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Tuberculosis is not just a basic clinical and general issue of the whole world. It has attracted worldwide attention of the entire scientific majority because of its alarming rate of incidence and mortality. Since history of early examination of tuberculosis and its drug resistance, it has been proved that the diagnosis upgrades that enhances the survival and early case detection related to early treatment initiation. Careful bacteriological assurance and general prosperity approach to manage TB rely upon initial microscopic examination, solid & liquid culture methods, rapid molecular and standard DST assays.

For each assay of detection, there are new procedures and advancements adopted since their inception. Developing diagnostic techniques having access to quick accurate results, near-patient point-of-care diagnostics are now vital to curb and control TB and HIV-TB burden in resource-poor countries. This chapter has focused on the journey of those diagnostic techniques which remain the mainstay of TB diagnosis from early diagnostic work of smear microscopy to latest techniques involving whole genome sequencing. Starting late it is basic to comprehend that at present, there is no autonomous test for the quick acknowledgment of tuberculosis in all patients. While some new frameworks are direct, others have complex components and require sophisticated infrastructure and trained manpower. It is therefore imperative to choose from different diagnostic assays individually or to combine them inside a country’s national TB control program.

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Acid-fast bacilli


Anti-tubercular therapy


Bacillus Calmette-Guerin


Cartridge-based nucleic acid amplification test


Center for disease control


Culture filtrate protein


Colony-forming unit


Colorimetric redox indicator




Deoxyribonucleic acid


Direct repeat


Drug susceptibility testing


Early secreted antigenic target


Food and Drug Administration


Foundation for Innovative Newer Diagnostics


Fluorescent microscopy


Human immunodeficiency virus


Interferon gamma


Interferon-gamma release assays




Insertion sequence


In vitro diagnostics




Loop-mediated amplification PCR


Light-emitting diode


Lowenstein Jensen


Liquid medium


Line probe assay


Latent tuberculosis infection


Multidrug resistance


Mycobacterium interspersed repeated units-variable number of tandem repeats


Microscopic observation of drug susceptibility


Mycobacterium tuberculosis


Mycobacterium tuberculosis complex


Next-generation sequencing


Nitrate reductase assay


Nontuberculous Mycobacterium


Oleic acid, albumin, dextrose, catalase


Polymyxin B, azlocillin, nalidixic acid, trimethoprim, amphotericin B


Purified protein derivative


Positive predictive value


Restriction fragment length polymorphism




Revised National Tuberculosis Control Program


Ribosomal ribonucleic acid


Second-line injectable drugs


Surface plasmon resonance


Turnaround time




Tuberculin skin test


Time to detection


Volatile organic compounds


Whole genome sequencing


World Health Organization


Extensive drug resistance


Ziehl Neelsen


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Foundation for Innovative Newer Diagnostics (FIND) India deserves a special acknowledgment for providing permission to cite a table (annexure) summarizing the TB diagnostic pipeline showing progress at different development stages.

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Vashistha, H., Chopra, K.K. (2019). TB Diagnostics: Journey from Smear Microscopy to Whole Genome Sequencing. In: Hasnain, S., Ehtesham, N., Grover, S. (eds) Mycobacterium Tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions. Springer, Singapore.

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