Serum Galactomannan

Indications

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)

Diagnosis of Mucormycosis (see Mucormycosis)

Recommendations (ESCMID/ECMM Mucormycosis Guidelines) (Clin Microbiol Infect, 2014) [MEDLINE]

  • 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]

False-Positive Serum Galactomannan

  • Administration of Contaminated Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin, Intravenous Immunoglobulin)
    • Epidemiology: in one study, transmission of galactomannan positivity occurred in some IVIG recipients (Clin Infect Dis, 2016) [MEDLINE]
  • Children
    • Epidemiology: controversial if children have higher rates of false-positive serum galactomannan than adults (Pediatr Infect Dis J, 2007) [MEDLINE]
  • Cross-Reactivity with Other Filamentous Ascomycetes Fungi
  • Following Hematopoietic Stem Cell Transplant (HSCT) (see Graft vs Host Disease, Graft vs Host Disease)
    • 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
  • Mucositis (see Mucositis, Mucositis)
    • 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]
  • Use of Amoxicillin-Clavulanic Acid (see Amoxicillin-Clavulanic Acid, Amoxicillin-Clavulanic Acid): however, this formulation is not available in the United States (J Clin Microbiol, 2004) [MEDLINE]
  • Use of Piperacillin-Tazobactam (Zosyn) (see Piperacillin-Tazobactam, Piperacillin-Tazobactam)
    • 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]
  • False-positive Aspergillus galactomannan antigenaemia after haematopoietic stem cell transplantation. J Antimicrob Chemother. 2008;61(2):411[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 testing during mold-active prophylaxis. Clin Infect Dis. 2014 Dec;59(12):1703-4 [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]