Evaluation of a point-of-care immunoassay test kit ‘StrongStep’ for cryptococcal antigen detection

Abstract

BackgroundHIV-associated cryptococcal meningitis is the leading cause of adult meningitis in Sub-Saharan Africa, accounting for 15%–20% of AIDS-attributable mortality. The development of point-of-care assays has greatly improved the screening and diagnosis of cryptococcal disease. We evaluated a point-of-care immunoassay, StrongStep (Liming Bio, Nanjing, Jiangsu, China) lateral flow assay (LFA), for cryptococcal antigen (CrAg) detection in cerebrospinal fluid (CSF) and plasma.MethodsWe retrospectively tested 143 CSF and 77 plasma samples collected from HIV-seropositive individuals with suspected meningitis from 2012–2016 in Uganda. We prospectively tested 90 plasma samples collected from HIV-seropositive individuals with CD4 cell count <100 cells/μL from 2016–2017 as part of a cryptococcal antigenemia screening program. The StrongStep CrAg was tested against a composite reference standard of positive Immy CrAg LFA (Immy, Norman, OK, USA) or CSF culture with statistical comparison by McNemar’s test.ResultsStrongStep CrAg had a 98% (54/55) sensitivity and 90% (101/112) specificity in plasma (P = 0.009, versus reference standard). In CSF, the StrongStep CrAg had 100% (101/101) sensitivity and 98% (41/42) specificity (P = 0.99). Adjusting for the cryptococcal antigenemia prevalence of 9% in Uganda and average cryptococcal meningitis prevalence of 37% in Sub-Saharan Africa, the positive predictive value of the StrongStep CrAg was 50% in plasma and 96% in CSF.ConclusionsWe found the StrongStep CrAg LFA to be a sensitive assay, which unfortunately lacked specificity in plasma. In lower prevalence settings, a majority of positive results from blood would be expected to be false positives.

Emerging concepts in HIV-associated cryptococcal meningitis

“…CM diagnosis has been revolutionised by the widespread availability of reliable point-of-care Lateral Flow Assays (LFAs) which detect CrAg. The IMMY LFA remains the most sensitive and specific rapid diagnostic test (RDT) available (12). A potential substitute to the IMMY LFA, the StrongStep, was found to have low sensitivity when used on plasma (12).…”

“…The IMMY LFA remains the most sensitive and specific rapid diagnostic test (RDT) available (12). A potential substitute to the IMMY LFA, the StrongStep, was found to have low sensitivity when used on plasma (12). A recently developed RDT, the semi-quantitative Biosynex/BioRad Crypto PS test, incorporates an additional positive line aimed to detect high titers of CrAg in both blood and CSF.…”

Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing

“…The StrongStep test performed well in CSF, with 100% (101/101) sensitivity and 98% (41/42) specificity (11). However, the specificity was only 90% (101/112) in plasma (11), with 98% sensitivity (54/55). The limited specificity of plasma in the setting of CrAg screening and the 9% CrAg prevalence rate equate to a positive predictive value of only 50% (11).…”

“…A third test is the StrongStep (Liming Bio, China). In a two-site validation study in Uganda, 143 CSF and 167 plasma samples were tested in comparison to the Immy CrAg LFA and CSF culture (11). The StrongStep test performed well in CSF, with 100% (101/101) sensitivity and 98% (41/42) specificity (11).…”

“…In a two-site validation study in Uganda, 143 CSF and 167 plasma samples were tested in comparison to the Immy CrAg LFA and CSF culture (11). The StrongStep test performed well in CSF, with 100% (101/101) sensitivity and 98% (41/42) specificity (11). However, the specificity was only 90% (101/112) in plasma (11), with 98% sensitivity (54/55).…”