title: Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis.
abstract: BACKGROUND
  Many deaths from cryptococcal meningitis (CM) may be preventable through early diagnosis and treatment. An inexpensive point-of-care (POC) assay for use with urine or a drop of blood would facilitate early diagnosis of cryptococcal infection in resource-limited settings. We compared cryptococcal antigen (CRAG) concentrations in plasma, serum, and urine from patients with CM, using an antigen-capture assay for glucuronoxylomannan (GXM) and a novel POC dipstick test.
  
  
  METHODS
  GXM concentrations were determined in paired serum, plasma, and urine from 62 patients with active or recent CM, using a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). A dipstick lateral-flow assay developed using the same monoclonal antibodies for the sandwich ELISA was tested in parallel. Correlation coefficients were calculated using Spearman rank test.
  
  
  RESULTS
  All patients had detectable GXM in serum, plasma, and urine using the quantitative ELISA. Comparison of paired serum and plasma showed identical results. There were strong correlations between GXM levels in serum/urine (r(s) = 0.86; P < .001) and plasma/urine (r(s) = 0.85; P < .001). Levels of GXM were 22-fold lower in urine than in serum/plasma. The dipstick test was positive in serum, plasma, and urine in 61 of 62 patients. Dipstick titers correlated strongly with ELISA. Correlations between the methods were 0.93 (P < .001) for serum, 0.94 (P < .001) for plasma, and 0.94 (P < .001) for urine.
  
  
  CONCLUSIONS
  This novel dipstick test has the potential to markedly improve early diagnosis of CM in many settings, enabling testing of urine in patients presenting to health care facilities in which lumbar puncture, or even blood sampling, is not feasible.
authors.affiliation: Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, Cranmer Terrace, United Kingdom.
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Jarvis
authors.forename: Ann
authors.initials: A
authors.lastname: Percival
authors.forename: Sean
authors.initials: S
authors.lastname: Bauman
authors.forename: Joy
authors.initials: J
authors.lastname: Pelfrey
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.forename: G Ntombomzi
authors.initials: GN
authors.lastname: Williams
authors.forename: Nicky
authors.initials: N
authors.lastname: Longley
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kozel
mesh_terms: D000328:Adult; D000946:Antigens, Fungal / Q000032:analysis* / Q000097:blood / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003455:Cryptococcus neoformans / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications / Q000175:diagnosis*; D019095:Point-of-Care Systems; D011134:Polysaccharides / Q000032:analysis* / Q000097:blood / Q000652:urine
chemical_list: D000946:Antigens, Fungal; D015415:Biomarkers; D011134:Polysaccharides; C027478:glucuronoxylomannan