Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies.

Abstract

BACKGROUND/OBJECTIVES:

Antibody detection is commonly used for diagnosis of histoplasmosis, and cross-reactions have been recognised due to endemic mycoses but not cryptococcosis. We observed cross-reactions in an anti-Histoplasma antibody enzyme immunoassay (EIA) in the cerebrospinal fluid (CSF) from a patient with cryptococcal meningitis and sought to assess the risk of cross-reactive anti-Histoplasma antibodies in persons with cryptococcal meningitis.

METHODS:

An anti-cryptococcal antibody EIA was developed to measure CSF antibody response in HIV-infected subjects from Kampala, Uganda and previously healthy, HIV-negative subjects at the National Institutes of Health (NIH) with cryptococcal meningitis. Specimens were tested for cross-reactivity in assays for IgG anti-Histoplasma, anti-Blastomyces and anti-Coccidioides antibodies.

RESULTS:

Among 61 subjects with cryptococcal meningitis (44 Kampala cohort, 17 NIH cohort), elevated CSF anti-cryptococcal antibody levels existed in 38% (23/61). Of the 23 CSF specimens containing elevated anti-cryptococcal antibodies, falsely positive results were detected in antibody EIAs for histoplasmosis (8/23, 35%), coccidioidomycosis (6/23, 26%) and blastomycosis (1/23, 4%). Overall, 2% (2/81) of control CSF specimens had elevated anti-cryptococcal antibody detected, both from Indiana.

CONCLUSIONS:

Cryptococcal meningitis may cause false-positive results in the CSF for antibodies against Histoplasma, Blastomyces and Coccidioides. Fungal antigen testing should be performed to aid in differentiating true- and false-positive antibody results in the CSF.

• Authors: Nathan C Bahr, Anil A Panackal, Michelle M Durkin, Melinda L Smedema, Wesley Keown, Thomas E Davis, Luke Raymond-Guillen, Yoon-Dong Park, Kieren A Marr, Bettina C Fries, Peter R Williamson, David R Boulware, L Joseph Wheat
• Journal: Mycoses (Mycoses) Vol. 62 Issue 3 Pg. 268-273 (Mar 2019) ISSN: 1439-0507 [Electronic] Germany
• PMID: 30565753 (Publication Type: Journal Article)
• Copyright: © 2018 Blackwell Verlag GmbH.

Chemical References

• Antibodies, Fungal

Topics

• Adult
• Antibodies, Fungal (analysis)
• Blastomyces (immunology)
• Cerebrospinal Fluid (chemistry)
• Coccidioides (immunology)
• Cross Reactions
• False Positive Reactions
• HIV Infections (complications)
• Histoplasma (immunology)
• Humans
• Meningitis, Cryptococcal (diagnosis)
• Prospective Studies
• Serologic Tests (methods)
• Uganda
• United States