title: Clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory.
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.
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Westmead, New South Wales, Australia. brendanoch@yahoo.co.uk
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: McMullan
authors.forename: Catriona
authors.initials: C
authors.lastname: Halliday
authors.forename: Tania C
authors.initials: TC
authors.lastname: Sorrell
authors.forename: David
authors.initials: D
authors.lastname: Judd
authors.forename: Sue
authors.initials: S
authors.lastname: Sleiman
authors.forename: Debbie
authors.initials: D
authors.lastname: Marriott
authors.forename: Tom
authors.initials: T
authors.lastname: Olma
authors.forename: Sharon C-A
authors.initials: SC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000946:Antigens, Fungal / Q000276:immunology*; D003453:Cryptococcosis / Q000175:diagnosis*; D003454:Cryptococcus / Q000276:immunology*; D005260:Female; D006801:Humans; D007159:Immunologic Tests / Q000379:methods*; D008297:Male; D008875:Middle Aged; D019095:Point-of-Care Systems; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000946:Antigens, Fungal