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The Future of Serology-Based Diagnosis for Tuberculosis in India

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Diagnosis of Mycobacterium

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Abstract

Tuberculosis (TB) is a major public health problem in India, with an estimated 2.42 million cases in 2022. Traditional diagnostic methods for tuberculosis (TB) in India are limited in their accuracy and specificity. Sputum smear microscopy is the most widely used method, but it has a sensitivity of around 30–50%. Culture-based methods are more sensitive, but they are expensive, time-consuming, and require specialized laboratory facilities. As a result, there is a need for alternative diagnostic methods that are more accurate, specific, and cost-effective.

Serology-based diagnosis has been proposed as an alternative approach for TB diagnosis. Serological tests detect antibodies against Mycobacterium tuberculosis (M. tuberculosis) antigens in the blood of patients. They are simple, rapid, and can be performed in a standard laboratory setting. However, the performance of serological tests in the diagnosis of pulmonary TB has been poor, with low sensitivity and specificity. In addition, the interpretation of serological markers remains a challenge, and the heterogeneity of M. tuberculosis strains can complicate the diagnosis of TB. Also, the economic implications of serological testing for TB are also substantial. Therefore, the use of serological tests for TB diagnosis in India needs to be carefully evaluated in terms of cost-effectiveness.

Despite the limitations, serology-based diagnosis has the potential to improve TB diagnosis in India. Serological tests can provide rapid results, allowing for early detection and timely initiation of treatment. This is crucial in a country like India, where TB is a major public health concern. Serological tests can also help improve the overall diagnostic accuracy and enhance the detection of TB cases. However, more research is needed to improve the accuracy and specificity of serological tests and to evaluate their cost-effectiveness. Overall, serology-based diagnosis is a promising approach for TB diagnosis in India. However, more research is needed to make it a more reliable and cost-effective diagnostic tool.

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References

  1. 5646719104TB_AR_2023_04-04-2023_LRP_final.pdf [Internet]. https://tbcindia.gov.in/WriteReadData/l892s/5646719104TB_AR_2023_04-04-2023_LRP_final.pdf. Accessed 23 May 2023.

  2. Kanabus A. TB facts—tests, drugs, statistics & lots more about “information about tuberculosis”. GHE. 2022 TBFacts. https://tbfacts.org/. Accessed 23 May 2023.

  3. Steingart KR, Ramsay A, Dowdy DW, Pai M. Serological tests for the diagnosis of active tuberculosis: relevance for India. Indian J Med Res. 2012;135(5):695–702.

    PubMed  PubMed Central  Google Scholar 

  4. Singh S, Singh J, Kumar S, Gopinath K, Balooni V, Singh N, et al. Poor performance of serological tests in the diagnosis of pulmonary tuberculosis: evidence from a contact tracing field study. PloS One. 2012;7(7):e40213.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Steingart KR, Dendukuri N, Henry M, Schiller I, Nahid P, Hopewell PC, et al. Performance of purified antigens for serodiagnosis of pulmonary tuberculosis: a meta-analysis. Clin Vaccine Immunol. 2009;16(2):260–76.

    CAS  PubMed  Google Scholar 

  6. Dowdy DW, Steingart KR, Pai M. Serological testing versus other strategies for diagnosis of active tuberculosis in India: a cost-effectiveness analysis. PLoS Med. 2011;8(8):e1001074.

    PubMed  PubMed Central  Google Scholar 

  7. Jarosławski S, Pai M. Why are inaccurate tuberculosis serological tests widely used in the Indian private healthcare sector? A root-cause analysis. J Epidemiol Glob Health. 2012;2(1):39–50.

    PubMed  PubMed Central  Google Scholar 

  8. Steingart KR, Henry M, Laal S, Hopewell PC, Ramsay A, Menzies D, et al. A systematic review of commercial serological antibody detection tests for the diagnosis of extrapulmonary tuberculosis. Postgrad Med J. 2007;83(985):705–12.

    PubMed  PubMed Central  Google Scholar 

  9. Weldingh K, Rosenkrands I, Okkels LM, Doherty TM, Andersen P. Assessing the Serodiagnostic potential of 35 mycobacterium tuberculosis proteins and identification of four novel serological antigens. J Clin Microbiol. 2005;43(1):57–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med. 2007;146(5):340–54.

    PubMed  Google Scholar 

  11. Tucci P, González-Sapienza G, Marin M. Pathogen-derived biomarkers for active tuberculosis diagnosis. Front Microbiol. 2014;5:549.

    PubMed  PubMed Central  Google Scholar 

  12. Burbelo PD, Keller J, Wagner J, Klimavicz JS, Bayat A, Rhodes CS, et al. Serological diagnosis of pulmonary mycobacterium tuberculosis infection by LIPS using a multiple antigen mixture. BMC Microbiol. 2015;15:205.

    PubMed  PubMed Central  Google Scholar 

  13. Yu X, Song L, Petritis B, Bian X, Wang H, Viloria J, et al. Multiplexed nucleic acid programmable protein arrays. Theranostics. 2017;7(16):4057–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. She RC, Litwin CM. Performance of a tuberculosis serologic assay in various patient populations. Am J Clin Pathol. 2015;144(2):240–6.

    CAS  PubMed  Google Scholar 

  15. Xu JN, Chen JP, Chen DL. Serodiagnosis efficacy and immunogenicity of the fusion protein of mycobacterium tuberculosis composed of the 10-kilodalton culture filtrate protein, ESAT-6, and the extracellular domain fragment of PPE68. Clin Vaccine Immunol. 2012;19(4):536–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Zagmignan A, da Costa AC, Viana JL, Lima Neto LG, de Monteiro C, Gaioso Neto AG, et al. Identification of specific antibodies against the Ag85C-MPT51-HspX fusion protein (CMX) for serological screening of tuberculosis in endemic area. Expert Rev Clin Immunol. 2017;13(8):837–43.

    CAS  PubMed  Google Scholar 

  17. Liu Z, Qie S, Li L, **u B, Yang X, Dai Z, et al. Identification of novel RD1 antigens and their combinations for diagnosis of sputum smear−/culture+ TB patients. Biomed Res Int. 2016;2016:7486425.

    PubMed  PubMed Central  Google Scholar 

  18. Bai XJ, Yang YR, Liang JQ, An HR, Wang J, Ling YB, et al. Diagnostic performance and problem analysis of commercial tuberculosis antibody detection kits in China. Mil Med Res. 2018;5(1):10.

    PubMed  PubMed Central  Google Scholar 

  19. Khaliq A, Ravindran R, Hussainy SF, Krishnan VV, Ambreen A, Yusuf NW, et al. Field evaluation of a blood based test for active tuberculosis in endemic settings. PloS One. 2017;12(4):e0173359.

    PubMed  PubMed Central  Google Scholar 

  20. Song L, Wallstrom G, Yu X, Hopper M, Van Duine J, Steel J, et al. Identification of antibody targets for tuberculosis serology using high-density nucleic acid programmable protein arrays. Mol Cell Proteomics. 2017;16(4 Suppl 1):S277–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Shete PB, Ravindran R, Chang E, Worodria W, Chaisson LH, Andama A, et al. Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda. PloS One. 2017;12(8):e0180122.

    PubMed  PubMed Central  Google Scholar 

  22. Singh A, Kumar Gupta A, Gopinath K, Sharma P, Singh S. Evaluation of 5 novel protein biomarkers for the rapid diagnosis of pulmonary and extra-pulmonary tuberculosis: preliminary results. Sci Rep. 2017;7:44121.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Lawn SD, Gupta-Wright A. Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications. Trans R Soc Trop Med Hyg. 2016;110(3):180–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Swaminathan S, Rekha VVB. Antigen detection as a point-of-care test for TB: the case of lipoarabinomannan. Future Microbiol. 2012;7(5):559–64.

    CAS  PubMed  Google Scholar 

  25. Flores LL, Steingart KR, Dendukuri N, Schiller I, Minion J, Pai M, et al. Systematic review and meta-analysis of antigen detection tests for the diagnosis of tuberculosis. Clin Vaccine Immunol. 2011;18(10):1616–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Flores J, Cancino JC, Chavez-Galan L. Lipoarabinomannan as a point-of-care assay for diagnosis of tuberculosis: how far are we to use it? Front Microbiol. 2021;12:638047.

    PubMed  PubMed Central  Google Scholar 

  27. Shah M, Hanrahan C, Wang ZY, Dendukuri N, Lawn SD, Denkinger CM, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults. Cochrane Database Syst Rev. 2016;5:CD011420.

    Google Scholar 

  28. Achkar JM, Ziegenbalg A. Antibody responses to mycobacterial antigens in children with tuberculosis: challenges and potential diagnostic value. Clin Vaccine Immunol. 2012;19(12):1898–906.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Pereira Arias-Bouda LM, Nguyen LN, Ho LM, Kuijper S, Jansen HM, Kolk AHJ. Development of antigen detection assay for diagnosis of tuberculosis using sputum samples. J Clin Microbiol. 2000;38(6):2278–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Anochie PI, Onyeneke EC, Ogu AC, Onyeozirila AC, Aluru S, Onyejepu N, et al. Recent advances in the diagnosis of mycobacterium tuberculosis. Germs. 2012;2(3):110–20.

    PubMed  PubMed Central  Google Scholar 

  31. Kashyap RS, Rajan AN, Ramteke SS, Agrawal VS, Kelkar SS, Purohit HJ, et al. Diagnosis of tuberculosis in an Indian population by an indirect ELISA protocol based on detection of antigen 85 complex: a prospective cohort study. BMC Infect Dis. 2007;7:74.

    PubMed  PubMed Central  Google Scholar 

  32. Bothamley GH, Rudd RM. Clinical evaluation of a serological assay using a monoclonal antibody (TB72) to the 38 kDa antigen of mycobacterium tuberculosis. Eur Respir J. 1994;7(2):240–6.

    CAS  PubMed  Google Scholar 

  33. Verma RK, Jain A. Antibodies to mycobacterial antigens for diagnosis of tuberculosis. FEMS Immunol Med Microbiol. 2007;51(3):453–61.

    CAS  PubMed  Google Scholar 

  34. Feng F, Zhang H, Zhu Z, Li C, Shi Y, Zhang Z. The application of anti-ESAT-6 monoclonal antibody fluorescent probe in ex vivo near-infrared fluorescence imaging in mice with pulmonary tuberculosis. Lumin J Biol Chem Lumin. 2014;29(6):614–20.

    CAS  Google Scholar 

  35. Leng J, Ding Y, Shou C, Wu Z, Zhuo G, Wang K, et al. Development of a novel anti ESAT-6 monoclonal antibody for screening of mycobacterium tuberculosis. Int J Clin Exp Med. 2014;7(11):4238–43.

    PubMed  PubMed Central  Google Scholar 

  36. Trilling AK, de Ronde H, Noteboom L, van Houwelingen A, Roelse M, Srivastava SK, et al. A broad set of different llama antibodies specific for a 16 kDa heat shock protein of mycobacterium tuberculosis. PloS One. 2011;6(10):e26754.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Jørstad MD, Marijani M, Dyrhol-Riise AM, Sviland L, Mustafa T. MPT64 antigen detection test improves routine diagnosis of extrapulmonary tuberculosis in a low-resource setting: a study from the tertiary care hospital in Zanzibar. PloS One. 2018;13(5):e0196723.

    PubMed  PubMed Central  Google Scholar 

  38. Chan CE, Götze S, Seah GT, Seeberger PH, Tukvadze N, Wenk MR, et al. The diagnostic targeting of a carbohydrate virulence factor from M. Tuberculosis. Sci Rep. 2015;5:10281.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Alavi-Naini R, Metanat M, Alijani E, Mozaffar H. Patho-TB test for the rapid diagnosis of pulmonary tuberculosis. J Res Med Sci. 2009;14(5):301–7.

    PubMed  PubMed Central  Google Scholar 

  40. Mudaliar AV, Kashyap RS, Purohit HJ, Taori GM, Daginawala HF. Detection of 65 kD heat shock protein in cerebrospinal fluid of tuberculous meningitis patients. BMC Neurol. 2006;6:34.

    PubMed  PubMed Central  Google Scholar 

  41. Tiwari D, Haque S, Tiwari RP, Jawed A, Govender T, Kruger HG. Fast and efficient detection of tuberculosis antigens using liposome encapsulated secretory proteins of mycobacterium tuberculosis. J Microbiol Immunol Infect. 2017;50(2):189–98.

    CAS  PubMed  Google Scholar 

  42. McNerney R, Wondafrash BA, Amena K, Tesfaye A, McCash EM, Murray NJ. Field test of a novel detection device for mycobacterium tuberculosis antigen in cough. BMC Infect Dis. 2010;10:161.

    PubMed  PubMed Central  Google Scholar 

  43. Harinath BC, Kumar S, Roy SS, Hirudkar S, Upadhye V, Shende N. A cocktail of affinity-purified antibodies reactive with diagnostically useful mycobacterial antigens ES-31, ES-43, and EST-6 for detecting the presence of mycobacterium tuberculosis. Diagn Microbiol Infect Dis. 2006;55(1):65–8.

    CAS  PubMed  Google Scholar 

  44. Dai Z, Liu Z, **u B, Yang X, Zhao P, Zhang X, et al. A multiple-antigen detection assay for tuberculosis diagnosis based on broadly reactive polyclonal antibodies. Iran J Basic Med Sci. 2017;20(4):360–7.

    PubMed  PubMed Central  Google Scholar 

  45. Houghton RL, Lodes MJ, Dillon DC, Reynolds LD, Day CH, McNeill PD, et al. Use of multiepitope polyproteins in Serodiagnosis of active tuberculosis. Clin Diagn Lab Immunol. 2002;9(4):883–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Mandal N, Anand PK, Gautam S, Das S, Hussain T. Diagnosis and treatment of paediatric tuberculosis: an insight review. Crit Rev Microbiol. 2017;43(4):466–80.

    PubMed  Google Scholar 

  47. Raqib R, Mondal D, Karim MA, Chowdhury F, Ahmed S, Luby S, et al. Detection of antibodies secreted from circulating mycobacterium tuberculosis-specific plasma cells in the diagnosis of pediatric tuberculosis. Clin Vaccine Immunol. 2009;16(4):521–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Lee CM, Lee E, Bang JH, Park SW, Park WB, Oh MD, et al. Prevalence of multidrug-resistant tuberculosis in HIV/tuberculosis co-infected patients. Infect Chemother. 2021;53(4):792–5.

    PubMed  PubMed Central  Google Scholar 

  49. Kwizera R, Cresswell FV, Mugumya G, Okirwoth M, Kagimu E, Bangdiwala AS, et al. Performance of Lipoarabinomannan assay using cerebrospinal fluid for the diagnosis of tuberculous meningitis among HIV patients. Wellcome Open Res. 2019;4:123.

    PubMed  PubMed Central  Google Scholar 

  50. Blok N, Visser DH, Solomons R, Van Elsland SL, den Hertog AL, van Furth AM. Lipoarabinomannan enzyme-linked immunosorbent assay for early diagnosis of childhood tuberculous meningitis. Int J Tuberc Lung Dis. 2014;18(2):205–10.

    CAS  PubMed  Google Scholar 

  51. Fahmi MN, Harti AP. A diagnostic approach for differentiating abdominal tuberculosis from ovarian malignancy: a case series and literature review. BMC Proc. 2019;13(Suppl 11):13.

    PubMed  PubMed Central  Google Scholar 

  52. Nurwidya F, Handayani D, Burhan E, Yunus F. Molecular diagnosis of tuberculosis. Chonnam Med J. 2018;54(1):1–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, et al. Commercial serological tests for the diagnosis of active pulmonary and Extrapulmonary tuberculosis: An updated systematic review and meta-analysis. PLoS Med. 2011;8(8):e1001062.

    PubMed  PubMed Central  Google Scholar 

  54. Commercial Serodiagnostic Tests for Diagnosis of Tuberculosis - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK304212/. Accessed 23 May 2023.

  55. WHO operational handbook on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection, 2021 update [Internet]. https://www.who.int/publications/i/item/9789240030589. Accessed 23 May 2023.

  56. Aggarwal D, Ramachandran A. One health approach to address zoonotic diseases. Indian J Commun Med. 2020;45(Suppl 1):S6–8.

    Google Scholar 

  57. Sun L, Chen Y, Yi P, Yang L, Yan Y, Zhang K, et al. Serological detection of mycobacterium tuberculosis complex infection in multiple hosts by one universal ELISA. PloS One. 2021;16(10):e0257920.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Nathavitharana RR, Garcia-Basteiro AL, Ruhwald M, Cobelens F, Theron G. Reimagining the status quo: how close are we to rapid sputum-free tuberculosis diagnostics for all? EBioMedicine. 2022;78:103939.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Singh S, Katoch VM. Commercial serological tests for the diagnosis of active tuberculosis in India: time for introspection. Indian J Med Res. 2011;134(5):583–7.

    PubMed  PubMed Central  Google Scholar 

  60. Morris K. WHO recommends against inaccurate tuberculosis tests. Lancet. 2011;377(9760):113–4.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, All India Institute of Medical Sciences, Bhopal, India

    Anvita Gupta Malhotra

  2. IRCH, All India Institute of Medical Sciences, New Delhi, India

    Anil Kumar Gupta

  3. Department of Gastroenterology & HNU, All India Institute of Medical Sciences, New Delhi, India

    Amit Singh

  4. Department of Microbiology, Central University of Punjab, Bathinda, India

    Amit Singh

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  1. Anvita Gupta Malhotra
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  2. Anil Kumar Gupta
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  3. Amit Singh
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Correspondence to Amit Singh .

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Editors and Affiliations

  1. Department of Gastroenterology & HNU, All India Institute of Medical Sciences, New Delhi, India

    Amit Singh

  2. Department of Microbiology, Maulana Azad Medical College, New Delhi, India

    Divakar Sharma

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Malhotra, A.G., Gupta, A.K., Singh, A. (2023). The Future of Serology-Based Diagnosis for Tuberculosis in India. In: Singh, A., Sharma, D. (eds) Diagnosis of Mycobacterium. Springer, Singapore. https://doi.org/10.1007/978-981-99-5624-1_9

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