MDR T.B.

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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Reported

MDR cases

from 18

districts of

Andhra

Pradesh

1

2

56

1

9

5

5

10

3

2

2

5

2

21

1

14

8

9

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 plans to combat T.B.

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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

Stop TB Strategy to reach the 2015 MDGs

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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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Thank You

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