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Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high-risk haematology patients.

Journal article
Authors Helena Hammarström
Anna Stjärne Aspelund
Bertil Christensson
Claus Peter Heußel
Jenny Isaksson
Nahid Kondori
Lennart Larsson
Pawel Markowicz
Johan Richter
Christine Wennerås
Vanda Friman
Published in Mycoses
Volume 61
Issue 9
Pages 623-632
ISSN 1439-0507
Publication year 2018
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Biomedicine, Department of Infectious Medicine
Pages 623-632
Language en
Subject categories Clinical Medicine, Infectious Medicine


We prospectively evaluated a combination of fungal biomarkers in adult haematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once to twice weekly for serum (1-3)-ß-d-glucan (BG), galactomannan (GM), bis-methyl-gliotoxin and urinary d-arabinitol/l-arabinitol ratio. In all, 13 cases with proven or probable invasive fungal disease (IFD) were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2 weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly specific for IFD. At a pre-test probability of 12%, both BG and GM had negative predictive values (NPV) >0.9 but low positive predictive values (PPV). In a subgroup analysis of patients with clinically suspected IFD (pre-test probability of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut-off 160 pg/mL. Among IFD patients, 91% had patterns of consecutively positive and increasing BG levels. Bis-methyl-gliotoxin was undetectable in 15 patients with proven, probable and possible IA. To conclude, BG was the superior fungal marker for IFD diagnosis. Quantification above the limit of detection and graphical evaluation of the pattern of dynamics are warranted in the interpretation of BG results.

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