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 A.; Davis, Thomas E.; Wright, Patty W.; Chow, Felicia C.; Woc-Colburn, Laila; Khairy, Raed N; Street, Alan; Yamamoto, Tomotaka; Albers, Amanda; Wheat, L. Joseph

doi:10.1093/cid/cix706

Cited by 54 publications

(69 citation statements)

References 17 publications

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“…CSF specimens from six subjects with cryptococcosis not involving the CNS from the NIH were also tested as controls. Additional controls included CSF specimens from 51 subjects at Indiana University Medical Center in whom fungal meningitis was not suspected clinically and in whom Histoplasma antigen testing was not performed from an IRB‐approved study . Additional CSF specimens were included from 10 subjects with Histoplasma meningitis and 10 subjects with Coccidioides meningitis with high levels of Histoplasma and Coccidioides antigen and anti‐ Histoplasma or anti‐ Coccidioides antibodies by EIA .…”

Section: Methodsmentioning

confidence: 99%

“…Additional controls included CSF specimens from 51 subjects at Indiana University Medical Center in whom fungal meningitis was not suspected clinically and in whom Histoplasma antigen testing was not performed from an IRB-approved study. 11 Additional CSF specimens were included from 10 subjects with Histoplasma meningitis and 10 subjects with Coccidioides meningitis with high levels of Histoplasma and Coccidioides antigen and anti-Histoplasma or anti-Coccidioides antibodies by EIA. 2,12 Cryptococcal meningitis was excluded by CSF fungal culture and/or CSF cryptococcal antigen testing via latex agglutination (ImmunoMyologics or Meridian Biosciences) in these subjects.…”

Section: Histoplasmosismentioning

confidence: 99%

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

Bahr

Panackal

Durkin³

et al. 2019

Mycoses

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Summary 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.

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Section: Methodsmentioning

confidence: 99%

Section: Histoplasmosismentioning

confidence: 99%

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

Bahr

Panackal

Durkin³

et al. 2019

Mycoses

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“…Endemic systemic mycoses are life-threatening diseases which are challenging from both diagnostic and therapeutic points of view. Serodiagnostic methods have been improved for many dimorphic-diphasic fungi, including Histoplasma capsulatum [64], Coccidioides immitis [65], Paracoccidioides brasiliensis [66], Blastomyces dermatitidis [67], Sporothrix schenckii [68], and Talaromyces marneffei [69]. However, most of these techniques are not currently available in developing countries.…”

Section: Dimorphic Mycosesmentioning

confidence: 99%

Identification of Mycoses in Developing Countries

Arastehfar

Wickes

İlkit

et al. 2019

JoF

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Extensive advances in technology offer a vast variety of diagnostic methods that save time and costs, but identification of fungal species causing human infections remains challenging in developing countries. Since the echinocandins, antifungals widely used to treat invasive mycoses, are still unavailable in developing countries where a considerable number of problematic fungal species are present, rapid and reliable identification is of paramount importance. Unaffordability, large footprints, lack of skilled personnel, and high costs associated with maintenance and infrastructure are the main factors precluding the establishment of high-precision technologies that can replace inexpensive yet time-consuming and inaccurate phenotypic methods. In addition, point-of-care lateral flow assay tests are available for the diagnosis of Aspergillus and Cryptococcus and are highly relevant for developing countries. An Aspergillus galactomannan lateral flow assay is also now available. Real-time PCR remains difficult to standardize and is not widespread in countries with limited resources. Isothermal and conventional PCR-based amplification assays may be alternative solutions. The combination of real-time PCR and serological assays can significantly increase diagnostic efficiency. However, this approach is too expensive for medical institutions in developing countries. Further advances in next-generation sequencing and other innovative technologies such as clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostic tools may lead to efficient, alternate methods that can be used in point-of-care assays, which may supplement or replace some of the current technologies and improve the diagnostics of fungal infections in developing countries.

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“…[51][52][53] IgM and IgG can be detected in CSF using a two-tiered test: first with EIA, which is sensitive but relatively nonspecific, followed by confirmatory complement fixation or immunodiffusion, which are specific but insensitive. 54,55 Several recent studies highlight the potential use of antigen for direct detection of pathogen, 54,56 but these assays are currently not U.S. Food and Drug Administration (FDA)-approved.…”

Section: Fungi Generally Diagnosed By Serologymentioning

confidence: 99%

Diagnostic Testing in Central Nervous System Infection

2019

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Several key points should guide providers managing a patient with suspected CNS infection. The first is the importance of developing a plan for the diagnostic workup. Clinicians are recommended to first test for the most likely and Keywords ► meningitis ► encephalitis ► diagnostic ► metagenomic sequencing AbstractPatients with central nervous system (CNS) infection experience very high levels of morbidity and mortality, in part because of the many challenges inherent to the diagnosis of CNS infection and identification of a causative pathogen. The clinical presentation of CNS infection is nonspecific, so clinicians must often order and interpret many diagnostic tests in parallel. This can be a daunting task given the large number of potential pathogens and the availability of different testing modalities. Here, we review traditional diagnostic techniques including Gram stain and culture, serology, and polymerase chain reaction (PCR). We highlight which of these are recommended for the pathogens most commonly tested among U.S. patients with suspected CNS infection. Finally, we describe the newer broadrange diagnostic approaches, multiplex PCR and metagenomic sequencing, which are increasingly used in clinical practice.This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.• What pathogen is being interrogated;• How to test for it (e.g., serology vs. PCR);• Where to look (e.g., CSF vs. blood);• When to test (e.g., need for paired acute/convalescent sera).Another important consideration is the turnaround time between ordering a test and receiving its results, since clinical decisions often need to be made empirically while awaiting test results. In general, PCR tests are rapid and often available in-house, while specialized serology tests may only be available at reference laboratories. However, there is substantial variation between clinical microbiology laboratories, so close communication with laboratory personnel is essential. Detection of Immune Response by SerologySerological tests are widely used in the diagnosis of CNS infections, particularly for pathogens present at low levels or for brief periods of time, and for diseases whose manifestations are primarily mediated by the host antibody response.

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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

Abstract: Improvements in the immunologic tests performed on cerebrospinal fluid have increased the sensitivity and reduced the turnaround time for diagnosis of central nervous system histoplasmosis over prior antigen and antibody detection methods and culture.

Cited by 54 publications

References 17 publications

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

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

Identification of Mycoses in Developing Countries

Diagnostic Testing in Central Nervous System Infection

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