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Multi drug resistant T.B. (MDR) Dr. Gopalrao M.D. Ph.D.
Professor of Community Medicine
CAR Medical College
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Global Fact sheet:
T.B. Incidence: 9 million people are
affected by TB annually world wide.
1.5 million deaths occur annually
world wide.
MDR-TB is defined as disease
having resistance to two or more of
the anti T.B. drugs with or without
resistance to other anti TB drugs
It is a major threat to TB control
program world wide.
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High burden countries for T.B.
Afghanistan Ethiopia
Indonesia China
India Cambodia
Democratic Republic of Congo Bangladesh
Brazil Mozambique
Kenya Myanmar
Pakistan Nigeria
South Africa Thailand
Philippines Russia
Uganda Tanzania
Vietnam Zimbabwe
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Countries having problem of MDR T.B.
Russia Peoples Republic of China India Western Europe United states United Kingdom Germany Central Europe Lithuania Latvia Estonia
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Indian Scenario Prevalence of MDR T.B. in new smear +ve cases is less than
3% and 12 to 17% amongst previously treated PTB cases.
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• India is the highest TB burden country in the world.
• India is 17th among 22 high burden countries in terms of
incidence rate
• Accounts for 20% of global burden of TB.
• Every year 2.3 million persons develop TB
• There are 0.8 million new smear positive cases. • The annual risk of becoming infected with TB is 1.5 %
Case study from Andhra Pradesh Study conducted on 75 MDR T.B. cases. Report from 18
districts of the state
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NO. OF PATIENTS
% OF PATIENTS
SOB, Cough, fever 38 50%
Cough, fever 20 27%
SOB, cough 6 8%
Cough, fever, lossof appetite
2 3%
SOB, cough, fever, loss of appetite
2 3%
cough 2 3%
SOB, Haemoptysis 1 1%
Cough, loss of appetite
1 1%
Cough, fever, haemoptysis
1 1%
SOB 1 1%
SOB, cough,haemoptysis
1 1%
Cough, fever,chestpain
1 1%
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Complaints
among
MDRTB
Patients
Clinical factors promoting resistance Delayed diagnosis and isolation Inappropriate drug regimen.
Inadequate initial therapy Incomplete course of treatment Inappropriate treatment modifications Adding single drug to a failing regimen Inappropriate use of chemoprophylaxis
Poor adherence and incomplete Follow up Failure to isolate MDR TB patients Failure to employ DOT Over the counter anti TB Faked drugs
Mechanism of Resistance TB specific drugs
INH, PZA, ETH
Antibiotics with activity against TB
RIF
Aminogycosides
Flouroquinolones
INH
Chromosomally mediated
Loss of catalase/peroxidase
Mutation in mycolic acid synthesis
Regulators of peroxide response
Mechanism of resistance
Rifampin
Reduced binding to RNA polymerase
Clusters of mutations at “Rifampin Resistance Determining Region” (RRDR)
Reduced Cell wall permeability
Mechanism of resistance
Treatment of MDR TB Factors determining Success
Culture of MDR TB
Reliable susceptibility
Reliable history of previous drug regimens
Program to assure delivery of prescribed drugs (DOT)
Correct choice of modified treatment regimen
Reliable follow up
New Chemotherapeutic Agents Not many. Low interest from pharmaceutical industry
Derivatives of Rifamycin Rifabutin: Sensitive subset of Rifampin resistant strains
Rifapentine: Extended half-life but more mono-resistance to rifamycins
KRM-1648. benzoxazinorifamycin. In vitro and animal models.
New flouroquinolones Gatifloxacin, Moxifloxacin, levofloxacin, sparfloxacin
Nitroimidazoles related to metronidazole. May work better against latent bacilli
Avoiding pro-drug problems
Chemoprophylaxis Determinants of intervention
Likelihood of infection with MDR TB
Low
Intermediate
High
Likelihood of developing MDR TB
Immune suppression
Global TB control targets
2005: World Health Assembly:
- To detect at least 70% of infectious TB cases
- To treat successfully at least 85% of detected cases
2015: 50% reduction in TB prevalence and death rates by 2015
2015: Goal 6: Combat HIV/AIDS, malaria and other
diseases
Target 8: to have halted by 2015 and begun to reverse
the incidence…
Indicator 23: prevalence and deaths associated with TB
Indicator 24: proportion of TB cases detected
and cured under DOTS
Beyond 2015 Shift from MDG to post 2015 development frame work
WHO has developed post 2015 global T.B. strategy that was approved by all members of WHO assembly
The overall goal of the strategy is to end the global T.B. epidemic, corresponding to 2035 targets
95% reduction T.B. deaths and 90% reduction in T.B. incidence (compared to 2015)
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