Journal of Public Health Policy

, Volume 37, Issue 3, pp 277–299 | Cite as

Management and control of multidrug-resistant tuberculosis (MDR-TB): Addressing policy needs for India

  • Sachin R AtreEmail author
  • Megan B MurrayEmail author
Review Article


Multidrug-resistant tuberculosis (MDR-TB) challenges TB control efforts because of delays in diagnosis plus its long-term treatment which has toxic effects. Of TB high-incidence countries, India carries the highest burden of MDR-TB cases. We describe policy issues in India concerning MDR-TB diagnosis and management in a careful review of the literature including a systematic review of studies on the prevalence of MDR-TB. Of 995 articles published during 2001–2016 and retrieved from the PubMed, only 20 provided data on the population prevalence of MDR-TB. We further reviewed and describe diagnostic criteria and treatment algorithms in use and endorsed by the Revised National TB Control Program of India. We discuss problems encountered in treating MDR-TB patients with standardized regimens. Finally, we provide realistic suggestions for policymakers and program planners to improve the management and control of MDR-TB in India.


MDR-TB policy India pathways to care primary acquired 



Sachin Atre gratefully acknowledges funding support from US Department of State through the United States India Educational Foundation (USIEF) toward his one-year Fulbright-Nehru Postdoctoral fellowship at Harvard Medical School from September 2013. The authors thank Ms. Caroline McCallum for her editorial assistance.

Notes and References

  1. Mitnick, C.D. et al (2013) Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality. PLoS ONE 8(3): e58664.CrossRefGoogle Scholar
  2. World Health Organization. (2015) Global Tuberculosis Control Report, (WHO/HTM/TB/2015.22) Geneva, Switzerland: World Health Organization.Google Scholar
  3. Udwadia, Z.F., Pinto, L.M. and Uplekar, M.W. (2010) Tuberculosis management by private practitioners in Mumbai, India: Has anything changed in two decades? PLoS ONE 5(8): e12023.CrossRefGoogle Scholar
  4. Uplekar, M., Pathania, V. and Raviglione, M. (2001) Private practitioners and public health: Weak links in tuberculosis control. The Lancet 358(9285): 912–916.CrossRefGoogle Scholar
  5. Yadav, A. et al (2012) Treatment practices in pulmonary tuberculosis by private sector physicians of Meerut, Uttar Pradesh. Indian Journal of Chest Diseases and Allied Sciences 54(3): 161–163.Google Scholar
  6. Dye, C. et al (2008) Measuring tuberculosis burden, trends and the impact of control programs. The Lancet Infectious Diseases 8(4): 233–243.CrossRefGoogle Scholar
  7. Kapoor, S.K., Venkat Raman, A., Sachdeva, K.S. and Satyanarayana, S. (2012) How did the TB patients reach DOTS services in Delhi? A study of patient treatment seeking behavior. PLoS ONE 7(8): e42458.CrossRefGoogle Scholar
  8. Satyanarayana, S. et al (2011) From where are tuberculosis patients accessing treatment in India? Results from a cross-sectional community based survey of 30 districts. PLoS ONE 6(9): e24160.CrossRefGoogle Scholar
  9. Indian Council of Medical Research. (1959) Tuberculosis in India-A National Sample Survey: 1955–58 ICMR Special Report Series, New Delhi, No. 34.Google Scholar
  10. International Institute for Population Sciences (IIPS) and Macro International. (2007) National family health survey (NFHS-3), 2005–06, Vol I. Mumbai, India: IIPS; pp. 411-418,, accessed 14 November 2014.
  11. WHO Report. (2007) Global Tuberculosis Control. Surveillance, Planning and Financing. Geneva, Switzerland, World Health Organization WHO/HTM/TB/2007.376.Google Scholar
  12. Chadha, V.K. et al (2012) Prevalence of Pulmonary Tuberculosis among Adults in a Rural Sub-District of South India. PLoS ONE 7(8): e42625.CrossRefGoogle Scholar
  13. Rao, V.G. et al (2012) Prevalence of pulmonary tuberculosis – A baseline survey in central India. PLoS ONE 7(8): e43225.CrossRefGoogle Scholar
  14. World Health Organization. (2013) Global Tuberculosis Control Report. Geneva, Switzerland: World Health Organization.(WHO/HTM/TB/2013.13).Google Scholar
  15. Institute of Medicine (USA). (2012) Facing the reality of drug-resistant tuberculosis in India: Challenges and potential solutions: Summary of a joint workshop by the institute of medicine, the Indian national science academy, and the Indian council of medical research. Washington DC: National Academies Press,, accessed 14 November 2014.
  16. Bhat, J. et al (2015) Situation of drug resistant tuberculosis in Saharia tribe of central India. Indian Journal of Medical Research 141(5): 636–639.Google Scholar
  17. Myneedu, V. et al (2015) First and second line drug resistance among treatment naïve pulmonary tuberculosis patients in a district under Revised National Tuberculosis Control Programme (RNTCP) in New Delhi. Journal of Epidemiology & Global Health 5: 365–373.Google Scholar
  18. Selvakumar, N. et al (2015) High rates of ofloxacin resistance in Mycobacterium tuberculosis among both new and previously treated patients in Tamil Nadu, South India. PLoS ONE 10(3): e0117421.CrossRefGoogle Scholar
  19. Salvo, F. et al (2014) Survey of tuberculosis drug resistance among Tibetan refugees in India. International Journal of Tuberculosis and Lung Disease 18(6): 655–662.CrossRefGoogle Scholar
  20. Das, D., Dwibedi, B. and Kar, S.K. (2014) Low levels of anti TB drug resistance in Rayagada district of Odisha, India. International Journal of Mycobacteriology 3(1): 76–78.CrossRefGoogle Scholar
  21. Gupta, H., Kant, S., Jain, A., Natu, S.M. and Ahluwalia, S. (2013) Initial drug resistance pattern among pulmonary tuberculosis patients. Indian Journal of Tuberculosis 60(3): 154–161.Google Scholar
  22. Yadav, R., Sethi, S., Dhatwalia, S., Gupta, D., Mewara, A. and Sharma, M. (2013) Molecular characterization of drug resistance in Mycobacterium tuberculosis isolates from North India. International Journal of Tuberculosis and Lung Disease 17(2): 251–257.CrossRefGoogle Scholar
  23. Sharma, S.K. et al (2011) Prevalence of multidrug-resistant tuberculosis among category II pulmonary tuberculosis patients. Indian Journal of Medical Research 133(3): 312–315.Google Scholar
  24. Sharma, S.K. et al (2011) Prevalence of multidrug-resistant tuberculosis among newly diagnosed cases of sputum-positive pulmonary tuberculosis. Indian Journal of Medical Research 133(3): 308–311.Google Scholar
  25. Ramachandran, R. et al (2009) Surveillance of drug-resistant tuberculosis in the state of Gujarat. India International Journal of Tuberculosis and Lung Disease 13(9): 1154–1160.Google Scholar
  26. D’Souza, D.T. et al (2009) High levels of multidrug resistant tuberculosis in new and treatment-failure patients from the Revised National Tuberculosis Control Program in an urban metropolis (Mumbai) in Western India. BMC Public Health 9: 211.CrossRefGoogle Scholar
  27. Joseph, B.V. et al (2009) Drug resistance in Mycobacterium tuberculosis isolates from tuberculosis patients in Kerala, India. International Journal of Tuberculosis and Lung Disease 13(4): 494–499.Google Scholar
  28. Jain, A., Mondal, R., Prasad, R., Singh, K. and Ahuja, R.C. (2008) Prevalence of multidrug resistant Mycobacterium tuberculosis in Lucknow, Uttar Pradesh. Indian Journal of Medical Research 128(3): 300–306.Google Scholar
  29. Joseph, M.R., Shoby, C.T., Amma, G.R., Chauhan, L.S. and Paramasivan, C.N. (2007) Surveillance of anti-tuberculosis drug resistance in Ernakulam District, Kerala State, South India. International Journal of Tuberculosis and Lung Disease 11(4): 443–449.Google Scholar
  30. Anuradha, B. et al (2006) Prevalence of drug resistance under the DOTS strategy in Hyderabad, South India, 2001–2003. International Journal of Tuberculosis and Lung Disease 10(1): 58–62.Google Scholar
  31. Dhingra, V.K., Rajpal, S., Bhalla, P., Yadav, A., Jain, S.K. and Hanif, M. (2003) Prevalence of initial drug resistance to M. tuberculosis in new sputum positive RNTCP patients. Journal of Communicable Diseases 35(2): 82–89.Google Scholar
  32. Negi, S.S., Gupta, S. and Lal, S. (2003) Drug resistance in tuberculosis in Delhi: A 2 year profile (2001–2002). Journal of Communicable Diseases 35(2): 74–81.Google Scholar
  33. Shah, A.R., Agarwal, S.K. and Shah, K.V. (2002) Study of drug resistance in previously treated tuberculosis patients in Gujarat, India. International Journal of Tuberculosis and Lung Disease 6(12): 1098–1101.Google Scholar
  34. Paramasivan, C.N., Venkataraman, P., Chandrasekaran, V., Bhat, S. and Narayanan, P.R. (2002) Surveillance of drug resistance in tuberculosis in two districts of South India. International Journal of Tuberculosis and Lung Disease 6(6): 479–484.Google Scholar
  35. Although India has 29 States and 7 Union territories as of 2014. at the time of analysis data was only available for 28 States.Google Scholar
  36. Government of India Planning Commission data book. (2014), accessed 9 November 2014.
  37. Government of India – TB India. (2014) Revised National TB Control Program Annual Status Report, New Delhi,, accessed 15 April 2014.
  38. Warner, D.F. and Mizrahi, V. (2006) Tuberculosis chemotherapy: The influence of bacillary stress and damage response pathways on drug efficacy. Clinical Microbiology Review 19(3): 558–570.CrossRefGoogle Scholar
  39. WHO/IUATLD. (2004) Global Project on Anti-Tuberculosis Drug Resistance Surveillance. Anti-Tuberculosis Drug Resistance in the World. Geneva, Switzerland: World Health Organization. Report No.3.Google Scholar
  40. Dye, C. et al (2002) Erasing the world’s slow stain: Strategies to beat multi drug-resistant tuberculosis. Science 295(5562): 2042–2046.CrossRefGoogle Scholar
  41. Billington, O.J., McHugh, T.D. and Gillespie, S.H. (1999) Physiological cost of rifampicin resistance induced in vitro in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy 43(8): 1866–1869.Google Scholar
  42. Nardell, E. and Dharmadhikari, A. (2010) Turning off the spigot: Reducing drug-resistant tuberculosis transmission in resource-limited settings. International Journal of Tuberculosis and Lung Disease 14(10): 1233–1243.Google Scholar
  43. Zhao, M. et al (2009) Transmission of MDR and XDR tuberculosis in Shanghai, China. PLoS ONE 4(2): e4370.CrossRefGoogle Scholar
  44. Grandjean, L. et al (2015) Transmission of multidrug-resistant and drug-susceptible tuberculosis within households: A prospective cohort study. PLoS Medicine 12(6): e1001843.CrossRefGoogle Scholar
  45. Cohen, T. and Murray, M. (2004) Modeling epidemics of multidrug-resistant M. tuberculosis of heterogeneous fitness. Nature Medicine 10(10): 1117–1121.CrossRefGoogle Scholar
  46. Cohen, T., Sommers, B. and Murray, M. (2003) The effect of drug resistance on the fitness of Mycobacterium tuberculosis. The Lancet Infectious Diseases 31: 13–21.CrossRefGoogle Scholar
  47. Waisbord, S. and Zimicki, S., accessed 9 November 2014.
  48. Weiss, M., Auer, C., Somma, D. and Abouihia, A (2006) Gender and tuberculosis: Cross-site analysis and implications of a multi-country study in Bangladesh, India, Malawi and Colombia. Special Programme for Research and Training in Tropical Diseases (UNICEF/UNDP/World Bank/WHO), TDR/SDR/SEB/RP/06.1. Geneva, Switzerland: WHO. Report Series No. 3,, accessed 5 May 2014.
  49. Atre, S. et al (2011) Gender and community views of stigma and tuberculosis in rural Maharashtra, India. Global Public Health 6(1): 56–71.CrossRefGoogle Scholar
  50. Somma, D. et al (2008) Gender and socio-cultural determinants of TB-related stigma in Bangladesh, India, Malawi and Colombia. International Journal of Tuberculosis and Lung Disease 12(7): 856–866.Google Scholar
  51. Jaramillo, E. (1998) Pulmonary tuberculosis and health-seeking behaviour: how to get a delayed diagnosis in Cali, Colombia. Tropical Medicine & International Health 3(2): 138–144.CrossRefGoogle Scholar
  52. Liefooghe, R. et al (1997) From their own perspectiveA Kenyan Community’s Perception of Tuberculosis. Tropical Medicine & International Health 2(8): 809–821.CrossRefGoogle Scholar
  53. Portero, L.J. and Rubio, M. (2003) Private practitioners and tuberculosis control in the Philippines: Strangers when they meet? Tropical Medicine & International Health 8(4): 329–335.CrossRefGoogle Scholar
  54. Pinto, L.M. and Udwadia, Z.F. (2010) Private patient perceptions about a public programme; what do private Indian tuberculosis patients really feel about directly observed treatment? BMC Public Health 10: 357.CrossRefGoogle Scholar
  55. Jaggarajamma, K., Balambal, R. and Muniyandi, M. (2009) Perceptions of tuberculosis patients about private providers before and after implementation of Revised National Tuberculosis Control Program. Indian Journal of Tuberculosis 56(4): 185–190.Google Scholar
  56. Uplekar, M. et al (1998) Tuberculosis patients and practitioners in private clinics in India. International Journal of Tuberculosis and Lung Disease 2(4): 324–329.Google Scholar
  57. Pathania, V., Almeida, J. and Kochi, A. (1997) TB Patients and Private for Profit Health Care Providers in India. Geneva, Switzerland: World Health Organization, WHO/TB/97.223.1997.Google Scholar
  58. Srivastava, D.K. et al (2011) An assessment of knowledge and practices regarding tuberculosis in the Context of RNTCP among non-allopathic practitioners in Gwalior District. Online Journal of Health and Allied Sciences 10(2): 5.Google Scholar
  59. Bhargava, A., Pinto, L. and Pai, M. (2011) Mismanagement of tuberculosis in India: Causes, consequences, and the way forward. Hypothesis 9(1): e7.CrossRefGoogle Scholar
  60. Datta, K., Bhatnagar, T. and Murhekar, M. (2010) Private practitioners’ knowledge, attitude and practices about tuberculosis, Hooghly district India. Indian Journal of Tuberculosis 57(4): 199–206.Google Scholar
  61. Uplekar, M., Juvekar, S. and Morankar, S. (1996) Tuberculosis patients and practitioners in private clinics, Bombay [Research Newsletter]. Foundation for Research in Community Health.Google Scholar
  62. Jagota, P. (1998) Case finding policy for national tuberculosis program. Indian Journal of Tuberculosis 45(1): 3–7.Google Scholar
  63. Central TB Division (CTD). (2012) Guidelines on programmatic management of drug resistant TB (PMDT) in India. Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi,, accessed 21 February 2016.
  64. Government of India – TB India. (2015) Revised National TB Control Program Annual Status Report, New Delhi,, accessed 25 November 2015.
  65. Sachdeva, K. (2013) Management of tuberculosis: Indian Guidelines 2013,, accessed 25 November 2015.
  66. Census of India (State Census). (2011), accessed on 25 November 2015.
  67. Chadha, S. et al (2011) Operational challenges in diagnosing multi-drug resistant TB and initiating treatment in Andhra Pradesh, India. PLoS ONE 6(11): e26659.CrossRefGoogle Scholar
  68. Global Alliance for TB drug development. (2007) Pathway to Patients: Charting the Dynamics of the Global TB Drug Market. New York: TB Alliance.Google Scholar
  69. Greaves, F., Ouyang, H., Pefole, M, MacCarthy, S. and Cash, R.A. (2007) Compliance with DOTS diagnosis and treatment recommendations by private practitioners in Kerala, India. International Journal of Tuberculosis and Lung Disease 11(1): 110–112.Google Scholar
  70. Pathania, V.S. (2001) Why the Indian TB control program must stop ignoring private practitioners. International Journal of Tuberculosis and Lung Disease 5(2): 201–203.Google Scholar
  71. Uplekar, M.W. and Shepard, D.S. (1991) Treatment of tuberculosis by private general practitioners in India. Tubercle 72(4): 284–290.CrossRefGoogle Scholar
  72. Gupta, S., Gupta, S. and Behera, D. (2011) Reasons for interruption of anti-tubercular treatment as reported by patients with tuberculosis admitted in a tertiary care institute. Indian Journal of Tuberculosis 58(1): 11–17.Google Scholar
  73. Atre, S. (2015) Notification of multidrug-resistant tuberculosis cases and their treatment outcomes from the private sector. International Journal of Tuberculosis and Lung Disease 19(9): 1126.CrossRefGoogle Scholar
  74. Sharma, S. and Mohan, A. (2006) Multidrug-resistant tuberculosis: A menace that threatens to destabilize tuberculosis control. Chest 130(1): 261–272.CrossRefGoogle Scholar
  75. Farmer, P. and Kim, J.Y. (1998) Community based approaches to the control of multidrug-resistant tuberculosis: Introducing ‘DOTS-plus’. BMJ 317(7159): 671–674.CrossRefGoogle Scholar
  76. Atre, S., D’Souza, D.T.B., Dholakia, Y.N. and Mistry, N.F. (2007) Observations on categorization of new TB cases: Implications for controlling drug resistance. International Journal of Tuberculosis and Lung Disease 11(10): 1152–1153.Google Scholar
  77. Mphahlele, M. et al (2008) Pyrazinamide resistance among South African multidrug-resistant Mycobacterium tuberculosis isolates. Journal of Clinical Microbiology 46(10): 3459–3464.CrossRefGoogle Scholar
  78. Khurram, M., Khaar, H.T. and Fahim, M. (2012) Multidrug-resistant tuberculosis in Rawalpindi, Pakistan. The Journal of Infection in Developing Countries 6(1): 29–32.CrossRefGoogle Scholar
  79. Whitfield, M.G. et al (2015) A global perspective on pyrazinamide resistance: Systematic review and meta-analysis. PLoS ONE 10(7): e0133869.CrossRefGoogle Scholar
  80. Otu, A., Umoh, V., Habib, A., Ameh, S., Lawson, L. and Ansa, V. (2013) Drug Resistance among Pulmonary Tuberculosis Patients in Calabar. Pulmonary Medicine doi: 10.1155/2013/235190.Google Scholar
  81. Franke, M. et al (2015) Counting pyrazinamide in regimens for multidrug – Resistant tuberculosis. Annals of American Thoracic Society 12(5): 674–679.CrossRefGoogle Scholar
  82. Laniado-Laborin, R. (2010) Multidrug-resistant tuberculosis: standardized or individualized treatment? The question has already been answered. Expert Review of Respiratory Medicine 4(2): 143–146.CrossRefGoogle Scholar
  83. Suárez, P. et al (2002) Feasibility and cost – effectiveness of standardized second-line drug treatment for chronic tuberculosis patients: A national cohort study in Peru. The Lancet 359(9322): 1980–1989.CrossRefGoogle Scholar
  84. Park, S., Lee, W.C., Lee, D.H., Mitnick, C.D., Han, L. and Seung, K.J. (2004) Self-administered, standardized regimens for multidrug-resistant tuberculosis in South Korea. International Journal of Tuberculosis and Lung Disease 8(3): 361–368.Google Scholar
  85. Mitnick, C. et al (2003) Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru. The New England Journal of Medicine 348: 119–128.CrossRefGoogle Scholar
  86. Leimane, V. et al (2005) Clinical outcome of individualized treatment of multidrug-resistant tuberculosis in Latvia: A retrospective cohort study. The Lancet 365(9456): 318–326.CrossRefGoogle Scholar
  87. Government of India. TB India. (2013) Revised national TB control program annual status report, New Delhi,, accessed 15 April 2014.
  88. World Bank. (2013) Public health expenditure data,, accessed 5 March 2014.
  89. Escombe, A.R. et al (2013) Upper-room ultraviolet light and negative air ionization to prevent tuberculosis transmission. PLoS Med 6(3): e1000043.Google Scholar

Copyright information

© Macmillan Publishers Ltd 2016

Authors and Affiliations

  1. 1.Department of Global Health and Social Medicine, Harvard Medical SchoolBoston, MA 02115USA
  2. 2.Maharashtra Association of Anthropological Sciences, Centre for Health Research and Development (MAAS-CHRD), Pune, and Savitribai Phule Pune UniversityPune, 411007India

Personalised recommendations