Significance of galactomannan antigen for aspergillosis diagnosis: A review

Document Type: Review Article

Authors

1 Mycology Research Center, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

2 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Mycology Research Center

4 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Abstract

Invasive aspergillosis is one the major causes of death in hematopoietic and solidtransplant
recipients. One of the most critical problems in medical mycology is the
inability to consistently make a convincing and early diagnosis of invasive fungal
infection. Conventional diagnosis methods such as culture-based approaches are limited
by the insufficient accessibility sensitivity and the non-culture-based approaches based on
the detection of specific fungal antigens, fungal metabolites, and fungal DNA are limited
by the slow speed of analysis. Early diagnosis of invasive aspergillosis is the main
complication in its treatment. Galactomannan is a polysaccharide present in the cell wall
of Aspergillus species. This carbohydrate is released into the serum during the invasion of
Aspergillus. Recently, a double-sandwich enzyme-linked immunosorbent assay (ELISA)
was developed for detecting galactomannan antigenemia in the serum. This assay is an
important advancement in the nonculture diagnosis of invasive aspergillosis. The level of
galactomannan in the serum may be an important indication of therapeutic response. In
this review, the role of galactomannan in the diagnosis of IA and its significance has been
highlighted.

Keywords


1. Rex, J. H., 2006. Galactomannan and the diagnosis of invasive aspergillosis. Clinical Infectious Diseases, 42(10):1428-1430.
2. Marr, K. A., Carter, R. A., Boeckh, M., Martin, P., & Corey, L., 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood, 100(13):4358-4366.
3. Fisher, C. E., Stevens, A. M., Leisenring, W., Pergam, S. A., Boeckh, M., & Hohl, T. M., 2013. The serum galactomannan index predicts mortality in hematopoietic stem cell transplant recipients with invasive aspergillosis. Clinical infectious diseases, 57(7):1001-1004.
4. Maertens, J., Verhaegen, J., Lagrou, K., Van Eldere, J., & Boogaerts, M., 2001. 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, 97(6):1604-1610.
5. Walsh, T. J., De Pauw, B., Anaissie, E., & Martino, P., 1994. Recent advances in the epidemiology, prevention and treatment of invasive fungal infections in neutropenic patients. Journal of medical and veterinary mycology, 32: 33-51.
6. Boutboul, F., Alberti, C., Leblanc, T., Sulahian, A., Gluckman, E., Derouin, F., & Ribaud, P., 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: increasing antigenemia is associated with progressive disease.Clinical Infectious Diseases, 939-943.
7. Chai, L. Y., Kullberg, B. J., Johnson, E. M., Teerenstra, S., Khin, L. W., Vonk, A. G., & Herbrecht, R., 2012. Early serum galactomannan trend as a predictor of outcome of invasive aspergillosis. Journal of clinical microbiology, 50(7):2330-2336.
8. Hadrich, I., Makni, F., Cheikhrouhou, F., Neji, S., Amouri, I., Sellami, H. & Ayadi, A., 2012. Clinical utility and prognostic value of galactomannan in neutropenic patients with invasive aspergillosis. Pathologie Biologie, 60(6):357-361.
9. Verweij, P. E., Meis, J. F. G. M., Dompeling, E. C., Donnelly, J. P., & Schattenberg, A. V. M. B., 1997. Serial monitoring of Aspergillus antigen in the early diagnosis of invasive aspergillosis. Preliminary investigations with two examples. Infection, 25(2):86-89.
10. Verweij, P. E., Erjavec, Z., Sluiters, W., Goessens, W., Rozenberg-Arska, M., Debets-Ossenkopp, Y. J., & Meis, J. F., 1998. Detection of antigen in sera of patients with invasive aspergillosis: intra-and interlaboratory reproducibility.Journal of clinical microbiology, 36(6):1612-1616.
11. Wald, A., Leisenring, W., van Burik, J. A., & Bowden, R. A., 1997. Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation. Journal of Infectious Diseases, 175(6):1459-1466.
12. Marr, K. A., Carter, R. A., Boeckh, M., Martin, P., & Corey, L., 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood, 100(13):4358-4366.
13. Fukuda, T., Boeckh, M., Carter, R. A., Sandmaier, B. M., Maris, M. B., Maloney, D. G. & Marr, K. A., 2003. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem 

cell transplants after nonmyeloablative conditioning. Blood, 102(3):827-833.
14. AISNER, J., SCHIMPFF, S. C., & WIERNIK, P. H., 1977. Treatment of invasive aspergillosis: relation of early diagnosis and treatment to response.Annals of Internal Medicine, 86(5):539-543.
15. Pfeiffer, C. D., Fine, J. P., & Safdar, N., 2006. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clinical Infectious Diseases, 42(10):1417-1727.
16. Maertens, J., Verhaegen, J., Lagrou, K., Van Eldere, J., & Boogaerts, M., 2001. 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, 97(6):1604-1610.
17. Bart-Delabesse, E., Basile, M., Al Jijakli, A., Souville, D., Gay, F., Philippe, B., & Datry, A., 2005. Detection of Aspergillus galactomannan antigenemia to determine biological and clinical implications of beta-lactam treatments. Journal of clinical microbiology, 43(10):5214-5220.
18. Matsudomi, N., Nakano, K., Soma, A., & Ochi, A., 2002. Improvement of gel properties of dried egg white by modification with galactomannan through the Maillard reaction. Journal of agricultural and food chemistry, 50(14), 4113-4118.
19. Cummings, J. R., Jamison, G. R., Boudreaux, J. W., Howles, M. J., Walsh, T. J., & Hayden, R. T., 2007. Cross-reactivity of non-Aspergillus fungal species in the Aspergillus galactomannan enzyme immunoassay. Diagnostic microbiology and infectious disease, 59(1):113-115.
20. Verdaguer, V., Walsh, T. J., Hope, W., & Cortez, K. J., 2007. Galactomannan antigen
detection in the diagnosis of invasive aspergillosis.
21. Mennink-Kersten, M. A., Klont, R. R., Warris, A., den Camp, H. J. O., & Verweij, P. E., 2004. Bifidobacterium lipoteichoic acid and false ELISA reactivity in aspergillus antigen detection. The Lancet, 363(9405), 325-327.
22. Stynen, D., Goris, A., Sarfati, J., & Latge, J. P., 1995. A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran in patients with invasive aspergillosis. Journal of Clinical Microbiology, 33(2):497-500.
23. Rovira, M., Jimenéz, M., de la Bellacasa, J. P., Mensa, J., Rafel, M., Ortega, M., & Montserrat, E., 2004. Detection of Aspergillus galactomannan by enzyme immunoabsorbent assay in recipients of allogeneic hematopoietic stem cell transplantation: a prospective study. Transplantation, 77(8):1260-1264.
24. Singh, N., & Paterson, D. L., 2005. Aspergillus infections in transplant recipients. Clinical microbiology reviews, 18(1):44-69.
25. Kawazu, M., Kanda, Y., Nannya, Y., Aoki, K., Kurokawa, M., Chiba, S., & Ogawa, S., 2004. Prospective comparison of the diagnostic potential of real-time PCR, double-sandwich enzyme-linked immunosorbent assay for galactomannan, and a (1→ 3)-β-d-glucan test in weekly screening for invasive aspergillosis in patients with hematological disorders. Journal of Clinical Microbiology, 42(6): 2733-2741.
26. Machetti, M., Feasi, M., Mordini, N., Van Lint, M. T., Bacigalupo, A., Latge, J. P., & Viscoli, C., 1998. Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow 

transplant recipients. Bone marrow transplantation, 21(9):917-921.
27. Maertens, J., Van Eldere, J., Verhaegen, J., Verbeken, E., Verschakelen, J., & Boogaerts, M., 2002. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients.Journal of Infectious Diseases, 186(9):1297-1306.
28. Maertens, J., Verhaegen, J., Demuynck, H., Brock, P., Verhoef, G., Vandenberghe, P., & Boogaerts, M., 1999. Autopsy-controlled prospective evaluation of serial screening for circulating galactomannan by a sandwich enzyme-linked immunosorbent assay for hematological patients at risk for invasive aspergillosis. Journal of Clinical Microbiology, 37(10):3223-3228.
29. Sulahian, A., Boutboul, F., Ribaud, P., Leblanc, T., Lacroix, C., & Derouin, F., 2001. Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4‐year prospective study. Cancer, 91(2):311-318.
30. Boutboul, F., Alberti, C., Leblanc, T., Sulahian, A., Gluckman, E., Derouin, F., & Ribaud, P., 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: increasing antigenemia is associated with progressive disease.Clinical Infectious Diseases, 939-943.
31. Bretagne, S., Marmorat-Khuong, A., Kuentz, M., Latgé, J. P., Bart-Delabesse, E., & Cordonnier, C., 1997. Serum Aspergillus galactomannan antigen testing by sandwich ELISA: practical use in neutropenic patients. Journal of Infection, 35(1):7-15.
32. Verdaguer, V., Walsh, T. J., Hope, W., & Cortez, K. J., 2007. Galactomannan antigen detection in the diagnosis of invasive aspergillosis.
33. Pinel, C., Fricker-Hidalgo, H., Lebeau, B., Garban, F., Hamidfar, R., Ambroise-Thomas, P., & Grillot, R., 2003. Detection of circulating Aspergillus fumigatus galactomannan: value and limits of the Platelia test for diagnosing invasive aspergillosis. Journal of clinical microbiology, 41(5): 2184-2186.
34. Adam, O., Aupérin, A., Wilquin, F., Bourhis, J. H., Gachot, B., & Chachaty, E., 2004. Treatment with piperacillin-tazobactam and false-positive Aspergillus galactomannan antigen test results for patients with hematological malignancies. Clinical infectious diseases, 38(6):917-920.
35. Shin, B., Koh, W. J., Jeong, B. H., Yoo, H., Park, H. Y., Suh, G. Y., & Jeon, K., 2014. Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis. Journal of Infection, 68(5): 494-499.