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 journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)268-273
Number of pages6
JournalMycoses
Volume62
Issue number3
DOIs
StatePublished - Mar 1 2019

Keywords

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

ASJC Scopus subject areas

  • Dermatology
  • Infectious Diseases

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    Bahr, N. C., Panackal, A. A., Durkin, M. M., Smedema, M. L., Keown, W., Davis, T. E., Raymond-Guillen, L., Park, Y. D., Marr, K. A., Fries, B. C., Williamson, P. R., Boulware, D. R., & Wheat, L. J. (2019). Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies. Mycoses, 62(3), 268-273. https://doi.org/10.1111/myc.12882