Retrospective Assessment of a National Reflex Cryptococcal Antigen Screening Program in South Africa Through Interlaboratory Comparison of Lateral Flow Assay Results.

Abstract

Reflex cryptococcal antigen (CrAg) screening of blood specimens with a CD4 count of <100 cells/µL was performed at 45 South African CD4 laboratories using a lateral flow assay (LFA). Our objective was to evaluate the reliability of routine LFA results through comparative interlaboratory testing. All CrAg-positive and a selected number of CrAg-negative samples from the CD4 laboratories were retested at paired microbiology laboratories using the same LFA. Samples with discordant results were tested at a reference laboratory, using the LFA (with CrAg titers). During interlaboratory testing, 12,502 samples were retested, with 93 (0.7%) discordant results and a between-laboratory agreement of 99.3% (Cohen's kappa, 0.98). The proportion of retested samples with discordant results ranged from 0.17% to 5.31% per laboratory pair (median 0.28%), with 3 reporting >3% of results as discordant. Routine CrAg screening results were reliable, with <1% of samples having discordant results, mainly due to interpretation and transcription errors.