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Invasive aspergillosis (IA) is a severe infection that occurs in patients with prolonged neutropenia following transplantation or in conjunction with aggressive immunosuppressive regimens (eg, prolonged corticosteroid use, chemotherapy). The incidence of IA is reported to vary from 5% to 20% depending on the patient population. IA has an extremely high mortality rate of 50% to 80%, due in part to the rapid progression of the infection (ie, 1-2 weeks from onset to death). Approximately 30% of cases remain undiagnosed and untreated at death.
Definitive diagnosis of IA requires histopathological evidence of deep-tissue invasion or a positive culture. However, this evidence is often difficult to obtain due to the critically ill nature of the patient and the fact that severe thrombocytopenia often precludes the use of invasive procedures to obtain a quality specimen. The sensitivity of culture in this setting also is low, reportedly ranging from 30% to 60% for bronchoalveolar lavage (BAL) fluid. Accordingly, the diagnosis is often based on nonspecific clinical symptoms (unexplained fever, cough, chest pain, dyspnea) in conjunction with radiologic evidence (computed tomography [CT] scan), and a definitive diagnosis is often not established before fungal proliferation becomes overwhelming and refractory to therapy.
Recently, a serologic assay was approved by the FDA for the detection of galactomannan, a molecule found in the cell wall of Aspergillus species. Serum galactomannan (Aspergillus antigen) can often be detected a mean of 7 to 14 days before other diagnostic clues become apparent, and monitoring of Aspergillus antigen can potentially allow initiation of preemptive antifungal therapy before life-threatening infection occurs.
The clinical utility of Aspergillus antigen testing in BAL specimens as an early prognostic indicator of IA has recently been assessed. These studies demonstrated equivalent or higher sensitivity compared to detection of Aspergillus antigen in serum.(1-4) This assay may be useful in the assessment of therapeutic response as antigen levels typically decline in response to effective antimicrobial therapy.
As an aid in the diagnosis of invasive aspergillosis and assessing response to therapy
A positive result in bronchoalveolar lavage (BAL) fluid supports a diagnosis of invasive, pulmonary aspergillosis. Positive results should be considered in conjunction with other diagnostic procedures, such as microbiologic culture, histological examination of biopsy specimens, and radiographic evidence (see Cautions).
A negative result in BAL fluid does not rule out the diagnosis of invasive aspergillosis (IA). Patients at risk of IA should be monitored twice a week for Aspergillus antigen levels in serum until determined to be clinically unnecessary.
Aspergillus antigen levels typically decline in response to effective antimicrobial therapy.
False-positive results are reported to occur at rates of 8% to 14% with this assay when performed on serum. Numerous foods (pasta, rice, etc) contain galactomannan. It is thought that damage to the gut wall by cytotoxic therapy, irradiation, or graft-versus-host disease enables translocation of the galactomannan from the gut lumen into the blood and may be partially responsible for the high false-positive rate of this assay when serum is tested. Whether false-positive results in bronchoalveolar lavage (BAL) fluid are associated with the consumption of certain foods, as is observed in serum samples, remains to be determined.
Other genera of fungi such as Penicillium and Paecilomyces have shown reactivity with the rat EBA-2 monoclonal antibody used in the assay. These species are rarely implicated in invasive fungal disease. Specimens containing Histoplasma antigen may cross-react in the Aspergillus antigen assay. Cross-reactivity with Alternaria species also has been reported.
Semisynthetic antibiotics such as piperacillin, amoxicillin, and Augmentin, which are based on natural compounds derived from the genus Penicillium, have been demonstrated to cross-react with the rat EBA-2 monoclonal antibody used in the assay.
The specificity of the assay for Aspergillus species cannot exclude the involvement of other fungal pathogens with similar clinical presentations such as Fusarium, Alternaria, and Mucorales.
The performance of the assay has not been evaluated other specimen types such as urine or cerebrospinal fluid.
The assay may exhibit reduced detection of Aspergillus antigen in patients with chronic granulomatous disease and Job's syndrome.
The concomitant use of antifungal therapy in some patients with invasive aspergillosis may result in reduced sensitivity of the assay.
False-positive results are possible in patients receiving PLASMA-LYTE for intravenous hydration or if PLASMA-LYTE is used during bronchoscopy for the collection of BAL fluid.
1. Park SY, Lee S, Choi S, et al: Aspergillus galactomannan antigen assay in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis. J Infect 2010;61:492-498
2. Husain S, Clancy CJ, Nguyen MH, et al: Performance characteristics of the Platelia aspergillus enzyme immunoassay for detection of Aspergillus galactomannan antigen in bronchoalveolar lavage fluid. Clin Vaccine Immunol 2008;15(12):1760-1763
3. Meersseman W, Lagrou K, Maertens J, et al: Galactomannan in bronchoalveolar lavage fluid a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med 2008;177:27-34
4. Becker MJ, Lugtenburg EJ, Cornelissen JJ, et al: Galactomannan detection in computerized tomography-based bronchoalveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis. Br J haematol 2003;121:448-457
5. Xavier MO, Pasqualotto AC, Cardoso IC, Severo LC. Cross-reactivity of Paracoccidioides brasiliensis, Histoplasma capsulatum, and Cryptococcus species in the commercial Platelia Aspergillus enzyme immunoassay. Clin Vaccine Immunol 2009 Jan;16(1):132-133