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Clinical features and cause analysis of false positive results of Aspergillus galactomannan assay in pulmonary cryptococcosis patients

  • Takahiro TakazonoEmail author
  • Tomomi Saijo
  • Nobuyuki Ashizawa
  • Kazuhiro Oshima
  • Keitaro Nishimura
  • Masato Tashiro
  • Kazuko Yamamoto
  • Yoshifumi Imamura
  • Taiga Miyazaki
  • Katsunori Yanagihara
  • Hiroshi Mukae
  • Koichi Izumikawa
  • Donald C. Sheppard
Original Article
  • 51 Downloads

Abstract

There have been conflicting reports of false positive galactomannan assay results in patients with systemic cryptococcosis. We sought to determine the frequency of GM positivity in patients with pulmonary cryptococcosis and confirm the source of this cross-reactivity in vitro. We conducted a retrospective study to elucidate the rate of galactomannan (GM) false positivity and cause in a cohort of 29 patients with pulmonary cryptococcal disease. The production of GM cross-reacting substances by clinical isolates and laboratory isolates of C. neoformans was tested in vitro. The mean serum GM index (Platelia Aspergillus) in patients with pulmonary cryptococcosis was 1.06, with 16 (55.2%) of patients having values above the positive cutoff value of 0.5. GM index values significantly decreased after treatment of cryptococcosis. There was no significant correlation between galactomannan and cryptococcal glucuronoxylomannan antigen (Eiken Latex test) results. Culture supernatants from clinical isolates and wild-type C. neoformans did not react in the GM assay; however, growth in the presence of 6% sodium chloride induced the production of cross-reacting GM antigens in culture supernatants from clinical isolates, wild type and a glucuronoxylomannan-deficient mutant of C. neoformans, but not in culture supernatants from a galactoxylomannan-deficient strain. Our results support the cross-reactivity of cryptococcal galactoxylomannan with the serum GM assay in vitro and in patients with pulmonary cryptococcal infection.

Keywords

Galactomannan Cryptococcosis Cryptococcus neoformans False positive Aspergillus Galactoxylomannan 

Notes

Acknowledgements

We gratefully acknowledge Dr. Jennifer K. Lodge, Washington University School of Medicine, and Dr. Guilhem Janbon, Pasteur Institute, for providing us with C. neoformans strains.

Funding

DCS was supported by a Foundation award from the Canadian Institutes of Health Research (FDN 159902) and a Research Chair from the Fonds de Recherche Quebec Santé.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Nagasaki University School of Medicine Research Ethics Committee (Approval no. 16082210).

Informed consent

As this study was a retrospective cohort study, written informed consent was not obtained. However, after approval from the ethics committee of our institute, we have shown the document of “Disclosure of information on clinical research” in our homepage to give the subjects opportunity to declare their will not to participate in this study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Takahiro Takazono
    • 1
    • 2
    • 3
    • 4
    Email author
  • Tomomi Saijo
    • 2
  • Nobuyuki Ashizawa
    • 2
  • Kazuhiro Oshima
    • 2
  • Keitaro Nishimura
    • 1
  • Masato Tashiro
    • 1
  • Kazuko Yamamoto
    • 2
  • Yoshifumi Imamura
    • 2
  • Taiga Miyazaki
    • 1
    • 2
  • Katsunori Yanagihara
    • 5
  • Hiroshi Mukae
    • 2
  • Koichi Izumikawa
    • 1
  • Donald C. Sheppard
    • 3
    • 4
  1. 1.Department of Infectious Diseases, Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan
  2. 2.Second Department of Internal MedicineNagasaki University HospitalNagasakiJapan
  3. 3.Departments of Medicine, Microbiology and ImmunologyMcGill UniversityQuébecCanada
  4. 4.Infectious Diseases and Immunity in Global Health ProgramResearch Institute of the McGill University Health CentreQuébecCanada
  5. 5.Department of Laboratory MedicineNagasaki University HospitalNagasakiJapan

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