Galactomannan and 1,3-β-d-Glucan Testing for the Diagnosis of Invasive Aspergillosis

Abstract

Invasive aspergillosis (IA) is a severe complication among hematopoietic stem cell transplant recipients or patients with hematological malignancies and neutropenia following anti-cancer therapy. Moreover, IA is increasingly observed in other populations, such as solid-organ transplant recipients, patients with solid tumors or auto-immune diseases, and among intensive care unit patients. Frequent delay in diagnosis is associated with high mortality rates. Cultures from clinical specimens remain sterile in many cases and the diagnosis of IA often only relies on non-specific radiological signs in the presence of host risk factors. Tests for detection of galactomannan- (GM) and 1,3-β-d-glucan (BDG) are useful adjunctive tools for the early diagnosis of IA and may have a role in monitoring response to therapy. However, the sensitivity and specificity of these fungal biomarkers are not optimal and variations between patient populations are observed. This review discusses the role and interpretation of GM and BDG testing for the diagnosis of IA in different clinical samples (serum, bronchoalveolar lavage fluid, cerebrospinal fluid) and different groups of patients (onco-hematological patients, solid-organ transplant recipients, other patients at risk of IA).

Keywords: ">d-glucan; 1,3-β-; Aspergillus fumigatus; fungal biomarkers; galactomannan; invasive aspergillosis.

Figure 1

Proposed algorithm for the use of galactomannan (GM) and 1,3-β-d-glucan (BDG) testing for the diagnosis of invasive aspergillosis (IA) in clinical practice. Based on the following parameters: (1) prevalence of IA in a given population and (2) assessment of the clinical signs and symptoms of IA in a given patient, the clinician may establish the individual pre-test probability on a scale from low to high. While testing of GM and/or BDG may be useful in cases with moderate-high pre-test probability (by changing the post-test probability), interpretation of a positive or negative test is often inconclusive in low risk settings. HSCT: hematopoietic stem cell transplantation. Yellow circles: + positive test, - negative test.