Monitoring Aspergillus Biomarkers : A Two Centres Approach

Ref ID: 19562

Author:

J Springer1*, RA Barnes2, WJ Heinz1, AJ Ullmann1, H Einsele1, J Loeffler1, PL White2

Author address:

1Medizinische Klinik und Poliklinik II, University Hospital, Wuerzburg, Germany
2Microbiology, Public Health Wales, Cardiff, United Kingdom

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Invasive aspergillosis (IA) remains a major complication in patients with haematological malignancies
(HM) and after allogeneic haematopoietic cell transplantation (HCT). In these patients, IA is the
most common cause of mortality due to infection. Early detection of Aspergillus infections would
have the potential to facilitate a more effective management of invasive disease. The optimal blood
fraction for detecting Aspergillus DNA has still to be determined and different fractions will provide
different DNA sources. Free circulating fungal DNA (DNAemia) is likely to be available in plasma
and serum, but the differences in obtaining these cell free fractions (presence of blood clot) may alter
the availability of free DNA.
Therefore we evaluated the sensitivity of different blood fractions (plasma and serum) for the
detection of free circulating Aspergillus DNA in patients with HM.
Methods:
The centres in Cardiff and Wuerzburg collected consecutive samples from HM patients undergoing
chemotherapy or HCT. Blood samples were collected twice weekly from all study patients classified
according to the European Organization for Research and Treatment of Cancer consensus criteria.
In detecting Aspergillus DNA in plasma (centre 1) or serum (centre 2) methods conforming with
European Aspergillus PCR Initiative recommendations were used. Galactomannan and PCR assays
were performed prospectively. Patients with less than 3 samples were excluded from this case
control study.
Results:
In total 65 patients were included over a one-year study period. There were 12 probable and
10 possible IA cases as well as 43 unclassified patients who served as controls.
Overall, 696 blood samples were collected. The PCR positivity for centre 1 testing 388 plasma
samples was 10.8% and for centre 2 testing 308 serum samples was 3.3%. Centre 1 detected 9 of
10 probable cases (90%), one possible IA case (100%) and 13 of 27 unclassified patients, three of
which were also GM ELISA positive. Ten of the 13 unclassified patients showed only one single
positive PCR result. If a threshold of two PCR positive results was used 8 of 10 probable cases
(80%) remained positive and specificity increased to 89%. Centre 2 detected 2 of 2 probable cases
(100%), 2 of 9 possible cases (22%) and 1 of 16 unclassified patients.
PCR positivity rate in centre 1 was 15.3%, 15.5% and 7.8% and for centre 2 8.9%, 3.5% and 0.9%
for probable, possible and unclassified patients, respectively. Negative Predictive Values (NPV)
were high for centre 1 and 2 (0.93 and 1.00; possible IA cases were excluded for the analysis).
Conclusion:
PCR positivity rates appear greater in plasma compared to serum. However, both blood fractions,
plasma and serum, allowed the detection of probable IA cases with high sensitivity. Plasma showed
a higher positivity rate in unclassified patients. Specificity can be increased, if plasma is used as
an add-on biomarker or if at least 2 positive PCR results are considered to start treatment. Further
research testing the concomitant serum samples at centre 1 and plasma samples at centre 2 is being
performed to permit direct performance comparison.

Abstract Number: 89

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17325 posts found.

  • Title

    Author

    Year

    Number

    Poster