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Background: Invasive aspergillosis (IA) is a leading cause of death among immunocompromised patients, particularly those with hematological malignancies. The use of galactomannan (GM) antigen as a biological marker for screening of IA in high-risk patients is attractive and non-invasive tool that detect evidence of IA prior to the appearance of clinical manifestations.
Objectives: The aim of this study was to compare the diagnostic value of the conventional blood culture technique to the serological detection of GM antigen using ELISA for screening of IA in neutropenic patients with hematological malignancies.
Methods: Forty patients with haematological malignancies from those admitted to the Clinical Oncology Department of Menoufia University Hospitals (MUH) were enrolled and classified to have either proven (5/40; 12.5%), probable (10/40; 25%) or possible (25/40; 62.5%) invasive aspergillosis based on the clinical criteria provided by the European Organization for research and treatment of Cancer (EORTC) and Mycoses Study Group (MSG). Blood samples were collected from all participants and subjected to conventional blood culture for isolation and identification of Aspergillus spp. ELISA technique was applied for serological detection of GM antigen in the patients’ serum samples.
Results: The sensitivity, specificity, PPV(positive predictive value) and NPV (negative predictive value of GM antigen ELISA testing were 100%, 74%, 36% and 100% respectively for both proven and probable cases. On applying the principle of test in series (the patient is positive if positive in both culture and the GM test), the results were improved to 100% sensitivity, 100% specificity, 100% PPV, 100% NPV and 100% accuracy. Galactomannan antigen testing proved excellent sensitivity (80%) compared to other clinical features and radiological criteria for diagnosis of probable aspergillosis and proved to be a good negative test.
Conclusion: With conjunction of clinical and radiological signs, Aspergillus GM test can assist physicians in the of diagnosis of IA in patients with hematological malignancies to allow initiation of effective antifungal therapy which is ultimately important in high-risk populations.
Ahmad A, Gupta P, Kumar A, et al. Evaluation of galactomannan for the diagnosis of invasive aspergillosis at different cutoff values in pediatric cancer patients. Life Science Informatics Publications RJLBPCS. 2017;3(3):125.
Riwes M, Wingard J. Diagnostic methods for invasive fungal diseases in patients with hematologic malignancies. Expert Rev Hematol. 2012;5(6):661–669.
Lamoth F. Galactomannan and 1,3-β-D-glucan testing for the diagnosis of invasive aspergillosis. J. Fungi. 2016;2:22.
Jenks J, Hoenig M. Treatment of aspergillosis. J Fungi (Basel). 2018;4(3): 98.
Zhou W, Li H, Zhang Y, et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis. J Clin Microbiol. 2017;55(7):2153–2161.
De Pauw B, Walsh TJ, Donnelly JP, et al. European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. 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. Clin. Infect. Dis. 2008; 46(12):1813–1821. [PubMed: 18462102]
Mennink-Kersten MA, Donnelly JP, Verweij PE. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis. 2004;4(6):349–357.
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. Antimicrob. Agents Chemother. 2005;49(9):3640–3645. [PubMed: 16127033]
Milne LJR. Fungi. In: Mackie and McCartney, Practical Medical Microbiology, Collee J.G., Marmion B. P., Fraser A.G. And Simmons A. (Eds). 14th Edition. Churchill Livingstone, New York. 1996;1:695-717.
Murray PR, Baron EJ, Faller MA, et al. Manual of clinical microbiology. 8th Ed. ASM Press, Washington, DC; 2003.
Cheesbrough M. Microbiological tests in: District laboratory practice in tropical countries, Part II: Microbiology. Cambridge University press. Great Britain. 2000;1-266.
Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin. Infect. Dis. 2010;50:1091–1100.
Boch T, Spiess B, Cornely OA, Vehreschild JJ, et al. Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-b-D-glucan, Aspergillus PCR, multifungal DNA-microarray, and Aspergillus azole resistance PCRs inblood and bronchoalveolar lavage samples: results of a prospective multicentre study. Clinical Microbiology and Infection. 2016;22:862-868.
Zhang S, Wang S, Wan Z, et al. The diagnosis of invasive and noninvasive pulmonary aspergillosis by serum and bronchoalveolar lavage fluid galactomannan assay. BioMed Research International. 2015;5. Article ID: 943691.
Dos Santosa JS, Hermesa DM, Pasqualotto AC. Galactomannan use in clinical practice: Providing free testing is not the full answer. Braz J Infect Dis. 2018;22(1):37–40.
Penack O, Rempf P, Graf BI, et al. Aspergillus galactomannan testing in patients with long-term neutropenia: Implications for clinical management. Ann. Oncol. 2008;19:984-989.
Foy PC, van Burik JH, Weisdorf DJ. Galactomannan antigen enzyme-linked immunosorbent assay for diagnosis of invasive aspergillosis after hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation. 2007;13:440-443.
Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: A meta-analysis. Clin Infect Dis. 2006;42(10):1417-27. Epub 2006 Apr 14.
Tănase AD, Coliţă A, Mărculescu A, et al. Using the galactomannan antigen assay in the diagnosis of invasive aspergillosis after hematopoietic stem cell transplantation. Rom J Morphol Embryol. 2012;53(2):379–382.
Sheppard DC, Marr KA, Fredricks DN, et al. Comparison of three methodologies for the determination of pulmonary fungal burden in experimental murine aspergillosis. Clin Microbiol Infect. 2006;12:376-380.
Maertens J, Verhaegen J, Lagrou K, et al. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: A prospective validation. Blood. 2001;97:1604–1610.
Racila Z, Weinbergerova B, Kocmanova I, et al. Invasive aspergillosis in patients with hematological malignancies in the Czech and Slovak republics: Fungal Infection Database (FIND) analysis, 2005–2009. International Journal of Infectious Diseases. 2013;17:101–109.