Spotting the Silent Threat: Early Detection of Subclinical Tuberculosis in High-Risk Individuals

  1. Evangeline Ann Daniel
  2. Manohar Nesakumar
  3. S Hemalatha
  4. Nancy Hilda
  5. Kannan Thiruvengadam
  6. Umashankar Vetrivel
  7. Anbalagan Selvaraj
  8. Sathyamurthi Pattabiraman
  9. Brindha Bhanu
  10. Amsaveni Sivaprakasam
  11. Sudhakar Natarajan
  12. Vandana Kulkarni
  13. Rajesh Karyakarte
  14. Mandar Paradkar
  15. Shri Vijay Bala Yogendra Shivakumar
  16. Vidya Mave
  17. Padmapriyadarsini Chandrasekaran
  18. Amita Gupta
  19. Luke Elizabeth Hanna

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Abstract

The dynamic spectrum of TB often results in underdiagnosis warranting the need for better diagnostics to accurately detect Mtb in diagnostically challenging cohorts. Household contacts of newly diagnosed TB patients who developed TB (Progressors) and those who remained healthy (Non-progressors) during a two-year follow-up cohort study were included. Mtb ccfDNA was detected in the plasma by targeting insertion sequences IS6110 and IS1081 using ddPCR. The assay yielded a sensitivity of 90·9% in detecting subclinical TB cases and 81·8% in possible TB cases. Further, the test detected Mtb ccfDNA in progressors even at six months prior to TB diagnosis at a sensitivity of 79·0%. In about 55·0% and 50·0% of cases Mtb ccfDNA could be detected as early as 12 months and 18 months prior to development of active disease, respectively. The test demonstrated excellent sensitivity (100·0%) in detecting extra-pulmonary TB cases up to six months prior to TB disease development.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Kimberlee Musser

    Review 3: "Spotting the Silent Threat: Early Detection of Subclinical Tuberculosis in High-Risk Individuals"

    These reviews underscore the assay’s promise for earlier, non-sputum-based TB detection, warranting broader validation.

  2. Rapid Reviews Infectious Diseases

    Siti Aishah Rashid, Nurul Farehah Shahrir

    Review 2: "Spotting the Silent Threat: Early Detection of Subclinical Tuberculosis in High-Risk Individuals"

    These reviews underscore the assay’s promise for earlier, non-sputum-based TB detection, warranting broader validation.

  3. Rapid Reviews Infectious Diseases

    Hongping Wei

    Review 1: "Spotting the Silent Threat: Early Detection of Subclinical Tuberculosis in High-Risk Individuals"

    These reviews underscore the assay’s promise for earlier, non-sputum-based TB detection, warranting broader validation.

  5. Version published to 10.1101/2025.02.24.25322763v1 on medRxiv