Validation of clinic-based cryptococcal antigen lateral flow assay screening in HIV-infected adults in South Africa

• Published in: Scientific reports Vol. 9; no. 1; p. 2687
• Main Authors: Drain, Paul K, Hong, Ting, Krows, Meighan, Govere, Sabina, Thulare, Hilary, Wallis, Carole L, Gosnell, Bernadett I, Moosa, Mahomed-Yunus, Bassett, Ingrid V, Celum, Connie
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 25.02.2019; Nature Publishing Group UK
• Subjects: Antigenemia; Antigens; Blood; CD4 antigen; Enzyme immunoassay; HIV; Human immunodeficiency virus; Meningitis; Urine; South Africa
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-37478-7

Since rapid cryptococcal antigen lateral flow assays (CrAg LFA) may expedite treatment of HIV-associated cryptococcal infections, we sought to validate clinic-based CrAg LFA testing. Among newly-diagnosed HIV-infected adults in South Africa, a trained nurse performed clinic-based testing of urine, fingerprick capillary and venous whole blood with rapid CrAg LFA (Immy Diagnostics, Norman, USA). We performed matched laboratory-based serum cryptococcal antigen testing with an enzyme immunoassay (EIA). We assessed diagnostic accuracy using EIA as the gold-standard, and performed additional validation testing on serum and among hospitalized adults with cryptococcal meningitis. Among 5,618 participants enrolled, 1,296 were HIV-infected and screened for cryptococcal antigenemia. Overall CrAg prevalence by serum EIA was 3.6% (95% CI 2.0-6.0%) for adults with CD4 < 200 cells/mm , and 5.7% (95% CI 2.8-10.2%) for adults with CD4 < 100 cells/mm . Using expanded screening guidelines (CD4 < 200 cells/mm ), CrAg LFA testing of venous whole blood, fingerprick capillary blood, and urine had diagnostic sensitivities of 46% (95% CI 19-75%), 38% (95% CI 14-68%), and 54% (95% CI 25-81%), and specificities of 97%, 97%, and 86%, respectively. When tested on serum samples, CrAg LFA had sensitivity of 93% (95% CI 66-100%) and specificity of 100% (95% CI 88-100%). All venous and fingerprick whole blood CrAg LFA tests were positive among 30 hospitalized adults with cryptococcal meningitis. Two independent readers had strong agreement for all LFA results (p < 0.0001). When performed at the point-of-care by trained nurses, CrAg LFA testing was feasible, had the highest accuracy on serum specimens, and may accelerate treatment of HIV-associated cryptococcal infections.