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Standardization of Aspergillus PCR is needed

Bone Marrow Transplantation volume 46, page 1018 (2011)Cite this article

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Meije et al. report in their letter ‘Silent and prolonged Aspergillus DNAemia in oncohematological patients receiving antifungal prophylaxis: a new phenomenon with clinical implications’ that Aspergillus PCR was a relevant and useful diagnostic tool in early detection of invasive aspergillosis (IA). This is in contrast to what we reported recently.1 Meije et al. report on six patients with IA for whom Aspergillus fumigatus PCR tests were persistently positive for several weeks before galactomannan Ag test turned positive and clinical symptoms developed. In our study, we followed patients undergoing reduced-intensity conditioning allogeneic hematopoietic SCT with weekly fungal PCR during the first 100 days post transplantation. We found that a single positive PCR test was not associated with IA. This is consistent with the findings of several other authors, including a study by Meije et al. that reported a low positive predictive value using a single positive PCR test.2 Regarding the association between multiple positive PCR tests and proven and probable IA that Meije et al. report in their letter, we could not draw any conclusion in our study because of low numbers.

Our study differs from the experience of Meije et al. in that we did not find Aspergillus PCR to be useful in establishing the diagnosis of IA. One possible explanation for the differences between our study and the report by Meije et al. is that they may be due to the different fungal prophylaxes, fluconazole in our study vs itraconazole in the study by Meije et al. Another important reason for the differences in results between different centers is the lack of standardization of Aspergillus PCR. This is also indicated in a recent study evaluating Aspergillus PCR within the AmBiLoad trial.3 Using a nested Aspergillus PCR assay, the authors found that 43% of patients with proven and 39% of patients with probable invasive fungal infection had at least one positive test.3 However, when the authors analyzed the 43 positive samples with a quantitative PCR assay, only three turned out to be positive. Hopefully, the ongoing work of the European Aspergillus PCR initiative4 will eventually lead to a standardization enabling multicenter studies and comparison between different clinical centers.

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References

  1. Blennow O, Remberger M, Klingspor L, Omazic B, Fransson K, Ljungman P et al. Randomized PCR-based therapy and risk factors for invasive fungal infection following reduced-intensity conditioning and hematopoietic SCT. Bone Marrow Transplant 2010; 45: 1710–1718.

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  2. Cuenca-Estrella M, Meije Y, Diaz-Pedroche C, Gomez-Lopez A, Buitrago MJ, Bernal-Martinez L et al. Value of serial quantification of fungal DNA by a real-time PCR-based technique for early diagnosis of invasive Aspergillosis in patients with febrile neutropenia. J Clin Microbiol 2009; 47: 379–384.

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  3. Hummel M, Spiess B, Cornely OA, Dittmer M, Morz H, Buchheidt D . Aspergillus PCR testing: results from a prospective PCR study within the AmBiLoad trial. Eur J Haematol 2010; 85: 164–169.

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  4. White PL, Bretagne S, Klingspor L, Melchers WJ, McCulloch E, Schulz B et al. Aspergillus PCR: one step closer to standardization. J Clin Microbiol 2010; 48: 1231–1240.

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, Karolinska University Hospital and Karolinska Institute, Huddinge, Stockholm, Sweden

    O Blennow

  2. Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Karolinska Institute, Huddinge, Stockholm, Sweden

    J Mattsson

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  1. O Blennow
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  2. J Mattsson
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Correspondence to O Blennow.

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Blennow, O., Mattsson, J. Standardization of Aspergillus PCR is needed. Bone Marrow Transplant 46, 1018 (2011). https://doi.org/10.1038/bmt.2010.220

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