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Performance of the CrAg LFA Assay

Jeffrey D. Klausner, MD, MPHProfessor of Medicine

Division of Infectious Diseases and Program in Global HealthDavid Geffen School of Medicine

Cryptococcal Antigen Lateral Flow AssayCrAg LFA

QualitativeSemi-Quantitative (titer)

FDA-cleared for serum and CSF

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Study(N)

SensitivitySpecificity

EIA

SensitivitySpecificity

Latex Agglutination

SensitivitySpecificity

Culture

Remarks

Lee, 2012 (209)

100% (35/35) 95.4% (166/174)

8 LFA+/EIA-

Jarvis, 2011(62)

100% (62/62) All 62 were patients with CM hx

Lindsley, 2011(464)

95.6% (87/91)99.5% (371/373)

Sensitivity of EIA vs Bcx was 94% (16/17)

Hansen, 2012 (589)

EIA-1: 100% (41/41) 96.3% (527/547)EIA-2: 96.8% (60/62) 100% (527/527)

20 LFA+/EIA-1-

18 EIA-2+/EIA-1-

2 LFA-/EIA-2+

CrAg LFA test performance in serum

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Study(N)

SensitivitySpecificity

EIA

SensitivitySpecificity

Latex Agglutination

SensitivitySpecificity

Culture

Remarks

Escandon, 2012(421)

100% (16/16) 96.9% (392/405)

13 LFA+/LA -

Iqbal, 2012(114)

100% (10/10) 98% (102/104)

2 LFA+/LA-

Vijayan, 2012 (197)

100% (101/101) 97.9% (94/96)

2 LFA+/LA- were EIA+

Bestrom, 2012(632)

100% 99.8%

Boulware , 2012(214)

100% (76/76) 96% (152/158)

Gold standard was CSF culture

Lindsley, 2011(17)

100% (17/17) Gold standard was blood culture

CrAg LFA test performance in serum

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Study(N)

SensitivitySpecificity

EIA

SensitivitySpecificity

Latex Agglutination

SensitivitySpecificity

Culture

Remarks

Boulware 2012(74)

100% (20/20) 100% (54/54)

Gold standard was CSF culture

Rolfes, 2012(112)

98.5%91.5%

Jarvis, 2011(62)

100% (62/62) 62 with prior CM

CrAg LFA test performance in plasma

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Study(N)

SensitivitySpecificity

EIA

SensitivitySpecificity

Latex Agglutination

SensitivitySpecificity

Culture

Remarks

Boulware , 2012(292)

99% (110/111)98% (178/181)

Gold standard was CSF culture

Jarvis, 2011(62)

98% (61/62) 62 with prior CM

Lindsley, 2011(74)

70.3% (52/74) 81% (51/63) vs. serum LFA

CrAg LFA test performance in urine

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Study(N)

Location

SensitivitySpecificity

EIA

SensitivitySpecificity

Latex Agglutination

SensitivitySpecificity

Culture

Remarks

Boulware , 2012(150)

100% (80/80) 99% (69/70)

Iqbal, 2012(10)

100% (6/6)100% (4/4)

Hansen, 2012(412)

EIA-1: 100% (15/15) 99.5% (395/397)EIA-2: 100% (16/16) 99.7% (394/395)

2 LFA+/EIA-1-1LFA+/EIA-2-

Rolfes, 2012(161)

(102)

96.2%96.4%

100% 93.5%

98.8%70.4%

100% 93.5%

Lee, 2012 100% (48/48) 98.5% (348/353)

Meridian EIA5 additional LFA+ EIA-

Jarvis, 2011 100% (62/62) 62 with prior CM

CrAg LFA test performance in CSF

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CrAg Performance Summary• Serum:

– Sensitivity: Median 100% (96.6%-100%)– Specificity: Median 98.0% (95.4%-100%

• Plasma– Sensitivity: Median 100% (98.5%-100%)– Specificity: Median 95.8% (91.5%-100%)

• Urine– Sensitivity: Median 98.0% (70.3-99%)– Specificity: Median 98.3% (98.3%-98.3%)

• CSF– Sensitivity: Median 100% (96.2%-100%)– Specificity: Median 96.4% (93.5%-100%)

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Conclusions• CrAg LFA is both highly sensitive and specific in various body fluid

specimens. FDA-cleared in serum and CSF.• “False positive” tests might reflect increased sensitivity of LFA vs.

gold standard• Urine and plasma provide exciting potential alternative specimen

types

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Acknowledgments

• Tara Vijayan, MD, MPH Clinical ID Fellow, UCSF• Sean Bauman, Immy Diagnostics• Tom Chiller, CDC Mycotic Diseases Branch• Monika Roy, CDC Mycotic Diseases Branch• Various researchers who have shared their data