Development of an Interferon-Gamma Release Assay (IGRA) to Aid Diagnosis of Histoplasmosis

Datta, Kausik; LaRue, Richard W.; Permpalung, Nitipong; Das, Sukanya; Zhang, Sean X.; Steinke, Seema Mehta; Bushkin, Yuri; Nosanchuk, Joshua D.; Marr, Kieren A.

doi:10.1128/jcm.01128-22

Cited by 4 publications

(3 citation statements)

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“…The graphical Bland–Altman approach is frequently used in analytical chemistry to compare two analytical methods for the quantitative determination of analytes in biological samples [ 5 ]. The ROC approach is also a graphical plot that is often used to measure differences between two methods of measurement of analytes, although the main aim of this approach is testing disagreement between two approaches, especially in clinical diagnosis [ 33 ]. Given the potentially very small differences in the retention times of isotopologs in chromatography [ 1 , 2 , 3 ], we investigated, in the present study, the utility of the Bland–Altman and ROC approaches in the GC-MS analyses of selected endogenous analytes in human plasma, serum and urine samples.…”

Section: Discussionmentioning

confidence: 99%

Application of the Bland–Altman and Receiver Operating Characteristic (ROC) Approaches to Study Isotope Effects in Gas Chromatography–Mass Spectrometry Analysis of Human Plasma, Serum and Urine Samples

Tsikas

2024

Molecules

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The Bland–Altman approach is one of the most widely used mathematical approaches for method comparison and analytical agreement. This work describes, for the first time, the application of Bland–Altman to study 14N/15N and 1H/2H (D) chromatographic isotope effects of endogenous analytes of the L-arginine/nitric oxide pathway in human plasma, serum and urine samples in GC-MS. The investigated analytes included arginine, asymmetric dimethylarginine, dimethylamine, nitrite, nitrate and creatinine. There was a close correlation between the percentage difference of the retention times of the isotopologs of the Bland–Altman approach and the area under the curve (AUC) values of the receiver operating characteristic (ROC) approach (r = 0.8619, p = 0.0047). The results of the study suggest that the chromatographic isotope effects in GC-MS result from differences in the interaction strengths of H/D isotopes in the derivatives with the hydrophobic stationary phase of the GC column. D atoms attenuate the interaction of the skeleton of the molecules with the lipophilic GC stationary phase. Differences in isotope effects in plasma or serum and urine in GC-MS are suggested to be due to a kind of matrix effect, and this remains to be investigated in forthcoming studies using Bland–Altman and ROC approaches.

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Section: Discussionmentioning

confidence: 99%

Application of the Bland–Altman and Receiver Operating Characteristic (ROC) Approaches to Study Isotope Effects in Gas Chromatography–Mass Spectrometry Analysis of Human Plasma, Serum and Urine Samples

Tsikas

2024

Molecules

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“…Screening these individuals for prior infection might be a useful approach but no such data exists. One candidate test could be an interferon-gamma release assay that assesses T-cell responses to H. capsulatum antigens, whether or not this would be effective is not clear [40]. Antigen testing would likely miss many at-risk cases.…”

Section: Histoplasmosismentioning

confidence: 99%

Endemic mycoses – are we making progress in management?

Bahr,

Thompson

2023

Current Opinion in Infectious Diseases

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Purpose of review The endemic fungi are a significant cause of morbidity and mortality in effected patients. The range of endemicity for these are expanding with infections observed outside of traditional locations. Enhanced diagnostic and treatment practices may significantly alter patient outcomes. Recent findings Recently completed clinical trials have focused on an assessment of improving efficacy while minimizing patient toxicity. Practice changing trials have been completed in histoplasmosis showing the utility of a single up-front liposomal amphotericin B dose followed by standard itraconazole dosing. The recent evaluation of several antifungal options including isauvconazole in the treatment of coccidioidomycosis also show promise for additional therapeutic agents. A recently conducted trial has also shown the superiority of amphotericin B therapy over itraconazole in the treatment of talaromycosis. Summary The increased range of endemic mycoses coupled with the growing immunocompromised patient population mandates continued investigation of improved diagnostic and therapeutic options. Advances in these areas have led to more rapid diagnosis and more efficacious antifungal therapy.

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“…Another assay is being investigated to improve the diagnosis of active or latent forms of HPM: Interferon-gamma release assays (IGRAs) [29]. Based on the promising preliminary results, further studies are needed to validate this assay.…”

Section: Serologic Testmentioning

confidence: 99%

Histoplasmosis: Laboratory Diagnosis

Dumea¹,

Danteş²

2023

Infectious Diseases

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The diagnosis of histoplasmosis is based on clinical, imaging, and laboratory evidence of the disease. The gold standards of laboratory diagnosis are the presence of the fungus in the pathological examination of tissues and its isolation (direct microscopy, histopathology, cytopathology) in mycological culture (4–6 weeks required) by clinical specimens. The antibody test, sometimes negative in immunocompromised patients, must be performed at least four weeks after acute infection to be positive. The antibody test is most useful in subacute and chronic forms of histoplasmosis. The antigen test is the most common method for establishing the diagnosis of acute pulmonary histoplasmosis or progressive disseminated histoplasmosis. The antigen test in urine or serum has good sensitivity, better in bronchoalveolar lavage fluid. There are skin sensitivity tests with low sensitivity that are used only for epidemiologic studies and are not recommended for diagnosis. Molecular diagnosis has improved the sensitivity of clinical specimens. Laboratory PCR assays with different molecular targets have been developed. Currently, the main procedure for molecular diagnosis of histoplasmosis is the application of a rapid DNA probe on a fungus isolated from a culture. This chapter summarizes the currently available tools for the laboratory diagnosis of histoplasmosis, focusing on the complexity of the assays and their performance in different clinical contexts.

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Development of an Interferon-Gamma Release Assay (IGRA) to Aid Diagnosis of Histoplasmosis

Abstract: Establishing diagnosis of latent and active histoplasmosis is challenging. Interferon gamma-release assays (IGRAs) may provide evidence of latent and active infection.

Cited by 4 publications

References 50 publications

Application of the Bland–Altman and Receiver Operating Characteristic (ROC) Approaches to Study Isotope Effects in Gas Chromatography–Mass Spectrometry Analysis of Human Plasma, Serum and Urine Samples

Application of the Bland–Altman and Receiver Operating Characteristic (ROC) Approaches to Study Isotope Effects in Gas Chromatography–Mass Spectrometry Analysis of Human Plasma, Serum and Urine Samples

Endemic mycoses – are we making progress in management?

Histoplasmosis: Laboratory Diagnosis

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