Evaluation of a newly developed lateral flow immunoassay for the diagnosis of cryptococcosis

Abstract

Background: Cryptococcosis is a common opportunistic infection of human immunodeficiency virus (HIV)-infected individuals mostly occurring in resource-limited countries. This study compares the performance of a recently developed lateral flow immunoassay (LFA) to blood culture and enzyme immunoassay (EIA) for the diagnosis of cryptococcosis.

Methods: Archived sera from 704 HIV-infected patients hospitalized for acute respiratory illness in Thailand were tested for cryptococcal antigenemia using EIA. All EIA-positive and a subset of EIA-negative sera were tested by LFA, with results recorded after 5 and 15 minutes incubation. Urine from patients with LFA- and EIA-positive sera was tested by LFA. Antigen results from patients with positive cryptococcal blood cultures were compared.

Results: Of 704 sera, 92 (13%) were positive by EIA; among the 91 EIA-positive sera tested by LFA, 82 (90%) and 87 (96%) were LFA positive when read after 5 and 15 minutes, respectively. Kappa agreement of EIA and LFA for sera was 0.923 after 5 minutes and 0.959 after 15 minutes, respectively. Two of 373 EIA-negative sera were LFA positive at both time points. Of 74 urine specimens from EIA-positive patients, 52 (70.3%) were LFA positive. EIA was positive in 16 of 17 sera from blood culture-positive patients (94% sensitivity), and all sera were positive by LFA (100% sensitivity).

Conclusions: A high level of agreement was shown between LFA and EIA testing of serum. The LFA is a rapid, easy-to-perform assay that does not require refrigeration, demonstrating its potential usefulness as a point-of-care assay for diagnosis of cryptococcosis in resource-limited countries.

Figure 1.

Flow chart of the specimen testing algorithm. A total of 704 sera were tested by cryptococcal antigen enzyme immunoassay (CrAg-EIA); 91 EIA-positive sera were tested by lateral flow immunoassay (LFA); a subset of CrAg-EIA–negative sera (n = 373) was further tested by LFA. Specimens from Cryptococcus blood culture–positive patients (n = 17) were tested by LFA and EIA. A total of 74 urine samples from serum CrAg-EIA–positive patients were tested by LFA. HIV, human immunodeficiency virus.