Table 1. Use of the Galactomannan Antigenemia Test for Monitoring at Risk Patients

 

Population: Prolonged neutropenia, allogeneic SCT

Frequency: Two or three times weekly during high level immunosuppression

Criteria for positivity:

  • Two consecutive serum specimens with GMI > 0.5
  • Always repeat the test before implementing therapy for invasive aspergillosis

Considerations:

  • The galactomannan antigenemia EIA does not replace other tests in the workup of invasive aspergillosis
  • Antibiotics produced by Penicillium spp. may cause false-positivity
  • Medications/IV additives containing materials produced by Aspergillus (sodium gluconate) or Penicillium (certain antibiotics) may cause false-positivity
  • Histoplasmosis (and other endemic mycoses) may cause false-positivity
  • Mold-active antifungal drugs may cause false-negativity: repeat the test before implementing therapy for invasive aspergillosis
  • Falsely-positivity or falsely-negativity may occur for other reasons: clinical correlation is imperative

 

 

Table 2. Causes for False-Positivity or Cross Reactivity in the Galactomannan Antigenemia Test

 

False-positivity caused by galactomannan contamination

Cross-reactivity caused by similar cell wall galactomannan

Piperacillin-tazobactam

Amoxacillin-clavulanate

Other beta-lactam antibiotics

Plasmalyte (sodium gluconate)

Other intravenous hydration or nutrition fluids containing sodium gluconate

Possibly cotton, cardboard, soybean protein

 

Penicillum spp. including P. marneffei

Histoplasma capsulatum

Geotrichum

Neosartoria

Possibly Paecilomyces, Alternaria, Trychophyton, Botrytis, Wallemia, Cladosporium, Bifidobacterium

 

Table 3. Diagnosis of Invasive Pulmonary Aspergillosis using the Galactomannan Antigenemia EIA on BAL Specimens

 

Population

 

Cutoff  0.5

Cutoff 1.0

Reference

Sensitivity-%

 

Specificity-%

Sensitivity-%

 

Specificity-%

 

Hematology

Not stated

Not stated

100

 

100

 

 (28)

Bone marrow transplant

76

94

61

98

 

 (29)

Solid organ transplant

 

100

84

100

91

 

 (30)

Solid organ transplant

 

67

95

67

98

 (31)

Intensive Care Unit 88 87 Not Stated Not Stated (33)

Nonimmunocompromised

100

78

100

88

 (32)


 

Table 4. Use of the Galactomannan Antigenemia Test for Diagnosis of Invasive Aspergillosis

 

BAL and serum for evaluation of suspected pulmonary invasive aspergillosis

Validate positive result by repeat testing before starting empiric therapy

Search for other evidence of invasive aspergillosis

ˇ  CT scan of lungs and sinuses and

ˇ  Histopathology and culture

Evaluate for causes for inaccurate results

ˇ  Galactomannan contamination

ˇ  Cross-reactive mycosis

ˇ  Mold-active antifungal therapy

 

 

Figure 1. Galactomannan antigenemia detection in the PlateliaŽ Aspergillus EIA.  The test specimen in heated at 100° C. for 3 minutes in the presence of 4% ethylenediaminetetraacetic acid (EDTA), after which the supernatant is removed and mixed with the enzyme labeled detector antibody. This mixture is incubated in the microplate wells precoated with the capture antibody. Then the plates are incubated with a chromogenic substrate, tetramethylbenzidine (TMB). If antigen is present color develops, which is recorded using a microplate reader.

 

Figure 2. Galactomannan antigenemia EIA on BAL fluid (BALF) versus serum. These represent data for 33 cases in which either BAL or serum, obtained within one week of one another, were positive. All 33 BAL specimens but only 9 of 33 serums specimens (27%) were positive. In 29 of the 33 (88%) BAL specimens the result was >1.0.