Evaluation of a New Cryptococcal Antigen Lateral Flow Immunoassay in Serum, Cerebrospinal Fluid and Urine for the Diagnosis of Cryptococcosis: A Meta-Analysis and Systematic Review

Abstract

BackgroundA new lateral flow immunoassay (LFA) for the detection of cryptococcal antigen was developed.ObjectiveWe aimed to systematically review all relevant studies to evaluate the diagnostic accuracy of the cryptococcal antigen LFA on serum, CSF and urine specimens.MethodsWe searched public databases including PubMed, Web of Science, Elsevier Science Direct and Cochrane Library for the English-language literature published up to September 2014. We conducted meta-analyses of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratios (DOR) and SROC of LFA in serum and CSF, respectively. The sensitivity of LFA in urine was also analyzed. Subgroup analyses were carried out to analyze the potential heterogeneity.Results12 studies were included in this study. The pooled sensitivity and specificity values of LFA in serum were 97.6% (95% CI, 95.6% to 98.9%) and 98.1% (95% CI, 97.4% to 98.6%), respectively. The average PLR of LFA in serum was 43.787 (95% CI, 22.60–84.81) and the NLR was 0.03 (95% CI, 0.01–0.09). The pooled DOR was 2180.30 (95% CI, 868.92–5471.00) and the AUC was 0.9968. The pooled sensitivity and specificity values of LFA in CSF were 98.9% (95% CI, 97.9% to 99.5%) and 98.9% (95% CI, 98.0% to 99.5%), respectively. The average PLR of LFA in serum was 48.83 (95% CI, 21.59–110.40) and the NLR was 0.02 (95% CI, 0.01–0.04). The pooled DOR was 2931.10 (95% CI, 1149.20–7475.90) and the AUC was 0.9974. The pooled sensitivity value of LFA in urine was 85.0% (95% CI, 78.7% to 90.1%)ConclusionsThe study demonstrates a very high accuracy of LFA in serum and CSF for the diagnosis of cryptococcosis in patients at risk. LFA in urine can be a promising sample screening tool for early diagnosis of cryptococcosis.

Cryptococcosis Today: It Is Not All About HIV Infection

“…In recent years, improvements in cryptococcal antigen (CrAg) testing with the introduction of lateral flow assays has been a significant development (65). A recent meta-analysis of 12 studies containing 4,622 samples reported the pooled sensitivity and specificity for serum samples at 97.6% and 98.1%, respectively and for CSF at 98.9% and 98.9%, respectively(66). Little data exists related specifically to differences in CrAg validity between different immune states.…”

Use of Fungal Diagnostics and Therapy in Pediatric Cancer Patients in Resource-Limited Settings

“…In a recent meta-analysis and systematic review [95], a new cryptococcal antigen LFA demonstrated high accuracy in serum and CSF for the diagnosis of cryptococcosis. LFA may eventually be extended to other fungal antigens, since the technology is inexpensive and requires little expertise, but produces accurate results.…”

Preclinical Assessment of a Fully Automated Multiplex PCR Panel for Detection of Central Nervous System Pathogens

“…Although the ARUP Laboratories-developed viral PCR assays appeared to be slightly more sensitive than the multiplex panel, we did not directly compare the analytical limits of detection, and the effects of freezethaw cycles may have impacted FA ME sensitivity and/or the abil- ity to confirm previous results. CrAG testing is a highly sensitive and accurate method for diagnosing cryptococcal meningitis (11,12), but we did not have fungal culture results to link to the FA ME and DNA sequence analyses. Furthermore, we did not have access to patient-level information to help adjudicate discrepancies across methods.…”