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Evaluation of a Novel Semiquantitative Cryptococcal Antigen Lateral Flow Assay in Patients with Advanced HIV Disease

Jarvis, JN; Tenforde, MW; Lechiile, K; Milton, T; Boose, A; Leeme, TB; Tawe, L; Muthoga, C; Rukasha, I; Mulenga, F; et al. Jarvis, JN; Tenforde, MW; Lechiile, K; Milton, T; Boose, A; Leeme, TB; Tawe, L; Muthoga, C; Rukasha, I; Mulenga, F; Rulaganyang, I; Molefi, M; Molloy, SF; Ngidi, J; Harrison, TS; Govender, NP; Mine, M (2020) Evaluation of a Novel Semiquantitative Cryptococcal Antigen Lateral Flow Assay in Patients with Advanced HIV Disease. J Clin Microbiol, 58 (9). ISSN 1098-660X https://doi.org/10.1128/JCM.00441-20
SGUL Authors: Harrison, Thomas Stephen Molloy, Sile

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Abstract

Background: Higher cryptococcal antigen (CrAg) titers are strongly associated with mortality risk in individuals with HIV-associated cryptococcal disease. Rapid tests to quantify CrAg level may provide important prognostic information and enable treatment stratification.Methods: We performed a laboratory-based validation of the semi-quantitative IMMY CrAgSQ assay against the current gold-standard CrAg tests. We assessed diagnostic accuracy of the CrAgSQ in HIV-positive individuals undergoing CrAg screening; determined the relationship between CrAgSQ scores and dilutional CrAg titers; assessed inter-rater reliability; and determined clinical correlates of CrAgSQ scores.Results: A total of 872 plasma samples were tested using both CrAgSQ and conventional IMMY CrAg LFA tests; 692 sequential samples from HIV-positive individuals undergoing CrAg screening and an additional 180 known CrAg-positive plasma samples archived from prior studies. Inter-rater agreement in CrAgSQ reading was excellent (98.17% agreement, Cohen's Kappa 0.962, p<0.001). Using IMMY LFA as a reference standard, CrAgSQ was 93.0% sensitive (95% confidence interval [CI] 80.9%-98.5%) and 93.8% specific (95%CI 91.7%-95.6%). After reclassification of discordant results using CrAg enzyme immunoassay testing, sensitivity was 98.1% (95%CI 90.1%-100%), and specificity 95.8% (95%CI 99.1%- 100%). Median CrAg titers were 1:10 (IQR 1:5-1:20) in the CrAgSQ1+ category; 1:40 (IQR 1:20-1:80) in the CrAgSQ2+ category; 1:640 (IQR 1:160-1:2560) in the CrAgSQ3+ category; and 1:5120 (IQR 1:2560-1:30720) in the CrAgSQ4+ category. Increasing CrAgSQ scores were strongly associated with 10-week mortality.Conclusions: The CrAgSQ test had high sensitivity and specificity compared to the IMMY CrAg LFA test and provided CrAg scores associated with both conventional CrAg titers and clinical outcomes.

Item Type: Article
Additional Information: Copyright © 2020 Jarvis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
Keywords: 06 Biological Sciences, 07 Agricultural and Veterinary Sciences, 11 Medical and Health Sciences, Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Clin Microbiol
ISSN: 1098-660X
Language: eng
Dates:
DateEvent
24 August 2020Published
27 May 2020Published Online
22 May 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
RP-2017-08-ST2-012National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272
P30AI045008National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
T32AI007044National Institute of Allergy and Infectious Diseaseshttp://dx.doi.org/10.13039/100000060
F32AI140511National Institute of Allergy and Infectious Diseaseshttp://dx.doi.org/10.13039/100000060
212638Wellcome Trusthttp://dx.doi.org/10.13039/100004440
950Chinese Center for Disease Control and Preventionhttp://dx.doi.org/10.13039/501100004476
PubMed ID: 32461286
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112018
Publisher's version: https://doi.org/10.1128/JCM.00441-20

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