Keywords
invasive aspergillosis
galactomannan test
How to Cite
Abstract
Invasive fungal diseases represent an increasing problem in the hospital environments, predominantly in the last two decades. The invasive aspergillosis (IA), induced by Aspergillus species, has been the main cause of death in severely immunocompromised patients, with mortality varying from 70 to 90%. Difficulties are found for diagnosing the IA. In vitro culture of biological material shows low sensitivity (<50%), besides the positivity usually occurs at the advanced stages of the infection. The test for detecting galactomannan has been the object of the present study, seeing that it represents a promising diagnostic tool, as a fast and non-invasive serological procedure. The objective of the present review is to survey the studies which have been performed by using methods for detecting galactomannan in samples from patients with distinct clinical pictures. Patients presenting suspicion and/or confirmed IA were also included, as well as the up-to-date trends in knowledge, application and utility of the test.
References
1. Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016; 63(4):433–42.https://dx.doi.org/10.1093/cid/ciw444
2. Bassetti M, Bouza E. Invasive mould infections in the ICU setting: complexities and solutions. J Antimicrob Chemother. 2017; 72 (syppl_1): i39-i47. https://dx.doi.org/10.1093/jac/dkx032
3. Giacomazzi J, Baethgen L, Carneiro LC, Millington MA, Denning DW, Colombo AL et al. The burden of serious human fungal infections in Brazil. Mycoses. 2016; 59(3):145-50. https://doi.org/10.1111/myc.12427
4. Chamilos G, Kontoyiannis DP. Defining the diagnosis of invasive aspergillosis. Med Mycol. 2006; 44: 5163-72. https://dx.doi.org/10.1080/13693780600823258
5. Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis. 2005;5(10):609-22. https://dx.doi.org/10.1016/S1473-3099(05)70238-3
6. Sun KS, Tsai CF, Chen SCC, Chen YY, Huang WC. Galactomannan testing and the incidence of invasive pulmonary aspergillosis: a 10-year nationwide population-based study in Taiwan. Plos One. 2016; 11 (2): e0149964. https://dx.doi.org/10.1371/journal.pone.0156566
7. Rijnders BJ, Cornelissen JJ, Slobbe L, Becker MJ, Doorduijn JK, Hop WCP et al. Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a ramdomized placebo-controlled trial. Clin Infect Dis. 2008; 46(9):1401-8. https://dx.doi.org/10.1086/586739
8. Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in intensive care unit. Clin Infect Dis. 2007;45(2):205-16. https://dx.doi.org/10.1086/518852
9. Barnes PD, Marr KA. Risks, diagnosis and outcomes of invasive fungal infections in haematopoietic stem cell transplant recipients. Br J Haematol. 2007; 139(4):519-31. https://dx.doi.org/10.1111/j.1365-2141.2007.06812.x
10. 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 National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus group. Clin Infect Dis. 2008; 46(12):1813-21. https://dx.doi.org/10.1086/588660
11. Aquino VR, Goldani LZ, Pasqualotto AC. Update on the contribution of galactomannan for the diagnosis of invasive aspergillosis. Mycopathologia. 2007;163(4):191-202. https://dx.doi.org/10.1007/s11046-007-9010-2
12. Warris A, Lehrnbecher T. Progress in the diagnosis of invasive fungal disease in children. Curr Fungal Infect Rep. 2017;11(2):35-44. https://dx.doi.org/10.1007/s12281-017-0274-9
13. Monteiro AA, Rubenich DS, Zandoná MR, Pasqualotto AC. Impact of pré-analytical variables in the determination of serum galactomannan. Med Mycol. 2017;55(6):635-41. https://dx.doi.org/ 10.1093/mmy/myw123
14. Alanio A, Menotti J, Gits-Museli M, Hamane S, Denis B, Rafoux E et al. Circulating Aspergillus fumigatus DNA is quantitatively correlated to galactomannan in serum. Front Microbiol. 2017;8:2040. https://dx.doi.org/10.3389/fmicb.2017.02040
15. Pedroza KC, de Matos SB, de Moura DL, Oliveira MB, Araújo MA, Nascimento RJ et al. Reproducibility of positive results for the detection of serum galactomannan by PlateliaTM Aspergillus EIA. Mycopathologia. 2013;176(3-4):295-7. https://dx.doi.org/ 10.1007/s11046-013-9670-z
16. Perlroth J, Choi B, Spellberg B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol. 2007;45(4):312-46. https://dx.doi.org/10.1080/13693780701218689
17. Arvanitis M, Anagnostou T, Mylonakis E. Galactomannan and polymerase chain reaction-based screening for invasive aspergillosis among high-risk hematology patients: a diagnostic meta-analysis. Clin Infect Dis. 2015;61(8):1263-72. https://dx.doi.org/10.1093/cid/civ555
18. D`Haese J, Theunissen K, Vermeulen E, Schoemans H, De Vlieger G, Lammertijn L et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol. 2012; 50(4):1258-63. https://dx.doi.org/10.1128/JCM.06423-11
19. Acosta J, Catalan M, del Palacio-Peréz-Medel A, Lora D, Montejo JC, Cuetara MS et al. A prospective comparison of galactomannan in bronchoalveolar lavage fluid for the diagnosis of pulmonary invasive aspergillosis in medical patients under intensive care: comparison with the diagnostic performance of galactomannan and of (1→3)-β-d-glucan chromogenic assay in serum samples. Clin Microbiol Infect. 2011;17(7):1053-60. https://dx.doi.org/10.1111/j.1469-0691.2010.03357.x
20. Reinwald M, Hummel M, Kovalevskaya E, Spiess B, Heinz WJ, Vehreschild JJ et al. Therapy with antifungals decreases the diagnostic performance of PCR for diagnosing invasive aspergillosis in bronchoalveolar lavage samples of patients with haematological malignancies. J Antimicrob Chemother. 2012;67(9):2260-7. https://dx.doi.org/10.1093/jac/dks208
21. Ahmad S, Khan ZU, Theyyathel M. Diagnostic value of DNA, (1-3) β-d-glucan, and galactomannan detection in serum and bronchoalveolar lavage of mice experimentally infected with Aspergillus terreus. Diagn Microbiol Infect Dis. 2007;59(2):165-71. https://dx.doi.org/ 10.1016/j.diagmicrobio.2007.04.009
22. Urabe N, Sakamoto S, Sano G, Suzuki J, Hebisawa A, Nakamura Y et al. Usefulness of two Aspergillus PCR assays and Aspergillus galactomannan and ß-d-glucan testinf of bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol. 2017;55(6):1738-46. https://dx.doi.org/10.1128/JCM.02497-16
23. Johnson GL, Sarker SJ, Hill K, Tsitsikas DA, Morin A, Bustin SA et al. Significant decline in Galactomannan signal during storage of clinical serum samples. Int J Mol Sci. 2013;14(7):12970-7. https:/doi.org/10.3390/ijms140712970
24. Eigl S, Prattes J, Reinwald M, Thornton CR, Reischies F, Spiess B et al. Influence of mould-active antifungal treatment on the performance of the Aspergillus-specific bronchoalveolar lavage fluid lateral-flow device test. Int J Antimicrob Agents. 2015;46(4):401-5. https://dx.doi.org/ 10.1016/j.ijantimicag.2015.05.017
25. Brownback KR, Pitts LR, Simpson SQ. Utility of galactomannan antigen detection in bronchoalveolar lavage fluid in immunocompromised patients. Mycoses. 2013;56(5):552-8. https://dx.doi.org/ 10.1111/myc.12074
26. Zheng F, Zha H, Yang D, Deng J, Zhang Z. Diagnostic values and limitations of (1,3)-β-d-glucans and galactomannan assays for invasive fungal infection in patients admitted to pediatric intensive care unit. Mycopathologia. 2017;182(3-4):331-8. https://dx.doi.org/ 10.1007/s11046-016-0063-y
27. Kim R, Koh Y, Shin DY, Choe PG, Kim NJ, Yoon et al. The limited role of serum galactomannan assay in screening for invasive pulmonary aspergillosis in allogeneic stem cell transplantation recipients on micafungin prophylaxis: a retrospective study. Blood Res. 2017;52(4):300-6. https://dx.doi.org/10.5045/br.2017.52.4.300
28. Hadrich I, Makni F, Cheikhrouhou F, Neji S, Amouri I, Sellami H et al. Clinical utility and prognostic value of galactomannan in neutropenic patients with invasive aspergillosis. Pathol Biol (Paris). 2012;60(6):357-61. https://dx.doi.org/ 10.1016/j.patbio.2011.10.011
29. Woods G, Miceli MH, Grazziutti ML, Zhao W, Barlogie B, Anaissie E. Serum Aspergillus galactomannan antigen values strongly correlate with outcome of invasive aspergillosis. Cancer. 2007;110(4):830-4. https://dx.doi.org/10.1002/cncr.2286330.
30. Fréalle E, Decrucq K, Botterel F, Bouchindhomme B, Camus D, Dei-Cas E et al. Diagnosis of invasive aspergillosis using bronchoalveolar lavage human DNA content on real-time PCR performance. Eur J Clin Microbiol Infect Dis. 2009;28(3):223-32. https://dx.doi.org/ 10.1007/s10096-008-0616-1
31. Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med. 2008;177(1):27-34. https://dx.doi.org/10.1164/rccm.200704-606OC
32. Boch T, Buchheidt D, Spiess B, Miethke T, Hofmann WK, Reinwald M. Direct comparison of galatomannan performance in concurrent serum and bronchoalveolar lavage samples in immunocompromissed patients at risk for invasive pulmonary aspergillosis. Mycoses. 2016;59(2):80-5. https://dx.doi.org/10.1111/myc.12434
33. Reinwald M, Spiess B, Heinz WJ, Vehreschild JJ, Lass-Flörl C, Kiehl M et al. Diagnosing pulmonary aspergillosis in patients with hematological malignancies: a multicenter prospective evaluation of an Aspergillus PCR assay and a galactomannan ELISA in bronchoalveolar lavage samples. Eur J Haematol. 2012;89(2):120-7. https://dx.doi.org/10.1111/j.1600-0609.2012.01806.x
34. de Mol M, de Jongste JC, van Westreenen M, Merkus PJ, de Vries AH, Hop WC et al. Diagnosis of invasive pulmonary aspergillosis in children with bronchoalveolar lavage galactomannan. Pediatr Pulmonol. 2013;48(8):789-96. https://dx.doi.org/10.1002/ppul.22670
35. Dinand V, Anjan M, Oberoi JK, Khanna S, Yadav SP, Wattal C et al. Threshold of galactomannan antigenemia positivity for early diagnosis of invasive aspergillosis in neutropenic children. J Microbiol Immunol Infect. 2016;49(1):66-73. https://dx.doi.org/10.1016/j.jmii.2013.12.003
36. Gupta A, Capoor MR, Shende T, Sharma B, Mohindra R, Suri JC et al. Comparative evaluation of galactomannan test with bronchoalveolar lavage and serum for the diagnosis of invasive aspergillosis in patients with hematological malignancies. J Lab Physicians. 2017;9(4):234-8. https://dx.doi.org/ 10.4103/JLP.JLP_127_16
37. Sav H, Atalay MA, Koc AN, Unal E, Demir G, Zararsiz G. Utility of the Aspergillus galactomannan antigen testing for neutropenic paediatric patients. Infez Med. 2017;25(1):38-44. Disponível em: https://www.infezmed.it/media/journal/Vol_25_1_2017_7.pdf
38. Badiee P, Hashemizadeh Z, Ramzi M, Karimi M, Mohammadi R. Non-invasive methods to diagnose fungal infection in pediatric patients with hematologic disorders. Jundishapur J Microbiol. 2016;9(11):e41573. https://dx.doi.org/ 10.5812/jjm.41573
39. Hachem RY, Kontoyiannis DP, Chemaly RF, Jiang Y, Reitzel R, Raad I. The utility of galactomannan enzyme immnunoassay and (1-3) β-d-Glucan in the diagnosis of invasive fungal infections: low sensitivity for Aspergillus fumigatus infection in hematologic malignancy patients. J Clin Microbiol. 2009;47(1):129-33. https://dx.doi.org/ 10.1128/JCM.00506-08
40. Zhang S, Wang S, Wan Z, Que C, Li R, Yu J. Quantitative real-time PCR and Platelia Galactomannan Assay for the diagnosis of invasive pulmonary aspergillosis: bronchoalveolar lavage fluid performs better than serum in non-neutropenic patients. Mycopathologia. 2016;181(9-10):625-9. https://dx.doi.org/ 10.1007/s11046-016-0024-5
41. Bassetti M, Peghin M, Vena A. Challenges and solution of invasive aspergillosis in non-neutropenic patients: a review. Infect Dis Ther. 2018;7(1):17-27. https://dx.doi.org/10.1007/s40121-017-0183-9
42. Fortún J, Martín-Dávila P, Gomez Garcia de la Pedrosa E, Silva JT, Garcia-Rodríguez J, Benito D et al. Galactomannan in bronchoalveolar lavage fluid for diagnosis of invasiveaspergillosis in non-hematological patients. J Infect. 2016;72(6):738-44. https://dx.doi.org/ 10.1016/j.jinf.2016.02.019
43. Zhang S, Wang S, Wan Z, Li R, Yu J. The diagnosis of invasive and noinvasive pulmonary aspergillosis by serum and bronchoalveolar lavage fluid galactomannan assay. Biomed Res Int. 2015;2015:943691. https://dx.doi.org/10.1155/2015/943691
44. Mohammadi S, Khalilzadeh S, Goudarzipour K, Hassanzad M, Mahdaviani A, Aarabi N et al. Bronchoalveolar galactomannan in invasive pulmonary aspergillosos: a prospective study in pediatric patients. Med Mycol. 2015;53(7):709-16. https://dx.doi.org/ 10.1093/mmy/myv053
45. Zhou W, Li H, Zhang Y, Huang M, He Q, Li P 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):2153-61. https://dx.doi.org/ 10.1128/JCM.00345-17
46. Savio J, Menon NR, Sudharma AR, Jairaj V, Mathew J. Galactomannan assay and invasive pulmonary aspergillosis – comparison of the test performance at an in-house and the kit cut-off. J Clin Diagn Res. 2016;10(8): DC01-4. https://dx.doi.org/ 10.7860/JCDR/2016/19175.8310
47. Ağca H, Ener B, Yılmaz E, Ursavaş A, Kazak E, Özkocaman V et al. Comparative evaluation of galactomannan optical density índices and culture results in bronchoscopic specimes obtained from neutropenic and non-neutropenic patients. Mycoses. 2014;57(3):169-75. https://dx.doi.org/10.1111/myc.12126
48. Izumikawa K, Yamamoto Y, Mihara T, Takazono T, Morinaga Y, Kurihara S et al. Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis. Med Mycol. 2012;50(8):811-7. https://dx.doi.org/10.3109/13693786.2012.682228
49. Özger S, Hızel K, Kalkancı A, Aydoğdu M, Civil F, Dizbay M et al. Evaluation of risk factors for invasive pulmonary aspergillosis and detection of diagnostic values of galactomannan and PCR methods in bronchoalveolar lavage samples from non-neutropenic intensive care unit patients. Mikrobiyol Bul. 2015;49(4):565-75.
50. He H, Ding L, Sun B, Li F, Zhan Q. Role of galactonannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Crit Care. 2012;16(4):R138. https://dx.doi.org/10.1186/cc11443
51. Russo A, Giuliano S, Vena A, Lucidi C, Falcone M, Raponi G et al. Predictors of mortality in non-neutropenic patients with invasive pulmonary aspergillosis: does galactomannan have a role? Diagn Microbiol Infect Dis. 2014;80(1):83-6. https://dx.doi.org/ 10.1016/j.diagmicrobio.2014.05.015
52. Clancy CJ, Jaber RA, Leather HL, Wingard JR, Staley B, Wheat LJ et al. Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients. J Clin Microbiol. 2007;45(6):1759-65. https://dx.doi.org/10.1128/JCM.00077-07
53. Husain S, Paterson DL, Studer SM, Crespo M, Pilewski J, Durkin M et al. Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients. Transplantation. 2007;83(10):1330-6. https://dx.doi.org/10.1097/01.tp.0000263992.41003.33
54. Tabarsi P, Soraghi A, Marjani M, Zandian P, Baghaei P, Najafizadeh K et al. Comparison of serum and bronchoalveolar lavage galactomannan in diagnosing invasive aspergillosis in solid-organ transplant recipients. Exp Clin Transplant. 2012;10(3):278-81. https://dx.doi.org/10.6002/ect.2011.0176
55. Swoboda-Kopec E, Golás M, Piskorska K, Dabkowska M, Niecwietajewa I, Paczek L et al. Aspergillus galactomannan detection in comparison to a real-time PCR assay in serum samples from a high-risk group of patients. Cent Eur J Immunol. 2015;40(4):454-60. https://dx.doi.org/10.5114/ceji.2015.56968
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2018 Sabrina Mesquita Rocha