Evaluation of serum cryptococcal antigen testing using two novel semiquantitative lateral flow assays in persons with cryptococcal antigenemia

Caleb Skipper, Kiiza Tadeo, Emily Martyn, Elizabeth Nalintya, Radha Rajasingham, David B. Meya, Bosco Kafufu, Joshua Rhein, David R. Boulware

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Early cryptococcal disease can be detected via circulating antigen in blood before fulminant meningitis develops, when early antifungal therapy improves survival. Two semiquantitative cryptococcal antigen (CrAg) lateral flow assays (LFAs) have been developed, but their diagnostic performance has not been defined. Cryopreserved serum samples from HIV-infected Ugandans obtained as part of a prospective CrAg-screening cohort were tested in duplicate for CrAg by the CrAgSQ (IMMY) and CryptoPS (Biosynex) lateral flow assays. Case-controlled diagnostic performance was measured using the FDA-approved CrAg LFA (IMMY) as a reference standard via McNemar's test. Of 99 serum samples tested, 57 were CrAg positive (CrAg+) by the CrAg LFA reference standard. By CrAgSQ, 57 were read as positive, with 98% sensitivity (56/57; 95% confidence interval [CI], 0.91 to 0.99) and 98% specificity (41/42; 95% CI, 0.88 to 0.99) (McNemar's, P = 0.99). The sample with a false-negative result by CrAgSQ (n = 1) had a titer of ≤1:5, while the sample with a false-positive result (n = 1) yielded a 1+ result. By CryptoPS, 52 samples were read as positive, with 88% sensitivity (50/57; 95% CI, 0.76 to 0.95) and 95% specificity (40/42; 95% CI, 0.84 to 0.99) (McNemar's, P = 0.18). The CryptoPS false-negative results included samples with titers of ≤1:5 (n = 1), 1:5 (n = 5), and 1:20 (n = 1), while samples with false-positive results by CryptoPS (n = 2) yielded Positive results. The CryptoPS assay missed 35% (7/20) of samples with CrAg LFA titers of ≤1:20. The new semiquantitative CrAg LFAs allow rapid estimation of titer levels in easy-to-perform platforms. The CrAgSQ demonstrated better qualitative sensitivity and specificity than the CryptoPS compared to the reference standard. The exact grading of the CrAgSQ results has some subjectivity, with interreader variability; however, qualitative reads were generally concordant for both assays.

Original languageEnglish (US)
Article numbere02046-19
JournalJournal of clinical microbiology
Volume58
Issue number4
DOIs
StatePublished - Mar 25 2020

Bibliographical note

Funding Information:
This research was made possible through support from the National Institute of Allergy and Infectious Diseases (grants number T32AI055433, U01AI089244, and K23AI138851), the National Institute of Neurologic Disorders and Stroke (grant number R01NS086312), the Fogarty International Center (grant number K01TW010268), and a combined National Institute of Neurologic Disorders and Stroke and Fogarty International Center award (grant number D43TW009345) via the Northern Pacific Global Health Fellows program.

Publisher Copyright:
© 2020 American Society for Microbiology. All Rights Reserved.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • CrAg
  • CrAg positive
  • Cryptococcal antigen
  • Cryptococcal antigenemia
  • Cryptococcal meningitis
  • Cryptococcus
  • Cryptococcus neoformans
  • HIV
  • Human immunodeficiency virus

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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