<p>False-Negative Serum Cryptococcal Antigen Lateral Flow Immunoassay Result for a Patient with Disseminated Cryptococcal Disease</p>

Abstract

Cryptococcus neoformans (C. neoformans) is an opportunistic fungal pathogen to humans, which can be acquired from environmental sources. Its most important virulence factor is its polysaccharide capsule, which can be used for diagnostic tests that identify the cryptococcal antigen (CrAg). The CrAg lateral flow assay (LFA) is a dipstick immunochromatographic assay with high sensitivity and specificity; however, several false-negative cases have been reported. Here, we present a case of a false-negative serum CrAg LFA, in which the blood culture from a matched sample was positive for C. neoformans, thus demonstrating the postzone phenomenon.

False-negative cerebral spinal fluid cryptococcal antigen lateral flow assay due to postzone phenomenon in a patient with disseminated cryptococcal disease: a case report

“…Thirteen cases of false-negative CrAg LFAs have been described in nine studies since 2014 (Table 1), including the current case. 4,[13][14][15][16][17][18][19] These were sporadic reports from four continents; United States, South Africa, Australia and China. 4,[13][14][15][16][17][18][19] The youngest patient was 25 years old and five patients were older than 50 years.…”

“…4,[13][14][15][16][17][18][19] These were sporadic reports from four continents; United States, South Africa, Australia and China. 4,[13][14][15][16][17][18][19] The youngest patient was 25 years old and five patients were older than 50 years. 4,[13][14][15][16][17][18][19] Of the 13 cases of false-negative CrAg LFAs, nine had CSF samples analysed; of these, eight were HIV-infected patients (Table 1).…”

“…4,[13][14][15][16][17][18][19] The youngest patient was 25 years old and five patients were older than 50 years. 4,[13][14][15][16][17][18][19] Of the 13 cases of false-negative CrAg LFAs, nine had CSF samples analysed; of these, eight were HIV-infected patients (Table 1). 4,[13][14][15][16][17][18][19] However, only the CSF specimens were tested.…”

“…4,13–19 These were sporadic reports from four continents; United States, South Africa, Australia and China. 4,13–19 The youngest patient was 25 years old and five patients were older than 50 years. 4,13–19…”

Disseminated cryptococcosis with gastrointestinal involvement and false-negative cryptococcal antigen testing due to postzone phenomenon: a case report and review of the literature

“…Cryptococcus species can routinely be isolated from cultures of various clinical specimens, including blood and CSF, when incubated on appropriate media such as Sabourad dextrose agar. However, growth often takes several days, and because CrAg LFA testing typically has excellent performance characteristics and is rapid and cheap, it is by far the favored modality to diagnose cryptococcal infection in clinical laboratories and resource-limited settings [10]. Both clinically-relevant species of Cryptococcus possess a polysaccharide capsule external to the cell wall that is a main virulence factor as well as the target of CrAg testing -specifically, the glucuronoxylomannan component of the capsule is specifically detected by most commercially available antigen assays [11].…”