Infect Chemother.  2009 Apr;41(2):82-89. 10.3947/ic.2009.41.2.82.

Diagnostic Usefulness of Galactomannan Assay for Invasive Aspergillosis

• Song KH
• Lee S
• Jang HC
• Jeon JH
• Park WB
• Park KU
• Park SW
• Oh MD
• Choe KW

• KMID: 2170255
• DOI: http://doi.org/10.3947/ic.2009.41.2.82

Abstract

BACKGROUND
Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. However, IA is difficult to diagnose, especially in the aforementioned patient group. Recently, galactomannan assay (GMA) using enzyme immunoassay has been introduced in Korea. We evaluated its diagnostic usefulness in the diagnosis of IA and we analyzed the results according to the underlying diseases. MATERIALS AND METHODS: All patients who underwent GMA during the period from October 2007 to June 2008 were evaluated retrospectively. According to the criteria of European Organization for Research and Treatment of Cancer/Mycoses Study Group, IA was classified into four clinical categories: 'proven', 'probable', 'possible', and 'non' IA. Patients with 'proven' and 'probable' IA were used as the reference standards for IA. GMA was performed using Platelia Aspergillus EIA (Bio-Rad, Hercules, CA, USA). Optical density index > or =0.5 was considered positive. RESULTS: Of the 144 patients who underwent GMA, two patients were classificed as 'proven' IA and sixteen patients were 'probable' IA. Overall sensitivity, specificity, positive predictive value, and negative predictive value of the assay were 50% (95% confidence interval [CI95], 26-74%), 88% (CI95, 81-93%), 38% (CI95, 19-59%), and 93% (CI95, 86-97%), respectively. Among the 99 patients with underlying hematologic diseases, GMA showed 67% (CI95, 35-90%) sensitivity and 89% (CI95, 80-94%) specificity, whereas in 45 patients with underlying diseases other than hematologic diseases, sensitivity and specificity of the assay were 17% (CI95, 0-64%) and 87% (CI95, 73-96%), respectively. CONCLUSION: GMA showed high specificity, irrespective of the patient population. However, sensitivity of GMA was low and the assay was less sensitive in patients with underlying diseases other than hematologic diseases than in patients with hematologic diseases.

Keyword

Aspergillosis; Diagnosis; Galactomannan; Antigen

MeSH Terms

Aspergillosis
Aspergillus
Hematologic Diseases
Humans
Immunocompromised Host
Immunoenzyme Techniques
Korea
Mannans
Retrospective Studies
Sensitivity and Specificity
Mannans

Reference

1. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002. 34:909–917.

2. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002. 347:408–415.

3. Bruno C, Minniti S, Vassanelli A, Pozzi-Mucelli R. Comparison of CT features of Aspergillus and bacterial pneumonia in severely neutropenic patients. J Thorac Imaging. 2007. 22:160–165.

4. Reichenberger F, Habicht J, Matt P, Frei R, Soler M, Bolliger CT, Dalquen P, Gratwohl A, Tamm M. Diagnostic yield of bronchoscopy in histologically proven invasive pulmonary aspergillosis. Bone Marrow Transplant. 1999. 24:1195–1199.

5. Mennink-Kersten MA, Donnelly JP, Verweij PE. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis. 2004. 4:349–357.

6. Stynen D, Goris A, Sarfati J, Latge JP. A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran in patients with invasive aspergillosis. J Clin Microbiol. 1995. 33:497–500.

7. Verweij PE, Stynen D, Rijs AJ, de Pauw BE, Hoogkamp-Korstanje JA, Meis JF. Sandwich enzyme-linked immunosorbent assay compared with Pastorex latex agglutination test for diagnosing invasive aspergillosis in immunocompromised patients. J Clin Microbiol. 1995. 33:1912–1914.

8. Lombardi G, Farina C, Andreoni S, D'Antonio D, Faggi E, Manso E, Mazzoni A. Multicenter evaluation of an enzyme immunoassay (Platelia Aspergillus) for the detection of Aspergillus antigen in serum. Mycopathologia. 2002. 155:129–133.

9. Yoo JH, Choi JH, Choi SM, Lee DG, Shin WS, Min WS, Kim CC. Application of nucleic acid sequence-based amplification for diagnosis of and monitoring the clinical course of invasive aspergillosis in patients with hematologic diseases. Clin Infect Dis. 2005. 40:392–398.

10. Sung H, Chung HJ, Pyo YJ, Namgoong S, Kim MN. The Evaluation of Clinical Utility of Platelia Aspergillus Antigen Immunoassay for Diagnosis of Invasive Aspergillosis. Korean J Clin Microbiol. 2005. 8:113–120.

11. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, Denning DW, Donnelly JP, Edwards JE, Erjavec Z, Fiere D, Lortholary O, Maertens J, Meis JF, Patterson TF, Ritter J, Selleslag D, Shah PM, Stevens DA, Walsh TJ. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002. 34:7–14.

12. Yoo JH. The Korean Society of Infectious Diseases. Outlines and principles of treatment of fungal infection. Infectious Diseases. 2007. 1st ed. Seoul: Koonja Co;841.

13. Wheat LJ, Walsh TJ. Diagnosis of invasive aspergillosis by galactomannan antigenemia detection using an enzyme immunoassay. Eur J Clin Microbiol Infect Dis. 2008. 27:245–251.

14. Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998. 17:857–872.

15. Fortun J, Martin-Davila P, Alvarez ME, Sanchez-Sousa A, Quereda C, Navas E, Barcena R, Vicente E, Candelas A, Honrubia A, Nuno J, Pintado V, Moreno S. Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients. Transplantation. 2001. 71:145–149.

16. Husain S, Kwak EJ, Obman A, Wagener MM, Kusne S, Stout JE, McCurry KR, Singh N. Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients. Am J Transplant. 2004. 4:796–802.

17. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a metaanalysis. Clin Infect Dis. 2006. 42:1417–1427.

18. Pasqualotto AC, Denning DW. Post-operative aspergillosis. Clin Microbiol Infect. 2006. 12:1060–1076.

19. Aquino VR, Goldani LZ, Pasqualotto AC. Update on the contribution of galactomannan for the diagnosis of invasive aspergillosis. Mycopathologia. 2007. 163:191–202.

20. Balloy V, Huerre M, Latge JP, Chignard M. Differences in patterns of infection and inflammation for corticosteroid treatment and chemotherapy in experimental invasive pulmonary aspergillosis. Infect Immun. 2005. 73:494–503.

21. Marr KA, Balajee SA, McLaughlin L, Tabouret M, Bentsen C, Walsh TJ. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J Infect Dis. 2004. 190:641–649.

22. Maertens J, Theunissen K, Verbeken E, Lagrou K, Verhaegen J, Boogaerts M, Eldere JV. Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol. 2004. 126:852–860.

23. Verweij PE, Erjavec Z, Sluiters W, Goessens W, Rozenberg-Arska M, Debets-Ossenkopp YJ, Guiot HF, Meis JF. Detection of antigen in sera of patients with invasive aspergillosis: intra- and interlaboratory reproducibility. The Dutch Interuniversity Working Party for Invasive Mycoses. J Clin Microbi. l. 1998. 36:1612–1616.

24. Wheat LJ. Rapid diagnosis of invasive aspergillosis by antigen detection. Transpl Infect Dis. 2003. 5:158–166.

25. Maertens J, Van Eldere J, Verhaegen J, Verbeken E, Verschakelen J, Boogaerts M. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis. 2002. 186:1297–1306.

26. Whiting P, Rutjes AW, Reitsma JB, Glas AS, Bossuyt PM, Kleijnen J. Sources of variation and bias in studies of diagnostic accuracy: a systematic review. Ann Intern Med. 2004. 140:189–202.

27. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE. 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. 46:1813–1821.