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Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis
  1. Elaine McCulloch1,
  2. Gordon Ramage2,
  3. Ranjith Rajendran2,
  4. David F Lappin2,
  5. Brian Jones3,
  6. Peter Warn4,
  7. Raghdaa Shrief4,
  8. William R Kirkpatrick5,
  9. Thomas F Patterson5,
  10. Craig Williams1
  1. 1Microbiology Department, Royal Hospital for Sick Children, Glasgow, UK
  2. 2Infection and Immunity Research Group, Glasgow Dental School, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  3. 3Glasgow Royal Infirmary, Glasgow, UK
  4. 4The School of Medicine, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  5. 5The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  1. Correspondence to Dr Craig Williams, Department of Microbiology, Royal Hospital for Sick Children, Dalnair Street, Glasgow G3 8SJ, UK; craig.williams{at}ggc.scot.nhs.uk

Abstract

Aims The purpose of this study was to investigate the performance of non-invasive diagnostic tests such as galactomannan enzyme immunoassay and quantitative PCR in the early diagnosis of invasive aspergillosis (IA), and how these tests are impacted upon by the use of different classes of antifungal agents in an in-vivo model of IA.

Methods A standardised rat inhalation model of IA was used to examine the effects of an azole, posaconazole, a polyene, amphotericin B and an echinocandin caspofungin. Daily blood samples were collected for subsequent analysis using a commercially available galactomannan assay and an inhouse qPCR assay.

Results No significant differences were observed in the CE/g of Aspergillus fumigatus in the lungs of each group. qPCR was statistically more sensitive than galactomannan for both the early detection of infected controls (p=0.045) and for overall detection (p=0.018). However, antifungal treatment significantly reduced the overall sensitivity of qPCR (p=0.020); these effects were due to posaconazole and caspofungin. In the latter stages of infection (days 4 and 5) there were no significant differences in the numbers of infections detected by galactomannan and qPCR; however, the antifungal class used caused significant qualitative differences (p=0.041). Galactomannan showed improved detection in posaconazole-treated animals.

Conclusions Previous exposure to antifungal therapy must be considered when interpreting either qPCR or galactomannan-based IA diagnostics as this study has shown that individual classes of antifungal agents impact upon the dynamics of antigen and DNA release into the circulation.

  • Aspergillosis
  • azole
  • diagnostics
  • echinocandin
  • galactomannan
  • haemato-oncology
  • PCR
  • polyene

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Footnotes

  • Funding The authors would like to acknowledge the financial support from Merck Sharp & Dohme and Schering Plough. This project was also supported in part with federal funds from the National Institute of Allergy and Infectious Diseases under contract no NOI-AI-30041.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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