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Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid.
Clin Infect Dis 2018; 66(1):89-94CI

Abstract

Background

Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis.

Methods

Residual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics.

Results

A total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immunocompromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases.

Conclusions

Testing CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis.

Authors+Show Affiliations

Vanderbilt University School of Medicine, Nashville, Tennessee.University of Kentucky School of Medicine, Lexington.Indiana University School of Medicine, Indianapolis.Indiana University School of Medicine, Indianapolis.Indiana University School of Medicine, Indianapolis.Vanderbilt University School of Medicine, Nashville, Tennessee.School of Medicine, University of California, San Francisco.Baylor College of Medicine, Houston, Texas.Sparks Center for Infectious Diseases, Fort Smith, Arkansas.Royal Melbourne Hospital, Parkville, Victoria, Australia.University of Tokyo Hospital, Japan.MiraVista Diagnostics, Indianapolis, Indiana.MiraVista Diagnostics, Indianapolis, Indiana.

Pub Type(s)

Evaluation Studies
Journal Article
Multicenter Study

Language

eng

PubMed ID

29020213

Citation

Bloch, Karen C., et al. "Improvement in Diagnosis of Histoplasma Meningitis By Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 66, no. 1, 2018, pp. 89-94.
Bloch KC, Myint T, Raymond-Guillen L, et al. Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid. Clin Infect Dis. 2018;66(1):89-94.
Bloch, K. C., Myint, T., Raymond-Guillen, L., Hage, C. A., Davis, T. E., Wright, P. W., ... Wheat, L. J. (2018). Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 66(1), pp. 89-94. doi:10.1093/cid/cix706.
Bloch KC, et al. Improvement in Diagnosis of Histoplasma Meningitis By Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid. Clin Infect Dis. 2018 01 6;66(1):89-94. PubMed PMID: 29020213.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid. AU - Bloch,Karen C, AU - Myint,Thein, AU - Raymond-Guillen,Luke, AU - Hage,Chadi A, AU - Davis,Thomas E, AU - Wright,Patty W, AU - Chow,Felicia C, AU - Woc-Colburn,Laila, AU - Khairy,Raed N, AU - Street,Alan C, AU - Yamamoto,Tomotaka, AU - Albers,Amanda, AU - Wheat,L Joseph, PY - 2017/03/29/received PY - 2017/08/07/accepted PY - 2017/10/12/pubmed PY - 2019/10/1/medline PY - 2017/10/12/entrez KW - antibody KW - antigen KW - diagnosis KW - histoplasmosis KW - meningitis SP - 89 EP - 94 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 66 IS - 1 N2 - Background: Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis. Methods: Residual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics. Results: A total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immunocompromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases. Conclusions: Testing CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/29020213/Improvement_in_Diagnosis_of_Histoplasma_Meningitis_by_Combined_Testing_for_Histoplasma_Antigen_and_Immunoglobulin_G_and_Immunoglobulin_M_Anti_Histoplasma_Antibody_in_Cerebrospinal_Fluid_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cix706 DB - PRIME DP - Unbound Medicine ER -