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
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.
Statistics
Item downloaded times since 27 Aug 2020.
Actions (login required)
![Edit Item](/style/images/action_view.png) |
Edit Item |