Skip to main content

Advertisement

Log in

State of the art diagnostic of mold diseases: a practical guide for clinicians

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

The epidemiology of fungal diseases changed, and molds have been increasingly associated with high mortality in severe immunocompromised patients. Invasive mold diseases may originate from the airborne conidia through inhalation or inoculation in skin fissures associated with indwelling catheters, wounds, burns, or onychomycosis. The diagnosis and treatment of fungal diseases is problematic and raises considerable challenges. Diagnosis of invasive mold diseases includes several methodologies, of which the most commonly used are the cultural methods, antigen testing, nucleic acid detection, and radiological imaging. Galactomannan and (1 → 3)-β-d-glucan detection significantly improved mold diagnosis in the last decade. Several molecular strategies have been proposed over the years but no consensus was achieved for standardized protocols or cut-off values. Recently, the first commercially available molecular assay for detection of Aspergillus was tested and the results were highly reproducible. In addition, blood cultures may also be helpful for invasive aspergillosis by following a novel procedure for the recovery of Aspergillus spp. from blood cultures. The association of distinct diagnostic methods, particularly molecular tests, galactomannan, and/or (1 → 3)-β-d-glucan detection, may provide earlier and more sensitive diagnosis of mold diseases and be indicative for early antifungal treatment. Accurate routine use of diagnostic tests can be cost-effective for laboratories and be of great value to patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. McNeil MM, Nash SL, Hajjeh RA, Phelan MA, Conn LA, Plikaytis BD, Warnock DW (2001) Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 33:641–647

    Article  PubMed  CAS  Google Scholar 

  2. Araujo R, Carneiro A, Costa-Oliveira S, Pina-Vaz C, Rodrigues AG, Guimaraes JE (2008) Fungal infections after haematology unit renovation: evidence of clinical, environmental and economical impact. Eur J Haematol 80:436–443

    Article  PubMed  Google Scholar 

  3. Hachem RY, Kontoyiannis DP, Chemaly RF, Jiang Y, Reitzel R, Raad I (2009) Utility of galactomannan enzyme immunoassay and (1,3) beta-D-glucan in diagnosis of invasive fungal infections: low sensitivity for Aspergillus fumigatus infection in hematologic malignancy patients. J Clin Microbiol 47:129–133

    Article  PubMed  CAS  Google Scholar 

  4. Wirk B, Wingard JR (2009) Current approaches in antifungal prophylaxis in high risk hematologic malignancy and hematopoietic stem cell transplant patients. Mycopathologia 168:299–311

    Article  PubMed  Google Scholar 

  5. Gavaldà J, Román A (2007) Infection in lung transplantation. Enferm Infecc Microbiol Clin 25:639–649

    Article  PubMed  Google Scholar 

  6. Patterson JE (1999) Epidemiology of fungal infections in solid organ transplant patients. Transpl Infect Dis 1:229–236

    Article  PubMed  CAS  Google Scholar 

  7. de Pablo A, Ussetti P, Cruz Carreño M, Lázaro T, Ferreiro MJ, López A, Mendaza P, Estada J (2000) Aspergillosis in pulmonary transplantation. Enferm Infecc Microbiol Clin 18:209–214

    PubMed  Google Scholar 

  8. García-Ruiz JC, Amutio E, Pontón J (2004) Invasive fungal infection in immunocompromised patients. Rev Iberoam Micol 21:55–62

    PubMed  Google Scholar 

  9. Lacombe C, Lewin M, Monnier-Cholley L, Pacanowiski J, Poirot JL, Arrivé L, Tubiana JM (2007) Imaging of thoracic pathology in patients with AIDS. J Radiol 88:1145–1154

    Article  PubMed  CAS  Google Scholar 

  10. Guazzelli LS, Unis G, Xavier MO, Severo CB, Picon PD, Severo LC (2009) Fungus ball in HIV-infected patients. Rev Inst Med Trop Sao Paulo 51:345–348

    Article  PubMed  Google Scholar 

  11. Chande C, Menon S, Gohil A, Lilani S, Bade J, Mohammad S, Joshi A (2010) Cutaneous histoplasmosis in AIDS. Indian J Med Microbiol 28:404–406

    Article  PubMed  CAS  Google Scholar 

  12. Almyroudis NG, Kontoyiannis DP, Sepkowitz KA, DePauw BE, Walsh TJ, Segal BH (2006) Issues related to the design and interpretation of clinical trials of salvage therapy for invasive mold infection. Clin Infect Dis 43:1449–1455

    Article  PubMed  Google Scholar 

  13. Nucci M, Anaissie E (2009) Infections in patients with multiple myeloma. Semin Hematol 46:277–288

    Article  PubMed  Google Scholar 

  14. Vagace JM, Sanz-Rodriguez C, Casado MS, Alonso N, Garcia-Dominguez M, de la Llna FG, Zarallo L, Fajardo M, Bajo R (2007) Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: a case report. BMC Infect Dis 7:40

    Article  PubMed  Google Scholar 

  15. Araujo R, Rodrigues AG (2004) Variability of germinative potential among pathogenic species of Aspergillus. J Clin Microbiol 42:4335–4337

    Article  PubMed  Google Scholar 

  16. Harun A, Blyth CC, Gilgado F, Middleton P, Chen SC, Meyer W (2011) Development and validation of a multiplex PCR for detection of Scedosporium spp. in respiratory tract specimens with cystic fibrosis. J Clin Microbiol 49:1508–1512

    Article  PubMed  CAS  Google Scholar 

  17. Cortez KJ, Roilides E, Quiroz-Telles F, Meletiadis J, Antachopoulos C, Knudsen T, Buchanan W, Milanovich J, Sutton DA, Fothergill A, Rinaldi MG, Shea YR, Zaoutis T, Kottilil S, Walsh TJ (2008) Infections caused by Scedosporium spp. Clin Microbiol Rev 21:157–197

    Article  PubMed  CAS  Google Scholar 

  18. Gomes MZ, Lewis RE, Kontoyannis DP (2011) Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species. Clin Microbiol Rev 24:411–445

    Article  PubMed  Google Scholar 

  19. Csomor J, Nikolova R, Sinkó J, Reményi P, Szabó Z (2004) Mucormycosis. Orv Hetil 145:2507–2513

    PubMed  Google Scholar 

  20. Kara IO, Tasova Y, Uguz A, Sahin B (2009) Mucormycosis-associated fungal infections in patients with haematologic malignancies. Int J Clin Pract 63:134–139

    Article  PubMed  CAS  Google Scholar 

  21. Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, Ito J, Andes DR, Baddley JW, Brown JM, Brumble LM, Freifeld AG, Hadley S, Herwaldt LA, Kauffman CA, Knapp K, Lyon GM, Morrison VA, Papanicolaou G, Patterson TF, Perl TM, Schuster MG, Walker R, Wannemuehler KA, Wingard JR, Chiller TM, Pappas PG (2010) Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 50:1091–1100

    Article  PubMed  Google Scholar 

  22. Chamilos G, Luna M, Lewis RE, Bodey GP, Chemaly R, Tarrand JJ, Safdar A, Raad II, Kontoyannis DP (2006) Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica 91:986–989

    PubMed  Google Scholar 

  23. Pontón J (2002) Microbiological diagnosis of mycoses. Rev Iberoam Micol 19:25–29

    PubMed  Google Scholar 

  24. Quindós G (2011) Candidiasis, aspergillosis and other invasive mycoses in recipients of solid organ transplants. Rev Iberoam Micol 28:110–119

    Article  PubMed  Google Scholar 

  25. Mayayo Artal E (2004) Histopathological diagnosis of mycoses. Rev Iberoam Micol 21:1–9

    PubMed  Google Scholar 

  26. Vanittanakom N, Cooper CR Jr, Fisher MC, Sirisanthana T (2006) Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects. Clin Microbiol Rev 19:95–110

    Article  PubMed  CAS  Google Scholar 

  27. Huang YT, Hung CC, Liao CH, Sun HY, Chang SC, Chen YC (2007) Detection of circulating galactomannan in serum samples for diagnosis of Penicillium marneffei infection and cryptococcosis among patients infected with human immunodeficiency virus. J Clin Microbiol 45:2858–2862

    Article  PubMed  Google Scholar 

  28. Klingspor L, Loeffler J (2009) Aspergillus PCR formidable challenges and progress. Med Mycol 47:S241–S247

    Article  PubMed  CAS  Google Scholar 

  29. Nucci M, Anaissie E (2007) Fusarium infections in immunocompromised patients. Clin Microbiol Rev 20:695–704

    Article  PubMed  CAS  Google Scholar 

  30. Rosa C, Araujo R, Rodrigues AG, Pinto-de-Sousa MI, Pina-Vaz C (2011) Detection of Aspergillus species in BACTEC blood cultures. J Med Microbiol 60:1467–1471

    Article  PubMed  Google Scholar 

  31. Ju MK, Joo DJ, Kim SJ, Chang HK, Kim MS, Kim SI, Kim YS (2009) Invasive pulmonary aspergillosis after solid organ transplantation: diagnosis and treatment based on 28 years of transplantation experience. Transplant Proc 41:375–378

    Article  PubMed  CAS  Google Scholar 

  32. Godet C, Elsendoorn A, Roblot F (2012) Benefit of CT scanning for assessing pulmonary disease in the immunodepressed patient. Diagn Interv Imaging 93:425–430

    Article  PubMed  CAS  Google Scholar 

  33. del Palacio A, Alhambra A, Cuétara MS, Pontón J (2007) Early diagnosis of invasive fungal infections caused by Aspergillus and other emerging mycelial fungi. Rev Iberoam Micol 24:187–197

    Article  PubMed  Google Scholar 

  34. Thornton CR (2010) Detection of invasive aspergillosis. Adv Appl Microbiol 70:187–216

    Article  PubMed  CAS  Google Scholar 

  35. Rovira M, Jimenéz M, De La Bellacasa JP, Mensa J, Rafel M, Ortega M, Almela M, Martínez C, Fernández-Avilés F, Martínez JA, Urbano-Ispizua A, Carreras E, Montserrat E (2004) Detection of Aspergillus galactomannan by enzyme immunoabsorbent assay in recipients of allogeneic hematopoietic stem cell transplantation: a prospective study. Transplantation 77:1260–1264

    Article  PubMed  CAS  Google Scholar 

  36. Guinea J, Jensen J, Peláez T, Gijón P, Alonso R, Rivera M, Muñoz P, Bouza E (2008) Value of a single galactomannan determination (Platelia) for the diagnosis of invasive aspergillosis in non-hematological patients with clinical isolation of Aspergillus spp. Med Mycol 46:575–579

    Article  PubMed  CAS  Google Scholar 

  37. Fortún J, Martín-Dávila P, Alvarez ME, Norman F, Sánchez-Sousa A, Gajate L, Bárcena R, Nuño SJ, Moreno S (2009) False-positive results of Aspergillus galactomannan antigenemia in liver transplant recipients. Transplantation 87:256–260

    Article  PubMed  Google Scholar 

  38. Kauffman CA (2008) Diagnosis of histoplasmosis in immunosuppressed patients. Curr Opin Infect Dis 21:421–425

    Article  PubMed  Google Scholar 

  39. Mori Y, Nagasaki Y, Kamezaki K, Takenaka K, Iwasaki H, Harada N, Miyamoto T, Abe Y, Shimono N, Akashi K, Teshima T (2010) High incidence of false-positive Aspergillus galactomannan test in multiple myeloma. Am J Hematol 85:449–451

    PubMed  Google Scholar 

  40. Kedzierska A, Kochan P, Pietrzyk A, Kedzierska J (2007) Current status of fungal cell wall components in the immunodiagnostics of invasive fungal infections in humans: galactomannan, mannan and (1– > 3)-beta-D-glucan antigens. Eur J Clin Microbiol Infect Dis 26:755–766

    Article  PubMed  CAS  Google Scholar 

  41. Alhambra A, Cuétara MS, Ortiz MC, Moreno JM, del Palacio A, Pontón J, del Palacio A (2007) False positive galactomannan results in adult hematological patients treated with piperacillin-tazobactam. Rev Iberoam Micol 24:106–112

    Article  PubMed  Google Scholar 

  42. Pickering JW, Sant HW, Bowles CA, Roberts WL, Woods GL (2005) Evaluation of a (1- > 3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol 43:5957–5962

    Article  PubMed  CAS  Google Scholar 

  43. Persat F, Ranque S, Derouin F, Michel-Nguyen A, Picot S, Sulahian A (2008) Contribution of the (1→3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol 46:1009–1013

    Article  PubMed  Google Scholar 

  44. Burco JD, Ziccardi MH, Clemons KV, Tell LA (2012) Evaluation of plasma (1– > 3) beta-D-glucan concentrations in birds naturally and experimentally infected with Aspergillus fumigatus. Avian Dis 56:183–191

    Article  PubMed  Google Scholar 

  45. Rácil Z, Kocmanova I, Lengerova M, Weinbergerova B, Buresova L, Toskova M, Winterova J, Timilsina S, Rodriguez I, Mayer J (2010) Difficulties in using 1,3-{beta}-D-glucan as the screening test for the early diagnosis of invasive fungal infections in patients with haematological malignancies – high frequency of false-positive results and their analysis. J Med Microbiol 59:1016–1022

    Article  PubMed  Google Scholar 

  46. Ostrosky-Zeichner L (2012) Invasive mycoses: diagnostic challenges. Am J Med 125:S14–S24

    Article  PubMed  Google Scholar 

  47. Singh N, Paterson DL (2005) Aspergillus infections in transplant recipients. Clin Microbiol Rev 18:44–69

    Article  PubMed  CAS  Google Scholar 

  48. Badiee P, Kordbacheh P, Alborzi A, Ramzi M, Shakiba E (2008) Molecular detection of invasive aspergillosis in hematologic malignancies. Infection 36:580–584

    Article  PubMed  CAS  Google Scholar 

  49. Luong ML, Filion C, Labbé AC, Roy J, Pépin J, Cadrin-Tourigny J, Carignan S, Sheppard DC, Laverdière M (2010) Clinical utility and prognostic value of bronchoalveolar lavage galactomannan in patients with hematologic malignancies. Diagn Microbiol Infect Dis 68:132–139

    Article  PubMed  Google Scholar 

  50. Kami M, Fukui T, Ogawa S, Kazuyama Y, Machida U, Tanaka Y, Kanda Y, Kashima T, Yamazaki Y, Hamaki T, Mori S, Akiyama H, Mutou Y, Sakamaki H, Osumi K, Kimura S, Hirai H (2001) Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis. Clin Infect Dis 33:1504–1512

    Article  PubMed  CAS  Google Scholar 

  51. Kawazu M, Kanda Y, Goyama S, Takeshita M, Nannya Y, Niino M, Komeno Y, Nakamoto T, Kurokawa M, Tsujino S, Ogawa K, Aoki K, Chiba S, Motokura T, Ohish N, Hirai H (2003) Rapid diagnosis of invasive pulmonary aspergillosis by quantitative polymerase chain reaction using bronchial lavage fluid. Am J Hematol 72:27–30

    Article  PubMed  Google Scholar 

  52. del Palacio A, Cuétara MS, Pontón J (2003) Invasive aspergillosis. Rev Iberoam Micol 20:77–78

    PubMed  Google Scholar 

  53. Schabereiter-Gurtner C, Selitsch B, Rotter ML, Hirschl AM, Willinger B (2007) Development of novel real-time PCR assays for detection and differentiation of eleven medically important Aspergillus and Candida species in clinical specimens. J Clin Microbiol 45:906–914

    Article  PubMed  CAS  Google Scholar 

  54. Deshpande P, Shetty A, Mehta A, Kapadia F, Hedge A, Soman R, Rodrigues C (2011) Standardization of fungal polymerase chain reaction for the early diagnosis of invasive fungal infection. Indian J Med Microbiol 29:406–410

    Article  PubMed  CAS  Google Scholar 

  55. Chen SC, Kontoyiannis DP (2010) New molecular and surrogate biomarker-based tests in the diagnosis of bacterial and fungal infection in febrile neutropenic patients. Curr Opin Infect Dis 23:567–577

    Article  PubMed  CAS  Google Scholar 

  56. Boudewijns M, Verweij PE, Melchers WJ (2006) Molecular diagnosis of invasive aspergillosis: the long and winding road. Future Microbiol 1:283–293

    Article  PubMed  CAS  Google Scholar 

  57. White PL, Perry MD, Moody A, Follett SA, Morgan G, Barnes RA (2011) Evaluation of analytical and preliminary clinical performance of Myconostica MycAssay Aspergillus when testing serum specimens for diagnosis of invasive aspergillosis. J Clin Microbiol 49:2169–2174

    Article  PubMed  Google Scholar 

  58. Torelli R, Sanguinetti M, Moody A, Pagano L, Caira M, De Carolis E, Fuso L, De Pascale G, Bello G, Antonelli M, Fadda G, Posteraro B (2011) Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay. J Clin Microbiol 49:4273–4278

    Article  PubMed  CAS  Google Scholar 

  59. De Pauw B, Walsh TJ, Donelly 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, Benett JE, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group (2008) 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 46:1813–1821

    Article  PubMed  Google Scholar 

  60. Walsh TJ, Wissel MC, Grantham KJ, Petraitiene R, Petraitis V, Kasai M, Francesconi A, Cotton MP, Hughes JE, Greene L, Bacher JD, Manna P, Salomoni M, Kleiboeker SB, Reddy SK (2011) Molecular detection and species-specific identification of medically important Aspergillus species by real-time PCR in experimental invasive pulmonary aspergillosis. J Clin Microbiol 49:4150–4157

    Article  PubMed  CAS  Google Scholar 

  61. Thornton C, Johnson G, Agrawal S (2012) Detection of invasive pulmonary aspergillosis in haematological malignancy patients by using lateral-flow technology. J Vis Exp 22:3721

    Google Scholar 

Download references

Acknowledgments and funding

This work was partially supported by a grant from Pfizer Inc. (nº. IIR#WS1948668). RA is supported by Fundação para a Ciência e a Tecnologia (FCT) Ciência 2007 and by the European Social Fund. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT.

Conflict of interest

The authors have no financial relationship with the organization that sponsored the research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Araujo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beirão, F., Araujo, R. State of the art diagnostic of mold diseases: a practical guide for clinicians. Eur J Clin Microbiol Infect Dis 32, 3–9 (2013). https://doi.org/10.1007/s10096-012-1722-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-012-1722-7

Keywords

Navigation