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Current Approaches Towards Development of Molecular Markers in Diagnostics of Invasive Aspergillosis

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Molecular Markers in Mycology

Part of the book series: Fungal Biology ((FUNGBIO))

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Abstract

The incidence of Invasive Aspergillosis (IA), an opportunistic infection is on the rise; mainly due to an increasing number of immunocompromised patients. Early diagnosis of IA remains challenging and treatment options are limited. Histopathologic or cytological evidence of fungus still remains main diagnostic criteria for proven invasive Aspergillosis cases. Detection of the fungus in the specimens of immunosuppressed patients is difficult. Detection methods based on cell-wall antigens of Aspergillus such as galactomannan and β-d-glucan has been reported and are in clinical use. However cross reactivity of these tests with other fungi limits their use. Recently an Aspergillus-specific monoclonal antibody, JF5, specifically bindinggalactomannan antigen, for point-of-care diagnosis of IPA using lateral-flow technology is being examined. Quantitative polymerase chain reaction assays for Aspergillus has theoretical advantages but is not validated for clinical use. This necessitates development of dependable, sensitive and specific methods for the detection of Aspergilli pathogens in clinical samples. Further extensive use of antifungal drugs in prophylactic and therapeutic practice has led to development of drug resistance. Development of novel strategies for finding new biomarkers to provide early and accurate diagnosis is thus vital. Proteomics approach can provide a means to screen for both host- and pathogen-derived biomarkers that could be suitable for the diagnosis, as well as to study the host-pathogen interaction in invasive pulmonary Aspergillosis. Identification of novel biomarkers from Aspergillus and its thoughtful use in molecular and serological diagnostic techniques into clinical practice will undoubtedly improve the scope of IA diagnosis.

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References

  • Abad-Diaz-De-Cerio A, Fernandez-Molina JV, Ramirez-Garcia A, Sendino J, Hernando FL, Peman J, Garaizar J, Rementeria A. The aspHS gene as a new target for detecting Aspergillus fumigatus during infections by quantitative real-time PCR. Med Mycol. 2013;51(5):545–54.

    CAS  PubMed  Google Scholar 

  • Agarwal R, Khan A, Garg M, Aggarwal AN, Gupta D. Pictorial essay: allergic bronchopulmonary aspergillosis. Indian J Radiol Imaging. 2011;21(4):242–52.

    PubMed  PubMed Central  Google Scholar 

  • Agarwal R, Denning DW, Chakrabarti A. Estimation of the burden of chronic and allergic pulmonary aspergillosis in India. PLoS One. 2014;9(12):e114745.

    PubMed  PubMed Central  Google Scholar 

  • Ananda-Rajah MR, Slavin MA, Thursky KT. The case for antifungal stewardship. Curr Opin Infect Dis. 2012;25(1):107–15.

    PubMed  Google Scholar 

  • Arvanitis M, Anagnostou T, Fuchs BB, Caliendo AM, Mylonakis E. Molecular and non molecular diagnostic methods for invasive fungal infections. Clin Microbiol Rev. 2014;27(3):490–526.

    PubMed  PubMed Central  Google Scholar 

  • Badiee P, Hashemizadeh Z. Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J Med Res. 2014;139(2):195–204.

    PubMed  PubMed Central  Google Scholar 

  • Bhetariya P, Shankar J, Singh Y, Madan T, Basir SF, Sarma PU. Multiplex PCR for detection of Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. J Allergy Clin Immunol. 2009;123(2):160.

    Google Scholar 

  • Blyth CC, Gilroy NM, Guy SD, Chambers ST, Cheong EY, Gottlieb T, McGuinness SL, Thursky KA. Consensus guidelines for the treatment of invasive mould infections in haematological malignancy and haemopoietic stem cell transplantation. Intern Med. 2014;J44(12b):1333–49.

    Google Scholar 

  • Boch T, Reinwald M, Postina P, Cornely OA, Vehreschild JJ, Heussel CP, Heinz WJ, Hoenigl M, Eigl S, Lehrnbecher T, Hahn J, Claus B, Lauten M, Egerer G, Muller MC, Will S, Merker N, Hofmann WK, Buchheidt D, Spiess B. Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA- microarray from primary clinical samples. Mycoses. 2015;58(12):735–45.

    CAS  PubMed  Google Scholar 

  • Bu R, Sathiapalan RK, Ibrahim MM, Al-Mohsen I, Almodavar E, Gutierrez MI, Bhatia K. Monochrome Light Cycler PCR assay for detection and quantification of five common species of Candida and Aspergillus. J Med Microbiol. 2005;54(3):243–8.

    CAS  PubMed  Google Scholar 

  • Bustin SA, Dorudi S. The value of microarray techniques for quantitative gene profiling in molecular diagnostics. Trends Mol Med. 2002;8(6):269–72.

    CAS  PubMed  Google Scholar 

  • Caillot D, Couaillier JF, Bernard A, Casasnovas O, Denning DW, Mannone L, Lopez J, Couillault G, Piard F, Vagner O, Guy H. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol. 2001;19(1):253–9.

    CAS  PubMed  Google Scholar 

  • Chen ST, Sorrell T, Nimmo G, Speed B, Currie B, Ellis D, Marriott D, Pfeiffer T, Parr D, Byth K. Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group. Clin Infect Dis. 2000;31(2):499–508.

    CAS  PubMed  Google Scholar 

  • Chen SC, Playford EG, Sorrell TC. Antifungal therapy in invasive fungal infections. Curr Opin Pharmacol. 2010;10(5):522–30.

    CAS  PubMed  Google Scholar 

  • Chong GL, Van de Sande WW, Dingemans DJ, Gaajetaan GR, Vonk AG, Hayette MP, Van Tegelen DW, Simons GF, Rijnders BJ. Validation of a new Aspergillus real-time PCR assay for direct detection of Aspergillus and azole resistance of Aspergillus fumigatus on bronchoalveolar lavage fluid. J Clin Microbiol. 2015;53(3):868–74.

    PubMed  PubMed Central  Google Scholar 

  • Chris K, Denning DW. The clinical spectrum of pulmonary aspergillosis. Postgrad Med J. 2015;91:403–10.

    Google Scholar 

  • De Pascale G, Tumbarello M. Fungal infections in the ICU: advances in treatment and diagnosis. Curr Opin Crit Care. 2015;21(5):421–9.

    PubMed  Google Scholar 

  • 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, Munoz 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(12):1813–21.

    PubMed  Google Scholar 

  • Domingo MP, Colmenarejo C, Martinez-Lostao L, Mullbacher A, Jarne C, Revillo KJ, Delgado P, Roc L, Meis JF, Rezusta A, Pardo J, Galvez EM. Bis(methyl)gliotoxin proves to be a more stable and reliable marker for invasive aspergillosis than gliotoxin and suitable for use in diagnosis. Diagn Microbiol Infect Dis. 2012;73(1):57–64.

    CAS  PubMed  Google Scholar 

  • Donnelly JP. Polymerase chain reaction for diagnosing invasive aspergillosis: getting closer but still a ways to go. Clin Infect Dis. 2006;42(4):487–9.

    CAS  PubMed  Google Scholar 

  • Dromer F, Mathoulin-Pelissier S, Launay O, Lortholary O. Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. PLoS Med. 2007;4(2):e21.

    PubMed  PubMed Central  Google Scholar 

  • Ellis M, Al-Ramadi B, Bernsen R, Kristensen J, Alizadeh H, Hedstrom U. Prospective evaluation of mannan and anti-mannan antibodies for diagnosis of invasive Candida infections in patients with neutropenic fever. J Med Microbiol. 2009;58(5):606–15.

    CAS  PubMed  Google Scholar 

  • Fernandez-Molina JV, Abad-Diaz-de-Cerio A, Sueiro-Olivares M, Pellon A, Ramirez-Garcia A, Garaizar J, Peman J, Hernando FL, Rementeria A. Rapid and specific detection of section Fumigati and Aspergillus fumigatus in human samples using a new multiplex real-time PCR. Diagn Microbiol Infect Dis. 2014;80(2):111–8.

    CAS  PubMed  Google Scholar 

  • Frias-de Leon MG, Acosta-Altamirano G, Duarte-Escalante E, Martinez-Hernandez JE, Martinez-Rivera Mde L, Mdel R-M. Molecular markers: an important tool in the diagnosis, treatment and epidemiology of invasive aspergillosis. Cir Cir. 2014;82(1):109–18.

    PubMed  Google Scholar 

  • Glass NL, Donaldson GC. Development of primer sets designed for use with the PCR to amplify conserved genes from filamentous ascomycetes. Appl Environ Microbiol. 1995;61(4):1323–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Godoy MC, Viswanathan C, Marchiori E, Truong MT, Benveniste MF, Rossi S, Marom EM. The reversed halo sign: update and differential diagnosis. Br J Radiol. 2012;85(1017):1226–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Greene RE, Schlamm HT, Oestmann JW, Stark P, Durand C, Lortholary O, Wingard JR, Herbrecht R, Ribaud P, Patterson TF, Troke PF, Denning DW, Bennett JE, De Pauw B, Rubin RH. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis. 2007;44(3):373–9.

    PubMed  Google Scholar 

  • Groll AH, Tragiannidis A. Recent advances in antifungal prevention and treatment. Semin Hematol. 2009;46(3):212–29.

    CAS  PubMed  Google Scholar 

  • Gupta P, Khare V, Kumar D, Ahmad A, Banerjee G, Singh M. Comparative evaluation of disc diffusion and E-test with Broth Micro-dilution in susceptibility testing of Amphotericin B, Voriconazole and Caspofungin against clinical Aspergillus isolates. J Clin Diagn Res. 2015;9(1):04–7.

    Google Scholar 

  • Hao W, Pan YX, Ding YQ, Xiao S, Yin K, Wang YD, Qiu LW, Zhang QL, Woo PC, Lau SK, Yuen KY, Che XY. Well-characterized monoclonal antibodies against cell wall antigen of Aspergillus species improve immunoassay specificity and sensitivity. Clin Vaccine Immunol. 2008;15(2):194–202.

    CAS  PubMed  Google Scholar 

  • Hinrikson HP, Hurst SF, Lott TJ, Warnock DW, Morrison CJ. Assessment of ribosomal large-subunit D1-D2, internal transcribed spacer 1, and internal transcribed spacer 2 regions as targets for molecular identification of medically important Aspergillus species. J Clin Microbiol. 2005;43(5):2092–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Houbraken J, Samson RA. Phylogeny of Penicillium and the segregation of Trichocomaceae into three families. Stud Mycol. 2011;70(1):1–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Isshiki A, Takeharu H, Aoki S, Kokaji M, Tanabe S, Kasetani T, Yoshida M. Development of a multiple detection technique for fungi by DNA microarray with the simultaneous use of internal transcribed spacer region of ribosomal RNA gene and beta-tubulin gene probes. Biocontrol Sci. 2014;19(3):139–45.

    PubMed  Google Scholar 

  • Jegorov A, Hajduch M, Sulc M, Havlicek V. Nonribosomal cyclic peptides: specific markers of fungal infections. J Mass Spectrom. 2006;41(5):563–76.

    CAS  PubMed  Google Scholar 

  • Jeong SJ, Lee JU, Song YG, Lee KH, Lee MJ. Delaying diagnostic procedure significantly increases mortality in patients with invasive mucormycosis. Mycoses. 2015;58(12):746–52.

    PubMed  Google Scholar 

  • Kanbe T, Arishima T, Horii T, Kikuchi A. Improvements of PCR-based identification targeting the DNA topoisomerase II gene to determine major species of the opportunistic fungi Candida and Aspergillus fumigatus. Microbiol Immunol. 2003;47(9):631–8.

    CAS  PubMed  Google Scholar 

  • Kim NY, Lee I, Ji GE. Reliable and simple detection of ochratoxin and fumonisin production in black Aspergillus. J Food Prot. 2014;77(4):653–8.

    CAS  PubMed  Google Scholar 

  • Kozel TR, Wickes B. Fungal diagnostics. Cold Spring Harb Perspect Med. 2014;4(4):a019299.

    PubMed  PubMed Central  Google Scholar 

  • Krel M, Petraitis V, Petraitiene R, Jain MR, Zhao Y, Li H, Walsh TJ, Perlin DS. Host biomarkers of invasive pulmonary aspergillosis to monitor therapeutic response. Antimicrob Agents Chemother. 2014;58(6):3373–8.

    PubMed  PubMed Central  Google Scholar 

  • Kumar A, Ahmed R, Singh PK, Shukla PK. Identification of virulence factors and diagnostic markers using immunosecretome of Aspergillus fumigatus. J Proteomics. 2011;74(7):1104–12.

    CAS  PubMed  Google Scholar 

  • Kuper KM, Coyle EA, Wanger A. Antifungal susceptibility testing: a primer for clinicians. Pharmacotherapy. 2012;32(12):1112–22.

    CAS  PubMed  Google Scholar 

  • Latge JP. The pathobiology of Aspergillus fumigatus. Trends Microbiol. 2001;9(8):382–9.

    CAS  PubMed  Google Scholar 

  • Liss B, Cornely OA, Hoffmann D, Dimitriou V, Wisplinghoff H (2015) 1,3- ß-D-glucanconcentrations in blood products predict false positive post-transfusion results. Mycoses 59(1):39–42. doi:10.1111/myc.12432

  • Lunel FM, Mennink-Kersten MA, Ruegebrink D, Van der Lee HA, Donnelly JP, Blijlevens NM, Verweij PE. Value of Candida serum markers in patients with invasive candidiasis after myeloablative chemotherapy. Diagn Microbiol Infect Dis. 2009;64(4):408–15.

    PubMed  Google Scholar 

  • Morelle W, Bernard M, Debeaupuis JP, Buitrago M, Tabouret M, Latge JP. Galactomannoproteins of Aspergillus fumigatus. Eukaryot Cell. 2005;4(7):1308–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morton CO, De Luca A, Romani L, Rogers TR. RT-qPCR detection of Aspergillus fumigatus RNA in vitro and in a murine model of invasive aspergillosis utilizing the PAXgene(R) and Tempus RNA stabilization systems. Med Mycol. 2012;50(6):661–6.

    CAS  PubMed  Google Scholar 

  • Neustadt M, Costina V, Kupfahl C, Buchheidt D, Eckerskorn C, Neumaier M, Findeisen P. Characterization and identification of proteases secreted by Aspergillus fumigatus using free flow electrophoresis and MS. Electrophoresis. 2009;30(12):2142–50.

    CAS  PubMed  Google Scholar 

  • Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Arroyo J, Berriman M, Abe K, Archer DB, Bermejo C, Bennett J, Bowyer P, Chen D, Collins M, Coulsen R, Davies R, Dyer PS, Farman M, Fedorova N, Feldblyum TV, Fischer R, Fosker N, Fraser A, Garcia JL, Garcia MJ, Goble A, Goldman GH, Gomi K, Griffith-Jones S, Gwilliam R, Haas B, Haas H, Harris D, Horiuchi H, Huang J, Humphray S, Jimenez J, Keller N, Khouri H, Kitamoto K, Kobayashi T, Konzack S, Kulkarni R, Kumagai T, Lafon A, Latge JP, Li W, Lord A, Lu C, Majoros WH, May GS, Miller BL, Mohamoud Y, Molina M, Monod M, Mouyna I, Mulligan S, Murphy L, O’Neil S, Paulsen I, Penalva MA, Pertea M, Price C, Pritchard BL, Quail MA, Rabbinowitsch E, Rawlins N, Rajandream MA, Reichard U, Renauld H, Robson GD, Rodriguez de Cordoba S, Rodriguez-Pena JM, Ronning CM, Rutter S, Salzberg SL, Sanchez M, Sanchez-Ferrero JC, Saunders D, Seeger K, Squares R, Squares S, Takeuchi M, Tekaia F, Turner G, Vazquez de Aldana CR, Weidman J, White O, Woodward J, Yu JH, Fraser C, Galagan JE, Asai K, Machida M, Hall N, Barrell B, Denning DW. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature. 2005;438(7071):1151–6.

    CAS  PubMed  Google Scholar 

  • Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ, Ketchum PA, Finkelman MA, Rex JH, Ostrosky-Zeichner L. 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. 2004;39(2):199–205.

    CAS  PubMed  Google Scholar 

  • Oliveira-Coelho A, Rodrigues F, Campos JA, Lacerda JF, Carvalho A, Cunha C. Paving the way for predictive diagnostics and personalized treatment of invasive aspergillosis. Front Microbiol. 2015;6:411.

    PubMed  PubMed Central  Google Scholar 

  • Oliveira M, Lackner M, Amorim A, Araujo R. Feasibility of mitochondrial single nucleotide polymorphisms to detect and identify Aspergillus fumigatus in clinical samples. Diagn Microbiol Infect Dis. 2014;80(1):53–8.

    CAS  PubMed  Google Scholar 

  • Orsi CF, Bettua C, Pini P, Venturelli C, La Regina A, Morace G, Luppi M, Forghieri F, Bigliardi S, Luppi F, Codeluppi M, Girardis M, Blasi E. 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. 2015;38(1):75–84.

    PubMed  Google Scholar 

  • Palumbo JD, O’Keeffe TL. Detection and discrimination of four Aspergillus section Nigri species by PCR. Lett Appl Microbiol. 2015;60(2):188–95.

    CAS  PubMed  Google Scholar 

  • Pan Z, Fu M, Zhang J, Zhou H, Fu Y, Zhou J. Diagnostic accuracy of a novel lateral-flow device in invasive aspergillosis: a meta-analysis. J Med Microbiol. 2015;64(7):702–7.

    CAS  PubMed  Google Scholar 

  • Pfaller MA, Diekema DJ. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol. 2004;42(10):4419–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20(1):133–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Posteraro B, Sanguinetti M. The future of fungal susceptibility testing. Future Microbiol. 2014;9(8):947–67.

    CAS  PubMed  Google Scholar 

  • Rachini A, Pietrella D, Lupo P, Torosantucci A, Chiani P, Bromuro C, Proietti C, Bistoni F, Cassone A, Vecchiarelli A. An anti-beta-glucan monoclonal antibody inhibits growth and capsule formation of Cryptococcus neoformans in vitro and exerts therapeutic, anticryptococcal activity in vivo. Infect Immun. 2007;75(11):5085–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schlageter AM, Kozel TR. Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide. Infect Immun. 1990;58(6):1914–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schutte M, Thullier P, Pelat T, Wezler X, Rosenstock P, Hinz D, Kirsch MI, Hasenberg M, Frank R, Schirrmann T, Gunzer M, Hust M, Dubel S. Identification of a putative Crf splice variant and generation of recombinant antibodies for the specific detection of Aspergillus fumigatus. PLoS One. 2009;4(8):e6625.

    PubMed  PubMed Central  Google Scholar 

  • Scotter JM, Chambers ST. Comparison of galactomannan detection, PCR-enzyme-linked immunosorbent assay, and real-time PCR for diagnosis of invasive aspergillosis in a neutropenic rat model and effect of caspofungin acetate. Clin Diagn Lab Immunol. 2005;12(11):1322–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Simitsopoulou M, Roilides E, Georgiadou E, Paliogianni F, Walsh TJ. Differential transcriptional profiles induced by amphotericin B formulations on human monocytes during response to hyphae of Aspergillus fumigatus. Med Mycol. 2011;49(2):176–85.

    CAS  PubMed  Google Scholar 

  • Singh B, Singh S, Asif AR, Oellerich M, Sharma GL. Allergic aspergillosis and the antigens of Aspergillus fumigatus. Curr Protein Pept Sci. 2014;15(5):403–23.

    CAS  PubMed  Google Scholar 

  • Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest. 2002;121(6):1988–99.

    PubMed  Google Scholar 

  • Speed B, Dunt D. Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis. 1995;21(1):28–34.

    CAS  PubMed  Google Scholar 

  • Spiess B, Buchheidt D, Baust C, Skladny H, Seifarth W, Zeilfelder U, Leib-Mosch C, Morz H, Hehlmann R. Development of a LightCycler PCR assay for detection and quantification of Aspergillus fumigatus DNA in clinical samples from neutropenic patients. J Clin Microbiol. 2003;41(5):1811–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Spiess B, Seifarth W, Hummel M, Frank O, Fabarius A, Zheng C, Morz H, Hehlmann R, Buchheidt D. DNA microarray-based detection and identification of fungal pathogens in clinical samples from neutropenic patients. J Clin Microbiol. 2007;45(11):3743–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stynen D, Sarfati J, Goris A, Prevost MC, Lesourd M, Kamphuis H, Darras V, Latge JP. Rat monoclonal antibodies against Aspergillus galactomannan. Infect Immun. 1992;60(6):2237–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sueiro-Olivares M, Fernandez-Molina JV, Abad-Diaz-de-Cerio A, Gorospe E, Pascual E, Guruceaga X, Ramirez-Garcia A, Garaizar J, Hernando FL, Margareto J, Rementeria A. Aspergillus fumigatus transcriptome response to a higher temperature during the earliest steps of germination monitored using a new customized expression microarray. Microbiology. 2015;161(Pt 3):490–502.

    CAS  PubMed  Google Scholar 

  • Sugui JA, Peterson SW, Clark LP, Nardone G, Folio L, Riedlinger G, Zerbe CS, Shea Y, Henderson CM, Zelazny AM, Holland SM, Kwon-Chung KJ. Aspergillus tanneri sp. nov., a new pathogen that causes invasive disease refractory to antifungal therapy. J Clin Microbiol. 2012;50(10):3309–17.

    PubMed  PubMed Central  Google Scholar 

  • Thursky KA, Playford EG, Seymour JF, Sorrell TC, Ellis DH, Guy SD, Gilroy N, Chu J, Shaw DR. Recommendations for the treatment of established fungal infections. Intern Med J. 2008;38(6b):496–520.

    CAS  PubMed  Google Scholar 

  • Tuntevski K, Durney BC, Snyder AK, Lasala PR, Nayak AP, Green BJ, Beezhold DH, Rio RV, Holland LA, Lukomski S. Aspergillus collagen-like genes (acl): identification, sequence polymorphism, and assessment for PCR-based pathogen detection. Appl Environ Microbiol. 2013;79(24):7882–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Turenne CY, Sanche SE, Hoban DJ, Karlowsky JA, Kabani AM. Rapid identification of fungi by using the ITS2 genetic region and an automated fluorescent capillary electrophoresis system. J Clin Microbiol. 1999;37(6):1846–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Van Peer A, Woestenborghs R, Heykants J, Gasparini R, Gauwenbergh G. The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects. Eur J Clin Pharmacol. 1989;36(4):423–6.

    PubMed  Google Scholar 

  • Varga J, Rigo K, Kocsube S, Farkas B, Pal K. Diversity of polyketide synthase gene sequences in Aspergillus species. Res Microbiol. 2003;154(8):593–600.

    CAS  PubMed  Google Scholar 

  • Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, Van Burik JA, Wingard JR, Patterson TF. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327–60.

    CAS  PubMed  Google Scholar 

  • Walsh TJ, Wissel MC, Grantham KJ, Petraitiene R, Petraitis V, Kasai M, Francesconi A, CottonMP HJE, Greene L, Bacher JD, Manna P, Salomoni M, Kleiboeker SB, Reddy SK. Molecular detection and species-specific identification of medically important Aspergillus species by real-time PCR in experimental invasive pulmonary aspergillosis. J Clin Microbiol. 2011;49(12):4150–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  • White PL, Mengoli C, Bretagne S, Cuenca-Estrella M, Finnstrom N, Klingspor L, Melchers WJ, McCulloch E, Barnes RA, Donnelly JP, Loeffler J. Evaluation of Aspergillus PCR protocols for testing serum specimens. J Clin Microbiol. 2011;49(11):3842–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wong B, Brauer KL, Tsai RR, Jayasimhulu K. Increased amounts of the Aspergillus metabolite D-mannitol in tissue and serum of rats with experimental aspergillosis. J Infect Dis. 1989;160(1):95–103.

    CAS  PubMed  Google Scholar 

  • Yoo JH, Choi SM, Lee DG, Park SH, Choi JH, Kwon EY, Shin WS. Comparison of the real-time nucleic acid sequence-based amplification (RTi-NASBA) with conventional NASBA, and galactomannan assay for the diagnosis of invasive aspergillosis. J Korean Med Sci. 2007;22(4):672–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zarrinfar H, Mirhendi H, Makimura K, Satoh K, Khodadadi H, Paknejad O. Use of mycological, nested PCR, and real-time PCR methods on BAL fluids for detection of Aspergillus fumigatus and A. flavus in solid organ transplant recipients. Mycopathologia. 2013;176(5–6):377–85.

    CAS  PubMed  Google Scholar 

  • Zhao Y, Park S, Kreiswirth BN, Ginocchio CC, Veyret R, Laayoun A, Troesch A, Perlin DS. Rapid real-time nucleic Acid sequence-based amplification-molecular beacon platform to detect fungal and bacterial bloodstream infections. J Clin Microbiol. 2009;47(7):2067–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Perlin DS. Quantitative detection of Aspergillus spp. by real-time nucleic acid sequence-based amplification. Methods Mol Biol. 2013;968:83–92.

    CAS  PubMed  Google Scholar 

  • Zmeili OS, Soubani AO. Pulmonary aspergillosis: a clinical update. QJM. 2007;100(6):317–34.

    CAS  PubMed  Google Scholar 

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Bhetariya, P.J., Madan, T., Sarma, P.U., Prakash, P.Y. (2017). Current Approaches Towards Development of Molecular Markers in Diagnostics of Invasive Aspergillosis. In: Singh, B.P., Gupta, V.K. (eds) Molecular Markers in Mycology. Fungal Biology. Springer, Cham. https://doi.org/10.1007/978-3-319-34106-4_13

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