title: Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast.
abstract: Cryptococcal meningitis is common in sub-Saharan Africa. Given the need for data for a rapid, point-of-care cryptococcal antigen (CRAG) lateral flow immunochromatographic assay (LFA), we assessed diagnostic performance of cerebrospinal fluid (CSF) culture, CRAG latex agglutination, India ink microscopy, and CRAG LFA for 832 HIV-infected persons with suspected meningitis during 2006-2009 (n = 299) in Uganda and during 2010-2012 (n = 533) in Uganda and South Africa. CRAG LFA had the best performance (sensitivity 99.3%, specificity 99.1%). Culture sensitivity was dependent on CSF volume (82.4% for 10 μL, 94.2% for 100 μL). CRAG latex agglutination test sensitivity (97.0%-97.8%) and specificity (85.9%-100%) varied between manufacturers. India ink microscopy was 86% sensitive. Laser thermal contrast had 92% accuracy (R = 0.91, p<0.001) in quantifying CRAG titers from 1 LFA strip to within <1.5 dilutions of actual CRAG titers. CRAG LFA is a major advance for meningitis diagnostics in resource-limited settings.
authors.forename: David R
authors.initials: DR
authors.lastname: Boulware
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Rolfes
authors.forename: Radha
authors.initials: R
authors.lastname: Rajasingham
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Hohenberg
authors.forename: Zhenpeng
authors.initials: Z
authors.lastname: Qin
authors.forename: Kabanda
authors.initials: K
authors.lastname: Taseera
authors.forename: Charlotte
authors.initials: C
authors.lastname: Schutz
authors.forename: Richard
authors.initials: R
authors.lastname: Kwizera
authors.forename: Elissa K
authors.initials: EK
authors.lastname: Butler
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.forename: Conrad
authors.initials: C
authors.lastname: Muzoora
authors.forename: John C
authors.initials: JC
authors.lastname: Bischof
authors.forename: David B
authors.initials: DB
authors.lastname: Meya
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis*; D000946:Antigens, Fungal / Q000276:immunology*; D002846:Chromatography, Affinity / Q000379:methods*; D003454:Cryptococcus / Q000276:immunology*; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000175:diagnosis*; D019095:Point-of-Care Systems; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000946:Antigens, Fungal
keywords: Cryptococcus spp.; HIV; India ink microscopy; South Africa; Uganda; cerebrospinal fluid; cryptococcal antigen; cryptococcal antigen latex agglutination; cryptococcal meningitis; culture; diagnostic techniques; fungi; laser thermal contrast measurement; lateral flow immunochromatographic assay; point-of-care systems; sensitivity; specificity; validation studies