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Immunoassays

Low Cryptococcus Antigen Titers as Determined by Lateral Flow Assay Should Be Interpreted Cautiously in Patients without Prior Diagnosis of Cryptococcal Infection

Marie Dubbels, Dane Granger, Elitza S. Theel
Peter Gilligan, Editor
Marie Dubbels
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Dane Granger
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Elitza S. Theel
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Peter Gilligan
UNC Health Care System
Roles: Editor
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DOI: 10.1128/JCM.00751-17
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    FIG 1

    Summary of patients for whom serum and/or CSF samples were tested with the CrAg LFA between 1 June 2014 and 31 December 2016.

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  • TABLE 1

    CrAg LFA and CALAS titers for patients with first-time diagnoses of cryptococcal disease confirmed by culture or histopathology (n = 20)

    Patient no.Age (yr)/sexSource for fungal cultureTime to growth (days)Source for CrAg assayaCrAg LFA titerCALAS titer
    188/MCSF4CSF1:20Negative
    SerumNDND
    270/MCSF2CSF≥1:2,560≥1:4,096
    Serum1:1601:32
    367/MBronchial wash7Serum1:5Negative
    478/FBronchial wash1Serum1:401:16
    573/MBlood2Serum≥1:2,560≥1:4,096
    678/MBlood2Serum≥1:2,560ND
    776/MCSF2CSF≥1:2,5601:2,048
    Serum≥1:2,5601:1,024
    857/MCSF2CSF≥1:2,5601:128
    Serum1:1601:32
    950/MBAL fluid3Serum1:201:4
    1072/MCSF2CSF≥1:2,5601:512
    Serum1:6401:64
    1171/MCSF7CSF≥1:2,5601:1,024
    SerumNDND
    1261/MCSF2CSF1:201:1
    Serum1:201:4
    1363/MUrine7Serum1:401:8
    1439/MCSF2CSF1:6401:64
    Serum1:2Negative
    1548/FCalf tissue5Serum≥1:2,5601:1,024
    1658/FCSF3CSF1:1601:16
    Serum1:1601:64
    1743/MCSF2CSF1:3201:128
    Serum≥1:2,5601:128
    1858/MLung tissue2Serum1:201:16
    1952/MLung tissuebNASerum1:101:2
    2030/MSputum2Serum≥1:2,560ND
    • ↵a CrAg, Cryptococcus antigen; ND, not done; NA, not applicable; BAL, bronchoalveolar lavage; LFA, lateral flow assay.

    • ↵b Organisms consistent with Cryptococcus spp. were observed in the histopathological assessment of a lung biopsy specimen, using both Gomori methenamine silver (GMS) and mucicarmine stains.

  • TABLE 2

    Review of data for patients tested by the CrAg LFA without culture or histopathological confirmation of cryptococcal disease (n = 18)a

    Patient no.Age (yr)/sexPresenting symptom(s)Comorbidity/immunosuppressionRadiological findingsCulture sourceCrAg LFA titer (source)CALAS titer (source)Final diagnosisAntifungal treatment initiated/response?Repeat CrAg LFA titer (days between tests)b
    133/MChronic dry coughS/p kidney Tx (2006); tacrolimus and mycophenolateBilateral innumerable small lung nodulesBlood, CSF1:10 (S)Neg. (S)Probable cryptococcal pulmonary infectionFluconazole/yes1:10 (3)
    280/FDyspnea, weight loss, fatigueIdiopathic pulmonary fibrosisGround glass lung opacitiesBlood, CSF1:10 (S)Neg. (S)Probable cryptococcal pulmonary infectionFluconazole/yes1:2 (96), 1:2 (111)
    360/FSOB, fever, HA, chronic coughS/p kidney Tx (2010), DM2; tacrolimusBilateral nodular lung opacitiesBlood1:1,280 (S)1:256 (S)Probable cryptococcal pneumoniaFluconazole and flucytosine/yes1:640 (13), 1:80 (153)
    474/MCough, weight loss, fatigue, feverAutoimmune hemolytic anemia; high-dose prednisoneCavitary lesion in right upper lobeBlood1:40 (S)NDProbable cryptococcal pulmonary infectionFluconazole/yes1:40 (30), 1:20 (123), neg. (10 mo)
    553/MSevere HA, neck pain, fever, photophobiaNewly diagnosed with HIV (48 CD4+ cells/mm3)NoneCSF≥1:2,560 (CSF)c≥1:4,096 (CSF)Cryptococcal meningitisAmphotericin B and flucytosine/yes≥1:2,560 (CSF, 34)
    668/MFever, rigors, anorexiaS/p liver Tx (2004), IBD; tacrolimusNoneBlood, CSF1:2 (S)Neg. (S)Possible cryptococcal granulomatous hepatitisFluconazole/noNeg. (2)
    773/MTremors, feverMonoclonal gammopathy, microscopic anemiaFew punctate lung nodulesBlood1:5 (S)Neg. (S)Possible subacute cryptococcal infection, Waldenström's macroglobulinemiaFluconazole/noND
    885/MHematuria, back painS/p aortic valve replacementNoneBlood, CSF, spinal tissue, urine1:2 (S)Neg. (S) Pseudomonas aeruginosa UTI, Streptococcusbovis spinal infectionNo/NA1:2 (1)
    951/FFever, abdominal painS/p liver Tx (2004); azathioprine and tacrolimusNoneBlood, urine1:2 (S)Neg. (S)Large diffuse B-cell lymphomaFluconazole/no1:2 (2), neg. (75)
    1042/FWeight loss, fatigue, ARDS at admissionCongenital urinary/lower GI abnormalitiesNoneBlood1:2 (S)Neg. (S)ARDS secondary to adrenal insufficiencyNo/NANeg. (2)
    1161/FFoot ulcer, hemodynamic instabilityRheumatoid arthritis, DM2, ESRD with hemodialysis; etanerceptNoneBlood, hip tissue1:2 (S)Neg. (S)Cellulitis and contiguous osteomyelitis due to Staphylococcus aureus and Streptococcus pyogenesNo/NAND
    1246/MFever, hip painTotal hip arthroplastyBilateral lung nodules/opacitiesBlood1:2 (S)Neg. (S) Candida albicans bloodstream infectionCaspofungin for C. albicans infection/yesND
    1388/FGait disturbance, difficulty swallowingNoneEnlargement of left lateral ponsCSF1:2 (CSF)cNeg. (CSF)GliomaNo/NAND
    1461/MSOB, coughS/p allogeneic PBSC Tx (2015)Bilateral lung consolidation and septal thickeningBlood, BAL fluid, CSF1:2 (S)Neg. (S)Pulmonary GVHDAmphotericin B, switched to fluconazole/noNeg. (3)
    1543/FRight upper extremity weaknessNoneFrontal lobe brain atrophyCSF1:5 (CSF), neg. (S)Neg. (CSF), ND (S)Corticobasal degenerationNo/NANeg. (S, 1)
    1688/MProgressive neurological symptomsCoronary artery disease, lumbar fusionNoneBlood, CSF1:2 (S)Neg. (S)Cauda equina nerve root enhancementNo/NAND
    1775/MFeverGout, hypothyroidismBilateral small lung nodulesBlood1:2 (S)NDResolution with empiric levofloxacinNo/NANeg. (5)
    1860/MSOB, chronic cough, fatigue, feverAdenocarcinoma s/p chemoradiation (2016), HCV s/p ledipasvir (2016)Cavitary lung lesion, ground glass opacitiesBlood1:2 (S)Neg. (S)Pneumonia due to Aspergillus fumigatus and Acinetobacterbaumannii/Acinetobacter calcoaceticusFluconazole (discontinued)/noNeg. (22)
    • ↵a S/p, status post; S, serum; UTI, urinary tract infection; BAL, bronchoalveolar lavage; NA, not applicable; ND, not done; neg., negative; Tx, transplant; ARDS, acute respiratory distress syndrome; GI, gastrointestinal; IBD, irritable bowel syndrome; PBSC, peripheral stem cell; GVHD, graft-versus-host disease; HA, headache; SOB, shortness of breath; DM2, diabetes mellitus type 2; ESRD, end-stage renal disease; HCV, hepatitis C virus.

    • ↵b Indicates the time between the initial CrAg LFA result and the repeat test(s) ordered as part of clinical care.

    • ↵c Serum samples were not evaluated for CrAg.

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Low Cryptococcus Antigen Titers as Determined by Lateral Flow Assay Should Be Interpreted Cautiously in Patients without Prior Diagnosis of Cryptococcal Infection
Marie Dubbels, Dane Granger, Elitza S. Theel
Journal of Clinical Microbiology Jul 2017, 55 (8) 2472-2479; DOI: 10.1128/JCM.00751-17

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Low Cryptococcus Antigen Titers as Determined by Lateral Flow Assay Should Be Interpreted Cautiously in Patients without Prior Diagnosis of Cryptococcal Infection
Marie Dubbels, Dane Granger, Elitza S. Theel
Journal of Clinical Microbiology Jul 2017, 55 (8) 2472-2479; DOI: 10.1128/JCM.00751-17
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KEYWORDS

Antigens, Fungal
Chromatography, Affinity
Cryptococcosis
Cryptococcus
Diagnostic Tests, Routine
Cryptococcus
antigen
lateral flow assay

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