Acta Scientific Microbiology

Review Article Volume 7 Issue 1

Molecular Detection of INH Susceptibility is also Required for Improved Performance in Pulmonary Tuberculosis

Amit Singh, Sohini Sengupta and Ashok Rattan*

Redcliffe National Reference Laboratory, Noida, India

*Corresponding Author: Ashok Rattan, Professor, Redcliffe National Reference Laboratory, Noida, India.

Received: November 23, 2023; Published: December 29, 2023


Diagnosis is the weakest link in our efforts to eliminate Tuberculosis. If detected early, screened for drug resistance and fully treated with appropriate multidrug regimen, TB can be cured. The diagnostic methods since 1882 had been smear microscopy. Subsequently culture was added to the diagnostic modalities. While smear was insensitive needing atleast 10,000 bacteria for reliable detection, culture was slow, taking weeks. The assessment and recommendation of Gene Xpert, a cartridge based molecular method which not only detected MTBC but also reported on Rifampicin susceptibility was a major improvement. Initially Rif resistant was thought to be a good surrogate marker for MDR TB. Recent evidence indicate that was not correct and may have been counter productive. If the isolate was INH susceptible but Rif mono resistance and as per recommendation treated as MDR TB, then INH, an excellent bactericidal drug would have been with-held. On the other hand if INH monoresistant (IMR) was present and patient was treated with standard regimen, then for four months in the continuation phase, patient would receive monotherapy which would encourage emergence of MDR TB, failure of treatment, relapse or death.

Keywords: Diagnosis; WHO; MTBC


  1. Madhukar Pai., et al. “Transforming tuberculosis diagnosis”. Nature Microbiology 8 (2023): 756-759.
  2. Leading the way. INDIA TB REPORT 2023. CHFW, March (2023).
  3. Giorgia Sulis and Madhukar Pai. “Isoniazid-resistant tuberculosis: A problem we can no longer ignore”. PLOS Medicine (2020).
  4. Anna S Dean., et al. “Prevalence and genetic profiles of isoniazid resistance in tuberculosis patients: A multicountry analysis of cross-sectional data”. PLoS Medicine1 (2021): e1003008.
  5. Karin Weyer., et al. “Rapid molecular TB diagnosis: evidence, policy making and global implementation of Xpert MTB/RIF”. European Respiratory Journal 42 (2013): 252-271.
  6. Xpert MTB/RIF implementation manual: technical and operational ‘how-to’; practical considerations WHO (2014).
  7. Claudia M Denkinger., et al. “Do We Need to Detect Isoniazid Resistance in Addition to Rifampicin Resistance in Diagnostic Tests for Tuberculosis?” PLOS ONE 9 (2014): e84197.
  8. Adithya Cattamanchi., et al. “Clinical Characteristics and Treatment Outcomes of Isoniazid Mono-Resistant Tuberculosis”. Clinical Infectious Disease2 (2009): 179-185.
  9. Tsai-Yu Wang., et al. “Clinical Characteristics and Treatment Outcomes of Patients with Low- and High-Concentration Isoniazid Monoresistant Tuberculosis”. PLOS ONE 9 (2014): e86316.
  10. Raymund Dantes., et al. “Impact of Isoniazid Resistance-Conferring Mutations on the Clinical Presentation of Isoniazid Monoresistant Tuberculosis”. PLoS ONE 7 (2012): e37956.
  11. Max O’Donnell. “Isoniazid Monoresistance: A Precursor to Multidrug-Resistant Tuberculosis?” Annals ATS 15 (2018).
  12. Digamber Behera., et al. “RNTCP Guidelines for TB and Extra-Pulmonary Tuberculosis” (2021).
  13. Bertin C Bisimwa., et al. “Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications”. Clinical Infectious Diseases® 2021;73 (2): e362-370.
  14. Medea Gegia., et al. “Treatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic review and meta-analysis”. Lancet (2017).
  15. Leonela Villegas., et al. “Risk Factors, and Treatment Outcomes of Isoniazid- and Rifampicin Mono-Resistant Pulmonary Tuberculosis in Lima, Peru”. PLOS ONE (20146): 0152933.
  16. Renata Ba´ez-Saldaña., et al. “Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010”. PLOS ONE 16 (2016): 0168955.
  17. Yuri F van der Heijden., et al. “Isoniazid mono-resistant tuberculosis is associated with poor treatment outcomes in Durban, South Africa”. International Journal of Tuberculosis and Lung Disease 6 (2017): 670-676.
  18. WHO treatment guidelines for isoniazid resistant tuberculosis. Supplement to the WHO treatment guidelines for drug-resistant tuberculosis (2018).
  19. Anna S Dean., et al. “Prevalence and genetic profiles of isoniazid resistance in tuberculosis patients: A multicountry analysis of cross-sectional data”. PLOS Medicine 13 (2020): 1371.
  20. Zubeida Salaam-Dreyer., et al. “Rifampicin-Monoresistant Tuberculosis Is Not the Same as Multidrug-Resistant Tuberculosis: a Descriptive Study from Khayelitsha, South Africa”. Antimicrobial Agents and Chemotherapy 65 (2021): e00364-21.
  21. Betty R Mchaki., et al. “Can resistance to either isoniazid or rifampicin predict multidrug resistance tuberculosis (MDR-TB)”. Bulletin of the National Research Centre 47 (2023): 23.
  22. WHO consolidated guidelines on tuberculosis Rapid diagnostics for tuberculosis detection (2021).
  23. Manual for selection of molecular WHO recommended rapid diagnostic tests for detection of tuberculosis and drug-resistant tuberculosis WHO (2022).
  24. Mikashmi Kohli., et al. “Diagnostic accuracy of centralised assays for TB detection and detection of resistance to rifampicin and isoniazid: a systematic review and meta-analysis”. European Respiratory Journal 57 (2021): 2000747.
  25. Maunank Shah., et al. “Multicenter Study of the Accuracy of the BD MAX Multidrug-resistant Tuberculosis Assay for Detection of Mycobacterium tuberculosis Complex and Mutations Associated With Resistance to Rifampin and Isoniazid”. Clinical Infectious Diseases®5 (2020): 1161-1167.
  26. Amit Singh., et al. “Application of New Molecular Methods for TB Eradication: Gene Xpert Revisited”. Acta Scientific Microbiology (2023): 31-36.
  27. Chawangwa Modongo., et al. “Tuberculosis Variant with Rifampin Resistance Undetectable by Xpert MTB/RIF, Botswana”. Emerging Infectious Diseases 29 (2023): 11.
  28. Andreas Diacon., et al. “Assessing whether isoniazid is essential during the first 14 days of tuberculosis therapy: a phase 2a, open-label, randomised controlled trial”. 1 (2020).
  29. Marwa Bachir., et al. “Molecular detection of isoniazid monoresistance improves tuberculosis treatment: a retrospective cohort in France” (2022).


Citation: Ashok Rattan., et al. “Molecular Detection of INH Susceptibility is Also Required for Improved Performance in Pulmonary Tuberculosis".Acta Scientific Microbiology 7.1 (2024): 82-88.


Copyright: © 2024 Ashok Rattan., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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