Sensitivity and specificity of cryptococcal antigen lateral flow assay for the diagnosis of HIV-associated cryptococcal meningitis in western Kenya

Abstract

Background: HIV-associated cryptococcal meningitis carries a high case-fatality-rate in sub-Saharan Africa. Diagnostic delays partly contribute to this. Rapid point-of-care tests may facilitate speedy diagnosis. This study aimed to determine the sensitivity and specificity of urine, serum and cerebrospinal fluid (CSF) cryptococcal antigen lateral flow assay for the diagnosis of HIV-associated cryptococcal meningitis compared with the gold standard CSF culture.

Methods: A cross-sectional study was conducted in the medical wards of Moi Teaching and Referral Hospital, Eldoret, Kenya. Adult (≥18years) HIV-infected in-patients suspected to have meningitis had paired samples of urine, serum and CSF collected and tested real time using the cryptococcal antigen lateral flow assay (rapid point of care test). CSF cultures were also conducted. Data were analyzed using STATA ® (Statacorp Texas USA®). Descriptive statistics were used to summarize demographic, clinical and laboratory parameters. Sensitivity and specificity of the rapid test were calculated with the CSF culture as the gold standard.

Results: Of the 302 participants included 172 (57%) were female, median age 37 years (IQR 30-45). The median CD4+ cell count was 183/ul (IQR 54-333). Among 288 participants with available CSF culture results, 50(17%) had culture-confirmed cryptococcal meningitis. Urine rapid test had a sensitivity and specificity of 86 %( 95% CI 73-94) and 95.7% (95% CI 92-98) respectively. Serum rapid test had a sensitivity and specificity of 92% (95%CI 81-98) and 94.9% (95%CI 91-97) respectively. CSF rapid test had a sensitivity and specificity of 92% (95%CI 81-98%) and 94.5% (95% CI 91-97) respectively.

Conclusion: Serum and CSF cryptococcal antigen lateral flow assay are highly sensitive and specific for the diagnosis of HIV-associated cryptococcal meningitis. Urine is relatively sensitive and specific. Serum and CSF cryptococcal antigen lateral flow assay can be used as a less expensive alternative to cryptococcal antigen latex agglutination method. Urine cryptococcal antigen lateral flow assay could be adopted as a rapid point of care diagnostic test in primary care clinics in low income settings without experience in handling CSF or serum, to fast track diagnosis of cryptococcal meningitis.