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Proven Invasive Pulmonary Aspergillosis in Stem Cell Transplant Recipient Due to Aspergillus sublatus, a Cryptic Species of A. nidulans

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Abstract

Invasive fungal disease represents one of the severe complications in haematopoietic stem cell transplant recipients. We describe a case of a patient treated for relapse of chronic lymphoblastic leukaemia 6 years after HSCT. The patient was treated for invasive pulmonary aspergillosis but died 3 months later from multiple organ failures consisting of haemorrhagic necrotizing fungal pneumonia, refractory chronic hepatic graft versus host disease and cytomegalovirus hepatitis. Autopsy samples revealed histopathological evidence of fungal hyphae and an unusual Aspergillus nidulans-like species was isolated in pure culture. More precise identification was achieved by using scanning electron microscopy of ascospores and sequencing of calmodulin gene, and the isolate was subsequently re-identified as A. sublatus (section Nidulantes) and showed good in vitro susceptibility against all classes of antifungals. Commonly used ITS rDNA region and β-tubulin gene fail to discriminate A. sublatus from related pathogenic species, especially A. quadrilineatus and A. nidulans. Although this is the first case of proven IPA attributed to A. sublatus, we demonstrated that at least some previously reported infections due to A. quadrilineatus were probably caused by this cryptic species.

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Acknowledgements

We want to acknowledge Dana Michalska for the performance of culture and molecular-biology-based methods, Milena Antuskova for the sequence analysis, Eva Klapkova for the HPLC performance, Alena Kubatova for providing SEM photos and Zeljko Jurjevic for providing environmental isolates of A. sublatus.

Author’s Contribution

Vanda Chrenkova—microbiological examination of autopsy samples, main text preparation, corresponding author Vit Hubka—phylogenetic analysis, identification of Aspergillus, methods and figure, discussion. Petr Cetkovsky—clinical case report. Michal Kouba—clinical case report, radiology findings. Barbora Weinbergerova—clinical data collection. Pavlina Lyskova—experimental work. Ludmila Hornofova—autopsy and histopathological examination, photography. Petr Hubacek—clinical case report, supervisor, main text revision.

Funding

This research was supported by the project of Ministry of Health of the Czech Republic for conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic), by the project BIOCEV (CZ.1.05/1.1.00/02.0109) provided by the Ministry of Education, Youth and Sports of CR and ERDF and by FIND (Fungal InfectioN Database)—the project of the CzEch Leukemia study group for Life (CELL). Vit Hubka is grateful for support from Czechoslovak Microscopy Society (CSMS scholarship 2016).

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Authors and Affiliations

  1. Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 15006, Prague 5, Czech Republic

    Vanda Chrenkova & Petr Hubacek

  2. Department of Botany, Faculty of Science, Charles University, Benátská 2, 128 01, Prague 2, Czech Republic

    Vit Hubka

  3. Laboratory of Fungal Genetics and Metabolism, Institute of Microbiology Academy of Science of the Czech Republic, v.v.i, Vídeňská 1083, 142 20, Prague 4, Czech Republic

    Vit Hubka

  4. Institute of Haematology and Blood Transfusion, Prague, Czech Republic

    Petr Cetkovsky & Michal Kouba

  5. Department of Internal Medicine - Haematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic

    Barbora Weinbergerova

  6. Laboratory of Medical Mycology, Department of Parasitology, Mycology and Mycobacteriology Prague, Public Health Institute in Usti nad Labem, Prague, Czech Republic

    Pavlina Lyskova

  7. Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

    Ludmila Hornofova

  8. Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

    Petr Hubacek

Authors
  1. Vanda Chrenkova
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  2. Vit Hubka
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  3. Petr Cetkovsky
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  5. Barbora Weinbergerova
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  6. Pavlina Lyskova
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  7. Ludmila Hornofova
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  8. Petr Hubacek
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Correspondence to Vanda Chrenkova.

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Chrenkova, V., Hubka, V., Cetkovsky, P. et al. Proven Invasive Pulmonary Aspergillosis in Stem Cell Transplant Recipient Due to Aspergillus sublatus, a Cryptic Species of A. nidulans . Mycopathologia 183, 423–429 (2018). https://doi.org/10.1007/s11046-017-0223-8

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  • DOI: https://doi.org/10.1007/s11046-017-0223-8

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