Download PDF
Semin Respir Crit Care Med 2018; 39(03): 286-296
DOI: 10.1055/s-0038-1660471
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Diagnostic Challenge of Tuberculosis Heterogeneity

Elisa Nemes
1   South African Tuberculosis Vaccine Initiative (SATVI) and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
,
Erin W. Meermeier
2   Department of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon
3   VA Portland Health Care System, Portland, Oregon
,
Thomas J. Scriba
1   South African Tuberculosis Vaccine Initiative (SATVI) and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
,
Gerhard Walzl
4   South African Medical Research Council, Centre for Tuberculosis Research, Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
5   Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
,
Stephanus T. Malherbe
4   South African Medical Research Council, Centre for Tuberculosis Research, Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
5   Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
,
David M. Lewinsohn
2   Department of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon
3   VA Portland Health Care System, Portland, Oregon
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2018 (online)

    Permissions and Reprints

Abstract

For the ICU physician, the failure to consider, diagnose, and treat tuberculosis (TB) results in increased morbidity and mortality, and poses risks to both patients and health care providers. At present, the diagnosis of TB depends on the detection of either mycobacteria or mycobacterial products from clinical specimens. Given the risks posed to both the patient and health care providers by undiagnosed and/or untreated TB, the ability to diagnose TB rapidly in the ICU cannot be understated. In this regard, nucleic acid amplification tests provide relatively quick information about the presence of Mycobacterium tuberculosis (Mtb) DNA. If available, a blood-based test that would accurately identify persons with TB would be of use in the ICU. Currently available tests such as the T-Spot.TB or QuantiFERON-TB Gold In-Tube can discern infection with Mtb, but are not recommended for the ICU as they cannot rule out TB. In this review, we will discuss the increasing literature that would suggest that a blood-based diagnostic that reflects the host response to TB could be used to diagnose TB in the ICU.

Keywords

tuberculosis - diagnosis - subclinical - host response
 

  • References

  • 1 Lewinsohn DM, Leonard MK, LoBue PA. , et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of tuberculosis in adults and children. Clin Infect Dis 2017; 64 (02) 111-115
    CrossrefPubMedGoogle Scholar
  • 2 Lewinsohn DM, Leonard MK, LoBue PA. , et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of tuberculosis in adults and children. Clin Infect Dis 2017; 64 (02) 111-115
    CrossrefPubMedGoogle Scholar
  • 3 Levy H, Kallenbach JM, Feldman C, Thorburn JR, Abramowitz JA. Acute respiratory failure in active tuberculosis. Crit Care Med 1987; 15 (03) 221-225
    CrossrefPubMedGoogle Scholar
  • 4 Balkema CA, Irusen EM, Taljaard JJ, Koegelenberg CF. Tuberculosis in the intensive care unit: a prospective observational study. Int J Tuberc Lung Dis 2014; 18 (07) 824-830
    CrossrefPubMedGoogle Scholar
  • 5 Silva DR, Menegotto DM, Schulz LF, Gazzana MB, Dalcin PT. Mortality among patients with tuberculosis requiring intensive care: a retrospective cohort study. BMC Infect Dis 2010; 10: 54
    CrossrefPubMedGoogle Scholar
  • 6 Calligaro GL, Theron G, Khalfey H. , et al. Burden of tuberculosis in intensive care units in Cape Town, South Africa, and assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a prospective burden of disease study with a nested randomized controlled trial. Lancet Respir Med 2015; 3 (08) 621-630
    CrossrefPubMedGoogle Scholar
  • 7 Global tuberculosis report 2017. Geneva: World Health Organization; 2017. . Licence: CC BY-NCSA 3.0 IGO.
    Google Scholar
  • 8 Comstock GW, Ferebee SH, Hammes LM. A controlled trial of community-wide isoniazid prophylaxis in Alaska. Am Rev Respir Dis 1967; 95 (06) 935-943
    PubMedGoogle Scholar
  • 9 Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974; 99 (02) 131-138
    CrossrefPubMedGoogle Scholar
  • 10 Zellweger JP, Sotgiu G, Block M. , et al; TBNET. Risk assessment of tuberculosis in contacts by IFN-γ release assays. A Tuberculosis Network European Trials Group Study. Am J Respir Crit Care Med 2015; 191 (10) 1176-1184
    CrossrefPubMedGoogle Scholar
  • 11 Doan TN, Eisen DP, Rose MT, Slack A, Stearnes G, McBryde ES. Interferon-gamma release assay for the diagnosis of latent tuberculosis infection: a latent-class analysis. PLoS One 2017; 12 (11) e0188631
    CrossrefPubMedGoogle Scholar
  • 12 Overton K, Varma R, Post JJ. Comparison of interferon-γ release assays and the tuberculin skin test for diagnosis of tuberculosis in human immunodeficiency virus: a systematic review. Tuberc Respir Dis (Seoul) 2018; 81 (01) 59-72
    CrossrefPubMedGoogle Scholar
  • 13 Latorre I, Mínguez S, Carrascosa JM. , et al. Immune-mediated inflammatory diseases differently affect IGRAs' accuracy for latent tuberculosis infection diagnosis in clinical practice. PLoS One 2017; 12 (12) e0189202
    CrossrefPubMedGoogle Scholar
  • 14 WHO. Latent TB Infection: Updated and Consolidated Guidelines for Programmatic Management. 2018
    PubMedGoogle Scholar
  • 15 Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev 2014; (01) CD009593
    PubMedGoogle Scholar
  • 16 Ober WB. Ghon but not forgotten: Anton Ghon and his complex. Pathol Annu 1983; 18 (Pt 2): 79-85
    PubMedGoogle Scholar
  • 17 Bomanji JB, Gupta N, Gulati P, Das CJ. Imaging in tuberculosis. Cold Spring Harb Perspect Med 2015; 5 (06) 5
    PubMedGoogle Scholar
  • 18 Jeong YJ, Lee KS. Pulmonary tuberculosis: up-to-date imaging and management. AJR Am J Roentgenol 2008; 191 (03) 834-844
    CrossrefPubMedGoogle Scholar
  • 19 Poulsen A. Some clinical features of tuberculosis. Acta Tuberc Pneumol Scand 1957; 33 (1-2): 37-92
    PubMedGoogle Scholar
  • 20 Pai M, Denkinger CM, Kik SV. , et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev 2014; 27 (01) 3-20
    CrossrefPubMedGoogle Scholar
  • 21 Esmail H, Lai RP, Lesosky M. , et al. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography. Nat Med 2016; 22 (10) 1090-1093
    CrossrefPubMedGoogle Scholar
  • 22 Sathekge M, Maes A, Van de Wiele C. FDG-PET imaging in HIV infection and tuberculosis. Semin Nucl Med 2013; 43 (05) 349-366
    CrossrefPubMedGoogle Scholar
  • 23 Tiemersma EW, van der Werf MJ, Borgdorff MW, Williams BG, Nagelkerke NJ. Natural history of tuberculosis: duration and fatality of untreated pulmonary tuberculosis in HIV negative patients: a systematic review. PLoS One 2011; 6 (04) e17601
    CrossrefPubMedGoogle Scholar
  • 24 Boshoff HI, Barry III CE. Tuberculosis - metabolism and respiration in the absence of growth. Nat Rev Microbiol 2005; 3 (01) 70-80
    CrossrefPubMedGoogle Scholar
  • 25 Jagirdar J, Zagzag D. . 2004. “A Good Current and Historical Overview of the Pathology of Different Forms of Tuberculosis in Humans”. In Tuberculosis - An Update, edited by S. M. Rom, W. N. & Garay, 2nd ed., Philidelphia: Lippincott Williams & Wilkins; 837-842
    Google Scholar
  • 26 Kritzinger FE, den Boon S, Verver S. , et al. No decrease in annual risk of tuberculosis infection in endemic area in Cape Town, South Africa. Trop Med Int Health 2009; 14 (02) 136-142
    CrossrefPubMedGoogle Scholar
  • 27 Bates JH. . 1984. “Transmission, Pathogenesis, Pathology and Clinical Manifestations of Tuberculosis”. In The Mycobacteria: A Sourcebook, edited by L. G. Kubica, G. P. & Wayne, New York: Marcel Dekker; 991-1005
    Google Scholar
  • 28 Ralph AP, Ardian M, Wiguna A. , et al. A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis. Thorax 2010; 65 (10) 863-869
    CrossrefPubMedGoogle Scholar
  • 29 Ors F, Deniz O, Bozlar U. , et al. High-resolution CT findings in patients with pulmonary tuberculosis: correlation with the degree of smear positivity. J Thorac Imaging 2007; 22 (02) 154-159
    CrossrefPubMedGoogle Scholar
  • 30 Via LE, Weiner DM, Schimel D. , et al. Differential virulence and disease progression following Mycobacterium tuberculosis complex infection of the common marmoset (Callithrix jacchus). Infect Immun 2013; 81 (08) 2909-2919
    CrossrefPubMedGoogle Scholar
  • 31 Coleman MT, Maiello P, Tomko J. , et al. Early changes by (18) fluorodeoxyglucose positron emission tomography coregistered with computed tomography predict outcome after mycobacterium tuberculosis infection in cynomolgus macaques. Infect Immun 2014; 82: 2400-2404
    CrossrefPubMedGoogle Scholar
  • 32 Lin PL, Ford CB, Coleman MT. , et al. Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing. Nat Med 2014; 20 (01) 75-79
    CrossrefPubMedGoogle Scholar
  • 33 Malherbe ST, Shenai S, Ronacher K. , et al; Catalysis TB–Biomarker Consortium. Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure. Nat Med 2016; 22 (10) 1094-1100
    CrossrefPubMedGoogle Scholar
  • 34 Allwood BW, Gillespie R, Galperin-Aizenberg M. , et al. Obstructive pulmonary disease in patients with previous tuberculosis: pathophysiology of a community-based cohort. S Afr Med J 2017; 107 (05) 440-445
    CrossrefPubMedGoogle Scholar
  • 35 Baig IM, Saeed W, Khalil KF. Post-tuberculous chronic obstructive pulmonary disease. J Coll Physicians Surg Pak 2010; 20 (08) 542-544
    PubMedGoogle Scholar
  • 36 Hnizdo E, Singh T, Churchyard G. Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatment. Thorax 2000; 55 (01) 32-38
    CrossrefPubMedGoogle Scholar
  • 37 Kriel M, Lotz JW, Kidd M, Walzl G. Evaluation of a radiological severity score to predict treatment outcome in adults with pulmonary tuberculosis. Int J Tuberc Lung Dis 2015; 19 (11) 1354-1360
    CrossrefPubMedGoogle Scholar
  • 38 Demura Y, Tsuchida T, Uesaka D. , et al. Usefulness of 18F-fluorodeoxyglucose positron emission tomography for diagnosing disease activity and monitoring therapeutic response in patients with pulmonary mycobacteriosis. Eur J Nucl Med Mol Imaging 2009; 36 (04) 632-639
    CrossrefPubMedGoogle Scholar
  • 39 Stelzmueller I, Huber H, Wunn R. , et al. 18F-FDG PET/CT in the initial assessment and for follow-up in patients with tuberculosis. Clin Nucl Med 2016; 41 (04) e187-e194
    CrossrefPubMedGoogle Scholar
  • 40 Vorster M, Sathekge MM, Bomanji J. Advances in imaging of tuberculosis: the role of 18F-FDG PET and PET/CT. Curr Opin Pulm Med 2014; 20 (03) 287-293
    PubMedGoogle Scholar
  • 41 Chegou NN, Sutherland JS, Namuganga AR. , et al; AE-TBC consortium. Africa-wide evaluation of host biomarkers in QuantiFERON supernatants for the diagnosis of pulmonary tuberculosis. Sci Rep 2018; 8 (01) 2675
    CrossrefPubMedGoogle Scholar
  • 42 Millington KA, Innes JA, Hackforth S. , et al. Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load. J Immunol 2007; 178 (08) 5217-5226
    CrossrefPubMedGoogle Scholar
  • 43 Day CL, Abrahams DA, Lerumo L. , et al. Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load. J Immunol 2011; 187 (05) 2222-2232
    CrossrefPubMedGoogle Scholar
  • 44 Day CL, Moshi ND, Abrahams DA. , et al. Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment. PLoS One 2014; 9 (04) e94949
    CrossrefPubMedGoogle Scholar
  • 45 Adekambi T, Ibegbu CC, Cagle S. , et al. Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response. J Clin Invest 2015; 125 (09) 3723
    PubMedGoogle Scholar
  • 46 Wilkinson KA, Oni T, Gideon HP, Goliath R, Wilkinson RJ, Riou C. Activation profile of Mycobacterium tuberculosis-specific CD4(+) T cells reflects disease activity irrespective of HIV status. Am J Respir Crit Care Med 2016; 193 (11) 1307-1310
    CrossrefPubMedGoogle Scholar
  • 47 Riou C, Berkowitz N, Goliath R, Burgers WA, Wilkinson RJ. Analysis of the phenotype of Mycobacterium tuberculosis-specific CD4+ T cells to discriminate latent from active tuberculosis in HIV-uninfected and HIV-infected individuals. Front Immunol 2017; 8: 968
    CrossrefPubMedGoogle Scholar
  • 48 Musvosvi M, Duffy D, Filander E. , et al. T-cell biomarkers for diagnosis of tuberculosis: candidate evaluation by a simple whole blood assay for clinical translation. Eur Respir J 2018; 51 (03) 51
    PubMedGoogle Scholar
  • 49 Portevin D, Moukambi F, Clowes P. , et al. Assessment of the novel T-cell activation marker-tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study. Lancet Infect Dis 2014; 14 (10) 931-938
    CrossrefPubMedGoogle Scholar
  • 50 Harari A, Rozot V, Bellutti Enders F. , et al. Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease. Nat Med 2011; 17 (03) 372-376
    CrossrefPubMedGoogle Scholar
  • 51 Rozot V, Vigano S, Mazza-Stalder J. , et al. Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease. Eur J Immunol 2013; 43 (06) 1568-1577
    CrossrefPubMedGoogle Scholar
  • 52 Lewinsohn DM, Tydeman IS, Frieder M. , et al. High resolution radiographic and fine immunologic definition of TB disease progression in the rhesus macaque. Microbes Infect 2006; 8 (11) 2587-2598
    CrossrefPubMedGoogle Scholar
  • 53 Nyendak MR, Park B, Null MD. , et al; Tuberculosis Research Unit and the Tuberculosis Trials Consortium. Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment. PLoS One 2013; 8 (12) e81564
    CrossrefPubMedGoogle Scholar
  • 54 Petruccioli E, Chiacchio T, Pepponi I. , et al. First characterization of the CD4 and CD8 T-cell responses to QuantiFERON-TB Plus. J Infect 2016; 73 (06) 588-597
    CrossrefPubMedGoogle Scholar
  • 55 Pieterman ED, Liqui Lung FG, Verbon A. , et al. A multicentre verification study of the QuantiFERON®-TB Gold Plus assay. Tuberculosis (Edinb) 2018; 108: 136-142
    CrossrefPubMedGoogle Scholar
  • 56 Petruccioli E, Vanini V, Chiacchio T. , et al. Analytical evaluation of QuantiFERON- Plus and QuantiFERON- Gold In-tube assays in subjects with or without tuberculosis. Tuberculosis (Edinb) 2017; 106: 38-43
    CrossrefPubMedGoogle Scholar
  • 57 Barcellini L, Borroni E, Brown J. , et al. First evaluation of QuantiFERON-TB Gold Plus performance in contact screening. Eur Respir J 2016; 48 (05) 1411-1419
    CrossrefPubMedGoogle Scholar
  • 58 Kamada A, Amishima M. QuantiFERON-TB® Gold Plus as a potential tuberculosis treatment monitoring tool. Eur Respir J 2017; 49 (03) 49
    CrossrefPubMedGoogle Scholar
  • 59 Godfrey DI, Uldrich AP, McCluskey J, Rossjohn J, Moody DB. The burgeoning family of unconventional T cells. Nat Immunol 2015; 16 (11) 1114-1123
    CrossrefPubMedGoogle Scholar
  • 60 De Libero G, Singhal A, Lepore M, Mori L. Nonclassical T cells and their antigens in tuberculosis. Cold Spring Harb Perspect Med 2014; 4 (09) a018473
    CrossrefPubMedGoogle Scholar
  • 61 van Meijgaarden KE, Haks MC, Caccamo N, Dieli F, Ottenhoff TH, Joosten SA. Human CD8+ T-cells recognizing peptides from Mycobacterium tuberculosis (Mtb) presented by HLA-E have an unorthodox Th2-like, multifunctional, Mtb inhibitory phenotype and represent a novel human T-cell subset. PLoS Pathog 2015; 11 (03) e1004671
    CrossrefPubMedGoogle Scholar
  • 62 Caccamo N, Pietra G, Sullivan LC. , et al. Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines. Eur J Immunol 2015; 45 (04) 1069-1081
    CrossrefPubMedGoogle Scholar
  • 63 Heinzel AS, Grotzke JE, Lines RA. , et al. HLA-E-dependent presentation of Mtb-derived antigen to human CD8+ T cells. J Exp Med 2002; 196 (11) 1473-1481
    CrossrefPubMedGoogle Scholar
  • 64 Joosten SA, van Meijgaarden KE, van Weeren PC. , et al. Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity. PLoS Pathog 2010; 6 (02) e1000782
    CrossrefPubMedGoogle Scholar
  • 65 Gilleron M, Stenger S, Mazorra Z. , et al. Diacylated sulfoglycolipids are novel mycobacterial antigens stimulating CD1-restricted T cells during infection with Mycobacterium tuberculosis. J Exp Med 2004; 199 (05) 649-659
    CrossrefPubMedGoogle Scholar
  • 66 Moody DB, Ulrichs T, Mühlecker W. , et al. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature 2000; 404 (6780): 884-888
    CrossrefPubMedGoogle Scholar
  • 67 Kwon YS, Cho YN, Kim MJ. , et al. Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity. Tuberculosis (Edinb) 2015; 95 (03) 267-274
    CrossrefPubMedGoogle Scholar
  • 68 Gold MC, Cerri S, Smyk-Pearson S. , et al. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol 2010; 8 (06) e1000407
    CrossrefPubMedGoogle Scholar
  • 69 Le Bourhis L, Martin E, Péguillet I. , et al. Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 2010; 11 (08) 701-708
    CrossrefPubMedGoogle Scholar
  • 70 Snyder-Cappione JE, Nixon DF, Loo CP. , et al. Individuals with pulmonary tuberculosis have lower levels of circulating CD1d-restricted NKT cells. J Infect Dis 2007; 195 (09) 1361-1364
    CrossrefPubMedGoogle Scholar
  • 71 Sutherland JS, Hill PC, Adetifa IM. , et al. Identification of probable early-onset biomarkers for tuberculosis disease progression. PLoS One 2011; 6 (09) e25230
    CrossrefPubMedGoogle Scholar
  • 72 Barry III CE, Boshoff HI, Dartois V. , et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 2009; 7 (12) 845-855
    CrossrefPubMedGoogle Scholar
  • 73 Scriba TJ, Penn-Nicholson A, Shankar S. , et al; Other Members of the ACS Cohort Study Team. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease. PLoS Pathog 2017; 13 (11) e1006687
    CrossrefPubMedGoogle Scholar
  • 74 Esmail H, Lai RP, Lesosky M. , et al. Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis. Proc Natl Acad Sci U S A 2018; 115 (05) E964-E973
    CrossrefPubMedGoogle Scholar
  • 75 Tameris MD, Hatherill M, Landry BS. , et al; MVA85A 020 Trial Study Team. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomized, placebo-controlled phase 2b trial. Lancet 2013; 381 (9871): 1021-1028
    CrossrefPubMedGoogle Scholar
  • 76 Andrews JR, Nemes E, Tameris M. , et al. Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study. Lancet Respir Med 2017; 5 (04) 282-290
    CrossrefPubMedGoogle Scholar
  • 77 Winje BA, White R, Syre H. , et al. Stratification by interferon-γ release assay level predicts risk of incident TB. Thorax 2018; 73: 652-661
    CrossrefPubMedGoogle Scholar
  • 78 Zak DE, Penn-Nicholson A, Scriba TJ. , et al; ACS and GC6-74 Cohort Study Groups. A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet 2016; 387 (10035): 2312-2322
    CrossrefPubMedGoogle Scholar
  • 79 Darboe F, Mbandi SK, Thompson EG. , et al; SATVI Clinical Immunology Team. Diagnostic performance of an optimized transcriptomic signature of risk of tuberculosis in cryopreserved peripheral blood mononuclear cells. Tuberculosis (Edinb) 2018; 108: 124-126
    CrossrefPubMedGoogle Scholar
  • 80 Berry MP, Graham CM, McNab FW. , et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 2010; 466 (7309): 973-977
    CrossrefPubMedGoogle Scholar
  • 81 Bloom CI, Graham CM, Berry MP. , et al. Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers. PLoS One 2013; 8 (08) e70630
    CrossrefPubMedGoogle Scholar
  • 82 Kaforou M, Wright VJ, Oni T. , et al. Detection of tuberculosis in HIV-infected and -uninfected African adults using whole blood RNA expression signatures: a case-control study. PLoS Med 2013; 10 (10) e1001538
    CrossrefPubMedGoogle Scholar
  • 83 Kaforou M, Wright VJ, Levin M. Host RNA signatures for diagnostics: an example from paediatric tuberculosis in Africa. J Infect 2014; 69 (Suppl. 01) S28-S31
    CrossrefPubMedGoogle Scholar
  • 84 Andersen P, Doherty TM, Pai M, Weldingh K. The prognosis of latent tuberculosis: can disease be predicted?. Trends Mol Med 2007; 13 (05) 175-182
    CrossrefPubMedGoogle Scholar
  • 85 Maertzdorf J, Ota M, Repsilber D. , et al. Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis. PLoS One 2011; 6 (10) e26938
    CrossrefPubMedGoogle Scholar
  • 86 Singhania A, Verma R, Graham CM. , et al. A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection. Nature Communications 2018; 9 (01) 2308 . Doi: 10.1038/s41467-018-04579-w
    CrossrefPubMedGoogle Scholar
  • 87 Sabin FR, Doan CA. The relation of monocytes and clasmatocytes to early infection in rabbits with bovine tubercle bacilli. J Exp Med 1927; 46 (04) 627-644
    CrossrefPubMedGoogle Scholar
  • 88 Rogers P. A study of the blood monocytes in children with tuberculosis. N Engl J Med 1928; 198: 740-749
    CrossrefPubMedGoogle Scholar
  • 89 Naranbhai V, Hill AV, Abdool Karim SS. , et al. Ratio of monocytes to lymphocytes in peripheral blood identifies adults at risk of incident tuberculosis among HIV-infected adults initiating antiretroviral therapy. J Infect Dis 2014; 209 (04) 500-509
    CrossrefPubMedGoogle Scholar
  • 90 Rakotosamimanana N, Richard V, Raharimanga V. , et al. Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study. Eur Respir J 2015; 46 (04) 1095-1103
    CrossrefPubMedGoogle Scholar
  • 91 Wang J, Yin Y, Wang X. , et al. Ratio of monocytes to lymphocytes in peripheral blood in patients diagnosed with active tuberculosis. Braz J Infect Dis 2015; 19 (02) 125-131
    CrossrefPubMedGoogle Scholar
  • 92 La Manna MP, Orlando V, Dieli F. , et al. Quantitative and qualitative profiles of circulating monocytes may help identifying tuberculosis infection and disease stages. PLoS One 2017; 12 (02) e0171358
    CrossrefPubMedGoogle Scholar
  • 93 Naranbhai V, Fletcher HA, Tanner R. , et al. Distinct transcriptional and anti-mycobacterial profiles of peripheral blood monocytes dependent on the ratio of monocytes: lymphocytes. EBioMedicine 2015; 2: 1619-1626
    CrossrefPubMedGoogle Scholar
  • 94 Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature 2010; 465 (7299): 793-797
    CrossrefPubMedGoogle Scholar
  • 95 Fletcher HA, Snowden MA, Landry B. , et al. T-cell activation is an immune correlate of risk in BCG vaccinated infants. Nat Commun 2016; 7: 11290
    CrossrefPubMedGoogle Scholar