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. 2012;7(11):e49541.
doi: 10.1371/journal.pone.0049541. Epub 2012 Nov 14.

Clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory

Brendan J McMullan  1 , Catriona Halliday, Tania C Sorrell, David Judd, Sue Sleiman, Debbie Marriott, Tom Olma, Sharon C-A Chen
Affiliations

Clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory

Brendan J McMullan et al. PLoS One. 2012.

Abstract

Background: Cryptococcus neoformans causes life-threatening meningitis. A recently introduced lateral flow immunoassay (LFA) to detect cryptococcal antigen (CRAG) is reportedly more rapid and convenient than standard latex agglutination (LA), but has not yet been evaluated in a diagnostic laboratory setting.

Methods: One hundred and six serum, 42 cerebrospinal fluid (CSF), and 20 urine samples from 92 patients with known or suspected cryptococcosis were tested by LA and LFA, and titres were compared. Results were correlated with laboratory-confirmed cryptococcosis. Serial samples were tested in nine treated patients.

Results: Twenty-five of 92 patients had confirmed cryptococcosis; all sera (n = 56) from these patients were positive by LFA (sensitivity 100%, 95% confidence interval (CI) 93.6-100%) compared with 51/56 positive by LA (sensitivity 91.1%, 95% CI 80.7-96.1%). Fifty sera from 67 patients without cryptococcosis tested negative in both assays. While LA yielded more false negative results (5/56) this did not reach statistical significance (p = 0.063). Nine CSF samples from patients with cryptococcal meningitis yielded positive results using both assays while 17/18 urine samples from patients with cryptococcosis were positive by the LFA. The LFA detected CRAG in C. gattii infection (n = 4 patients). Agreement between titres obtained by both methods (n = 38 samples) was imperfect; correlation between log-transformed titres (r) was 0.84. Turn-around-time was 20 minutes for the LFA and 2 h for LA. The cost per qualitative sample was 18USD and 91 USD, respectively and per quantitative sample was 38USD and 144USD, respectively.

Conclusions: Qualitative agreement between the LFA and LA assays performed on serum and CSF was good but agreement between titres was imperfect. Ease of performance of the LFA and the capacity for testing urine suggest it has a role in the routine laboratory as a rapid diagnostic test or point-of-care test.

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Conflict of interest statement

Competing Interests: The authors would like to declare the following funding-related matter: they received the first 500 LFA kits free-of-charge from ABACUS, ALS Australia. The authors declare no other commercial funding or association, including consultancy, patents or products. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Serum Cryptococcal Antigen Results by Assay.
Flow chart of detection of serum cryptococcal antigen for 92 patients by lateral flow assay (LFA) and latex agglutination (LA). (S) specimens, (N) patients.
Figure 2
Figure 2. Agreement between Assays.
Correlation (above) and Bland-Altman plot (below) for 38 samples tested by lateral flow assay (LFA) and latex agglutination (LA). Ln = loge.
See this image and copyright information in PMC

References

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