(1-3)-Beta-D-Glucan Assay: Lab and Clinical Application

Abstract and Introduction

Abstract

A new fungal surrogate marker, (1–3)-β-D glucan, offers a noninvasive method for the potential surveillance and diagnosis of invasive fungal infections. Invasive fungal infections have long been associated with significantly high morbidity and mortality on hematology-oncology wards and recipients of either solid-organ or hematopoietic stem cell transplantation. The diagnoses of invasive fungal infections have historically been made difficult by the need for invasive methods. (1–3)-β-D-glucan testing requires a minimally invasive sample that can be used to aid in the diagnosis of an invasive fungal infection as well as monitor the response to treatment. One disadvantage of (1–3)-β-D-glucan testing is that a positive test alone lacks sufficient sensitivity and specificity for a definitive diagnosis. While formal guidelines for the use of (1–3)-β-D-glucan testing are lacking, this chromogenic assay provides a new opportunity for testing at-risk populations. A review and recommendation for its laboratory and clinical application are provided.
Glossary
(1–3)-β-D-glucan: A polysaccharide component of the cell wall of most fungi pyrogen test. An assay used to determine if a pharmaceutical or medical device intended for human use will stimulate fever.

Introduction

Invasive fungal infections remain a significant problem in hematopoietic stem cell transplant (HSCT) and solid organ transplantation (SOT) recipients with changing epidemiologic patterns during the previous 2 decades.^[1,2] Despite advances in technology and therapy, invasive fungal infections are still associated with significantly high morbidity and mortality.^[3] Among SOT recipients, Candida and Aspergillus pathogens continue to be most often implicated as the cause of infections.^[1] However, Aspergillus species and other filamentous molds, such as Fusarium, Scedosporium, and the Zygomycetes, are more commonly associated with invasive fungal infections in HSCT recipients.^[2]

Measurement of biologic markers, such as the galactomannan Aspergillus antigen and the fungal wall component (1–3)-β-D-glucan, offers a noninvasive method for the detection of invasive fungal infections. Historically, the diagnosis of invasive fungal infections has been made difficult by the need for tissue biopsies for cultures and histological examination.4 Furthermore, clinical and radiological findings do not have sufficient diagnostic sensitivity and specificity to be helpful. This review will discuss the U.S. Food & Drug Administration (FDA) approved fungal wall component (1–3)-β-D-glucan assay and its role as a surrogate marker for invasive fungal infections.

Cite this: (1–3)-β-D-Glucan Assay - Medscape - Nov 01, 2011.

Table 1. Available Beta-D-Glucan Assays
Kit	Manufacturer	FDA Approved	Crab Species	Cut-off Value
Fungitell	Associates of Cape Cod (U.S.)	Yes	Limulus polyphemus (colormetric)	60–80 pg/Ml
Endosafe-PTS glucan	Charles River Laboratories (U.S.)	No	Limulus polyphemus (colormetric)	10–1000 pg/mL
Fungitec G-MK	Seikagaku Biobusiness (Japan)	No	Tachypleus tridentalus (colormetric)	20 pg/mL
β-glucan test	Waco Pure Chemical Industries (Japan)	No	Tachypleus tridentalus (turbidimetric)	11 pg/mL
BGSTAR β-glucan test	Maruha (Japan)	No	Tachypleus tridentalus (colormetric)	11 pg/mL

Table 2. Sources of Error for the Beta-Glucan Assay
A. Assay Procedure
1. Mislabeled or unlabeled samples
2. Bacterial or fungal contaminated equipment
3. Non-calibrated spectrophotometer
B. False-positive reactions
1. Concurrent bacteremia (most commonly Streptococcus species)
2. Hemodialysis cellulose membranes and filters
3. Immunoglobulin products (eg, IVIG)
4. Human serum (due to inherent yellow color)
5. Drugs such as Crestin, Lentinan, Schizophyllan, and Scleroglucan
C. False-negative reactions
1. Lipemic blood samples
2. Hemolyzed blood samples
3. Certain fungi that lack significant levels of (1–3)-β-D-glucan such as Zygomycetes, Cryptococcus neoformans, and Blastomyces dermatitidis.[4,7–9]

Table 3. Summary of Trials for the Fungitell Assay for the Diagnosis of an Invasive Fungal Infection Using 1 Serum Sample at the Various Cut-off Values
Trial	Sensitivity	Specificity	PPV	NPV
Odabasi and colleagues[17] (>60 pg/mL)	100%	90.0%	43.0%	100%
Pazos and colleagues[20] (>120 pg/mL)	87.5%	89.6%	70.0%	96.3%
Racil and colleagues[22] (>60 pg/mL)	88.9%	19.8%	10.4%	94.4%
Racil and colleagues[22] (>80 pg/mL)	88.9%	32.6%	12.1%	96.6%
Ostrosky-Zeichner and colleagues[24] (>60 pg/mL)	69.9%	87.1%	83.8%	75.1%
Ostrosky-Zeichner and colleagues[24] (>80 pg/mL)	64.4%	92.4%	89.0%	75.1%
Pickering and colleagues[23] (>60 pg/mL)	93.3%	77.2%	51.9%	97.8%

Table 4. Proposed Recommendations for the Use of the (1–3)-β-D-Glucan Assay
Testing should be used in conjunction with other methods for the diagnosis of invasive fungal infections Testing should precede antifungal therapy. Twice-weekly testing should be used for surveillance of infections in at-risk patients. Once-weekly testing should be used to assess the response to treatment. Positive test results should be confirmed with a second new specimen or repeated from the initial specimen prior to acceptance as a true positive. Further study is needed to determine the usefulness of testing on specimens other than serum.

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