Serum (1–3)-β-D-Glucan (Fungitell, etc)

Indications

Diagnosis of Invasive Aspergillosis (see Aspergillus, [[Aspergillus]])

  • Recommendations (Infectious Diseases Society of America 2016 Practice Guidelines) (Clin Infect Dis, 2016) [MEDLINE]
    • Serum (1–3)-β-D-Glucan is Recommended for Diagnosing Invasive Aspergillus in High-Risk Patients (Hematologic Malignancy, Hematopoietic Stem Cell Transplant), But is Notably Not Specific for Aspergillus (Strong Recommendation, Moderate-Quality Evidence)

Diagnosis of Candidal Infection (see Candida, [[Candida]])

  • xxx

Diagnosis of Pneumocystis Jirovecii Infection (see Pneumocystis Jirovecii, [[Pneumocystis Jirovecii]])

  • xxx

Background/Physiology

Polysaccharides are the Main Structural Constituents of the Fungal Cell Wall

  • Glucan: most abundant polysaccharide component in the cell wall of most fungi
    • Glucan is Composed Mostly of Glucose Polymers: branching of chains is specific to the fungal species
  • Chitin
  • Mannan

(1–3)-β-D-Glucan

  • Rationale for (1–3)-β-D-Glucan Testing: (1–3)-β-D-Glucan is a fungal cell wall component that can be used as a non-invasive test to detect invasive fungal infections
  • Functional Aspects of (1–3)-β-D-Glucan Structure: within the fungal cell wall, (1–3)-β-D-Glucan exists as an insoluble structure
    • In the presence of blood or other body fluids, (1–3)-β-D-Glucan transforms into triple helix (most commonly) or single helix/random coil forms (less commonly) -> rendered soluble
    • Soluble (1–3)-β-D-Glucan functions to inhibit leukocyte phagocytosis

Clinical Aspects of (1–3)-β-D-Glucan Assays

Commercial (1–3)-β-D-Glucan Assays

  • Fungitell (Associates of Cape Cod, East Falmouth, MA): only FDA-approved kit
  • Fungitec-G (Seikagaku Biobusiness, Tokyo, Japan)
  • BGSTAR β-Glucan Test (Maruha, Tokyo, Japan)
  • Endosafe-PTS (Charles River Laboratories, Charleston, SC): intended only for research use
  • Beta-Glucan Test (Waco Pure Chemical Industries, Osaka, Japan): intended only for research use

Specimens

  • Serum: standardly used
  • Bronchoalveolar Lavage (BAL): unclear utility
  • Cerebrospinal Fluid: unclear utility

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 Anti-Fungal 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 Required to Determine the Usefulness of testing on Non-Serum Specimens

References

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  • Plasma (1–>3)-beta-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes. Lancet. 1995;345:17–20
  • Plasma (1–3)-beta-D-glucan and fungal antigenemia in patients with candidemia, aspergillosis, and cryptococcosis. J Clin Microbiol. 1995;33:3115–3118
  • Signaling toward yeast 1,3-beta-glucan synthesis. Cell Struct Funct. 1996;21:395–402
  • (Clinical significance of [1–>3]-beta-D-glucan in pleural effusion and liquor). (Japanese) Kansenshogaku Zasshi. 1997;71:1210–1215
  • (1–>3) beta-D-glucan as a quantitative serological marker for Pneumocystis carinii pneumonia. Clin Diagn Lab Immunol. 1996;3:197–199
  • (1–>3)-beta-D-glucan determination in rat organs with limulus coagulation factor G. Res Exp Med (Berl). 1997;196:339–343
  • Evaluation and Safety Center for Devices and Radiological Health, FDA. 21 May 2004, posting date. Glucatell (1–3-beta-d-glucan serological assay). Available at: www.fda.gov/cdrh/pdf3/k032373.pdf
  • Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: Validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis. 2004;39:199–205
  • Immune recognition of fungal β-glucans. Cell Microbiol. 2005;7:471–479
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  • Multicenter clinical evaluation of the (1–>3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis. 2005;41:654–659
  • Contribution of (1–>3)-beta-D-glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: A comparison with serial screening for circulating galactomannan. J Clin Microbiol. 2005;43:299–305
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  • Usefulness of beta-D glucan in diagnosing Pneumocystis carinii pneumonia and monitoring its treatment in a living-donor liver-transplant recipient. J Hepatobiliary Pancreat Surg. 2007;14:308–311
  • Current status of fungal cell wall components in the immunodiagnostics of invasive fungal infections in humans: Galactomannan, mannan and (1–3)-β-D-glucan antigens. Eur J Clin Microbiol Infect Dis. 2007;26:755–766
  • The cell wall: A carbohydrate armour for the fungal cell. Mol Microbiol. 2007;66:279–290
  • Candida lusitaniae arthritis in an intravenous drug user. Mycoses. 2007;50:430–432
  • Observations on (1–3)-beta-D-glucan detection as a diagnostic tool in endemic mycosis caused by Histoplasma or Blastomyces. J Med Microbiol. 2007;56(Pt 7):1001–1002
  • Cerebrospinal fluid and plasma (1–>3)-beta-D-glucan as surrogate markers for detection and monitoring of therapeutic response in experimental hematogenous Candida meningoencephalitis. Antimicrob Agents Chemother. 2008;52:4121–4129
  • Treatment of aspergillosis: Clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–360
  • Contribution of the (1–>3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol. 2008;46:1009–1013
  • Role of (1–>3)-beta-D-glucan in the diagnosis of invasive aspergillosis. Med Mycol. 2009;47(suppl 1):S233-S240
  • Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:503–535
  • Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: Analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis. 2009;48:265–273
  • Biomedical Applications of Limulus Amebocyte Lysate. Biology and Conservation of Horseshoe Crabs 2009; Part 2: 315–329
  • Difficulties in using 1,3-(beta)-D-glucan as the screening test for the early diagnosis of invasive fungal infections in patients with haematological malignancies: High frequency of false-positive results and their analysis. J Med Microbiol. 2010;59(Pt 9):1016–1022
  • Fungal infections in transplant and oncology patients. Infect Dis Clin North Am. 2010;24:439–459
  • Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients. Transpl Infect Dis. 2010;12:220–229
  • Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60. doi: 10.1093/cid/ciw326. Epub 2016 Jun 29 [MEDLINE]