tests Utilized in the Diagnosis of Endemic Mycoses
| Diagnostic Test | Sensitivity, % | Specificity, % | Strengths | Limitations |
|---|---|---|---|---|
| Histoplasma | ||||
| Sputum/BAL culture [10, 11, 15, 16, 19, 20] | 15–84 | Inadequate data but presumed ~100 in most studies based on reference standard definitions | More useful in SPH and CPH | Slow growth, 4–8 wk Less useful in APH |
| Cytopathologic examination [8, 16, 17, 19, 20] | 9–50 | Inadequate data available, generally considered fairly specific but presence of Histoplasma in tissue may indicate past rather than current infection; may also be misidentified | Rapid results (hours) More likely to be positive in SPH and CPH |
Sensitivity and specificity vary based on pathologist experience Requires invasive procedures Less useful in pulmonary disease without dissemination |
| Serum antigen [13, 19, 21–23] | 30–87 | 98 | Fast results (days) Improving availability Most useful in APH |
Cross-reacts with other fungi Less useful in SPH and CPH |
| Urine antigen [8, 13, 15, 17, 19, 21, 24] | 40–95 | 95–99 | Fast results (days) Improving availability Most useful in APH |
Cross-reacts with other fungi Less useful in SPH and CPH |
| Antibody [8–10, 13, 14] | 40–95 | 91 | Fast results (days) More useful in SPH and CPH |
Take 4–8 wk to develop antibodies Can be negative in immunocompromised individuals Cross-reacts with other endemic mycoses |
| Blastomyces | ||||
| Sputum/BAL culture [1, 25–28] | 66–90 | Inadequate data but presumed ~100 in most studies based on reference standard definitions | Gold standard for diagnosis Commercial DNA (AccuProbe; GenProbe Inc., San Diego, CA, USA) testing can provide rapid results once there is sufficient growth |
Slow growth, up to 5 wk Diagnostic yield varies based on site DNA probe can cross-react with Paracoccidioides |
| Histologic or cytopathologic examination [26–30] | 38–93 | Inadequate data, generally considered highly specific, but misidentification may occur; presence of Blastomyces in tissue typically indicates active infection |
Rapid results (hours) | Sensitivity varies based on pathologist experience Atypical forms of B. dermatitidis may require special stains |
| Potassium hydroxide smear [25, 27, 28] | 48–90 | No data available, generally considered highly specific but false positives possible |
Rapid results | Varied sensitivity |
| Serum EIA antigen [1, 25, 29, 31, 32] | 36–82 | 99 compared with nonfungal infections or healthy controls but 95.6% cross-reactivity with 90 cases of histoplasmosis | EDTA heat treatment improves sensitivity | Cross-reacts with other fungi Only available at reference labs |
| Urine EIA antigen [1, 27, 29, 31–33] | 76–93 | 79–99 | Can be utilized to monitor response to treatment | Cross-reacts with other fungi Only available at reference labs |
| Antibody testing via complement fixation [28, 34, 35] | 16–77 | 30–100 | Fast results (days) | Difficult to perform, variable performance |
| Antibody testing via immunodiffusion [28, 29, 34, 36] | 32–80 | 100 in 1 study, possibility for cross-reaction remains | Fast results (days) | Can be negative in immunocompromised patients |
| Antibody testing via EIA (BAD-1) [33, 36] | 88 | 94–99 | Low rate of cross-reactivity Increased sensitivity when combined with antigen testing |
May be negative early in infection and in immunocompromised individuals Not commercially available |
| Coccidioides | ||||
| Culture [37] | 56–60 | 100 | Grows well on most media in 2–7 d, specificity | Biohazard to laboratory staff |
| Histologic or cytopathologic examination [37, 38] | 22–55 | 99.6 | Rapid results | Requires invasive procedures Endospores may be mistaken for Histoplasma, Blastomyces, or Cryptococcus |
| Serum antigen [39, 40] | 28–73 | 90–100 | Most useful in immunocompromised and severe disease | Cross-reactivity with Histoplasma and Blastomyces |
| Urine antigen [39, 41, 42] | 50–71 | 90–98 | Most useful in immunocompromised and severe disease | Cross-reactivity with Histoplasma and Blastomyces |
| Immunodiffusion antibody assays (IDTP and IDCF) [42, 43] | 60.2–71 | 98.8 | Quantitative titers correlated to disease severity and can monitor treatment response Commonly used as confirmatory test |
Only available at reference labs Less useful in immunosuppressed patients May be negative early in disease |
| EIA antibody assay [40, 43–49] | 83–100 | 75–98.5 | Commercially available Faster results |
Needs confirmatory testing Not quantitative IgM cross-reacts with other mycoses Less useful in immunosuppressed patients May be negative early in disease |
| Skin testing (Spherusol) [50] | >98 | >98 for prior exposure | Negative test may mean Coccidioides infection less likely |
Only indicates prior exposure, unclear role in active infection |
| Paracoccidioides | ||||
| Culture [51] | 25–44 | 100 | Specificity | Requires 2–4 wk to grow, infrequently used |
| Histologic or cytopathologic examination [52, 53] | 55–97 | Presumed highly specific but inadequate data and misclassification possible |
Gold standard test, results in hours–days | Requires invasive procedures |
| Double immunodiffusion antibody assay [52–56] | 80–90 | >90, inadequate data | Most commonly utilized antibody test |
Cross-reactivity with other fungi Less useful for diagnosis of P. lutzii |
| ELISA antibody assay [52, 57, 58] | 95.7 | 85–100 | Simple to perform Fast results Antibodies can be detected at low concentrations |
Cross-reacts with other fungi Requires confirmatory DID Ab Less useful for diagnosis of P. lutzii |
| Latex agglutination antibody testing [56] | 69.5–84.3 | 81.1 | Simple to perform | Poor reproducibility Limited availability Less useful for diagnosis of P. lutzii |
| Talaromyces | ||||
| Blood culture [59–62] | 72.8–83 | 100 | Gold standard Highly specific May culture other sterile sites as well |
Takes up to 4 wk to grow More likely to be positive in late stages of infection |
| Sputum culture [59, 60, 63] | 11–34 | Inadequate data, presumed highly specific | Highly specific | Takes up to 4 wk to grow |
| Culture from other tissues [59–61] | Inadequate data, presumed highly specific | High specificity, for some tissues high sensitivity | ||
| -Skin | 6–90 | -Yield only accurate if the area is involved, slow growth | ||
| -Bone marrow | 17–100 | -Painful, variable sensitivity–invasive, variable sensitivity | ||
| -Lymph node | 34–100 | -Invasive, small numbers studied | ||
| -Cerebrospinal fluid | 15 | -Invasive, small numbers studied | ||
| -Palatal/pharynx papule | 10 | -Painful, small numbers studied | ||
| -Liver | 5 | -Invasive, small numbers studied | ||
| -Pleural fluid | 5 | -Invasive, small numbers studied | ||
| Cytology [63] | 46 | Inadequate data, presumed highly specific, but misidentification may occur |
Specificity | Small numbers in studies, requires invasive procedures in most cases |
| Lateral flow immunochromatographic antigen assay (4D1) [64] | 87.9 | 100 | Rapid results Easy to perform |
Not commercially available Urine testing only |
| Antigen via EIA (Mp1p antigen) [62] | 86.3 | 98.1 | Rapid results Sensitivity further increased when both urine and serum tested |
Not commercially available |
| Mab 4D1 inhibitory ELISA antigen assay [65] | 100 | 100 | Low cross-reactivity Can be utilized on serum |
Only tested on small sample size (n = 45), results need confirmation |
Adapted from Poplin et al. [159].
Abbreviations: Ab, antibody; APH, acute pulmonary histoplasmosis, CPH, subacute pulmonary histoplasmosis; DID, double immunodiffusion; EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay; IDCF, immunodiffusion complement fixation; IDTP, immunodiffusion tube precipitin; SPH, subacute pulmonary histoplasmosis.