T-cell assay conversions and reversions among household contacts of tuberculosis patients in rural India.

BACKGROUND: Interferon-gamma assays (IGRAs) are alternatives to the tuberculin skin test (TST), but IGRA conversions and reversions are not well understood. In a pilot study, we determined conversions and reversions using QuantiFERON-TB Gold In-Tube((R)) (QFT) among household contacts of TB cases, and evaluated the effect of using various definitions and criteria for conversions. DESIGN: In a cohort of 250 contacts in India, 46% were TST-positive at baseline and 54% were QFT-positive. We re-tested this cohort after 12 months. Conversion rates were estimated using several definitions. RESULTS: Of the 250 contacts, 205 (82%) underwent repeat testing. Among 85 contacts with baseline TST-negative/QFT-negative results, TST conversion rates ranged between 7.5% and 13.8%, and QFT conversion rates ranged between 11.8% and 21.2%, depending on the definitions used. Among 109 contacts who were QFT-positive at baseline, seven (6.4%) had QFT reversions. QFT reversions were most likely when the baseline TST was negative and QFT results were just above the diagnostic cut-off. CONCLUSIONS: QFT conversions and reversions occurred among contacts of TB cases. Conversion rates seemed to vary, depending on the test and definitions used for conversions. These findings need to be verified in larger studies in various settings.

GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis.

The global extensively drug-resistant tuberculosis (TB) response plan calls for implementation of rapid tests to screen patients at risk of drug-resistant TB. Currently, two line probe assays exist, the INNO-LiPA(R)Rif.TB assay (Innogenetics, Ghent, Belgium) and the GenoType MTBDR assay (Hain LifeScience GmbH, Nehren, Germany). While LiPA studies have been reviewed, the accuracy of GenoType assays has not been systematically reviewed. The present authors carried out a systematic review and used meta-analysis methods appropriate for diagnostic accuracy. After the literature searches, 14 comparisons for rifampicin and 15 comparisons for isoniazid were identified in 10 articles that used GenoType MTBDR assays. Accuracy results were summarised in forest plots and pooled using bivariate random-effects regression. The pooled sensitivity (98.1%, 95% confidence interval (CI) 95.9-99.1) and specificity (98.7%, 95% CI 97.3-99.4) estimates for rifampicin resistance were very high and consistent across all subgroups, assay versions and specimen types. The accuracy for isoniazid was variable, with lower sensitivity (84.3%, 95% CI 76.6-89.8) and more inconsistent than specificity (99.5%, 95% CI 97.5-99.9). GenoType MDTBR assays demonstrate excellent accuracy for rifampicin resistance, even when used on clinical specimens. While specificity is excellent for isoniazid, sensitivity estimates were modest and variable. Together with data from demonstration projects, the meta-analysis provides evidence for policy making and clinical practice.

Novel tests for diagnosing tuberculous pleural effusion: what works and what does not?

Tuberculous pleuritis is a common manifestation of extrapulmonary tuberculosis and is the most common cause of pleural effusion in many countries. Conventional diagnostic tests, such as microscopic examination of the pleural fluid, biochemical tests, culture of pleural fluid, sputum or pleural tissue, and histopathological examination of pleural tissue, have known limitations. Due to these limitations, newer and more rapid diagnostic tests have been evaluated. In this review, the authors provide an overview of the performance of new diagnostic tests, including markers of specific and nonspecific immune response, nucleic acid amplification and detection, and predictive models based on combinations of markers. Directions for future development and evaluation of novel assays and biomarkers for pleural tuberculosis are also suggested.