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      True facets of TB diagnosis in 2012: Hypes and realities

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          Tuberculosis takes a heavy toll of ∼5000 lives every day from the disease; responsible for the 86% of DALY burden. Despite having drugs to treat TB efficiently, we have failed to control the disease. Mycobacterium tuberculosis has exploited it to their advantage evolving with multiple mutations making it resistant to first-line and second-line drugs. Most of the high-burden countries are low-medium income countries, their national TB program (NTP) still use sputum smear microscopy as the tool of diagnosis. Many new molecular tools are emerging, but confuse the larger TB clinical scientific community at the NTPs. Coherent information need to be disseminated, encouraging TB scientific community to generate evidences within NTPs assessing new tools through critical analyses in terms of value addition and cost benefit before considering rolling out in the program. It is also imperative that the scientific community need to have an open mind to use different tools in the right permutation and combination than being exclusive of one another. This article portrays an overview of the diagnostics landscape in 2012 with pros and cons of different tools to be able to generate a step-wise algorithm for optimal exploitation of the tools within available resources in each of the settings.

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          Most cited references 29

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          Tuberculosis, drug resistance, and the history of modern medicine.

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            Point-of-care breath test for biomarkers of active pulmonary tuberculosis.

            Volatile organic compounds (VOCs) in breath provide biomarkers of tuberculosis (TB) because Mycobacterium tuberculosis manufactures VOC metabolites that are detectable in the breath of infected patients. We evaluated breath VOC biomarkers in subjects with active pulmonary TB, using an internet-linked rapid point-of-care breath test. 279 subjects were studied at four centers in three countries, Philippines, UK, and India, and data was analyzed from 251 (130 active pulmonary TB, 121 controls). A point-of-care system collected and concentrated breath and air VOCs, and analyzed them with automated thermal desorption, gas chromatography, and surface acoustic wave detection. A breath test was completed in 6 min. Chromatograms were converted to a series of Kovats Index (KI) windows, and biomarkers of active pulmonary TB were identified by Monte Carlo analysis of KI window alveolar gradients (abundance in breath minus abundance in room air). Multiple Monte Carlo simulations identified eight KI windows as biomarkers with better than random performance. Four KI windows corresponded with KI values of VOCs previously identified as biomarkers of pulmonary TB and metabolic products of M. tuberculosis, principally derivatives of naphthalene, benzene and alkanes. A multivariate predictive algorithm identified active pulmonary TB with 80% accuracy (area under curve of receiver operating characteristic curve), sensitivity=71.2%, and specificity = 72%. Accuracy increased to 84% in age-matched subgroups. In a population with 5% prevalence, the breath test would identify active pulmonary TB with 98% negative predictive value and 13% positive predictive value. A six-minute point-of-care breath test for volatile biomarkers accurately identified subjects with active pulmonary TB. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Multicenter evaluation of the BACTEC MGIT 960 system for recovery of mycobacteria.

              We evaluated the BACTEC MGIT 960 system, which is a fully automated, noninvasive system for the growth and detection of mycobacteria with a capacity to incubate and continuously monitor 960 7-ml culture tubes. We studied 3,330 specimens, 2,210 respiratory and 1,120 nonrespiratory specimens, collected from 2,346 patients treated at six sites. Processed specimens were inoculated into the BACTEC MGIT 960 and BACTEC 460 TB systems, as well as onto Lowenstein-Jensen slants and Middlebrook 7H11/7H11 selective plates. From all culture systems, a total of 362 isolates of mycobacteria were recovered; these were recovered from 353 specimens collected from 247 patients. The greatest number of isolates of mycobacteria (289, or 80% of the 362 isolates) was recovered with the BACTEC MGIT 960, followed by the BACTEC 460 TB (271, or 75%) and solid media (250, or 69%). From all culture systems a total of 132 isolates of Mycobacterium tuberculosis complex were recovered. The greatest number of isolates of M. tuberculosis complex was recovered when liquid medium was combined with conventional solid media; the number recovered with BACTEC 460 TB plus solid media was 128 (97%), that recovered with BACTEC MGIT 960 plus solid media was 121 (92%), that recovered with BACTEC 460 TB was 119 (90%) and that recovered with all solid media combined was 105 (79%). The recovery with BACTEC MGIT 960 alone was 102 (77%). The mean times to detection (TTD) for M. tuberculosis complex were 14.4 days for BACTEC MGIT, 15.2 days for BACTEC 460 TB, and 24.1 days for solid media. The numbers of isolates of Mycobacterium avium complex (MAC) recovered were 172 (100%) for all systems, 147 (85%) for BACTEC MGIT 960, 123 (72%) for BACTEC 460 TB, and 106 (62%) for all solid media combined. The TTD for MAC in each system were 10.0 days for BACTEC MGIT 960, 10.4 days for BACTEC 460 TB, and 25.9 days for solid media. Breakthrough contamination rates (percentages of isolates) for each of the systems were 8.1% for BACTEC MGIT 960, 4.9% for BACTEC 460 TB, and 21.1% for all solid media combined.

                Author and article information

                European Journal of Microbiology and Immunology
                Akadémiai Kiadó, co-published with Springer Science+Business Media B.V., Formerly Kluwer Academic Publishers B.V.
                1 December 2012
                : 2
                : 4
                : 275-281
                [ 1 ] Berlin, Germany
                [ 2 ] Vaccine Grand Challenge Program, Dept of Biotechnology, Ministry of Science & Technology, Govt of India, New Delhi, India
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