Document Type : Original Article

Authors

1 M.Sc., Department of Biochemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran

2 Assistant Professor, Molecular pathology and cytogenetics division, Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran

3 Assistant Professor, Department of Hematology and Medical Oncology, Shiraz University of Medical Sciences, Shiraz, Iran

4 M.Sc., Motahari Polyclinic, Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Introduction: Fungal infections are a major concern in immunocompromised patients, such as patients with hematologic malignancies and bone marrow transplants. Opportunistic infections such as invasive fungal infections can lead to poor outcomes and a high probability of death in such patients. Gold standard methods of fungi detection are intrusive and time-consuming. Therefore, they may not be the method of choice to detect such infections rapidly; however, they are always mandatory. Next to gold-standard methods, serologic methods are rapid and non-invasive methods that have been approved for use as an adjunct to classic methods for quicker detection of fungal infections.
Methods: In this study, 68 patients diagnosed with hematologic malignancies and suspicious of fungal infection were enrolled to detect fungi with serologic testing of Beta D-Glucan using ELISA. The authors evaluated the association of malignancy type, clinical signs, and patients’ para-clinical data with positive Beta D-Glucan tests.
Results: Out of 43 men and 25 women participating in this study, 79% had positive test results.
Conclusion: There was no significant association between malignancy type, clinical signs, patients’ para-clinical data, and their positive serology tests. Considering the probable false-positive results due to infection and the use of certain antibiotics in such immunocompromised patients, the authors concluded that the Beta D-Glucan ELISA test might not be a sensitive diagnosis means to diagnose fungal infections in patients with hematologic malignancies.

Keywords

  1. Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ, et al. β-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clinical Infectious Diseases. 2004;39(2):199-205.
  2. Pickering JW, Sant HW, Bowles CA, Roberts WL, Woods GL. Evaluation of a (1→ 3)-β-D-glucan assay for diagnosis of invasive fungal infections. Journal of clinical microbiology. 2005;43(12):5957-62.
  3. Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91(8):1068-75.
  4. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clinical Infectious Diseases. 2002;34(7):909-17.
  5. Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clinical Infectious Diseases. 2006;43(Supplement_1):S3-S14.
  6. Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrobial agents and chemotherapy. 2005;49(9):3640-5.
  7. Heussel CP, Kauczor H-U, Heussel GE, Fischer B, Begrich M, Mildenberger P, et al. Pneumonia in febrile neutropenic patients and in bone marrow and blood stem-cell transplant recipients: use of high-resolution computed tomography. Journal of Clinical Oncology. 1999;17(3):796-.
  8. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer/invasive fungal infections cooperative group and the national institute of allergy and infectious diseases mycoses study group (EORTC/MSG) consensus group. Clinical infectious diseases. 2008;46(12):1813-21.
  9. Wirk B, Wingard JR. Current approaches in antifungal prophylaxis in high risk hematologic malignancy and hematopoietic stem cell transplant patients. Mycopathologia. 2009;168(6):299-311.
  10. Ellepola AN, Morrison CJ. Laboratory diagnosis of invasive candidiasis. Journal of microbiology. 2005;43(spc1):65-84.
  11. Reimer LG, Wilson ML, Weinstein MP. Update on detection of bacteremia and fungemia. Clinical microbiology reviews. 1997;10(3):444-65.
  12. Preuner S, Lion T. Towards molecular diagnostics of invasive fungal infections. Expert review of molecular diagnostics. 2009;9(5):397-401.
  13. Tzianabos AO. Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clinical microbiology reviews. 2000;13(4):523-33.
  14. Koo S, Bryar JM, Page JH, Baden LR, Marty FM. Diagnostic performance of the (1→ 3)-β-d-glucan assay for invasive fungal disease. Clinical infectious diseases. 2009;49(11):1650-9.
  15. Cuenca-Estrella M, Bassetti M, Lass-Flörl C, Ráčil Z, Richardson M, Rogers TR. Detection and investigation of invasive mould disease. Journal of antimicrobial chemotherapy. 2011;66(suppl_1):i15-i24.
  16. Chen SC, Kontoyiannis DP. New molecular and surrogate biomarker-based tests in the diagnosis of bacterial and fungal infection in febrile neutropenic patients. Current opinion in infectious diseases. 2010;23(6):567-77.
  17. He S, Hang J-P, Zhang L, Wang F, Zhang D-C, Gong F-H. A systematic review and meta-analysis of diagnostic accuracy of serum 1, 3-β-D-glucan for invasive fungal infection: focus on cutoff levels. Journal of Microbiology, Immunology and Infection. 2015;48(4):351-61.
  18. Senn L, Robinson JO, Schmidt S, Knaup M, Asahi N, Satomura S, et al. 1, 3-β-D-glucan antigenemia for early diagnosis of invasive fungal infections in neutropenic patients with acute leukemia. Clinical Infectious Diseases. 2008;46(6):878-85.
  19. Pazos C, Pontón J, Palacio AD. Contribution of (1→ 3)-β-d-glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening for circulating galactomannan. Journal of clinical microbiology. 2005;43(1):299-305.
  20. Marty FM, Lowry CM, Lempitski SJ, Kubiak DW, Finkelman MA, Baden LR. Reactivity of (1→ 3)-β-D-glucan assay with commonly used intravenous antimicrobials. Antimicrobial agents and chemotherapy. 2006;50(10):3450-3.
  21. Metan G, Ağkuş C, Buldu H, Koc A. The interaction between piperacillin/tazobactam and assays for Aspergillus galactomannan and 1, 3-beta-D-glucan in patients without risk factors for invasive fungal infections. Infection. 2010;38(3):217-21.
  22. Ito S, Ashizawa M, Sasaki R, Ikeda T, Toda Y, Mashima K, et al. False-positive elevation of 1, 3-beta-D-glucan caused by continuous administration of penicillin G. Journal of Infection and Chemotherapy. 2018;24(10):812-4.
  23. Albert O, Toubas D, Strady C, Cousson
     J, Delmas C, Vernet V, et al. Reactivity of (1→ 3)-β-d-glucan assay in bacterial bloodstream infections. European journal of clinical microbiology & infectious diseases. 2011;30(11):1453-60.
  24. Racil Z, Kocmanova I, Lengerova M, Weinbergerova B, Buresova L, Toskova M, et al. Difficulties in using 1, 3-β-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. Journal of medical microbiology. 2010;59(9):1016-22.
  25. Pazos C, Moragues M-D, Quindós G, Pontón J, del Palacio A. Diagnostic potential of (1, 3)-b-D-glucan and anti-Candida albicans germ tube antibodies for the diagnosis and therapeutic monitoring of invasive candidiasis in neutropenic adult patients. Rev Iberoam Micol. 2006;23:209-15.
  26. White PL, Price JS, Posso RB, Barnes RA. An evaluation of the performance of the Dynamiker® Fungus (1-3)-β-D-Glucan Assay to assist in the diagnosis of invasive aspergillosis, invasive candidiasis and Pneumocystis pneumonia. Medical mycology. 2017;55(8):843-50.