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Aspergillus Galactomannan

Invasive aspergillosis primarily occurs in patients who have specific risk factors, such as prolonged neutropenia, history of allogeneic hematopoietic stem cell or solid organ transplantation, use of high-dose corticosteroids or inherited severe immunodeficiency. Invasive aspergillosis has an extremely high mortality rate of 50% to 80%. Approximately 30% of cases remain undiagnosed and untreated at death.

Dense, well-circumscribed nodular lesion(s) on CT scan, with or without surrounding hazy infiltrate (halo sign) and cavitary lesions, are characteristic but not specific for invasive pulmonary aspergillosis. Definitive diagnosis requires histopathological confirmation or positive culture. However, patients are often too critical to undergo biopsy. Culture of bronchoalveolar lavage fluid has a low sensitivity of 30 to 60%.

Platelia Aspergillus EIA (Bio-Rad, Redmond, WA) is an immunoassay that has been approved by the Food and Drug Administration (FDA) for detection of galactomannan, a component in the cell wall of Aspergillus species. Galactomannan can be detected in serum and bronchoalveolar lavage fluid during invasive infection. Serum galactomannan can be detected 7 to 14 days before other diagnostic modalities become apparent. Testing for galactomannan can facilitate initiation of preemptive antifungal therapy before life-threatening infection occurs. Reference value is <0.5 index.

The performance of the galactomannan immunoassay has been most closely evaluated in neutropenic patients and allogeneic hematopoietic cell transplant recipients. In these patient groups, the reported sensitivity of the assay in serum is 70% to 82% and specificity is 81% to 92%. In bronchoalveolar lavage fluid, sensitivity is 73% to 100% and specificity is 68% to 92%. In solid organ transplant recipients, sensitivity is 21% to 86% and specificity is 80% to 89% in serum, and sensitivity is 60% to 90% and specificity is 90% to 96% in bronchoalveolar lavage fluid. Sensitivity of the assay is higher in bronchoalveolar lavage fluid than in serum, especially in lung transplant recipients.

A positive result supports a diagnosis of invasive aspergillosis, but a negative result does not rule it out. Repeat testing is recommended if the result is negative and invasive aspergillosis is suspected. Patients at risk of invasive aspergillosis should have a baseline serum tested and then be monitored twice a week for increasing galactomannan antigen levels.False-negative results occur in patients who are receiving antifungal agents other than fluconazole.

False-positive results are reported to occur at rates of 8% to 14% with this assay. False-positive results occur in patients who are colonized but not infected with Aspergillus species and in those who have infection with Fusarium species, Histoplasma capsulatum, and Blastomyces dermatitidis because these fungi have similar galactomannans in their cell walls. False-positive reactions with piperacillin-tazobactam have been reported in the past, but manufacturing changes have eliminated this problem. Damage to the gut wall by cytotoxic therapy (mucositis), irradiation, or graft-versus-host disease enables galactomannan to move from the gut lumen into the bloodstream and cause false-positive results.  Other reported causes of false-positive results include blood products collected in certain commercially available infusion bags, multiple myeloma (IgG type), and flavored ice pops or frozen desserts containing sodium gluconate.

For all positive patients, it is recommended that a new aliquot of the same specimen be repeated, as well as collection of a new specimen from the patient for follow-up testing. Two or more consecutive positive results should be obtained from separately drawn specimens before the patient is considered to have a positive Aspergillus antigen test.

Specimen requirement is a red top tube of blood or 1.5 mL of bronchoalveolar lavage fluid.

Reference

 

Micelli MH and Kauffman CA. Aspergillus galactomannan for diagnosing invasive aspergillosis. JAMA Sep 26, 2017;318:1175

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