Rapid Diagnostics Aspergillosis L' Joseph Wheat

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Rapid Diagnostics AspergillosisL. Joseph Wheat

• Notes in normal view

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Aspergillosis Diagnosis
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New Lung Nodules
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CT Findings

• Nodules infiltrate
• -Non-specific
• Halo sign
• -60 but nonspecific
• Air crescent/cavitation
• -Late

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Evolution of CT Findings

• Halo early and clears
• Air crescent later as neutopenia resolves

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CNS Involvement Common
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Platelia Aspergillus EIA
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Monitoring in Neutropenia

• AML, MDS, allo HSCT on intense chemoRx or ALL
  on chronic steroids
• Prophylaxis itra capsules or flu if intolerant
• Serum collected twice weekly frozen
• Platelia GM tested twice weekly
• Mean 13 specimens/patient
• Results reported as positive if gt1.0 used in
  patient management

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Confirm Positive by 2nd Test

• Authors conclusions
• Single gt0.5
• lower specificity
• Single gt0.8 or 0.5 x 2
• Improved specificity
• Earlier AFT in 70

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GM CT ? Preemptive Rx

• 19/117 (7.7) consecutive gt0.5
• 9/19 febrile
• Reduction LAmB
• 8 GM directed preemptive Rx
• 35 if not GM directed
• 78 reduction L-AmB
• No missed IA
• Breakthrough IFI
• 2 C. glabrata fungemia dgn by BC
• 1 Zygomycosis dgn at autopsy
• Survival 63

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Anti-Mold Rx ?False-Negative?

• Marr JID 2004
• Cutoff 1.0-reduced sensitivity, 85?15
• Cutoff 0.5-no reduction, 80
• Maertens Br J Haematol 2004
• Itra capsules standard
• Sensitivity 96.5
• Yohnee IDSA 2004, 616
• Overall sensitivity IA 36 (4/11)
• 6/7 false-negative cases on mold-active Rx

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Pip-Tazo ?False-Positive
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Galactomannan Detection in BAL

• Authors conclusions
• GM BAL high PPV
• GM serum less sensitive
• BAL GM neg after 3 days treatment

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Asp GM in BAL at CO gt1.0
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Factors associated with IPA in SOT
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Aspergillus GM in BAL vs. Serum
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False-positive BAL Post Lung TP

• 19 consecutive BALs strongly positive
• GMI 4.1-8.2 ( 10 ng/ml)
• Plasmalyte used for lavage
• 4 lots Plasmalyte strongly positive
• GMI 5.4-5.6 ( 10 ng/ml)
• Na gluconate 500 mg/100 ml
• Produced by A. flavus

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Asp GM False-pos in Histoplasmosis
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Asp GM False-pos in Histoplasmosis
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Hc GM not False-pos in Aspergillosis
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Aspergillus GM Clearance
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Comparion to ß-glucan PCR
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Use Asp GM Ag

• Monitoring antigenemia HSCT
• Always verify in second specimen
• Reduction in treatment
• Workup suspected IA
• BAL superior to serum
• Monitoring treatment?
• Prospective study in progress

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(1?3) Beta-D-glucan (BG) Assay
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BG Sensitivity in IFI
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BG in ICU
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BG Specificity Without IFI
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Causes False-Positive BG

• Foods grains, soybeans, mushrooms, brewers
  yeast, sorghum, brown seaweed, raspberry juice
• Cotton bandages
• Hemodialysis-cellulose membrane
• Blood products albumin, immunoglobulins
• Medicationslentinan, crestin, scleroglucan
• Antimicrobialscolistin, azithromycin,
  pentamidine
• Reagents, glass and plastic ware
• Heatstroke
• Eosinophilic pneumonia/tobacco

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Limitations of BG Assay

• Rapid availability
• lt12h after BC drawn
• Glucan contamination
• Interference
• lipid, hemolysis, bilirubin, turbid
• Difficulty
• Cost

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Summary

• Platelia Aspergillus EIA
• Twice weekly screening
• Always verify positive result!!
• BAL gt serum for diagnosis of IPA
• Histoplasmosis false-positive
• Beta Glucan assay
• Not specific for fungi
• Too many false-positives
• More difficult and expensive
• PCR
• Not standardized, commercially available or
  validated