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. 2011 Nov;53(10):1019-23.
doi: 10.1093/cid/cir613. Epub 2011 Sep 21.

Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis

Joseph N Jarvis  1 , Ann Percival, Sean Bauman, Joy Pelfrey, Graeme Meintjes, G Ntombomzi Williams, Nicky Longley, Thomas S Harrison, Thomas R Kozel
Affiliations

Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis

Joseph N Jarvis et al. Clin Infect Dis. 2011 Nov.

Abstract

Background: Many deaths from cryptococcal meningitis (CM) may be preventable through early diagnosis and treatment. An inexpensive point-of-care (POC) assay for use with urine or a drop of blood would facilitate early diagnosis of cryptococcal infection in resource-limited settings. We compared cryptococcal antigen (CRAG) concentrations in plasma, serum, and urine from patients with CM, using an antigen-capture assay for glucuronoxylomannan (GXM) and a novel POC dipstick test.

Methods: GXM concentrations were determined in paired serum, plasma, and urine from 62 patients with active or recent CM, using a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). A dipstick lateral-flow assay developed using the same monoclonal antibodies for the sandwich ELISA was tested in parallel. Correlation coefficients were calculated using Spearman rank test.

Results: All patients had detectable GXM in serum, plasma, and urine using the quantitative ELISA. Comparison of paired serum and plasma showed identical results. There were strong correlations between GXM levels in serum/urine (r(s) = 0.86; P < .001) and plasma/urine (r(s) = 0.85; P < .001). Levels of GXM were 22-fold lower in urine than in serum/plasma. The dipstick test was positive in serum, plasma, and urine in 61 of 62 patients. Dipstick titers correlated strongly with ELISA. Correlations between the methods were 0.93 (P < .001) for serum, 0.94 (P < .001) for plasma, and 0.94 (P < .001) for urine.

Conclusions: This novel dipstick test has the potential to markedly improve early diagnosis of CM in many settings, enabling testing of urine in patients presenting to health care facilities in which lumbar puncture, or even blood sampling, is not feasible.

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Figures

Figure 1.
Figure 1.
A, Correlation of glucuronoxylomannan concentrations in paired serum and plasma, serum and urine, and plasma and urine measured by quantitative enzyme-linked immunosorbent assay (ELISA). B, correlation of cryptococcal antigen (CRAG) titers from the quantitative ELISA and lateral flow assay (LFA) in serum, plasma, and urine from 62 subjects with recent or current cryptococcal meningitis. Correlations were calculated using Spearman rank-order correlation. Abbreviation: EIA, enzyme immunoassay.
Figure 2.
Figure 2.
Signal strength of lateral flow dipstick with purified serotype A glucuronoxylomannan (GXM) at various concentrations.
See this image and copyright information in PMC

Comment in

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