Gewählte Publikation:
Eigl, S.
Invasive Mould Infections in Patients with Haematological Malignancies: Novel Diagnostic Approaches
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2019. pp.115
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
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Flick Holger
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Hönigl Martin
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Neumeister Peter
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- Abstract:
- Introduction
The inability to make an early and convincing diagnosis still remains a central problem in the diagnosis of invasive aspergillosis (IA). In the last years new diagnostic tests were developed. Galactomannan testing (GM) and Aspergillus PCR have both become essential for diagnosis of IA in patients with haematological malignancies. Whether or not PCR and GM need to be performed in bronchoalveolar lavage fluid (BALF), a sample from the direct site of infection, or testing of blood samples is sufficient, remains unknown.
Methods
We evaluated the diagnostic performance of GM ELISA, and Aspergillus specific PCR by using BALF samples and blood specimens obtained at the same day. In case of suspected IA and when a diagnostic bronchoscopy was performed in clinical routine, BALF aliquots were reserved for study purposes and additionally whole blood sample were collected within 24 hours of bronchoscopy. GM testing was performed at the Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria. BALF aliquots together with whole blood samples, were shipped overnight to the scientific laboratory in Mannheim, Germany for BALF Aspergillus specific and panfungal PCR testing. Additionally, we expand our cohort by including cases from Mannheim, which were enrolled retrospectively.
Results
A total of 53 immunosuppressed patients were included in the final analysis, with 16 probable/proven IA and 37 with no evidence of IA according to the revised EORTC/MSG criteria. 38 patients with haematological malignancies were prospectively enrolled at the Medical University of Graz, Austria, 15 patients with mixed underlying diseases at the Mannheim University Hospital, Germany. Patients with possible IA were excluded from this analysis. A total of 34/53 (64%) of all patients and12/16(75%) of patients with probable/proven IA received antifungal treatment at the time of the BALF recovery. Sensitivities of Aspergillus PCR and GM were 44% and 38% in BALF, and 0% and 31% in blood, respectively. BALF PCR results demonstrated to be superior (sensitivity 44%, specificity 100%) compared to blood PCR. Combination of BALF Aspergillus PCR, BALF GM (>1.0 ODI), BALF-culture and/or serum GM (>0.5ODI) resulted in the highest sensitivity (75%) for probable/proven IA cases.
Conclusion
In conclusion sensitivity was low in every evaluated diagnostic test when interpreted on their own (low in BALF and even lower in blood). In our patient cohort diagnostic test combination resulted in a significant higher diagnostic performance and could improve diagnosis and management of invasive aspergillosis. In addition, combination of PCR and GM testing and culture from BALF resulted in higher sensitivities, without markedly impacting specificity.