Diagnosis of invasive aspergillosis by galactomannan antigenemia detection using an enzyme immunoassay

  • L. J. WheatEmail author
  • T. J. Walsh


Invasive aspergillosis is a serious and often fatal infection in patients who are neutropenic or have undergone solid organ or stem cell transplantation. Delayed diagnosis and therapy may lead to poor outcomes. Diagnosis may be facilitated by a test for galactomannan antigen detection using an enzyme immunoassay. Other rapid methods for diagnosis include (1→3)-β-d-glucan determination and polymerase chain reaction. The sensitivity and specificity of galactomannan antigenemia testing in serum and bronchoalveolar lavage specimens are high in patients with hematological malignancy, neutropenia, and receipt of stem-cell transplants. False positivity can be seen with concomitant administration of some antibiotics and infection by fungi other than Aspergillus.


Antifungal Therapy Invasive Aspergillosis Galactomannan Horseshoe Crab Pulmonary Invasive Aspergillosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Conflict of interest statement

Dr. Wheat is the President of MiraVista Diagnostics, a company that performs the Platelia® Aspergillus EIA as a commercial service, and has served as a consultant to BioRad Laboratories, the manufacturer of the test.


  1. 1.
    Denning DW, Kibbler CC, Barnes RA (2003) British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections. Lancet Infect Dis 3(4):230–240PubMedCrossRefGoogle Scholar
  2. 2.
    Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E, Wilmer A, Verhaegen J, Boogaerts M, Van Eldere J (2005) Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis 41(9):1242–1250PubMedCrossRefGoogle Scholar
  3. 3.
    Wheat L (2003) Rapid diagnosis of invasive aspergillosis by antigen detection. Transpl Infect Dis 5(4):158–166PubMedCrossRefGoogle Scholar
  4. 4.
    Hope WW, Walsh TJ, Denning DW (2005) Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis 5(10):609–622PubMedCrossRefGoogle Scholar
  5. 5.
    Mennink-Kersten MA, Donnelly JP, Verweij PE (2004) Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis 4(6):349–357PubMedCrossRefGoogle Scholar
  6. 6.
    Wheat LJ (2005) Galactomannan Antigenemia Detection for Diagnosis of Invasive Aspergillosis, Part I. Clinical Microbiology Newsletter 27(7):51–57CrossRefGoogle Scholar
  7. 7.
    Wheat LJ (2005) Galactomannan Antigenemia Detection for Diagnosis of Invasive Aspergillosis, Part II. Clinical Microbiology Newsletter 27(8):59–63CrossRefGoogle Scholar
  8. 8.
    Stynen D, Sarfati J, Goris A, Prevost MC, Lesourd M, Kamphuis H, Darras V, Latge JP (1992) Rat monoclonal antibodies against Aspergillus galactomannan. Infect Immun 60(6):2237–2245PubMedGoogle Scholar
  9. 9.
    Maertens JA, Klont R, Masson C, Theunissen K, Meersseman W, Lagrou K, Heinen C, Crepin B, Van Eldere J, Tabouret M, Donnelly JP, Verweij PE (2007) Optimization of the cutoff value for the Aspergillus double-sandwich enzyme immunoassay. Clin Infect Dis 44(10):1329–1336PubMedCrossRefGoogle Scholar
  10. 10.
    Pfeiffer CD, Fine JP, Safdar N (2006) Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 42(10):1417–1727PubMedCrossRefGoogle Scholar
  11. 11.
    Aubry A, Porcher R, Bottero J, Touratier S, Leblanc T, Brethon B, Rousselot P, Raffoux E, Menotti J, Derouin F, Ribaud P, Sulahian A (2006) Occurrence and kinetics of false-positive Aspergillus galactomannan test results following treatment with beta-lactam antibiotics in patients with hematological disorders. J Clin Microbiol 44(2):389–394PubMedCrossRefGoogle Scholar
  12. 12.
    Racil Z, Kocmanova I, Lengerova M, Winterova J, Mayer J (2007) Intravenous PLASMA-LYTE as a Major Cause of False-Positive Results of Platelia Aspergillus Test for Galactomannan Detection in Serum. J Clin Microbiol 45(9):3141–3142PubMedCrossRefGoogle Scholar
  13. 13.
    Surmont I, Stockman W (2007) Gluconate-containing intravenous solutions: another cause of false-positive galactomannan assay reactivity. J Clin Microbiol 45(4):1373PubMedCrossRefGoogle Scholar
  14. 14.
    Girmenia C, Ballaro D, Martino P (2007) Contamination by cardboard particles as a cause of false-positive results for Aspergillus galactomannan enzyme immunoassays. Clin Vaccine Immunol 14(7):929PubMedCrossRefGoogle Scholar
  15. 15.
    Murashige N, Kami M, Kishi Y, Fujisaki G, Tanosaki R (2005) False-positive results of Aspergillus enzyme-linked immunosorbent assays for a patient with gastrointestinal graft-versus-host disease taking a nutrient containing soybean protein. Clin Infect Dis 40(2):333–334PubMedCrossRefGoogle Scholar
  16. 16.
    Mennink-Kersten MASH, Ruegebrink D, Klont RR, Warris A, Gavini F, Op den Camp HJM, Verweij PE (2005) Bifidobacterial Lipoglycan as a New Cause for False-Positive Platelia Aspergillus Enzyme-Linked Immunosorbent Assay Reactivity. J Clin Microbiol 43(8):3925–3931PubMedCrossRefGoogle Scholar
  17. 17.
    Steinbach WJ, Addison RM, McLaughlin L, Gerrald Q, Martin PL, Driscoll T, Bentsen C, Perfect JR, Alexander BD (2007) Prospective Aspergillus Galactomannan Antigen Testing in Pediatric Hematopoietic Stem Cell Transplant Recipients. Pediatr Infect Dis J 26(7):558–564PubMedCrossRefGoogle Scholar
  18. 18.
    Swanink CMA, Meis JFGM, Rijs AJMM, Donnelly JP, Verweij PE (1997) Specificity of a sandwich enzyme-linked immunosorbent assay for detecting Aspergillus galactomannan. J Clin Microbiol 35(1):257–260PubMedGoogle Scholar
  19. 19.
    Wheat LJ, Hackett E, Durkin M, Connolly P, Petraitiene R, Walsh TJ, Knox K, Hage C (2007) Histoplasmosis-Associated Cross-Reactivity in the BioRad Platelia Aspergillus Enzyme Immunoassay. Clin Vaccine Immunol 14(5):638–640PubMedCrossRefGoogle Scholar
  20. 20.
    Dalle F, Charles PE, Blanc K, Caillot D, Chavanet P, Dromer F, Bonnin A (2005) Cryptococcus neoformans Galactoxylomannan contains an epitope(s) that is cross-reactive with Aspergillus Galactomannan. J Clin Microbiol 43(6):2929–2931PubMedCrossRefGoogle Scholar
  21. 21.
    De Jesus M, Hackett E, Durkin M, Connolly P, Casadevall A, Petraitiene R, Walsh TJ, Wheat LJ (2007) Galactoxylomannan Does Not Exhibit Cross-Reactivity in the Platelia Aspergillus Enzyme Immunoassay. Clin Vaccine Immunol 14(5):624–627PubMedCrossRefGoogle Scholar
  22. 22.
    Huang YT, Hung CC, Liao CH, Sun HY, Chang SC, Chen YC (2007) Detection of Circulating Galactomannan in Penicillium marneffei Infection and Cryptococcosis Among Patients Infected with Human Immnunodeficiency Virus. J Clin Microbiol 49(9):2858–2862CrossRefGoogle Scholar
  23. 23.
    Giacchino M, Chiapello N, Bezzio S, Fagioli F, Saracco P, Alfarano A, Martini V, Cimino G, Martino P, Girmenia C (2006) Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay Cross-Reactivity Caused by Invasive Geotrichum capitatum. J Clin Microbiol 44(9):3432–3434PubMedCrossRefGoogle Scholar
  24. 24.
    Jarv H, Lehtmaa J, Summerbell RC, Hoekstra ES, Samson RA, Naaber P (2004) Isolation of Neosartorya pseudofischeri from blood: first hint of pulmonary Aspergillosis. J Clin Microbiol 42(2):925–928PubMedCrossRefGoogle Scholar
  25. 25.
    Marr KA, Laverdiere M, Gugel A, Leisenring W (2005) Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis 40(12):1762–1769PubMedCrossRefGoogle Scholar
  26. 26.
    Bruno C, Minniti S, Vassanelli A, Pozzi-Mucelli R (2007) Comparison of CT features of Aspergillus and bacterial pneumonia in severely neutropenic patients. J Thorac Imaging 22(2):160–165PubMedCrossRefGoogle Scholar
  27. 27.
    Reichenberger F, Habicht J, Matt P, Frei R, Solèr M, Bolliger CT, Dalquen P, Gratwohl A, Tamm M (1999) Diagnostic yield of bronchoscopy in histologically proven invasive pulmonary aspergillosis. bmt 24(11):1195–1199Google Scholar
  28. 28.
    Becker MJ, Lugtenburg EJ, Cornelissen JJ, Van Der SC, Hoogsteden HC, De Marie S (2003) Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis. Br J Haematol 121(3):448–457PubMedCrossRefGoogle Scholar
  29. 29.
    Musher B, Fredricks D, Leisenring W, Balajee SA, Smith C, Marr KA (2004) Aspergillus Galactomannan Enzyme Immunoassay and Quantitative PCR for Diagnosis of Invasive Aspergillosis with Bronchoalveolar Lavage Fluid. J Clin Microbiol 42(12):5517–5522PubMedCrossRefGoogle Scholar
  30. 30.
    Clancy CJ, Jaber RA, Leather HL, Wingard JR, Staley B, Wheat LJ, Cline CL, Rand KH, Schain D, Baz M, Nguyen MH (2007) Bronchoalveolar lavage galactomannan in the diagnosis of invasive pulmonary aspergillosis among solid organ transplant recipients. J Clin Microbiol 45:1759–1765PubMedCrossRefGoogle Scholar
  31. 31.
    Husain S, Paterson DL, Studer SM, Crespo M, Pilewski J, Durkin M, Wheat JL, Johnson B, McLaughlin L, Bentsen C, McCurry KR, Singh N (2007) Aspergillus Galactomannan Antigen in the Bronchoalveolar Lavage Fluid for the Diagnosis of Invasive Aspergillosis in Lung Transplant Recipients. Transplantation 83(10):1330–1336PubMedCrossRefGoogle Scholar
  32. 32.
    Nguyen MH, Jaber R, Leather HL, Wingard JR, Staley B, Wheat LJ, Cline CL, Baz M, Rand KH, Clancy CJ (2007) Use of bronchoalveolar lavage to detect galactomannan for diagnosis of pulmonary aspergillosis among non-immunocompromised hosts. J Clin Microbiol 45:2787–2792PubMedCrossRefGoogle Scholar
  33. 33.
    Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S, Spriet I, Verbeken E, Van Wijngaerden E (2008) Galactomannan in broncho-alveolar lavage fluid: a tool for diagnosing Aspergillosis in ICU patients. Am J Respir Crit Care Med 177:27–34PubMedCrossRefGoogle Scholar
  34. 34.
    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 34(7):939–943PubMedCrossRefGoogle Scholar
  35. 35.
    Rohrlich P, Sarfati J, Mariani P, Duval M, Carol A, Saint-Martin C, Bingen E, Latge JP, Vilmer E (1996) Prospective sandwich enzyme-linked immunosorbent assay for serum galactomannan: early predictive value and clinical use in invasive aspergillosis. Pediatr Infect Dis J 15(2):232–237PubMedGoogle Scholar
  36. 36.
    Salonen J, Lehtonen OP, Terasjarvi MR, Nikoskelainen J (2000) Aspergillus antigen in serum, urine and bronchoalveolar lavage specimens of neutropenic patients in relation to clinical outcome. Scand J Infect Dis 32(5):485–490PubMedCrossRefGoogle Scholar
  37. 37.
    Woods G, Miceli MH, Grazziutti ML, Zhao W, Barlogie B, Anaissie E (2007) Serum Aspergillus galactomannan antigen values strongly correlate with outcome of invasive aspergillosis: a study of 56 patients with hematologic cancer. Can 110(4):830–834CrossRefGoogle Scholar
  38. 38.
    Miceli MH, Maertens J, Buve K, Grazziutti M, Woods G, Rahman M, Barlogie B, Anaissie EJ (2007) Immune reconstitution inflammatory syndrome in cancer patients with pulmonary aspergillosis recovering from neutropenia: Proof of principle, description, and clinical and research implications. Can 110(1):112–120CrossRefGoogle Scholar
  39. 39.
    El Saleeby CM, Allison KJ, Knapp KM, Walsh TJ, Hayden RT (2005) Discordant rise in galactomannan antigenemia in a patient with resolving Aspergillosis, renal failure, and ongoing hemodialysis. J Clin Microbiol 43(7):3560–3563PubMedCrossRefGoogle Scholar
  40. 40.
    Miyazaki T, Kohno S, Mitsutake K, Maesaki S, Tanaka KI, Ishikawa N, Hara K (1995) Plasma (1–>3)-b-D-glucan and fungal antigenemia in patients with candidemia, aspergillosis, and cryptococcosis. J Clin Microbiol 33:3115–3118PubMedGoogle Scholar
  41. 41.
    Kawazu M, Kanda Y, Nannya Y, Aoki K, Kurokawa M, Chiba S, Motokura T, Hirai H, Ogawa S (2004) Prospective Comparison of the diagnostic potential of real-time PCR, duble-sandwich enzyme-linked immunosorbent assay for galactomannan, and a (1->3)-{beta}-D-Glucan test in weekly screening for invasive aspergillosis in patients with hematological disorders. J Clin Microbiol 42(6):2733–2741PubMedCrossRefGoogle Scholar
  42. 42.
    Pazos C, Ponton J, Palacio AD (2005) 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 43(1):299–305PubMedCrossRefGoogle Scholar
  43. 43.
    Pickering JW, Sant HW, Bowles CAP, Roberts WL, Woods GL (2005) Evaluation of a (1->3)-{beta}-D-Glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol 43(12):5957–5962PubMedCrossRefGoogle Scholar
  44. 44.
    Digby J, Kalbfleisch J, Glenn A, Larsen A, Browder W, Williams D (2003) Serum glucan levels are not specific for presence of fungal infections in intensive care unit patients. Clin Diagn Lab Immunol 10(5):882–885PubMedCrossRefGoogle Scholar
  45. 45.
    Marty FM, Lowry CM, Lempitski SJ, Kubiak DW, Finkelman MA, Baden LR (2006) Reactivity of (1–>3)-beta-d-glucan assay with commonly used intravenous antimicrobials. Antimicrob Agents Chemother 50(10):3450–3453PubMedCrossRefGoogle Scholar
  46. 46.
    Wheat LJ (2006) Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host. Transpl Infect Dis 8(3):128–139PubMedCrossRefGoogle Scholar
  47. 47.
    Buchheidt D, Hummel M, Schleiermacher D, Spiess B, Schwerdtfeger R, Cornely OA, Wilhelm S, Reuter S, Kern W, Sudhoff T, Morz H, Hehlmann R (2004) Prospective clinical evaluation of a LightCycler-mediated polymerase chain reaction assay, a nested-PCR assay and a galactomannan enzyme-linked immunosorbent assay for detection of invasive aspergillosis in neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol 125(2):196–202PubMedCrossRefGoogle Scholar
  48. 48.
    White PL, Linton CJ, Perry MD, Johnson EM, Barnes RA (2006) The evolution and evaluation of a whole blood polymerase chain reaction assay for the detection of invasive aspergillosis in hematology patients in a routine clinical setting. Clin Infect Dis 42(4):479–486PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.MiraVista Diagnostics and MiraBella TechnologiesMiraVista DiagnosticsIndianapolisUSA
  2. 2.Pediatric Oncology Branch, Immunocompromised Host SectionNational Cancer InstituteBethesdaUSA

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