Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis

Elaine McCulloch, Gordon Ramage, Ranjith Rajendran, David F Lappin, Brian Jones, Peter Warn, Raghdaa Shrief, William R Kirkpatrick, Thomas F Patterson, Craig Williams

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)83-6
Number of pages4
JournalJournal of Clinical Pathology
Volume65
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

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Aspergillosis
Clinical Laboratory Techniques
caspofungin
Antifungal Agents
Therapeutics
Echinocandins
Polyenes
Azoles
Aspergillus fumigatus
Amphotericin B
Infection
Immunoenzyme Techniques
Routine Diagnostic Tests
Inhalation
galactomannan
Early Diagnosis
Antigens
Polymerase Chain Reaction
Lung
DNA

Keywords

  • Amphotericin B
  • Animals
  • Antifungal Agents
  • Aspergillus fumigatus
  • Biomarkers
  • DNA, Fungal
  • Disease Models, Animal
  • Early Diagnosis
  • Echinocandins
  • Immunoenzyme Techniques
  • Invasive Pulmonary Aspergillosis
  • Mannans
  • Microbiological Techniques
  • Mycological Typing Techniques
  • Predictive Value of Tests
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Time Factors
  • Triazoles

Cite this

McCulloch, Elaine ; Ramage, Gordon ; Rajendran, Ranjith ; Lappin, David F ; Jones, Brian ; Warn, Peter ; Shrief, Raghdaa ; Kirkpatrick, William R ; Patterson, Thomas F ; Williams, Craig. / Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis. In: Journal of Clinical Pathology. 2012 ; Vol. 65, No. 1. pp. 83-6.
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McCulloch, E, Ramage, G, Rajendran, R, Lappin, DF, Jones, B, Warn, P, Shrief, R, Kirkpatrick, WR, Patterson, TF & Williams, C 2012, 'Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis' Journal of Clinical Pathology, vol. 65, no. 1, pp. 83-6. https://doi.org/10.1136/jcp.2011.090464

Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis. / McCulloch, Elaine; Ramage, Gordon; Rajendran, Ranjith; Lappin, David F; Jones, Brian; Warn, Peter; Shrief, Raghdaa; Kirkpatrick, William R; Patterson, Thomas F; Williams, Craig.

In: Journal of Clinical Pathology, Vol. 65, No. 1, 01.2012, p. 83-6.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis

AU - McCulloch, Elaine

AU - Ramage, Gordon

AU - Rajendran, Ranjith

AU - Lappin, David F

AU - Jones, Brian

AU - Warn, Peter

AU - Shrief, Raghdaa

AU - Kirkpatrick, William R

AU - Patterson, Thomas F

AU - Williams, Craig

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N2 - 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.

AB - 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.

KW - Amphotericin B

KW - Animals

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KW - Aspergillus fumigatus

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KW - DNA, Fungal

KW - Disease Models, Animal

KW - Early Diagnosis

KW - Echinocandins

KW - Immunoenzyme Techniques

KW - Invasive Pulmonary Aspergillosis

KW - Mannans

KW - Microbiological Techniques

KW - Mycological Typing Techniques

KW - Predictive Value of Tests

KW - Rats

KW - Real-Time Polymerase Chain Reaction

KW - Time Factors

KW - Triazoles

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DO - 10.1136/jcp.2011.090464

M3 - Article

VL - 65

SP - 83

EP - 86

JO - Journal of Clinical Pathology

JF - Journal of Clinical Pathology

SN - 0021-9746

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