Diagnosis of Invasive Aspergillosis in High-Risk Patients (Hematologic Malignancy, Hematopoietic Stem Cell Transplant (see Invasive Aspergillosis)
Recommendations (Infectious Diseases Society of America 2016 Practice Guidelines) (Clin Infect Dis, 2016) [MEDLINE]
Serum Galactomannan is Recommended as an Accurate Marker for the Diagnosis of Invasive Aspergillosis in Adult and Pediatric Patients in Specific Populations (Hematologic Malignancy, Hematopoietic Stem Cell Transplant) (Strong Recommendation, High-Quality Evidence)
Serum Galactomannan is Not Recommended for Routine Blood Screening in Patients Receiving Mold-Active Antifungal Therapy or Prophylaxis, But Can Be Applied to Bronchoscopy Specimens from Those Patients (Strong Recommendation, High-Quality Evidence)
Serum Galactomannan is Not Recommended for Screening in Solid Organ Transplants or Patients with Chronic Granulomatous Disease (Strong Recommendation, High-Quality Evidence)
Serum/Bronchoalveolar Lavage (BAL) Galactomannan May Be Used, But Sensitivity is an Issue (Strength of Recommendation B, Quality of Evidence III)
Technique
Assay
Galactomannan is a Major Polysaccharide Component of the Aspergillus Cell Wall
Commercially Available Platelia Assay Uses a Double Sandwich Enzyme Immunoassay (EIA): FDA-approved for serum and bronchoalveolar lavage (BAL) testing
Galactofuranose is the 6-Member Ring Form of Galactose Synthesized by Non-Mammalian Eukaryotic Pathogens (and Some Prokaryotic Pathogens)
Monoclonal EB-A2 Antibody Detects Multiple Epitopes on Galactofuranose Side Chains (Which Link to the Large Polymer Mannan Backbone)
Importantly, Galactofuranose is Also Present in Some Other Fungi and in Other Substances
Technical Aspects
Sensitivity/Specificity
Meta-Analysis of Serum Galactomannan in the Diagnosis of Invasive Aspergillosis in Immunocompormised Patients (Clin Infect Dis, 2006) [MEDLINE]
Serum Galactomannan Assay Performs Better in Patients with Hematologic Malignancy or Who Have Undergone HSCT
Serum Galactomannan Assay Performance is More Limited in Solid Organ Transplant Recipients
Systematic Review and Meta-Analysis of 50 Studies of Serum Galactomannan for the Diagnosis of Invasive Aspergillosis in Immunocompromised Patients (Cochrane Database Syst Rev, 2015 [MEDLINE]: n = 5660
Using Cut-Off ODI of 0.5 in Population with Disease Prevalence of 9% (Overall Median Prevalence)
Sensitivity: 82% (18% false-negative rate)
Specificity: 81% (19% false-negative rate)
Using Cut-Off ODI of 1.5 in Population with Disease Prevalence of 9% (Overall Median Prevalence)
Sensitivity: 61% (39% false-negative rate)
Specificity: 93% (7% false-negative rate)
False-Negative Serum Galactomannan
Presence of Anti-Aspergillus Antibodies
Localized or Encapsulated Infections
Concurrent Antifungal Therapy
Sensitivity of Galactomannan Assay is Decreased with Concurrent Mold-Active Antifungal Therapy (Clin Infect Dis, 2005) [MEDLINE] (Clin Infect Dis, 2014) [MEDLINE] (Clin Infect Dis, 2014) [MEDLINE]
Epidemiology: false-positive serum galactomannan results are more common during the first 100 days following HSCT and in patients with gastrointestinal tract mucositis (due to chemotherapy or graft vs host disease) (J Antimicrob Chemother, 2008) [MEDLINE]
Physiology: due to gut translocation of galactomannan found in foods and bacteria (Lancet Infect Dis, 2004) [MEDLINE]
Ingestion of Galactomannan-Contaminated Foods (in the Setting of Mucositis)
Foods
Cereals
Ice Pops: have been reported as source when ingested in the setting of gastrointestinal graft vs host disease (N Engl J Med, 2013) [MEDLINE]
Milk
Physiology: ingestion of Aspergillus or Penicillium-contaminated foods (which are sources of galactomannan) with subsequent gut translocation of galactomannan
Epidemiology: false-positive serum galactomannan results are more common during the first 100 days following HSCT and in patients with gastrointestinal tract mucositis (due to chemotherapy or graft vs host disease) (J Antimicrob Chemother, 2008) [MEDLINE]
Physiology: due to gut translocation of galactomannan found in foods and bacteria (Lancet Infect Dis, 2004) [MEDLINE]
Transfusion of Blood Products from Contaminated Bags from Specific Manufacturer (Fresenius Kabi, Germany)
Epidemiology: cases have been reported (Clin Infect Dis, 2012) [MEDLINE]
Historically, the Use of Piperacillin-Tazobactam was Believed to Result in False-Positive Galactomannan Assay Results Due to the Presence of Galactomannan (or Another Cross-Reactive Antigen) in the Antibiotic Formulation
However, More Recent Studies Indicate that Piperacillin-Tazobactam Rarely Reacts with the Assay (J Antimicrob Chemother, 2012)[MEDLINE] (J Clin Microbiol, 2014) [MEDLINE]
References
False-positive Aspergillus galactomannan antigenaemia after haematopoietic stem cell transplantation. Journal of Antimicrobial Chemotherapy (2008) 61, 411–416
False-positive results of Aspergillus enzyme-linked immunosorbent assays for a patient with gastrointestinal graft-versus-host disease taking a nutrient containing soybean protein. Clin Infect Dis 2005; 40: 333 – 4
False-positive Aspergillus galactomannan enzyme-linked immunosorbent assay results in vivo during amoxicillin-clavulanic acid treatment. J Clin Microbiol. 2004;42(11):5362 [MEDLINE]
False-positive results of Aspergillus enzyme-linked immunosorbent assay in a patient with chronic graft-versus-host disease after allogeneic bone marrow trans- plantation. Bone Marrow Transplant 2001; 28: 633–4
False-Positive Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay Results In Vivo during Amoxicillin-Clavulanic Acid Treatment. J Clin Microbiol, Nov. 2004, p. 5362–5363
Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis. 2004;4(6):349 [MEDLINE]
Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis. 2005;40(12):1762 [MEDLINE]
Occurrence and Kinetics of False-Positive Aspergillus Galactomannan Test Results following Treatment with Beta-Lactam Antibiotics in Patients with Hematological Disorders. JOURNAL OF CLINICAL MICROBIOLOGY, Feb. 2006, p. 389–394
Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis. 2006;42(10):1417 [MEDLINE]
False positive galactomannan results in adult hematological patients treated with piperacillin-tazobactam. Rev Iberoam Micol 2007; 24: 106-112
Prospective Aspergillus galactomannan antigen testing in pediatric hematopoietic stem cell transplant recipients. Pediatr Infect Dis J. 2007;26(7):558 [MEDLINE]
Piperacillin/tazobactam (Tazocin™) seems to be no longer responsible for false-positive results of the galactomannan assay. J Antimicrob Chemother. 2012 Jul;67(7):1746-8 [MEDLINE]
False-positive Aspergillus antigenemia due to blood product conditioning fluids. Clin Infect Dis. 2012;55(4):e22 [MEDLINE]
False positive galactomannan test after ice-pop ingestion. N Engl J Med. 2013 Jul;369(1):97-8 [MEDLINE]
Reduction in false-positive Aspergillus serum galactomannan enzyme immunoassay results associated with use of piperacillin-tazobactam in the United States. J Clin Microbiol. 2014 Jun;52(6):2199-201 [MEDLINE]
ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect. 2014 Apr;20 Suppl 3:5-26 [MEDLINE]
Serum galactomannan-based early detection of invasive aspergillosis in hematology patients receiving effective antimold prophylaxis. Clin Infect Dis. 2014 Dec;59(12):1696-702 [MEDLINE]
Galactomannan detection for invasive aspergillosis in immunocompromised patients. Cochrane Database Syst Rev. 2015 [MEDLINE]
Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60. doi: 10.1093/cid/ciw326 [MEDLINE]
Transmission of Hepatitis B Core Antibody and Galactomannan Enzyme Immunoassay Positivity via Immunoglobulin Products: A Comprehensive Analysis. Clin Infect Dis. 2016;63(1):57 [MEDLINE]
