Challenges in the development of an immunochromatographic interferon-gamma test for diagnosis of pleural tuberculosis
| Autor: | Devasahayam J. Christopher, Claudia M. Denkinger, Joy Sarojini Michael, Samuel G Schumacher, Robert F. Luo, T Balamugesh, Deepa Shankar, Madhukar Pai, Nira R. Pollock, Yatiraj Kalantri, Arvind Saxena, N. Sriram |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Tuberculosis Adolescent Pleural tuberculosis lcsh:Medicine Enzyme-Linked Immunosorbent Assay Gastroenterology Sensitivity and Specificity Chromatography Affinity Mycobacterium tuberculosis Cohort Studies 03 medical and health sciences Interferon-gamma 0302 clinical medicine Internal medicine medicine Humans Interferon gamma 030212 general & internal medicine lcsh:Science Multidisciplinary biology business.industry lcsh:R Tuberculosis Pleural Middle Aged biology.organism_classification medicine.disease Confidence interval 3. Good health 030220 oncology & carcinogenesis Clinical diagnosis Immunology Pleural fluid Biomarker (medicine) lcsh:Q Female business Biomarkers medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 12, p e85447 (2013) |
| ISSN: | 1932-6203 |
| Popis: | Existing diagnostic tests for pleural tuberculosis (TB) have inadequate accuracy and/or turnaround time. Interferon-gamma (IFNg) has been identified in many studies as a biomarker for pleural TB. Our objective was to develop a lateral flow, immunochromatographic test (ICT) based on this biomarker and to evaluate the test in a clinical cohort. Because IFNg is commonly present in non-TB pleural effusions in low amounts, a diagnostic IFNg-threshold was first defined with an enzyme-linked immunosorbent assay (ELISA) for IFNg in samples from 38 patients with a confirmed clinical diagnosis (cut-off of 300 pg/ml; 94% sensitivity and 93% specificity). The ICT was then designed; however, its achievable limit of detection (5000 pg/ml) was over 10-fold higher than that of the ELISA. After several iterations in development, the prototype ICT assay for IFNg had a sensitivity of 69% (95% confidence interval (CI): 50-83) and a specificity of 94% (95% CI: 81-99%) compared to ELISA on frozen samples. Evaluation of the prototype in a prospective clinical cohort (72 patients) on fresh pleural fluid samples, in comparison to a composite reference standard (including histopathological and microbiologic test results), showed that the prototype had 65% sensitivity (95% CI: 44-83) and 89% specificity (95% CI: 74-97). Discordant results were observed in 15% of samples if testing was repeated after one freezing and thawing step. Inter-rater variability was limited (3%; 1 out of 32). In conclusion, despite an iterative development and optimization process, the performance of the IFNg ICT remained lower than what could be expected from the published literature on IFNg as a biomarker in pleural fluid. Further improvements in the limit of detection of an ICT for IFNg, and possibly combination of IFNg with other biomarkers such as adenosine deaminase, are necessary for such a test to be of value in the evaluation of pleural tuberculosis. |
| Databáze: | OpenAIRE |
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