Mold-Associated Infections

  • Diagnosis
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Criteria for Diagnosis

  • Primary diagnostic criteria for allergic bronchopulmonary aspergillosis (IDSA, 2008)
    • Asthma
    • Peripheral eosinophilia
    • Immediate scratch test reactivity to Aspergillus antigen
    • Precipitating antibodies to Aspergillus antigen
    • Elevated serum IgE concentrations
    • History of pulmonary infiltrates (transient or fixed)
    • Central bronchiectasis

Diagnosis of Mold-Associated Syndromes

Differential Diagnosis

  • Galactomannan antigen
    • May be used to monitor immunocompromised patients who are experiencing neutropenia
      • Limited sensitivity in non-neutropenic patients
    • Requires a moderate prevalence of invasive aspergillosis in the community; not as useful for monitoring if prevalence is low
  •  (1,3)-β-D-glucan (Fungitell)
    • May be used to monitor immunocompromised patients who are experiencing neutropenia; most experience is with monitoring for invasive aspergillosis and candidiasis
    • Test has high negative predictive value; false negatives uncommon

Mold infections range in spectrum from colonization to hypersensitivity reactions. In addition, opportunistic molds have become increasingly recognized as a cause of life-threatening invasive infection in severely ill or immunocompromised patients.

Epidemiology

  • Invasive fungal disease occurs most commonly in immunocompromised patients

Etiology

  • Molds most often associated with significant disease include the following
    • Hyaline molds (three most common)
      • Aspergillus fumigatus (A)
      • Fusarium spp (F)
      • Scedosporium spp (S)
    • Zygomycetes
      • Hallmarks of Zygomycetes infection are vascular invasion and tissue necrosis (presence of black tissue)
    • Dematiaceous fungi
      • Includes a large group of darkly pigmented organisms

Risk Factors

Mold-associated Signs and Symptoms – Pulmonary

Mold-associated Signs and Symptoms – Sites Other than Pulmonary

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Aspergillus Antibodies by CF and ID 0050101
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion

Allergen, Fungi and Molds, Aspergillus fumigatus 0055061
Method: Quantitative ImmunoCAP Fluorescent Enzyme Immunoassay

Aspergillus Galactomannan Antigen by EIA, Serum 0060068
Method: Semi-quantitative Enzyme Immunoassay

Limitations 

Negative results do not rule out invasive aspergillosis

Many agents may cross-react with test (food, antibiotics, etc)

Follow-up 

Recommend serial sampling for high-risk patients if suspicion is high

Single positive test result (index ≥0.5) should be confirmed by separate serum specimen

Aspergillus Galactomannan Antigen by EIA, Bronchoscopy 2003150
Method: Semi-quantitative Enzyme Immunoassay

Fungal Culture 0060149
Method: Culture/Identification

Fungal Stain, KOH with Calcofluor White 2004589
Method: Microscopy

Limitations 

Difficult to identify type of fungus from a smear

Fungal (Mold/Yeast) Identification 0060163
Method: Identification. Methods may include biochemical, mass spectrometry, or sequencing.

Limitations 

Testing to differentiate between Candida albicans and C. dubliniensis performed by request only 

Blood Culture, Fungal 0060070
Method: Continuous Monitoring Blood Culture/Identification

Limitations 

Poor sensitivity for Aspergillus spp, Zygomycetes, and dematiaceous fungi

Aspergillus fumigatus Antibody, IgG by ELISA 0097771
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

(1,3)-Beta-D-Glucan (Fungitell) 2002434
Method: Semi-Quantitative Colorimetry

Limitations 

Does not detect fungal species that produce very low levels of (1,3)-β-D-glucan (eg, Cryptococcus)

Does not detect Zygomycetes spp, which are not known to produce (1,3)-β-D-glucan (eg, Absidia, Mucor, Rhizopus)

In addition, the yeast phase of Blastomyces dermatitidis may not be detected by the assay

Antimicrobial Susceptibility - Fungal (Yeasts and Molds) 2009257
Method: Broth Microdilution

General References

Ambasta A, Carson J, Church DL. The use of biomarkers and molecular methods for the earlier diagnosis of invasive aspergillosis in immunocompromised patients Med Mycol. 2015; 53(6): 531-57. PubMed

Chandrasekar P. Diagnostic challenges and recent advances in the early management of invasive fungal infections. Eur J Haematol. 2010; 84(4): 281-90. PubMed

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. Infections caused by Scedosporium spp. Clin Microbiol Rev. 2008; 21(1): 157-97. PubMed

Dannaoui E. Molecular tools for identification of Zygomycetes and the diagnosis of zygomycosis. Clin Microbiol Infect. 2009; 15 Suppl 5: 66-70. PubMed

Hage CA, Knox KS, Davis TE, Wheat LJ. Antigen detection in bronchoalveolar lavage fluid for diagnosis of fungal pneumonia. Curr Opin Pulm Med. 2011; 17(3): 167-71. PubMed

Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. β-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011; 52(6): 750-70. PubMed

Mantadakis E, Samonis G. Clinical presentation of zygomycosis. Clin Microbiol Infect. 2009; 15 Suppl 5: 15-20. PubMed

O'Bryan TA. Pseudallescheriasis in the 21st century. Expert Rev Anti Infect Ther. 2005; 3(5): 765-73. PubMed

Oz Y, Kiraz N. Diagnostic methods for fungal infections in pediatric patients: microbiological, serological and molecular methods. Expert Rev Anti Infect Ther. 2011; 9(3): 289-98. PubMed

Rodriguez-Tudela JL, Berenguer J, Guarro J, Kantarcioglu S, Horre R, de Hoog S, Cuenca-Estrella M. Epidemiology and outcome of Scedosporium prolificans infection, a review of 162 cases. Med Mycol. 2009; 47(4): 359-70. PubMed

Vennewald I, Klemm E. Otomycosis: Diagnosis and treatment. Clin Dermatol. 2010; 28(2): 202-11. PubMed

Wheat LJ, Walsh TJ. Diagnosis of invasive aspergillosis by galactomannan antigenemia detection using an enzyme immunoassay. Eur J Clin Microbiol Infect Dis. 2008; 27(4): 245-51. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Blaschke AJ, Bender J, Byington CL, Korgenski K, Daly J, Petti CA, Pavia AT, Ampofo K. Gordonia species: emerging pathogens in pediatric patients that are identified by 16S ribosomal RNA gene sequencing. Clin Infect Dis. 2007; 45(4): 483-6. PubMed

Hanson KE, Pfeiffer CD, Lease ED, Balch AH, Zaas AK, Perfect JR, Alexander BD. β-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study. PLoS One. 2012; 7(8): e42282. PubMed

Hurst SF, Kidd SE, Morrissey CO, Snelders E, Melchers WJ, Castelli MV, Mellado E, Simmon K, Petti CA, Richardson S, Zhang S, Romanelli AM, Wickes BL, de Valk HA, Klaassen CH, Balajee A. Interlaboratory reproducibility of a single-locus sequence-based method for strain typing of Aspergillus fumigatus. J Clin Microbiol. 2009; 47(5): 1562-4. PubMed

Pickering JW, Sant HW, Bowles CA, Roberts WL, Woods GL. Evaluation of a (1->3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol. 2005; 43(12): 5957-62. PubMed

Pounder JI, Hansen D, Woods GL. Identification of Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species by repetitive-sequence-based PCR. J Clin Microbiol. 2006; 44(8): 2977-82. PubMed

Pounder JI, Simmon KE, Barton CA, Hohmann SL, Brandt ME, Petti CA. Discovering potential pathogens among fungi identified as nonsporulating molds. J Clin Microbiol. 2007; 45(2): 568-71. PubMed

Pounder JI, Williams S, Hansen D, Healy M, Reece K, Woods GL. Repetitive-sequence-PCR-based DNA fingerprinting using the Diversilab system for identification of commonly encountered dermatophytes. J Clin Microbiol. 2005; 43(5): 2141-7. PubMed

Rickerts V, Khot PD, Ko DL, Fredricks DN. Enhanced fungal DNA-extraction from formalin-fixed, paraffin-embedded tissue specimens by application of thermal energy. Med Mycol. 2012; 50(6): 667-72. PubMed

Medical Reviewers

Last Update: August 2016