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Diagnosis of Tuberculosis: Current Pipeline, Unmet Needs, and New Developments

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Handbook of Global Tuberculosis Control

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Abstract

Rapid and accurate diagnosis is critical for timely initiation of anti-TB treatment, but many people with TB do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and roll-out of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics; several companies are actively engaged in product development and many tests have been reviewed by WHO for policy endorsement. However, new diagnostics are yet to reach scale, and there needs to be greater convergence between diagnostics development and development of shorter TB drug regimens. Another concern is the relative absence of non-sputum-based diagnostics in the pipeline for children, and of biomarker tests for triage, cure, and latent TB progression. Increased investments are necessary to support biomarker discovery, validation, and translation into clinical tools. While transformative tools are being developed, high-burden countries will need to improve the efficiency of their healthcare delivery systems, ensure better uptake of new technologies, and achieve greater linkages across the TB and HIV care continuum.

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References

  • Abe, C., Hirano, K., & Tomiyama, T. (1999). Simple and rapid identification of the Mycobacterium tuberculosis complex by immunochromatographic assay using anti-MPB64 monoclonal antibodies. Journal of Clinical Microbiology, 37(11), 3693–3697.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Agranoff, D., Fernandez-Reyes, D., Papadopoulos, M. C., Rojas, S. A., Herbster, M., Loosemore, A., et al. (2006). Identification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum. Lancet, 368(9540), 1012–1021.

    Article  CAS  PubMed  Google Scholar 

  • Albert, H., Manabe, Y., Lukyamuzi, G., Ademun, P., Mukkada, S., Nyesiga, B., et al. (2010). Performance of three LED-based fluorescence microscopy systems for detection of tuberculosis in Uganda. PloS One, 5(12), e15206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andersen, P., Munk, M. E., Pollock, J. M., & Doherty, T. M. (2000). Specific immune-based diagnosis of tuberculosis. Lancet, 356(9235), 1099–1104.

    Article  CAS  PubMed  Google Scholar 

  • Angeby, K. A., Klintz, L., & Hoffner, S. E. (2002). Rapid and inexpensive drug susceptibility testing of Mycobacterium tuberculosis with a nitrate reductase assay. Journal of Clinical Microbiology, 40(2), 553–555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnard, M., Warren, R., Gey Van Pittius, N., van Helden, P., Bosman, M., Streicher, E., et al. (2012). Genotype MTBDRsl line probe assay shortens time to diagnosis of extensively drug-resistant tuberculosis in a high-throughput diagnostic laboratory. American Journal of Respiratory and Critical Care Medicine, 186(12), 1298–1305.

    Article  PubMed  Google Scholar 

  • Barry, C. E., 3rd, Boshoff, H. I., Dartois, V., Dick, T., Ehrt, S., Flynn, J., et al. (2009). The spectrum of latent tuberculosis: Rethinking the biology and intervention strategies. Nature Reviews Microbiology, 7(12), 845–855.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boehme, C. C., Nabeta, P., Henostroza, G., Raqib, R., Rahim, Z., Gerhardt, M., et al. (2007). Operational feasibility of using loop-mediated isothermal amplification for diagnosis of pulmonary tuberculosis in microscopy centers of developing countries. Journal of Clinical Microbiology, 45(6), 1936–1940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boehme, C. C., Nabeta, P., Hillemann, D., Nicol, M. P., Shenai, S., Krapp, F., et al. (2010). Rapid molecular detection of tuberculosis and rifampin resistance. New England Journal of Medicine, 363(11), 1005–1015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonnet, M., Ramsay, A., Gagnidze, L., Githui, W., Guerin, P. J., & Varaine, F. (2007). Reducing the number of sputum samples examined and thresholds for positivity: An opportunity to optimise smear microscopy. The International Journal of Tuberculosis and Lung Disease, 11(9), 953–958.

    CAS  PubMed  Google Scholar 

  • Bonnet, M., Gagnidze, L., Githui, W., Guerin, P. J., Bonte, L., Varaine, F., et al. (2011). Performance of LED-based fluorescence microscopy to diagnose tuberculosis in a peripheral health centre in Nairobi. PloS One, 6(2), e17214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bwanga, F., Hoffner, S., Haile, M., & Joloba, M. L. (2009). Direct susceptibility testing for multi drug resistant tuberculosis: A meta-analysis. BMC Infectious Diseases, 9, 67.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cattamanchi, A., Davis, J. L., Pai, M., Huang, L., Hopewell, P. C., & Steingart, K. R. (2010). Does bleach processing increase the accuracy of sputum smear microscopy for diagnosing pulmonary tuberculosis? Journal of Clinical Microbiology, 48(7), 2433–2439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cattamanchi, A., Smith, R., Steingart, K. R., Metcalfe, J. Z., Date, A., Coleman, C., et al. (2011a). Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: A systematic review and meta-analysis. Journal of Acquired Immune Deficiency Syndromes, 56(3), 230–238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cattamanchi, A., Huang, L., Worodria, W., den Boon, S., Kalema, N., Katagira, W., et al. (2011b). Integrated strategies to optimize sputum smear microscopy: A prospective observational study. American Journal of Respiratory and Critical Care Medicine, 183(4), 547–551.

    Article  PubMed  Google Scholar 

  • Caviedes, L., Lee, T. S., Gilman, R. H., Sheen, P., Spellman, E., Lee, E. H., et al. (2000). Rapid, efficient detection and drug susceptibility testing of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. The Tuberculosis Working Group in Peru. Journal of Clinical Microbiology, 38(3), 1203–1208.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cobelens, F., van den Hof, S., Pai, M., Squire, S. B., Ramsay, A., & Kimerling, M. E. (2012). Which new diagnostics for tuberculosis, and when? Journal of Infectious Diseases, 205(Suppl 2), S191–S198.

    Article  PubMed  Google Scholar 

  • Cruciani, M., Scarparo, C., Malena, M., Bosco, O., Serpelloni, G., & Mengoli, C. (2004). Meta-analysis of BACTEC MGIT 960 and BACTEC 460 TB, with or without solid media, for detection of mycobacteria. Journal of Clinical Microbiology, 42(5), 2321–2325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuevas, L. E., Yassin, M. A., Al-Sonboli, N., Lawson, L., Arbide, I., Al-Aghbari, N., et al. (2011). A multi-country non-inferiority cluster randomized trial of frontloaded smear microscopy for the diagnosis of pulmonary tuberculosis. PLoS Medicine, 8(7), e1000443.

    Article  PubMed  PubMed Central  Google Scholar 

  • Davis, J. L., Huang, L., Worodria, W., Masur, H., Cattamanchi, A., Huber, C., et al. (2011). Nucleic acid amplification tests for diagnosis of smear-negative TB in a high HIV-prevalence setting: A prospective cohort study. PloS One, 6(1), e16321.

    Article  PubMed  PubMed Central  Google Scholar 

  • Denkinger, C. M., Dheda, K., & Pai, M. (2011). Guidelines on interferon-gamma release assays for tuberculosis infection: Concordance, discordance or confusion? Clinical Microbiology and Infection, 17(6), 806–814.

    Article  CAS  PubMed  Google Scholar 

  • Denkinger, C., Kik, S. V., & Pai, M. (2013). Robust, reliable and resilient: designing molecular tuberculosis tests for microscopy centers in developing countries. Expert Review of Molecular Diagnostics, (8):763–767.

    Google Scholar 

  • Dheda, K., Ruhwald, M., Theron, G., Peter, J., & Yam, W. C. (2013). Point-of-care diagnosis of tuberculosis: Past, present and future. Respirology, 18(2), 217–232.

    Article  PubMed  Google Scholar 

  • Dinnes, J., Deeks, J., Kunst, H., Gibson, A., Cummins, E., Waugh, N., et al. (2007). A systematic review of rapid diagnostic tests for the detection of tuberculosis infection. Health Technology Assessment, 11(3), 1–314.

    Article  CAS  PubMed  Google Scholar 

  • Dorman, S. E., Belknap, R., Graviss, E. A., Reves, R., Schluger, N., Weinfurter, P., et al. (2014). Interferon-gamma release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States. American Journal of Respiratory and Critical Care Medicine, 189(1), 77–87.

    PubMed  Google Scholar 

  • Dowdy, D., Steingart, K. R., & Pai, M. (2011). Serological testing versus other strategies for diagnosis of active tuberculosis in India: A cost-effectiveness analysis. PLoS Medicine, 8(8), e1001074.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ehrlich, P. (1882). Verein fur innere Medicin zu Berlin, Sitzung vom 1. Mai 1882. Deutsche med Wochenschrift. 1882:269.

    Google Scholar 

  • Feng, Y., Liu, S., Wang, Q., Wang, L., Tang, S., Wang, J., et al. (2013). Rapid diagnosis of drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol using genotype MTBDRsl assay: A meta-analysis. PloS One, 8(2), e55292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finnie, R. K., Khoza, L. B., van den Borne, B., Mabunda, T., Abotchie, P., & Mullen, P. D. (2011). Factors associated with patient and health care system delay in diagnosis and treatment for TB in sub-Saharan African countries with high burdens of TB and HIV. Tropical Medicine and International Health, 16(4), 394–411.

    Article  PubMed  Google Scholar 

  • Flores, L. L., Pai, M., Colford, J. M., Jr., & Riley, L. W. (2005). In-house nucleic acid amplification tests for the detection of Mycobacterium tuberculosis in sputum specimens: Meta-analysis and meta-regression. BMC Microbiology, 5, 55.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fortune, S. M., & Rubin, E. J. (2010). Host transcription in active and latent tuberculosis. Genome Biology, 11(9), 135.

    Article  PubMed  PubMed Central  Google Scholar 

  • Garcia-Pachon, E., Soler, M. J., Padilla-Navas, I., Romero, V., & Shum, C. (2005). C-reactive protein in lymphocytic pleural effusions: A diagnostic aid in tuberculous pleuritis. Respiration, 72(5), 486–489.

    Article  CAS  PubMed  Google Scholar 

  • Geng, E., Kreiswirth, B., Burzynski, J., & Schluger, N. W. (2005). Clinical and radiographic correlates of primary and reactivation tuberculosis: A molecular epidemiology study. JAMA, 293(22), 2740–2745.

    Article  CAS  PubMed  Google Scholar 

  • Glickman, S. E., Kilburn, J. O., Butler, W. R., & Ramos, L. S. (1994). Rapid identification of mycolic acid patterns of mycobacteria by high-performance liquid chromatography using pattern recognition software and a Mycobacterium library. Journal of Clinical Microbiology, 32(3), 740–745.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goto, M., Noguchi, Y., Koyama, H., Hira, K., Shimbo, T., & Fukui, T. (2003). Diagnostic value of adenosine deaminase in tuberculous pleural effusion: A meta-analysis. Annals of Clinical Biochemistry, 40(Pt 4), 374–381.

    Article  CAS  PubMed  Google Scholar 

  • Greco, S., Girardi, E., Masciangelo, R., Capoccetta, G. B., & Saltini, C. (2003). Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: A meta-analysis. The International Journal of Tuberculosis and Lung Disease, 7(8), 777–786.

    CAS  PubMed  Google Scholar 

  • Green, C., Huggett, J. F., Talbot, E., Mwaba, P., Reither, K., & Zumla, A. I. (2009). Rapid diagnosis of tuberculosis through the detection of mycobacterial DNA in urine by nucleic acid amplification methods. Lancet Infectious Diseases, 9(8), 505–511.

    Article  CAS  PubMed  Google Scholar 

  • Guerra, R. L., Hooper, N. M., Baker, J. F., Alborz, R., Armstrong, D. T., Maltas, G., et al. (2007). Use of the amplified Mycobacterium tuberculosis direct test in a public health laboratory: Test performance and impact on clinical care. Chest, 132(3), 946–951.

    Article  PubMed  Google Scholar 

  • Hasegawa, N., Miura, T., Ishii, K., Yamaguchi, K., Lindner, T. H., Merritt, S., et al. (2002). New simple and rapid test for culture confirmation of Mycobacterium tuberculosis complex: A multicenter study. Journal of Clinical Microbiology, 40(3), 908–912.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hill, P. C., Jackson-Sillah, D. J., Fox, A., Brookes, R. H., de Jong, B. C., Lugos, M. D., et al. (2008). Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts. PLoS ONE, 3(1), e1379.

    Article  PubMed  PubMed Central  Google Scholar 

  • Horne, D. J., Pinto, L. M., Arentz, M., Lin, S. Y., Desmond, E., Flores, L. L., et al. (2013). Diagnostic accuracy and reproducibility of WHO-endorsed phenotypic drug susceptibility testing methods for first-line and second-line antituberculosis drugs. Journal of Clinical Microbiology, 51(2), 393–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jafari, C., Thijsen, S., Sotgiu, G., Goletti, D., Dominguez Benitez, J. A., Losi, M., et al. (2009). Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: A tuberculosis network European trialsgroup study. American Journal of Respiratory and Critical Care Medicine, 180(7), 666–673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeong, Y. J., & Lee, K. S. (2008). Pulmonary tuberculosis: Up-to-date imaging and management. AJR American Journal of Roentgenology, 191(3), 834–844.

    Article  PubMed  Google Scholar 

  • Krysl, J., Korzeniewska-Kosela, M., Muller, N. L., & FitzGerald, J. M. (1994). Radiologic features of pulmonary tuberculosis: An assessment of 188 cases. Canadian Association of Radiologists Journal, 45(2), 101–107.

    CAS  PubMed  Google Scholar 

  • Lee, H., Yoon, T. J., & Weissleder, R. (2009). Ultrasensitive detection of bacteria using core-shell nanoparticles and an NMR-filter system. Angewandte Chemie International Edition in English, 48(31), 5657–5660.

    Article  CAS  Google Scholar 

  • Leung, A. N., Muller, N. L., Pineda, P. R., & FitzGerald, J. M. (1992). Primary tuberculosis in childhood: Radiographic manifestations. Radiology, 182(1), 87–91.

    Article  CAS  PubMed  Google Scholar 

  • Liao, C. H., Chou, C. H., Lai, C. C., Huang, Y. T., Tan, C. K., Hsu, H. L., et al. (2009). Diagnostic performance of an enzyme-linked immunospot assay for interferon-gamma in extrapulmonary tuberculosis varies between different sites of disease. Journal of Infection, 59(6), 402–408.

    Article  CAS  PubMed  Google Scholar 

  • Lienhardt, C., Fielding, K., Hane, A. A., Niang, A., Ndao, C. T., Karam, F., et al. (2010). Evaluation of the prognostic value of IFN-gamma release assay and tuberculin skin test in household contacts of infectious tuberculosis cases in Senegal. PLoS ONE, 5(5), e10508.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ling, D. I., Zwerling, A. A., & Pai, M. (2008). GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: A meta-analysis. European Respiratory Journal, 32(5), 1165–1174.

    Article  CAS  PubMed  Google Scholar 

  • Maciel, E. L., Golub, J. E., Peres, R. L., Hadad, D. J., Favero, J. L., Molino, L. P., et al. (2010). Delay in diagnosis of pulmonary tuberculosis at a primary health clinic in Vitoria, Brazil. International Journal of Tuberculosis and Lung Disease, 14(11), 1403–1410.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martin, A., Portaels, F., & Palomino, J. C. (2007). Colorimetric redox-indicator methods for the rapid detection of multidrug resistance in Mycobacterium tuberculosis: A systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy, 59(2), 175–183.

    Article  CAS  PubMed  Google Scholar 

  • Mase, S. R., Ramsay, A., Ng, V., Henry, M., Hopewell, P. C., Cunningham, J., et al. (2007). Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: A systematic review. The International Journal of Tuberculosis and Lung Disease, 11(5), 485–495.

    CAS  PubMed  Google Scholar 

  • Meintjes, G., Schoeman, H., Morroni, C., Wilson, D., & Maartens, G. (2008). Patient and provider delay in tuberculosis suspects from communities with a high HIV prevalence in South Africa: A cross-sectional study. BMC Infectious Diseases, 8, 72.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mejia, G. I., Castrillon, L., Trujillo, H., & Robledo, J. A. (1999). Microcolony detection in 7H11 thin layer culture is an alternative for rapid diagnosis of Mycobacterium tuberculosis infection. The International Journal of Tuberculosis and Lung Disease, 3(2), 138–142.

    CAS  PubMed  Google Scholar 

  • Metcalfe, J. Z., Everett, C., Steingart, K., Cattamanchi, A., Huang, L., Hopewell, P. C., et al. (2011). Interferon-gamma release assays for active pulmonary TB diagnosis in adults in low- and middle-income countries: Systematic review and meta-analysis. Journal of Infectious Diseases, 204(Suppl 4), S1120–S1129.

    Article  PubMed  PubMed Central  Google Scholar 

  • Minion, J., Leung, E., Menzies, D., & Pai, M. (2010). Microscopic-observation drug susceptibility and thin layer agar assays for the detection of drug resistant tuberculosis: A systematic review and meta-analysis. Lancet Infectious Diseases, 10(10), 688–698.

    Article  CAS  PubMed  Google Scholar 

  • Minion, J., Leung, E., Talbot, E., Dheda, K., Pai, M., & Menzies, D. (2011). Diagnosing tuberculosis with urine lipoarabinomannan: Systematic review and meta-analysis. European Respiratory Journal, 38(6), 1398–1405.

    Article  CAS  PubMed  Google Scholar 

  • Moon, W. K., Im, J. G., Yeon, K. M., & Han, M. C. (1997). Tuberculosis of the central airways: CT findings of active and fibrotic disease. AJR American Journal of Roentgenology, 169(3), 649–653.

    Article  CAS  PubMed  Google Scholar 

  • Pai, M., Flores, L. L., Pai, N., Hubbard, A., Riley, L. W., & Colford, J. M., Jr. (2003). Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: A systematic review and meta-analysis. Lancet Infectious Diseases, 3(10), 633–643.

    Article  CAS  PubMed  Google Scholar 

  • Pai, M., Flores, L. L., Hubbard, A., Riley, L. W., & Colford, J. M., Jr. (2004). Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: A systematic review and meta-analysis. BMC Infectious Diseases, 4, 6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pai, M., Minion, J., Steingart, K., & Ramsay, A. (2010). New and improved tuberculosis diagnostics: Evidence, policy, practice, and impact. Current Opinion in Pulmonary Medicine, 16(3), 271–284.

    PubMed  Google Scholar 

  • Pai, N. P., Vadnais, C., Denkinger, C., Engel, N., & Pai, M. (2012). Point-of-care testing for infectious diseases: diversity, complexity, and barriers in low- and middle-income countries. PLoS Medicine, 9(9), e1001306.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pai, M., Denkinger, C. M., Kik, S. V., Rangaka, M. X., Zwerling, A., Oxlade, O., et al. (2014). Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clinical Microbiology Reviews, 27(1), 3–20.

    Article  PubMed  PubMed Central  Google Scholar 

  • Phillips, M., Basa-Dalay, V., Bothamley, G., Cataneo, R. N., Lam, P. K., Natividad, M. P., et al. (2010). Breath biomarkers of active pulmonary tuberculosis. Tuberculosis (Edinburgh, Scotland), 90(2), 145–151.

    Article  CAS  Google Scholar 

  • Pinto, L. M., Grenier, J., Schumacher, S., Denkinger, C. M., Steingart, K. R., & Pai, M. (2011). Immunodiagnosis of tuberculosis: Prospects and challenges. Med Princ Pract 2012;21:4–13.

    Google Scholar 

  • Rabinovitch, B., & Pai, M. (2013). Radiology of tuberculosis: Case studies for the GP. GP Clinics, 4(1), 21–29.

    Google Scholar 

  • Ramsay, A., Yassin, M. A., Cambanis, A., Hirao, S., Almotawa, A., Gammo, M., et al. (2009). Front-loading sputum microscopy services: An opportunity to optimise smear-based case detection of tuberculosis in high prevalence countries. Journal of Tropical Medicine, 2009, 398767.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rangaka, M. X., Wilkinson, K. A., Glynn, J. R., Ling, D., Menzies, D., Mwansa-Kambafwile, J., et al. (2012). Predictive value of interferon-gamma release assays for incident active tuberculosis: A systematic review and meta-analysis. Lancet Infectious Diseases, 12(1), 45–55.

    Article  CAS  PubMed  Google Scholar 

  • Rebollo, M. J., San Juan Garrido, R., Folgueira, D., Palenque, E., Diaz-Pedroche, C., Lumbreras, C., et al. (2006). Blood and urine samples as useful sources for the direct detection of tuberculosis by polymerase chain reaction. Diagnostic Microbiology and Infectious Disease, 56(2), 141–146.

    Article  CAS  PubMed  Google Scholar 

  • Riquelme, A., Calvo, M., Salech, F., Valderrama, S., Pattillo, A., Arellano, M., et al. (2006). Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous peritonitis: A meta-analysis. Journal of Clinical Gastroenterology, 40(8), 705–710.

    Article  CAS  PubMed  Google Scholar 

  • Sester, M., Sotgiu, G., Lange, C., Giehl, C., Girardi, E., Migliori, G. B., et al. (2011). Interferon-gamma release assays for the diagnosis of active tuberculosis: A systematic review and meta-analysis. European Respiratory Journal, 37(1), 100–111.

    Article  CAS  PubMed  Google Scholar 

  • Shenai, S., Minion, J., Vadwai, V., Tipnis, T., Shetty, S., Salvi, A., et al. (2011). Evaluation of light emitting diode-based fluorescence microscopy for the detection of mycobacteria in a tuberculosis-endemic region. The International Journal of Tuberculosis and Lung Disease, 15(4), 483–488.

    Article  CAS  PubMed  Google Scholar 

  • Smith, R., Cattamanchi, A., Steingart, K. R., Denkinger, C., Dheda, K., Winthrop, K. L., et al. (2011). Interferon-gamma release assays for diagnosis of latent tuberculosis infection: Evidence in immune-mediated inflammatory disorders. Current Opinion in Rheumatology, 23(4), 377–384.

    Article  CAS  PubMed  Google Scholar 

  • Sreeramareddy, C. T., Qin, Z. Z., Satyanarayana, S., Subbaraman, R., & Pai, M. (2014). Delays in diagnosis and treatment of pulmonary tuberculosis in India: A systematic review. The International Journal of Tuberculosis and Lung Disease, 18(3), 255–266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steingart, K. R., Ng, V., Henry, M., Hopewell, P. C., Ramsay, A., Cunningham, J., et al. (2006a). Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: A systematic review. Lancet Infectious Diseases, 6(10), 664–674.

    Article  PubMed  Google Scholar 

  • Steingart, K. R., Henry, M., Ng, V., Hopewell, P. C., Ramsay, A., Cunningham, J., et al. (2006b). Fluorescence versus conventional sputum smear microscopy for tuberculosis: A systematic review. Lancet Infectious Diseases, 6(9), 570–581.

    Article  PubMed  Google Scholar 

  • Steingart, K. R., Flores, L., Dendukuri, N., Schiller, I., Laal, S., Ramsay, A., et al. (2011). Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: An updated systematic review and meta-analysis. PLoS Medicine, 8(8), e1001062.

    Article  PubMed  PubMed Central  Google Scholar 

  • Steingart, K. R., Schiller, I., Horne, D. J., Pai, M., Boehme, C. C., & Dendukuri, N. (2014). Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database of Systematic Reviews, 1, CD009593.

    Google Scholar 

  • Torrea, G., Van de Perre, P., Ouedraogo, M., Zougba, A., Sawadogo, A., Dingtoumda, B., et al. (2005). PCR-based detection of the Mycobacterium tuberculosis complex in urine of HIV-infected and uninfected pulmonary and extrapulmonary tuberculosis patients in Burkina Faso. Journal of Medical Microbiology, 54(Pt 1), 39–44.

    Article  CAS  PubMed  Google Scholar 

  • Tuon, F. F., Higashino, H. R., Lopes, M. I., Litvoc, M. N., Atomiya, A. N., Antonangelo, L., et al. (2010). Adenosine deaminase and tuberculous meningitis—A systematic review with meta-analysis. Scandinavian Journal of Infectious Diseases, 42(3), 198–207.

    Article  CAS  PubMed  Google Scholar 

  • Valdes, L., San Jose, E., Alvarez, D., Sarandeses, A., Pose, A., Chomon, B., et al. (1993). Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma. Chest, 103(2), 458–465.

    Article  CAS  PubMed  Google Scholar 

  • von Pirquet, C. (1907). Die allergieprobe zur diagnose der tuberkulose im kindesalter. Wiener Medizinische Wochenschrift, 57, 1370–1374.

    Google Scholar 

  • Wallis, R. S., Pai, M., Menzies, D., Doherty, T. M., Walzl, G., Perkins, M. D., et al. (2010). Biomarkers and diagnostics for tuberculosis: Progress, needs, and translation into practice. Lancet, 375(9729), 1920–1937.

    Article  CAS  PubMed  Google Scholar 

  • Wilson, D., Badri, M., & Maartens, G. (2011). Performance of serum C-reactive protein as a screening test for smear-negative tuberculosis in an ambulatory high HIV prevalence population. PloS One, 6(1), e15248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodring, J. H., Vandiviere, H. M., Fried, A. M., Dillon, M. L., Williams, T. D., & Melvin, I. G. (1986). Update: The radiographic features of pulmonary tuberculosis. AJR American Journal of Roentgenology, 146(3), 497–506.

    Article  CAS  PubMed  Google Scholar 

  • WHO. (2009). New WHO policy and retooling activities for liquid culture systems. Geneva: World Health Organization.

    Google Scholar 

  • WHO. (2010a). Strategic and Technical Advisory Group (STAG-TB). In Report of the 10th Meeting. Geneva: World Health Organization. Retrieved Feb 22, 2011, from http://www.who.int/tb/advisory_bodies/stag_tb_report_2010.pdf%5D

  • WHO. (2010b). Fluorescent light emitting diode (LED) microscopy for diagnosis of tuberculosis. Geneva: World Health Organization.

    Google Scholar 

  • WHO. (2011a). Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system. Geneva: World Health Organization.

    Google Scholar 

  • WHO. (2011b). Commercial serodiagnostic tests for diagnosis of tuberculosis. Geneva: World Health Organization.

    Google Scholar 

  • WHO. (2012). Global tuberculosis control: WHO report 2012. Geneva: World Health Organization.

    Google Scholar 

  • WHO. (2013a). Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system for the diagnosis of pulmonary and extrapulmonary TB in adults and children. Geneva: World Health Organization.

    Google Scholar 

  • WHO. (2013b). WHO monitoring of Xpert MTB/RIF roll-out. Geneva: World Health Organization.

    Google Scholar 

  • Xu, H. B., Jiang, R. H., Li, L., Sha, W., & Xiao, H. P. (2010). Diagnostic value of adenosine deaminase in cerebrospinal fluid for tuberculous meningitis: A meta-analysis. The International Journal of Tuberculosis and Lung Disease, 14(11), 1382–1387.

    PubMed  Google Scholar 

  • Zar, H. J., Hanslo, D., Apolles, P., Swingler, G., & Hussey, G. (2005). Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: A prospective study. Lancet, 365(9454), 130–134.

    Article  PubMed  Google Scholar 

  • Zwerling, A., Behr, M., Varma, A., Brewer, T. F., Menzies, D., & Pai, M. (2011). The BCG world atlas: A database of global BCG vaccination policies and practices. PLoS Medicine, 8(3), e1001012.

    Article  PubMed  PubMed Central  Google Scholar 

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Conflicts of Interest

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. M. Pai is supported by the Fonds de recherche du Québec—Santé (FRQS) and consults for the Bill & Melinda Gates Foundation. C.M. Denkinger is supported by a Richard Tomlinson Fellowship at McGill University and a fellowship of the Burroughs-Wellcome Fund from the American Society of Tropical Medicine and Hygiene. These agencies had no involvement in this manuscript.

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Authors and Affiliations

  1. Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Claudia M. Denkinger M.D., Ph.D.

  2. Department of Epidemiology and Biostatistics, McGill International TB Centre, McGill University, Montreal, QC, Canada, H3A 1A2

    Claudia M. Denkinger M.D., Ph.D. & Madhukar Pai M.D., Ph.D.

  3. Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, QC, Canada

    Madhukar Pai M.D., Ph.D.

Authors
  1. Claudia M. Denkinger M.D., Ph.D.
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  2. Madhukar Pai M.D., Ph.D.
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Corresponding author

Correspondence to Madhukar Pai M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Haikou VTI Biological Institute, Boston, Massachusetts, USA

    Yichen Lu

  2. Chinese Nat’l Ctr Disease Control and Prevention, Nat’l Center for TB Control & Prevention Chinese Nat’l Ctr Disease Control and Prevention, Beijing, China

    Lixia Wang

  3. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

    Hongjin Duanmu

  4. Brookline, Massachusetts, USA

    Chris Chanyasulkit

  5. Vaccine Technologies, Inc., Wellesley, Massachusetts, USA

    Amie J. Strong

  6. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

    Hui Zhang

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Denkinger, C.M., Pai, M. (2017). Diagnosis of Tuberculosis: Current Pipeline, Unmet Needs, and New Developments. In: Lu, Y., Wang, L., Duanmu, H., Chanyasulkit, C., Strong, A., Zhang, H. (eds) Handbook of Global Tuberculosis Control. Springer, Boston, MA. https://doi.org/10.1007/978-1-4939-6667-7_7

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  • DOI: https://doi.org/10.1007/978-1-4939-6667-7_7

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