1552. Diagnosis of Central Nervious System Histoplasmosis by Cerebrospinal Fluid EIA Antibody Detection
Session: Poster Abstract Session: Mycology: Diagnostic
Friday, October 28, 2016
Room: Poster Hall
  • CNShistofinalKCB.pdf (253.8 kB)
  • Background: Central nervous system (CNS) histoplasmosis is a life-threatening condition, and represents a diagnostic and therapeutic challenge. Culture of H. capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic, however this test is insensitive and slow growth may result in significant treatment delay. We performed a multicenter case-control study to evaluate the use of CSF EIA antibody (Ab) testing to expedite and improve diagnosis of CNS histoplasmosis. Methods: Cases were classified as patients with CNS inflammation (CSF WBC>5 mm3/ml) plus laboratory confirmation of H. capsulatum in CNS samples or from extra-CNS sites with no alternative etiology for pleocytosis. Controls were patients who were evaluated for CNS histoplasmosis by antigen testing of the CSF with either an alternative diagnosis (n=134) or histoplasmosis with no evidence of CNS involvement (n=10). Histoplasma EIA IgG and IgM Ab assay was performed on CSF as previously described, except that CSF was diluted 1:25. Results of >10 units were considered positive.

    Results: 52 cases and 144 controls were identified (Table). More than half of patients with CNS histoplasmosis were immunocompromised. CSF EIA IgG assay had a sensitivity=79.6%, specificity=97.2%, PPV= 90.7% and NPV=93.3%. The combination of elevated CSF EIA Ab and/or antigen resulted in a sensitivity=98.1%, specificity= 97.2%, PPV=92.7%, and NPV=99.3%


    Cases (%)

    Controls (%)


    28/52 (53.8)

    56/144 (38.9)


    11/52 (21.1)

    20/144 (13.9)

    Organ transplant

    6/52 (11.5)

    12/144 (8.3)

    TNF-alpha inhibitor

    2/52 (3.8)

    4/144 (2.8)

    CSF testing


    9/50 (18)

    0/144 (0)

    Immunodiffusion (ID) Ab

    15/44 (34.1)

    0/13 (0)

    Complement fixation (CF) Ab

    6/12 (50)

    1/12 (8.3)


    25/47 (53.2)

    12/111 (10.8)

    Antigen (Ag)

    42/51 (82.4)

    0/140 (0)

    EIA IgG Ab

    39/49 (79.6)

    4/144 (2.8)

    EIA IgM Ab

    14/48 (29.2)

    4/144 (2.8)

    EIA or Ag

    51/52 (98.1)

    4/144 (2.8)

    Extra-CSF testing

    Urine Ag

    34/49 (69.4)

    10/47 (21.3)

    Serum Ag

    18/31 (58.1)

    6/30 (20)

    Urine or serum Ag

    37/49 (75.5)

    10/47 (21.3)

    Conclusion: Detection of CSF EIA Ab is superior to fungal culture, commercially available CSF ID or CF assays, and CSF β-D-Glucan (BDG) detection for the diagnosis of CNS histoplasmosis. CSF EIA Ab offers an additional tool in the rapid diagnosis and treatment of CNS histoplasmosis.

    Karen Bloch, MD, MPH, FIDSA1, Thein Myint, MBBS2, Luke Guillen, MD3, Amanda Albers, BS4 and L. Joseph Wheat, MD, FIDSA4, (1)Medicine & Health Policy, Vanderbilt University Medical Center, Nashville, TN, (2)Division of Infectious Diseases, University of Kentucky, Lexington, KY, (3)Medicine, Indiana University School of Medicine, Indianapolis, IN, (4)MiraVista Diagnostics, Indianapolis, IN


    K. Bloch, None

    T. Myint, None

    L. Guillen, None

    A. Albers, MiraVista Diagnostics: Employee , Salary

    L. J. Wheat, MiraVista Diagnostics: Owner and director , Owner

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