Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid

Karen C. Bloch, Thein Myint, Luke Raymond-Guillen, Chadi Hage, Thomas Davis, Patty W. Wright, Felicia C. Chow, Laila Woc-Colburn, Raed N. Khairy, Alan C. Street, Tomotaka Yamamoto, Amanda Albers, L. Joseph Wheat

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalClinical Infectious Diseases
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Histoplasma
Meningitis
Immunoglobulin M
Cerebrospinal Fluid
Anti-Idiotypic Antibodies
Immunoglobulin G
Antigens
Histoplasmosis
Antibodies
Immunoenzyme Techniques
Central Nervous System
Immunodiffusion
Multicenter Studies
Retrospective Studies

Keywords

  • antibody
  • antigen
  • diagnosis
  • Histoplasmosis
  • meningitis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid. / Bloch, Karen C.; Myint, Thein; Raymond-Guillen, Luke; Hage, Chadi; Davis, Thomas; Wright, Patty W.; Chow, Felicia C.; Woc-Colburn, Laila; Khairy, Raed N.; Street, Alan C.; Yamamoto, Tomotaka; Albers, Amanda; Wheat, L. Joseph.

In: Clinical Infectious Diseases, Vol. 66, No. 1, 01.01.2018, p. 89-94.

Research output: Contribution to journalArticle

Bloch, Karen C. ; Myint, Thein ; Raymond-Guillen, Luke ; Hage, Chadi ; Davis, Thomas ; Wright, Patty W. ; Chow, Felicia C. ; Woc-Colburn, Laila ; Khairy, Raed N. ; Street, Alan C. ; Yamamoto, Tomotaka ; Albers, Amanda ; Wheat, L. Joseph. / Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid. In: Clinical Infectious Diseases. 2018 ; Vol. 66, No. 1. pp. 89-94.
@article{f43941318cc64510880e617d3ccdcf88,
title = "Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid",
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.",
keywords = "antibody, antigen, diagnosis, Histoplasmosis, meningitis",
author = "Bloch, {Karen C.} and Thein Myint and Luke Raymond-Guillen and Chadi Hage and Thomas Davis and Wright, {Patty W.} and Chow, {Felicia C.} and Laila Woc-Colburn and Khairy, {Raed N.} and Street, {Alan C.} and Tomotaka Yamamoto and Amanda Albers and Wheat, {L. Joseph}",
year = "2018",
month = "1",
day = "1",
doi = "10.1093/cid/cix706",
language = "English (US)",
volume = "66",
pages = "89--94",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "1",

}

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

AU - Davis, Thomas

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 - 2018/1/1

Y1 - 2018/1/1

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.

AB - 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.

KW - antibody

KW - antigen

KW - diagnosis

KW - Histoplasmosis

KW - meningitis

UR - http://www.scopus.com/inward/record.url?scp=85040598460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040598460&partnerID=8YFLogxK

U2 - 10.1093/cid/cix706

DO - 10.1093/cid/cix706

M3 - Article

VL - 66

SP - 89

EP - 94

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 1

ER -