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Publications

Journal Article Ahead of print

PubMed: 42858895 DOI: 10.1016/j.cmi.2026.10.002

Non-invasive diagnosis of invasive aspergillosis in patients with haematological malignancies: a prospective diagnostic accuracy study.

Clin Microbiol Infect

Authors: Rutuja H Patil, Radim Dobiáš, Yuri Vanbiervliet, Robina Aerts, Katrien Lagrou, Johan Maertens, David A Stevens, Vladimír Havlíček

Affiliations

  • Institute of Microbiology of the Czech Academy of Sciences, 142 20 Prague, Czechia; EFISG-ESCMID Fungal Infection Study Group, 4051 Basel, Switzerland.
  • Public Health Institute in Ostrava, Ostrava, Czechia; Institute of Laboratory Medicine, Faculty of Medicine, University of Ostrava, Ostrava, Czechia; Lab4Life Ostrava FNOU, Ostrava, Czechia.
  • EFISG-ESCMID Fungal Infection Study Group, 4051 Basel, Switzerland; Department of Haematology, University Hospitals Leuven, Leuven, Belgium; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • EFISG-ESCMID Fungal Infection Study Group, 4051 Basel, Switzerland; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; Department of Pneumology, University of Antwerp, Antwerp, Belgium.
  • EFISG-ESCMID Fungal Infection Study Group, 4051 Basel, Switzerland; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; Department of Laboratory Medicine and National Reference Centre for Mycosis, University Hospitals Leuven, Leuven, Belgium.
  • Department of Haematology, University Hospitals Leuven, Leuven, Belgium; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, United States of America.
  • Institute of Microbiology of the Czech Academy of Sciences, 142 20 Prague, Czechia; EFISG-ESCMID Fungal Infection Study Group, 4051 Basel, Switzerland; Department of Analytical Chemistry, Palacký University, Olomouc, Czechia.

Abstract

OBJECTIVES

To evaluate a non-invasive panel integrating urinary triacetylfusarinine C normalised to creatinine (uTafC/Cr), serum galactomannan (sGM) and serum pentraxin-3 (sPtx3) for detection of invasive aspergillosis (IA) in patients with haematological malignancies.

METHODS

Prospectively collected urine and serum from 148 clinical episodes in 138 high-risk patients with haematological malignancies (Leuven, 2018-2021) were analysed in a diagnostic accuracy study (37 proven/probable IA episodes from 37 patients; 111 control episodes from 104 patients). Median sampling days relative to the diagnostic reference day (day 0) were +1 for urine uTafC/Cr, 0 for sGM and +2 for sPtx3. uTafC/Cr was quantified by liquid chromatography-mass spectrometry (LC-MS); sGM and sPtx3 by enzyme immunoassays. Prespecified cut-offs were used for sGM and uTafC/Cr; sPtx3 positivity was receiver operating characteristic-derived. Analytical TafC stability and the relative analytical sensitivity of LC-MS and MALDI-MS were assessed in validation experiments.

RESULTS

sGM and uTafC/Cr showed no false positives in available control episodes (sGM, 0/98; uTafC/Cr, 0/111) and each detected 51.4% of IA episodes (19/37). sPtx3 alone showed sensitivity of 70.3% (26/37) and specificity of 58.3% (21/36). Adding sPtx3 to the uTafC/Cr or sGM pair increased case detection to 83.8% (31/37), with lower specificity in the complete-case control episode subset (57.6%; 19/33 control episodes). In a ±72 h paired-window analysis, bronchoalveolar lavage fluid (BALF) mycology, defined as BALF GM, Aspergillus PCR and/or fungal culture, was positive in 19/23 tested IA episodes (82.6%; 95% CI, 62.9-93.0%). TafC was stable at 4 °C, and LC-MS was more sensitive than MALDI-MS.

CONCLUSIONS

uTafC/Cr or sGM provides an Aspergillus-focused non-invasive adjunct to BALF-based testing; sPtx3 increased case detection but had limited specificity and requires prospective validation.

MeSH

Serum, Microbiology, Parasitic Diseases, Diagnosis, Communicable Diseases, Aspergillosis, Infections, Pentraxins