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Cryptococcal meningitis diagnosis.

Q During a recent CAP inspection, the inspector recommended we use the cryptococcal antigen test as a replacement for the microscopic examination of CSF (cerebrospinal fluid) specimens by the India ink method. Is there a reason to offer both tests for the diagnosis of cryptococcal meningitis?

A The addition of India ink or nigrosin to CSF sediment and subsequent examination by light microscopy has been commonly used to detect encapsulated strains of Cryptococcus neoformans. (1) A distinctive halo is produced around the yeast cells because the large polysaccharide capsule produced by most cryptococcal strains excludes the ink particles. False-positive results can occur, however, if an inexperienced reader mistakes lymphocytes for cryptococci. The India ink test is simple to perform, rapid, and, when positive, is diagnostic for cryptococcal meningitis. The test's downside is the poor sensitivity, which is approximately 50% in non-AIDS and 80% in AIDS patients, compared to culture; the lower limit of detection is approximately 1,000 yeast cells/mL CSF. (2) In some laboratories, the India ink method is used as a rapid screening test on CSF specimens collected from AIDS patients, who often present with numerous cryptococci in the CSF.

The current test of choice for the laboratory diagnosis of cryptococcal meningitis, however, is the cryptococcal antigen test. This test detects the presence of the cryptococcal capsule in both CSF and serum specimens and is available in different assay formats. The sensitivity of the assay is over 90% (99% in some studies) and varies with the presence of poorly encapsulated strains, the stage of infection, the patient population, the number of organisms present, and the assay methodology. (1,3) Although the test performed on serum is useful for the diagnosis of nonmeningeal cryptococcosis, the sensitivity is lower. Because more reliable results are obtained with the cryptococcal antigen test, it should replace the India ink examination or be performed in addition to the India ink test.


1. Reiss E, Kaufman L, Kovacs JA, Lindsley MD. Clinical immunomycology. In: Rose NR, Hamilton RG, Detrick B, eds. Manual of Clinical Laboratory Immunology. 6th ed. Washington, DC: ASM Press; 2002:559-583.

2. Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am. 2002;16:837-874.

3. Warren NG, Hazen KC. Candida, cryptococcus, and other yeasts of medical importance. In: Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, eds. Manual of Clinical Microbiology. 7th ed. Washington, DC: ASM Press; 1999:1184-1199.

--David Sewell, PhD, ABMM

Director of Microbiology

Veterans Affairs Medical Center

Portland, OR

Edited by Daniel M. Baer, MD

MLO's "Tips from the Clinical Experts" provides practical, up-to-date solutions to readers' technical and clinical issues from a panel of experts in various fields. Readers may send questions to Dan Baer by e-mail at
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Title Annotation:Answering your questions
Author:Sewell, David
Publication:Medical Laboratory Observer
Date:Mar 1, 2005
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