Evaluation of a point-of-care immunoassay test kit 'StrongStep' for cryptococcal antigen detection.

Edward Mpoza,Liliane Mukaremera,Reuben Kiggundu,Lillian Tugume,Elizabeth Nalintya,Kiiza Kandole Tadeo,Joshua Rhein,Radha Rajasingham,Conrad Muzoora,Didas Atwebembere Kundura,David B Meya,David R Boulware,Andrew Akampurira,Mahsa Abassi,Darlisha A Williams ,Tonny Stone Luggya ,Katelyn A Pastick ,Abdu K Musubire ,Sarah Bridge

doi:10.1371/journal.pone.0190652

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.

Highlights

HIV-associated cryptococcal meningitis is the leading cause of adult meningitis in Sub-Saharan Africa and accounts for 15%–20% of AIDS-attributable mortality[1,2,3]
StrongStep cryptococcal antigen (CrAg) had a 98% (54/55) sensitivity and 90% (101/112) specificity in plasma (P = 0.009, versus reference standard)
We found the StrongStep CrAg lateral flow assay (LFA) to be a sensitive assay, which lacked specificity in plasma

Summary

Introduction

HIV-associated cryptococcal meningitis is the leading cause of adult meningitis in Sub-Saharan Africa and accounts for 15%–20% of AIDS-attributable mortality[1,2,3]. Despite recent advancements in diagnostic tools, CrAg screening, as well as the rapid and accurate diagnosis of cryptococcal meningitis, continues to remain a challenge due to the unavailability of point-of-care assays, interruptions in the supply chain resulting in unreliable, non-continuous screening, and lack of expertise and/or laboratory facilities for CrAg testing in resource-limited settings[6,7,8]. HIV-associated cryptococcal meningitis is the leading cause of adult meningitis in SubSaharan Africa, accounting for 15%–20% of AIDS-attributable mortality. 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

Methods

Results

Conclusion