What is Galactomannan?
Galactomannan is a polysaccharide component of the Aspergillus cell wall that is released into circulation during fungal growth and serves as a highly sensitive and specific biomarker for diagnosing invasive aspergillosis in immunocompromised patients. 1, 2
Structure and Detection
Galactomannan (GM) is a polysaccharide antigen located in the cell wall structure of Aspergillus species that is released by growing hyphae into the host's bloodstream and other body fluids. 2, 3
The antigen is detected using an enzyme-linked immunosorbent assay (ELISA), commercially available as Platelia® Aspergillus, which measures galactomannan concentration as an optical density index (ODI). 1
Diagnostic Performance in High-Risk Patients
In granulocytopenic and hematologic malignancy patients, galactomannan ELISA demonstrates 80-100% sensitivity and 90-100% specificity, with a negative predictive value exceeding 90% for excluding invasive aspergillosis. 1, 4
The test performs optimally when two consecutive serum samples show an ODI ≥0.5, which is the current recommended cut-off for positivity. 1, 4
At the 0.5 ODI threshold, sensitivity is 82% and specificity is 81%; increasing the cut-off to 1.5 ODI improves specificity to 93% but reduces sensitivity to 61%. 5
Galactomannan may become positive before clinical suspicion of infection arises, enabling pre-emptive diagnosis and earlier treatment initiation. 1
Testing Strategy and Frequency
Testing should be performed at least twice weekly (every 3-4 days) in high-risk patients because galactomannan circulation is transient. 1, 4
Routine screening is recommended for patients with hematologic malignancies, neutropenia, hematopoietic stem cell transplant recipients, and solid organ transplant recipients. 4
The test can detect galactomannan from several Aspergillus species, not just Aspergillus fumigatus. 1
Detection in Other Body Fluids
Galactomannan detection in bronchoalveolar lavage (BAL) fluid is superior to serum testing for localized pulmonary disease, with sensitivity of 80-100% and optimal cut-off values between 0.5 and 1.0 ODI. 4, 6
In cerebrospinal fluid (CSF), galactomannan detection appears superior to culture and some PCR assays for identifying CNS aspergillosis. 1
BAL fluid testing is strongly recommended when serum galactomannan is negative but clinical suspicion remains high. 4
Critical Limitations: False Positives
False-positive results occur in up to 8% of blood samples, most commonly in patients receiving piperacillin-tazobactam or other β-lactam antibiotics. 1, 6
Antibiotic interference accounts for 50-58.3% of false-positive BAL galactomannan results. 6
Other causes of false positivity include infection with non-Aspergillus fungi and certain food products. 7
Despite potential false positives, high-risk patients with positive galactomannan should be treated immediately given the high mortality of untreated invasive aspergillosis. 6
Role in Therapeutic Monitoring
Serial galactomannan testing can facilitate therapeutic monitoring, with progressive decreases in ODI during the first two weeks predicting satisfactory treatment response. 1, 8, 6
However, duration of therapy should be determined by resolution of clinical and radiological findings, not solely by normalization of galactomannan antigenemia. 1
The use of serial galactomannan for therapeutic monitoring remains investigational. 1
Clinical Impact on Diagnosis
Introduction of routine galactomannan testing significantly increases detection rates of invasive aspergillosis compared to conventional culture-based methods alone. 9
The test is particularly valuable when invasive diagnostic procedures (bronchoscopy, biopsy) are contraindicated due to thrombocytopenia, coagulopathy, or hemodynamic instability. 1
Not Recommended For
Galactomannan testing is NOT recommended for diagnosing allergic bronchopulmonary aspergillosis (ABPA) due to poor diagnostic accuracy in this non-invasive condition. 1
- Routine Aspergillus antibody testing is also not recommended in immunocompromised patients, as antibodies are frequently undetectable in this population. 1