Coccidioidomycosis

Thompson, George R.; Sharma, Shobha; Bays, Derek; Pruitt, Rachel; Engelthaler, David M.; Bowers, Jolene R.; Driebe, Elizabeth M.; Davis, Michael R.; Libke, Robert; Cohen, Stuart H.; Pappagianis, Demosthenes

doi:10.1378/chest.12-1312

Cited by 33 publications

(13 citation statements)

References 19 publications

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“…(234), Coccidioides spp. (235), and Fusarium spp. (236), but the possibility for clinical implementation of these assays seems unlikely for the foreseeable future, either because serologic assays are already highly sensitive and specific, thus lowering the need for molecular techniques, as is the case for Cryptococcus spp.…”

Section: Pcrmentioning

confidence: 98%

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

et al. 2014

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SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use.

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Section: Pcrmentioning

confidence: 98%

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

et al. 2014

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“…Specimens producing discrepant results between the culture and GeneSTAT Coccidioides assay in the prospective section of the study were tested further using a different validated PCR assay (TGen reference assay) and bidirectional sequencing to resolve the discrepancy. The TGen reference assay was a completely independent PCR assay targeting the internal transcribed spacer (ITS) region, whereas the GeneSTAT assay targets a genus-specific transposon genome, the specifics of which have been published elsewhere ( 15 ).…”

Section: Methodsmentioning

confidence: 99%

Multicenter Clinical Validation of a Cartridge-Based Real-Time PCR System for Detection of Coccidioides spp. in Lower Respiratory Specimens

et al. 2018

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Available methods for the diagnosis of coccidioidomycosis have significant shortcomings relative to accuracy and timeliness. We retrospectively and prospectively evaluated the diagnostic performance and reproducibility of a new cartridge-based real-time PCR assay for Coccidioides spp. directly in lower respiratory secretions and compared them to today's “gold standard,” fungal culture. The GeneSTAT Coccidioides assay uses a 106-bp target sequence repeated multiple times (∼60×) per genome, thus lowering the limit of detection (LOD) for extracted DNA to 10 genome equivalents/ml. A total of 332 prospective and retrospective individual patient specimens were tested. The retrospective samples consisted of 100 bronchoalveolar lavage or bronchial wash (BAL/BW) (51 positive and 49 negative by culture) specimens that had been collected previously and stored at −70°C. These samples were tested by the GeneSTAT Coccidioides assay across three clinical test sites. The sensitivity was 100%, and the specificity ranged between 93.8% and 100%. There was minimal variance in the percent agreement across the three sites, 95.6% to 100%. Additionally, a total of 232 fresh (prospective) deidentified BAL/BW specimens were tested across the three clinical sites, which included a number of specimens from Southern California to provide a diversity of isolates. Specimens were tested by fungal culture, with any isolates of Coccidioides, except for one, being confirmed by molecular means (AccuProbe). The sensitivity of the GeneSTAT Coccidioides assay across the three sites was 100% (4/4) for positive fresh specimens, and the overall specificity of the assay was 99.6% (227/228), ranging from 98.1% to 100%. In testing for cross-reactivity, the assay was 100% specific when screened against 47 different bacterial, viral, and fungal species.

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“…Nucleic acid amplification using polymerase chain reaction (PCR) tests are not commercially available for the endemic mycoses, but detection of DNA in clinical specimens has been evaluated for: Blastomyces (sensitivity 60–86%) [ 125 , 126 , 127 ], Coccidioides (~50%) [ 128 , 129 ], Histoplasma (18–65%) [ 106 , 130 ], Paracoccidioides (91–100%) [ 114 , 131 ] Sporothrix (83–92%) [ 132 , 133 , 134 ], and Talaromyces (70–86%) [ 135 ].…”

Section: Consensus Recommendationsmentioning

confidence: 99%

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

Jenks

Gangneux

Schwartz

et al. 2020

JoF

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Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity to conventional culture techniques, serologic tests, and PCR-based assays in patients undergoing 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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Coccidioidomycosis

Cited by 33 publications

References 19 publications

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

Multicenter Clinical Validation of a Cartridge-Based Real-Time PCR System for Detection of Coccidioides spp. in Lower Respiratory Specimens

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

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