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Drug Resistant   Tuberculosis A Great Human Concern Dr.T.V.Rao MD
MDR TB –Great Human Concern
HISTORY of Tuberculosis ,[object Object]
A Tribute to Robert Koch  Discoverer of Mycobacterium Tuberculosis
Global Status ,[object Object],[object Object],[object Object]
USAID   Report on Tuberculosis in India ,[object Object]
Nobody is absolutely Immune to Tuberculosis
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Pharmacological discoveries
Selman Abraham Waksman   Nobel Prize for his discovery in 1952 .    
Pharmacological discoveries ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Introduction ,[object Object],[object Object]
Typical tubercle bacilli ,[object Object],[object Object],[object Object],[object Object]
Multi Drug Resistant Tuberculosis MDR-TB
Definition ,[object Object],[object Object],[object Object]
MDR-TB & XDR-TB THE 2008 REPORT % of MDR-TB among new TB cases 1994-2007
Classification of Drugs   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Several Drugs becoming resistant
Basic concepts – Keep facts ,[object Object],[object Object],[object Object],[object Object]
What is multidrug-resistant tuberculosis (MDR TB)? ,[object Object]
When to suspect MDR TB ,[object Object],[object Object],[object Object],[object Object],[object Object]
What is extensively drug resistant tuberculosis (XDR TB)? ,[object Object]
Why XDR - TB a grave concern ,[object Object],[object Object]
Global Estimates 16,000 27,000 XDR TB 1,16,000, 4,24,000 MDR TB 1.6 million 8.8 million All forms TB Estimated Number of Deaths Estimated Number of Cases Classification
Extensively Drug-Resistant  Mycobacterium tuberculosis , India ,[object Object]
Global incidence of tuberculosis  Still rising as a result of the growing epidemic in Africa 0 100 200 300 400 500 600 1990 1995 2000 2005 2010 2015 Incidence per 100,000 per year World Cent. Euro,  East. Europe Est Market  East. Medit. Lat. America West. Pacific Sth East Asia AFR high HIV AFR low HIV
Are we Returning  to a Pre-antibiotic Era   Drug susceptible TB*§ MDR-TB 1990§ XDR-TB 2006§ Total DR ? Resistance to H&R –  Treatable with 2 nd  line drugs Resistance to 2 nd  line drugs – Treatment options seriously restricted Resistance to all available drugs –  No treatment options *or limited resistance manageable with 4 drug regimen - DOTS
WHO Surveillance and Incidence of MDR TB Dye et al. Global Burden of Multidrug-Resistant TB. JID 185(8), 2002 5.3 Ivory Cost 6.6 Dominican 5.8 Iran 3.4 India 6.0 Russia 2.8 China (DOTS) 7.7 China (non-DOTS) 9.0 Latvia 14.1 Estonia % MDR TB of all new cases Country
Genesis of MDR TB ,[object Object],[object Object],[object Object],[object Object]
Strains with genetic  drug resistance Wild M. TB strain Acquired drug  resistance Primary drug  resistance Spontaneous mutation Selection: inadequate treatment Transmission Development of anti-tuberculosis drug resistance Pablos-Mendez et al. WHO, 1997
Factors Contributing to Development  and Spread of MDR and XDR TB ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],Mechanism of resistance
[object Object],[object Object],[object Object],[object Object],Mechanism of resistance
Gene location associated  Drug-Resistant M.tuberculosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Drug Susceptibility Testing
Susceptibility Testing ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Drug susceptibility testing (DST) ,[object Object],[object Object],[object Object],[object Object]
Drug susceptibility Testing ,[object Object],[object Object]
Other accredited  Methods ,[object Object],[object Object]
Drug susceptibility testing (DST ) ,[object Object]
Detection of Rifampicin Drug susceptibility testing (DST) is more important . ,[object Object],[object Object]
Drug susceptibility testing ,[object Object]
Secondary Drugs testing:[lack of standardized methods!] ,[object Object],[object Object],[object Object],[object Object],[object Object]
MODS   M icroscopic   O bservation of   D rug Susceptibility  T esting
MODS affordable Technically Feasible  ,[object Object]
Review Article in Indian Journal of Medical Microbiology ,[object Object]
Observation of Grwoth in liquid Media ,[object Object]
Least time required for detection of MDR ,[object Object]
MODS more streamlined ,[object Object]
Inverted Microscope a minimal need ,[object Object]
MODS for detection of  MDR - TB ,[object Object]
Advantages of MODS methodology in MDR detection ,[object Object],[object Object],[object Object],[object Object]
Performing MODS Assay ,[object Object],[object Object]
MODS Assay ( Contd) ‏ ,[object Object],[object Object],[object Object]
Sample layout on MODS plate  (2 samples per plate) No plate contained 2 samples from the same patient
Drug susceptibility Testing In MODS ,[object Object],[object Object],[object Object],[object Object],[object Object]
Differentiation from Typical and Atypical Mycobacterium ,[object Object]
In MODS growth is identified by cording on Microscopy
MODS assay ( Contd) ‏ ,[object Object]
Observation of growth in MODS ,[object Object]
MODS in Atypical Mycobacterium ,[object Object]
Contamination in MODS Assay ,[object Object],[object Object]
Honduras study comparing the LJ medium ,[object Object]
PCR: Molecular susceptibility testing RMP resistance INH resistance Hain Genotype MTBDR Hain Genotype MTBDR INNO-LiPA Rif.TB assay
Confirming  MODS  results ,[object Object]
MODS  and  MDR  detection ,[object Object],[object Object],[object Object]
Why MODS is a better method for MDR TB detection ,[object Object],[object Object]
Biosafety concerns in MODS technology ,[object Object]
Lower Grade Biosafety  is adequate
N 95 mask protects from Biohazard
No transfer of Materials needed in MODS ,[object Object]
Computer pattern recognition of  Mycobacterium tuberculosis in MODS culture
Automation in MODS
M . tuberculosis  in MODS x10 objective  (sputum sample inoculation ) Day 6  Day 16 Day 17 Day 7  Day 8  Day 9  Day 10  Day 11  Day 12  Day 13  Day 14  Day 15
MODS can be used in Extra pulmonary Tuberculosis
Draw backs of MODS ,[object Object]
Other WHO-Endorsed Tools ,[object Object],[object Object],[object Object],[object Object],[object Object]
WHO Controls the Tuberculosis related work ,[object Object]
XDR-TB in South Africa August 2006 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Molecular Fingerprinting ,[object Object],[object Object],[object Object]
CDC Updates Guidelines for Nucleic Acid Amplification Techniques to Diagnose Tuberculosis ,[object Object],[object Object],[object Object]
Selection from automated systems for molecular and bacteriological rapid diagnostics ,[object Object],[object Object],[object Object],[object Object],[object Object]
Microscopy and Culturing still a top priority
Is PCR methods a solution ? ,[object Object]
No testing method replaces clinical assessment
Extreme Drug resistant Tuberculosis (XDR-TB) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
XDR-TB: 8/23/06   ,[object Object],[object Object],[object Object],[object Object]
Czech Republic The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.  Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.    WHO 2005. All rights reserved Ecuador Georgia Argentina Bangladesh Germany Republic of Korea Armenia Russian Federation South Africa Portugal Latvia Mexico Peru USA Brazil UK Sweden Thailand Chile Based on information provided to WHO Stop TB Department  13 September 2007   Spain Islamic Republic of Iran China, Hong Kong SAR France Japan Norway Canada Italy Netherlands Estonia Lithuania Ireland Romania Israel Azerbaijan Poland Slovenia  India Australia Mozambique Vietnam Countries with confirmed XDR-TB cases as of September 2007
Summary  Drug resistant TB ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Health Care Workers and MDR TB ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Koch failed to conquer tuberculosis, which still causes enormous health problems worldwide 100 years after his Nobel award.   ,[object Object],[object Object]
Are there any solutions for effective Diagnosis in TB ?
Many more powerful hands needed to Control  Tuberculosis
Contribute your Knowledge, Wisdom, to prevent spread and control of Tuberculosis
Created by Dr.T.V.Rao MD for  ‘e’ learning  Programme Email [email_address]

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Drugresistanttuberculosis 100227020029 Phpapp01

  • 1. Drug Resistant Tuberculosis A Great Human Concern Dr.T.V.Rao MD
  • 2. MDR TB –Great Human Concern
  • 3.
  • 4. A Tribute to Robert Koch Discoverer of Mycobacterium Tuberculosis
  • 5.
  • 6.
  • 7. Nobody is absolutely Immune to Tuberculosis
  • 8.
  • 9. Selman Abraham Waksman Nobel Prize for his discovery in 1952 .   
  • 10.
  • 11.
  • 12.
  • 13. Multi Drug Resistant Tuberculosis MDR-TB
  • 14.
  • 15. MDR-TB & XDR-TB THE 2008 REPORT % of MDR-TB among new TB cases 1994-2007
  • 16.
  • 18.
  • 19.
  • 20.
  • 21.
  • 22.
  • 23. Global Estimates 16,000 27,000 XDR TB 1,16,000, 4,24,000 MDR TB 1.6 million 8.8 million All forms TB Estimated Number of Deaths Estimated Number of Cases Classification
  • 24.
  • 25. Global incidence of tuberculosis Still rising as a result of the growing epidemic in Africa 0 100 200 300 400 500 600 1990 1995 2000 2005 2010 2015 Incidence per 100,000 per year World Cent. Euro, East. Europe Est Market East. Medit. Lat. America West. Pacific Sth East Asia AFR high HIV AFR low HIV
  • 26. Are we Returning to a Pre-antibiotic Era Drug susceptible TB*§ MDR-TB 1990§ XDR-TB 2006§ Total DR ? Resistance to H&R – Treatable with 2 nd line drugs Resistance to 2 nd line drugs – Treatment options seriously restricted Resistance to all available drugs – No treatment options *or limited resistance manageable with 4 drug regimen - DOTS
  • 27. WHO Surveillance and Incidence of MDR TB Dye et al. Global Burden of Multidrug-Resistant TB. JID 185(8), 2002 5.3 Ivory Cost 6.6 Dominican 5.8 Iran 3.4 India 6.0 Russia 2.8 China (DOTS) 7.7 China (non-DOTS) 9.0 Latvia 14.1 Estonia % MDR TB of all new cases Country
  • 28.
  • 29. Strains with genetic drug resistance Wild M. TB strain Acquired drug resistance Primary drug resistance Spontaneous mutation Selection: inadequate treatment Transmission Development of anti-tuberculosis drug resistance Pablos-Mendez et al. WHO, 1997
  • 30.
  • 31.
  • 32.
  • 33.
  • 35.
  • 36.
  • 37.
  • 38.
  • 39.
  • 40.
  • 41.
  • 42.
  • 43. MODS M icroscopic O bservation of D rug Susceptibility T esting
  • 44.
  • 45.
  • 46.
  • 47.
  • 48.
  • 49.
  • 50.
  • 51.
  • 52.
  • 53.
  • 54. Sample layout on MODS plate (2 samples per plate) No plate contained 2 samples from the same patient
  • 55.
  • 56.
  • 57. In MODS growth is identified by cording on Microscopy
  • 58.
  • 59.
  • 60.
  • 61.
  • 62.
  • 63. PCR: Molecular susceptibility testing RMP resistance INH resistance Hain Genotype MTBDR Hain Genotype MTBDR INNO-LiPA Rif.TB assay
  • 64.
  • 65.
  • 66.
  • 67.
  • 68. Lower Grade Biosafety is adequate
  • 69. N 95 mask protects from Biohazard
  • 70.
  • 71. Computer pattern recognition of Mycobacterium tuberculosis in MODS culture
  • 73. M . tuberculosis in MODS x10 objective (sputum sample inoculation ) Day 6 Day 16 Day 17 Day 7 Day 8 Day 9 Day 10 Day 11 Day 12 Day 13 Day 14 Day 15
  • 74. MODS can be used in Extra pulmonary Tuberculosis
  • 75.
  • 76.
  • 77.
  • 78.
  • 79.
  • 80.
  • 81.
  • 82. Microscopy and Culturing still a top priority
  • 83.
  • 84. No testing method replaces clinical assessment
  • 85.
  • 86.
  • 87. Czech Republic The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.  WHO 2005. All rights reserved Ecuador Georgia Argentina Bangladesh Germany Republic of Korea Armenia Russian Federation South Africa Portugal Latvia Mexico Peru USA Brazil UK Sweden Thailand Chile Based on information provided to WHO Stop TB Department 13 September 2007 Spain Islamic Republic of Iran China, Hong Kong SAR France Japan Norway Canada Italy Netherlands Estonia Lithuania Ireland Romania Israel Azerbaijan Poland Slovenia India Australia Mozambique Vietnam Countries with confirmed XDR-TB cases as of September 2007
  • 88.
  • 89.
  • 90.
  • 91. Are there any solutions for effective Diagnosis in TB ?
  • 92. Many more powerful hands needed to Control Tuberculosis
  • 93. Contribute your Knowledge, Wisdom, to prevent spread and control of Tuberculosis
  • 94. Created by Dr.T.V.Rao MD for ‘e’ learning Programme Email [email_address]