Coccidioidomycosis Complement Fixation Titer Trends in the Age of Antifungals

Mchardy, Ian Howard; Dinh, Bao Tran; Waldman, Sarah; Stewart, Ethan R.; Bays, Derek; Pappagianis, Demosthenes; Thompson, George R.

doi:10.1128/jcm.01318-18

Cited by 48 publications

(45 citation statements)

References 19 publications

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“…Whether the high false-positive rate in IgM ELISA was due to the usage of crude multi-component reference antigens in the diagnostic kit remains to be determined. Nonetheless, the reported findings and data from this study suggest that a combination of anti-rBGL2ur IgM-ELISA and anti-rCTS1ur IgG-ELISA could improve clinical serodiagnosis of potential coccidioidomycosis cases [35] and may potentially provide suitable cut-off values for assessment of coccidioidomycosis patients who may require immediate antifungal therapy [36].…”

Section: Discussionmentioning

confidence: 99%

Characterization of an Uncinocarpus reesii-expressed recombinant tube precipitin antigen of Coccidioides posadasii for serodiagnosis

Yu¹,

Holbrook²,

Liao³

et al. 2019

PLoS ONE

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Early and accurate diagnosis of coccidioidomycosis, also known as Valley fever, is critical for appropriate disease treatment and management. Current serodiagnosis is based on the detection of patient serum antibodies that react with tube precipitin (TP) and complement fixation (CF) antigens of Coccidioides . IgM is the first class of antibodies produced by hosts in response to coccidioidal insults. The highly glycosylated β-glucosidase 2 (BGL2) is a major active component of the TP antigen that stimulates IgM antibody responses during early Coccidioides infection. The predominant IgM epitope on BGL2 is a unique 3-O-methyl-mannose moiety that is not produced by commonly used protein expression systems. We genetically engineered and expressed a recombinant BGL2 (rBGL2ur), derived from Coccidioides , in non-pathogenic Uncinocarpus reesii , a fungus phylogenetically related to the Coccidioides pathogen. The rBGL2ur protein was purified from the culture medium of transformed U . reesii by nickel affinity chromatography, and the presence of 3-O-methyl mannose was demonstrated by gas chromatography. Seroreactivity of the purified rBGL2ur protein was tested by enzyme-linked immunosorbent assays using sera from 90 patients with coccidioidomycosis and 134 control individuals. The sensitivity and specificity of the assay with rBGL2ur were 78.8% and 87.3%, respectively. These results were comparable to those obtained using a proprietary MiraVista Diagnostic (MVD) IgM (63.3% sensitivity; 96.3% specificity), but significantly better than the ID-TP assay using non-concentrated patient sera (33.3% sensitivity; 100% specificity). Expression of rBGL2ur in U . reesii retains its antigenicity for coccidioidomycosis serodiagnosis and greatly reduces biosafety concerns for antigen production, as Coccidioides spp. are biological safety level 3 agents.

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Section: Discussionmentioning

confidence: 99%

Characterization of an Uncinocarpus reesii-expressed recombinant tube precipitin antigen of Coccidioides posadasii for serodiagnosis

Yu¹,

Holbrook²,

Liao³

et al. 2019

PLoS ONE

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“…In this group, serology has been found to be helpful diagnostically, but also correlates with patient symptoms and is useful to follow prognostically as a biomarker of infection. Relapse of infection is typically accompanied by a rise in the complement fixation (CF) antibody titer (89). Serology of blastomycosis is less helpful due to the lower sensitivity and specificity of testing (90)(91)(92).…”

Section: Serologymentioning

confidence: 99%

“…It is important to recall that in the immunosuppressed patient population the endemic mycoses, particularly Coccidioides or Histoplasma, may recur years after initial infection, and serology may not be positive or may have aberrant kinetics compared to immunocompetent hosts (89,100,101).…”

Section: Serologymentioning

confidence: 99%

Diagnosis of Breakthrough Fungal Infections in the Clinical Mycology Laboratory: An ECMM Consensus Statement

Jenks¹,

Gangneux²,

Schwartz³

et al. 2020

Preprint

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Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity of conventional culture techniques, serologic tests, and PCR-based assays in patients on antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.

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“…Complement fixation IgG is additionally useful to monitor disease activity over time and can help inform risk of disseminated disease. 15 The gold standard of diagnosis of disseminated coccidioidomycosis infection remains histopathologic confirmation either by direct visualization of a spherule or growth in fungal cultures. 16 Polymerase chain reaction testing of sputum samples is an emerging diagnostic technique that has been found to have similar sensitivity rates to fungal culture.…”

Section: Commentarymentioning

confidence: 99%