Evaluation of the Diagnostic Performance of a Semiquantitative Cryptococcal Antigen Point-of-Care Assay among HIV-Infected Persons with Cryptococcal Meningitis

Kiiza Kandole Tadeo, Audrey Nimwesiga, Richard Kwizera, Lucy Apeduno, Emily Martyn, Michael Okirwoth, Elizabeth Nalintya, Radha Rajasingham, Darlisha A. Williams, Joshua Rhein, David B. Meya, Bosco Kafufu, David R. Boulware, Caleb P. Skipper

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

A newly developed cryptococcal antigen (CrAg) semiquantitative (SQ) lateral flow assay (LFA) provides a semiquantitative result in a rapid one-step test instead of performing serial dilutions to determine CrAg titer. We prospectively compared the diagnostic performance of the CrAgSQ assay (IMMY) with the CrAg LFA (IMMY) on cerebrospinal fluid (CSF) samples collected from persons with HIV-associated meningitis. The CrAgSQ grades (11 to 51) were compared with CrAg LFA titers and quantitative CSF fungal cultures. Among 87 participants screened for HIV-associated meningitis, 60 had cryptococcal meningitis (59 CrAg positive [CrAg1] by LFA and 1 false negative due to prozone with CrAg LFA titer of 1:1,310,000 and culture positivity), and 27 had no cryptococcal meningitis by CrAg LFA or culture. The CrAgSQ on CSF had 100% (60/60) sensitivity and 100% specificity (27/27). CSF CrAg titers ranged from 1:5 to 1:42 million. CrAgSQ grades of 11, 21, 31, 41, and 51 corresponded to median CrAg LFA titers of 1:,10, 1:60, 1:7,680, 1:81,920, and 1:1,474,000, respectively. CSF CrAgSQ grades 31 or higher were always CSF culture positive. Mortality at 14 days for those with low CrAgSQ grade (11 to 31) was 5% (1/22) versus 21% (8/38) with high CrAgSQ grades (41 to 51) (P = 0.084). The CrAgSQ demonstrates excellent diagnostic performance, maintaining both the sensitivity and specificity of the CrAg LFA, and counters false-negative prozone effects. The CrAgSQ assay reading is more complex but does provide useful clinical information about disease burden and probability of culture positivity in a single rapid diagnostic test.

Original languageEnglish (US)
Article numbere00860-21
JournalJournal of clinical microbiology
Volume59
Issue number8
DOIs
StatePublished - Jul 2021

Bibliographical note

Funding Information:
This research was made possible through support from the National Institute of Allergy and Infectious Diseases (T32AI055433, U01AI089244, and K23AI138851), National Institute of Neurologic Disorders and Stroke (R01NS086312), the Fogarty International Center (K01TW010268), and a combined National Institute of Neurologic Disorders and Stroke and Fogarty International Center award (D43TW009345) via the Northern Pacific Global Health Fellows Program. R.K. and D.B.M. are currently supported through the DELTAS Africa Initiative grant number DEL-15-011 to THRiVE-2, from Wellcome Trust grant number 107742/Z/15/Z, and the UK government.

Publisher Copyright:
© 2021 American Society for Microbiology.

Keywords

  • Cryptococcus
  • HIV
  • cryptococcal antigen
  • cryptococcal meningitis
  • semiquantitative assay
  • semiquantitative lateral flow assay

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