Assay Sheet

  

For in vitro diagnostic use  

Test ID Code

CPT Code

Clinical Utility

Procedure

Specimens 

  

Causes for Rejection

• Lipemic, icteric, or hemolyzed specimens.
• Specimens that have been stored at ambient temperature.
• Specimens that have been stored at 2 to 8°C for >5 days.
• If storage longer than 5 days is needed, samples should be frozen at -70°C. Unless indicated as stored frozen, the specimenwill be rejected if the draw date is >5 days from receipt at ViraCor.

Assay Limitations

• A negative test result cannot rule out the diagnosis of Invasive Aspergillosis. Patients at risk for Invasive Aspergillosis should be tested twice per week.
• If a positive result is obtained, a second specimen should be collected and sent for testing immediately.
• The performance of the Aspergillus Galactomannan EIA has not been evaluated with neonatal specimens.
• The Aspergillus Galactomannan EIA may exhibit reduced detection in patients with chronic granulomatous disease and Job’s Syndrome.
• The concomitant use of mold-active, anti fungal therapy in some patients with Invasive Aspergillosis may result in reduced sensitivity of the Aspergillus Galactomannan EIA.
• There are reports in the literature of positive galactomannan test results in patients receiving piperacillin/tazobactam,therefore, results in these patients should be interpreted with caution and confirmed with other diagnostic methods.
• There are reports in the literature of positive galactomannan test results in patients with intestinal mucositis caused by chemotherapy and irradiation, which allows for extra absorption of dietary galactomannan.

Assay Range

Diagnonsis and Monitoring

Turnaround Time

Shipping

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Pathogen Overview

 

Organism

Aspergillus is a ubiquitous, filamentous fungus found in nature. It is commonly isolated from soil, plant debris, and indoor air environment. The genus Aspergillus contains nearly 200 species, of which 33 have been associated with human disease.  Most human infections are caused by A. fumigatus, A. terreus, A. flavus, and A. niger.  

Clinical Manifestations

Many hundreds of Aspergillus conidia are inhaled daily, and in the immunocompetent host, are cleared without clinical consequence, However, Aspergillus spp. can act as opportunistic pathogens in populations with compromised immune systems, leading to Invasive Aspergillosis (IA).  Risk factors for IA include prolonged neutropenia or neutrophil dysfunction, steroid therapy, haematological malignancy, cytotoxic drugs, AIDS, and solid organ transplantation. The risk is pronounced in bone marrow transplantation, where IA has been reported in up to 13% of allograft and autograft recipients.^1,2 Among solid-organ transplant patients, lung and heart-lung transplant recipients are at greatest risk of infection, where IA affects 14 to 18% of patients.^1,3  Inadequate blood flow, episodes of rejection, graft-versus-host-disease (GVHD), and cytomegalovirus (CMV) infection are also risk factors.  In immunocompromised and debilitated hosts, primary lesions are usually found in the lung, but widespread hematogenous dissemination with involvement of the heart valves, brain, liver, spleen, and kidneys is common.  At the site of the initial lesion, growth of hyphae into and along blood vessels is universal in the markedly neutropenic patient, leading to hemorrhagic infarction and necrosis. Among all filamentous fungi, Aspergillus is the most commonly isolated in invasive infections.  It is the second most commonly recovered fungus in opportunistic mycoses following Candida.  Despite advances in diagnostics and treatment protocols, mortality rates among high-risk patients with IA range from 50 to 90%.⁴

Diagnosis

An early, accurate diagnosis of IA has become essential in light of growing evidence that timely diagnosis is associated with improved patient survival.  Additionally, tests with high positive and negative predictive values may allow physicians to more precisely tailor treatment plans, as to avoid indiscriminate use of expensive and potentially toxic antifungal drugs.  An enormous challenge in the diagnosis of IA is the inadequate sensitivity of current “gold standard” diagnostic methods.  BAL cultures demonstrate sensitivity under 20%, and blood cultures are rarely positive.⁵  Therefore, diagnosis is based on a combination of clinical symptoms, radiological findings, histopathology, culture, and molecular assays.  Specifically, recent studies have indicated the value of molecular assays that detect fungal cell-wall components such as galactomannan (GM) and β-D-glucans.  When utilized to monitor IA, sensitivity has been assessed at over 90% for both assays.^6-9  Moreover, antigenemia declines during therapy, indicating the utility of these tests to monitor the effectiveness of antifungal treatment.^4,8 

Treatment

Due to the potentially devastating effects of IA, either prophylactic or empirical therapy is often warranted to manage high-risk populations.  Historically, the drug of choice has been amphotericin B, but voriconazole is now preferred, as it appears to be more effective and may have fewer side effects.  If treatment is not successful or the disease is aggressive, combination medications can be administered, including itraconazole, caspofungin, micafungin, and posaconazole.  The duration of therapy depends on many factors, including disease site, host's underlying disease, and response to the therapy.  All antifungals can cause serious problems, including kidney and liver damage, and may interact with other medications given to patients with weakened immune systems.  Therefore, using the proper tools to accurately diagnose and monitor the course of IA is essential to increase the likelihood of positive outcomes.

References