Latent tuberculosis diagnostics: current scenario and review

Submitted: March 9, 2024
Accepted: April 3, 2024
Published: May 3, 2024
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This review presents a comprehensive examination of the contemporary landscape pertaining to latent tuberculosis infection (LTBI) diagnostics, with a particular emphasis on the global ramifications and the intricacies surrounding LTBI diagnosis and treatment. It accentuates the imperative of bolstering diagnostic, preventive, and treatment modalities for tuberculosis (TB) to fulfill the ambitious targets set forth by the World Health Organization aimed at reducing TB-related mortalities and the incidence of new TB cases. The document underscores the significance of addressing LTBI as a means of averting the progression to active TB, particularly in regions burdened with high TB prevalence, such as India. An in-depth analysis of the spectrum delineating latent and active TB disease is provided, elucidating the risk factors predisposing individuals with LTBI to progress towards active TB, including compromised immune functionality, concurrent HIV infection, and other immunosuppressive states. Furthermore, the challenges associated with LTBI diagnosis are elucidated, encompassing the absence of a definitive diagnostic assay, and the merits and demerits of tuberculin skin testing (TST) and interferon-γ release assays (IGRAs) are expounded upon. The document underscores the necessity of confronting these challenges and furnishes a meticulous examination of the advantages and limitations of TST and IGRAs, along with the intricacies involved in interpreting their outcomes across diverse demographics and settings. Additionally, attention is drawn towards the heritability of the interferon-γ response to mycobacterial antigens and the potential utility of antibodies in LTBI diagnosis.

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World Health Organization. Global TB report 2022. Available from: https://iris.who.int/bitstream/handle/10665/363752/9789240061729-eng.pdf?sequence=1.
World Health Organization. The END TB strategy; 2015. Available from: https://apps.who.int/iris/bitstream/handle/10665/331326/WHO-HTM-TB-2015.19-eng.pdf?sequence=1&isAllowed=y. Accessed on:20/02/2023.
World Health Organization. WHO consolidated guidelines on tuberculosis: module 1: prevention. Tuberculosis preventive treatment. 2020. Available from: https://iris.who.int/bitstream/handle/10665/331170/9789240001503-eng.pdf?sequence=1.
World Health Organization. WHO consolidated guidelines on tuberculosis: Module 4: treatment. Drug-susceptible tuberculosis treatment. 2022. Available from: https://iris.who.int/bitstream/handle/10665/353829/9789240048126-eng.pdf?sequence=1.
Indian Council of Medical Research, ICMR-National Institute for Research in Tuberculosis, Ministry of Health and Family Welfare, Government of India, Central TB Division and National Tuberculosis Elimination Programme, World Health Organization India Office, State TB Cells of all States and Union Territories. National prevalence survey in India 2019-2021. Available from: https://tbcindia.gov.in/showfile.php?lid=3659. Accessed on: 20/02/2023.
Global Tuberculosis Programme. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. 2018. Available from: http://www.ncbi.nlm.nih.gov/books/NBK531235/. Accessed on: 20/04/2020.
Houben RMGJ, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med 2016;13:e1002152. DOI: https://doi.org/10.1371/journal.pmed.1002152
Kyu HH, Maddison ER, Henry NJ, et al. Global, regional, and national burden of tuberculosis, 1990–2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study. Lancet Infect Dis 2018;18:1329-49. DOI: https://doi.org/10.1016/S1473-3099(18)30625-X
Saha S, Kumar A, Saurabh K, et al. Current status of treatment of latent tuberculosis infection in India. Indian J Med Sci 2020;71:54-9. DOI: https://doi.org/10.25259/IJMS_18_2019
Dye C, Scheele S, Dolin P, et al. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO global surveillance and monitoring project. JAMA 1999;282:677-86. DOI: https://doi.org/10.1001/jama.282.7.677
Ayelign B, Negash M, Genetu M, et al. Immunological impacts of diabetes on the susceptibility of Mycobacterium tuberculosis. J Immunol Res 2019;2019:6196532. DOI: https://doi.org/10.1155/2019/6196532
Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med 2008;5:e152. DOI: https://doi.org/10.1371/journal.pmed.0050152
Flynn JL, Chan J. Tuberculosis: latency and reactivation MINIREVIEW tuberculosis: latency and reactivation. Infect Immunity 2001;69:4195-201. DOI: https://doi.org/10.1128/IAI.69.7.4195-4201.2001
Berry MPR, Graham CM, McNab FW, et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 2010;466:973-7. DOI: https://doi.org/10.1038/nature09247
Ottenhoff THM, Dass RH, Yang N, et al. Genome-wide expression profiling identifies type 1 interferon response pathways in active tuberculosis. PLoS One 2012;7:e45839. DOI: https://doi.org/10.1371/journal.pone.0045839
Thompson EG, Du Y, Malherbe ST, et al. Host blood RNA signatures predict the outcome of tuberculosis treatment. Tuberculosis (Edinb) 2017;107:48-58. DOI: https://doi.org/10.1016/j.tube.2017.08.004
Pai M, Riley LW, Colford JM. Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Infect Dis 2004;4:761-76. DOI: https://doi.org/10.1016/S1473-3099(04)01206-X
Nayak S, Acharjya B. Mantoux test and its interpretation. Indian Dermatol Online J 2012;3:2-6. DOI: https://doi.org/10.4103/2229-5178.93479
Deck F, Guld J. The WHO tuberculin test. Bull Int Union Tuberc 1964;34:53-70.
Howard A, Mercer P, Nataraj HC, Kang BC. Bevel-down superior to bevel-up in intradermal skin testing. Ann Allergy Asthma Immunol 1997;78:594-6. DOI: https://doi.org/10.1016/S1081-1206(10)63222-X
Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med 2000;161:S221-47. DOI: https://doi.org/10.1164/ajrccm.161.supplement_3.ats600
Druszczynska M, Wlodarczyk M, Kielnierowski G, et al. CD14-159C/T polymorphism in the development of delayed skin hypersensitivity to tuberculin. PLoS One 2017;12:e0190106. DOI: https://doi.org/10.1371/journal.pone.0190106
Babu S, Bhat SQ, Kumar NP, et al. Regulatory T cells modulate Th17 responses in tuberculin skin test positive (TST+) individuals. J Infect Dis 2010;201:20-31. DOI: https://doi.org/10.1086/648735
Cobat A, Gallant CJ, Simkin L, et al. Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis. J Exp Med 2009;206:2583-91. DOI: https://doi.org/10.1084/jem.20090892
Kim Y, Dawes-Higgs E, Zagarella S. Foreign body reaction involving a Mantoux test site. Australas J Dermatol 2005;46:169-71. DOI: https://doi.org/10.1111/j.1440-0960.2005.00172.x
Jonas DE, Riley SR, Lee LC, et al. Screening for latent tuberculosis infection in adults: updated evidence report and systematic review for the US preventive services task force. JAMA 2023;329:1495-509. DOI: https://doi.org/10.1001/jama.2023.3954
Bierrenbach AL, Floyd S, Cunha SC, et al. A comparison of dual skin test with mycobacterial antigens and tuberculin skin test alone in estimating prevalence of Mycobacterium tuberculosis infection from population surveys. Int J Tuberc Lung Dis 2003;7:312-9.
Fine PE, Floyd S, Stanford JL, et al. Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy. Epidemiol Infect 2001;126:379-87. DOI: https://doi.org/10.1017/S0950268801005532
Farhat M, Greenaway C, Pai M, Menzies D. False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria?. Int J Tuberc Lung Dis 2006;10:1192-204.
von Reyn CF, Horsburgh CR, Olivier KN, et al. Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States. Int J Tuberc Lung Dis 2001;5:1122-8.
Cohn DL. The effect of BCG vaccination on tuberculin skin testing. Does it matter?. Am J Respir Crit Care Med 2001;164:915-6. DOI: https://doi.org/10.1164/ajrccm.164.6.2107090c
Menzies D. Interpretation of repeated tuberculin tests: boosting, conversion, and reversion. Am J Respir Crit Care Med 1999;159:15-21. DOI: https://doi.org/10.1164/ajrccm.159.1.9801120
Watkins RE, Brennan R, Plant AJ. Tuberculin reactivity and the risk of tuberculosis: a review. Int J Tuberc Lung Dis 2000;4:895-903.
Deniz S, Aydemir Y, Sengül A, et al. Factors affecting TST level in patients undergoing dialysis: a multicenter study. Hemodial Int 2019;23:81-7. DOI: https://doi.org/10.1111/hdi.12676
van Soelen N, Mandalakas AM, Kirchner HL, et al. Effect of ascaris lumbricoides specific IgE on tuberculin skin test responses in children in a high-burden setting: a cross-sectional community-based study. BMC Infect Dis 2012;12:211. DOI: https://doi.org/10.1186/1471-2334-12-211
Burl S, Adetifa UJ, Cox M, et al. The tuberculin skin test (TST) is affected by recent BCG vaccination but not by exposure to non-tuberculosis mycobacteria (NTM) during early life. PLoS One 2010;5:e12287. DOI: https://doi.org/10.1371/journal.pone.0012287
Zellweger JP, Sotgiu G, Corradi M, Durando P. The diagnosis of latent tuberculosis infection (LTBI): currently available tests, future developments, and perspectives to eliminate tuberculosis (TB). Med Lav 2020;111:170-83.
Arend SM, Geluk A, Van Meijgaarden KE, et al. Antigenic equivalence of human T-cell responses to Mycobacterium tuberculosis-specific RD1-encoded protein antigens ESAT-6 and culture filtrate protein 10 and to mixtures of synthetic peptides. Infect Immun 2000;68:3314-21. DOI: https://doi.org/10.1128/IAI.68.6.3314-3321.2000
HarboeM, Oettinger T,Wiker HG, et al. Evidence for occurrence of the ESAT-6 protein inMycobacteriumtuberculosis and virulent Mycobacterium bovis and for its absence inMycobacterium bovis BCG. Infect Immun 1996;64:16-22. DOI: https://doi.org/10.1128/iai.64.1.16-22.1996
T-SPOT.TB. The T-SPOT.TB test technology. Available from: https://www.tspot.com/why-the-t-spot-tb-test/technology/. Accessed on: 8/09/2020.
Diel R, Goletti D, Ferrara G, et al. Interferon- release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J 2011;37:88-99. DOI: https://doi.org/10.1183/09031936.00115110
Cobat A, Gallant CJ, Simkin L, et al. High heritability of antimycobacterial immunity in an area of hyperendemicity for tuberculosis disease. J Infect Dis 2010;201:15-9. DOI: https://doi.org/10.1086/648611
Tao L, Zalwango S, Chervenak K, et al. Genetic and shared environmental influences on interferon-g production in response to mycobacterium tuberculosis antigens in a ugandan population. Am J Trop Med Hyg 2013;89:169-73. DOI: https://doi.org/10.4269/ajtmh.12-0670
Metcalfe JZ, Everett CK, Steingart KR, et al. Interferon-γ Release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis. J Infect Dis 2011;204:S1120-9. DOI: https://doi.org/10.1093/infdis/jir410
Sester M, Sotgiu G, Lange C, Giehl C, Girardi E, Migliori GB, et al. Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J 2011;37:100-11. DOI: https://doi.org/10.1183/09031936.00114810
Zwerling A, Pai M. The BCG world atlas: a new, open-access resource for clinicians and researchers. Expert Rev Anti Infect Ther 2011;9:559-61. DOI: https://doi.org/10.1586/eri.11.71
Arend SM, van Meijgaarden KE, de Boer K, et al. Tuberculin skin testing and in vitro t cell responses to esat‐6 and culture filtrate protein 10 after infection with Mycobacterium marinum or M. kansasii. J Infect Dis 2002;186:1797-807. DOI: https://doi.org/10.1086/345760
van Zyl-Smit RN, Zwerling A, Dheda K, Pai M. Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review. PLoS One 2009;4:e8517. DOI: https://doi.org/10.1371/journal.pone.0008517
Hiza H, Fenner L, Hella J, et al. Boosting effect of IL-7 in interferon gamma release assays to diagnose Mycobacterium tuberculosis infection. PLoS One 2018;13:e0202525. DOI: https://doi.org/10.1371/journal.pone.0202525
Pérez I, Roig C, GilM, Torrent P, et al. Concordancia entre la prueba de la tuberculina y el interferon gamma release assay-IGRA en pacientes con enfermedades inflamatorias mediadas por la inmunidad. Rev Española Quimioter 2019;32:445-50.
Bua A, Ruggeri M, Zanetti S, Molicotti P. Effect of teriflunomide on QuantiFERON-TB gold results. Med Microbiol Immunol 2017;206:73-5. DOI: https://doi.org/10.1007/s00430-016-0482-x
Hakimian S, Popov Y, Rupawala AH, et al. The conundrum of indeterminate QuantiFERON-TB gold results before anti-tumor necrosis factor initiation. Biol Targets Therapy 2018;12:61-7. DOI: https://doi.org/10.2147/BTT.S150958
Walsh MC, Camerlin AJ, Miles R, et al. The sensitivity of interferon-gamma release assays is not compromised in tuberculosis patients with diabetes. Int J Tuberculosis Lung Dis 2011;15:179-84. DOI: https://doi.org/10.5588/ijtld.11.0650
Pai M, Behr M. Latent Mycobacterium tuberculosis infection and interferon-gamma release assays. Microbiol Spectrum 2016;4. DOI: https://doi.org/10.1128/microbiolspec.TBTB2-0023-2016
Dheda K, Smit R van Z, Badri M, Pai M. T-cell interferon-γ release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden vs. low-burden settings: Curr Opin Pulm Med 2009;15:188-200. DOI: https://doi.org/10.1097/MCP.0b013e32832a0adc
Cattamanchi A, Smith R, Steingart KR, et al. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in hiv-infected individuals: a systematic review and meta-analysis. J Acquir Immune Defic Synd 2011;56:230-8. DOI: https://doi.org/10.1097/QAI.0b013e31820b07ab
Denkinger CM, Pai M, Patel M, Menzies D. Gamma interferon release assay for monitoring of treatment response for active tuberculosis: an explosion in the spaghetti factory. J Clin Microbiol 2013;51:607-10. DOI: https://doi.org/10.1128/JCM.02278-12
Chiappini E, Fossi F, Bonsignori F, et al. Utility of interferon-γ release assay results to monitor anti-tubercular treatment in adults and children. Clin Ther 2012;34:1041-8. DOI: https://doi.org/10.1016/j.clinthera.2012.03.006
Pathakumari B, Devasundaram S, Raja A. Altered expression of antigenspecific memory and regulatory T-cell subsets differentiate latent and active tuberculosis. Immunology 2018;153:325-36. DOI: https://doi.org/10.1111/imm.12833
Menzies D, Pai M, Zwerling A. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Internal Med 2008;149:177-84. DOI: https://doi.org/10.7326/0003-4819-149-3-200808050-00241
Caño-muñiz S, Anthony R, Niemann S, Alffenaar JC. New approaches and therapeutic options for mycobacterium. Clin Microbiol Rev 2018;31:e00060-17. DOI: https://doi.org/10.1128/CMR.00060-17
Lewis K. Persister cells. Annu Rev Microbiol 2010;64:357-72. DOI: https://doi.org/10.1146/annurev.micro.112408.134306
Goletti D, Butera O, Vanini V, et al. Response to Rv2628 latency antigen associates with cured tuberculosis and remote infection. Eur Respir J 2010;36:135-42. DOI: https://doi.org/10.1183/09031936.00140009
Chegou NN, Black GF, Loxton AG, et al. Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting. BMC Infect Dis 2012;12:10. DOI: https://doi.org/10.1186/1471-2334-12-10
Doddam SN, Peddireddy V, Ahmed N. Mycobacterium tuberculosis DosR regulon gene Rv2004c encodes a novel antigen with pro-inflammatory functions and potential diagnostic application for detection of latent tuberculosis. Front Immunol 2017;8:712. DOI: https://doi.org/10.3389/fimmu.2017.00712
Ziegenbalg A, Prados-Rosales R, Jenny-Avital ER, et al. Immunogenicity of mycobacterial vesicles in humans: Identification of a new tuberculosis antibody biomarker. Tuberculosis (Edinb) 2013;93:448-55. DOI: https://doi.org/10.1016/j.tube.2013.03.001
Kimby E. Tolerability and safety of rituximab (MabTheraR ). Cancer Treat Rev 2005;31:456-73. DOI: https://doi.org/10.1016/j.ctrv.2005.05.007
de Araujo LS, da Silva NBM, Leung JAM, et al. IgG subclasses’ response to a set of mycobacterial antigens in different stages of Mycobacterium tuberculosis infection. Tuberculosis 2018;108:70-6. DOI: https://doi.org/10.1016/j.tube.2017.10.010
Fletcher HA, Snowden MA, Landry B, et al. Tcell activation is an immune correlate of risk in BCG vaccinated infants. Nat Commun 2016;7:11290. DOI: https://doi.org/10.1038/ncomms11290
Coppola M, Arroyo L, van Meijgaarden KE, et al. Differences in IgG responses against infection phase related Mycobacterium tuberculosis (Mtb) specific antigens in individuals exposed or not to Mtb correlate with control of TB infection and progression. Tuberculosis (Edinb) 2017;106:25-32. DOI: https://doi.org/10.1016/j.tube.2017.06.001
Amiano NO, Morelli MP, Pellegrini JM, et al. IFN-g and IgG responses to Mycobacterium tuberculosis latency antigen Rv2626c differentiate remote from recent tuberculosis infection. Sci Rep 2020;10:7472. DOI: https://doi.org/10.1038/s41598-020-64428-z
Pollock KM, Whitworth HS, Montamat-Sicotte DJ, et al. T-cell immunophenotyping distinguishes active from latent tuberculosis. J Infect Dis 2013;208:952-68. DOI: https://doi.org/10.1093/infdis/jit265
Latorre I, Fernández-Sanmartín MA, Muriel-Moreno B, et al. Study of CD27 and CCR4 markers on specific CD4+ T-cells as immune tools for active and latent tuberculosis management. Front Immunol 2019;10:03094. DOI: https://doi.org/10.3389/fimmu.2018.03094
Weyer K, Gilpin C, Mirzayev F, et al. Use of tuberculosis interferon-gamma release assays (IGRAs) in low- and middle-income countries: policy statement. 2011. Geneva, Switzerland: World Health Organization.
Pai M, Menzies D. Interferon‐γ RELEASE ASSAYS: WHAT IS THEIR ROLE IN THE DIAGNOSIS OF ACTIVE TUBERCULOsis?. Clin Infect Dis 2007;44:74-7. DOI: https://doi.org/10.1086/509927
Ministry of Health and Family Welfare, Government of India. NTEP guidelines for programmatic management of TB preventive treatment in India. 2021. Available from: https://tbcindia.gov.in/showfile.php?lid=3625.

How to Cite

Gupta, Amitesh, Eshutosh Chandra, Shipra Anand, Naresh Kumar, Richa Arora, Divyanshi Rana, and Parul Mrigpuri. 2024. “Latent Tuberculosis Diagnostics: Current Scenario and Review”. Monaldi Archives for Chest Disease, May. https://doi.org/10.4081/monaldi.2024.2984.