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β-D-glucan testing is important for diagnosis of invasive fungal infections
Elitza S Theel1, Christopher D Doern
1Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract:
Invasive fungal infections are a significant cause of morbidity and mortality in patients who receive immunosuppressive therapy, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients. Many of the fungi associated with these infections are angioinvasive and are best diagnosed by visualizing the organism in or culturing the organism from deep tissue. However, obtaining such tissue often requires an invasive procedure. Many HSCT recipients are thrombocytopenic, making such procedure too risky because of potential bleeding complications. Additionally, positive blood cultures are rare for patients with angioinvasive fungal infections, making this diagnostic strategy of little value. Undiagnosed fungal infections in these patient populations are a significant cause of mortality. Prophylactic use of antifungal agents, such as the echinocandins, during periods of neutropenia or graft-versus-host disease may prevent some fungal infections but increase the risk for others. Detection of fungal antigens in body fluids, including cryptococcus capsular polysaccharide, histoplasma antigen, galactomannan, and β-d-glucan, is viewed as being clinically useful for at least the presumptive diagnosis of invasive fungal infections. β-d-Glucan is an attractive antigen in that it is found in a broad range of fungal agents, including the commonly encountered agents Candida spp., Aspergillus spp., and Pneumocystis jirovecii. Cross-reactions with certain hemodialysis filters, beta-lactam antimicrobials, and immunoglobulins, which raise concerns about false-positive tests, have also been described. As a result, the use of this testing must be closely monitored. In this point-counterpoint, we have asked Elitza Theel, who directs the Infectious Disease Serology Laboratory at the Mayo Clinic, to address why she believes that this test has value in the diagnosis of invasive fungal infections. We have asked Christopher Doern, Director of Clinical Microbiology at Children's Medical Center of Dallas, why he questions the clinical value of β-d-glucan testing.
Insights
Diagnosing invasive fungal infections in immunocompromised patients is challenging. The clinical utility of beta-D-glucan testing for early detection of these infections is debated due to potential false positives.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Clinical Diagnostics
Background:
- Invasive fungal infections pose a significant threat to immunocompromised individuals, particularly solid organ and hematopoietic stem cell transplant (HSCT) recipients.
- Traditional diagnostic methods like tissue biopsy and blood cultures have limitations, including invasiveness, bleeding risks in thrombocytopenic patients, and low sensitivity for angioinvasive fungi.
- Prophylactic antifungal use can alter infection risks, highlighting the need for accurate diagnostic tools.
Purpose of the Study:
- To evaluate the clinical value of beta-D-glucan antigen testing in the diagnosis of invasive fungal infections.
- To present contrasting viewpoints on the utility and limitations of beta-D-glucan testing in specific patient populations.
Main Methods:
- Review of diagnostic strategies for invasive fungal infections in immunocompromised patients.
- Discussion of fungal antigen detection, focusing on beta-D-glucan as a broad-spectrum biomarker.
- Consideration of potential confounding factors and false-positive results associated with beta-D-glucan assays.
Main Results:
- Beta-D-glucan is present in a wide range of fungi, including Candida, Aspergillus, and Pneumocystis species.
- Concerns exist regarding false-positive test results due to cross-reactions with hemodialysis filters, certain antibiotics, and immunoglobulins.
- The interpretation of beta-D-glucan test results requires careful monitoring within the clinical context.
Conclusions:
- Beta-D-glucan testing is proposed as a clinically useful tool for the presumptive diagnosis of invasive fungal infections.
- Skepticism remains regarding the definitive clinical value due to potential false positives and the need for further validation.
- The ongoing debate underscores the importance of experienced interpretation in utilizing this diagnostic biomarker.
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