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

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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)268-273
Number of pages6
Issue number3
StatePublished - Mar 1 2019

Bibliographical note

Funding Information:
This study was supported, in part, by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (AI001123, AI001124) as well as extramural grants from the National Institute of Allergy and Infectious Diseases (T32AI055433, U01AI089244, UO1AI109657, RO1AIO59681 and RO1AI127704). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Publisher Copyright:
© 2018 Blackwell Verlag GmbH


  • Blastomycosis
  • Cryptococcosis
  • Histoplasmosis
  • antibody detection
  • coccidioidomycosis
  • cross-reactivity


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