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Published in: European Journal of Clinical Microbiology & Infectious Diseases 8/2018

01-08-2018 | Review

Invasive pulmonary aspergillosis: current diagnostic methodologies and a new molecular approach

Authors: S. Moura, L. Cerqueira, A. Almeida

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 8/2018

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Abstract

The fungus Aspergillus fumigatus is the main pathogenic agent responsible for invasive pulmonary aspergillosis. Immunocompromised patients are more likely to develop this pathology due to a decrease in the immune system’s defense capacity. Despite of the low occurrence of invasive pulmonary aspergillosis, this pathology presents high rates of mortality, mostly due to late and unspecific diagnosis. Currently, the diagnostic methods used to detect this fungal infection are conventional mycological examination (direct microscopic examination, histological examination, and culture), imaging, non-culture-based tests for the detection of galactomannan, β(1,3)-glucan and an extracellular glycoprotein, and molecular tests based on PCR. However, most of these methods do not detect the species A. fumigatus; they only allow the identification of genus Aspergillus. The development of more specific detection methods is of extreme importance. Fluorescent in situ hybridization-based molecular methods can be a good alternative to achieve this purpose. In this review, it is intended to point out that most of the methods used for the diagnosis of invasive pulmonary aspergillosis do not allow to detect the fungus at the species level and that fluorescence in situ hybridization-based molecular method will be a promising approach in the A. fumigatus detection.
Literature
7.
go back to reference Hage CA (2010) Breathing in America: diseases, progress, and hope. In: Schraufnage DE (ed) Fungal lung disease. American Thoracic Society, New York, pp 89–97 Hage CA (2010) Breathing in America: diseases, progress, and hope. In: Schraufnage DE (ed) Fungal lung disease. American Thoracic Society, New York, pp 89–97
19.
go back to reference Zarrinfar H, Saber S, Kordbacheh P, Makimura K, Fata A, Geramishoar M et al (2012) Mycological microscopic and culture examination of 400 bronchoalveolar lavage (BAL) samples. Iran J Public Health 41:70–76PubMedPubMedCentral Zarrinfar H, Saber S, Kordbacheh P, Makimura K, Fata A, Geramishoar M et al (2012) Mycological microscopic and culture examination of 400 bronchoalveolar lavage (BAL) samples. Iran J Public Health 41:70–76PubMedPubMedCentral
20.
go back to reference Nosari A, Anghilieri M, Carrafiello G, Guffanti C, Marbello L, Montillo M et al (2003) Utility of percutaneous lung biopsy for diagnosing filamentous fungal infections in hematologic malignancies. Haematol 88:1405–1409 Nosari A, Anghilieri M, Carrafiello G, Guffanti C, Marbello L, Montillo M et al (2003) Utility of percutaneous lung biopsy for diagnosing filamentous fungal infections in hematologic malignancies. Haematol 88:1405–1409
21.
go back to reference Hayden RT, Isotalo PA, Parrett T, Wolk DM, Qian X, Roberts GD et al (2003) In situ hybridization for the differentiation of Aspergillus, Fusarium, and Pseudallescheria species in tissue section. Diagn Mol Pathol Am J Surg Pathol 12:21–26CrossRef Hayden RT, Isotalo PA, Parrett T, Wolk DM, Qian X, Roberts GD et al (2003) In situ hybridization for the differentiation of Aspergillus, Fusarium, and Pseudallescheria species in tissue section. Diagn Mol Pathol Am J Surg Pathol 12:21–26CrossRef
26.
go back to reference Xu S-C, Qiu L-H, Liu W-Y, Feng Y-L (2012) Initial computed tomography findings of invasive pulmonary aspergillosis in non-hematological patients. Chin Med J 125:2979–2985PubMed Xu S-C, Qiu L-H, Liu W-Y, Feng Y-L (2012) Initial computed tomography findings of invasive pulmonary aspergillosis in non-hematological patients. Chin Med J 125:2979–2985PubMed
33.
go back to reference Bölük G, Kazak E, Özkalemkaş F, Ener B, Akalin H, Ağca H et al (2016) Comparison of galactomannan, beta-D-glucan, and Aspergillus DNA in sera of high-risk adult patients with hematological malignancies for the diagnosis of invasive aspergillosis. Turk J Med Sci 46:335–342. https://doi.org/10.3906/sag-1408-100 CrossRefPubMed Bölük G, Kazak E, Özkalemkaş F, Ener B, Akalin H, Ağca H et al (2016) Comparison of galactomannan, beta-D-glucan, and Aspergillus DNA in sera of high-risk adult patients with hematological malignancies for the diagnosis of invasive aspergillosis. Turk J Med Sci 46:335–342. https://​doi.​org/​10.​3906/​sag-1408-100 CrossRefPubMed
45.
go back to reference Boch T, Spiess B, Cornely OA, Vehreschild JJ, Rath PM, Steinmann J et al (2016) Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-β-D-glucan, Aspergillus PCR, multifungal DNA-microarray, and Aspergillus azole resistance PCRs in blood and bronchoalveolar lavage samples: results of. Clin Microbiol Infect 22:862–868. https://doi.org/10.1016/j.cmi.2016.06.021 CrossRefPubMed Boch T, Spiess B, Cornely OA, Vehreschild JJ, Rath PM, Steinmann J et al (2016) Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-β-D-glucan, Aspergillus PCR, multifungal DNA-microarray, and Aspergillus azole resistance PCRs in blood and bronchoalveolar lavage samples: results of. Clin Microbiol Infect 22:862–868. https://​doi.​org/​10.​1016/​j.​cmi.​2016.​06.​021 CrossRefPubMed
46.
47.
go back to reference Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ et al (2004) Beta-D-Glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis 39:199–205. https://doi.org/10.1086/421944 CrossRefPubMed Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ et al (2004) Beta-D-Glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis 39:199–205. https://​doi.​org/​10.​1086/​421944 CrossRefPubMed
51.
go back to reference Koo S, Bryar JM, Page JH, Baden LR, Marty FM (2009) Diagnostic performance of the (1→3)-β-d-glucan assay for invasive fungal disease. Clin Infect Dis 49:1650–1659CrossRefPubMed Koo S, Bryar JM, Page JH, Baden LR, Marty FM (2009) Diagnostic performance of the (1→3)-β-d-glucan assay for invasive fungal disease. Clin Infect Dis 49:1650–1659CrossRefPubMed
52.
go back to reference Kato A, Takita T, Furuhashi M, Takahashi T, Maruyama Y, Hishida A (2001) Elevation of blood (1 → 3 )-beta-D-glucan concentrations in hemodialysis patients. Nephron 89:15–19CrossRefPubMed Kato A, Takita T, Furuhashi M, Takahashi T, Maruyama Y, Hishida A (2001) Elevation of blood (1 → 3 )-beta-D-glucan concentrations in hemodialysis patients. Nephron 89:15–19CrossRefPubMed
53.
go back to reference Ogawa M, Hori H, Niiguchi S, Azuma E, Komada Y (2004) False-positive plasma (1-->3)-beta-D-glucan test following immunoglobulin product replacement in an adult bone marrow recipient. Int J Hematol 80:97–98CrossRefPubMed Ogawa M, Hori H, Niiguchi S, Azuma E, Komada Y (2004) False-positive plasma (1-->3)-beta-D-glucan test following immunoglobulin product replacement in an adult bone marrow recipient. Int J Hematol 80:97–98CrossRefPubMed
58.
go back to reference Ohata A, Usami M, Horiuchi T, Nagasawa K, Kinoshita K (2003) Release of (1-->3)-beta-D-glucan from depth-type membrane filters and their in vitro effects on proinflammatory cytokine production. Artif Organs 27:728–735CrossRefPubMed Ohata A, Usami M, Horiuchi T, Nagasawa K, Kinoshita K (2003) Release of (1-->3)-beta-D-glucan from depth-type membrane filters and their in vitro effects on proinflammatory cytokine production. Artif Organs 27:728–735CrossRefPubMed
60.
go back to reference Chong GM, van der Beek MT, von dem Borne PA, Boelens J, Steel E, Kampinga GA et al (2016) PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay ® in 201 patients with haematological disease suspected for invasive aspergillosis. J Antimicrob Chemother 71:3528–3535. https://doi.org/10.1093/jac/dkw323 CrossRefPubMed Chong GM, van der Beek MT, von dem Borne PA, Boelens J, Steel E, Kampinga GA et al (2016) PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay ® in 201 patients with haematological disease suspected for invasive aspergillosis. J Antimicrob Chemother 71:3528–3535. https://​doi.​org/​10.​1093/​jac/​dkw323 CrossRefPubMed
61.
go back to reference Orsi CF, Bettua C, Pini P, Venturelli C, La Regina A, Morace G et al (2015) Detection of Pneumocystis jirovecii and Aspergillus spp. DNa in bronchoalveolar lavage fluids by commercial real-time PCR assays: comparison with conventional diagnostic tests. New Microbiol 38:75–84PubMed Orsi CF, Bettua C, Pini P, Venturelli C, La Regina A, Morace G et al (2015) Detection of Pneumocystis jirovecii and Aspergillus spp. DNa in bronchoalveolar lavage fluids by commercial real-time PCR assays: comparison with conventional diagnostic tests. New Microbiol 38:75–84PubMed
64.
go back to reference Markoulatos P, Siafakas N, Moncany M (2002) Multiplex polymerase chain reaction: a practical approach. J Clin Lab Anal 16:47–51CrossRefPubMed Markoulatos P, Siafakas N, Moncany M (2002) Multiplex polymerase chain reaction: a practical approach. J Clin Lab Anal 16:47–51CrossRefPubMed
66.
go back to reference Silverman AP, Kool ET (2007) Oligonucleotide probes for RNA-targeted fluorescence in situ hybridization. Adv Clin Chem 43:79–115CrossRefPubMed Silverman AP, Kool ET (2007) Oligonucleotide probes for RNA-targeted fluorescence in situ hybridization. Adv Clin Chem 43:79–115CrossRefPubMed
67.
go back to reference Amann R, Fuchs BM, Behrens S (2001) The identification of microorganisms by fluorescence in situ hybridisation. Curr Opin Biotechnol 12:231–236CrossRefPubMed Amann R, Fuchs BM, Behrens S (2001) The identification of microorganisms by fluorescence in situ hybridisation. Curr Opin Biotechnol 12:231–236CrossRefPubMed
68.
go back to reference Muro MA (2005) Medical biomethods handbook. In: Walker JM, Rapley R (eds) Probe design, production, and applications. Humana press, Totowa, NJ, pp 13–23 Muro MA (2005) Medical biomethods handbook. In: Walker JM, Rapley R (eds) Probe design, production, and applications. Humana press, Totowa, NJ, pp 13–23
71.
go back to reference Shinozaki M, Okubo Y, Nakayama H, Mitsuda A, Ide T, Yamagata Murayama S et al (2009) Application of in situ hybridization to tissue sections for identification of molds causing invasive fungal infection. Jpn J Med Mycol 50:75–83CrossRef Shinozaki M, Okubo Y, Nakayama H, Mitsuda A, Ide T, Yamagata Murayama S et al (2009) Application of in situ hybridization to tissue sections for identification of molds causing invasive fungal infection. Jpn J Med Mycol 50:75–83CrossRef
76.
go back to reference Moter A, Göbel UB (2000) Fluorescence in situ hybridization (FISH) for direct visualization of microorganisms. J Microbiol Methods 41:85–112CrossRefPubMed Moter A, Göbel UB (2000) Fluorescence in situ hybridization (FISH) for direct visualization of microorganisms. J Microbiol Methods 41:85–112CrossRefPubMed
81.
go back to reference Smith JJ, Gunasekera TS, Barardi CRM, Veal D, Vesey G (2004) Determination of Cryptosporidium parvum oocyst viability by fluorescence in situ hybridization using a ribosomal RNA-directed probe. J Appl Microbiol 96:409–417CrossRefPubMed Smith JJ, Gunasekera TS, Barardi CRM, Veal D, Vesey G (2004) Determination of Cryptosporidium parvum oocyst viability by fluorescence in situ hybridization using a ribosomal RNA-directed probe. J Appl Microbiol 96:409–417CrossRefPubMed
89.
go back to reference Cerqueira L, Fernandes RM, Ferreira RM, Oleastro M, Carneiro F, Brandão C et al (2013) Probe4pylori: a new kit for the rapid detection of H. pylori and associated clarithromycin resistance in gastric biopsies. Helicobacter 18:123–123 Cerqueira L, Fernandes RM, Ferreira RM, Oleastro M, Carneiro F, Brandão C et al (2013) Probe4pylori: a new kit for the rapid detection of H. pylori and associated clarithromycin resistance in gastric biopsies. Helicobacter 18:123–123
90.
go back to reference Cerqueira LIM, Almeida CMF, Azevedo NFRPO, Vieira MJLC (2015) Peptide nucleic acid probe (PNA), kit and method for detection of Aspergillus fumigatus and applications thereof Cerqueira LIM, Almeida CMF, Azevedo NFRPO, Vieira MJLC (2015) Peptide nucleic acid probe (PNA), kit and method for detection of Aspergillus fumigatus and applications thereof
Metadata
Title
Invasive pulmonary aspergillosis: current diagnostic methodologies and a new molecular approach
Authors
S. Moura
L. Cerqueira
A. Almeida
Publication date
01-08-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 8/2018
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-018-3251-5

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