Sensitivity and specificity of a new cryptococcal antigen lateral flow assay in serum and cerebrospinal fluid.

Abstract

Cryptococcus neoformans and C. gattii are ubiquitous environmental pathogens and major causes of opportunistic infection in immunocompromised individuals. Among patients with HIV/AIDS, cryptococcal disease contributes to more than 600.000 deaths per year globally.1 (Please visit www.mlo-online/201303ci) to read the references for this article). Sub-Saharan Africa has the greatest burden of disease with more than 75% of the cases and 80% of the deaths due to cryptococcal disease worldwide.1 Furthermore, in the United States cryptococcal infection is increasingly recognized as a major cause of invasive fungal infection in solid organ transplant recipients. A recent review of more than 1,000 such patients identified cryptococcal infection as the third-most common fungal infection, following candida species and aspergillus species.2 The limited use of strategies to diagnose cryptococcal disease early, prior to the onset of meningitis, likely contributes to ongoing morbidity and mortality, particularly in low-resource settings. Currently, the diagnostic tests most commonly used in the developed world for identifying cryptococcal antigen are the latex agglutination test (LA) and the enzyme immunoassay (EIA). In resource-limited settings, both are difficult to use, as they require refrigeration, pretreatment with additional enzymes such as pronase in the case of the LA, and specialized equipment such as a spectrophotometer in the case of the EIA.3 Use of the EIA often also results in a delayed turnaround time due to batch testing as well as the wastage of 96-well plates due to low sample volume. In 2009, a new lateral flow assay (LFA) was developed that enables the rapid detection of the cryptococcal polysaccharide capsule glucuoronoxylomannan. Similar to other point-of-care diagnostic tests, the LFA functions as a dip-stick.4 (Please visit www.mlo-onUne.com/201303ci) to view a Figure that illustrates a schematic showing operation of lateral flow immunochromatographic assay for the detection of cryptococcal antigen and images of positive and negative LFA.) The assay utilizes monoclonal antibodies with broad reactivity across the four major cryptococcal serotypes (A and D for var neoformans, B and C for vargattii) and provides both qualitative and semi-quantitative results in ten minutes with no specimen pretreatment.4 Test materials do not require any refrigeration or cold-chain transport. Quantitative titers may be ascertained by mixing the specimen with diluent solution; the highest sample dilution that produces a positive result is considered the LFA titer.4 In July 2011, the Food and Drug Administration cleared the LFA for use in serum and cerebrospinal fluid (CSF) specimens based on a high level of agreement with the LA. We aimed to review the current available literature and data on the test performance characteristics of the cryptococcal antigen LFA in serum and CSF specimens.