Evaluation of cryptococcal antigen lateral flow assay in human immunodeficiency virus-negative cryptococcosis: a diagnostic accuracy study.

OBJECTIVES

This study aims to evaluate the diagnostic accuracy of cryptococcal antigen lateral flow assay (CrAg LFA) in HIV-negative populations.

METHODS

The CrAg LFA results of 2918 paired serum and cerebrospinal fluid (CSF) from 1459 HIV-negative inpatients (including 354 cryptococcosis and 1105 non-cryptococcosis) who underwent both serum and CSF CrAg LFA tests were retrospectively collected. Time-series analysis of sensitivity values for CrAg LFA from 2019 to 2024 was performed using linear interpolation and Gaussian smoothing. The diagnostic capability of serum CrAg LFA for predicting cryptococcal meningitis (CM) was assessed by logistic regression. Spearman's rank correlation analysed the relationship between serum and CSF CrAg LFA titres.

RESULTS

The sensitivity of serum CrAg LFA test for diagnosing cryptococcosis was 97.7% (95% CI: 96.2-99.3%), with a specificity of 99.1% (95% CI: 98.5-99.7%), positive predictive value of 97.2% (95% CI: 95.5-98.9%), and negative predictive value of 99.3% (95% CI: 98.8-99.8%). False-positive serum CrAg LFA were identified in ten patients without cryptococcosis. The sensitivity, specificity, positive predictive value, and negative predictive value of CSF CrAg LFA test for the diagnosis of CM were 100% (95% CI: 100-100%), 99.9% (95% CI: 99.7-100%), 99.7% (95% CI: 99.1-100%), and 100% (95% CI: 100-100%), respectively. One case with a false-positive CSF CrAg LFA was identified. The receiver operating characteristic curve demonstrated an area under the curve of 0.96 (95% CI: 0.959-0.963) for CM in serum CrAg LFA-positive patients with neurological symptoms.

DISCUSSION: This study highlights the high sensitivity and specificity of the CrAg LFA test in HIV-negative patients. This test can be used as an effective tool for the first-line rapid diagnosis of cryptococcosis in HIV-negative populations, regardless of the determination of the CrAg LFA titre.