Background HIV-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. Methods We 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. Results StrongStep 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. Conclusions We 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.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Neurologic Diseases and Stroke and Fogarty International Center, R01NS086312, https://www.ninds.nih.gov, DRB; Fogarty International Center, K01TW010268, https://www. fic.nih.gov, JR; Fogarty International Center, R25TW009345, https://www.fic.nih.gov; National Institute of Allergy and Infectious Diseases, T32AI055433, https://www.niaid.nih.gov/, DRB; National Institute of Allergy and Infectious Diseases, U01AI089244, https://www.niaid.nih. gov/ DRB; Doris Duke International Clinical Research Fellows Program, https://www.dom. umn.edu/ SCB; United kingdom Medical Research Council, MR/M007413/1, https://www.mrc.ac.uk, DBM. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank all the members of the ASTRO-CM research team at the Infectious Disease Institute, Kampala Uganda for providing leadership, patient care, sample storage, and data collection including: team lead Dr. David Meya (firstname.lastname@example.org), Alisat Sadiq, Jane Ndyetukira, Cynthia Ahimbisibwe, Carol Namujju, Alice Namudde, Kwizera Richard and Paul Kirumira. We also thank the Makerere University Medical School Microbiology Laboratory team.
© 2018 Mpoza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.